Evaluating the Effectiveness and Feasibility of Reactive Focal Mass Drug Administration vs. Reactive Case Detection as a Community Level Intervention in Response to a Passively Identified Index Malaria Case in Swaziland
Phase: PHASE3
Conditions: Malaria
Sponsor: University of California, San Francisco

 
 
 
 
 
REACTIVE TARGETED PARASITE ELIMINATION (TPE) 
 
 
 
 
 
 
Study Title: Evaluating the effectiveness and feasibility of reactive 
targeted parasite elimination vs. reactive case detection as a community-
level intervention in response to a passively identified index case in 
Swaziland 
 
 
 
 
 
 
 
 
 
 
 
Funded by: The Bill and Melinda Gates Foundation 
 
 
Principal Investigators: Michelle Hsiang, Roly Gosling, Simon Kunene 
 
 
ClinicalTrials.gov Number: NCT02315690 
 
 
 
 
 
 
 
 
 
Protocol Version 1.10, 30 March 2016 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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Table of Contents 
Study summary ........................................................................................................................................................................................... 5 
Study personnel and institutions ........................................................................................................................................................ 6 
Principal Investigators......................................................................................................................................................................... 6 
Other Key Personnel and Collaborators ...................................................................................................................................... 6 
Study members and responsibilities.......................................................................................................................................... 10 
Administrative contacts .................................................................................................................................................................. 14 
Institutional review boards ............................................................................................................................................................ 14 
Primary Funder ................................................................................................................................................................................... 15 
Abbreviations & acronyms .................................................................................................................................................................. 16 
1 
Background ....................................................................................................................................................................................... 17 
1.1 
Malaria in Swaziland ....................................................................................................................................................... 17 
1.2 
Challenges for Malaria Elimination ........................................................................................................................... 17 
1.3 
Reactive case detection (RACD) ................................................................................................................................. 17 
1.4 
Targeted parasite elimination (TPE) ......................................................................................................................... 19 
1.5 
RACD vs. reactive TPE ..................................................................................................................................................... 19 
1.6 
Drug regimens .................................................................................................................................................................... 20 
2 
Rationale ............................................................................................................................................................................................ 21 
3 
Study aims ......................................................................................................................................................................................... 23 
4 
Study design & methods.............................................................................................................................................................. 24 
4.1 
Overview .............................................................................................................................................................................. 24 
4.2 
Study site and study population ................................................................................................................................ 24 
4.3 
Randomization of localities (clusters) ...................................................................................................................... 24 
4.4 
Target Areas ........................................................................................................................................................................ 28 
4.5 
Inclusion and exclusion criteria .................................................................................................................................. 30 
5 
Baseline Preventative Interventions – LLINs and IRS ...................................................................................................... 31 
6 
Enrollment ......................................................................................................................................................................................... 31 
6.1 
Sensitization ........................................................................................................................................................................ 31 
6.2 
Identification of Target Areas (through immediate case notification and Case investigation of the 
index case) ....................................................................................................................................................................................... 32 
6.3 
Informed consent ............................................................................................................................................................. 32 
7 
Study intervention.......................................................................................................................................................................... 33 
7.1 
Household-level questionnaire................................................................................................................................... 33 
7.2 
RACD arm - Perform RDT and refer secondary cases to health facilities ................................................. 34 
7.3 
TPE arm - Administration of DP .................................................................................................................................. 34 
7.4 
Management of sick participants .............................................................................................................................. 35 
7.5 
Adherence assessment .................................................................................................................................................. 35 
8 
Adverse event monitoring .......................................................................................................................................................... 37 
8.1 
Overview .............................................................................................................................................................................. 37 

 
 
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8.2 
Definitions ........................................................................................................................................................................... 37 
8.3 
Passive identification of SAEs ...................................................................................................................................... 37 
8.4 
SAE report forms............................................................................................................................................................... 37 
8.5 
Expedited reporting of SAEs and SUSARs ............................................................................................................... 38 
8.6 
Management of participants with SAEs .................................................................................................................. 38 
9 
Follow-up surveys ........................................................................................................................................................................... 38 
9.1 
Overview .............................................................................................................................................................................. 38 
9.2 
Follow-up blood survey at 6-9 months ................................................................................................................... 38 
9.3  
End-line survey (at the end of the study, expected mid 2017) .................................................................... 39 
10 Acceptability Assessment ............................................................................................................................................................ 39 
10.1 
Background and Rationale ......................................................................................................................................... 39 
10.2 
Aims of the Acceptability Assessment .................................................................................................................. 40 
10.3 
Methods for the Acceptability Assessment ........................................................................................................ 40 
11 Cost-effectiveness assessment ................................................................................................................................................. 42 
12 Laboratory procedures ................................................................................................................................................................. 42 
12.1 
Rapid diagnostic tests .................................................................................................................................................. 42 
12.2 
Filter paper sample collection .................................................................................................................................. 42 
12.3 
Microtainer blood collection .................................................................................................................................... 43 
12.4 
Antibody and DNA extraction ................................................................................................................................... 43 
12.5 
LAMP ................................................................................................................................................................................... 43 
12.6 
PCR ....................................................................................................................................................................................... 43 
12.7 
Genotyping ....................................................................................................................................................................... 43 
12.8 
QT-NASBA for gametocytes....................................................................................................................................... 43 
12.9 
ELISA .................................................................................................................................................................................... 43 
12.10 
Sample storage for future studies (for research purposes only) ............................................................ 44 
13 Data management.......................................................................................................................................................................... 44 
13.1 
Quality assurance & quality control ...................................................................................................................... 44 
13.2 
Records & storage ......................................................................................................................................................... 44 
14 Statistical issues............................................................................................................................................................................... 44 
14.1 
Study population ............................................................................................................................................................ 44 
14.2 
Outcome measures ....................................................................................................................................................... 46 
14.3 
Estimates of study power ........................................................................................................................................... 46 
14.4 
Analytical plan ................................................................................................................................................................. 49 
15 Advisory Committee ...................................................................................................................................................................... 51 
15.1 
Role of the Advisory Committee ............................................................................................................................. 51 
15.2 
Membership of Advisory Committee .................................................................................................................... 51 
15.3 
Activities of the Advisory Committee ................................................................................................................... 51 
16 Data and Safety Monitoring Committee............................................................................................................................... 52 
16.1 
Data and Safety Monitoring Committee .............................................................................................................. 52 

 
 
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16.2 
Meetings ............................................................................................................................................................................ 52 
16.3 
Stopping guidelines ....................................................................................................................................................... 52 
17 Ethical considerations ................................................................................................................................................................... 52 
17.1 
Institutional review boards........................................................................................................................................ 52 
17.2 
Informed consent process ......................................................................................................................................... 52 
17.3 
Risks and discomforts .................................................................................................................................................. 53 
17.4 
Compensation ................................................................................................................................................................. 54 
18 Timeline .............................................................................................................................................................................................. 55 
19 References ......................................................................................................................................................................................... 56 
 
 
Appendices 
Appendix A:  
Study information for stakeholders 
 
Appendix B:  
Index case immediate notification form 
Appendix C:  
Index case, Case investigation form 
Appendix D:  
Unsuccessful Case Investigation 
Appendix E:  
Informed Consent Forms for Resident Enrollment, Intervention, RACD Arm 
Appendix F: 
Informed Consent Forms for Resident Enrollment, Intervention, TPE Arm  
Appendix G: 
Neighborhood information 
Appendix H: 
Household level RACD questionnaire 
Appendix I: 
Individual level RACD questionnaire 
Appendix J 
Household level TPE questionnaire 
Appendix K: 
Individual level TPE questionnaire 
Appendix L: 
Informed Consent Forms for 6-9 month follow-up visit 
Appendix M: 
6-9 month follow-up visit questionnaire 
Appendix N: 
Informed Consent Forms for Resident Enrollment, End-line Survey  
Appendix O: 
End-line survey household questionnaire 
Appendix P: 
End-line survey individual questionnaire 
Appendix Q:   
DP weight-based dosing guidelines 
Appendix R:  
Modified DOT dosing schedule 
Appendix S: 
Serious adverse event report form 
Appendix T: 
WHO Grading for Determining Severity of Adverse Events 
Appendix U: 
Informed Consent Forms for Acceptability Assessment 
Appendix V: 
Qualitative questionnaires for the Acceptability Assessment – Individual Interviews with 
Refusers 
Appendix W: 
Qualitative questionnaires for the Acceptability Assessment – Focus Groups with 
Participants 
Appendix X: 
Qualitative questionnaires for the Acceptability Assessment – Focus Groups with Malaria 
Surveillance Team 
Appendix Y:  
Swaziland Malaria Elimination Advisory Group (SMEAG) Terms of Reference 
Appendix Z:  
TPE Safety Monitoring Committee Terms of Reference 
 
 
 
 
 
 

 
 
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Study summary 
 
Title 
Evaluating the effectiveness and feasibility of reactive targeted parasite elimination (TPE) vs. reactive case 
detection (RACD) as a community-level intervention in response to a passively identified index case in Swaziland 
Study design 
Cluster randomized controlled trial 
Aims 
Primary aim: To compare the impact of TPE versus RACD on malaria incidence. 
Secondary aims 
Effectiveness:  
1. 
To compare the impact of TPE versus RACD on seroprevalence. 
2. 
To compare the impact of TPE versus RACD on prevalence of infection. 
3. 
To compare the impact of TPE versus RACD on proportion of imported incident cases. 
4. 
To compare the impact of TPE versus RACD on time to first post-intervention incident local case. 
5. 
To compare the impact of TPE versus RACD on transmission potential as measured by relatedness 
of infections by microsatellite genotyping. 
Feasibility: 
1. 
To determine the feasibility of reaching 80% coverage for TPE versus RACD. 
2. 
To evaluate the safety of TPE versus RACD. 
3. 
To compare the acceptability of TPE versus RACD. 
4.     To compare the costs and cost-effectiveness of TPE versus RACD. 
5.     To measure the adherence to modified DOT with DP in the TPE arm. 
Study site 
Eastern endemic region of Swaziland, a very low endemic malaria elimination setting. A total of 287 health 
facilities and their catchment areas are located in this area. 
Time frame 
September 2015 until two transmission seasons completed (mid-2017)  
Cluster or unit of 
randomization 
At risk localities will be randomized to either TPE or RACD using a block stratified randomization based on 
risk rank (1-3) and population 
Target area 
For TPE localities: Neighborhood of individuals residing within 200m of an index case detected in passive 
surveillance. Individuals residing immediately beyond 200m will be included if a minimum of 30 individuals 
are not enrolled within 200m. For RACD localities: Neighborhood of individuals residing within 500m of an 
index case detected in passive surveillance.  
Intervention 
All individuals residing in study localities will receive vector control preventative measures as per program. In 
the TPE arm, all individuals in the Target Area will receive dihydroartemisinin-piperaquine (DP) once daily for 
3 days with the first dose taken no later than 5 weeks from the index case presentation (goal within one 
week). Individuals in RACD Target Areas will be tested by RDT and taken to the nearest health facility for 
treatment as per program operating procedures. 
Evaluation 
methods 
The primary outcome measure of incidence will be obtained routine surveillance data. 
Secondary outcomes will be measured through Target area-level surveys: 
1) Blood surveys. At the time of enrollment of a new Target area in RACD arm and at study conclusion in 
both arms (LAMP, QT-NASBA, serology, genotyping). DBS collected in incident cases as part of routine 
surveillance will also be utilized for genotyping. 
2) Feasibility measurements: Coverage of RACD or TPE in the target population, serious adverse event (SAE) 
reports, costing of every 10th RACD and TPE event, pill count in TPE arm. 
3) Acceptability assessment. Focus group discussions with TPE study participants and RACD/TPE surveillance 
team members. 
Sample size 
The sample size is based on the number of study localities that experienced at least one incident case of 
malaria in the previous season. Within 77 randomized localities, we expect that 63 localities will have an 
incident case of malaria and receive an intervention.  For the primary objective, we hypothesize that TPE will 
be more effective than RACD. At the current sample size the study is powered to detect a difference in 
cumulative incidence if incidence in the TPE arm is reduced 50% compared to the RACD arm. Incidence will 
be measured at the locality level and among the at-risk population, or all individuals in an enumeration area 
(EA) where at least one case was identified (expected to be approximately 55928 among total study 
population of 211,189, or a harmonic mean of 656 per locality (41,328 effective population). Secondary 
outcomes of seroprevalence and prevalence will be measured on individuals residing in Target Areas (total 
N=5400) with a harmonic mean of 60 persons receiving intervention per locality (3780 effective population). 
Primary outcome 
Incidence of malaria cases 
Secondary 
outcomes 
1) Seroprevalence by ELISA 
2) Prevalence of infection 
3) Proportion of imported to locally acquired incident cases 
4) Time to first post-intervention incident local case 
5) Transmission potential as measured by microsatellite genotyping 
6) Coverage of the intervention: proportion of the target population that receives a finger prick in the RACD 
arm or that receives an initial dose of DP in the TPE arm (intention to treat analysis) 
7) Adherence to DP in TPE arm. 
8) Prevalence of serious adverse events (SAEs) related to treatment 
9) Acceptance as evaluated by refusal rates and a qualitative assessment 

 
 
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10) Cost per intervention episode, per case averted 
Study personnel and institutions 
Principal Investigators 
 
Michelle Hsiang, MD 
Role in project: Principal investigator (PI) 
Deputy Lead, Operational Research, Malaria Elimination Initiative, UCSF Global Health Group 
Assistant Adjunct Professor, Pediatric Infectious Diseases, Department of Pediatrics, UCSF Benioff 
Children’s Hospital 
University of California, San Francisco 
Assistant Professor, Pediatric Infectious Diseases, Department of Pediatrics, University of Texas 
Southwestern Medical Center 
Phone Number: +1 415 595 5978 
Email: hsiangm@peds.ucsf.edu, michelle.hsiang@utsouthwestern.edu 
 
Simon Kunene 
Role in project: Co-PI 
Program Manager 
Swaziland National Malaria Control Program 
Swaziland Ministry of Health 
Phone Number: +268 2505 3804 
Email: manager@malaria.org.sz 
 
Roly Gosling, MD, PhD 
Role in project: Co-PI 
Lead, Malaria Elimination Initiative, UCSF Global Health Group 
Associate Adjunct Professor, Department of Epidemiology and Biostatistics 
University of California, San Francisco 
Phone Number: +1 415 597 8114 
Email: GoslingR@Globalhealth.ucsf.edu 
 
Other Key Personnel and Collaborators 
 
CHAI – Study team 
 
Nyasatu Ntshalintshali 
Study Role: Study Supervisor 
Regional Malaria Manager 
Clinton Health Access Initiative 
UCSF Global Health Group 
Umkhiwa Building, Lot 195, Karl Grant Street 
P. O. Box 6080, Mbabane H100  
Phone Number: +268 7608 8595 
Email: nntshalintshali@clintonHealthAccess.org 
 
TBD 
Study Role: Study Manager 
Malaria Program Manager 
Clinton Health Access Initiative 
UCSF Global Health Group 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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Umkhiwa Building, Lot 195, Karl Grant Street 
P. O. Box 6080, Mbabane H100  
Phone Number: TBD 
Email: TBD 
 
Bongani Dlamini 
Study Role: Research Associate 
Malaria Research Associate 
Clinton Health Access Initiative 
Umkhiwa Building, Lot 195, Karl Grant Street 
P. O. Box 6080, Mbabane H100  
Phone Number: +268 7621 6237 
Email: bongani.dlamini@clintonhealthaccess.org 
 
Lunga Dlamini  
Study Role: Field Coordinator 
Swaziland National Malaria Control Program 
Study Lubombo office 
Phone Number: +268 76545841 
 
Dr. Muhindo Kalungero 
Study Role: Study physician 
Institution Good Shepherd Hospital 
Phone number: +268 76345025 
 
Dr. Getahun Tesfa 
Study Role: Study physician 
Institution: Raleigh Fitkin Memorial Hospital 
Phone number: +268 76080680 
 
 
NMCP 
 
Nomcebo Mkhonta 
Study Role: Data focal point 
Chief Surveillance Officer 
Swaziland National Malaria Control Program 
Swaziland Ministry of Health 
Phone Number: +268 76261015 
Email: cso@malaria.org.sz 
 
Calsile Malambe 
Study Role: Field operations focal point 
Surveillance Supervisor 
Swaziland National Malaria Control Program 
Swaziland Ministry of Health 
Phone Number: +268 76146609 
Email: surveillance@malaria.org.sz 
 
Swaziland Laboratory Health Services 
 
Gugu Maphalala 
Study role: Collaborator 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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Principal Technologist - Research 
Swaziland Laboratory Health Services 
Swaziland Ministry of Health 
Phone Number: +268 7604 6747 
Email: sindydlamini36@yahoo.com 
 
Nomcebo Nhlabathi 
Study role: Molecular technologist 
Molecular Technologist 
Swaziland Laboratory Health Services 
Swaziland National Malaria Control Program, Swaziland Ministry of Health 
Phone Number: +268 761 83281 
Email: labtech@malaria.org.sz 
 
Cebsile Tshabalala 
Study role: Assistant Molecular technologist 
Swaziland Laboratory Health Services 
Swaziland National Malaria Control Program, Swaziland Ministry of Health 
Phone Number: +268 767 79424 
Email: labtech2@malaria.org.sz 
 
UCSF 
Lisa Prach, PhD, MPH 
Study Role: Research Specialist 
Department of Global Health Sciences, Global Health Group, Malaria Elimination Initiative 
550 16th Street, 3rd Floor 
San Francisco, CA  94158-2549 
Phone Number: +1 510-206-6847 
Email: lisa.prach@ucsf.edu 
 
Bryan Greenhouse, MD, MA 
Study Role: Co-Investigator 
Assistant Professor 
Dept. of Medicine / Div. of Infectious Diseases 
University of California, San Francisco 
Box 0811 
San Francisco, CA 94143, USA 
Phone Number: +1 415 317 2263 (m) 
Email: bgreenhouse@medsfgh.ucsf.edu 
 
Maxwell Murphy Laboratory Manager 
Dept. of Medicine / Div. of Infectious Diseases 
University of California, San Francisco 
Phone Number: +1 401 301 6679 
Email: acs0292@gmail.com 
 
Mi-suk Kang Dufour, PhD 
Study Role: Statistician 
Assistant Professor 
Division of Prevention Science 
University of California, San Francisco 
550 16th Street, 3rd Floor 
San Francisco, CA  94158-2549 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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Phone Number: +1 415 476 6287 
Email: mi-suk.kangdufour@ucsf.edu 
 
Kim Baltzell, RN, MS, PhD 
Study Role: Co-Investigator 
University of California San Francisco 
Associate Director, Global Health Science Master’s Program 
Associate Professor - Department of Family Health Care Nursing 
Phone Number: +1 415 215 7701 
Email: kimberly.baltzell@ ucsf.edu 
 
Ranju Baral, PhD 
Study Role: Economist 
Phone Number; +1 (917) 859-1733, Email: Ranju.Baral@ucsf.edu 
 
Grant Dorsey, MD, PhD 
Study Role: Senior Advisor 
Associate Professor 
Dept. of Medicine / Div. of Infectious Diseases 
University of California, San Francisco 
Phone Number: +1 415 206 8666 
Email: gdorsey@medsfgh.ucsf.edu 
 
Adam Bennett, PhD 
Study Role: Collaborator 
Assistant Professor 
Malaria Elimination Initiative, UCSF Global Health Group 
University of California, San Francisco 
Phone Number: +1 415 597 4981 
Email: bennettA@globalhealth.ucsf.edu 
 
Hugh Sturrock, PhD 
Assistant Professor 
Study Role: Collaborator 
Malaria Elimination Initiative, UCSF Global Health Group 
University of California, San Francisco 
Phone Number: +1 415 597 4669 
Email: SturrockH@globalhealth.ucsf.edu 
 
CHAI Global Team 
 
Deepika Kandula, MPH, MBA 
Study Role: Collaborator 
Associate Director, Malaria Elimination 
Clinton Health Access Initiative 
Phone Number: +263 7721 43358 
Email: dkandula@clintonhealthaccess.org 
 
Justin Cohen, PhD 
Study Role: Collaborator 
Director of Malaria 
Clinton Health Access Initiative 
Phone Number: 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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Email: jcohen@clintonhealthaccess.org 
 
Arnaud Le Menach, PhD 
Study Role: Collaborator 
Associate Director, Malaria Research 
Clinton Health Access Initiative 
Phone Number: 
Email: alemenach@clintonhealthaccess.org 
 
FIND 
 
Iveth Gonzalez, PhD 
Study Role: Collaborator 
Head of Malaria and AFS Programme 
Foundation for Innovative New Diagnostics 
Campus Biotech 
9 Ch. des Mines 
1202 Geneva, Switzerland 
Phone Number: 
Email: iveth.gonzalez@finddiagnostics.org 
 
LSHTM 
 
Chris Drakeley, PhD 
Study Role: Collaborator 
Professor of Infection and Immunity, Director of LSHTM Malaria Centre  
London School of Hygiene & Tropical Medicine 
Department: Immunology and Infection, Malaria Centre 
Phone Number: +44 20 7927 2289 
Email: chris.drakeley@lshtm.ac.uk 
 
Study members and responsibilities 
 
Principal Investigators 
 
Michelle Hsiang, Principal Investigator: Responsible for oversight of the project, study design, data 
collection management, ethical approval, oversight of laboratory procedures, data analysis, and report and 
manuscript writing. 
 
Simon Kunene, Co- Principal Investigator: Responsible for oversight of the project with a focus on 
coordination, and management of Global Fund/NMCP supported aspects of the project. Will provide input 
on study design, data analysis and report and manuscript preparation. Will ensure that study findings 
impact future program implementation as indicated. 
 
Roly Gosling, Co- Principal Investigator: Provide support to oversight of the project with focus on study 
design, data collection management, safety monitoring, data analysis, and report and manuscript 
preparation. Will align study activities with others involving the Malaria Elimination Initiative, UCSF Global 
Health Group. 
 
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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CHAI 
 
Nyasatu Ntshalintshali, Study Supervisor: Based in Swaziland at the CHAI office, will supervise all aspects of 
the project implemented in Swaziland (including coordination, field work, lab work, administration) and 
maintain relationships between GHG, NMCP, MoH, Swaziland Laboratory  Health Services, and CHAI. Will 
report to Charlotte Lejune (CHAI Swaziland Country Director) and Deepika Kandula. Will directly support 
collaboration between GHG, GHG-supported study staff, NCMP, and CHAI. Will support tablet development 
and maintenance in collaboration with NMCP Information Technology (IT) Officer. Will serve as focal point 
for in-country IRB. Participate in analysis and preparation of reports and manuscripts, and support 
translation of study findings into program implementation as indicated. Will help align study work with 
other CHAI-supported malaria work in Swaziland and elsewhere. 
 
TBD: Based in Swaziland at the CHAI office, the Study Manger will provide day to day management all 
aspects of the project implemented in Swaziland (including coordination, field work, lab work, 
administration) and maintain relationships between GHG, NMCP, MoH, Swaziland Laboratory  Health 
Services, and CHAI. Will report to Charlotte Lejune (CHAI Swaziland Country Director) and Nyasatu 
Ntshalintshali. Will directly support collaboration between GHG, GHG-supported study staff, NCMP, and 
CHAI. Will supervise Research Associate as well as UCSF Research Specialist when in Swaziland. Will support 
subcontract development and associated reporting. Will participate in analysis and preparation of reports 
and manuscripts, and support translation of study findings into program implementation as indicated. Will 
help align study work with other CHAI-supported malaria work in Swaziland and elsewhere. 
 
Bongani Dlamini, Research Associate: Responsible for overall study coordination on the group. Will report 
to Nyasatu Ntshalintshali. Will supervise Field Coordinator and Drivers. Will support development of study 
SOPs. Will work closely with the NMCP surveillance and vector management team to ensure that study 
goals and procedures are aligned with those of NMCP. Coordinate trainings and re-trainings.  Coordinate 
Pharmacovigilance and Adverse Drug Reactions Committee. Responsible for ordering supplies (including 
laboratory supplies) and accounting. Will assure to security and maintenance of study materials and blood 
samples. Will manage transportation. Will organize and lead weekly skype conferences as well as biannual 
meetings to include all study personnel and prepare meeting minutes. Work with Study Supervisor, Study 
Manager, and Principal Investigators to troubleshoot when challenges arise. Will help host and make 
arrangement for team members visiting from UCSF. 
 
Field Coordinator: Responsible for coordinating field data collection. Will work closely with NMCP Field 
operations focal point to ensure prompt response to cases for RACD or TPE and adherence to study 
protocols. Will ensure that procedures are aligned with standard NMCP surveillance and response 
procedures. Coordinates use of study vehicles. Will supervise field staff. Will coordinate all activities with 
Rural Health Motivators. Will coordinate and help implement data collection for the acceptability and cost-
effectiveness study. 
 
Study Physicians: Responsible for overseeing safety aspects of the study. Will review records of DP or AL 
administration as well as reports on adverse events. Will be on call to address adverse events as they occur. 
Will ensure that alternate medical care is available when not available. Will participate in and lead safety 
related portions of the Pharmacovigilance and Adverse Drug Reactions Committee.   
 
NMCP 
 
Nomcebo Mkhonta, Chief Surveillance Officer, Study Surveillance Focal Point: Oversees surveillance team 
and will provide support to Study Supervisor and Research Associate so that field work is completed 
thoroughly and accurately.  Will work closely with the Study Research Associate and Field Coordinator to 
ensure that case investigations, and RACD or TPE are performed in a timely manner and according to 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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protocol. Will help troubleshoot as issues arise. Will help align study with standard programme procedures. 
Will review data weekly with Data Manager and UCSF Research Specialist, ensuring data quality and 
completeness. Will join for biannual update meetings and participate in weekly calls as needed. 
 
Calsile Malambe, Surveillance Officer, Study Field Operations Focal Point: Oversees NMCP surveillance 
agents and serves as the focal point for field operations particularly in Lubombo. Will work closely with 
Study Research Associate and Field Coordinator to ensure that case investigations, and RACD or TPE are 
performed in a timely manner and according to protocol. Will help align study with standard program 
procedures. Will review field operations with the Field Coordinator and Research Associate on a weekly 
basis ensuring data quality and completeness. 
 
Swaziland Laboratory Health Services 
 
Gugu Maphalala, Principal Technologist (Research): Oversees laboratory technicians. Will ensure that study 
laboratory procedures including storage of samples and performing of laboratory assays, are integrated 
into regular workflow and structure of National Reference lab. Will support technologists and UCSF 
Research Specialist to ensure proper functioning of equipment and maintenance of laboratory space. 
 
Molecular Technologist: In close collaboration with other laboratory staff in in Swaziland Laboratory Health 
Services, will perform LAMP and ELISA on DBS collected through surveillance as well as for the TPE study. 
Will maintain blood samples in the lab, assure that adequate stocks of laboratory supplies are maintained, 
and liaise with NMCP or Research Associate to order new supplies as needed. Will enter results into 
database. Will work closely with UCSF Research Specialist to ensure timely and quality sample processing, 
and to trouble shoot as needed. Will participate in telephone conferences to share results and 
troubleshoot.  Will supervise Assistant Molecular Technologist and report to the Head of the Molecular Lab. 
 
Assistant Molecular Technologist: Will perform LAMP and ELISA on DBS collected through surveillance as 
well as for the TPE study. Will support Molecular Technologist to maintain blood samples in the lab, assure 
that adequate stocks of laboratory supplies are maintained. Will enter results into database. Will work 
closely with UCSF Research Specialist to ensure timely and quality sample processing, and to trouble shoot 
as needed. Will participate in telephone conferences to share results and troubleshoot.  Will report to 
Molecular Technologist and the Head of the Molecular Lab. 
 
UCSF 
 
Research Specialist: The UCSF Research Specialist will support study coordination while also leading data 
management, data analysis, and laboratory aspects of the project.  The Research Specialist will be based at  
UCSF but also spend 3-6 months/year based at the CHAI Swaziland office, reporting to Michelle Hsiang, and 
also to the Study Manager when in country. Specific activities will be to: support development of protocol, 
lead SOP writing with guidance from PIs, Study Supervisor, Study Manager, and support from the Research 
Associate. Support Research Associate and Study Manager in field coordination. Help Research Associate 
coordinate field trainings and re-trainings. Lead laboratory trainings and re-trainings as needed. Manage 
and perform laboratory assays, working closely with Molecular Technologist and Assistant Molecular 
Technologist. Track progress of LAMP testing for surveillance samples (passive and active). Prepare study 
updates for Swaziland Laboratory Health Services leadership. Manage data with NMCP IT Officer, perform 
data cleaning and monitor data quality. Perform data analyses and prepare reports and manuscripts. 
Submit and maintain UCSF IRB.  
 
Maxwell Murphy, UCSF laboratory manager: Will perform PCR, LAMP, serology, and genotyping at UCSF. 
Will support laboratory trainings and ordering of laboratory supplies. Will work with UCSF post doc to help 
troubleshoot when needed. Reports to Bryan Greenhouse. Will coordinate weekly meetings to review 
laboratory findings and plans. 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
13 
 
Bryan Greenhouse, Collaborator: Will provide guidance to the project, particularly with regards with PCR 
and serology work, as well spatial analysis, overall data analysis and manuscript preparation.  Will supervise 
Maxwell Murphy.  
 
Mi-suk Dufour: Will provide support to study design, data analysis, and preparation of reports and 
manuscripts.  Reports to Michelle Hsiang and will work closely with UCSF Research Specialist. 
 
Kim Baltzell, Qualitative Research Scientist: Lead the study design, survey development and protocol writing 
for the Acceptability Assessment. May supervise a student or other study staff on the study coordination, 
SOP development, data collection, analysis, and writing of the project. 
 
Ranju Baral, Economist: Lead the study design, protocol writing, and preparation of data collection tools for 
costing and cost-effectiveness study. Will support data analysis and writing of the project. 
 
Grant Dorsey, Senior Advisor: Will provide high-level guidance to the project particularly with regards to 
study design, troubleshooting with data collection, interim and final data analyses as well as manuscript 
preparation. 
 
Adam Bennett: Will provide input on study design and data analysis. Will align work with other surveillance 
and response activities of UCSF Global Health Group, Malaria Elimination Initiative. 
 
Hugh Sturrock: Will provide support on GIS related aspects of the study including spatial analysis. Will align 
work with similar reactive surveillance studies in Namibia. 
CHAI Global 
 
Deepika Kandula, Collaborator: Through supervision of Nyasatu Ntshalintshali, will provide guidance on 
collaboration between UCSF GHG, CHAI, NCMP, and MoH. Will provide input on study coordination and 
translation of study findings into program implementation as indicated. Will help align study work with 
other CHAI-supported malaria work in Swaziland and southern Africa. 
 
Justin Cohen, Collaborator: Will provide input on study design, data analysis and writing. Will help align 
work with CHAI- Global malaria elimination activities. Will help translate findings into policy level decisions. 
 
Arnaud Le Menach, Collaborator: Will provide technical support to research activities. Will help align work 
with CHAI- Global malaria elimination activities. Will help translate findings into policy level decisions. 
 
FIND 
 
Iveth González, Collaborator: Will provide technical support to LAMP activities including troubleshooting, 
quality assurance, and interpretation of findings. Will provide linkages to other sites using LAMP. Will liaise 
with Eiken Chemicals regarding price negotiation and ordering of LAMP kits. 
 
LSHTM 
 
Chris Drakeley, Collaborator: Will collaborate on serology studies, particularly with regards to experimental 
design, troubleshooting, analysis and interpretation of results. Will also support antigen procurement and 
exchange of ideas from ongoing work in London and elsewhere.  
 
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
14 
 
Administrative contacts 
 
Amanda Chung 
Study Role: Administrative Manager 
Program Manager, Malaria Elimination Initiative 
UCSF Global Health Group 
Mission Hall, 550 16th Street, 3F, Box 1224 
San Francisco, CA  94158  
Email: Amanda.chung@ucsf.edu 
 
Melissa Melgar 
Study Role: Administrative Analyst 
Program Manager, Malaria Elimination Initiative 
UCSF Global Health Group 
Mission Hall, 550 16th Street, 3F, Box 1224 
San Francisco, CA  94158  
Email: Melissa.melgar@ucsf.edu 
 
 
Darin Lum 
Study Role: Financial Manager 
Operations Manager 
UCSF Global Health Group 
550 16th Street, 3rd Floor 
San Francisco, CA 94158 
Email: darin.lum@ucsf.edu 
 
Thomas How 
Deputy Country Director 
Clinton Health Access Initiative 
Umkhiwa Building, Lot 195, Karl Grant Street 
P. O. Box 6080, Mbabane H100  
Email: thow@clintonhealthaccess.org 
 
 
Institutional review boards 
 
Scientific Ethics Committee (SEC), Swaziland Ministry of Health 
Address: PO Box 5, Mbabane 
Contact Person: Sisi Lukhele, Phone Number: +268 404 2431, Fax: +268 404 2092 
 
 
 
 
University of California, San Francisco, Committee for Human Research 
Address:  Office of Research, 3333 California Street Suite 315, San Francisco, CA 94118, USA 
Contact Person: Danica Helb, Phone Number: TBD 
 
University of Texas Southwestern IRB 
Address: 5323 Harry Hines Blvd., Dallas, TX 75390, USA 
Contact Person: Michelle Hsiang, Phone Number: 214-648-3060, Fax Number: 214-648-2171 
 
 
 
 
 
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
15 
 
Primary Funder 
 
Bill and Melinda Gates Foundation 
Contact Person: Diana Measham 
Senior Program Officer 
Malaria& NID, Bill and Melinda Gates Foundation 
Seattle Washington 
Email: Diana.Measham@gatesfoundation.org 
 
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
16 
 
Abbreviations & acronyms 
ACT 
 
artemisinin-based combination therapy 
AL 
 
artemether-lumefantrine, Coartem 
CHAI 
 
Clinton Health Access Initiative 
DBS 
 
Dried blood spot 
DOT 
 
directly observed therapy 
DP                        dihydroartemisin-piperaquine, Eurartesim 
EDTA 
 
ethylene-diamine-tetra-acetic acid 
EIR 
 
Entomological Inoculation Rate  
ELISA 
 
enzyme-linked immunoabsorbent assay  
FGD 
 
Focus Group Discussion 
FIND 
 
Foundation for Innovative New Diagnostics 
G6PD  
Glucose-6-phosphate dehydrogenase 
GEE 
 
Generalized Estimating Equation 
GPS 
 
global positioning system 
HH 
 
Household 
IRB 
 
Institutional Review Board 
IRS 
 
indoor residual spraying 
ITN 
 
insecticide treated bednet 
IPT 
intermittent preventative therapy 
ITT 
intention to treat 
LLIN 
 
long-lasting insecticide treated bed net 
LAMP  
loop-mediated isothermal amplification 
LSHTM  
London School of Hygiene and Tropical Medicine 
MDA 
 
mass drug administration 
MEI 
 
Malaria Elimination Initiative 
MoH 
 
Ministry of Health 
NMCP  
National Malaria Control Program 
OR 
 
odds ratio 
PI 
 
Principal Investigator 
PCR 
 
polymerase chain reaction 
Pan-LAMP 
LAMP assay detecting all Plasmodium species 
Pf 
 
Plasmodium falciparum 
Pf-LAMP 
LAMP assay detecting Pf only 
QTc 
 
corrected QT interval 
QT-NASBA 
quantitative nucleic acid sequence-based amplification 
RACD  
reactive case detection 
RDT 
 
rapid diagnostic test, a point of care assay to diagnose malaria 
RHM 
 
Rural Health Motivator 
RR 
 
relative risk 
SAE 
 
serious adverse event 
SLHS 
 
Swaziland Laboratory Health Services 
SMEAG  
Swaziland Malaria Elimination Advisory Group 
SNP 
 
Single Nucleotide Polymorphism 
SOP 
 
standard operating procedure 
SUSAR  
Suspected Unexpected Serious Adverse Reactions 
TPE 
 
Targeted Parasite Elimination 
UCSF 
 
University of California, San Francisco 
UCSF GHG 
UCSF Global Health Group 
UNICEF United Nations Children’s Fund 
UNISWA 
University of Swaziland 
UTSW  
University of Texas Southwestern 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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1 
Background 
 
1.1 
Malaria in Swaziland 
Swaziland is a small country in southern Africa that was the first country in sub-Saharan Africa to embark on 
an elimination campaign in 2008.[1]The country has made remarkable progress towards this goal, mainly 
through the roll-out of artemisinin-based combination therapies (ACTs), laboratory confirmation of all 
clinical cases using rapid diagnostic tests (RDTs), vector control using insecticide treated bednets (ITNs) and 
indoor residual spraying (IRS) in historically at-risk areas, health education, as well as an active surveillance 
program whereby household members and neighbors of index cases (individuals infected with Plasmodium) 
are screened using RDTs and treated if positive. The population at risk is 285,972, representing 30% of the 
population that lives in the Eastern endemic region (Figure 1). The number of locally acquired cases fell 
from 186 in 2010-11 to 84 in 2012-13. Imported malaria from Mozambique on the northeastern border is a 
challenge with the proportion of imported cases increasing from 51 to 71% during the same time period. 
The main parasite is Plasmodium falciparum (Pf) and the main vector is A. arabiensis. The high malaria 
transmission starts in November and ends in June; however, in recent years, the burden of local cases does 
not follow a seasonal pattern (Figure 2). 
 
 
 
1.2 
Challenges for Malaria Elimination 
In recent years, many countries like Swaziland have experienced reductions in malaria transmission in 
association with the scaling up of effective interventions and are now moving toward malaria elimination. 
[2] In malaria control, the goal is to reduce the clinical burden of malaria. In malaria elimination, the aim is 
to interrupt transmission, and it becomes necessary to treat not only symptomatic malaria but also 
asymptomatic infections that perpetuate transmission. Malaria transmission is geographically 
heterogeneous, thus elimination activities should target hot spots, or areas where the risk of future 
infection is highest. Hence, in the transition from control to elimination, enhanced surveillance and 
response is necessary to target hot spots with interventions to interrupt transmission. [3, 4] 
 
1.3 
Reactive case detection (RACD) 
For elimination, active surveillance in the communities around passively detected index cases, reactive 
surveillance or reactive case detection, is recommended as a strategy to identify secondary cases and hot 
Figure 2. Local and Imported cases by month and year 
Figure 1. Predicted risk of local case  

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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spots.[2-4]However, re-active surveillance can be low yield, labor-intensive, and costly.[4] Microscopy is 
being replaced by antigen-based rapid diagnostic tests (RDTs) that provide convenience but have 
limitations in the sensitivity to detect low parasite density and non-falciparum infections.[5, 6] PCR offers 
markedly improved sensitivity, but it requires hours of processing time, sophisticated technical skill, and 
expensive equipment to perform. Loop mediated isothermal amplification (LAMP) offers the sensitivity of 
PCR and is easier to perform but the requirement that samples be performed in a laboratory limit its 
usefulness for population level screening and treatment. 
 
Household members and neighbors around index cases harbor infection 
In Swaziland, reactive case detection involves the screening of household members and neighbors residing 
within 500 meters of the index case. Preliminary data from reactive case detection in Swaziland show that 
reactive case detection is a useful strategy to find asymptomatic infections and hot spots. From September 
2012 to April 2014, 74 additional infections were identified by LAMP in households and neighbors of 263 
index cases, resulting in a 28% increase in the detection of infections. Residence near the index case was 
associated with a higher risk of infection. Residing within 100 meters of index case was associated with a 
4.6 higher odds (95% CI 2.0 to 10.6) of infection compared to a baseline OR of 1.0 at 201-500m. Travel 
outside Swaziland and Mozambican nationality were associated with infection. However, excluding these 
individuals resulted in a similar finding: residing within 100 meters of index case was associated with a 4.2 
higher odds (95% CI 1.7 to 10.4) of infection compared to a baseline OR of 1.0 at 201-500m (Figure 3). 
 
 
 
Challenges with reactive case detection 
There have been challenges with reactive case detection. Firstly, achieving high coverage is challenging.  At 
present, coverage is about 60% of the individuals residing in the Target Area. Working individuals and 
school children are often not available when the study team visits, and some, albeit few, do refuse to give 
blood. Of those reached, the work is low yield. Of 8355 people screened from September 2012 to May 
2014, there have only been 42 (0.5%) RDT positives. Further, the sensitivity of RDT is poor for detecting 
low-density infections in asymptomatic individuals. The sensitivity of RDT compared to PCR as gold 
standard to detect these asymptomatic infection is 20%. LAMP increases the detection of infection by 1.6 
fold but the positive rate is still extremely low at 0.9%. Furthermore, due to the long turnaround time, it 
has been logistically challenging to treat in a timely fashion based on LAMP results.   
Figure 3. LAMP positivity by distance from index case  

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
19 
 
 
Also, it is suspected that even LAMP using dried blood spots is missing infections. Others have reported 
prevalence of infection in low transmission areas to increase by 1.4 fold when performing PCR using a 
higher volume of whole blood (200uL) compared to using 5uL of blood, about the amount of blood 
available from a punch from a DBS (Canier and Menard, unpublished data from Cambodia). Using PCR, 
Imwong et al. showed sometimes 50x higher sensitivity using 1 mL of blood compared to DBS. [7] 
Interestingly, 11.4% of reactive case detection events resulted in the identification of at least one additional 
infection by RDT.  16.7% of reactive case detection events resulted in the identification of at least one 
additional infection by LAMP. The apparent discordance between neighborhood versus individual level 
positivity rates suggests that there might be more infections that are being missed by even LAMP. To 
collect higher volumes of blood in a focal screening and treatment setting would be impractical. 
 
1.4 
Targeted parasite elimination (TPE) 
Given the limitations in a reactive case detection approach to identifying low-density infections, as well as 
the logistical challenges and cost associated with the screening process, presumptive treatment may be a 
more effective for reducing and interrupting transmission and more feasible to implement. Treatment may 
also have a prophylactic effect, particularly if the drug has a long half-life such as dihydroartemisinin-
piperaquine (DP). 
 
TPE is a form of mass drug administration (MDA); some have called it focal or targeted MDA. Instead of 
targeting large populations, TPE is directed at the highest risk individuals. In China, an “outbreak” or 
reactive TPE strategy that targets the household members and neighbors of index cases detected through 
passive surveillance has been shown to have likely contributed to interruption of transmission [8]. 
Previously when transmission was higher, entire counties were targeted. However, as transmission 
declined, local officials found that there was increased resistance to take drugs.  Household members and 
neighbors of index cases perceived a higher risk of malaria and were more likely to take drugs. Using this 
strategy, only about 20-50 individuals are targeted. Modeling suggests that coverage rates of at least 80% 
are needed for MDA to be effective, and targeting a smaller population size helps to maximize acceptance 
and adherence. 
 
When TPE should be implemented is not known and likely needs to be tailored to the local epidemiology. 
For example, in areas where there is a known reservoir of infection, using a proactive approach, e.g. before 
the transmission season, may help to eliminate the local reservoir to prevent onward transmission.  
However, in an area such as Swaziland, where a larger proportion of infections are imported and these may 
be seeding local transmission, a reactive or outbreak approach may be more effective and operationally 
feasible. 
 
1.5 
RACD vs. reactive TPE 
TPE is a promising strategy, but evidence does not yet exist to prove its effectiveness in Africa.1 There are 
also questions about the feasibility in terms of coverage, safety, acceptability to the community, and cost-
effectiveness. The advantages, disadvantages, and uncertainties around reactive case detection versus TPE 
are summarized in Table 1. 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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RACD 
TPE 
Rationale 
Identification/treatment 
low-density infections 
- misses low density infections 
+ does not rely on insensitive diagnostics 
+ may provide prophylactic effect 
Effectiveness 
Effectiveness to decrease 
transmission 
? not well established 
? not well established 
Feasibility 
 
Coverage of intervention 
+/- high acceptability facilitates good 
coverage but logistics of testing make 
high coverage challenging 
?ease of giving drug (without testing) may 
facilitate high coverage at first encounter, 
but logistics to complete 3 day course of 
drug but be challenging 
Acceptability 
+/- acceptability high but occasional 
refusals due to community dislike for 
giving blood 
+/-  anticipate some refusals to take drug, 
but acceptability may be high (e.g. 
sensitization from deworming campaigns) 
Safety using ACT 
+treatment of only test positive 
individuals is safe 
?treatment of many asymptomatic 
individuals is likely to be safe but not 
known 
Adherence to drug 
regimen 
+adherence among persons with 
known infection likely to be good  
- adherence among persons without 
known infection may be poor without 
some sort of directly observed therapy 
+ adherence may be good if treatment 
course is simple and short and perceived 
risk of malaria is high 
Cost-effectiveness 
+/- /?  costs high but usually a 
reasonable expense for a low 
transmission setting where the 
intervention can be targeted, not 
know where there could be cost-
savings 
?relative cost-effectiveness to the 
standard of care (RACD) not known 
 
 
1.6 
Drug regimens 
For an individual receiving TPE, the goal is to treat any existing reservoir of infection. Prevention of future 
infection, as possible given the half-life of the drug is an added bonus. In Swaziland, Artemether-
lumefantrine (AL or Coartem) is the first line therapy for Pf infection. The drug is generally well tolerated 
with minimal adverse effects. Doses are weight adjusted for children and a pediatric dissolvable version is 
available. One challenge is that the drug requires frequent administration. The second dose is administered 
8 hours after the first dose and then 1 dose is given twice daily for 2 more days. Also, due to lack of data, it 
is not indicated for children <5kg. Pregnancy during the first trimester is also a contraindication. Animal 
studies suggest that fetal absorption could lead to early pregnancy loss.  
 
Dihydroartemisinin-piperaquine (DP) is another safe and efficacious ACT regimen recommended by the 
WHO, and now recommended as a second line therapy for uncomplicated malaria in many countries. A 
recent Cochrane review of DP included 27 trials conducted between 2002 and 2010, enrolling 16,382 adults 
and children[9]. Most trials excluded infants aged less than six months or <5 kg as well as women who were 
pregnant or breastfeeding. In Africa, over 28 days, DP was superior to AL in that there was less treatment 
failure (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high 
quality evidence). Although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently 
lower with DP (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials, 5417 participants, 
high quality evidence). DP has a longer prophylactic effect on new infections that may last for up to 63 days 
(PCR-unadjusted treatment failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high quality 
evidence). In a previous review of DP, an association was noted between DP and prolongation of the QT 
interval in two small observational trials. Prolonged QT interval is a cardiac conduction defect that can 
sometimes lead to fatal arrhythmias[10]. However, in the same Cochrane review, compared to AL, no 
difference was seen in prolonged QTc, and no cardiac arrhythmias were reported. The frequency of other 
adverse events is probably similar with both combinations. 
Table 1. RACD vs. TPE  

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
21 
 
A Ugandan study of regimens available for intermittent preventative therapy (IPT) - an MDA strategy used 
in high transmission settings - identified DP as the most effective and best-tolerated regimen among school 
children [11]. Studies of DP in Uganda, including trials of very young children,[12, 13] children under 
ten,[14, 15] and school-aged children,[11] have found no increase in safety risk associated with DP 
consistent with other studies. Additional benefits of DP are that it can be administered just once daily and 
the long half-life of the partner drug piperaquine provides a protection again subsequent infection. Given 
these characteristics, DP has been suggested as an optimal candidate for community based MDA.[16] 
 
ACTs treat early gametocytes, the parasite stage responsible for subsequent transmission, but they do not 
treat mature gametocytes. The use of single dose primaquine in addition to ACT has been proposed as a 
strategy to help interrupt malaria transmission and it is currently recommend by WHO for symptomatic 
cases. However, no there are no guidelines for use in asymptomatics. The potential risk is hemolysis in 
individuals with underlying G6PD-deficiency. The unavailability of a simple and inexpensive rapid test for 
G6PD deficiency complicates the use of primaquine. Recent modeling suggests limited added benefit of 
primaquine to ACT alone in MDA. In an individual with asymptomatic parasitemia, ACT alone is likely to 
decrease the period of gametocytemia from months to about 2-6 weeks. The addition of primaquine will 
decrease that period to about one week. The slightly prolonged period of gametocytemia may not be 
relevant in a low transmission setting, particularly considering the potential risks. 
 
It has been proposed that MDA be administered by directly observed therapy of DOT, the rationale being 
that high coverage is critical to the success of MDA. Individuals who are not ill may be less adherent with 
medication, though adherence may be high when the perceived risk of infection is high such as in this study 
where a family member or neighbor will have recently been diagnosed with malaria. In a review of the 
published MDA literature, 12 successful studies reported the method of drug delivery and six utilized DOT 
or modified DOT. Drug distribution and observation was performed by community volunteers, local health 
workers, study authors and/or external organizations. [17] While strict DOT would ensure the highest 
adherence, it may not be practical for under-resourced malaria programs, particularly during the high 
transmission season when malaria staff are busy. Also, many individuals may be away at school or work 
during the day, making strict DOT challenging. In order to evaluate a strategy that can be feasibly 
implemented by malaria programs, drugs will be delivered using a modified DOT strategy.  
 
 
2 
Rationale 
 
Overall Rationale 
Current work in RACD suggests that it is useful in the identification of asymptomatic infections and 
hotspots, but there are some logistical challenges such as specimen collection, laboratory testing, and the 
need for return visits to treat asymptomatic individuals that were initially missed by RDT or microcopy but 
subsequently positive by molecular testing. Even with use of a molecular test such as LAMP that has a 
relatively fast turnaround time, subjects can be lost to follow-up. In addition, even molecular detection 
methods that are more sensitive than RDT or microscopy, they may still be missing very low parasite 
density infections. TPE has potential to be more feasible to implement and potentially more effective.  
 
Current strategies in Swaziland may not be sufficient to achieve elimination. In the past year, the number of 
locally acquired cases has increased relative to the two prior years (Figure 2). In order to achieve 
elimination in Swaziland, there is an urgency to pilot and evaluate new strategies. These findings will not 
only benefit Swaziland but also other eliminating countries. 
 
Rationale for the study design and selected study outcomes 
In this study, we will utilize a cluster randomized controlled study design to evaluate TPE and compare it to 
RACD in response to a passive identified index case.  As both locally acquired and imported infections 
contribute to Swaziland’s overall malaria burden and can cause onward transmission, individuals who 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
22 
 
acquired their Plasmodium infections within their community and abroad will both be included as index 
cases triggering a response.  
 
Effectiveness to interrupt transmission is an obvious outcome of interest for this study. Entomologic 
inoculation rate (EIR) is the gold standard measure of transmission; however, given the extremely low 
sporozoite rates among mosquitoes in low transmission settings such as Swaziland, this is an impractical 
measure for this study. Instead, for our primary outcome, we will measure the locality or cluster-level 
cumulative incidence of malaria cases over two transmission seasons. As secondary outcomes measures of 
effectiveness, we will also measure proportion of imported incident cases, as well as the time to first 
subsequent incident local case post-intervention. While incidence is a standard measure captured through 
health facility reports, it does not capture asymptomatic infections in the community. Therefore, we will 
also conduct a cross sectional survey toward the end of the study (estimated mid 2017) at the end of the 
transmission season to measure seroprevalence and prevalence. Finally, we will measure transmission 
potential as measured by relatedness of detected infections (from passive surveillance or the follow-up 
survey) using genotyping. These additional measures of transmission were not selected as primary outcome 
measures for several reasons. Seroprevalence and genotyping are exciting but still investigational 
diagnostic methods. Post-intervention prevalence of asexual and sexual stages may be too low for 
comparison though we will optimize our chances of detecting infection by collected higher volumes of 
blood and focusing in the highest risk areas (Target Areas). Nonetheless, we will evaluate these measures of 
effectiveness and may be able to find that one arm is superior to another for a particular outcome 
measure. These findings will be useful for Swaziland and for higher endemic settings where it might be 
easier to evaluate impact.  
 
For MDA to be effective, it has been proposed that at least 80% coverage of the target population is 
necessary[18]. A TPE experience from China  - targeting household members and neighbors of index case, 
as in this study – also suggests that high, generally >85% coverage, is needed to interrupt transmission [8]. 
There is no evidence to show that high coverage of TPE is feasible. Some challenges for high coverage of 
TPE versus RACD include willingness to take drug without knowing infection status and time it takes for 
staff to explain rationale for taking drugs. As high coverage is critical for effectiveness but is mainly an 
implementation challenge, a secondary goal of this study will be to determine the feasibility of achieving at 
least 80% coverage. We will also compare coverage to that achieved in RACD arm but we will not be 
powered to detect superiority of either approach (RACD coverage is expected to be at least 80%), or non-
inferiority of TPE given the high sample size that would be required.  
 
Other key aspects of feasibility will also be evaluated, including safety, acceptability, costs, and adherence. 
The ideal study to evaluate safety would involve a placebo arm. As the primary aim of this study is not to 
evaluate safety, and because there is already robust evidence to suggest that AL and DP are safe, including 
in asymptomatic individuals (e.g. with IPT), we will not include a placebo in the study but we will record 
serious adverse events in both the RACD and TPE arms. Acceptability of TPE vs. RACD will be evaluated 
through a qualitative assessment (the Acceptability Assessment) and quantitative analysis of refusal rates.  
The costs and relative cost-effectiveness of TPE vs. RACD will be evaluated by a detailed costing exercise. In 
order to evaluate a strategy that can be feasibly implemented by malaria programs, drugs will be delivered 
using a modified DOT strategy. Ingestion of the first dose of drug will be directly observed, and then the 
two subsequent doses will be left with the subject to self-administer at the same time on the subsequent 2 
days. During up to 2 return visits, study staff may: document reported intake, make reminders, or observe 
ingestion of the drug. Adherence to DP will be measured by performing a pill count amongst residents of 
Target areas surrounding the first index case detected in each transmission season in each locality in the 
TPE arm.  
 
Finally, cluster randomized controlled trials are the gold standard to compare health services and policy 
interventions, but significant inputs in time and resources are usually required rendering this study design 
impractical in program settings. However, as we propose in this project, when many cases are easily 
available (index cases reported through passive surveillance), existing infrastructure is in place (the current 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
23 
 
surveillance team), and the outcome measures can be feasibly measured (incidence will be collected 
through routine case reporting data, with secondary outcomes measures mainly collected through minimal 
follow-up visits), a cluster randomized controlled trial can be performed quickly and efficiently. 
3 
Study aims 
 
The overall objective of this proposal is to critically evaluate TPE vs. RACD as a surveillance and response 
strategy for malaria elimination.  
 
Our primary aim is to: 
Compare the impact of TPE versus RACD on incidence of malaria cases. We will test the hypothesis 
that TPE compared to RACD will result in a lower cumulative incidence. 
 
In addition, the following secondary aims will be addressed: 
 
Effectiveness: 
1. To compare the impact of TPE versus RACD on seroprevalence. We will test the hypothesis that 
TPE, compared to RACD, will result in lower exposure to malaria, as assessed by antibodies to 
antigenic markers of recent exposure near the end of the study period (expected mid 2017). 
2. To compare the impact of TPE versus RACD on prevalence of infection. We will test the hypothesis 
that TPE, compared to RACD, will be more effective in decreasing the prevalence of infection near 
the end of the study period (expected mid 2017). 
3. To compare the impact of TPE versus RACD on the proportion of imported incident cases. We will 
test the hypothesis that TPE compared to RACD will result in a higher proportion of imported 
incident cases. 
4. To compare the impact of TPE versus RACD on time to first incident local case subsequent to the 
intervention. We will test the hypothesis that TPE compared to RACD will result in a longer time to 
the first incident local case. 
5. To compare the impact of TPE versus RACD on transmission potential, measured by relatedness of 
strains by microsatellite genotyping. We will test the hypothesis strains detected in TPE versus 
RACD are less related to ancestor infections. 
 
Feasibility: 
1. To determine the feasibility of obtaining at least 80% coverage of TPE, and compare coverage to 
that attained using RACD. Coverage will be defined as receipt of and adherence to the first dose of 
DP within initial visits by the study team in the TPE arm or receipt of a blood test in the RACD arm.  
Our hypothesis is that the coverage attainable for TPE will be at least 80%. We also hypothesize 
that coverage for TPE will be equivalent to RACD but we will not be powered to prove this 
hypothesis. 
2. To measure adherence to a 3-day regimen of DP administered by modified DOT delivery system in 
the TPE arm. We hypothesize adherence will be 80%. 
3. To compare potential serious adverse events associated with TPE and RACD. We will test the 
hypothesis that the risk of serious adverse events will not be higher in individuals receiving TPE 
versus RACD.  
4. To compare the acceptability of TPE versus RACD as assessed by refusal rates and a qualitative 
assessment. We hypothesize that TPE will not be inferior to RACD in terms of acceptability and may 
be more desired. 
5. To compare the costs of TPE versus RACD. We will test the hypothesis that the costs per event will 
not be higher for individuals receiving TPE compared to RACD and may be cost-saving. 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
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4 
Study design & methods 
 
4.1 
Overview 
We will evaluate the impact and feasibility of TPE versus RACD as a surveillance and response strategy in 
the communities around passively detected index cases using a cluster-randomized trial umbrella study 
design. To facilitate operations of the trial and subsequent roll-out of the TPE intervention should it be 
shown to be effective and feasible, the randomization will occur at the administrative level of the locality. A 
total of 77 historically at-risk study localities or clusters will be included in the trial; 39 will be randomized 
to the TPE intervention, and 38 to the control intervention (RACD) (Figure 4). If new malaria hotspots are 
detected during the study period, these additional localities may also be included in the study at the 
discretion of the study team, in consultation with the Swaziland National Malaria Control Programme. 
These additional study localities will be randomly assigned to receive either the RACD or the TPE 
intervention. Target areas for localities randomized to receive TPE will be defined as all individuals residing 
within 200m of an index case that is detected in passive surveillance and resides in a TPE locality, with 
individuals residing immediately beyond 200m included if a minimum of 30 individuals are not enrolled 
within 200m. Target areas for localities randomized to receive RACD will be defined as all individuals 
residing within 500m of an index case that is detected in passive surveillance and resides in a RACD locality 
(as per current policy in Swaziland), while focusing on maximizing coverage within the immediate 200m 
radius around the index case. Per current policy, for individuals receiving RACD, blood will be collected for 
RDT and DBS and subjects testing positive on RDT will be referred to a local clinic for treatment with AL. In 
the TPE arm, blood will not be collected and presumptive treatment will be administered by modified DOT. 
Incidence data will be collected passively during the study period. For secondary outcome measures, in 
select Target Areas, a pill count will be conducted 7-10 days after the first visit day and a qualitative 
Acceptability Assessment will be conducted with study participants  at the time of the pill count. Passive 
monitoring for serious adverse events (SAEs) will occur in both the TPE and the RACD arms. To measure 
prevalence and seroprevalence, a cross sectional survey will be conducted in Target Areas near the end of 
the study (during the end-line survey, expected to take place mid 2017). Finally, to validate the serological 
markers, a follow-up survey will be conducted at 6-9 months among any individuals who were infected at 
baseline (index cases in both arms as well as secondary cases detected by RDT at baseline in the RACD 
arm). 
 
 
 
 
4.2 
Study site and study population 
The control and test interventions for this study will take place in the eastern half of Swaziland where RACD 
is currently conducted and focus in 77 localities (or sub-districts) which contains 431 EA (enumeration 
areas) but only 139 historically at-risk EA (Figure 4). To recruit Target Areas, the study will utilize the 
existing health infrastructure throughout Swaziland. Laboratory confirmed index cases present through 
passive surveillance and are reported through a toll free “977 Hotline.” Health facilities are shown in Figure 
5. Although all index cases are targeted for a follow-up case investigation (questionnaire with capture of 
GPS coordinates at the home of the index case), only index cases residing in the study localities will be 
enrolled in the study. Index cases not residing in study localities will not directly contribute to the study, but 
samples from these cases will also be genotyped (see section 12.7) to allow for more accurate classification 
of study subjects as having acquired their infection locally vs. being imported based on circulating parasite 
genotypes. Both locally acquired and imported cases can trigger the study intervention. The six catchment 
areas are covered by different surveillance agents with one officer covering Vuvulane and Ndzevane 
(Lubombo region) and another officer covering the other four catchment areas. 
4.3 
Randomization of localities (clusters) 
The randomization will be conducted by a member of the study personnel who is not directly involved in 
the field activities. A block stratified randomization method will be used to randomize the localities by risk 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
25 
 
rank as well as population within 139 historically at-risk EA. The local surveillance group has ranked 
localities into three groups by risk of incident malaria. Before the study is launched, additional at risk 
localities may be added if the area is confirmed to have had local cases in the past 3 years. The risk rank 
stratification will ensure equal distribution of higher and lower risk localities between the TPE and RACD 
arms. Randomization will take place before the study to facilitate sensitization of the community. All Target 
Areas within a randomized locality will follow the same intervention protocol. A list of the 77 randomised 
localities is shown in Table 2. The table also shows total population of the 431 EA in these 77 localities as 
well as the population in historically at-risk EAs (139 EA in 77 localities), and finally the expected at-risk 
population (105 EA in 63 localities with cases sept 2012-mar2015) used for sample size and power 
calculations (see section 14).. 
 
 
 
 
Figure 5. Map of Health Facilities. 
Figure 4. Study Localities outlined in black with 
historically at-risk enumeration areas (EA) 
shaded in yellow  
Study Localities 
Historically  
At-risk EAs 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
26 
 
Table 2. List of study localities with case reports over the last 3 years with risk rank and total population 
(431 EA in 77 localities) and expected at-risk population (based on 105 EA with cases sept 2012-march 
2015) 
Data from Sept 2012-March 2015 
 
Locality 
Code 
Unique Locality Name 
Risk 
Rank 
Local 
Cases  
Impor
ted 
Cases 
 
Incide
nt 
Cases 
(Local
+ 
Impor
ted) 
Second
ary 
Cases 
Total 
Populati
on 
Histori
cally 
at-risk 
popula
tion 
Expect
ed at-
risk 
popula
tion 
139000 
MANZINIMAFUTSENIMafutseniBhudla 
1 
0 
0 
0 
0 
3498 
1245 
0 
365000 
LUBOMBOTIKHUBATikh
ubaMatsenjwa 
2 
0 
0 
0 
0 
2293 
545 
0 
421000 
LUBOMBOLUGONGOLWENIMlawulaSiweni 
3 
0 
0 
0 
0 
176 
176 
0 
188000 
HHOHHONTFONJENIEmsahweniTimpisini 
2 
0 
0 
0 
0 
719 
719 
0 
428000 
LUBOMBOMHLUMENgomaneNgomane 
2 
0 
0 
0 
0 
2118 
330 
0 
487000 
LUBOMBODVOKODVWENIMacetjeniMphos
i 
3 
0 
0 
0 
0 
2419 
529 
0 
482000 
LUBOMBONKILONGOBig- 
BendMndobandoba 
3 
0 
0 
0 
0 
2470 
558 
0 
129000 
MANZINIMAFUTSENINgculwiniNtabamhlos
hana 
1 
0 
0 
0 
0 
1609 
637 
0 
378000 
SHISELWENIZOMBODZEZombodzeMahlaba
thini 
3 
0 
0 
0 
0 
1947 
344 
0 
195000 
HHOHHOMAYIWANEHerefordsJacks 
3 
0 
0 
0 
0 
1954 
492 
0 
140000 
MANZINIMAFUTSENIMafutseniEkuchwaleni 
1 
0 
0 
0 
0 
1824 
287 
0 
471000 
LUBOMBONKILONGOSithobelaNkonjwa 
3 
0 
0 
0 
0 
50 
50 
0 
180000 
HHOHHOTIMPISINIEmvembiliMvembili 
1 
0 
0 
0 
0 
2534 
436 
0 
419000 
LUBOMBOMHLUMESimunyeLusoti 
3 
0 
0 
0 
0 
4014 
576 
0 
426000 
LUBOMBOMHLUMETshaneniVuvulane 
3 
1 
0 
1 
0 
279 
279 
279 
350000 
LUBOMBOLUGONGOLWENISitekiMhlumeni 
3 
1 
0 
1 
0 
547 
503 
454 
438000 
LUBOMBOLOMAHASHALomahashaNgulube
ni 
1 
1 
0 
1 
0 
894 
394 
394 
425000 
LUBOMBOMHLUMETshaneniTshaneni 
3 
0 
1 
1 
0 
2366 
962 
441 
439000 
LUBOMBOLOMAHASHALomahashaMatfunt
ini 
1 
1 
0 
1 
0 
1404 
677 
677 
367000 
LUBOMBOMPOLONJENIMaphungwaneMag
wanyana 
1 
1 
0 
1 
0 
1779 
767 
767 
480000 
LUBOMBONKILONGOBig- BendMayaluka 
3 
1 
0 
1 
0 
2305 
353 
353 
366000 
LUBOMBOTIKHUBAMambaneMambane 
2 
1 
0 
1 
0 
4179 
686 
686 
406000 
LUBOMBOMPOLONJENIMpholonjeniLokha
yiza 
2 
1 
0 
1 
1 
5561 
592 
592 
412000 
LUBOMBOMPOLONJENINgcinaNyetane 
1 
1 
0 
1 
0 
612 
612 
593 
209000 
HHOHHOMHLANGATANENkambeniMabiya 
2 
1 
0 
1 
0 
541 
541 
541 
211000 
HHOHHOMHLANGATANESihhoyeMbangav
e 
2 
1 
0 
1 
1 
3722 
550 
550 
351000 
LUBOMBOMPOLONJENIMaphungwaneSigw
enyameni 
2 
0 
1 
1 
0 
2037 
494 
494 
383000 
SHISELWENIMATSANJENIMatsanjeniMaban
de 
2 
0 
1 
1 
0 
3410 
762 
762 
381000 
SHISELWENIMATSANJENINsalitjeSitilo 
2 
1 
0 
1 
0 
1901 
607 
607 
128000 
MANZINIMAFUTSENINgculwiniThulwane 
1 
1 
0 
1 
0 
1789 
630 
630 
147000 
HHOHHOMHLANGATANENkambeniNkamb
eni 
2 
1 
0 
1 
0 
1604 
399 
399 
359000 
LUBOMBOLUBULILubuliNsoko 
2 
0 
1 
1 
0 
2636 
501 
501 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
27 
 
362000 
LUBOMBONKILONGOBig- 
BendMahlabaneni 
3 
1 
0 
1 
2 
1493 
831 
224 
255000 
HHOHHOMAYIWANENdlalambiMbasheni 
3 
0 
1 
1 
1 
9079 
518 
518 
203000 
HHOHHONTFONJENIKaLomshiyoLomshiyo 
3 
1 
0 
1 
2 
1901 
368 
368 
120000 
MANZINIMKHIWENILuveMfangibhekile 
3 
1 
0 
1 
0 
2911 
532 
532 
116000 
MANZINIMKHIWENIKa-KhuphukaMliba 
1 
1 
0 
1 
0 
1885 
900 
900 
484000 
LUBOMBOSIPHOFANENISiphofaneniMadle
nya 
1 
2 
0 
2 
0 
7166 
891 
891 
475000 
LUBOMBOSITHOBELAGucukaMalayinini 
1 
2 
0 
2 
0 
5292 
972 
972 
183000 
HHOHHOTIMPISINIMashobeniMashobeni 
3 
2 
0 
2 
1 
1402 
485 
485 
346000 
LUBOMBODVOKODVWENISitekiSiteki 
3 
1 
1 
2 
2 
4031 
1369 
805 
441000 
LUBOMBOLOMAHASHATsambokhuluMaca
kula 
3 
2 
0 
2 
0 
1210 
826 
445 
347000 
LUBOMBOMPOLONJENISitekiSiteki 
1 
0 
2 
2 
1 
500 
500 
500 
464000 
LUBOMBOLOMAHASHAMambaneLucaceni 
1 
2 
0 
2 
1 
868 
485 
485 
114000 
MANZINIMKHIWENIKa-KhuphukaMnjoli 
1 
2 
0 
2 
0 
1053 
504 
504 
148000 
HHOHHOMADLANGAMPISINkambeniNkam
beni 
2 
3 
0 
3 
1 
1841 
509 
509 
416000 
LUBOMBOLOMAHASHAShewulaShewula 
2 
1 
2 
3 
0 
4578 
1349 
921 
403000 
LUBOMBOSIPHOFANENIKa-MkhweliKa-
Mkhweli 
2 
3 
0 
3 
1 
5488 
1394 
1394 
146000 
HHOHHOMHLANGATANEMhlangataneNhla
nguyavuka 
1 
2 
2 
4 
1 
3654 
1060 
1060 
182000 
HHOHHOTIMPISINIEmvembiliNkonjaneni 
1 
4 
0 
4 
2 
470 
470 
470 
189000 
HHOHHOTIMPISINIEmsahweniTimpisini 
2 
4 
0 
4 
0 
2467 
601 
601 
256000 
HHOHHOMHLANGATANELuhlangotsiniLuhl
angotsini 
2 
4 
0 
4 
0 
1215 
819 
819 
418000 
LUBOMBOMHLUMETabankuluTabankulu 
1 
3 
1 
4 
1 
1498 
562 
562 
437000 
LUBOMBOLOMAHASHALomahashaMafucul
a 
3 
4 
0 
4 
0 
1607 
741 
741 
363000 
LUBOMBONKILONGOBig- BendMatata 
3 
2 
3 
5 
0 
903 
726 
726 
417000 
LUBOMBOLOMAHASHAShewulaNhlungwini 
3 
0 
5 
5 
1 
1145 
692 
692 
212000 
HHOHHOMADLANGAMPISIMadlangempisi
Mandlangempisi 
2 
4 
1 
5 
1 
4550 
1093 
1093 
423000 
LUBOMBOHLANEHlaneHlane 
3 
4 
1 
5 
1 
3326 
844 
844 
435000 
LUBOMBODVOKODVWENIMpakaMpaka 
2 
3 
2 
5 
0 
6885 
3260 
1333 
463000 
HHOHHOMADLANGAMPISIDvokolwakoMa
nzana 
1 
5 
0 
5 
0 
6047 
1094 
1094 
207000 
HHOHHOMHLANGATANENyakatfoZwayimb
ane 
2 
2 
3 
5 
0 
4964 
1227 
1227 
407000 
LUBOMBODVOKODVWENIKa-LangaLukhula 
3 
2 
4 
6 
2 
9015 
2123 
926 
452000 
LUBOMBOLUBULINqandweniSicelwini 
2 
3 
3 
6 
3 
3557 
1536 
1536 
345000 
LUBOMBOLUGONGOLWENISitsatsaweniBh
andeni 
1 
7 
0 
7 
2 
2363 
1796 
1271 
427000 
LUBOMBOMHLUMEVuvulaneVuvulane 
1 
6 
1 
7 
3 
2853 
1765 
1765 
115000 
MANZINIMKHIWENIKa-KhuphukaKa-Bheni 
1 
8 
0 
8 
2 
2755 
1408 
1408 
432000 
LUBOMBODVOKODVWENIMalindzaSikhuph
e 
2 
6 
2 
8 
1 
3526 
2920 
2293 
404000 
LUBOMBODVOKODVWENISitekiKhushweni 
2 
5 
4 
9 
5 
1773 
799 
799 
349000 
LUBOMBOTIKHUBAMaphungwaneMhlabub
ovu 
1 
9 
1 
10 
5 
2172 
1115 
542 
150000 
HHOHHOMHLANGATANEMhlangataneZiny
ane 
1 
12 
2 
14 
6 
5869 
2328 
1745 
179000 
HHOHHONTFONJENIEmvembiliMvembili 
1 
13 
1 
14 
4 
1456 
689 
689 
440000 
LUBOMBOLOMAHASHALomahashaLomaha
sha 
1 
5 
10 
15 
4 
2485 
1960 
1573 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
28 
 
420000 
LUBOMBOLOMAHASHAShewulaNduma 
1 
13 
4 
17 
7 
3894 
3043 
3043 
481000 
LUBOMBONKILONGOBig- BendVillages, Ka-
Goboyane 
1 
2 
15 
17 
14 
890 
418 
418 
415000 
LUBOMBOLUGONGOLWENISiteki 
TownSiteki Town 
2 
9 
13 
22 
6 
4796 
2377 
2377 
436000 
LUBOMBOLOMAHASHALomahashaNkalash
ane 
1 
22 
3 
25 
3 
4154 
2307 
1886 
473000 
LUBOMBOSITHOBELAKa-
NgcamphalalaMahlabatsini 
1 
35 
6 
41 
20 
5011 
2222 
2222 
Totals: 
236 
97 
333 
108 
211189 
71661 
55928 
 
 
 
Unique Locality Name generated using names of Region, Constituency, Name1 and Name2 from Shapefiles. 
Risk ranks 1 to 3 (highest risk being risk rank 1) assigned by NMCP according to historical and recent transmission. 
Secondary case data based on LAMP data from reactive case detection, shown but not used for randomization as trigger for the 
study intervention, and primary outcome measure for the study is only based on incident cases.  
Total population data from 2007 census data.  
Historically at-risk population calculated as population of enumerations areas with recent and historical transmission. 
Expected at-risk population calculated as population of enumerations areas with recent cases (sept 2012-mar2015). 
 
4.4 
Target Areas 
The Target Area will be defined for TPE localities as all individuals residing within 200m of an index case 
that is detected in passive surveillance and resides in a TPE study locality, with individuals residing 
immediately beyond 200m included if a minimum of 30 individuals are not enrolled within 200m. This 
Target Area size was selected based on the existing RACD data whereby the mean number of individuals 
screened per index case was 32.  
 
The Target Area will be defined for RACD localities as all individuals residing within 500m of an index case 
that is detected in passive surveillance and resides in a RACD locality. The malaria surveillance team will be 
trained to focus on maximizing coverage within the immediate 200m radius around the index case. This 
Target Area size was selected based on the current RACD policy in Swaziland. 
 
Based on collected data on missing individuals, the estimated total number of individuals residing within 
200m of an index case is 53. Thus, coverage to date for RACD has been 60%. However return visits do not 
typically occur at off hours (mornings and evenings). Moving forward, at least one return visit must occur 
during off-hours to ensure better capture and to maximize the sample size. 
 
If a subsequent index case is reported in a target area (identified either through health facilities or RACD (all 
secondary cases identified in RACD become index cases)), the RACD intervention will not be repeated 
within 5 weeks (per current national policy). For the TPE arm, the intervention will not be repeated within 8 
weeks or more than twice within the past year (DP drug insert recommends no repeat course within 8 
weeks, and no more than 2 courses within one year).  
 
Target Areas that reside on the border between two localities that were randomized to different arms will 
receive the intervention according to the locality randomization of the index case. For outcome measures, 
some contamination of the intervention arm's effect may occur if a neighboring locality is randomized to a 
different intervention. In the analysis we will adjust for distance from an index case for whom the 
surrounding area received TPE intervention.  It will not be necessary to adjust for distance from an area 
where RACD was conducted because RACD is the current standard of care in all receptive areas of the 
country. 
 
Based on past surveillance data, we expect about 134 index cases per study year. To demonstrate the 
seasonal pattern, Figure 6 shows the number of RACD events by month from 2012 to 2014. Due to capacity 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
29 
 
limitations, not all eligible index cases received RACD. However after more staff were hired, almost all 
eligible index cases received RACD. 
 
 
 
Figure 6. RACD events by month 
 
 
0	
5	
10	
15	
20	
25	
30	
35	
40	
45	
50	
9	 10	 11	 12	 1	
2	
3	
4	
5	
6	
7	
8	
9	 10	 11	 12	 1	
2	
3	
4	
Number	of	RACD	events	
Month	of	Index	case	presenta on	
RACD	performed	
RACD	not	done	
2012	
2013	
2014	

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
30 
 
4.5 
Inclusion and exclusion criteria 
 
Table 3. Inclusion and exclusion criteria 
 
Inclusion criteria 
Exclusion criteria 
Index case 
(as trigger for 
RACD or TPE 
in their 
household 
members 
and 
neighbors)  
 Malaria infection (either locally transmitted or 
imported) detected at a health facility through 
passive surveillance, and 
 Resided in a study locality. 
 Malaria infection identified through screening. 
 
RACD 
intervention 
 Non-index case, and 
 Resided or spent at least one night in the Target 
Area in the past 5 weeks. 
 Target Area overlaps with prior Target Area that 
received the RACD intervention within the past 5 
weeks. 
TPE 
intervention 
 Non-index case, and 
 Resided or spent at least one night in the Target 
Area in the past 5 weeks. 
 
 Target Area overlaps with prior Target Area that 
received the TPE intervention within the past 8 
weeks, and 
 For DP specifically (though still eligible for 
interview): 
— 
Temperature > 38.0⁰C, report of fever in the past 
48 hours, or other illness (will be referred to the 
nearest health facility for further evaluation) 
— 
Pregnancy, breastfeeding, and women who have 
had menarche but no menses in the past 4 
weeks 
— 
Children <9 months of age or <7 kg 
— 
Known allergy or history of adverse reaction to 
DP  
— 
Already taken 2 courses of DP in the past year or 
taken 1 course within the past 2 months 
— 
Moderate or severe renal or hepatic insufficiency 
— 
Currently with severe malaria 
— 
Family history of sudden death or of congenital 
prolongation of the QTc interval. 
— 
Known congenital prolongation of the QTc-
interval or any clinical condition known to 
prolong the QTc interval. 
— 
History of symptomatic cardiac arrhythmias or 
with clinically relevant bradycardia. Any 
predisposing cardiac conditions for arrhythmia 
such as severe hypertension, left ventricular 
hypertrophy (including hypertrophic 
cardiomyopathy) or congestive cardiac failure 
accompanied by reduced left ventricle ejection 
fraction. 
— 
Electrolyte disturbances, particularly 
hypokalaemia, hypocalcaemia or 
hypomagnesaemia (including vomiting in child) 
— 
Recent treatment with medicinal products 
known to prolong the QTc interval that may still 
be circulating at the time that DP is commenced 
(e.g. mefloquine, halofantrine, lumefantrine, 
chloroquine, quinine and other antimalarial 
agents)  
Pill count 
 Resides in the first Target Area to receive the 
intervention for each locality during each 
transmission season, and 
 Received antimalarial drugs through the TPE 
intervention. 
 Resides in a locality randomized to the RACD arm. 
Acceptability 
Assessment 
 Received the TPE intervention, or 
  Member of surveillance team in both RACD and 
TPE arms. 
 < 18 years of age. 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
31 
 
6-9 month 
Follow-up 
visit 
 Index case residing in either RACD or TPE study 
locality, or 
 Secondary case (RDT or LAMP positive at the RACD 
intervention), or 
 Non-infected control (RDT and LAMP negative at 
the RACD intervention). 
 Non-index resident of a locality randomized to the 
TPE arm. 
End-line 
survey (end 
of study) 
 All individuals who resided or spent at least one 
night in the Target Area in the past 5 weeks 
(includes index cases and individuals who did not 
receive a study intervention). 
 None. 
NOTE: Medicinal products that are known to prolong the QTc interval include: 
 
Antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol). 
 
Neuroleptics (e.g. phenothiazines, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide, or thioridazine), antidepressive 
agents. 
 
Certain antimicrobial agents, including agents of the following classes: - macrolides (e.g. erythromycin, clarithromycin), - fluoroquinolones (e.g. 
moxifloxacin, sparfloxacin), - imidazole and triazole antifungal agents, - and also pentamidine and saquinavir. 
 
Certain non-sedating antihistamines (e.g. terfenadine, astemizole, mizolastine). 
 
Cisapride, droperidol, domperidone, bepridil, diphemanil, probucol, levomethadyl, methadone, vinca alkaloids, arsenic trioxide 
5 
Baseline Preventative Interventions – LLINs and IRS 
 
Individuals residing in endemic areas will receive or will have received LLINs and IRS per standard 
procedures by NCMP. IRS is conducted once yearly before the transmission season, usually beginning in 
August and running through to February To maximize benefit of IRS to study participants, study staff with 
work with the vector control program to ensure high coverage of all target communities. During visits by 
spray teams, households will be sprayed if people are home.  If not, return visits will be conducted to 
ensure a high coverage of IRS.  LLINs will be provided to households that do not already have functioning 
insecticide treated bednets. We will monitor coverage of ITNs and IRS as well as timeliness of IRS. 
 
 
6 
Enrollment 
 
6.1 
Sensitization 
Prior to starting the study, we plan to build awareness, secure commitment, and encourage participation 
from stakeholders at the national, regional, and local level.  We will meet with members of the Ministry of 
Health, NMCP, Swaziland Laboratory Health Services, Swaziland Malaria Elimination Advisory Group for 
both Case Management and Surveillance, the Regional Health Management Teams from the receptive 
regions, local chiefdoms through Regional Administrators, and other appropriate officials in the health 
sector.  Once approval has been granted by the appropriate officials, we will sensitize health facility 
workers and rural health motivators with an information sheet (Appendix A).We will also work with the 
health promotion and surveillance teams in sensitizing the community members in the localities selected 
for TPE. 
 
The Target Areas for this study (whether randomized to TPE or RACD) will be identified as they have been 
for the current RACD program, therefore, there will be little time for sensitization prior to the visit by the 
study team. With the current RACD program, the index case is contacted by telephone before the visit and 
asked to notify other members of the household about the upcoming visit. Although neighboring 
households are not notified, refusals are rare. The overall high acceptance is thought to be due to 
perceived risk of malaria when it is known that a household member or neighbor had malaria.  This 
perceived risk may facilitate acceptance of TPE. Indeed during RACD, community members have sometimes 
requested drugs when they do not want to give blood for screening.  Also, Swaziland provides free malaria 
prophylaxis to individuals travelling to Mozambique. It is possible that familiarity with this strategy will also 
help facilitate acceptability of TPE. To further facilitate acceptability we will utilize rural health motivators. 
The study team will contact the rural health motivator prior to the visit and ask him or her to notify all 
eligible participants about the project. Rural health motivators will have already been sensitized about the 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
32 
 
project (Appendix A). This pre-visit notification to all community members in the Target Area by the rural 
health motivator will also help improve coverage.  
6.2 
Identification of Target Areas (through immediate case notification and Case investigation of the 
index case) 
Study participants will be recruited starting with index cases that are identified through a Case report/Case 
investigation system. After a laboratory confirmed index case is identified at a health facility, the health 
worker completes an Immediate Notification Form investigation (Appendix B) and reports the case through 
the country’s toll-free Immediate Disease Notification System (977). The NMCP Surveillance Team is 
notified by an SMS text. A Surveillance Agent visit the health facility to collect the DBS, RDT, and slide, and 
visits the home of the index case within 48 hours and to administer a questionnaire and capture GPS 
coordinates, as part of the case investigation (Appendix C). Also, if a DBS was not collected by the health 
facility at the time of presentation, the surveillance agent also collects a DBS.  
 
If the index case resides in a study locality, that neighborhood or Target Area will become enrolled in the 
study. During intervention resident enrollment, the study staff will begin recruiting study participants from 
the home of the index case, and then move on to neighboring households. On the first visit, the team will 
map the location of the index case and visualize the 200 or 500 meter radius on google maps while in the 
field. The team will attempt to enroll all individuals residing within 200 or 500 meters, depending on 
whether that Target Area has been randomized to receive TPE or RACE. On the second visit, the team must 
come at a time during which persons previously absent will be present (usually morning or late 
afternoon/early evening) and re-visit all households in which 100% coverage was not achieved. If 100% 
coverage is obtained, that Target Area intervention is complete. If not, on the 3rd visit, the team must also 
come at a time during which persons previously absent will be present (usually morning or late 
afternoon/early evening) and the study team must re-visit households in which 100% coverage was not 
achieved. If during this 3rd visit 30 individuals are not yet enrolled (participated in study intervention), the 
team will move onto the next closest house (but not beyond 500m) to screen individuals until at least 30 
individuals are enrolled (but completing the screening in all individuals in that last household). 
6.3 
Informed consent 
Informed consent will not be obtained from index cases for the Case Investigation as such procedures are 
part of standard surveillance in Swaziland. Informed consent will also be obtained from the household 
members and neighbors of the index case during the intervention resident enrollment visit. Informed 
consent will be obtained at all follow-up visits (the 6-9 month follow-up visit to collect blood for serologic 
testing and the end-line survey visit near the end of the study, expected mid 2017) for that day’s study 
activities. Additionally, for the qualitative Acceptability Assessment (which will take place during the follow 
up pill count visit or 7-10 days after the intervention ), informed consents will be obtained from selected 
residents at least 18 years of age in TPE Target Areas.  Additionally, informed consent will be obtained from 
members of the surveillance team in both RACD and TPE arms for focus group discussions at 3 months 
intervals for the duration of the study. 
 
Consents will be conducted in the participant's house prior to study activities. Consents will be collected 
from all members of the household at once. Parents will be able to sign one form to consent for themselves 
and all of their children at once. Separate consent forms will be signed by each additional adult member of 
the house. Also, separate assent forms will be signed by each minor (12-17yrs).Informed consent will be 
conducted in the local language, SiSwati, or English, and a translator will be used if necessary (e.g. for 
Portuguese, though most Mozambicans are able to speak SiSwati). Consent forms will be available in 
English and SiSwati. As part of the informed consent process, study personnel will assess the participants 
understanding of the study procedures that were explained by the study staff using a checklist comprised 
of key components of the study. Subjects scoring at least 80% on the checklist will be asked to sign the 
written consent form.  If the subject scores less than 80%, the consent discussion will be repeated, before 
asking for a signature. The consent form will be read again, focusing on areas where understanding was 
limited, and encouraging the subject to ask questions. If the subject is unable to read or write, their 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
33 
 
fingerprint will substitute for a signature. If an interpreter is used, their signature will also be obtained. The 
informed consents that will be conducted and the study activities they cover are listed in Table 4. 
 
For individuals <18 years of age, informed consent will be obtained from one parent or guardian, as is 
customary in Swaziland. Assent for adolescents 12-17 years of age will be obtained, as is customary in 
Swaziland. 
 
Table 4. Informed Consents 
Subject/Activity 
Informed consent covers 
Index case 
 
 
No informed consent as case investigation (questionnaire and DBS 
collection for malaria testing) is part of standard surveillance. 
Resident Enrollment, 
Intervention (Appendices E, F) 
 
All residents of Target 
Areas 
RACD 
TPE 
 At enrollment:  
 Brief questionnaire and GPS 
mapping. 
 Intervention blood testing 
with RDT & referral to health 
facility if RDT positive.  
 Storage of blood with DBS, 
and with microtainer 
collection in RDT positives. 
 At enrollment: 
 Brief questionnaire and GPS 
mapping. 
 If eligible for DP, 3 day course 
of DP by modified DOT. 
 If not eligible for DP, blood 
testing by RDT & referral to 
health facility if RDT positive. 
Storage of blood with DBS, 
and with microtainer 
collection in RDT positives. 
 7-10 days post intervention: 
 Potential pill count. 
6-9 month Follow-up  
(Appendix L) 
 
All Index cases residing 
in Target Areas. 
 
All secondary cases and 
some RDT-negative 
controls from RACD 
localities. 
 At 6-9 months after diagnosis (Note: The study team will seek consent to 
collect a 6-9 month sample from index cases and RDT-positive residents 
who were diagnosed within in the 9 months prior to study launch): 
 
Follow-up blood testing with RDT & referral to health facility if RDT 
positive. 
 
Storage of blood with microtainer and DBS. 
End-line survey (Appendix N) 
 
All residents of Target 
Areas. 
 At end-line survey, end of study:  
 Brief questionnaire and GPS mapping. 
 Follow-up blood testing by RDT & referral to health facility if RDT 
positive. 
 Storage of blood with DBS. 
 Brief interview. 
Acceptability Assessment  
(Appendix U) 
 
TPE Study participants 
selected for inclusion in 
the Acceptability 
Assessment 
 
Surveillance team 
members in both RACD 
& TPE arms 
 TPE Participants: qualitative focus group discussions 7-10 days after 
intervention at pill count visits. 
 Surveillance team: focus group discussions every 3 months for duration of 
study. 
7 
Study intervention 
 
A schematic of the study interventions is shown in Figure 7. 
7.1 
Household-level questionnaire 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
34 
 
A household will be defined as any single permanent or semi-permanent dwelling structure acting as the 
primary residence for a person or group of people that generally cook and eat together.  Some households 
may include members who sleep in other dwelling structures within the same compound, if the members 
are still dependent on the head of household in the main household. A household resident will be defined 
as any person who has spent at least one night in the household in the past 5 weeks. 
 
For each household enrolled in the study, a brief questionnaire will be conducted with the acting household 
head. The purpose of this questionnaire will be to determine household size and obtain information about 
the household structure as well as coverage of vector control interventions. If certain individuals are not 
present, the questionnaire will also aim to schedule a more suitable time to reach absent individuals. 
Separate questionnaires will be used for the RACD and TPE arms.  The RACD household level questionnaire 
will collect blood testing results. The TPE questionnaire will collect information about doses of drugs 
administered (Appendix K). 
 
7.2 
RACD arm - Perform RDT and refer secondary cases to health facilities 
Individuals residing in RACD clusters will be tested by RDT using the Pf-specific First Response RDT during 
the intervention visit. At the time that blood is collected for RDT testing, the same finger prick will be used 
to generate a slide and dried blood spot. Four spots of blood will be collected for each DBS. Subjects testing 
positive by RDT will be referred to the closest health facility for treatment according to national policy (first 
line AL, second line Oral quinine for uncomplicated malaria). 
 
Secondary cases detected by RDT will become index cases (using the same unique study ID) and receive a 
case investigation. For these secondary cases, a second finger prick will also be performed to collect 250uL 
blood in a microtainer.  These secondary cases will also be invited to participate in the 6-9 months follow-
up as well as the end-line survey at the end of the study (expected mid 2017). 
 
The microtainer samples collected from secondary cases will be used to develop serologic and genotyping 
methods. The rationale for a larger volume of blood is that serum is the gold standard sample for serologic 
assessment. Although DBS collection is more practical and has been validated for use in population level 
serologic assessments (as will be done at the end-line survey at the end of the study, expected mid 2017) 
[19], this microtainer sample will be used to develop and validate our serologic assay. A larger volume of 
blood draw will also facilitate genotyping. Secondary cases are mainly asymptomatic individuals with low-
density infections. In our experience, microsatellites do not usually amplify well when using DBS in 
asymptomatics. 
 
7.3 
TPE arm - Administration of DP 
Individuals enrolled in the TPE arm will be interviewed to determine if it is safe for them to receive DP 
(Eurartesim, Sigma Tau).  
 
For individuals who can safely be given DP, the dose is one daily dose for 3 consecutive days. Participants 
will be weighed at enrollment, and DP will be dosed according to weight-based guidelines (Appendix Q). 
Half-strength DP tablets (20/160mg) or full strength DP tablets (40/320 mg) that have been cut into half will 
be given to children weighing <12kg, and full-strength tablets (40/320mg) will be given to those weighing 
>12kg.  
 
The first DP dose will be administered by DOT. Subsequent doses will be left with the subject or guardian 
and subjects will be instructed to self-administer at the same time on Days 2 and 3. If a dose is missed, it 
should be taken as soon as realized and then the recommended regimen continued until the full course of 
treatment has been completed. No more than one dose on the same day should be taken to make up for 
any missed dose. Study staff will be revisiting neighborhoods for up to 2 additional days to enroll more 
subjects.  On those days, the study staff may remind subjects. 
  

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
35 
 
The drug insert suggests that DP should be taken orally with water and without food, the concern being 
that food may increase absorption of piperaquine. However, there is limited data to support this practice. A 
trial by Lwin et al. in Thailand compared DP ingestion with or without chocolate milk and found both 
approaches to be safe, with no difference in drug levels or efficacy. [20] Several trials from Africa using DP 
in symptomatic as well as asymptomatic individuals have not required administration without food and 
have not found safety risks.[11-15, 21]. Given the limited data to show adverse events with food 
administration, and the practical challenges of administering DP without food in the field, we will not 
impose this restriction. 
 
The shelf life of DP is 24 months. Expired drugs will not be used.  As recommended, DP will not be stored 
above 30°C.  
 
If an individual cannot safely be given DP, that individual will not be given medication for presumptive 
treatment. Pregnant women and breastfeeding women will be excluded.  All girls ≥10 years of age will also 
be asked about menses. Those who have had menarche but have not menstruated in the past 4 weeks will 
also be excluded. Infants <9 months of age or <7 kg will also be excluded. For infants and children unable to 
take tablets, drugs will be crushed, mixed with water and administered as a suspension. No more than two 
courses of DP may be given within a 12-month period. Additionally, a second course of DP should not be 
given within 2 months after the first course due to the long elimination half-life of piperaquine. Other 
contraindications include: severe malaria, young children who vomit (electrolyte disturbances can increase 
QTc), heart problems or rhythm disturbances, kidney or hepatic insufficiency, recent treatment with certain 
medications (antiarrhythmics, neuroleptics, antibiotics, non-sedating antihistamines, antimalarial agents, 
and others (cisapride, droperidol, domperidone, bepridil, dephemanil, probucol, levomethadyl, methadone, 
vinca alkaloids, and arsenic trioxide). 
 
Individuals who cannot safely be given DP will be tested by RDT using the Pf-specific First Response RDT 
during the intervention visit. At the time that blood is collected for RDT testing, the same finger prick will be 
used to generate a slide and dried blood spot. Four spots of blood will be collected for each DBS. A second 
finger prick will be used to collect microtainer blood samples from RDT-positive individuals.  Subjects 
testing positive by RDT will be referred to the closest health facility for treatment with a drug that is safe 
for them according to national policy. 
 
7.4 
Management of sick participants 
During the intervention, individuals who have a temperature of > 38.0⁰C, report having a fever in the past 
48 hours, or have other illness will be referred to the nearest health facility for further evaluation. 
 
7.5 
Adherence assessment 
In order to evaluate adherence to DP via modified DOT in the TPE arm, study staff may return in 7-10 days 
to perform a pill count. There is limited data on the expected adherence to the 3 day regimen among 
asymptomatic individuals. Among symptomatic individuals, the reported adherence ranges from 39 to 
100%. [22] Due to the return visits by study staff, engagement of rural health motivators, and perceived risk 
among individuals residing near an index case, we hypothesize that adherence to a 3 day regimen will be 
80%.  
 
 

 
 
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36 
 
 
Figure 7. Study procedures. 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
37 
 
8 
Adverse event monitoring 
 
8.1 
Overview 
The safety risks associated with participation in this trial are expected to be minimal. AL, the current 
standard of care in Swaziland, is generally well tolerated and, at least by passive monitoring, has been 
associated with only minimal adverse effects in Swaziland. DP is one of the ACT regimens recommended by 
the WHO[23], and is recommended as a second line treatment for uncomplicated malaria in many 
countries[24].The safety and tolerability of DP have been closely evaluated in clinical trials evaluating DP for 
treatment and prevention of malaria, and DP has been shown to have an excellent safety profile[10, 11, 25, 
26]. In the TPE arm, prior to drug administration, subjects will be asked about known allergy, past adverse 
reactions felt to be associated with treatment, and other contraindications (see Table 3) and will be 
excluded from taking drug if such a history is reported. 
 
Adverse event monitoring of SAEs potentially related to AL or DP will occur passively. Subjects will be 
instructed to seek care at their local health facility if they experience any serious adverse reactions that 
may be related to AL or DP. Health facility physicians will determine if a participant should continue or stop 
treatment due to safety concerns. Health facility staff will be asked to notify study staff of all adverse 
events. For any adverse events that are reported in either arm, we will attempt to assess causality by 
collecting additional data on the relationship between the drug and the event. This information will be 
reported and reviewed by the Pharmacovigilance and Adverse Drug Reactions Committee (the Data Safety 
& Monitoring Board for this study). 
 
8.2 
Definitions 
 
Serious adverse event (SAE): An experience that results in (1) death during the study period; (2) life-
threatening experience (one that puts a participant at immediate risk of death at the time of the 
event); (3) inpatient hospitalization during the study period; (4) persistent or significant disability or 
incapacity, (4) specific medical or surgical intervention to prevent one of the other serious 
outcomes listed above.  
 
 
Suspected Unexpected Serious Adverse Reactions (SUSAR):  An adverse drug reaction that is 
suspected of having a causal relationship to the trial medication and is unexpected 
 
8.3 
Passive identification of SAEs 
Participants will be instructed to seek care at the nearest health facility if they develop a serious illness (see 
Appendices E & F). Also, the national emergency ‘977 Hotline’ can be used to allow participants to receive 
care for urgent medical conditions. Health facility physicians, in consultation with the study physician, will 
decide if a participant should continue or stop treatment due to safety concerns. For less serious 
symptoms, participants should contact the attending study nurse to advise and quickly attend to the 
participant’s needs. Study personnel will assist with referrals as needed. Participants will be instructed to 
notify their attending Study Nurse with any adverse events that may be related to either AL or DP. Health 
facilities will also be notified about the study and asked to call the attending Study Nurse who will be 
available by telephone 24 hours/day, 7 days/week. 
 
For any potential serious adverse events that are reported in either arm, the study team will arrange 
follow-up visits within 24 hours at a convenient location (at home, school, or a health care facility) to 
complete an SAE form. This information will be reported to and reviewed by the Pharmacovigilance and 
Adverse Drug Reactions Committee. 
 
8.4 
SAE report forms 
For each serious illness identified, an adverse event report form will be completed (Appendix S).  The 
following information will be recorded for all experiences that are reported:  
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
38 
 
― Description of the subject (ID number, age, gender, weight) 
― Name of the event 
― Description of the event and management of illness 
― SAE criteria met 
― Date of event onset, date of resolution, and date event reported 
― Maximum severity (Appendix T) 
― Causality and expectedness  
― Drug history (names, doses, dates administered for all drugs taken one month prior) 
― Past medical history, including known allergies 
― Management and outcome of the event 
 
8.5 
Expedited reporting of SAEs and SUSARs 
All reports of serious adverse events that are classified as at least ‘possibly’ related to administration of 
study drugs, including those classified as possibly, probably, or definitely related, and reports of all 
suspected & unexpected serious adverse reactions will be entered into a database and a listing of these 
events will be submitted to the IRBs, the Pharmacovigilance and Adverse Drug Reactions Committee, and 
the drug manufacturer according to their guidelines for expedited reporting.   
8.6 
Management of participants with SAEs 
If a study participant experiences a SAE classified as related to a study drug, decisions on whether the 
participant should complete treatment or stop will be made by the health facility worker providing 
treatment at the health center. Health facility workers may consult with the Study Nurse or the Study 
Physician. Factors that will be considered will include the type and severity of the event, and suspected 
strength of the association between drug and the event (possibly, probably, or definitely related). In all 
cases, the potential risks and benefits will be weighed, and decisions will be guided by the best interest of 
the patient. The Study Physician will investigate to assess associations and severity, and will follow up with 
cases to ensure resolution. The Study Physician may consult with his or physician colleagues to review 
associations and severity. 
9 
Follow-up surveys 
 
9.1 
Overview 
Prior to implementing the intervention in each Target Area, a baseline blood survey will only be conducted 
in the RACD arm. Blood testing will not be performed pre-intervention in the TPE arms as the trial was 
designed to be operationally relevant so that feasibility (coverage, acceptability, etc.) could be assessed. In 
both the TPE and RACD arms, a follow-up blood survey will be conducted toward the end of the study 
during the end-line survey, expected to take place mid 2017. In index and secondary cases and a subset of 
RDT-negative control subjects from the RACD arm, a follow-up survey will also be conducted at 6-9 months 
for serological assessment. Finally, using routine health facility data from blood draws in symptomatic 
individuals, incidence data will be collected for the entire study period. Locality level incidence data will be 
collected over the entire study period. 
 
9.2 
Follow-up blood survey at 6-9 months 
About 6-9 months after the intervention, all index cases, secondary cases, and two controls for every case 
will be targeted for blood collection by 250uL microtainer as well as a DBS. Samples will be labeled with a 
barcode and the date of sample collection. Controls must report no known history of malaria within the last 
year and will be matched to cases by age, gender, and geography. Study staff will return for up to 2 
additional visits to ensure high capture. These samples will be used to study antibody kinetics and refine 
our current serologic panel of markers of recent versus past exposure in low endemic settings. This 
serological panel will be used in the end-line survey at the end of the study, expected mid 2017, to measure 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
39 
 
seroprevalence. More broadly, this information will help inform future tools used in Swaziland to measure 
exposure and document interruption of transmission.  
9.3  
End-line survey (at the end of the study, expected mid 2017) 
Towards the end of the study, all residents of Target Areas will be requested to participate in blood 
collection by DBS. Subjects who did not participate in the intervention are eligible for participation as the 
goal of the study is to evaluate the impact of the intervention on the community level. In addition to blood 
collection, we will ask a few short questions about malaria exposure since the intervention. The same 
barcode will be used to label the blood sample, linking the sample to the same participant. The date of 
collection will also be used to label the blood sample to differentiate this blood sample from previously 
collected blood samples (Appendices H & I). Study staff will return for up to 1 additional visit to ensure high 
capture. 
 
The main purpose of the end-line survey is to perform serology. A serological assessment looking at 
markers of recent exposure will enable comparisons of recent transmission (and thus impact of RACD vs. 
TPE) between the two arms. A serological assessment looking at markers of past exposure will enable 
comparisons of baseline exposure between the two arms. We will also use this measure to look at antibody 
kinetics (in relation to the baseline and 6-9 month capture points). These samples will also be used to 
measure infection prevalence.  
 
While the total sample size for the study is expected to be 6000 based on RACD data, we anticipate that 
10% of these encounters will occur in individuals that will have received the intervention twice (repeat 
Target Area enrolled more than 5 weeks since the prior RACD intervention, or more than 8 weeks since the 
last TPE intervention). These individuals only need to be sampled once. Therefore, we expect to screen 
about 5400 individuals. While some may not be present to participate in the end-line survey, we expect to 
also recruit new individuals who were not previously present at the time of the intervention. This sample 
size will enable us to detect a difference of 3% seroprevalence in the TPE versus 0.6% in the RACD arm 
(Table 8). 
 
9.4 
Passive collection of incidence data 
Incidence data from each locality will be collected passively for the entire study period starting from the 
first incident case reported in that locality. As this data will be de-identified and is part of standard 
surveillance, IRB approval will not be necessary for this data collection. Incidence data will be collected as: 
incidence of local cases (not counting the first case), proportion of imported cases (a surrogate measure of 
Rc [27]), and time to first end-line local incident case. 
10 
Acceptability Assessment 
 
10.1 
Background and Rationale 
For the quantitative portion of the Acceptability Assessment, acceptability of TPE versus RACD will be 
evaluated by comparing refusal rates and analyzing answers from a short survey.   
 
This qualitative portion of the Acceptability Assessment proposes to explore the acceptability of TPE from 
two vantage points; 1) among study participants and participants and 2) among members of the RACD and 
TPE surveillance teams. We will target only members of the TPE arm for acceptability assessment since 
RACD is the current standard in this setting and acceptability has been high. Additionally, the surveillance 
team will participate in qualitative exercises to enhance understanding of acceptance and refusal during 
the study given their constant exposure to community members offered the interventions. The results of 
the Acceptability Assessment will be used to refine strategies for malaria elimination in Swaziland and other 
malaria-eliminating settings. 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
40 
 
We will use focus group discussions (FGDs)to understand participants situational perspective in regard to 
the clinical trial [28]. The importance of using qualitative methods as an adjunct to clinical trials has been 
documented [29]. Additionally, this approach has been validated, as previous studies have successfully used 
FGDs to capture important information regarding community acceptability of new treatment modalities 
[30, 31]. All data will be collected by members of the field surveillance team who are native SiSwati 
speakers. 
 
We will conduct the Acceptability Assessment with community participants approximately 7-10 days after 
an intervention (during the follow-up pill count) has occurred in a TPE community with a positive malaria 
case. We anticipate enrolling participants in the TPE arm for the duration of the study. We will conduct the 
acceptability assessment with the malaria surveillance team every 3 months for the duration of the study, 
beginning 3 months after the study launch. 
10.2 
Aims of the Acceptability Assessment 
 
Aim 1:  To compare refusal rates between the RACD and TPE arms. A short survey of those who refuse 
testing or treatment will be administered at the time of refusal.  The short survey of refusers will ask 
questions about past participation in malaria screening and reasons for refusing participation in this clinical 
trial. 
 
Aim 2: To understand reasons for adherence among TPE study participants receiving treatment without 
testing. 
 
To appreciate the reasons for accepting TPE, we will identify study participants to explore acceptability of 
both practices.  Methods will entail FGDs with community members who have agreed to participate in the 
clinical trial.  The FGDs will explore past experience with malaria testing, impact of testing or treatment on 
daily life, and beliefs surrounding malaria transmission and possible elimination.  
 
Aim 3: To explore the surveillance team’s perception of community acceptance of RACD versus TPE.  
 
During the clinical trial to compare RACD versus TPE around positive malaria index cases, the field 
surveillance team interacts with the community members to facilitate the study. Using FGDs, we will 
explore the acceptability of both arms of the clinical trial from the vantage point of these field surveillance 
team members. FGDs will be used to explore their experience consenting participants for the study and 
reasons community members agree or disagree to receive testing and/or treatment.   
 
10.3 
Methods for the Acceptability Assessment  
 
Aim 1: 
 
At the time of refusal, we will ask all community members who refuse participation in either study arm to 
answer a short survey. The survey will be administered by the surveillance team member on site and 
uploaded to an excel spreadsheet during the study. These surveys will be anonymous and take 
approximately 5-10 minutes. Questions include but are not limited to: “Have you ever refused to take part 
in a malaria screening in the past?” “If yes, why did you refuse?” “Has anything in the past with medication 
influenced your decision not to participate in the intervention?” (Appendix V). Participation will be 
completely voluntary and all refuser information will be de-identified before analysis.  Information from the 
short survey will be evaluated during the study so that information may be used to inform the study team 
activities.  Information from the refuser survey will be aggregated and reviewed by the study team to 
identify any apparent reasons for refusals.  
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
41 
 
Aim 2:  
 
From each TPE study locality, we will ask participants if they agree to be part of a group discussion 7-10 
days after the intervention (at the pill count follow up visit). From those we will choose 3-7 study 
participants at each site to form a focus group. As we intend to conduct a FGD in all TPE study localities 
beginning at the study launch, we anticipate a total of 30 FGDs during the course of the study. FGDs will be 
conducted 7-10 days after the TPE intervention; therefore data collection will take place on a rolling basis 
throughout the study. Our intent is to capture information for the duration of the study and begin analysis 
with the first focus group. We will evaluate changes in community uptake over time by using an iterative 
approach to analysis.  
 
The goal of Aim 2 is to understand why TPE community members agree to participate in interventions 
around a malaria index case. FGDs will be audio-recorded and the interviewers will take notes during the 
sessions. Interviewers will consist of two members of the field surveillance team who are native siSwati 
speakers. All FGDs will take place in the village where the participants reside and be audio-recorded with 
written consent from the study participant. FGDs will last an estimated 1 hour and we will inquire about the 
participants’ experience with the interventions, their personal history of malaria, their experience with 
testing and treatment and the impact of these interventions on daily life. Sample questions include but are 
not limited to: “Have you ever been part of the NMCPs screening for malaria in affected communities?” 
“How was your experience with the screening test done by the NMCP officers?” What do you think about 
getting tested for malaria before you take medication? Is it important? Why or why not?” “How did the 
medication make you feel after taking it?” (Appendix W). Afterwards, the audio-recordings will be 
translated, transcribed and a brief summary will be written for each interview. We will upload and code the 
FGDs transcripts using an analytical software program, ATLAS.ti5, with the assistance of the study team. 
Major themes will be identified by two members of the study team independently. Any discrepancies will 
be resolved by inviting a 3rd member of the study team to verify findings. Data will then be analyzed to 
provide a description of the barriers and facilitators to participation in TPE. The themes that emerge will 
enable us to design future interventions to improve elimination strategies. 
 
Aim 3: 
 
Qualitative methods described in Aim 2 will be employed in Aim 3. However, the goal of Aim 3 is to explore 
how members of the study surveillance team (who interact with community members enrolled in both the 
RACD and TPE arms) perceive community acceptance of the interventions (Appendix X). We will conduct 
FGDs with the entire surveillance team every 3 months, beginning 3 months after the study launch and 
continue for the duration of the study. FGDs will be conducted in siSwati and led by a member outside the 
surveillance group who is indirectly involved in the study. All participants will provide written informed 
consent prior to the conduct of interviews. The FGDs will be semi-structured and will focus on the 
observations of these surveillance team members during the study. Specifically, we will focus on their 
experience consenting participants for both intervention arms, reasons community members gave for 
accepting or refusing participation, experience with DOT and their perceptions of how to engage 
community members in malaria elimination strategies. The FGDs will last an estimated 1 hour. All 
interviews will be audio-recorded with written consent from the participants, then transcribed and 
uploaded to Atlas.ti for management and analysis. Participants will be assured that their responses will not 
impact their position on the surveillance team. Data will then be analyzed to identify major themes 
associated with the acceptance of malaria elimination strategies by both community members and 
surveillance team members. Ultimately, we will describe facilitators and barriers to these strategies with 
the goal of identifying the most acceptable way to engage the community in malaria elimination.  
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
42 
 
Table 5. Acceptability Assessment – Study population, sample size, inclusion and exclusion criteria 
Aim 
Study population and 
sample size 
Inclusion criteria for 
Acceptability Assessment 
Exclusion criteria for the 
Acceptability Assessment 
1: Refusers 
All eligible residents of 
the TPE arm who refuse 
participation 
 Male and female refusers at 
time of study intervention 
 Agrees to a short anonymous 
survey 
 Resides in RACD study locality 
 Age <18 years 
 Refusal to participate in the 
refuser survey 
2: FGDs with 
TPE study 
participants 
Non-index cases residing 
within TPE study 
localities, 3-7 participants 
per FGD, anticipate 30 
TPE study localities over 
duration of study. 
 Male and female participants 
 Residents of index household 
 Residents of neighboring 
households 
 Provide informed consent 
(participants) 
 Resides in RACD study locality 
 Refusal to participate in the 
Acceptability Assessment 
 Speaks language not understood 
or able to be translated to 
interviewer. 
 Age < 18 years 
3: FGDs with 
TPE & RACD 
surveillance 
team members 
All members of the 
surveillance team in both 
TPE & RACD study arms 
 Provide informed consent 
 Refusal to participate 
11 
Cost-effectiveness assessment 
 
The goal of the cost effectiveness assessment will be compare TPE versus RACD in terms of costs per 
response or incident case of as well as cost per population and case averted as measured through the 
difference in asymptomatic and symptomatic infections identified at the end of the intervention. Our 
hypothesis is that the costs of TPE versus RACD will be lower due to the cost savings from not performing a 
diagnostic test as well as the cases averted due to higher effectiveness to prevent future infections. 
 
We will collect detailed expenditure data on costs of delivery of TPE and RACD interventions. Calculations 
will include costs for all consumables as well as staff time, which will be prospectively collected every 10th 
TPE or RACD event. 
12 
Laboratory procedures 
 
12.1 
Rapid diagnostic tests 
Pf-specific RDTs (First Response) will be performed on participants every time a blood sample is collected.  
RDTs will be performed according to the directions provided, using the blood transfer device and reagents 
provided by the manufacturer. Tests will be performed by study personnel, and results will be available 
within 15 minutes. The results of the RDT will be provided to the participant or their parent/guardian 
verbally, and will be recorded. Symptomatic and asymptomatic participants who test positive for malaria 
will be brought to their local health care facility for appropriate work-up and treatment with AL.  
12.2 
Filter paper sample collection 
Blood spots will be collected onto filter paper for future molecular studies for research purposes only. Filter 
paper (Whatman 3MM) will be pre-cut into individual squares and stapled to a thick card that will serve as 
its cover. Blood spots will be collected onto the filter paper in volumes of approximately 25µl aliquots per 
blood spot (4 blood spots per sample). Filter paper samples will be labelled with the individual’s bar code or 
ID number on the covering cardboard, and will be allowed to dry at ambient temperature and relative 
humidity before closing the card over the filter paper (like closing a matchbook).  Filter paper samples will 
be transported from the field in a zip lock bag and will be placed into a stock card filter paper box for final 
storage at -20C. 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
43 
 
12.3 
Microtainer blood collection 
Microtainers with dry EDTA anticoagulant will be used to collect 250µl of blood for research purposes only. 
This blood will be collected from secondary cases identified at the RACD intervention visit during case 
investigation. Microtainer blood samples will also be collected from index cases, secondary cases, and a 
sample of RDT-negative controls at the 6-9 month follow-up survey. Whole blood samples may be stored at 
4C for up to 24 hours before centrifugation to separate plasma from blood cells. 
12.4 
Antibody and DNA extraction  
Antibodies and DNA will be extracted from dried blood spots using the Chelex method with saponin.  
 
Whole blood samples (collected at the 6-9 month Follow-up visit and at the end-line survey visit near the 
end of the study, expected mid 2017) should be centrifuged within 24 hours to separate out the plasma. 
Pelleted blood cells will be resuspended with PBS buffer, and can be stored at 4C for up to one week 
before DNA is extracted using a Qiagen blood extraction kit at the National Reference lab for the 
appropriate molecular tests. 
 
Plasma and DBS antibodies will be stored in cryovials ideally at -20C or lower. DNA will be stored in 
cryovials at -20C. 
12.5 
LAMP 
DNA samples will first undergo LAMP testing using the Pan-LAMP detection kit (which detects DNA 
sequences common to all Plasmodium species), followed by testing with the Pf-LAMP detection kit if Pan-
LAMP positive.  These studies will be performed only for research purposes and will have no impact on the 
clinical management of study participants. 
12.6 
PCR 
All RDT or LAMP positive samples as well as 10% of negative samples will undergo nested cytochrome B 
PCR testing with species specific identification using a restrict digest,.8–10[32] Other molecular studies may 
include analyses of polymorphisms in parasite and/or human genes for mutations that may impact on 
clinical malaria, and genotyping of malaria parasites. These studies will be performed only for research 
purposes and will have no impact on the clinical management of study participants.  
12.7 
Genotyping 
Genotyping of Pf will consist of a panel of microsatellites and/or SNPs located throughout the genome. 
Briefly, DNA samples will be amplified in a multiplex pre-amplification step followed by amplification of 
microsatellites in individual reactions using fluorescently tagged primers, and sized using denaturing 
capillary electrophoresis. Multi-locus genotypes from mixed infections will be reconstructed, where 
possible, by quantifying alleles at each locus. Genotyping of additional loci will be performed as needed. 
These studies will be performed only for research purposes and will have no impact on the clinical 
management of study participants. 
12.8 
QT-NASBA for gametocytes 
RNA will be extracted from DBS using the Boom extraction method.[33]Sub-microscopic gametocyte 
density will be measured using the Pf 25S mRNA real time QT-NASBA.[34] These studies will be performed 
only for research purposes and will have no impact on the clinical management of study participants. 
12.9 
ELISA 
Serology, a test of past infection as assessed by the presence of antimalarial antibodies, may improve the 
identification of hot spots. ELISA assays will be performed using previously described methods[6]. Briefly, 
plasma or DBS antibodies will be assayed to detect antibodies against the Pf blood stage antigens 
merozoite surface protein-1 (MSP-142) and apical membrane antigen-1 (AMA-1), both biomarkers of P. 
falciparum exposure.[35] Other antigens that are sensitive and specific for recent exposure (currently 
undergoing evaluation) may also be used. ELISA assays will be performed in duplicate and optical densities 
recorded with an ELISA reader. Other serologic platforms (bead array, protein microarray) may also be used 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
44 
 
analyze responses to multiple antigens if available. These studies will be performed only for research 
purposes and will have no impact on the clinical management of study participants. 
12.10 Sample storage for future studies (for research purposes only) 
After the study period, samples will be stored for future research. The consent forms for this study include 
a statement about future testing for research purposes only. Samples will be stored for 25 years, reason 
being that if there are new malaria cases after elimination, it will be helpful to have past samples for 
molecular testing. The WHO recommends an isolate bank because comparing new strains to past strains 
will help distinguish between imported and local infection[36]. Re-emergence of new cases could occur 
more than 20 years after elimination. For example, North and South Korea eliminated malaria in the 1970s, 
but then experienced a re-emergence of the disease in the 1990s. 
13 
Data management 
 
13.1 
Quality assurance & quality control 
All members of the study personnel will be trained in the project objectives, methods of effective 
communication with study participants, collection of high quality data and principles of ethical research 
practice. Study personnel members will receive additional training specific to the tasks they will perform 
within the project including interviewing techniques, administration of surveys, completing questionnaires, 
and use of tablet devices. Standard Operating Procedures (SOPs) will be written for all project activities and 
booklets of all relevant documents provided to each member of the project team. Study group meetings 
will be conducted by the principal investigator to assess progress of the study, address any difficulties, and 
provide performance feedback to the members of the study group. Any corrections to data collection forms 
will be made by striking through the incorrect entry with a single line and entering the correct information 
adjacent to it, according to Good Clinical Practice guidelines.[37] The correction will be initialed and dated 
by the investigator.  
 
13.2 
Records & storage 
The principal investigator will maintain appropriate medical and research records for this study in 
compliance with the principles of good clinical practice and regulatory and institutional requirements and in 
compliance of the requirements for the protection of confidentiality of participants. Only study personnel 
members will have access to these records. All forms with participant names will be kept in a locked 
cabinet, when not in use, and the key kept by the local investigators. Participants will be identified by their 
study ID number, and participant names will not be entered into the computerized database. Data will be 
stored for at least 5 years.  Authorized representatives of the sponsor, the ethics committee(s) or 
regulatory bodies may inspect all documents and records required to be maintained by the investigator. 
The investigators will allow all requested monitoring visits, audits or reviews. 
14 
Statistical issues 
 
 
14.1 
Study population 
 
Overall: 
Based on the most recent census data, the overall population in the 77 study localities is estimated at 
211,189 individuals. However we expect that some localities will have no incident cases and therefore not 
receive any intervention. In the previous two transmission seasons, only 63 of the 77 localities had at least 
one case. Our sample size calculations are further based on the expected at-risk population within the 63 
localities, or EA that had at least one case in the previous three seasons, a total of 55,928 individuals. The 
size of the expected at-risk within localities varies greatly, therefore we used the harmonic mean of 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
45 
 
population size in localities with at least one case (656 per locality) to represent the effective sample size of 
the study in calculations of the design effect.  
 
Target Area: 
As defined above in section 4.4, the Target Area for TPE localities is defined as all individuals residing within 
200m of an index case that is detected in passive surveillance and resides in a TPE study locality, with 
individuals residing immediately beyond 200m included if a minimum of 30 enrolled individuals is not 
reached within 200m. The Target Area for RACD localities is defined as all individuals residing within 500m 
of an index case that is detected in passive surveillance and resides in a RACD study locality. Sample size 
calculations for the secondary outcome measures of seroprevalence and infection prevalence are based on 
the population of the Target Areas. 
 
The sample size for the Target Area assessments is estimated from incidence in the previous transmission 
season, and the expected drop in incidence among those in the TPE arm; resulting in an estimated 200 
index cases total with 30 individuals screened or treated in the Target Areas around each case. With 200 
index cases, we expect about 6000 encounters where individuals will receive a study intervention (either 
TPE or RACD). Based on preliminary RACD data, we anticipate 10% of these encounters will occur in 
individuals who previously received an intervention during the study period (repeated or overlapping 
Target Areas). For the follow-up end-line seroprevalence survey, these individuals will only be sampled 
once. Thus the effective sample size for the seroprevalence outcome measured in the Target Area 
population is expected to be 5400. Of note, the first index case for each Target Area will not be included 
since this person’s malaria exposure occurred pre-intervention. 
 
For the follow-up end-line infection prevalence survey, index cases will also be included as they will also be 
at risk for subsequent infection. Thus the effective sample size for the infection prevalence outcome 
measured in the Target Area population will be 5400 individuals screened plus 200 index cases, or 5600 
individuals.  
 
Adherence evaluation: 
Adherence will be measured on a subsample that includes only the individuals in the Target Areas 
surrounding the first index case in each locality. We expect that 22 localities in the TPE arm will have at 
least one index case, and at least 30 individuals will be assessed for DP treatment per Target Area, for a 
total sample of 660 individuals. 
 
 
 

 
 
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46 
 
14.2 
Outcome measures 
 
Table 6. Outcome measures 
Outcome 
Indicator 
Primary Aim 
Incidence 
Cumulative incidence of all cases (Pf infection) identified by passive 
surveillance in the locality subsequent to the first reported case during the 
study period (not including additional cases found through RACD). Cases 
include both locally acquired and imported infections.  
Secondary aims (effectiveness) 
 
Exposure 
(seroprevalence) 
Seroprevalence to markers of recent exposure using ELISA in end-line 
survey samples taken from residents in Target Areas near the end of the 
study (expected mid 2017), excluding index cases detected through passive 
surveillance. 
Infection prevalence 
Prevalence of infection by LAMP and QTNASBA testing for gametocytes in 
LAMP positives in end-line survey samples taken from residents in Target 
Areas near the end of the study (expected mid 2017),  including index 
cases detected through passive surveillance. 
Time to first local post-intervention 
incident case 
Time to first incident local case in the Target Area subsequent to the 
intervention. Target Areas that receive a repeat intervention will qualify to 
be included again at subsequent interventions. 
Proportion of imported incident 
cases  
Proportion of imported incident cases in the locality subsequent to the first 
reported case will be measured through passive surveillance. Additional 
cases found through RACD will not be included. 
Transmission potential  
(by genotyping) 
Microsatellite genotyping will be performed on samples collected from 
index cases as well as secondary cases. 
 
Secondary aims (feasibility) 
Coverage 
Proportion of persons residing within approximately 200m (TPE  localities) 
or 500m (RACD localities) of the index case who consented to participate in 
the study and who completed the initial procedures for their study arm 
(finger prick for RDT in the RACD arm, initial dose of DP in the TPE arm) 
Adherence 
Proportion of persons who completed 3 days of therapy among all 
individuals initiated on DP in the TPE arm, as assessed by pill count 
Prevalence of SAEs related to 
treatment 
Proportion of subjects experiencing SAEs deemed possibly, probably, or 
definitely related to DP or AL, out of the total number of subjects enrolled 
Acceptability 
Qualitative assessment (See Section 10) 
Cost 
Cost per index case-level intervention, cost per case averted. 
 
14.3 
Estimates of study power 
 
Sample sizes and design effect estimates: 
Sample size was driven by the number of localities within the area in the country considered to be at-risk 
for malaria transmission and the number of index cases we expect will be identified within those localities 
during the study period. The overall, Target Area, and adherence evaluation samples are described above in 
section 14.1. To estimate power to detect differences in cumulative incidence we used sample size of 
55,928 for the overall sample. To estimate power to detect differences in seroprevalence, we used sample 
size of 5400 for the Target Area sample based on the assumptions as described above. As noted we used 
harmonic means for locality size (cluster size) in our estimates of power and design effect rather than 
arithmetic means to estimate more conservatively and to reduce the impact of the few localities with large 
population sizes.  
 
We conducted sample size calculations to determine our ability to detect a difference in the effectiveness 
of TPE compared to RACD on incidence. We used the equations suggested by Hayes and Moulton (Cluster 
Randomized Trials, CRC Press, 2009) to calculate sample size required to detect a difference between arms. 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
47 
 
Calculations are made for differences in proportion and assuming a coefficient of variation of 0.9 based on 
census and surveillance data from September 2012 to March 2015 to estimate the number of localities with 
cases, index cases and cluster size as described above. The power calculations are sensitive to sample size, 
but—in our study—the cluster population size is fixed. Sample sizes for primary and secondary outcomes 
can be found in Table 9. 
 
Primary outcome – Cumulative Incidence: 
 
Our primary study outcome is cumulative incidence of passively detected malaria infections in the overall 
population of the randomized study area localities. If incidence in the RACD arm remains as it was during 
the 2012-2015 transmission seasons (during which RACD was the standard of care) then given the above 
assumptions, we would expect cumulative incidence in the RACD arm to be 0.4% or approximately 4 per 
1000 persons. If this is the case, our study would have 80% power to detect a reduction in cumulative 
incidence to 0.2% or 2 per 1000 persons if at least 51 of the 77 study localities had at least one index case 
(Table 7). Should cumulative incidence in the RACD arm rise to 0.5%, the reduction to 0.25 or 2.5 per 1000 
persons in the TPE arm would be detectable with at least 47 localities with at least one case. Should 
cumulative incidence in the RACD arm fall to 0.3%, reduction to 0.15% or 1.5 per 1000 persons in the TPE 
arm would be detectable with 57 localities with at least one case. Because of the clustered nature of the 
data and the variability in cluster size, we used the harmonic mean of the population size (656 per locality, 
or 41328 total population using the harmonic mean of locality population). 
 
Secondary outcome of effectiveness – Seroprevalence: 
In the end-line survey near the end of the study (expected mid 2017), non-index cases residing in Target 
Areas will undergo blood testing to measure seroprevalence. Index cases will also be included as long as 
they were not the first index case for a Target Area. The first index case will not be included as this person’s 
malaria exposure was known to occur pre-intervention. The sample size for the seroprevalence measure is 
expected to be 5400. Based on preliminary data, we expect seroprevalence to be approximately 3% prior to 
any intervention.[6] 
 
End-line seroprevalence for RACD was calculated based on an estimate that only 20% of individuals with 
infection will be detected by RACD and treated, leading to a 20% effectiveness of RACD, or a drop from 
3.0% pre-intervention to 2.4% end-line seroprevalence. We believe that TPE will be more effective than 
RACD in reducing seroprevalence near the end of the study (expected mid 2017). Because of the clustered 
nature of the data and the variability in cluster size, we used the harmonic mean number of observations 
expected per locality (60) to generate the effective sample size for analytic power (3780). Using these 
assumptions, our study would have 80% power to detect a decrease in seroprevalence to 1.18% in the TPE 
arm if 63 of the 77 localities had at least one case (Table 8). 
 
Secondary outcome on feasibility – Coverage: 
For the feasibility outcome measure on coverage, estimates were based on the goal TPE coverage of 80%. 
This goal is based on modeling data which suggests at least 80% coverage is needed for MDA to be 
successful, as well as experience from some settings that have successfully interrupted transmission in the 
setting of MDA [8, 18]. If estimates of incidence in the TPE arm are accurate, approximately 66 index cases 
will be identified and 1782 individuals will be treated in the TPE-assigned Target Areas. If the true coverage 
is 80% coverage, we would have a 95% confidence interval between 77% and 83% with this sample size 
[38]. 
 
Secondary outcome on feasibility – Adherence: 
To measure adherence to DP, we will perform a pill count in individuals residing in the first Target Area for 
each TPE locality each transmission season. We will have 5% absolute precision to detect 80% adherence 
when the sample size reaches 532. If adherence is lower than expected, we will still have 10% absolute 
precision to detect 50% adherence when the sample size 208.  
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
48 
 
Table 7. Detectable Reductions in cumulative incidence given different assumptions about Incidence in the 
RACD 
 
# Total 
localities 
with at 
least one 
index case 
# 
localiti
es per 
arm 
Number 
assessed per 
locality (n) 
Cumulative 
Incidence 
Km (coeff 
of 
variation) 
Z 
beta 
Power 
 
RACD 
TPE 
RACD (π0) 
TPE(π1) 
47.0 
23.5 
656 
656 
0.500% 
0.250% 
0.9 
0.84 
80% 
50.6 
25.3 
656 
656 
0.400% 
0.200% 
0.9 
0.84 
80% 
56.6 
28.3 
656 
656 
0.300% 
0.150% 
0.9 
0.84 
80% 
61.4 
30.7 
656 
656 
0.250% 
0.125% 
0.9 
0.84 
80% 
68.5 
34.3 
656 
656 
0.200% 
0.100% 
0.9 
0.84 
80% 
80.5 
40.2 
656 
656 
0.150% 
0.075% 
0.9 
0.84 
80% 
Based on equation 4 from Hayes and Bennett International Journal of Epidemiology 1999;28:319-32 
Assumes that population is only those in the EAs that have at least one case. 
Sample size calculation based on harmonic mean of population size.  
 
Table 8. Detectable reductions in seroprevalence given varying assumptions about prevalence in the RACD 
arm 
# Total 
localities 
with at 
least one 
index 
case 
# 
localiti
es per 
arm 
Number 
assessed 
per locality 
(n) 
Outcome proportion  Km (coeff 
of 
variation) 
Z 
beta 
Power 
 
RACD TPE 
RACD (π0) 
TPE (π1) 
46.6 
23.3 
60 
60 
3.00% 
1.35% 
0.9 
0.84 
80% 
62.3 
31.2 
60 
60 
2.40% 
1.18% 
0.9 
0.84 
80% 
49.3 
24.7 
60 
60 
2.00% 
0.83% 
0.9 
0.84 
80% 
50.8 
25.4 
60 
60 
1.50% 
0.57% 
0.9 
0.84 
80% 
  
  
  
  
  
  
  
  
  
 
Based on equation 4 from Hayes and Bennett International Journal of Epidemiology 1999; 28:319-326 
Assumes we are including only persons in the target areas in the denominator but evaluating at locality level 
Assumes 3 per 100 is the background seroprevalence 
 
 
Table 9. Sample sizes for primary and secondary aims. 
 
Outcome 
Result* 
 
Actual sample size (Effective 
sample size, based on 
harmonic mean in clusters) 
 
Primary aim 
 
 
Incidence 
0.4% (RACD) vs. 0.2% (TPE) 
55,928 (41,328) 
Secondary aims (effectiveness) 
 
 
Exposure (seroprevalence) 
2.4% (RACD) vs. 1.18% (TPE) 
5400 not including index cases 
(3720) 
Infection prevalence 
n/a 
5600 includes index cases 
Time to first post-intervention incident case 
n/a 
55,928 (41,328) 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
49 
 
Outcome 
Result* 
 
Actual sample size (Effective 
sample size, based on 
harmonic mean in clusters) 
 
Proportion of imported incident cases 
n/a 
55,928 (41,328) 
Transmission potential  
n/a 
Genotyping estimated to be 
performed in 800 index cases** 
and 35 infections from follow-
up cross sectional survey 
Secondary aims (feasibility) 
 
 
Coverage in TPE Arm 
80% (95% CI: 77%-83%) 
1782 
Adherence in TPE Arm 
80% 
532 
Prevalence of SAEs related to treatment 
n/a 
5400 not including index cases 
(3720) 
Acceptability 
n/a 
5400 not including index cases 
(3720) 
Cost 
n/a 
10 Target Areas/arm 
*for some secondary outcomes, power calculations were not performed however effective sample size is shown. 
** 200 index cases will be from the study area but an estimated 600 DBS that are already collected as standard surveillance from 
other parts of the country will also be used to characterize the background genotypes/transmission potential in Swaziland, as it 
relates to the transmission potential in the study areas. 
 
14.4 
Analytical plan 
 
Preliminary Analyses and Missing Data: 
One-way frequency tables for all categorical variables and distributions, ranges, and outliers for continuous 
variables will be generated to perform range checks, quantify the amount of missing data, and yield 
valuable descriptive findings that will characterize coverage and cluster and Target Area characteristics in 
the study population. These analyses will also be stratified by randomization group (i.e., TPE vs RACD) using 
cluster-based two-group comparison methods (e.g., Rao-Scott chi-square) to check the equality of group 
covariates at baseline. Although we expect the randomization to produce balanced covariate structures, we 
will consider methods of adjustment to balance baseline covariates should there be significant differences 
between the TPE and RACD groups. To look for areas where there is a possibility of contamination by 
proximity of index cases assigned to different arms, we will describe the distances between TPE and RACD 
assigned index cases as well as the number of RACD assigned index cases who were within 2km of an index 
case assigned to TPE. 
 
Primary Analysis: 
For the primary analysis comparing incidence between the TPE and RACD arms, we will follow an intention-
to-treat (ITT) approach. We hypothesize that cumulative incidence in the TPE localities will be lower than in 
the RACD assigned localities. For the initial ITT analyses, estimates of effect will be unadjusted for any 
variables other than intervention group. To check for possible contamination of effects by proximity to an 
index case treated with TPE, a second set of ITT analyses will be conducted adjusting for intervention group 
and distance of index case from an index case assigned to TPE.  Outcomes are assessed at the individual 
level. Because of the clustered nature of the data, our modeling approach will also adjust for correlation of 
observations by locality for analyses using the overall sample and by locality and index case for analyses 
using the Target Area sample. Generalized estimating equations (GEE) will be used to perform the proposed 
primary analyses. GEE accounts for the correlation of persons within clusters and localities. GEE estimates 
are consistent even if the correlation structure is miss-specified, though GEE's statistical efficiency improves 
as the working correlation structure more closely approximates the actual correlation structure. Thus, 
several working correlation structures suitable for the study's design will be considered (e.g., unstructured, 
Autoregressive order 1, exchangeable). The QIC statistic will be used to select the final working correlation 
structure. Robust Huber-White "sandwich" standard errors will be used to obtain correct inferences even if 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
50 
 
the chosen correlation structure remains slightly miss-specified. Alpha will be set at 0.05 for all planned 
comparisons. 
 
Should the preliminary analyses reveal an imbalance in the baseline covariates between the TPE and RACD 
arms, a second set of models will be run for all primary analyses. Adjusted models will reweight the data 
(through inverse probability weighting, or targeted minimum loss based estimation) to recover effect 
estimates that reflect an equal distribution of baseline covariates.  
 
Subgroup analyses: Although there is limited power with our constrained sample size, we will describe 
summary measures of incidence and intervention effects for some specific subgroups of interest within our 
study area population. Of particular interest are those who did or did not have insecticide spraying of their 
household areas, strata of risk as determined by the National Malaria Control Program, and season of index 
case presentation.  
 
Secondary analyses: 
Assessments of secondary outcomes will also be conducted using GEE techniques to account for the 
clustered nature of the data collection as described above. Secondary analyses for prevalence and 
seroprevalence are restricted to individuals in the Target Areas who will be participating in blood testing 
surveys conducted towards the end of the study (expected mid 2017). As noted, for analyses of outcomes 
in the Target Area sample, clustering by both locality and index case area will be accounted for in the 
modeling approach. To account for possible contamination by proximity to another index assigned to the 
TPE arm, models will also include adjustment for distance to the nearest index case treated with TPE.  
Planned secondary analyses and hypotheses are as follows: 
 
Hypotheses regarding the effectiveness of TPE compared to RACD: 
1. Comparison of seroprevalence using antibodies to markers of recent exposure. Using the samples 
collected in the end-line survey near the end of the study (expected mid 2017), we expect that 
seroprevalence will be lower in the Target Areas receiving TPE than in those receiving RACD. 
2. Comparison of prevalence of malaria infection. Using the samples collected in the end-line survey 
near the end of the study (expected mid 2017), we expect prevalence to be lower in the Target 
Areas receiving TPE than in those receiving RACD. 
3. Comparison of proportion of incident cases that are imported. We expect that local transmission 
will be reduced by TPE and thus the proportion of subsequent cases imported will be higher in the 
TPE arm than in the RACD arm. This outcome will be summarized at the locality level and analyzed 
with locality as the unit of analysis.    
4. Comparison of time to first post-intervention incident infection. We hypothesize that time to the 
first post-intervention index case within the Target Area will be longer for Target Areas receiving 
TPE compared to those receiving RACD. Analysis for this outcome will use a standard cox 
proportional hazards model to estimate the time to a subsequent incident infection among 
individuals in the Target Area. 
5. Comparison of transmission potential using genotyping. Microsatellite genotyping will be used to 
measure transmission potential. DNA samples for genotyping will be collected from index cases and 
secondary cases. Based on malaria rates in Swaziland over the past three years, we expect 
approximately 200 index cases over the study period and 35 infections from the follow-up cross 
sectional survey (1.6% prevalence in the TPE arm and 0.4% in the RACD arm). We expect 
transmission potential to be lower in the TPE versus RACD arm. Relatedness of infections within 
Target Areas and within localities will be used as a surrogate for transmission potential. 
 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
51 
 
Planned Analyses of Operational Feasibility and expected findings: 
1. Coverage of the intervention. The numbers and proportion of the population completing finger 
prick testing (if RACD arm) or receiving at least the first dose of medication (if TPE) will be 
calculated by arm. The proportion of the individuals living in Target Areas around an index case that 
receive the TPE intervention is expected to be 80% with a 95% confidence interval from 76% to 
84%. 
2. Adherence to TPE. In the subsample of Target Areas surrounding the first index case in each locality 
assigned to TPE, we will assess adherence to the 3 day regimen of DP in TPE using pill count. We 
expect adherence to be 80%. 
3. Safety of the TPE treatment. The number and percent of individuals experiencing an adverse event 
will be recorded by study arm. We expect that compared to RACD, TPE will be safely administered 
with few or no serious adverse events related to treatment, and no difference in SAEs compared to 
AL based on analysis of the adverse events report forms. 
4. Acceptability of the intervention.  See Section 10. 
5. Costs per incident infection and per population. Detailed costing will be performed in 10 Target 
Areas per arm. We expect that costs per incident infection and per population for implementing 
the TPE intervention will be no higher than for RACD, the current standard of care.  
15 
Advisory Committee 
 
15.1 
Role of the Advisory Committee 
The role of Advisory Committee will be to support the implementation of research, interpretation of 
findings, and broader dissemination of findings to produce national and international impact. By making 
recommendations, the Advisory Committee will provide oversight to ensure that the research is well 
coordinated, scientifically and ethically sound, and in line with the Ministry of Health’s goals for elimination 
in Swaziland. Not all committee members are expected to be directly involved in the project. 
15.2 
Membership of Advisory Committee 
The General Committee of the Swaziland Malaria Elimination Advisory Group (SMEAG) will serve as the 
Advisory Committee for this study. The SMEAG was established in 2010 to establish policy, to provide 
technical guidance on implementation of policies, and to monitor policy implementation and progress 
toward elimination. The SMEAG includes senior representatives from major partners to the NMCP including 
the World Health Organization (WHO), United Nations Children’s Fund (UNICEF), CHAI, UCSF, the Swaziland 
National Association, the Swaziland Medical and Dental Association, Swaziland Nurses Association, Red 
Cross, and University of Swaziland (UNISWA) (Appendix Y).  To provide additional technical expertise as well 
as a global perspective, senior representatives from UCSF Department of Medicine and the Bill and Melinda 
Gates Foundation will also be invited to join in meetings about this study. 
15.3 
Activities of the Advisory Committee 
The Advisory Committee will meet once yearly in Swaziland to review and provide recommendations this 
project. The first meeting will serve to review and approve the protocol. Subsequent meetings will be to 
report on progress and review data. International members of the Advisory Committee will be encouraged 
to join meeting in person, however may join by teleconference if schedules limit travel to Swaziland. 
Advisory Committee members will also have ongoing interactions with study team members on an as 
needed basis. 
 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
52 
 
16 
Data and Safety Monitoring Committee 
16.1 
Data and Safety Monitoring Committee 
A Data and Safety Monitoring Committee (the Pharmacovigilance and Adverse Drug Reactions Committee) 
will be assembled in conjunction, consisting of a minimum of four members who are independent of the 
project and who have made no significant input into the project’s design. Members will include experts in 
statistics, epidemiology, clinical trial design, and include at least one local clinician. One member will serve 
as the Chair of the Committee and one will serve as the Secretary. Depending on the agenda, independent 
advisors or experts can be invited to the meeting, upon approval by the chair and secretary. The 
Committee, investigators, and the sponsor will agree on the rules for reporting safety data during the 
course of the project, frequency of formal meetings (likely quarterly), and the rules for recommending 
premature termination of the project on grounds of safety. The Committee will review the study protocol 
and analytical plan prior to the onset of the study, and will review SAE and SUSAR reports during the course 
of the trial. The Committee will also assess cumulative SAE throughout the course of the study to assess 
study safety and make decisions on necessary protocol changes. Full details in the Terms of Reference 
(Appendix Z). 
16.2 
Meetings 
An initial meeting will be held to introduce the project to committee members.  Following this introductory 
meeting, the committee will meet at regular agreed upon intervals. These meetings will be planned around 
observed and regular reports of suspected adverse drug reactions. Committee members are expected to 
attend meetings and should not rely upon substitute representatives. Members will participate in email 
discussions as necessary and will be updated regularly on TPE progress and activities. However, the busy 
schedules of members will be respected and meetings convened their availability. 
16.3 
Stopping guidelines 
Decisions about discontinuation of the study will be made by the members of the Committee. Stopping 
guidelines will be based on the prevalence of serious adverse events (for the TPE vs. RACD groups) deemed 
to have a causal association with study drugs.   
 
17 
Ethical considerations 
 
17.1 
Institutional review boards 
This protocol and the informed consent documents and any subsequent amendments or modifications will 
be reviewed and approved by all institutional review boards (IRBs) before the study begins, including the 
Swaziland Ministry of Health Ethics Committee and the UCSF Committee for Human Research.  A Data and 
Safety Monitoring Committee (the Pharmacovigilance and Adverse Drug Reactions Committee) will be 
established to oversee the trial. 
17.2 
Informed consent process 
Approval from local leaders will be sought before beginning activities in the project area.  All informed 
consent discussion will be conducted in SiSwati or English and a translator will be used if necessary. All 
information sheets and consent forms will be available in SiSwati and English, describing the purpose of the 
project and the procedures to be followed, and the risks and benefits of participation. During the consent 
discussions, each section of the consent form will be read exactly as it is written either by study personnel 
or by the translator, and then further explained as necessary. Consent for future use of biological 
specimens for research purposes only will be obtained. All participants, parents/guardians will be informed 
that participation in the study is completely voluntary and that they may withdraw from the study at any 
time. 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
53 
 
Written consent to participate in the research study will be documented for the relevant study procedures 
(Table 4). For children <18 years of age, consent will be obtained from one parent or guardian, as is 
customary in Swaziland.  For participants between 12-17 years of age, we will also obtain minor assent as is 
customary in Swaziland. If the person asked to provide consent is unable to read or write, their fingerprint 
will substitute for a signature. 
17.3 
Risks and discomforts 
 
Randomization: 
In this cluster-randomized trial, half of participating communities will be randomly assigned to TPE, while 
half will be randomly assigned to standard of care RACD. The TPE intervention may prove to be more or less 
efficacious, more or less well-tolerated, and/or more or less safe than standard care. Thus, there is the risk 
that localities will be randomized to a less efficacious, less well-tolerated, and/or less safe study arm. 
However, the risks associated with randomization in this study are likely to be low.   
 
Dihydroartemisinin-piperaquine: 
DP has an excellent efficacy and safety profile, including in asymptomatics. However some adverse events 
that have been reported in association with DP including nausea, diarrhea, vomiting, abdominal pain, 
anorexia, pruritus, rash, and dizziness. An increased risk of early vomiting has been reported in children 
with uncomplicated malaria treated with DP, as compared to those receiving artemether-lumefantrine, 
however, this was reported in young children (aged 6-24 months) and was higher in those that were breast-
fed.[39] In a large multicenter trial of 4116 African children under five with uncomplicated malaria, in which 
1,468 children were treated with DP, the most commonly reported adverse events related to DP were 
anemia (6.5%) and vomiting (3.3%).  Serious adverse events occurred in 10 children, but only 4 (0.3%) were 
felt to be related to DP.  Five deaths occurred in the study; the one death in the DP arm was due to 
diarrheal disease.[40] A prospectively pooled analysis of six trials conducted in Asia and Africa, indicated 
that the risk of adverse events associated with DP was lower than with comparator ACTs, and that most 
adverse events were commonly reported in relation to clinical malaria.[25] 
 
DP was evaluated for use as IPT in schoolchildren in Uganda in a trial comparing DP, sulfadoxine-
pyrimethamine (SP), and amodiaquine + sulfadoxine-pyrimethamine (AQ+SP), to placebo.[11] In this study 
of 780 children, those receiving DP were at no higher risk of adverse events than those receiving placebo. In 
another recent study of IPT in schoolchildren using DP in Uganda, no safety concerns were identified. The 
most commonly reported adverse events in this study were cough, headache, and abdominal pain, but 
children receiving DP monthly or once a term were at no higher risk for these events than those receiving 
placebo. There was also no difference in the risk of anorexia, nausea, vomiting, diarrhea, or pruritus 
between the groups[21]. 
 
In general, ACTs are not recommended for use in the first-trimester of pregnancy due to insufficient safety 
data.[41]In second and third trimester, ACTs may be used with the exception of DP, for which safety data in 
late pregnancy are lacking. A recent review of published data on 945 women exposed to an artemisinin 
during pregnancy, including 123 during first trimester, and 822 during the second or third trimester, did not 
identify an association between use of artemisinins and adverse pregnancy outcomes.[41] However, these 
studies were limited by small sample sizes and lacked power to detect rare serious adverse events and 
heterogeneity between studies precluded pooled analysis. 
 
To minimize any safety risks associated with DP treatment, we plan to exclude all pregnant or breastfeeding 
women as well women who have experienced menarche, but no menses in the past 4 weeks from DP 
treatment. Due to limited data in infants <9 months of age or <7kg, these subjects will also be excluded 
from DP treatment. Individuals excluded from DP treatment will be given an RDT to determine if they have 
a malaria infection, and will be advised to seek treatment at their health facility if they test positive for 
malaria. In addition, we will monitor for SAEs. 
 

 
 
Swaziland TPE protocol V1.10, 30 March 2016   
 
54 
 
Blood draws: 
The potential risks of drawing blood from a finger-prick include temporary discomfort, pain, transient 
bleeding, bruising, skin infection, and fainting.  The volumes of blood taken will be too small to produce any 
adverse effects from the blood drawing, and overall the risks associated with blood draws are likely to be 
low. To reduce the potential risks, study staff will be trained in the proper conduct of a finger-prick 
according to standard operating procedures to minimize the risk of discomfort and infection.  
 
Positive malaria tests: 
In the RACD arm, RDT results will be provided to participants and treatment will be offered if RDT results 
are positive.  Participants with positive tests will be referred to the local health facility and escorted by 
study staff when feasible. It is possible that for some cases in the community, the RDT will be negative, but 
the molecular test will be positive. This most commonly occurs when parasitemia is very low, below the 
level of detection for RDTs, but not below the level for LAMP or PCR. These subjects will not treated as the 
performance of LAMP or PCR is for research purposes. The risk of developing symptomatic or severe illness 
is very low from a presumably low parasitemia in an RDT-negative asymptomatic individual. Of note, RDTs 
are used nationally at the point of care in health facilities, with treatment based on the result of the RDT, 
without confirming the RDT result by a molecular test.  
 
Confidentiality: 
Participation in a research study may involve a loss of privacy, but successful implementation of the study 
will require that the confidentiality of all study participants be strictly maintained. The risks associated with 
loss of privacy in this study are likely to be low. To ensure confidentiality is maintained, all information 
gathered will be treated as private by the study personnel, and records will be kept securely in locked filing 
cabinets and offices. For all data collected as part of the study, participants will be assigned a unique 
identification number. No personal identification information such as names will be used in any reports 
arising out of this research. All project staff will be trained on procedures for maintaining confidentiality. 
Study staff will routinely discuss what other measures can be taken to minimize risk as issues arise during 
the study.  
17.4 
Compensation 
Participants will not be paid for taking part in this study.  Most assessments will be conducted at 
households, which will eliminate the need for travel and minimize opportunity costs for the participants.  If 
study participants are referred by study personnel to a health facility for further assessment, transportation 
may be facilitated by the project on a case to case basis. Any diagnosis and treatment associated with the 
study will be provided free of charge. 

18 
Timeline 
 
 
 
Expected outcomes and 
related activities 
Year or Quarter 
Milestones 
Year 1  
1/14-12/14 
Year 2  
1/15-12/15 
Year 3  
1/16-12/16 
Year 4  
1/17-12/17 
Study preparation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Develop, review, and finalize work plan & protocol. In-country review of work plan & protocol; 
incorporate feedback into protocol. Finalize protocol. 
 Randomize ½ of localities in the receptive area to the intervention, ½ to control. Sensitization of 
participating localities. 
 Complete & submit applications to UCSF and local IRBs.  
 Finalize & translate informed consents 
 Finalize questionnaires 
Trainings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Finalize & translate training materials. 
 Conduct trainings for lab and field personnel. 
Study intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Finalize SOPs for field procedures. 
 Order supplies (DP, field supplies) 
 Field team conducts case investigations & deploys RACD or TPE. 
 
RACD arm - perform RDT and refer secondary cases to health facilities. 
 
TPE arm - Administration of DP 
Adverse event monitoring 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 When adverse events occur, collecting additional data to assess causality. 
 Prepare reports of serious adverse events. 
Data collection:  
Laboratory assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Finalize SOPs for lab procedures. 
 Order supplies. 
 Ongoing blood surveys for LAMP in RACD arm, 6-9 month blood collection for serology validation 
Data collection: outcome 
measures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Perform routine surveillance for incidence data, time to subsequent cases, imported/local ratio. 
 Collect & coordinate the end-line survey near the end of the study, expected mid 2017 (blood 
samples for infection prevalence and serology) 
 Collection operational feasibility outcome measures – coverage, safety (adverse event monitoring 
above), costs, adherence through pill count 
Data collection:  
Qualitative assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Finalize SOPs for qualitative assessment of acceptability. 
 Field team performs in-depth interviews with study participants and key informants. 
Project Monitoring 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Develop and finalize SOP for monitoring project data. 
 Database check-ins. 
 Coordinate and hold annual and ad-hoc meetings of  the Pharmacovigilance and Adverse Drug 
Reactions Committee and the Advisory Committee 
Preliminary data analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Develop and finalize SOP for data analysis. 
 Preliminary analysis on coverage, acceptability, cost-effectiveness, safety, and incidence 
Final data analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Final analysis of coverage, prevalence of SAEs, acceptance, cost-effectiveness, incidence, parasite 
prevalence, seroprevalence, etc. 
Prepare final manuscripts and 
reports 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Prepare manuscripts for publication. 
 Review with collaborators, incorporate feedback into manuscripts. 

19 
References 
 
1. 
Swaziland National Malaria Elimination Policy, 2010, Ministry of Health: Mbabane. 
2. 
Ferreira, M. and M. Da Silva-Nunes, Evidence-based public health and prospects for malaria control in 
Brazil. J Infect Dev Ctries, 2010. 4(9): p. 533-545. 
3. 
Carter, R., K. Mendis, and D. Roberts, Spatial targeting of interventions against malaria. Bull World 
Health Organ, 2000. 78(12): p. 1401-1411. 
4. 
Moonen, B., et al., Operational strategies to achieve and maintain malaria elimination. Lancet, 2010. 
376(9752): p. 1592-603. 
5. 
Ishengoma, D.S., et al., Accuracy of malaria rapid diagnostic tests in community studies and their 
impact on treatment of malaria in an area with declining malaria burden in north-eastern Tanzania. 
Malar J, 2011. 10(1): p. 176. 
6. 
Hsiang, M.S., et al., Surveillance for malaria elimination in Swaziland: A national cross-sectional study 
using pooled PCR and serology. PLoS ONE, 2011. 7(1): p. e29550. 
7. 
Imwong, M., et al., High-throughput ultrasensitive molecular techniques for quantifying low-density 
malaria parasitemias. J Clin Microbiol, 2014. 52(9): p. 3303-9. 
8. 
Hsiang, M.S., et al., Mass drug administration for the control and elimination of Plasmodium vivax 
malaria: An ecological study from Jiangsu Province, China. in review, 2013. 
9. 
Zani, B., et al., Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum 
malaria. Cochrane Database Syst Rev, 2014. 1: p. CD010927. 
10. 
Myint, H.Y., et al., Efficacy and safety of dihydroartemisinin-piperaquine. Trans R Soc Trop Med Hyg, 
2007. 101(9): p. 858-66. 
11. 
Nankabirwa, J., et al., Efficacy, safety, and tolerability of three regimens for prevention of malaria: a 
randomized, placebo-controlled trial in Ugandan schoolchildren. PLoS One, 2010. 5(10): p. e13438. 
12. 
Arinaitwe, E., et al., Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum 
malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis, 2009. 49(11): p. 
1629-37. 
13. 
Katrak, S., et al., Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-
piperaquine for malaria in young HIV-infected and uninfected children. Malar J, 2009. 8: p. 272. 
14. 
Kamya, M.R., et al., Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment 
of Malaria: A Randomized Trial. PLoS Clin Trials, 2007. 2(5): p. e20. 
15. 
Yeka, A., et al., Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating 
uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One, 2008. 3(6): p. e2390. 
16. 
White, N.J., Intermittent presumptive treatment for malaria. PLoS Med, 2005. 2(1): p. e3. 
17. 
The UCSF Global Health Group, Review of Mass Drug Administration and Primaquine Use, 2014, UCSF 
Global Health Sciences, The Global Health Group: San Francisco, CA. 
18. 
Okell, L.C., et al., The potential contribution of mass treatment to the control of Plasmodium 
falciparum malaria. PLoS One, 2011. 6(5): p. e20179. 
19. 
Corran, P.H., et al., Dried blood spots as a source of anti-malarial antibodies for epidemiological 
studies. Malar J, 2008. 7: p. 195. 
20. 
Lwin, K.M., et al., Randomized, double-blind, placebo-controlled trial of monthly versus bimonthly 
dihydroartemisinin-piperaquine chemoprevention in adults at high risk of malaria. Antimicrob Agents 
Chemother, 2012. 56(3): p. 1571-7. 
21. 
Nankabirwa, J.I., et al., Impact of intermittent preventive treatment with dihydroartemisinin-
piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial. Clin Infect 
Dis, 2014. 58(10): p. 1404-12. 
22. 
Banek, K., et al., Adherence to artemisinin-based combination therapy for the treatment of malaria: a 
systematic review of the evidence. Malar J, 2014. 13: p. 7. 
23. 
World Health Organisation, Guidelines for the treatment of malaria, 2010, World Health 
Organization: Geneva. 
24. 
National Malaria Control Program, Integrated management of malaria training: a practical guide for 
health workers, U.M.o. Health, Editor 2012. 
25. 
Zwang, J., et al., Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a 
prospective multi-centre individual patient data analysis. PLoS One, 2009. 4(7): p. e6358. 

 
 
 
57
26. 
Cisse, B., et al., Randomized trial of piperaquine with sulfadoxine-pyrimethamine or 
dihydroartemisinin for malaria intermittent preventive treatment in children. PLoS One, 2009. 4(9): p. 
e7164. 
27. 
Churcher, T.S., et al., Public health. Measuring the path toward malaria elimination. Science, 2014. 
344(6189): p. 1230-2. 
28. 
Denzen, N.K. and Y.S. Lincoln (eds), Handbook of Qualitative Research, 2nd ed. 2000: Sage 
Publications. 
29. 
O’Cathain, A., et al., What can qualitative research do for randomized controlled trials? A systematic 
mapping review. BMJ Open, 2013. 
30. 
Hunt, L., Practicing oncology in provincial Mexico: a narrative analysis. . Social Science Medicine, 
1994: p. 843-853. 
31. 
Simmons, R.E., The study of client-provider interactions: a review of methodological issues. Studies in 
Family Planning. 1994: p. 1-17. 
32. 
Hsiang, M.S., et al., PCR-based pooling of dried blood spots for detection of malaria parasites: 
optimization and application to a cohort of Ugandan children. Journal of clinical microbiology, 2010. 
48(10): p. 3539-43. 
33. 
Boom, R., et al., Rapid and simple method for purification of nucleic acids. Journal of clinical 
microbiology, 1990. 28(3): p. 495-503. 
34. 
Schneider, P., et al., Quantification of Plasmodium falciparum gametocytes in differential stages of 
development by quantitative nucleic acid sequence-based amplification. Molecular and biochemical 
parasitology, 2004. 137(1): p. 35-41. 
35. 
Angov, E., et al., Heterologous protein expression is enhanced by harmonizing the codon usage 
frequencies of the target gene with those of the expression host. PLoS One, 2008. 3(5): p. e2189. 
36. 
WHO, A Field Manual for Low and Moderate Endemic Countries, 2007, World Health Organization: 
Geneva. 
37. 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH), Guidance for Industry: Good Clinical Practice: Consolidated 
Guidance (ICH-E6). 1996, Rockville, MD: U.S. Department of Health and Human Services, Food and 
Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation 
and Research (CBER). 
38. 
Rothman KJ and J. Boice JD, Epidemiologic Analysis with a Programmable Calculator (NIH Publication 
79-1649). . 1979, Washington DC: US Government Printing Office. 
39. 
Creek, D., et al., Increased risk of early vomiting among infants and young children treated with 
dihydroartemisinin-piperaquine compared with artemether-lumefantrine for uncomplicated malaria. 
The American journal of tropical medicine and hygiene, 2010. 83(4): p. 873-5. 
40. 
A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated 
malaria in African children: a randomized trial. PLoS medicine, 2011. 8(11): p. e1001119. 
41. 
Dellicour, S., et al., The safety of artemisinins during pregnancy: a pressing question. Malar J, 2007. 6: 
p. 15. 
 
 
 
 

 
 
 
58
Appendix A. Study information for stakeholders 
 
An Evaluation of TPE (targeted parasite elimination) for Malaria Elimination in Swaziland - Study 
Information for Stakeholders 
 
In 2007, the Swaziland Ministry of Health (MoH) established a goal to eliminate malaria. In order to interrupt 
malaria transmission, it is necessary to implement preventative measures (such as vector control, health 
education) as well as find and treat all infections, whether symptomatic or asymptomatic. Swaziland’s 
transition from a malaria control to elimination program required the scaling up of community-based 
interventions including:   
 
Reactive Case Detection (RACD): household members and neighbors of index cases residing in 
malaria receptive are screened for malaria using rapid diagnostic tests (RDTS) to identify secondary 
infections 
 
Universal coverage of Long Lasting Insecticide Net (LLIN) in receptive areas: community members are 
provided with free LLINs and are encouraged to sleep under a net  
 
Indoor Residual Spraying (IRS): community members are encouraged to allow their houses to be 
sprayed with insecticide before and during malaria seasons. 
 
Promoting appropriate health seeking behavior.  
 
Targeted Parasite Elimination (TPE), which involves the treatment of all high-risk individuals with an effective 
drug irrespective of and without knowledge of that individuals’ infection status, has been proposed as a 
strategy to complement the above mentioned community strategies. The goal of TPE is to treat existing 
reservoirs of infection and prevent future infection through the drug’s prophylactic effect. An advantage of 
TPE, over RACD, is that it does not depend on RDTs which often miss low density infections among 
asymptomatics. In collaboration the University of California, San Francisco Global Health Group (UCSF GHG), 
Clinton Health Access Initiative (CHAI) and other partners, MoH will pilot TPE in selected high-risk localities 
while studying the feasibility and effectiveness of this approach compared to RACD. 
 
Study stakeholders in Swaziland include, but are not limited to: 
 
Members of the MoH 
o Swaziland Laboratory Health Services (SLHS) 
o Regional Health Management Teams  
o Rural Health Motivators (RHMs)  
 
Swaziland Malaria Elimination Advisory Group (SMEAG) Members 
 
Chiefdoms (Regional Administrators office) 
Informational Sessions for National and Regional level stakeholders: 
The Ministry of Health (MoH) and its national level partners are invited to attend a briefing of the proposed 
TPE study before its commencement on the 01st of November 2014.  
Regional health management teams will be briefed during their monthly meetings before study 
commencement and regularly updated during study progression. As a key facet of the study includes the 
administration of a drug to asymptomatic community members, one goal of these meetings will be to utilize 
regional networks to ensure that clinical and public health workers within targeted localities are made aware 
of the study goals and activities.  
 
Informational Sessions for Community level stakeholders: 
Study staff will work with Regional Administrators to identify chiefdoms in study areas and their relevant 
leaders, including Bandlancane (community leaders committee) and clinic committees. These community 
level leaders will be invited to attend informational sessions about the TPE study.  
Stakeholder engagement is critical to ensure successful implementation of novel community interventions 
such as TPE. Making all levels of the health delivery process aware of the study will provide the NMCP with 
the needed support to effectively deliver and engage the community in proposed interventions. Knowledge 
of TPE by health care workers in targeted localities will also assist with management of potential but rare 
adverse reactions to the study drug.   
 

 
 
 
59
Appendix B. Index case immediate notification form 
 
 
 
 

 
 
 
60
Appendix C. Index Case, Case Investigation Form 
 
Greetings! My name is _____________.  I am conducting surveillance with the National Malaria Control 
Program within the Ministry of Health. You or your child recently had malaria and we would like to better 
understand why you were infected. I will talk with you to learn about your potential risk factors for malaria. If 
a blood sample was not collected at the time of your malaria diagnosis, I will perform a finger prick for blood 
testing. The questionnaire and blood collection will be performed in your home and will take about 10-15 
minutes.  
 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive 
questions and measures are in place to keep the information you provide confidential. If blood collection 
being performed: One may feel a brief moment of pain when the blood is being collected, but the risk is 
minimal because the process will be done by a well trained officer. 
 
As malaria is spread by mosquitoes, your family and neighbours may be at risk for malaria. For this reason, 
we would like to protect them from contracting malaria and/or treat them if they are already infected. We 
are currently conducting a study to evaluate community based inteventions and will invite them to 
participate. 
 
We would like to return in 6-9 months to check on the resolution of your infection.  We would also like to 
return in near the end of the study (expected mid 2017) to check on whether there continues to be malaria in 
your community. Each of these visits will include blood collection and only take a few minutes. Your 
participation in these follow-up studies will be voluntary. 
 
The information gathered from this work will be useful for planning future programmes in the fight against 
malaria. You and your family will be able to receive all benefits or assistance from any future program. If you 
have any questions, you can contact Mr. Simon Kunene, Program Manager, National Malaria Control 
Program, Ministry of Health, at 5053804. 
 
 
Patient Details (data available on immediate notification form, but also confirm with patient) 
1. Scan barcode 
2.  Patient Name _____________________________________  
 
3.  Date of birth 
|___|___|/|___|___|/|___|___| 
 
 
date         month       year 
4.  Gender 
 Male Female 
5. Pregnant  
 Yes (Trimester________)   No 
6. Inkhundla 
_____________________________________ 
7. Locality 
_____________________________________ 
8. Patient contact information 
a. Telephone number 1: ________________________ 
b. Telephone number 2: ________________________ 
 
Case Report (data available on immediate notification form) 
9. Date Case Reported   |___|___|/|___|___|/|___|___| 
 
 
                day       month      year 
10. Case Identified by:  
 
977 Hotline (If yes, EPR case ID #__________) 
 

 
 
 
61
 
Active Case Detection 
 
Quality Assurance Program 
 
Health facility site visit  
 
Phone Call to NMCP 
 
Other ______________________________ 
 
Presentation at Health Facility (data available from immediate notification form or health facility worker) 
11. Health Facility Name 
 _____________________________________  not applicable 
12. Presentation Date 
|___|___|/|___|___|/|___|___| not applicable 
 
 
        day       month       year 
13. Disease severity  Uncomplicated Severe    Unknown 
 
Diagnosis (data available from health facility worker and/or NMCP) 
14. Original diagnosis confirmed by (may check more than one if applicable) 
 
 RDT    Microscopy 
 
If diagnosed by microscopy, specify:          
 
 ______ parasites per microliter (µl) 
 
Species:    PfPmPoPvUnknown 
Second Confirmation of Diagnosis  
15. Blood smear taken for second confirmation 
 
Yes   No Unknown  
 
If yes, was blood smear read to confirm diagnosis? 
 Yes   No Unknown 
 
Slide read by 
_____________________________________ (slide reader) 
 
Slide read at 
_____________________________________ (location) 
 
 
If yes, what was the slide result? 
 
 
 Malaria Parasites Present, specify: 
 
______ parasites per microliter (µl) 
 
Species:    PfPmPoPvUnknown 
 
 No Malaria Parasites Seen  
 
 Undetermined 
 
 
 Unknown 
 
16. DBS collected  Yes   No 
If DBS not collected, why? 
Patient refusedOther ___________________ 
 
17. DBS collected from before treatment collected?  Yes   No 
If no, why?   
 
Health facility staff not aware of policy to collect DBS before treatment  
Health facility staff forgot about policy to collect DBS before treatment   
 Sample lost 
 Patient refused 
Other ___________________ 
 
18. If DBS collected as part of QA program, note QAID _______________ 
 
Investigation Details 
19. Investigation date |___|___|/|___|___|/|___|___| 
 
date         month       year 
20. Conducted at   

 
 
 
62
 
 Homestead of case 
 
 Work place of case 
 
 Health facility where case presented 
 
 Health facility where patient currently admitted 
 
 Other______________________________  
 
 
 
 
 
21. If investigation not conducted at home, Address 
__________________________________________________________________________________
__________________ 
__________________________________________________________________________________
__________________ 
 
22. Investigation conducted by, (check all that apply) 
 
BadelisileCalsileGcinumuziKhayaMathokozaMduduziMpenduloNombuso 
NomceboNomkhosiSenzoThulaniVusani Other___________________ 
 
23. GPS coordinates of home (can skip and record later, as interview may not be conducted at subject’s 
home) 
 
S ____° ____’ ____”  
 
E ____° ____’ ____” 
 
Other Patient Details 
24. Nationality 
 
 
 Swaziland 
 
 Mozambique 
 
 South Africa 
 
 Other (specify _______________________) 
 
25. Occupation 
 
 Student 
 Child or minor but not student 
Unemployed 
 
Farming/Agriculture 
 
Manufacturing/Factory 
 
Other Manual Labor 
 
Small-market sales or trade 
 
Office or Clerical Work 
 
Other (specify _______________________) 
 
26. Location of occupation/education  
Inkhundla 
_____________________________________ 
Locality 
_____________________________________ 
27. Other, specify: _____________________________________ 
 
Clinical 
28. Ask: How long were you experiencing symptoms before you sought treatment at the health facility?  
____ days 
 
29. Ask: Please describe to me the anti-malarial treatment you took. Check all that apply 
Artemether Lumefantrine 
 Single dose primaquine 
 
 Oral Quinine 
 IV Quinine 
 IM Quinine 
Chloroquine 

 
 
 
63
 SP/Fansidar 
 Other (specify _______________________ 
Unknown 
 
30. Was full course of anti-malarial treatment completed?  Yes   No 
 
31. Ask: Have you experienced any side effects? 
 
 Yes (specify________________)   No 
 
32. Ask: Do you still feel sick?  
 Yes  No   
If no, skip to next question. 
If yes, ask: What malaria signs and symptoms still remain? 
 Fever 
 
 
 Chills 
 
 
 Sweating 
 
 
 Headache 
 
 
 Abdominal Pain 
 
 
 Anemia  
 
 
 Motor weakness 
 
 
 Joint pain 
 
 
 Abdominal Pain 
 
 
 Nausea, Vomiting 
 
 
 Diarrhea 
 
 
 Other (Specify_____________________) 
 
33. Ask: Have you ever previously had malaria? (yes/no) 
If no, skip to next question 
If yes, ask:  
Approximately how many times have you had laboratory confirmed malaria in your life?  
________ 
 If 1 episode, ask: 
o Approximately how long ago was it that you had malaria? _____ yrs _____ mo 
 If >1 episode, ask:  
o Approximately how long ago was the first time you had malaria? 
 _____ yrs  _____ mos  (Enter 0 for years or months if indicated) 
o Approximately how long ago was the most recent time you had malaria?  
 _____ yrs  _____ mos (Enter 0 for years or months if indicated) 
 
Prior Residence and/or Travel History 
34. Have you ever lived or stayed in Mozambique for at least 30 consecutive days? 
If yes, approximately how long ago was this visit or stay? _____ yrs _____ mos 
35.  Have you spent at least one night anywhere else besides your current residence in the past 8 weeks? 
 Yes   No   Don’t know 
 
If no, skip to next question. 
 
If yes, ask: Where did you sleep overnight, when did you sleep there, why did you sleep there, 
and personal protection?  If slept outside Swaziland, also ask about means of travel and border 
post of re-entry.

 
Within Swaziland 
Town / Locality / 
Tinkhundla 
Duration of Stay 
Reason for sleeping away from current 
residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal protection  
-chemoprophylaxis (specify___) 
-bednet 
-mosquito repellent or coil 
-None 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
a. 
 
 
 
 
b.  
 
 
 
 
c.  
 
 
 
 
d.  
 
 
 
 
e.  
 
 
 
 
 
Outside of Swaziland 
Country 
Province 
/ Town 
Duration of Stay 
Reason for sleeping away 
from current residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal 
protection  
-
chemoprophylax
is (specify___) 
-bednet 
-mosquito 
repellent or coil 
-None 
Means of travel 
-Large bus 
-Kombi (van) 
-Personal car 
-Ride share (catch a 
ride/got a lift) 
-Airplane 
-Bicycle 
-Walked 
-Other 
(specify_____________) 
Border Post of Re-Entry 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
- Lavumisa/ Golela 
- Salitje/ Onverwacht 
- Mahamba 
- Gege/ Bothashoop 
- Sicunusa/ Houtkop 
- Sandlane/ Nerston 
- Ngwenya/ Oshoek 
 
- Bulembu/ Josefsdal 
- Matsamo/ Jeppe’s Reef 
- Mananga 
- Lomahasha/ Namaacha 
- Mhlumeni/ Goba 
- Matsapha International 
Airport 
- Other 
 
a. 
 
 
 
 
 
 
 
b.  
 
 
 
 
 
 
 
c.  
 
 
 
 
 
 
 
d.  
 
 
 
 
 
 
 
e.  
 
 
 
 
 
 
 
 

Household information 
36. Including you, how many people live in the household? ___________ 
37. Are you the household head or acting household head? Yes   No 
 
Vector Control and Personal Protection Measures 
38. Have you slept outside in the past week?  
                   Yes   No 
 
39.  Ask: Do you regularly sleep inside a structure?                                     Yes   No 
 If yes, Ask: Which structure do you regularly sleep in? 
 
40. Observe: What are the exterior walls of the house primarily made of? 
 Mud (includes stick and mud) 
Cane, grass, or shrub 
Plywood/wood 
 Cement block or brick 
 No observation conducted 
 
41. Observe: What are the interior walls of the house primarily made of? 
 Mud (includes stick and mud) 
Cane, grass, or shrub 
Plywood/wood 
 Cement block or brick 
 Plaster 
 No observation conducted 
 
42. Observe: What is the roof primarily comprised of? 
 Grass or palm 
Metal sheets or tile 
 
 No observation conducted 
 
43. Observe: Does the structure where the person sleeps have windows?     Yes       No 
If yes, observe: Are the windows screened or covered?  
   Yes       No 
 
44. Observe: Are there cracks/spaces at the eaves of the structure?               Yes       No 
 
45. Ask: Has this home be sprayed in the past year?          Yes   No    Don’t Know 
 
If yes, ask to see spray card to confirm house has been sprayed.           
 Spray card confirmed 
 
          
 No spray card 
          
 Cannot find spray card 
 
 
If yes, were all the houses sprayed?          Yes    No   Don’t Know 
 
 
If yes, do you sleep under a sprayed structure?           Yes    No   Don’t Know 
 
46. Ask: Does your household own a bed net? 
 Yes     No 
If yes, ask: How many bed nets do you have in the household? ___________ 
How many are treated with insecticide? 
___________ 
 
 
    Did you sleep under your bed net anytime within the past week? 
 Yes   No 
 
If yes, ask: Is your bed net treated with insecticide? 
     Yes  No  Don’t Know 
 
If no, ask: Why didn’t you sleep under a bed net within the past week? 
 Too hot 

 
 
 
66
 Too cold 
 Used by someone else 
 Net not hung up 
 Net worn out/poor condition 
 Net dirt 
 Net bad for health 
 Don’t like shape or color 
 Other ___________________ 
 
47. Are there any water bodies around or near the house? Yes  No   Don’t Know 
If yes, ask: what kind of body of water (check all that apply): 
 
 
river   lake  reservoir  pond  other, specify: ________________ 
If yes, ask: What is the closest distance to a water body? 
<50m 50-99m100-499m  500m-999m  ≥1 km 
 
Thank you for our participation in this study. 
 
48.   
As mentioned, we would like to return in 6-9 months to check on the resolution of your 
infection.  We would also like to return in mid 2017 to check on whether there continues to be 
malaria in your community; at this visit we would like to collection in your family and neighbours in 
addition to you. Each visit will only take a few minutes. Your participation in these follow-up studies 
will be voluntary. Are you willing to be contacted for these follow-up visits?   
 Yes   No   Don’t Know 
 
49. Case Investigation Comments: Is there any other information that is relevant for this case 
investigation? 
__________________________________________________________________________________
__________________ 
__________________________________________________________________________________
__________________ 
__________________________________________________________________________________
__________________ 
 
Case Determination (To be conducted by supervisors following completion of investigation) 
50. Origin of infection 
Local  
Imported from another country   
 Imported from another area of Swaziland   
 Unknown 
Other 
 
51. Case epidemiology 
Index 
Secondary case from RACD   
 Secondary case but identified in health facility   
 Unknown 
Other 
 
Response Determination (To be conducted by supervisors following completion of investigation) 
52. Please check all that apply regarding the response: 
Receptive area –TPE study locality 

 
 
 
67
TPE planned 
TPE not planned as already completed in the past 8 weeks, note aciid: ____________ and 
patient name ________________ 
 
Receptive area: RACD study locality 
RACD planned 
RACD not planned as already completed in the past 5 weeks, note aciid: ____________ and 
patient name ________________ 
 
Receptive area: Non-Study locality 
RACD planned 
RACD not planned as already completed in the past 5 weeks, note aciid: ____________ and 
patient name ________________ 
Imported Network screening planned 
Other, explain ___________________________ 
 
Non -receptive area 
Imported Network screening planned 
RACD planned, explain why __________________________ 
Other, explain ___________________________ 
 
 
53. Response comments 
_____________________________________________________________________________________
_______________ 
_____________________________________________________________________________________
_______________ 
_____________________________________________________________________________________
_______________ 
 
54. Determination conducted by________________________ 
 

 
 
 
68
Appendix D. Unsuccessful Case Investigation  
(Malaria Cases table) 
 
1. Malaria Case ID (Scan Barcode) ____________________ 
 
Investigation Details 
2. Investigation date   |___|___|/|___|___|/|___|___| 
 
      date         month       year 
3. Investigation conducted by,  (check all that apply)  
Calsile Sandile Khaya Mathokoza Mduduzi Mukelwe Nombuso 
Nomcebo Nolwazi Senzo Thulani Fanele  Other___________________ 
4. Conducted at  
 
 
 Homestead of case 
 
 Work place of case 
 
 Health facility where case presented 
 
 Health facility where patient currently admitted 
 
 NMCP 
 
 Other______________________________ 
5. GPS coordinates of home (if subject’s home visited) 
Latitude: _______________________________ 
Longitude: ______________________________  
 
 
Case Report (data available on immediate notification form) 
6. Date Case Reported   |___|___|/|___|___|/|___|___| 
 
 
      date         month       year 
7. Case Identified by: 
 
 
977 Hotline (If yes, EPR case ID #__________)  
 
Active Case Detection 
 
Quality Assurance Program 
 
Health facility site visit  
 
Phone Call to NMCP 
 
Other ______________________________ 
 
Presentation at Health Facility (data available from immediate notification form or health facility worker) 
8. Health Facility Name 
 _____________________________________  not applicable 
9. Presentation Date 
 |___|___|/|___|___|/|___|___|                not applicable 
 
 
date         month       year 
10. Disease severity  Uncomplicated Severe    Unknown 
 
Patient Details 
11. Patient Name: ______________________________ 
12. Age: ___ years  ___ months 
13. Gender:    Male   Female  Unknown 
14. Contact Number  ____________________ 
15. Name of household head if any____________________ 
16. Region ____________________  Inkhundla ____________________   Locality ____________________ 
17. Reason case investigation was unsuccessful, check reason that best describes the situation: 
 
Not reported   
 
No SMS notification 
 
 Contact information is incomplete, inaccurate, not updated 
 
 Not reachable by phone 
 
 Not able to locate home 
 
 Patient is not available (at work, busy etc.) 
 
 Patient has left the country 
 
 Patient resides here but is currently staying elsewhere (within Swaziland) 
 
 Patient has since moved 
 
 Refused 
 
 Patient died 
 
House physically inaccessible 
 
Transport limitations 

 
 
 
69
 
Language barrier 
 
 Found in ACD and no case investigation completed   
Other, specify ______________ 
 
Diagnosis (data available from health facility worker and/or NMCP) 
18. Original diagnosis confirmed by (may check more than one if applicable) 
 
 RDT    Microscopy 
 
If diagnosed by microscopy, specify:          
 
 ______ parasites per microlitre (µl) 
 
Species:    Pf Pm Po PvUnknown 
        Second Confirmation of Diagnosis  
19. Blood smear taken for second confirmation  
Yes   No Unknown  
 
If yes, was blood smear read to confirm diagnosis? 
 Yes   No Unknown 
 
Slide read by 
_____________________________________(slide reader) 
 
Slide read at 
_____________________________________ (location) 
 
 
If yes, what was the slide result? 
 
 
 Malaria Parasites Present, specify: 
 
______ parasites per microlitre (µl) 
 
Species:    Pf Pm Po PvUnknown 
 
 No Malaria Parasites Seen  
 
 Undetermined  
 
 Unknown 
 
20. DBS collected from patient before treatment?  Yes   No 
If no, why?   
 
 
Health facility staff not aware of policy to collect DBS before treatment  
 
Health facility staff forgot about policy to collect DBS before treatment   
 
 Sample lost  
 
 Patient refused 
 
Other ___________________ 
21. If DBS collected as part of QA programme, note QAID _______________ 
22. Comments 
___________________________________________________________________________________________
___________________________________________________________________________________________
___________________________________________________________________________________________
___________________________________________________________________________ 
23. Directions to homestead: 
___________________________________________________________________________________________
___________________________________________________________________________________________
___________________________________________________________________________________________
___________________________________________________________________________ 
 
Case Determination (based on discussion with family, health facility workers, conducted by CSO or Surveillance 
Supervisors) 
24. Presumed origin of infection 
Local  
Imported from another country   
 Intraported (Imported from another area of Swaziland  ) 
 Unknown 
 
25. Date first entered |___|___|/|___|___|/|___|___|   Date last modified |___|___|/|___|___|/|___|___| 
 
date              month        year 
 
date                month           year 

 
 
 
70
 Appendix E. (1) Resident Enrollment, Intervention, RACD Arm:  
Adult Informed Consent Form  
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. A member from your household or neighbor had malaria. You may also be at risk for malaria and we would like to invite you to 
participate in a study where we would implement and evaluate interventions to treat and prevent malaria. Your participation is important, although 
entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates Foundation.    
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone will be tested for malaria and only people who have malaria will be referred for treatment. In another group 
of communities (the second group), everyone will receive treatment and prevention for malaria, whether or not they have malaria. Communities will 
receive either one of these two interventions. Your community has been selected to test everyone for malaria and treat individuals who are infected 
(the first group of communities).   
 
How many people will take part in this study?  
About 4500 people will be in the first group of communities and 4500 people will be in the second group of communities.  
 
What will happen if I take part in this research study? 
Right now, you are only being asked to provide consent for the study activities occurring today. Before you participate in any future visit study 
activities, we will ask you to provide consent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your experiences with malaria and will record your answers on a tablet. If 
you are the head of your household, we will also ask you a few additional questions about how you protect your family against mosquito 
bites in your home. We will collect your name, address, and contact information so that we can follow up with you in the future. By finger 
prick, we will collect a small amount of blood (1/20th of a teaspoon) for malaria testing and for research purposes related to malaria. If you 
are found to be infected with malaria, we will perform a second finger prick to collect a second sample of blood (1/20th of a teaspoon) for 
research purposes. We will also refer you to the nearest health facility for malaria treatment. 
 
In 6-9 months from today: 
If today’s test shows that you are infected with malaria, our study team will return to collect a small amount of blood (1/10th of a teaspoon) 
by finger prick. This will allow us to follow the course of your infection. If today’s test shows that you are not infected, we may still return at 
this time to collect a small blood sample so that we can better understand the body’s response to malaria infection.  
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect an 
additional small amount of blood (1/20th of a teaspoon) by finger prick from you. We will also ask you a few basic questions about your 
experiences with malaria and will record your answers on a tablet. 
 
We will perform a rapid test for malaria each time we take a blood sample from you and, if the rapid test shows that you have malaria, we will refer 
you to the nearest health facility for treatment. We would also like to save a portion of each blood draw for future research studies related to malaria 
only.   
 
How long will I be in the study? 
Today’s questionnaire and blood collection will be performed in your home and will take about 10-15 minutes. The future visits for blood collection 
will occur in your home and take 5-10 minutes.  
 
Can I stop being in the study?  
You may choose either to take part or not to take part in the study. If you decide to take part in this study, you may leave the study at any time. If at 
any time, you would like to withdraw your information and/or withdraw blood samples from malaria testing, you can contact us. If you choose not to 
participate in the study or leave the study, there will be no penalty to you or your family. You will not lose any regular benefits and it will not affect 
your medical care.  
 
What risks can I expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the 
information you provide confidential. You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at 
the site of the finger prick, but the risk is minimal because the process will be done by a well-trained officer.  
 
Medical care 
We do not expect any problems with participating in the study. Contact our Study Coordinator if you experience a potential side effect from your 
participation.  For urgent and concerning symptoms, such as chest pain, dizziness or feeling faint, having trouble breathing, flushing, or hives (an itchy 
swollen rash) visit your local health facility or call the national emergency “977 Hotline.” If you become ill, you should seek care at your local health 
facility, where you will be evaluated and treated as indicated for malaria and other illnesses.  
 
Are there benefits to taking part in the study? 
If you are found to have malaria on rapid testing today or at future visits, you will benefit from being refered for malaria treatment. 
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you. You will still get care 
from the health facility the way you usually do. Even if you do not take part in the study today, you are still eligible to participate in the follow-up 
blood test near the end of the study. 
 
How will information about me be kept confidential? 

 
 
 
71
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will 
be used throughout the study. There may be situations where we need your name, for example for follow up visits. Therefore, we will keep a key 
linking your name to your study number/identifier. But only key study staff will have access to this information. All information from the study will be 
kept in locked cabinets or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the 
Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name will not 
appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
You may choose either to take part or not to take part in the study. If you decide to take part in the study, you may leave the study at any time. No 
matter what decision you make, there will be no penalty to you in any way. You will not lose any of your regular benefits, and you can still get your 
care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you were found to have 
malaria today and experience any adverse health events that may be related to treatment, contact your attending Study Nurse at +268 #### ####. If 
you wish to voice any problems or concerns you may have about how this study is being conducted, please call the office of the Swaziland Ministry of 
Health’s Ethics Committee at +268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or 
to withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, 
you should indicate how you would like to participate and sign below. 
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
  
I agree to provide a blood sample for malaria testing today (by a rapid diagnostic test).  
 
 
 Yes       No 
   
I agree to allow a part my blood sample to be saved for research purposes related to malaria only.  
 
 Yes       No   
 
If I am found to be infected with malaria, I agree to provide a second blood sample, which will be saved for  
research purposes related to malaria only.  
 
 
 
 
 
 
 Yes       No     
 
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                                        Name   
 
 
 
Signature or finger print  
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                    Name   
 
 
 
Signature or finger print of witness 
 
 

 
 
 
72
Appendix E. (2) Resident Enrollment, Intervention, RACD Arm: 
Adult Consent & Parent/Guardian Permission Form for Children  
(one form per Parent/Guardian: obtains consent from the Parent/Guardian and permission for 
multiple children) 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. A member from your household or neighbor had malaria. You and your child(ren) may also be at risk for malaria and we would like 
to invite you and your child(ren) to participate in a study where we would implement and evaluate interventions to treat and prevent malaria. You and 
your child(ren)’s participation is important, although entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates Foundation.    
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone will be tested for malaria and only people who have malaria will be referred for treatment. In another group 
of communities (the second group), everyone will receive treatment and prevention for malaria, whether or not they have malaria. Communities will 
receive either one of these two interventions. Your community has been selected to test everyone for malaria and treat individuals who are infected 
(the first group of communities).   
 
How many people will take part in this study?  
About 4500 people will be in the first group of communities and 4500 people will be in the second group of communities.  
 
What will happen if we take part in this research study? 
Right now, you are only being asked to provide consent for the study activities occurring today. Before you participate in any future visit study 
activities, we will ask you to provide consent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your child(ren) and your experiences with malaria and will record your 
answers on a tablet. We will collect the name(s), address(s), and contact information for you and your child(ren) so that we can follow up 
with you in the future.  By finger prick, I will collect a small amount of blood (1/20th of a teaspoon) from you and your child(ren) for malaria 
testing  and for research purposes related to malaria only. If any of you are found to be infected with malaria, we will perform a second 
finger prick on the infected individual(s) to collect a second sample of blood (1/20th of a teaspoon) for research purposes. We will also 
refer infected individual(s) to the nearest health facility for malaria treatment. 
 
In 6-9 months from today: 
If today’s test shows that you or your child(ren) are infected with malaria, our study team will return to collect a small amount of blood 
(1/10th of a teaspoon) by finger prick from the infected individual(s). This will allow us to follow the course of your or your child(ren)’s 
infection. If today’s test shows that you and your child(ren) are not infected, we may still return at this time to collect a small blood sample 
so that we can better understand the body’s response to malaria infection.  
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect an 
additional small amount of blood (1/20th of a teaspoon) by finger prick from you and your child(ren). We will also ask you a few basic 
questions about you and your child(ren)’s experiences with malaria and will record your answers on a tablet. 
 
We will perform a rapid test for malaria each time we take a blood sample from you and your child(ren) and, if the rapid test shows that any of you 
have malaria, we will refer the infected individual(s) to the nearest health facility for treatment. We would also like to save a portion of each blood 
draw for future research studies related to malaria only.   
 
How long will we be in the study? 
Today’s questionnaire and blood collection will be performed in your home. The questionnaire will take about 10 minutes and blood collection will 
take about 5 minutes per person. The future visits for blood collection will occur in your home and take 5-10 minutes per person.  
 
Can we stop being in the study? 
You may choose either to have you and your child(ren) take part or not to take part in the study. If you decide to take part in this study, you and/or 
your child(ren) may leave the study at any time. If at any time, you would like to withdraw your or your child(ren)’s information and/or withdraw 
blood samples from malaria testing, you can contact us. If you choose not to participate in the study or leave the study, there will be no penalty to you 
or your family. You and your child(ren) will not lose any regular benefits and it will not affect your or your child(ren)’s medical care.  
 
What risks can we expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the 
information you provide confidential. There may be a brief moment of pain when the blood is being collected and there is a small risk of infection at 
the site of the finger prick, but the risk is minimal because the process will be done by a well trained officer. Participation or refusal to participate in 
this study will not affect you or your child(ren)’s care in any way. 
 
Medical care 
We do not expect any problems with participating in the study. Contact our Study Coordinator if you or your child(ren) experience a potential side 
effect from participation. For urgent and concerning symptoms, such as chest pain, dizziness or feeling faint, having trouble breathing, flushing, or 
hives (an itchy swollen rash), bring your child(ren) to your local health facility or call the national emergency “977 Hotline.” If you or your child(ren) 
become ill, go to your local health facility for evaluation and treatment as indicated for malaria and other illnesses.  
 
Are there benefits to taking part in the study? 
If you or your child(ren) are found to have malaria on rapid testing today or at future visits, the infected individual(s) will benefit from being refered 
for malaria treatment.  
 
What other choices do I have if we do not take part in the study? 

 
 
 
73
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you or your child(ren). You 
all will still get care from the health facility the way you usually do.  Even if you and your child(ren) do not take part in the study today, you are all are 
still eligible to participate in the follow-up blood test near the end of the study. 
 
How will information about us be kept confidential? 
We will not inform anyone of you or your child(ren)’s participation in the study and your names will be kept confidential by replacing them with 
numbers/identifiers that will be used throughout the study. There may be situations where we need your or your child(ren)’s name, for example for 
follow up visits. Therefore, we will keep a key linking your names to the numbers/identifiers. But only key study staff will have access to this 
information. All information from the study will be kept in locked cabinets or computers. Organizations that will examine the data are the National 
Malaria Control Program in Manzini, Swaziland, the Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San 
Francisco, United States of America. Your names will not appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will we be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are our rights if we take part in this study? 
You may choose to have you and your child(ren) either to take part or not to take part in the study. If you decide to take part in the study, you and 
your child(ren) may leave the study at any time. No matter what decision you make, there will be no penalty in any way. You and your child(ren) will 
not lose any regular benefits, and you all can still get your care from your health facility the way you usually do. 
 
Who can we contact if we have future questions about the study? 
If you have any questions about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you or your child(ren) 
were found to have malaria today and experience any adverse health events that may be related to treatment, contact your attending Study Nurse at 
+268 #### ####.  If you wish to voice any problems or concerns you may have about how this study is being conducted, please call the office of the 
Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  Your child(ren) are unable to consent for 
themselves because they are less than 18 years old. By signing this form, you are giving permission for you and your child(ren) or ward(s) to participate 
in the study. You have the right to decline to participate or to withdraw yourself or your child(ren) at any point in this study without penalty or loss of 
benefits to which you or your family are otherwise entitled. If you wish to participate in this study, you should indicate how you would like to 
participate and sign below. 
 
Number of children (<18 years old) that I consent may participate in the study:                                . 
 
I agree to be interviewed today.                                                                              
 Yes       No 
 
I agree to have my child(ren) be interviewed today, if requested by study staff.                                                                              
 Yes       No 
 
I agree to provide a blood sample for malaria testing today (by a rapid diagnostic test). 
 Yes       No 
 
I agree to have my child(ren) provide blood sample(s) for malaria testing today (by a rapid diagnostic test). 
 Yes       No 
 
I agree to allow a part of my blood sample to be saved for research purposes related to malaria only. 
 Yes       No   
 
I agree to allow part of my child(ren)’s blood sample(s) to be saved research purposes  
related to malaria only. 
 Yes       No   
 
If I am found to be infected with malaria, I agree to provide a second blood sample, which will be saved for  
research purposes related to malaria only. 
 Yes       No 
 
If my child(ren) are found to be infected with malaria, I agree to have all infected child(ren) provide a second  
blood sample, which will be saved for research purposes related to malaria only. 
 Yes       No 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                     
Name of Parent/Guardian 
 
Signature or fingerprint of Parent/Guardian  
 
 
Name(s) of children (If indicated, list names of additional children on the back of the form): 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #1 
 
 
     Child #2                     
            Child #3 
 
 
         Child #4 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #5 
 
 
     Child #6                     
            Child #7 
 
 
         Child #8 
 
 
 
 

 
 
 
74
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                     Name   
 
 
 
Signature or finger print of witness 
 
 

 
 
 
75
Appendix E. (3) Resident Enrollment, Intervention, RACD Arm:  
Minor (12-17yrs) Assent Form  
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. A member from your household or neighbor had malaria. You may also be at risk for malaria and we would like to invite you to 
participate in a study where we would implement and evaluate interventions to treat and prevent malaria. Your parents or guardian have given their 
permission, but you get to decide if you want to be in this study or not.  Your participation is important, although entirely voluntary. Funding for this 
study is provided by the Bill & Melinda Gates Foundation.    
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone will be tested for malaria and only people who have malaria will be referred for treatment. In another group 
of communities (the second group), everyone will receive treatment and prevention for malaria, whether or not they have malaria. Communities will 
receive either one of these two interventions. Your community has been selected to test everyone for malaria and treat individuals who are infected 
(the first group of communities).   
 
How many people will take part in this study?  
About 4500 people will be in the first group of communities and 4500 people will be in the second group of communities.  
 
What will happen if I take part in this research study? 
Right now, you are only being asked to provide assent for the study activities occurring today. Before you participate in any future visit study activities, 
we will ask you to assent again that day. 
 
Today: 
Our study team will ask you and/or your parent or guardian a few basic questions about you and your experiences with malaria and will 
record your answers on a tablet. We will collect your name, address, and contact information so that we can follow up with you in the 
future.  By finger prick, we will collect a small amount of blood (1/20th of a teaspoon) for malaria testing and for research purposes related 
to malaria only. If you are found to be infected with malaria, we will perform a second finger prick to collect a second sample of blood 
(1/20th of a teaspoon) for research purposes. We will also refer you to the nearest health facility for malaria treatment. 
 
In 6-9 months from today: 
If today’s test shows that you are infected with malaria, our study team will return to collect a small amount of blood (1/10th of a teaspoon) 
by finger prick. This will allow us to follow the course of your infection. If today’s test shows that you are not infected, we may still return at 
this time to collect a small blood sample so that we can better understand the body’s response to malaria infection.  
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect an 
additional small amount of blood (1/20th of a teaspoon) by finger prick from you. We will also ask you a few basic questions about your 
experiences with malaria and will record your answers on a tablet.  
 
We will perform a rapid test for malaria each time we take a blood sample from you and, if the rapid test shows that you have malaria, we will refer 
you to the nearest health facility for treatment. We would also like to save a portion of each blood draw for future research studies related to malaria 
only.   
 
How long will I be in the study? 
Today’s questionnaire and blood collection will be performed in your home and will take about 10-15 minutes. The future visits for blood collection 
will occur in your home and take 5-10 minutes.  
 
Can I stop being in the study? 
With your parent or guardian’s permission, you may choose either to take part or not to take part in the study. If you decide to take part in this study, 
you may leave the study at any time. If at any time, you would like to withdraw your information and/or withdraw blood samples from malaria testing, 
you can have your parent or guardian contact us. If your parent or guardian wants you to withdraw from the study, you must withdraw.  If you choose 
not to participate in the study or leave the study, there will be no penalty to you or your family. You will not lose any regular benefits and it will not 
affect your medical care.   
 
What risks can I expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the 
information you provide confidential. You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at 
the site of the finger prick, but the risk is minimal because the process will be done by a well trained officer. Participation or refusal to participate in 
this study will not affect your care in any way. 
 
Medical care 
We do not expect any problems with participating in the study. Have your parent/guardian contact our Study Coordinator if you experience a potential 
side effect.  For urgent and concerning symptoms, such as chest pain, dizziness or feeling faint, having trouble breathing, flushing, or hives (an itchy 
swollen rash), have your parent/guardian bring you to your local health facility or call the national emergency “977 Hotline.” If you become ill, you 
should seek care at your local health facility, where you will be evaluated and treated as indicated for malaria and other illnesses.  
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you. You will still get care 
from the health facility the way you usually do. Even if you do not take part in the study today, you are still eligible to participate in the follow-up 
blood test near the end of the study. 
 
Are there benefits to taking part in the study? 
If you are found to have malaria on rapid testing today or at future visits, you will benefit from being refered for malaria treatment.  

 
 
 
76
 
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will 
be used throughout the study. There may be situations where we need your name, for example for follow up visits. Therefore, we will keep a key 
linking your name to your study number/identifier. But only key study staff will have access to this information. All information from the study will be 
kept in locked cabinets or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the 
Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name will not 
appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
With your parent or guardian’s permission, you may choose either to take part or not to take part in the study. If you decide to take part in the study, 
you may leave the study at any time. No matter what decision you make, there will be no penalty to you in any way. You will not lose any of your 
regular benefits, and you can still get your care from your health facility the way you usually do.  
 
Who can I contact if I am injured or I have future questions about the study? 
If you have any questions about this study or your participation, you can have your parent/guardian contact our Study Coordinator at +268 #### ####. 
If you were found to have malaria today and experience any adverse health events that may be related to treatment, have your parent/guardian 
contact your attending Study Nurse at +268 #### ####. If you wish to voice any problems or concerns you may have about how this study is being 
conducted, please have your parent/guardian call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
ASSENT 
You have been given a copy of this assent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or to 
withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, you 
should indicate how you would like to participate and sign below. 
 
This study was explained to me clearly. 
 
 
 
 
 
 
 Yes       No  
 
I agree to be interviewed today.  
 
 
 
 
 
 
 Yes       No  
  
I agree to provide a blood sample for malaria testing today (by a rapid diagnostic test).  
 
 Yes       No 
   
I agree to allow a part of my blood sample to be saved for research purposes  
related to malaria only. 
 
 
 
 
 
 
 
 Yes       No   
 
If I am found to be infected with malaria, I agree to provide a second blood sample,  
which will be saved for research purposes related to malaria only.  
 
 
 
 Yes       No     
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                     
Name of Minor 
 
 
Signature or finger print of Minor  
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
WITNESS (only necessary if assent conducted in language other than English or SiSwati) 
I witness that this assent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study. 
Language that assent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                     Name   
 
 
 
Signature or finger print of witness 
 
 

 
 
 
77
Appendix F. (1) Resident Enrollment, Intervention, TPE Arm:  
Adult Informed Consent Form  
 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. A member from your household or neighbor had malaria. You may also be at risk for malaria and we would like to invite you to 
participate in a study where we would implement and evaluate interventions to treat and prevent malaria. Your participation is important, although 
entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone will be tested for malaria and only people who have malaria will be referred for treatment. In another group 
of communities (the second group), everyone will receive treatment and prevention for malaria, whether or not they have malaria. Communities will 
receive either one of these two interventions. Your community has been selected to give everyone medication for treatment and prevention of 
malaria without testing for infection (the second group of communities).   
 
How many people will take part in this study?  
About 4500 people will be in the first group of communities and 4500 people will be in the second group of communities.  
 
What will happen if I take part in this research study? 
Right now, you are being asked to provide consent for the study activities occurring today and for a return visit in 7-10 days. Before you participate in 
any future visit study activities, we will ask you to provide consent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your experiences with malaria and record your answers on a tablet. If you are 
the head of your household, we will also ask you a few additional questions about how you protect your family against mosquito bites in your 
home. We will collect your name, address, and contact information so that we can follow up with you in the future. We will also ask you a few 
questions about your and your family’s medical history and use of medications to see if it is safe for you to be given a malaria medicine called 
dihydroartemisinin-piperaquine, also called DP for short.  
 
If it is safe for you to be given DP, our study team will explain to you how to take this medication. Each daily dose consists of 3 pills that should be 
taken together. You will take the first dose of a 3-day course of DP today. We will leave you with the second and third doses, which should be 
taken approximately the same time tomorrow and the day after, respectively. If a dose is missed, it should be taken as soon as possible. But do 
not take more than 1 dose of DP each day. You will not be given DP if it is unsafe for you. Everyone in your community is being given 3 days of DP 
to treat malaria, whether or not they have it. DP is useful for treatment of malaria, and may also prevent malaria infection in the near future. 
 
If it is not safe for you to be given DP, we will collect a small amount of blood (1/20th of a teaspoon) for malaria testing and for research 
purposes related to malaria only by finger prick. If you are found to be infected with malaria, we will perform a second finger prick to collect a 
second sample of blood (1/20th of a teaspoon) for research purposes. We will also refer you to the nearest health facility for malaria treatment 
with a medication that is safe for you. 
 
In 7-10 days from today: 
We may return to perform a pill count. Therefore, please keep your medicine packaging for at least 10 days. Additionally, we may invite you to 
participate in a group discussion about your experience with the intervention. 
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect a small 
amount of blood (1/20th of a teaspoon) by finger prick from you. We will also ask you a few basic questions about your experiences with malaria 
and will record your answers on a tablet. We will perform a rapid test for malaria and, if the rapid test shows that you have malaria, we will refer 
you to the nearest health facility for treatment. We would also like to save a portion of this blood draw for future research studies related to 
malaria only.   
 
How long will I be in the study? 
Today’s questionnaire and administration of malaria medicine will be performed in your home and will take about 10-15 minutes. The future visits for 
pill counts and blood collection will occur in your home and take 5-10 minutes. If you are selected, the group discussion 7-10 days from today will take 
an hour. 
 
Can I stop being in the study? 
You may choose either to take part or not to take part in the study. If you decide to take part in this study, you may leave the study at any time. If you 
experience symptoms related to taking DP, it is safe to stop taking DP before completing your pills. If at any time, you would like to withdraw your 
information and/or withdraw blood samples from malaria testing, you can contact us. If you choose not to participate in the study or leave the study, 
there will be no penalty to you or your family. You will not lose any regular benefits and it will not affect your medical care. The study doctor may also 
stop you from taking part in this study at any time if he/she believes it is in your best interest, if you do not follow the study rules, or if the study is 
stopped.  
 
What risks can I expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the 
information you provide confidential. You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at 
the site of the finger prick, but the risk is minimal because the process will be done by a well trained officer.  
 
DP has been shown to be safe and very effective for treatment and prevention of malaria in all ages, including children. Serious health problems have 
rarely been reported. There may be some side effects that no one knows about yet. The researchers will let you know if they learn anything that might 
make you change your mind about participating in the study. If you do experience side effects, please ask your rural health motivator to contact study 

 
 
 
78
staff or you may contact study staff directly. For urgent issues, you should stop taking DP, call our study staff, and seek care at a local health facility. 
The risks and side effects related to the study medication, DP, include those which are: 
— 
Likely: No side effect is likely, but the most common is cough or fever 
— 
Less Likely: low red blood cells, headache, lack of energy, vomiting, diarrhea, abdominal pain 
— 
Rare but serious: itching, inflammation or enlargement of the liver, heart rhythm problems 
 
Medical care. 
We do not expect any problems with participating in the study. While DP is safe and not expected to cause any side effects, contact your attending 
Study Nurse if you experience a potential side effect. For urgent and concerning symptoms, such as chest pain, dizziness or feeling faint, having trouble 
breathing, flushing, or hives (an itchy swollen rash), visit your local health facility or call the national emergency “977 Hotline.” Even if it is not safe for 
you to be given the DP medicine, this does not mean that you cannot be treated for malaria with other medication. Therefore, if you think you have 
malaria, or are ill, you should still go to the health care clinic.  
 
Are there benefits to taking part in the study? 
The medication we will give you today will treat malaria if you are infected and it may prevent future infection. If you are found to have malaria by 
rapid testing at future visits, you will benefit from being referred for malaria treatment. DP is NOT a substitute for medicine to prevent malaria when 
traveling to areas where you will be at high risk of malaria infection. If you are traveling, please visit your health facility to assess your risk and if you 
should take medicine to prevent malaria during your trip. 
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you. You will still get care 
from the health facility the way you usually do.  Similarly, if you do not qualify for malaria medicine, and you become ill, you can still get care from the 
health facility and be evaluated and treated as indicated for malaria and other illnesses. Even if you do not take part in the study today, you are still 
eligible to participate in the follow-up blood test near the end of the study.  
 
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will 
be used throughout the study. There may be situations where we need your name, for example for follow up visits. Therefore, we will keep a key 
linking your name to your study number/identifier. But only key study staff will have access to this information. All information from the study will be 
kept in locked cabinets or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the 
Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name will not 
appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures or medications. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
You may choose either to take part or not to take part in the study. If you decide to take part in the study, you may leave the study at any time. No 
matter what decision you make, there will be no penalty to you in any way. You will not lose any of your regular benefits, and you can still get your 
care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you have experienced 
any adverse health events that may be related to DP, please contact your attending Study Nurse at +268 #### ####. If you wish to voice any problems 
or concerns you may have about how this study is being conducted, please call the office of the Swaziland Ministry of Health’s Ethics Committee at 
+268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or 
to withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, 
you should indicate how you would like to participate and sign below. 
 
I agree to be interviewed today.  
 
 
 
 
 
 
      
 
 Yes       No  
 
I agree to take anti-malarial medication, if eligible. 
 
 
 
 
             
     
 
 Yes       No       
   
I agree to a possible pill count and group discussion in 7-10 days.  
 
 
 
      
 
 Yes       No       
 
If I am not eligible to receive DP, I agree to provide a blood sample for malaria testing today  
(by a rapid diagnostic test).   
  
 
 Yes       No       
 
If I am not eligible to receive DP, I agree to allow a part of my blood sample to be saved for research  
purposes related to malaria only). 
 
 
 
 
      
 
      
 
 Yes       No       
 
If I am not eligible to DP and I am found to be infected with malaria, I agree to provide a second blood  
sample, which will be saved for research purposes related to malaria only. 
      
 
 
 
 
 Yes       No       
 
 
 

 
 
 
79
 
 
                   
 
                    
                    
 
 
 
 
Date 
                                        Name   
 
 
 
 Signature or finger print  
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                
 Name   
 
 
 
  Signature or finger print of witness 
 
 

 
 
 
80
Appendix F. (2) Resident Enrollment, Intervention, TPE Arm:  
Adult Consent & Parent/Guardian Permission Form for Children  
(one form per Parent/Guardian: obtains consent from the Parent/Guardian and permission for 
multiple children) 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. A member from your household or neighbor had malaria. You and your child(ren) may also be at risk for malaria and we would like 
to invite you and your child(ren) to participate in a study where we would implement and evaluate interventions to treat and prevent malaria. You and 
your child(ren)’s participation is important, although entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone will be tested for malaria and only people who have malaria will be referred for treatment. In another group 
of communities (the second group), everyone will receive treatment and prevention for malaria, whether or not they have malaria. Communities will 
receive either one of these two interventions. Your community has been selected to give everyone medication for treatment and prevention of 
malaria without testing for infection (the second group of communities).   
 
How many people will take part in this study?  
About 4500 people will be in the first group of communities and 4500 people will be in the second group of communities.  
 
What will happen if we take part in this research study? 
Right now, you are being asked to provide consent for the study activities occurring today and for a return visit in 7-10 days. Before you or your 
child(ren) participate in any future visit study activities, we will ask you to provide consent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your child(ren) and your  experiences with malaria and record your answers on 
a tablet. We will collect the names, addresses, and contact information for you and your child(ren) so that we can follow up with you in the 
future. We will also ask you a few questions about you, your child(ren)’s and your family’s medical history and use of medications to see if it is 
safe for you and your child(ren) to be given a malaria medicine called dihydroartemisinin-piperaquine, also called DP for short.  
 
For individual(s) who can safely be given DP, our study team will explain to you how to take this medication and give this medication to your 
child(ren). You will be given an adult dose of DP. Your child(ren) will be weighed, and the appropriate weight-based dose will be given for each 
child. All pills for each daily dose should be taken together. You and your child(ren) will be given the first dose of a 3-day course of DP today. We 
will leave you with the second and third doses, which should be taken at approximately the same time tomorrow and the day after, respectively. 
If a dose is missed, it should be taken as soon as possible. But do not take more than 1 dose of DP each day. You and your child(ren) will not be 
given DP if it is unsafe. Everyone in your community is being given 3 days of DP to treat malaria, whether or not they have it. DP is useful for 
treatment of malaria, and may also prevent malaria infection in the near future. 
 
If it is not safe for you or your child(ren) to be given DP, we will collect a small amount of blood (1/20th of a teaspoon) for malaria testing and for 
research purposes related to malaria only by finger prick. If you or your child(ren) are found to be infected with malaria, we will perform a 
second finger prick on the infected individual(s) to collect a second sample of blood (1/20th of a teaspoon) for research purposes. We will also 
refer the infected individual(s) to the nearest health facility for malaria treatment with a medication that is safe for you and/or your child(ren). 
 
In 7-10 days from today: 
We may return to perform a pill count. Therefore, please keep all medicine packaging for at least 10 days. Additionally, we may invite you to 
participate in a group discussion about your experience with the intervention. 
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect a small 
amount of blood (1/20th of a teaspoon) by finger prick from you and your child(ren). We will also ask you a few basic questions about you and 
your child(ren)’s experiences with malaria and will record your answers on a tablet. We will perform a rapid test for malaria on you and your 
child(ren) and, if the rapid test shows that any of you have malaria, we will refer the infected individual(s) to the nearest health facility for 
treatment. We would also like to save a portion of these blood draws for future research studies related to malaria only.   
 
How long will we be in the study? 
Today’s questionnaire and administration of malaria medicine will be performed in your home and will take about 10-15 minutes. The future visits for 
pill counts and blood collection will occur in your home and take 5-10 minutes per person. If you or your child(ren) are selected, the group discussion 
in 7-10 days from today will take an hour. 
 
Can we stop being in the study? 
You may choose either have you and your child take part or not take part in the study. If you decide to take part in this study, you or your child(ren) 
may leave the study at any time.  If you or your child(ren) experience symptoms related to taking DP, it is safe for that individual to stop taking DP 
before completing the pills.  If at any time you would like to withdraw your or your child(ren)’s information and/or withdraw blood samples from 
malaria testing, you can contact us. If you choose not to participate in the study or leave the study, there will be no penalty to you or your family. You 
and your child(ren) will not lose any regular benefits and it will not affect your or your child(ren)’s medical care. The study doctor may also stop you or 
your child(ren) from taking part in this study at any time if he/she believes it is in your best interest, if you do not follow the study rules, or if the study 
is stopped.   
 
What risks can we expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the 
information you provide confidential. There may be a brief moment of pain when the blood is being collected and there is a small risk of infection at 
the site of the finger prick, but the risk is minimal because the process will be done by a well trained officer.  
 

 
 
 
81
DP has been shown to be safe and very effective for treatment and prevention of malaria in all ages, including children. Serious health problems have 
rarely been reported. There may be some side effects that no one knows about yet. The researchers will let you know if they learn anything that might 
make you change your mind about your or your child(ren)’s participation in the study. If you or your child(ren) experience side effects, please ask your 
rural health motivator to contact study staff or you may contact study staff directly.  For urgent issues, you or your child(ren) should stop taking DP 
and be brought for care at a local health facility and you should call our study staff. The risks and side effects related to the study medication, DP, 
include those which are: 
— 
Likely: No side effect is likely, but the most common is cough or fever 
— 
Less Likely: low red blood cells, headache, lack of energy, vomiting, diarrhea, abdominal pain  
— 
Rare but serious: itching, inflammation or enlargement of the liver, heart rhythm problems 
 
Medical care 
We do not expect any problems with participating in the study. While DP is safe and not expected to cause any side effects, contact your attending 
Study Nurse if you or your child(ren) experiences a potential side effect. For urgent and concerning symptoms, such as chest pain, dizziness or feeling 
faint, having trouble breathing, flushing, or hives (an itchy swollen rash), seek care at your local health facility or call the national emergency “977 
Hotline.” Even if it is not safe for you or your child(ren) to be given the DP medicine, this does not mean that you cannot be treated for malaria with 
other medication. Therefore, if you think you or your child(ren) have malaria, or are ill, you should still go to the health care clinic. 
 
Are there benefits to taking part in the study? 
The medication you and your child(ren) will be given today will treat malaria if you are infected and it may prevent future infection. DP is NOT a 
substitute for medicine to prevent malaria when traveling to areas where you will be at high risk of malaria infection. If you or your child(ren) are 
traveling, please visit your health facility to assess your risk and see if you or your child(ren) should take medicine to prevent malaria during your trip. 
 
What other choices are there if we do not take part in the study? 
If you decide not to take part in the study, there will be no penalty. You and your child(ren) will still get care from the health facility the way you 
usually do. Similarly, if you or your child(ren) do not qualify for malaria medicine, and become ill, you can still get care from the health facility and be 
evaluated and treated as indicated for malaria and other illnesses. Even if you or your child(ren) do not take part in the study today, you are all still 
eligible to participate in the follow-up blood test near the end of the study. 
 
How will information about us be kept confidential? 
We will not inform anyone of your or your child(ren)’s participation in the study and your names(s) will be kept confidential by replacing them with 
numbers/identifiers that will be used throughout the study. There may be situations where we need your or your child(ren)’s name, for example for 
follow up visits. Therefore, we will keep a key linking your names to your study numbers/identifiers. But only key study staff will have access to this 
information. All information from the study will be kept in locked cabinets or computers. Organizations that will examine the data are the National 
Malaria Control Program in Manzini, Swaziland, the Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San 
Francisco, United States of America. Your and your child(ren)’s names will not appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures or medications. 
 
Will we be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are our rights if we take part in this study? 
You may choose to have you and your child(ren) either to take part or not to take part in the study. If you decide to take part in the study, you and 
your child(ren) may leave the study at any time. No matter what decision you make, there will be no penalty in any way. You and your child(ren) will 
not lose any regular benefits, and you all can still get your care from your health facility the way you usually do. 
 
Who can we contact if we have future questions about the study? 
If you have any questions about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you or your child(ren) 
child experienced any adverse health events that may be related to DP, contact your attending Study Nurse at +268 #### ####.  If you wish to voice 
any problems or concerns you may have about how this study is being conducted, please call the office of the Swaziland Ministry of Health’s Ethics 
Committee at +268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  Your child(ren) are unable to consent for 
themselves because they are less than 18 years old. By signing this form, you are giving permission for you and your child(ren) or ward(s) to participate 
in the study. You have the right to decline to participate or to withdraw yourself or your child(ren) at any point in this study without penalty or loss of 
benefits to which you or your family are otherwise entitled. If you wish to participate in this study, you should indicate how you would like to 
participate and sign below. 
 
 
Number of children (<18 years old) that I consent may participate in the study:                                . 
 
I agree to be interviewed today.                                                                              
 
 Yes 
 No 
 
I agree have my child(ren) be interviewed today, if requested by study staff. 
 
 Yes 
 No 
 
I agree to take antimalarial medication, if eligible. 
             
 Yes 
 No 
  
I agree to have my child(ren) take antimalarial medication, if eligible.      
 
 Yes 
 No 
   
I agree to a possible pill count and group discussion in 7-10 days. 
 
 Yes 
 No 
 
If I am not eligible to receive DP, I agree to provide a blood sample for malaria testing today  
(by a rapid diagnostic test). 
 Yes 
 No 
 

 
 
 
82
If my child(ren) are not eligible to receive DP, I agree to have them provide blood sample(s) for malaria  
testing today (by a rapid diagnostic test).      
 Yes 
 No 
 
If I am not eligible to receive DP, I agree to allow a part of my blood sample to be saved for research  
purposes related to malaria only). 
 
 
 
 
 
 
 
 Yes 
 No 
 
If my child(ren) are not eligible to receive DP, I agree to allow a part of their blood sample(s) to be saved for  
research purposes related to malaria only).  
 
 
 
 
 
 
 Yes 
 No 
 
If I am not eligible to receive DP and I am found to be infected with malaria, I agree to provide a second  
Blood sample, which will be saved for research purposes related to malaria only. 
      
 
 
 Yes 
 No 
 
If my child(ren) are not eligible to receive DP and they are found to be infected with malaria,  
I agree to provide a second blood sample, which will be saved for research purposes related to malaria only. 
      
 Yes 
 No 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                     
Name of Parent/Guardian 
 
Signature or fingerprint of Parent/Guardian  
 
 
Name(s) of children (If indicated, list names of additional children on the back of the form): 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #1 
 
 
     Child #2                     
            Child #3 
 
 
         Child #4 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #5 
 
 
     Child #6                     
            Child #7 
 
 
         Child #8 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                     Name   
 
 
 
Signature or finger print of witness 

 
 
 
83
Information to help parent/guardian keep track of dosing regimen for all of their child(ren): 
 
Illiterate mothers can be assisted by any family member who can read during administration of the drugs. Different color coded 
stickers will be used for different children of different weight/age groups.  
 
If no family member is capable of providing assistance for keeping track of the drug doses for different children, it will be the 
responsibility of the study nurse to revisit the family to administer the drugs. Families provided 3 day DOT by a study nurse due to 
illiteracy will be excluded from the measurement of adherence.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight band 
Regimen 
Number of days 
Number of pills each day 
Packaging 
<7kg 
Not eligible 
 
 
 
7-12 kg 
320mg /40mg  
3 
½ 
Pink Bottle 
 
 
 
 
 
13-23 kg 
320mg /40mg  
3 
1 
Green box 
24-35 kg 
320mg /40mg  
3 
2 
Orange box 
36-74 kg 
320mg /40mg  
3 
3 
Purple box 
> 74 kg 
320mg /40mg  
3 
4 
Blue bag 
 
Child’s name 
Eligible for 
DP? 
Weight 
Number 
of days 
Number of 
pills each day 
Packaging 
1 
 
 
 
3 
 
 
2 
 
 
 
3 
 
 
3 
 
 
 
3 
 
 
4 
 
 
 
3 
 
 
5 
 
 
 
3 
 
 
6 
 
 
 
3 
 
 
7 
 
 
 
3 
 
 
8 
 
 
 
3 
 
 
9 
 
 
 
3 
 
 
10 
 
 
 
3 
 
 
11 
 
 
 
3 
 
 
12 
 
 
 
3 
 
 
13 
 
 
 
3 
 
 
14 
 
 
 
3 
 
 
15 
 
 
 
3 
 
 
16 
 
 
 
3 
 
 
17 
 
 
 
3 
 
 
18 
 
 
 
3 
 
 
19 
 
 
 
3 
 
 
20 
 
 
 
3 
 
 

 
 
 
84
Appendix F.  (3) Resident Enrollment, Intervention, TPE Arm:  
Minor (12-17yrs) Assent Form 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. A member from your household or neighbor had malaria. You may also be at risk for malaria and we would like to invite you to 
participate in a study where we would implement and evaluate interventions to treat and prevent malaria. Your participation is important, although 
entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone will be tested for malaria and only people who have malaria will be referred for treatment. In another group 
of communities (the second group), everyone will receive treatment and prevention for malaria, whether or not they have malaria. Communities will 
receive either one of these two interventions. Your community has been selected to give everyone medication for treatment and prevention of 
malaria without testing for infection (the second group of communities).   
  
How many people will take part in this study?  
About 4500 people will be in the first group of communities and 4500 people will be in the second group of communities.  
 
What will happen if I take part in this research study? 
Right now, you are being asked to provide assent for the study activities occurring today and for a return visit in 7-10 days. Before you participate in 
any future visit study activities, we will ask you to provide assent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your experiences with malaria and record your answers on a tablet. We will 
collect your name, address, and contact information so that we can follow up with you in the future. We will also ask you a few questions about 
your and your family’s medical history and use of medications to see if it is safe for you to be given a malaria medicine called dihydroartemisinin-
piperaquine, also called DP for short.   
 
If it is safe for you to be given DP, our study team will explain to your parent or guardian how you should take this medication. You will be 
weighed, and will be given an appropriate weight-based dose of DP. All pills for each daily dose should be taken together. You will be given the 
first weight-based dose of a 3-day course of DP today. We will leave the second and third doses with your parent or guardian, which should be 
taken approximately the same time tomorrow and the day after, respectively. If a dose is missed, it should be taken as soon as possible. But do 
not take more than 1 dose of DP each day. You will not be given DP if it is unsafe for you. Everyone in your community is being given 3 days of DP 
to treat malaria, whether or not they have it. DP is useful for treatment of malaria, and may also prevent malaria infection in the near future. 
 
If it is not safe for you to be given DP, we will collect a small amount of blood (1/20th of a teaspoon) for malaria testing and for research 
purposes related to malaria only by finger prick. If you are found to be infected with malaria, we will perform a second finger prick to collect a 
second sample of blood (1/20th of a teaspoon) for research purposes. We will also refer you to the nearest health facility for malaria treatment 
with a medication that is safe for you. 
 
In 7-10 days from today: 
We may return to perform a pill count. Therefore, please have your parent or guardian keep your medicine packaging for at least 10 days.  
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect a small 
amount of blood (1/20th of a teaspoon) by finger prick from you. We will also ask you a few basic questions about your experiences with malaria 
and will record your answers on a tablet. We will perform a rapid test for malaria and, if the rapid test shows that you have malaria, we will refer 
you to the nearest health facility for treatment. We would also like to save a portion of this blood draw for future research studies related to 
malaria only.   
 
How long will I be in the study? 
Today’s questionnaire and administration of malaria medicine will be performed in your home and will take about 10-15 minutes. The future visits for 
pill counts and blood collection will occur in your home and take 5-10 minutes. If you are selected, the group discussion 7-10 days from today will take 
an hour. 
 
Can I stop being in the study? 
With your parent or guardian’s permission, you may choose either to take part or not to take part in the study. If you decide to take part in this study, 
you may leave the study at any time. If you experience symptoms related to taking DP, it is safe to stop taking DP before completing your pills. If at any 
time, you would like to withdraw your information and/or withdraw blood samples from malaria testing, you can have your parent or guardian contact 
us. If your parent or guardian wants you to withdraw from the study, you must withdraw. If you choose not to participate in the study or leave the 
study, there will be no penalty to you or your family. You will not lose any regular benefits and it will not affect your medical care. The study doctor 
may also stop you from taking part in this study at any time if he/she believes it is in your best interest, if you do not follow the study rules, or if the 
study is stopped.  
 
What risks can I expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the 
information you provide confidential. You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at 
the site of the finger prick, but the risk is minimal because the process will be done by a well trained officer.  
 
DP has been shown to be safe and very effective for treatment and prevention of malaria in all ages, including children. Serious health problems have 
rarely been reported. There may be some side effects that no one knows about yet. The researchers will let you know if they learn anything that might 
make you change your mind about participating in the study. If you do experience side effects, please ask your rural health motivator to contact study 
staff or you may contact study staff directly. For urgent issues, you should stop taking DP and have your parent or guardian contact our study staff and 
bring you for care at a local health facility. The risks and side effects related to the study medication, DP, include those which are: 
 

 
 
 
85
— 
Likely: No side effect is likely, but the most common is cough or fever 
— 
Less Likely: low red blood cells, headache, lack of energy, vomiting, diarrhea, abdominal pain  
— 
Rare but serious: itching, inflammation or enlargement of the liver, heart rhythm problems 
 
Medical care. 
We do not expect any problems with participating in the study. While DP is safe and not expected to cause any side effects, have your parent/guardian 
contact your attending Study Nurse if you experience a potential side effect. For urgent and concerning symptoms, such as chest pain, dizziness or 
feeling faint, having trouble breathing, flushing, or hives (an itchy swollen rash), have your parent/guardian bring you to your local health facility or call 
the national emergency “977 Hotline.” Even if it is not safe for you to be given the DP medicine, this does not mean that you cannot be treated for 
malaria with other medication. Therefore, if you think you have malaria, or are ill, you should still go to the health care clinic. 
 
Are there benefits to taking part in the study? 
The medication we will give you today will treat malaria if you are infected and it may prevent future infection. If you are found to have malaria by 
rapid testing future visits, you will benefit from being referred for malaria treatment. DP is NOT a substitute for medicine to prevent malaria when 
traveling to areas where you will be at high risk of malaria infection. If you are traveling, please visit your health facility to assess your risk and see if 
you should take medicine to prevent malaria during your trip. 
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you. You will still get care 
from the health facility the way you usually do.  Similarly, if you do not qualify for malaria medicine, and you become ill, you can still get care from the 
health facility and be evaluated and treated as indicated for malaria and other illnesses. Even if you do not take part in the study today, you are still 
eligible to participate in the follow-up blood test near the end of the study.  
 
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will 
be used throughout the study. There may be situations where we need your name, for example for follow up visits. Therefore, we will keep a key 
linking your name to your study number/identifier. But only key study staff will have access to this information. All information from the study will be 
kept in locked cabinets or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the 
Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name will not 
appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
With your parent or guardian’s permission, you may choose either to take part or not to take part in the study. If you decide to take part in the study, 
you may leave the study at any time. No matter what decision you make, there will be no penalty to you in any way. You will not lose any of your 
regular benefits, and you can still get your care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can have your parent/guardian contact our Study Coordinator at +268 #### ####. 
If you have experienced any adverse health events that may be related to DP, please have your parent/guardian contact your attending Study Nurse at 
+268 #### ####. If you wish to voice any problems or concerns you may have about how this study is being conducted, please have your 
parent/guardian call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
ASSENT 
You have been given a copy of this assent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or to 
withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, you 
should indicate how you would like to participate and sign below. 
 
This study was explained to me clearly. 
 
 
 
 
 
 
 
 Yes         No 
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
  
I agree to take antimalarial medication, if elegible. 
 
 
 
 
 
             
 Yes       No 
   
I agree to a possible pill count and group discussion in 7-10 days.  
 
 
 
 
 Yes       No   
 
If I am not eligible to receive DP, I agree to provide a blood sample for malaria testing today  
(by a rapid diagnostic test).   
 Yes       No       
 
If I am not eligible to receive DP, I agree to allow a part of my blood sample to be saved for research  
purposes related to malaria only). 
 
 
 
 
      
 
 
 Yes       No       
 
If I am not eligible to receive DP and I am found to be infected with malaria, I agree to provide a second  
blood sample, which will be saved for research purposes related to malaria only. 
      
 
 
 Yes       No       
 
 
 
 
 
 
 
 
 
                    
                    
 
 
 
 

 
 
 
86
Date 
                                   
Name of Minor 
 
 
  Signature or fingerprint of Minor 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
 
WITNESS (only necessary if assent conducted in language other than English or SiSwati) 
I witness that this assent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study. 
Language that assent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                Name   
 
 
 
Signature or finger print of witness 
 
 
 

 
 
 
87
Quiz to assess participant’s understanding of the study (to be given at time of TPE intervention 
visit only) 
 
If the participant does not answer at least 4 out of the 5 questions correctly, the study team should reread the consent form and 
reassess the participant’s understanding again. The study team should ensure that the participant is able to answer question 3 
correctly, and re-explain how DP should be taken and given to child(ren). 
 
 
1. Is participation in this study voluntary? 
 
2. How should you take the malaria medication (DP) / How should you give the malaria medication (DP) to your child(ren)?  
 
 
 

 
 
 
88
Appendix G: Neighborhood Information 
 
Index case ID (aciid): ____________ 
 
Neighborhood ID:  ______  
(NOTE This is a unique ID automatically generated by the tablet. If the same neighborhood has multiple interventions 
at different time points, it will receive a neighborhood ID with each episode) 
 
Response determination: 
Study area- RACD 
Study area – TPE 
Non study area- RACD 
 
Visit 1: Date and Time of arrival 
Date: ________________________ (dd/mm/yyyy) 
Time of arrival: ____: ______ (hh:mm) 
Time of departure: ____: ______ (hh:mm) 
Result code: _____ 
 
Visit 2: Date and Time of arrival 
Date: ________________________ (dd/mm/yyyy) 
Time of arrival: ____: ______ (hh:mm) 
Time of departure: ____: ______ (hh:mm) 
Result code: _____ 
 
Visit 3: Date and Time of arrival 
Date: ________________________ (dd/mm/yyyy) 
Time of arrival: ____: ______ (hh:mm) 
Time of departure: ____: ______ (hh:mm) 
Result code: _____ 
 
RESULT CODES: 
(1) COMPLETED, 100% of individuals within 200m & at least 30 individuals enrolled (stayed within 200m) (TPE 
localities only) 
(2) COMPLETED, 100% of individuals within 200m & at least 30 individuals enrolled (went beyond 200m) (TPE 
localities only) 
(3) COMPLETED, <100% of individuals within 200m but at least 30 individuals enrolled & 3 visits completed 
(stayed within 200m) (TPE localities only) 
(4) COMPLETED, <100% of individuals within 200m but at least 30 individuals enrolled & 3 visits completed (went 
beyond 200m) (TPE localities only) 
(5) COMPLETED, 100% of individuals within 500m & at least 30 individuals enrolled (RACD localities only) 
(6) COMPLETED, <100% of individuals within 500m but at least 30 individuals enrolled & 3 visits completed (RACD 
localities only) 
(7) INCOMPLETE with plans to return 
(8) INCOMPLETE with no plans to return 
(88) OTHER (SPECIFY)   
 
 
 
 
 
 
 
 
 
 

 
 
 
89
Appendix H. Household level RACD questionnaire 
Complete for all households (including households of the index case and households where no one is home or there is no 
consenting adult available). If this household has previously participated in RACD, a new Household level RACD 
questionnaire should still be completed. 
 
Screen Type:  Mass Screen  
  Fever Screen 
 
Neighborhood ID:______ 
Automatically generated by the tablet based on index case GPS 
coordinates.  If GPS coordinates within the same 500 m radius as 
previously implemented index case investigation then assign same 
Neighborhood ID. Make sure automated number is unique for all tablets. 
 
Index case ID (aciid): ____________ 
Surveillance Agent assigns barcode number to index case 
 
Visit 1: Date: ________________________ (YY/MM/DD) Time of arrival: ____: ______ ___ (hh:mm AM/PM) 
Visit 2: Date: ________________________ (YY/MM/DD) Time of arrival: ____: ______ ___ (hh:mm AM/PM) 
Visit 3: Date: ________________________ (YY/MM/DD) Time of arrival: ____: ______ ___ (hh:mm AM/PM) 
For Visit 1, Date and Time captured automatically when household level questionnaire is saved.  There should be 3 date fields, First Entered, Last 
Modified and Final Entered.  On first visit same date is saved on all 3 fields. 
For Visit 2, Last Modified and Final Entered should be modified to reflect that day’s date and time, this should be done on the Individual level 
questionnaire and not the household level questionnaire unless edits were made to the household level questionnaire. 
For Visit 3, Final entered should be modified to reflect that day’s date and time, this should be done on the Individual level questionnaire and not the 
household level questionnaire unless edits were made to the household level questionnaire. 
 
RACD Household Information 
1. Household ID (automatically generated by tablet) ______________ 
Automatically generated by tablet and should be unique for all tablets to prevent duplication 
 
2. Household description (if household not a residential premise e.g. Church, describe here) _______________ 
 
3. GPS Coordinates 
Latitude: _____________________ 
Longitude: ____________________ 
 
Automatically captured by tablet when household level questionnaire is saved, allow functionality to edit GPS coordinates by Agents 
 
4. Surveillance Agent Name, check all that apply  
Calsile Sandile Khaya Mathokoza Mduduzi Mukelwe Nombuso 
Nomcebo Nolwazi Senzo Thulani Fanele  Other___________________ 
 
5. Is household abandoned?  Yes  No   
 
If Yes, continue to next question. 
 
If No, close and save questionnaire. 
 
6. Is a consenting adult available?   Yes  No   
If Yes, continue to next question. 
If No, please indicate number of household members if known _____ (based on neighbor report, otherwise 
default is “999”) and skip to end of questionnaire and move to next home. 
 
999 denotes unknown number of households members 
 
7. Has this home been sprayed in the past year?  Yes  No   Don’t Know 
 
If yes, ask to see spray card to confirm house has been sprayed. 
 
 
 
 Spray card confirmed 
 
 
 No spray card 
 
 
 Cannot find spray card 
 
 
If yes, we’re all the houses sprayed? 
 Yes  No   Don’t Know 
 
 
If yes, do you sleep under a sprayed structure? 
 Yes  No   Don’t Know 
 
8. Has this household previously participated in RACD before (during this TPE study period)? 
 Yes  No  Don’t Know  
If yes, how many times before?   _____ 
If yes, indicate month(s) and year(s) of all previous RACD interventions during this TPE study period  
1. ___________ (dd/mm/yyyy) 
2. ___________ (dd/mm/yyyy)           
3. ___________ (dd/mm/yyyy)

8. List individuals in the household: 
 
Household 
head? 
(check if 
yes) 
Index 
case? 
(check 
if yes) 
Name 
Scan 
Barcode 
Gender 
Date 
of 
birth 
Present 
(yes/no) 
Notes 
(why person not 
present at home 
and best time to 
return to speak 
with person) 
Consent 
obtained 
for 
questionn
aire 
(yes/no/
not yet) 
Consent 
obtained for 
blood 
collection 
today (yes/no) 
Agreed to be 
contacted for 
accepability study 
(yes/no/ <18 yo, 
not applicable) 
If subject refused blood 
collection, indicate if 
refuser survey adminstered 
(yes/no) 
1. 
 
 
 
 
 
 
 
 
 
 
 
 
2.  
 
 
 
 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Surveillance Agent to assign a barcode even if individual is not present 
 
RACD Household level Dashboard (automatically generated) 
 
Barcode 
Name 
Household 
head? 
(check if 
yes) 
Index 
case? 
(check 
if yes) 
Gender 
Age 
Consent 
obtained for 
questionnaire 
(yes/no/not 
yet) 
Consent 
obtained 
for blood 
collection 
today 
(yes/no) 
Blood testing 
completed 
(yes/no) 
RACD 
Questionnaire 
completed 
(yes/no) 
Refuser 
Questionnaire 
completed 
(yes/no) 
Notes 
 
1. 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
2. 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
3. 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add 
Individual 
 
Editable table listing all household members rising in a household, when a Surveillance Agent clicks on the ‘Edit’ button they will be shown the questionnaire below to insert information on additional questions not previously posed.  
When RACD questionnaire for household member is completed the table should refresh and ‘Yes’ should appear under column for RACD Questionnaire completed and other fields that have since been completed. 
 
RACD Neighborhood Dashboard (automatically generated and includes missed homes) 
Note: Use outlined boxes for the “30” criteria  
House-hold 
number 
Home of the 
index case, 
check if yes 
Name of 
Household 
head 
# of individuals 
eligible for 
participation 
# of individuals 
reached 
(informed 
consent 
performed) 
# of individuals 
providing 
consent for 
questionnaire 
# of 
questionnaire
s completed  
# of 
individuals 
providing 
consent for 
initial blood 
testing  
# of 
individuals 
RDT 
performed 
# of 
individuals 
DBS 
collected  
# of 
individuals 
RDT positive 
# of RDT+ 
individuals 
microtainer 
collected 
# of 
individuals 
RDT+ referred 
for treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Totals: 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
91
Appendix I. RACD Individual questionnaire 
 
 
1. Barcode: _________________ 
This field should auto populate after Surveillance Agent clicks on ‘Edit’ button from RACD Household Level dashboard as barcode was already assigned.  
 
2. Household ID:  _________________ 
This field should auto populate after Surveillance Agent clicks on ‘Edit’ button from RACD Household Level dashboard as Household ID was already assigned.  
 
3. Consent obtained:  Yes  No   Not yet 
If no, trigger the Refuser Survey 
Questionnaire will only be administered if household member is found at home.  Auto-populate ‘Not yet’ option for consent obtained based on information 
collected from household level questionnaire.  The ‘Not yet’ option must be greyed out (disabled) though showing that it was a previous selection option.  
Surveillance Agents must then either select ‘Yes’ or ‘No’, with the ‘No’ option triggering the refuser survey 
 
4. Relation to index case (check all that apply):  
 Immediate Family  Extended family  Neighbor  Visitor  Co-worker  Unknown 
 
5. Nationality:   
 
 Swaziland Mozambique  South Africa  Other (specify _______________________) 
(Provide drop down list of all nationalities) 
 
 
6. Occupation (Drop down list): 
Student  
 
Child or minor but not a student   
Unemployed   
Farming/Agriculture  
Manufacturing/Factory   
Other Manual Labor    
Small-market sales or trade  
Office or Clerical Work   
Other (specify _________________) 
 
7. Ask: Have you been diagnosed with malaria in the past 12 months?  Yes   No  
If yes, ask when,  
 6 months to a year ago < 6 months ago  Within the last month  Within the last 2 weeks 
 Don’t know 
If yes ask, have you had fever in the last 2 weeks? 
 Yes  No   Don’t know 
If yes ask, have you been diagnosed with malaria in the last 2 weeks?  Yes  No   Don’t know 
If diagnosed in the last 2 weeks: 
Was the diagnosis confirmed by a test?    Yes  No   Don’t know 
What treatment was prescribed? Check all that apply 
 
 
 
 Artemether-lumefantrine 
 
 
 
 Single dose primaquine 
 
 Oral Quinine 
 
 
 
 IV Quinine 
 
 
 
 IM Quinine 
 IV Artesunate 
 
 
 
 IM Artesunate 
 
 
 
 Chloroquine 
 
 
 
 SP/Fansidar 
 
 
 
 Other (specify _______________________ 
 
 
 
 Unknown 
Was full treatment course completed?      Yes   No  Don’t know

Prior Residence and/or Travel History 
8. Have you ever lived or stayed in Mozambique for at least 30 consecutive days? 
If yes, approximately how long ago was this visit or stay? _____ yrs _____ mos 
9. Have you spent at least one night anywhere else besides your current residence in the past 8 weeks?  
 Yes   No   Don’t know 
 
If no, skip to question 10. 
 
If yes, ask: Where did you sleep overnight, when did you sleep there, why did you sleep there, and personal protection?  If slept outside Swaziland, also ask about 
means of travel and border post of re-entry. 
 
Within Swaziland 
Town / Locality / 
Inkhundla 
Duration of Stay 
Reason for sleeping away 
from current residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal protection  
-chemoprophylaxis 
(specify___) 
-bednet 
-mosquito repellent or coil 
-None 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
a. 
 
 
 
 
b.  
 
 
 
 
c.  
 
 
 
 
d.  
 
 
 
 
e.  
 
 
 
 
 
 
Outside of Swaziland 
Country 
Province 
/ Town 
Duration of Stay 
Reason for 
sleeping away 
from current 
residence:  
-previous residence 
-business 
-holiday 
-visiting friends / 
family 
-other 
(specify__________) 
Personal 
protection  
-chemoprophylaxis 
(specify___) 
-bednet 
-mosquito repellent 
or coil 
-None 
Means of travel 
-Large bus 
-Kombi (van) 
-Personal car 
-Ride share (catch a ride 
/ got a lift) 
-Airplane 
-Bicycle 
-Walked 
-Other (specify__________) 
Border Post of Re-Entry 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
- Lavumisa/Golela 
- Salitje/Onverwacht 
- Mahamba 
- Gege/Bothashoop 
- Sicunusa/Houtkop 
- Sandlane/Nerston 
- Ngwenya/Oshoek 
 
- Bulembu/Josefsdal 
- Matsamo/Jeppe’s Reef 
- Mananga 
- Lomahasha/Namaacha 
- Mhlumeni/Goba 
- KMIII International 
Airport 
- Other 
 
a. 
 
 
 
 
 
 
 
b.  
 
 
 
 
 
 
 
c.  
 
 
 
 
 
 
 
d.  
 
 
 
 
 
 
 
e.  
 
 
 
 
 
 
 

10. Comments or any other information that is relevant? 
_____________________________________________________________________________________________________________ 
 
11. RDT result:positive   negative   not done 
If positive, patient referred to local health facility    Yes   No   
If no, why? _______________________________________________________________________________________________ 
DBS collected  Yes   No 
 Not Done 
If DBS not done, why? Patient refused   Other_______________________________ 
 
Thank you for our participation in this study. 
 

 
Appendix J. Household level TPE questionnaire 
Complete for all households (including households of the index case and households where no one is home or there is no 
consenting adult available). Note, in the event that this household has already previously participated in TPE, a new 
Household level TPE questionnaire should still be completed. 
 
Neighborhood ID:______ 
Automatically generated by the tablet based on index case GPS 
coordinates.  If GPS coordinates within the same 200 m radius as 
previously implemented index case investigation then assign same 
Neighborhood ID. Make sure automated number is unique for all tablets. 
 
Index case ID (aciid): ____________ 
Surveillance Agent assigns barcode number to index case 
 
 
Visit 1: Date: ________________________ (YY/MM/DD) Time of arrival: ____: ______ ___ (hh:mm AM/PM) 
Visit 2: Date: ________________________ (YY/MM/DD) Time of arrival: ____: ______ ___ (hh:mm AM/PM) 
Visit 3: Date: ________________________ (YY/MM/DD) Time of arrival: ____: ______ ___ (hh:mm AM/PM) 
For Visit 1, Date and Time captured automatically when household level questionnaire is saved.  There should be 3 date fields, First Entered, Last 
Modified and Final Entered.  On first visit same date is saved on all 3 fields. 
For Visit 2, Last Modified and Final Entered should be modified to reflect that day’s date and time, this should be done on the Individual level 
questionnaire and not the household level questionnaire unless edits were made to the household level questionnaire. 
For Visit 3, Final entered should be modified to reflect that day’s date and time, this should be done on the Individual level questionnaire and not the 
household level questionnaire unless edits were made to the household level questionnaire. 
 
TPE Household Information 
9. Household ID (automatically generated by tablet) ______________ 
Automatically generated by tablet and should be unique for all tablets to prevent duplication 
 
10. Household description (if household not a residential premise e.g. Church, describe here) _______________ 
 
11. GPS Coordinates 
Latitude: _____________________ 
Longitude: ____________________ 
 
Automatically captured by tablet when household level questionnaire is saved, allow functionality to edit GPS coordinates by Agents 
 
12. Surveillance Agent Name, check all that apply  
Calsile Sandile Khaya Mathokoza Mduduzi Mukelwe Nombuso 
Nomcebo Nolwazi Senzo Thulani Fanele  Other___________________ 
 
13. Is household abandoned?  Yes  No   
 
If Yes, continue to next question. 
 
If No, close and save questionnaire. 
 
14. Is a consenting adult available?   Yes  No   
If Yes, continue to next question. 
If No, please indicate number of household members if known _____ (based on neighbor report, otherwise 
default is “999”) and skip to end of questionnaire and move to next home. 
 
999 denotes unknown number of households members 
 
15. Has this home been sprayed in the past year?  Yes  No   Don’t Know 
 
If yes, ask to see spray card to confirm house has been sprayed. 
 
 
 
 Spray card confirmed 
 
 
 No spray card 
 
 
 Cannot find spray card 
 
 
If yes, we’re all the houses sprayed? 
 Yes  No   Don’t Know 
 
 
If yes, do you sleep under a sprayed structure? 
 Yes  No   Don’t Know 
 
16. Has this household previously participated in TPE before (during this TPE study period)? 
 Yes  No  Don’t Know  
If yes, how many times before?   _____ 
If yes, indicate month(s) and year(s) of all previous TPE interventions during this TPE study period  
1. ___________ (dd/mm/yyyy) 
2. ___________ (dd/mm/yyyy)           
3. ___________ (dd/mm/yyyy

 
 
 
95
8. List individuals in the household: 
 
Household 
head? 
(check if 
yes) 
Index 
case? 
(check 
if yes) 
Name 
Scan 
Barcode 
Gender 
Date 
of 
birth 
Present 
(yes/no) 
Notes 
(why person not present at 
home and best time to 
return to speak with person) 
Consent obtained for 
questionnaire 
(yes/no/not yet) 
1. 
 
 
 
 
 
 
 
 
 
2.  
 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
Note: Surveillance Agent to assign a barcode even if individual is not present 
 
 
TPE Household level Dashboard (automatically generated) 
 
Barcode 
Name 
Household 
head? 
(check if 
yes) 
Index 
case? 
(check 
if yes) 
Gender 
Age 
Consent 
obtained for 
questionnaire 
(yes/no/not 
yet) 
Questionnaire 
completed 
(yes/no) 
Eligible for 
medication 
Medication 
consent 
# doses 
completed 
Notes 
 
1. 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
2. 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
3. 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add 
Individual 
 
Editable table listing all household members rising in a household, when a Surveillance Agent clicks on the ‘Edit’ button they will be shown the questionnaire below to insert information on 
additional questions not previously posed.  When TPE questionnaire for household member is completed the table should refresh and ‘Yes’ should appear under column for TPE  Questionnaire 
completed and other fields that have since been completed. 
 
TPE Neighborhood Dashboard (automatically generated and includes missed homes) 
Note: Use outlined boxes for the “30” criteria  
Household 
number 
Home of 
the index 
case, check 
if yes 
Name of 
Househol
d head 
# of 
individuals 
eligible for 
participation 
# of individuals 
reached (informed 
consent 
performed) 
# of individuals 
providing 
consent for 
questionnaire 
# of 
questionnai
res 
completed  
# of individuals 
eligible and 
consented to receive 
medication 
# of 
individuals 
received 
dose 1 
# of 
individuals 
received 
dose 2 
# of 
individuals 
received 
dose 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Totals: 
 
 
 
 
 
 
 
 

 
 
 
96
Appendix K. TPE Individual questionnaire 
 
 
1. Barcode: _________________ 
This field should auto populate after Surveillance Agent clicks on ‘Edit’ button from TPE Household Level dashboard as barcode was 
already assigned.  
 
2. Household ID:  _________________ 
This field should auto populate after Surveillance Agent clicks on ‘Edit’ button from TPE Household Level dashboard as Household ID 
was already assigned.  
 
3. Consent obtained:  Yes  No   Not yet 
If no, trigger the Refuser Survey 
Questionnaire will only be administered if household member is found at home.  Auto-populate ‘Not yet’ option for consent obtained 
based on information collected from household level questionnaire.  The ‘Not yet’ option must be greyed out (disabled) though showing 
that it was a previous selection option.  Surveillance Agents must then either select ‘Yes’ or ‘No’, with the ‘No’ option triggering the 
refuser survey 
 
4. Relation to index case (check all that apply):  
 Immediate Family  Extended family  Neighbor  Visitor  Co-worker  Unknown 
 
5. Nationality:  
 
 
 Swaziland Mozambique  South Africa  Other (specify _______________________) 
(Provide drop down list of all nationalities) 
 
 
6. Occupation (Drop down list): 
Student  
 
Child or minor but not a student   
Unemployed   
Farming/Agriculture  
Manufacturing/Factory   
Other Manual Labor    
Small-market sales or trade  
Office or Clerical Work   
Other (specify _________________) 
 
7. Ask: Have you been diagnosed with malaria in the past 12 months?  Yes   No  
If yes, ask when,  
 6 months to a year ago < 6 months ago  Within the last month  Within the last 2 weeks 
 Don’t know 
If yes ask, have you had fever in the last 2 weeks? 
 Yes  No   Don’t know 
If yes ask, have you been diagnosed with malaria in the last 2 weeks?  Yes  No   Don’t know 
If diagnosed in the last 2 weeks: 
Was the diagnosis confirmed by a test?    Yes  No   Don’t know 
What treatment was prescribed? Check all that apply 
 
 
 
 Artemether-lumefantrine 
 
 
 
 Single dose primaquine 
 
 Oral Quinine 
 
 
 
 IV Quinine 
 
 
 
 IM Quinine 
 IV Artesunate 
 
 
 
 IM Artesunate 
 
 
 
 Chloroquine 
 
 
 
 SP/Fansidar 
 
 
 
 Other (specify _______________________ 
 
 
 
 Unknown 
Was full treatment course completed?      Yes   No  Don’t know

Prior Residence and/or Travel History 
12. Have you ever lived or stayed in Mozambique for at least 30 consecutive days? 
If yes, approximately how long ago was this visit or stay? _____ yrs _____ mos 
13. Have you spent at least one night anywhere else besides your current residence in the past 8 weeks?  
 Yes   No   Don’t know 
 
If no, skip to question 10. 
 
If yes, ask: Where did you sleep overnight, when did you sleep there, why did you sleep there, and personal protection?  If slept outside Swaziland, also ask about 
means of travel and border post of re-entry. 
 
Within Swaziland 
Town / Locality / 
Inkhundla 
Duration of Stay 
Reason for sleeping away from current residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal protection  
-chemoprophylaxis (specify___) 
-bednet 
-mosquito repellent or coil 
-None 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
a. 
 
 
 
 
b.  
 
 
 
 
c.  
 
 
 
 
d.  
 
 
 
 
e.  
 
 
 
 
 
 
Outside of Swaziland 
Country 
Province 
/ Town 
Duration of Stay 
Reason for sleeping 
away from current 
residence:  
-previous residence 
-business 
-holiday 
-visiting 
friends/family 
- Other 
(specify___________) 
Personal 
protection  
-chemoprophylaxis 
(specify___) 
-bednet 
-mosquito 
repellent or coil 
-None 
Means of travel 
-Large bus 
-Kombi (van) 
-Personal car 
-Ride share (catch a 
ride/got a lift) 
-Airplane 
-Bicycle 
-Walked 
-Other (specify_________) 
Border Post of Re-Entry 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
- Lavumisa/Golela 
- Salitje/Onverwacht 
- Mahamba 
- Gege/Bothashoop 
- Sicunusa/Houtkop 
- Sandlane/Nerston 
- Ngwenya/Oshoek 
 
- Bulembu/Josefsdal 
- Matsamo/Jeppe’s Reef 
- Mananga 
- Lomahasha/Namaacha 
- Mhlumeni/Goba 
- KMIII International 
Airport 
- Other 
 
a. 
 
 
 
 
 
 
 
b.  
 
 
 
 
 
 
 
c.  
 
 
 
 
 
 
 
d.  
 
 
 
 
 
 
 
e.  
 
 
 
 
 
 
 

 
 
 
98
Medical History 
 
10. Weight:  __ __. __ kg  
Tablet should make this question compulsory for all ages 
 
Ask the following questions to assess for potential criteria excluding participant from receiving antimalarial medication: 
 
11. Are you pregnant or breastfeeding?  Yes   No  Don’t know 
12. Have you menstruated in the past but not within the past 4 weeks?  Yes   No  Don’t know 
13. Are you less than 9 months of age?  Yes   No  Don’t know 
Tablet should automatically complete this question based on date of birth, select an option and not allow Agent to make 
changes 
 
14. Are you allergic to have had a past adverse reaction to DP?  Yes   No  Don’t know 
15. Have you already taken 2 courses of DP in the past year?  Yes   No  Don’t know 
16. Have you taken DP within the last 2 months?  Yes   No  Don’t know 
17. Do you have heart, kidney, or liver problems?  Yes   No  Don’t know 
18. Does your family have a history of heart problems or sudden death?  Yes   No  Don’t know 
19. In the past month have you taken antimalarial drugs for either treatment or prevention of malaria (mefloquine, halofantrine, 
lumefantrine, chloroquine, or quinine)?   Yes   No  Don’t know 
20. Have you had a fever in the past 48 hours, or are otherwise feeling ill?  Yes   No  Don’t know 
If Yes, was subject taken to local health facility?  Yes   No 
21. Are you currently taking any medications?  Yes   No  Don’t know 
 
If Yes, are you taking any of the following medications? (check all that apply) 
 
a. 
 Medicines that effect heart rhythms (such as amiodarone, disopyramide, dofetilide, ibutilide, 
procainamide, quinidine, hydroquinidine, or sotalol)  
 
b.  Medicines that treat depression 
 
c. 
 Medicines that treat mental health problems (such as phenothiazines, sertindole, sultopride, 
chlorpromazine, haloperidol, mesoridazine, pimozide, or thioridazine)  
 
d.  Medicines that treat infection (macrolides [such as erythromycin or clarithromycin], fluoroquinolones 
[such as moxifloxacin or sparfloxacin], medicines for fungal infections [such as imidazole and 
fluconazole], as well as pentamadine [used to treat a specific type of pnuemonia] and saquinavir [for 
treatment of HIV]) 
 
e. 
 Antihistamines used to treat allergies or inflammation (such as terfenadine, astemizole, mizolastine)  
 
f. 
 Medicines that treat stomach problems such as cisapride, droperidol, domperidone, or diphemanil 
 
g. 
 Medicines to treat cancers (vinca alkaloids, arsenic trioxide), chest pain (bepridil), drug addiction 
(levomethadyl, methadone), and high cholesterol levels (probucol) 
 
Drug Administration: (Subject is eligible to receive medication if they weigh at least 7kg and answered “No” to questions 10-19 
and are not taking any of the medications listed in 20a-20g) 
 
 
22. Is the subject eligible to receive medication?   Yes   No  
Tablet to automatically say Yes or No for eligibility of individual to receive medication based on responses above and criteria 
provided, options should be greyed out (disabled). 
a. 
If yes, indicate regimen administered: 
Check 
one 
Weight 
band 
Color of box 
Regimen administered 
Subscription 
 
7-12 kg 
Bottle 
320 mg piperaquine /40 mg dihydroartemisinin tablets, 3 half tablets 
½ tablet daily x 3 days 
 
7-12 kg 
Pink box 
160 mg piperaquine /20 mg dihydroartemisinin tablets, 3 tablets 
1 tablet daily x 3 days 
 
13-23 kg 
Green box 
320 mg piperaquine /40 mg dihydroartemisinin tablets, 3 tablets 
1 tablet daily x 3 days 
 
24-35 kg 
Orange box 
320 mg piperaquine /40 mg dihydroartemisinin tablets, 6 tablets 
2 tablet daily x 3 days 
 
36-74 kg 
Purple box 
320 mg piperaquine /40 mg dihydroartemisinin tablets, 9 tablets 
3 tablet daily x 3 days 

 
 
 
99
NOTE: Give lower weight band if weight falls between weight bands. 
NOTE: Use of the 320/40 mg or 160/20 mg tablet for children 7-12 kg will depend on drug availability. 
 
b. Was dose #1 directly observed?  Yes  No, indicate reason _____________ 
 
23. Comments or any other information that is relevant? 
_____________________________________________________________________________________________________________ 
24. Modified DOT record 
Encounter 
# 
Date 
YY/MM/DD 
Time  
##:##  
AM/PM 
Oversight (check one) 
Comments 
1 
 
 
[ ] Dose #2 DOT by study staff 
[ ] Dose #2 Self-reported self-administration 
[ ] Dose #2 Self-administered (reported by someone other than the subject) 
[ ] Dose #2 Reminded patient to take drug  
[ ] Dose #2 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #2 Other, specify _______ 
 
2 
 
 
[ ] Dose #2 DOT by study staff 
[ ] Dose #2 Self-reported self-administration 
[ ] Dose #2 Self-administered (reported by someone other than the subject) 
[ ] Dose #2 Reminded patient to take drug  
[ ] Dose #2 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #2 Other, specify _______ 
----------------------------------------------------------- 
[ ] Dose #3 DOT by study staff 
[ ] Dose #3 Self-reported self-administration 
[ ] Dose #3 Self-administered (reported by someone other than the subject) 
[ ] Dose #3 Reminded patient to take drug  
[ ] Dose #3 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #3 Other, specify _______  
 
3 
 
 
[ ] Dose #2 DOT by study staff 
[ ] Dose #2 Self-reported self-administration 
[ ] Dose #2 Self-administered (reported by someone other than the subject) 
[ ] Dose #2 Reminded patient to take drug  
[ ] Dose #2 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #2 Other, specify _______ 
----------------------------------------------------------- 
[ ] Dose #3 DOT by study staff 
[ ] Dose #3 Self-reported self-administration 
[ ] Dose #3 Self-administered (reported by someone other than the subject) 
[ ] Dose #3 Reminded patient to take drug  
[ ] Dose #3 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #3 Other, specify _______ 
 
Rx #3etc. 
 
 
[ ] Dose #2 DOT by study staff 
[ ] Dose #2 Self-reported self-administration 
[ ] Dose #2 Self-administered (reported by someone other than the subject) 
[ ] Dose #2 Reminded patient to take drug  
[ ] Dose #2 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #2 Other, specify _______ 
----------------------------------------------------------- 
[ ] Dose #3 DOT by study staff 
[ ] Dose #3 Self-reported self-administration 
[ ] Dose #3 Self-administered (reported by someone other than the subject) 
[ ] Dose #3 Reminded patient to take drug  
[ ] Dose #3 Indirectly reminded patient to take drug (via close contact) 
[ ] Dose #3 Other, specify _______Check one: 
[ ] DOT by study staff 
[ ] Self-reported self-administration 
[ ] Self-administered (reported by someone other than the subject) 
[ ] Reminded patient to take drug  
[ ] Indirectly reminded patient to take drug (via close contact) 
[ ] Other, specify _______ 
 
For return visits for DOT, allow editing of above table for all individuals. 
 
> 74 kg 
Blue bag 
320 mg piperaquine /40 mg dihydroartemisinin tablets, 12 tablets 
4 tablet daily x 3 days 

 
 
 
100
25. Pill count 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date of pill 
count 
 
Regimen 
administered 
Is your 
medication 
packaging still 
available? 
IF blister pack 
available, count 
number of pills 
remaining 
 
IF blister pack not available, 
Ask: Approximately how may 
pills did you take?  
Other comments 
DD/MM/YY 
automatically 
generated per 
22a 
[]  yes 
[]  no 
half tabs 
[] 1 []2  []3  
 
full tabs (120/20 
or 320/40) 
[ ] 0    
[ ] 1   
[ ] 2    
[ ] 3 
[ ] 4     
[ ] 5     
[ ] 6 
[ ] 7    
[ ] 8     
[ ] 9 
half tabs 
[] 1 []2  []3  
 
full tabs (120/20 or 
320/40) 
[ ] 0    
[ ] 1   
[ ] 2    
[ ] 3 
[ ] 4     
[ ] 5     
[ ] 6 
[ ] 7    
[ ] 8     
[ ] 9 
 
 
 
 
 
 
 
For return visits for pill count, allow editing of above table for all individuals. 
 
 
26.  Ask: Have you experienced any potential side effects from the medication?                        Yes    No 
 
 
26a  If YES, specify: 
 
 cough 
 fever 
 headache 
 lack of energy 
 abdominal pain 
 pale complexion or pallor 
 yellow discoloration of skin or eyes (jaundice) 
 weakness 
 joint pain 
 dark urine 
 nausea 
 vomiting 
 diarrhea 
 chest pain 
 heart palpitations 
 other (specify_____________________) 
 
If YES, complete Appendix S. Adverse drug reaction (ADR) Report Form 
 
 
27. Please explain all measures taken to alleviate these adverse reactions related to the drug 
 
28. Other comments ____________________ 
 
 
Thank you for our participation in this study. 

 
 
 
101
Appendix L. (1) 6-9 month Follow-Up:  
Adult Informed Consent Form  
 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the Ministry of Health. 
[You / A member of your community] had malaria about 6-9 months ago. We would like to invite you to participate in a study that will help us understand how to 
eliminate malaria in your community. Your participation is important, although entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates 
Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of communities (the 
first group), everyone was tested for malaria and only people who have malaria were referred for treatment. In another group of communities (the second group), 
everyone received treatment and prevention for malaria, whether or not they had malaria. Communities received either one of these two interventions.   Your 
community was involved in one of these programs.   
 
Why am I being asked to be a part of this study? 
As [you / a member of your community] had malaria 6-9 months ago, we would like to collect a sample of your blood today in order to better understand the body’s 
response to malaria infection. Additionally, near the end of the study, we would like to test everyone in your community for malaria to understand the impact the 
intervention had on your community. We would like to include you in these follow-up tests. 
 
How many people will take part in this study?  
About 600 people will be invited to participate in the study to understand the body’s response malaria infection.  
 
What will happen if I take part in this research study? 
Right now, you are only being asked to provide consent for the study activities occurring today. Before you participate in any future visit study activities, we will ask 
you to provide consent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your experiences with malaria and record your answers on a tablet. We will perform 2 
finger pricks to collect a small amount of blood (1/10th of a teaspoon).  
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect an additional small 
amount of blood (1/20th of a teaspoon) by finger prick from you. Our study team will also ask you a few basic questions about you and your experiences 
with malaria and will record your answers on a tablet. 
 
We will perform a rapid test for malaria each time we take a blood sample from you and, if the rapid test shows that you have malaria, we will refer you to the 
nearest health facility for treatment. We would also like to save a portion of each blood draw for future research studies related to malaria only. 
 
How long will I be in the study? 
Today’s questionnaire and blood collection will be performed in your home and will take about 10 minutes. The future visit for blood collection will occur in your 
home and take 5 minutes each time.  
 
Can I stop being in the study? 
You may choose either to take part or not to take part in the study. If you decide to take part in this study, you may leave the study at any time. If at any time, you 
would like to withdraw your information and/or blood samples from malaria testing, you can contact us. If you choose not to participate in the study or leave the 
study, there will be no penalty. You will not lose any regular benefits and it will not affect your medical care.  
 
What risks can I expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the information you 
provide confidential. You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at the site of the finger prick, but the 
risk is minimal because the process will be done by a well trained officer. Participation or refusal to participate in this study will not affect your care in any way. 
 
Medical care 
We do not expect any problems with participating in the study. However, in case you feel unwell at any point during the study as a potential side effect from your 
participation, you should contact our Study Coordinator and go to your local health facility.  
 
Are there benefits to taking part in the study? 
If you are found to have malaria by rapid testing today or at the future visit, you will benefit from being refered for malaria treatment.  
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you. You will still get care from the health 
facility the way you usually do. Even if you do not take part in the study today, you are still eligible to participate in the follow-up blood test near the end of the study. 
 
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will be used 
throughout the study. There may be situations where we need your name, for example for follow up visits. Therefore, we will keep a key linking your name to your 
study number/identifier. But only key study staff will have access to this information. All information from the study will be kept in locked cabinets or computers. 

 
 
 
102
Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the Clinton Health Access Initiative in Mbabane, Swaziland 
and the University of California San Francisco, United States of America. Your name will not appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
You may choose either to take part or not to take part in the study. If you decide to take part in the study, you may leave the study at any time. No matter what 
decision you make, there will be no penalty to you in any way. You will not lose any of your regular benefits, and you can still get your care from your health facility 
the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you contact our Study Coordinator at +268 #### ####. If you were found to have malaria today and 
experience any adverse health events that may be related to treatment, contact your attending Study Nurse at +268 #### ####. If you wish to voice any problems or 
concerns you may have about how this study is being conducted, please call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or to withdraw at 
any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, you should indicate how you 
would like to participate and sign below. 
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
  
I agree to provide a blood sample for malaria testing today (by a rapid diagnostic test).   
 
 
 Yes       No 
   
I agree to allow a part of today’s blood sample to be saved for research purposes related to malaria only. 
 
 Yes       No   
 
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                                
Name   
 
 
 
 Signature or finger print  
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  Language that 
consent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                    Name   
 
 
 
 
Signature or finger print of witness 
 
 

 
 
 
103
Appendix L. (2) 6-9 month Follow-Up: Parent/Guardian 
Permission Form for Children  
(one form per Parent/Guardian: obtains consent from the Parent/Guardian and permission for multiple 
children) 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the Ministry of Health. 
[You and/or your child(ren) / a member of your community] had malaria about 6-9 months ago. We would like to you to participate in a study that will help us 
understand how to eliminate malaria in your community. Your participation is important, although entirely voluntary. This study is implemented by the National 
Malaria Control Program. Funding for this study is provided by the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of communities (the 
first group), everyone was tested for malaria and only people who have malaria were referred for treatment. In another group of communities (the second group), 
everyone received treatment and prevention for malaria, whether or not they had malaria. Communities received either one of these two interventions. Your 
community was involved in one of these programs.   
 
Why are we being asked to be a part of this study? 
As [you and or your child(ren) / a member of your community] had malaria 6-9 months ago, we would like to collect a sample of your blood today in order to better 
understand the body’s response to malaria infection. Additionally, near the end of the study, we would like to test everyone in your community for malaria to 
understand the impact the intervention had on your community. We would like to include you in these follow-up tests. 
 
How many people will take part in this study?  
About 600 people will be invited to participate in the study to understand the body’s response malaria infection.  
 
What will happen if we take part in this research study? 
Right now, you are only being asked to provide consent for the study activities occurring today. Before you or your child(ren) participate in any future visit study 
activities, we will ask you to provide consent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your family’s experiences with malaria and record your answers on a tablet. We will 
perform 2 finger pricks to collect a small amount of blood (1/10th of a teaspoon) from you and your child(ren).  
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect an additional small 
amount of blood (1/20th of a teaspoon) by finger prick from your family. Our study team will also ask you a few basic questions about your family’s 
experiences with malaria and will record your answers on a tablet. 
 
We will perform a rapid test for malaria each time we take a blood sample and, if the rapid test shows that any of you have malaria, we will refer all infected 
individual(s) to the nearest health facility for treatment. We would also like to save a portion of each blood draw for future research studies related to malaria only. 
 
How long will we be in the study? 
Today’s questionnaire and blood collection will be performed in your home. The questionnaire will take about 5 minutes and blood collection will take about 5 
minutes per person. The future visit for blood collection will occur in your home and take 5 minutes per person.  
 
What are our rights if we take part in this study? Can we stop being in the study? 
You may choose either to take part or not to take part in the study. If you decide to take part in this study, you or your child(ren) may leave the study at any time. If at 
any time, you would like to withdraw your and/or your child(ren)’s information and/or withdraw blood samples from malaria testing, you can contact us. If you 
choose not to participate in the study or leave the study, there will be no penalty to you or your family. You will not lose any regular benefits and it will not affect 
your medical care.  
 
What risks can we expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the information you 
provide confidential. There may be a brief moment of pain when the blood is being collected and there is a small risk of infection at the site of the finger prick, but the 
risk is minimal because the process will be done by a well trained officer. Participation or refusal to participate in this study will not affect your care in any way. 
 
Medical care. 
We do not expect any problems with participating in the study. However, in case you or your child(ren) feel unwell at any point during the study as a potential side 
effect from your participation, you should contact our Study Coordinator and go to your local health facility.  
 
Are there benefits to taking part in the study? 
If you or your child(ren) are found to have malaria by rapid testing today or at the future visit, they will benefit from being refered for malaria treatment.  
 
What other choices do we have if we do not take part in the study? 
If you decide not to take part in the study, there will be no penalty. You and your child(ren) will still get care from the health facility the way you usually do. Even if 
you do not take part in the study today, you and your child(ren) are still eligible to participate in the follow-up blood test near the end of the study. 
 
How will information about us be kept confidential? 

 
 
 
104
We will not inform anyone of you or your child(ren)’s participation in the study and your names will be kept confidential by replacing them with numbers/identifiers 
that will be used throughout the study. There may be situations where we need your or your child(ren)’s name(s), for example for follow up visits. Therefore, we will 
keep a key linking your names to your study numbers/identifiers. But only key study staff will have access to this information. All information from the study will be 
kept in locked cabinets or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the Clinton Health 
Access Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your and your child(ren)’s name will not appear in 
any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will we be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are our rights if we take part in this study? 
If you decide to take part in the study, you and/or your child(ren) may leave the study at any time. No matter what decision you make, there will be no penalty in any 
way. Your family will not lose any regular benefits, and your family can still get care from the health facility the way they usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your or your child(ren)’s participation, you can contact our Study Coordinator at +268 #### ####. If you or your 
child(ren) were found to have malaria today and experienced any adverse health events that may be related to treatment, contact your attending Study Nurse at 
+268 #### ####. If you wish to voice any problems or concerns you may have about how this study is being conducted, please call the office of the Swaziland Ministry 
of Health’s Ethics Committee at +268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  Your child(ren) are unable to consent for themselves because 
they are less than 18 years old. By signing this form, you are giving permission for your child(ren) or ward(s) to participate in the study. You have the right to decline 
to participate or to have your child(ren) or ward(s) participate or to withdraw them at any point in this study without penalty or loss of benefits to which you or your 
family are otherwise entitled. If you wish to participate and have your child(ren) participate in this study, you should indicate how you would like to participate and 
sign below. 
 
Number of children (<18 years old) that I consent may participate in the study:                                . 
 
I agree to be interviewed today.                                                                              
 Yes       No 
 
I agree have my child(ren) be interviewed today, if requested by study staff.  
 
 
 
 
 Yes       No  
 
I agree to provide a blood sample for malaria testing today (by a rapid diagnostic test), if requested by study staff. 
 Yes       No 
 
I agree to have my child(ren) provide a blood sample for malaria testing today (by a rapid diagnostic test),  
if requested by study staff. 
 
 
 
 
 
 
 
 
 
 Yes       No 
   
I agree to allow a part of my blood sample to be saved for for research purposes related to malaria only. 
 Yes       No   
 
I agree to allow a part of my child(ren)’s blood sample(s) to be saved for research purposes related to malaria only. 
 
 Yes       No   
 
 
                   
 
                    
                    
 
 
 
 
Date 
                     
Name of Parent/Guardian 
 
Signature or fingerprint of Parent/Guardian  
 
 
Name(s) of children (If indicated, list names of additional children on the back of the form): 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #1 
 
 
     Child #2                     
            Child #3 
 
 
         Child #4 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #5 
 
 
     Child #6                     
            Child #7 
 
 
         Child #8 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  Language that 
consent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                     Name   
 
 
 
Signature or finger print of witness 

 
 
 
105
Appendix L. (3) 6-9 month Follow-Up:  
Minor (12-17yrs) Assent Form  
 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the Ministry of Health. 
[You / A member of your community] had malaria about 6-9 months ago. We would like to invite you to participate in a study that will help us understand how to 
eliminate malaria in your community. Your participation is important, although entirely voluntary. Funding for this study is provided by the Bill & Melinda Gates 
Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of communities (the 
first group), everyone was tested for malaria and only people who have malaria were referred for treatment. In another group of communities (the second group), 
everyone received treatment and prevention for malaria, whether or not they had malaria. Communities received either one of these two interventions.   Your 
community was involved in one of these programs.   
 
Why am I being asked to be a part of this study? 
As [you / a member of your community] had malaria 6-9 months ago, we would like to collect a sample of your blood today in order to better understand the body’s 
response to malaria infection. Additionally, near the end of the study, we would like to test everyone in your community for malaria to understand the impact the 
intervention had on your community. We would like to include you in these follow-up tests. 
 
How many people will take part in this study?  
About 600 people will be invited to participate in the study to understand the body’s response malaria infection.  
 
What will happen if I take part in this research study? 
Right now, you are only being asked to provide assent for the study activities occurring today. Before you participate in any future visit study activities, we will ask 
you to provide assent again that day. 
 
Today: 
Our study team will ask you a few basic questions about you and your experiences with malaria and record your answers on a tablet. We will perform 2 
finger pricks to collect a small amount of blood (1/10th of a teaspoon).  
 
Near the end of the study: 
In order to assess the impact of our study intervention, our study team will return again near the end of the study (mid 2017) to collect an additional small 
amount of blood (1/20th of a teaspoon) by finger prick from you. Our study team will also ask you a few basic questions about you and your experiences 
with malaria and will record your answers on a tablet. 
 
We will perform a rapid test for malaria each time we take a blood sample from you and, if the rapid test shows that you have malaria, we will refer you to the 
nearest health facility for treatment. We would also like to save a portion of each blood draw for future research studies related to malaria only. 
 
How long will I be in the study? 
Today’s questionnaire and blood collection will be performed in your home and will take about 10 minutes. The future visit for blood collection will occur in your 
home and take 5 minutes each time.  
 
What are my rights if I take part in this study? Can I stop being in the study? 
With the permission of your parent or guardian, you may choose either to take part or not to take part in the study. If you decide to take part in this study, you may 
leave the study at any time. If at any time, you would like to withdraw your information and/or withdraw blood samples from malaria testing, you can have your 
parent or guardian contact us. If your parent or guardian wants you to withdraw from the study, you must withdraw.  If you choose not to participate in the study or 
leave the study, there will be no penalty to you or your family. You will not lose any regular benefits and it will not affect your medical care.  
 
What risks can I expect from being in the study? 
There are minimal risks from participating in the interview. The questionnaire does not ask sensitive questions and measures are in place to keep the information you 
provide confidential. You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at the site of the finger prick, but the 
risk is minimal because the process will be done by a well trained officer. Participation or refusal to participate in this study will not affect your care in any way. 
 
Medical care. 
We do not expect any problems with participating in the study. However, in case you feel unwell at any point during the study as a potential side effect from your 
participation, you should have your parent/guardian contact our Study Coordinator and bring you to your local health facility.  
 
Are there benefits to taking part in the study? 
If you are found to have malaria by rapid testing today or at the future visit, you will benefit from being refered for malaria treatment.  
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you. You will still get care from the health 
facility the way you usually do. Even if you do not take part in the study today, you are still eligible to participate in the follow-up blood test near the end of the study. 
 
 
 

 
 
 
106
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will be used 
throughout the study. There may be situations where we need your name, for example for follow up visits. Therefore, we will keep a key linking your name to your 
study number/identifier. But only key study staff will have access to this information. All information from the study will be kept in locked cabinets or computers. 
Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the Clinton Health Access Initiative in Mbabane, Swaziland 
and the University of California San Francisco, United States of America. Your name will not appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
With your parent or guardian’s permission, you may choose either to take part or not to take part in the study. If you decide to take part in the study, you may leave 
the study at any time. No matter what decision you make, there will be no penalty to you in any way. You will not lose any of your regular benefits, and you can still 
get your care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can have your parent/guardian contact our Study Coordinator at +268 #### ####. If you were 
found to have malaria today and experience any adverse health events that may be related to treatment, have your parent/guardian contact your attending Study 
Nurse at +268 #### ####. If you wish to voice any problems or concerns you may have about how this study is being conducted, please have your parent/guardian 
call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
ASSENT 
You have been given a copy of this assent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or to withdraw at 
any point in this study without penalty or loss of benefits to which you are otherwise entitled. 
 
If you wish to participate in this study, you should indicate how you would like to participate and sign below. 
 
This study was explained to me clearly. 
 
 
 
 
 
 
 
 Yes       No  
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
  
I agree to provide a blood sample for malaria testing today (by a rapid diagnostic test).  
 
 
 Yes       No 
   
I agree to allow a part of today’s blood sample to be saved for research purposes related to malaria only. 
 
 Yes       No   
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                     
Name of Minor 
 
 
  Signature or finger print of Minor  
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
  Signature of Person Obtaining Consent 
 
 
WITNESS (only necessary if assent conducted in language other than English or SiSwati) 
I witness that this assent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study. Language that 
assent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                     Name   
 
 
 
Signature or finger print of witness  
 
 
 
 

 
 
 
107
Appendix M. 6-9 month follow-up questionnaire 
 
1. Investigation conducted by, (check all that apply)  
BadelisileCalsileGcinumuziKhayaMathokozaMduduziMpenduloNombuso 
NomceboNomkhosiSenzoThulaniVusani Other___________________ 
 
2. Scan Barcode 
 
3. Subject’s Name __________________________________________ 
 
4. Gender  Male Female 
 
5. Date of birth 
|___|___|/|___|___|/|___|___| 
 
       date          month           year 
6. Inkhundla 
_____________________________________ 
 
7. Locality 
_____________________________________ 
 
8. Patient contact information 
a. 
Telephone number 1: ________________________ 
b. Telephone number 2: ________________________ 
 
9. GPS coordinates of home (can skip and record later, as interview may not be conducted at subject’s home) 
 
S ____° ____’ ____”  
 
E ____° ____’ ____” 
 
10. Consent obtained:  Yes  No   
 
11. Ask, have you had fever in the last 2 weeks? 
 Yes  No   Don’t know 
 
12. Ask: Have you been diagnosed with malaria in the past 12 months?  Yes   No  
 
If yes, ask when,  
 6 months to a year ago  
< 6 months ago  
 Within the last month  
 Within the last 2 weeks 
 Don’t know 
 
If diagnosed in the last 2 weeks: 
Was the diagnosis confirmed by a test?    
 Yes   
No  
 Don’t know 
 
 
What treatment was prescribed? Check all that apply 
 
 
 
 
 Artemether-lumefantrine 
 
 
 
 
 Single dose primaquine 
 
 Oral Quinine 
 
 
 
 
 IV Quinine 
 
 
 
 
 IM Quinine 
 IV Artesunate 
 
 
 
 
 IM Artesunate 
 
 
 
 
 Chloroquine 
 
 
 
 
 SP/Fansidar 
 
 
 
 
 Other (specify _______________________ 
 
 
 
 
 Unknown 
Was full treatment course completed?      Yes   No  Don’t know 

 
 
 
 
Prior Residence and/or Travel History 
14. Have you ever lived or stayed in Mozambique for at least 30 consecutive days? 
If yes, approximately how long ago was this visit or stay? _____ yrs _____ mos 
15. Have you spent at least one night anywhere else besides your current residence in the past 8 weeks?  
 Yes   No   Don’t know 
 
If no, skip to question 10. 
 
If yes, ask: Where did you sleep overnight, when did you sleep there, why did you sleep there, and personal protection?  If slept outside Swaziland, also ask about 
means of travel and border post of re-entry. 
 
Within Swaziland 
Town / Locality / 
Inkhundla 
Duration of Stay 
Reason for sleeping away 
from current residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal protection  
-chemoprophylaxis 
(specify___) 
-bednet 
-mosquito repellent or coil 
-None 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
a. 
 
 
 
 
b.  
 
 
 
 
c.  
 
 
 
 
d.  
 
 
 
 
e.  
 
 
 
 
 
Outside of Swaziland 
Country 
Province 
/ Town 
Duration of Stay 
Reason for 
sleeping away 
from current 
residence:  
-previous residence 
-business 
-holiday 
-visiting friends / 
family 
-other 
(specify__________) 
Personal 
protection  
-chemoprophylaxis 
(specify___) 
-bednet 
-mosquito repellent 
or coil 
-None 
Means of travel 
-Large bus 
-Kombi (van) 
-Personal car 
-Ride share (catch a ride 
/ got a lift) 
-Airplane 
-Bicycle 
-Walked 
-Other (specify__________) 
Border Post of Re-Entry 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
- Lavumisa/Golela 
- Salitje/Onverwacht 
- Mahamba 
- Gege/Bothashoop 
- Sicunusa/Houtkop 
- Sandlane/Nerston 
- Ngwenya/Oshoek 
 
- Bulembu/Josefsdal 
- Matsamo/Jeppe’s Reef 
- Mananga 
- Lomahasha/Namaacha 
- Mhlumeni/Goba 
- KMIII International 
Airport 
- Other 
 
a. 
 
 
 
 
 
 
 
b.  
 
 
 
 
 
 
 
c.  
 
 
 
 
 
 
 
d.  
 
 
 
 
 
 
 
e.  
 
 
 
 
 
 
 

16. Comments or any other information that is relevant? 
_____________________________________________________________________________________________________________ 
 
17. RDT result:positive   negative   not done 
If positive, patient referred to local health facility    Yes   No   
If no, why? _______________________________________________________________________________________________ 
DBS collected  Yes   No 
 Not Done 
If DBS not done, why? Patient refused   Other_______________________________ 
 
Thank you for our participation in this study. 
 

 
Appendix N. (1) Resident End-line Survey  
Adult Informed Consent Form  
 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. We recently implemented a malaria intervention in your community. In order to evaluate the impact of that intervention, we have 
now returned for blood testing in your community. Your participation is important, although entirely voluntary. Funding for this study is provided by 
the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone was tested for malaria and only people who have malaria were referred for treatment. In another group of 
communities (the second group), everyone received treatment and prevention for malaria, whether or not they had malaria. Communities received 
either one of these two interventions. Your community was involved in one of these programs. We are now testing everyone to see how many people 
have malaria after the program.  
 
How many people will take part in this study?  
About 4500 people were in the first group of communities and 4500 people were in the second group of communities. 8100 people will be included in 
the end-line survey. 
 
What will happen if I take part in this research study? 
We would like to collect a small amount of blood from you today, 1/20th of a teaspoon by finger prick. We will perform a rapid test for malaria and 
will provide a referral to the nearest health facility for treatment if you are found to be infected. We would also like to save a portion of the blood 
draw for future research studies related to malaria only. Our study team will also ask you a few basic questions about you and your experiences with 
malaria and will record your answers on a tablet. 
 
How long will I be in the study? 
Today’s blood collection and interview will be performed in your home and will take about 5 minutes.  
 
Can I stop being in the study? 
If you decide to take part in this study, you may leave the study at any time. If at any time, you would like to withdraw your blood samples from 
malaria testing, you can contact us. If you choose not to participate in the study or leave the study, there will be no penalty to you or your family. You 
will not lose any regular benefits and it will not affect your medical care.  
 
What risks can I expect from being in the study? 
You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at the site of the finger prick, but the risk is 
minimal because the process will be done by a well trained officer.  
 
Medical care. 
We do not expect any problems with participating in the study. However, in case you feel unwell at any point during the study as a potential side 
effect from your participation, you should contact our Study Coordinator and go to your local health facility.  
 
Are there benefits to taking part in the study? 
If you are found to have malaria by rapid testing today, you will benefit from being refered for malaria treatment.  
 
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will 
be used throughout the study. Only key study staff will have access to this information. All information from the study will be kept in locked cabinets 
or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the Clinton Health Access 
Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name will not appear in any reports or 
publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
You may choose either to take part or not to take part in the study. If you decide to take part in the study, you may leave the study at any time. No 
matter what decision you make, there will be no penalty to you in any way. You will not lose any of your regular benefits, and you can still get your 
care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you were found to have 
malaria today and experience any adverse health events that may be related to treatment, contact your attending Study Nurse at +268 #### ####. If 
you wish to voice any problems or concerns you may have about how this study is being conducted, please call the office of the Swaziland Ministry of 
Health’s Ethics Committee at +268 2404 7253. 
 
 

 
 
 
111
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or 
to withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, 
you should indicate how you would like to participate and sign below.  
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
 
I agree to provide a blood sample for malaria testing today (by a rapid diagnositc test).  
 
 
 Yes       No 
   
I agree to allow a part of my blood sample to be saved for research purposes related to malaria only. 
 
 
 Yes       No   
 
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                                Name   
 
 
 
  Signature or finger print  
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study. 
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                Name   
 
 
 
  Signature or finger print of witness 
 
 

 
 
 
112
Appendix N. (2) Resident End-line Survey 
Parent / Guardian Permission Form for Children <12 years  
(one form per Parent/Guardian: obtains consent from the Parent/Guardian and permission for 
multiple children) 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. We recently implemented a malaria intervention in your community. In order to evaluate the impact of that intervention, we have 
now returned for blood testing in your community. Your participation is important, although entirely voluntary. Funding for this study is provided by 
the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone was tested for malaria and only people who have malaria were referred for treatment. In another group of 
communities (the second group), everyone received treatment and prevention for malaria, whether or not they had malaria. Communities received 
either one of these two interventions. Your community was involved in one of these programs. We are now testing everyone to see how many people 
have malaria after the program.  
 
How many people will take part in this study?  
About 4500 people were in the first group of communities and 4500 people were in the second group of communities. 8100 people will be included in 
the end-line survey. 
 
What will happen if we take part in this research study? 
We would like to collect a small amount of blood from you and your child(ren) today, 1/20th of a teaspoon by finger prick. Each blood collection 
should take about 5 minutes. We will perform a rapid test for malaria and will provide a referral to the nearest health facility for treatment if you or 
your child(ren) are found to be infected. We would also like to save a portion of the blood draw for future research studies related to malaria only. Our 
study team will also ask you a few basic questions about your family’s experiences with malaria and will record your answers on a tablet. 
 
How long will we be in the study? 
Today’s blood collection and interview will be performed in your home and will take about 5 minutes per person.  
 
Can we stop being in the study? 
If you decide to take part in this study, you and/or your child(ren) may leave the study at any time. If at any time, you would like to withdraw your 
and/or your child(ren)’s blood samples from malaria testing, you can contact us. If you choose not to participate in the study or leave the study, there 
will be no penalty to your child(ren) or your family. You will not lose any regular benefits and it will not affect your family’s medical care.  
 
What risks can we expect from being in the study? 
There may be a brief moment of pain when the blood is being collected and there is a small risk of infection at the site of the finger prick, but the risk 
is minimal because the process will be done by a well trained officer. 
 
Medical care. 
We do not expect any problems with participating in the study. However, in case you or your child(ren) feel unwell at any point during the study as a 
potential side effect from their participation, you should contact our Study Coordinator and go to your local health facility.  
 
Are there benefits to taking part in the study? 
If you or your child(ren) are found to have malaria on rapid testing today, they will benefit from being refered for malaria treatment.  
 
How will information about us be kept confidential? 
We will not inform anyone of your or your child(ren)’s participation in the study and your name(s) will be kept confidential by replacing them with 
number(s)/identifier(s) that will be used throughout the study. Only key study staff will have access to this information. All information from the study 
will be kept in locked cabinets or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, 
the Clinton Health Access Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name(s) will 
not appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will we be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are our rights if we take part in this study? 
You may choose either to take part or not to take part in the study. If you decide to take part in the study, you and/or your child(ren) may leave the 
study at any time. No matter what decision you make, there will be no penalty to you or your family in any way. You and your child(ren) will not lose 
any of your regular benefits, and you can still get care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you or your child(ren) 
were found to have malaria today and experience any adverse health events that may be related to treatment, contact your attending Study Nurse at 
+268 #### ####. If you wish to voice any problems or concerns you may have about how this study is being conducted, please have your 
parent/guardian call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
 

 
 
 
113
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY. Your child(ren) are unable to consent for 
themselves because they are less than 18 years old. By signing this form, you are giving permission for you and your child(ren) or ward(s) to participate 
in the study.  You have the right to decline participate or to withdraw at any point in this study without penalty or loss of benefits to which you or your 
family are otherwise entitled. If you wish to participate or have your child(ren) participate in this study, you should indicate how you would like to 
participate and sign below. 
 
Number of children (<18 years old) that I consent may participate in the study:                                . 
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
 
I agree to have my child(ren) be interviewed today, if requested by study staff. 
 
 
 
 Yes       No  
 
I agree to provide a blood sample for malaria testing today (by a rapid diagnositc test).  
 
 
 Yes       No 
 
I agree to have my child(ren) provide a blood sample for malaria testing today (by a rapid diagnositc test). 
 
 Yes       No 
   
I agree to allow a part of my blood sample to be saved for research purposes related to malaria only.  
 
 Yes       No   
 
I agree to allow a part of my child(ren)’s blood sample(s) to be saved for research purposes  
related to malaria only. 
 
 
 
 
 
 
 
 
 Yes       No   
 
   
 
                   
 
                    
                    
 
 
 
 
Date 
                     
Name of Parent/Guardian 
 
Signature or fingerprint of Parent/Guardian  
 
 
Name(s) of children (If indicated, list names of additional children on the back of the form): 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #1 
 
 
     Child #2                     
            Child #3 
 
 
         Child #4 
 
 
 
           ___________        ______                    __________        ______ 
                   __________     ______ 
                   _____ 
Child #5 
 
 
     Child #6                     
            Child #7 
 
 
         Child #8 
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                     Name   
 
 
 
Signature or finger print of witness 
 
 

 
 
 
114
Appendix N. (3) Resident End-line Survey 
Minor (12-17yr) Assent Form 
 
 
Introduction 
Greetings! My name is _____________.  I am conducting surveillance and a research project with the National Malaria Control Program within the 
Ministry of Health. We recently implemented a malaria intervention in your community. In order to evaluate the impact of that intervention, we have 
now returned for blood testing in your community. Your participation is important, although entirely voluntary. Funding for this study is provided by 
the Bill & Melinda Gates Foundation. 
 
Why is this study being done? 
The purpose of this study is to help Swaziland eliminate malaria. We are evaluating different ways of trying to eliminate malaria. In one group of 
communities (the first group), everyone was tested for malaria and only people who have malaria were referred for treatment. In another group of 
communities (the second group), everyone received treatment and prevention for malaria, whether or not they had malaria. Communities received 
either one of these two interventions. Your community was involved in one of these programs. We are now testing everyone to see how many people 
have malaria after the program.  
 
How many people will take part in this study?  
About 4500 people were in the first group of communities and 4500 people were in the second group of communities. 8100 people will be included in 
the end-line survey. 
 
What will happen if I take part in this research study? 
We would like to collect a small amount of blood from you today, 1/20th of a teaspoon by finger prick. We will perform a rapid test for malaria and 
will provide a referral to the nearest health facility for treatment if you are found to be infected. We would also like to save a portion of the blood 
draw for future research studies related to malaria only. Our study team will also ask you a few basic questions about you and your experiences with 
malaria and will record your answers on a tablet. 
 
How long will I be in the study? 
Today’s blood collection and interview will be performed in your home and will take about 5 minutes.  
 
Can I stop being in the study? 
If you decide to take part in this study, you may leave the study at any time. If at any time, you would like to withdraw your information and/or 
withdraw blood samples from malaria testing, your parent or guardian can contact us. If your parent or guardian wants you to withdraw from the 
study, you must withdraw. If you choose not to participate in the study or leave the study, there will be no penalty to you or your family. You will not 
lose any regular benefits and it will not affect your medical care.  
 
What risks can I expect from being in the study? 
You may feel a brief moment of pain when the blood is being collected and there is a small risk of infection at the site of the finger prick, but the risk is 
minimal because the process will be done by a well trained officer.  
 
Medical care. 
We do not expect any problems with participating in the study. However, in case you feel unwell at any point during the study as a potential side 
effect from your participation, you should have your parent/guardian contact our Study Coordinator and bring you to your local health facility.  
 
Are there benefits to taking part in the study? 
If you are found to have malaria by rapid testing today, you will benefit from being refered for malaria treatment.  
 
How will information about me be kept confidential? 
We will not inform anyone of your participation in the study and your name will be kept confidential by replacing it with a number/identifier that will 
be used throughout the study. Only key study staff will have access to this information. All information from the study will be kept in locked cabinets 
or computers. Organizations that will examine the data are the National Malaria Control Program in Manzini, Swaziland, the Clinton Health Access 
Initiative in Mbabane, Swaziland and the University of California San Francisco, United States of America. Your name will not appear in any reports or 
publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
What are my rights if I take part in this study? 
With your parent or guardian’s permission, you may choose either to take part or not to take part in the study. If you decide to take part in the study, 
you may leave the study at any time. No matter what decision you make, there will be no penalty to you in any way. You will not lose any of your 
regular benefits, and you can still get your care from your health facility the way you usually do. 
 
Who can I contact in case of injury or if I have future questions about the study? 
If you have any questions about this study or your participation, you can have your parent/guardian contact our Study Coordinator at +268 #### ####. 
If you were found to have malaria today and experience any adverse health events that may be related to treatment, have your parent/guardian 
contact your attending Study Nurse at +268 #### ####. If you wish to voice any problems or concerns you may have about how this study is being 
conducted, please have your parent/guardian call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
 

 
 
 
115
ASSENT 
You have been given a copy of this assent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY.  You have the right to decline to participate or to 
withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, you 
should indicate how you would like to participate and sign below. 
 
This study was explained to me clearly. 
 
 
 
 
 
 
 
 Yes       No  
 
I agree to be interviewed today.  
 
 
 
 
 
 
 
 Yes       No  
 
I agree to provide a blood sample for malaria testing today (by a rapid diagnositc test).  
 
 
 Yes       No 
   
I agree to allow a part of today’s blood sample to be saved by 
study staff for future testing (for research purposes only). 
 
 
 
 
 
 Yes       No   
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                  Name of Minor 
 
 
Signature or fingerprint of Minor 
 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
WITNESS (only necessary if assent conducted in language other than English or SiSwati) 
I witness that this assent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study. 
Language that assent was conducted in:                                                            . 
 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                Name   
 
 
 
Signature or finger print of witness 
 
 
  
 
 

Appendix O. Household level end-line survey (to be completed mid 2017) 
 
 
Barcode 
(from 
last 
visit) 
Name 
House
hold 
head 
(check 
if yes) 
Index 
case 
(check if 
yes) 
Gender 
Date of 
birth 
Consent  
obtained 
for 
today’s 
blood 
collection 
(yes/no) 
Participa
ted in 
interven
tion 
(yes/no) 
Have you been diagnosed 
with malaria since you first 
participated in the study 
intervention? Yes/No 
 
If yes list date or dates 
__________ 
YY/MM/DD 
 
Have you 
had fever 
in the 
past 2 
weeks? 
(yes/no) 
Have you take 
antimalarial medication 
in the past 2 months?  
Yes/No 
 
If yes, what treatment 
was prescribed? 
Check all that apply 
AL (Coartem) 
 Single dose 
primaquine 
 Oral Quinine 
 IV Quinine 
 IM Quinine 
 IV Artesunate 
 IM Artesunate 
Chloroquine 
 SP/Fansidar 
 Other (specify_____) 
Unknown 
 
Was full treatment 
course completed?  
Yes  No Don’t 
know 
 
On what day was the 
last treatment 
started? 
__________ 
YY/MM/DD 
 
Have you 
spent at least 
one night 
outside of this 
village in the 
past 8 weeks? 
 
If yes, 
complete 
travel 
information 
below. 
DBS 
collected 
today? 
(yes/no) 
Notes 
1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
2.  
 
 
 
 
 
 
 
 
 
 
 
 
 
Edit 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add 
Individual 
Note: Shaded areas will be automatically generated from the all previous visits to this household.  For each individual, confirm this data.  If  
Note: Add a new line for individuals  
 
Travel information 
Within Swaziland 
Outside of Swaziland 
Village / town/ District where you have 
spent the night(s)  
Duration of stay 
Country/Province/Town where you 
have spent the night(s) 
Duration of stay 
First Night 
DD/MM/YY 
Last Night 
DD/MM/YY 
First Night 
DD/MM/YY 
Last Night 
DD/MM/YY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Appendix P. End-line Individual questionnaire 
 
Patient Details 
1.  Patient Name 
_____________________________________ 
 
 
2.  Date of birth 
|___|___|/|___|___|/|___|___| 
 
 
  date         month       year 
3.  Gender 
 Male Female 
4. Inkhundla 
_____________________________________ 
5. Locality 
_____________________________________ 
6. Study ID:  _________________ 
 
7. Household ID:  _________________ 
 
8. Consent obtained:  Yes  No   
 
9. Ask: Did you participate in the initial study intervention?  
 TPE Arm  
 RACD Arm  
 Did not participate 
 
If yes, ask: Have you taken malaria medication as a part of this study?  Yes   No 
 
If yes, ask: What malaria medication did you take?  
 Dihydroartemisinin-piperaquine (Eurartesim) 
Artemether-lumefantrine (Coartem)   
 
 
 Other (specify _______________________ 
 
 
Unknown 
If yes, ask: Did you experience any adverse events that you think may have been related to the malaria 
medication?  Yes   No 
 
If yes, ask: Please describe these adverse events.  
___________________________________________________________________________________________
___________________________________________________________________________________________ 
 
10. Ask: Have you been diagnosed with malaria in the past 12 months?  Yes   No  
If yes, ask when,  
 6 months to a year ago 
< 6 months ago 
 Within the last month 
 Within the last 2 weeks 
 Don’t know 
If yes ask, have you had fever in the last 2 weeks?  Yes  No   Don’t know 
If yes ask, have you been diagnosed with malaria in the last 2 weeks?  Yes  No   Don’t know 
If diagnosed in the last 2 weeks: 
Was the diagnosis confirmed by a test?    Yes  No   Don’t know 
What treatment was prescribed? Check all that apply 
 
 
 
Artemether-lumefantrine 
 
 
 
 Single dose primaquine  
 Oral Quinine 
 
 
 
 IV Quinine 
 
 
 
 IM Quinine 
 
 
 
Chloroquine 
 
 
 
 SP/Fansidar 
 
 
 
 Other (specify _______________________ 
 
 
 
Unknown 
Was full treatment course completed?      Yes   No  Don’t know 

Prior Residence and/or Travel History 
11. Have you ever lived or stayed in Mozambique for at least 30 consecutive days? 
If yes, approximately how long ago was this visit or stay? _____ yrs _____ mos 
12. Have you spent at least one night anywhere else besides your current residence in the past 8 weeks?  
 Yes   No   Don’t know 
 
If no, skip rest of questions. 
 
If yes, ask: Where did you sleep overnight, when did you sleep there, why did you sleep there, and personal protection?  If slept outside Swaziland, also ask about means of 
travel and border post of re-entry. 
 
Within Swaziland 
Town / Locality / 
Tinkhundla 
Duration of Stay 
Reason for sleeping away from current residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal protection  
-chemoprophylaxis (specify___) 
-bednet 
-mosquito repellent or coil 
-None 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
a. 
 
 
 
 
b.  
 
 
 
 
c.  
 
 
 
 
d.  
 
 
 
 
e.  
 
 
 
 
 
Outside of Swaziland 
Country 
Province / 
Town 
Duration of Stay 
Reason for sleeping away 
from current residence:  
-previous residence 
-business 
-holiday 
-visiting friends/family 
-other (specify, _____) 
Personal 
protection  
-chemoprophylaxis 
(specify___) 
-bednet 
-mosquito 
repellent or coil 
-None 
Means of travel 
-Large bus 
-Kombi (van) 
-Personal car 
-Ride share (catch a 
ride/got a lift) 
-Airplane 
-Bicycle 
-Walked 
- other (specify, _____) 
Border Post of Re-Entry 
First Night 
YY/MM/DD 
Last Night 
YY/MM/DD 
- Lavumisa/Golela 
- Salitje/Onverwacht 
- Mahamba 
- Gege/Bothashoop 
- Sicunusa/Houtkop 
- Sandlane/Nerston 
- Ngwenya/Oshoek 
 
- Bulembu/Josefsdal 
- Matsamo/Jeppe’s Reef 
- Mananga 
- Lomahasha/Namaacha 
- Mhlumeni/Goba 
- Matsapha International 
Airport 
- Other 
 
a. 
 
 
 
 
 
 
 
 
b.  
 
 
 
 
 
 
 
 
c.  
 
 
 
 
 
 
 
 
d.  
 
 
 
 
 
 
 
 
e.  
 
 
 
 
 
 
 
 

13. Comments or any other information that is relevant? 
__________________________________________________________________________________________________
___________ 
 
14. RDT result:positive   negative   not done 
If positive, patient referred to local health facility    Yes   No   
If no, why? 
_________________________________________________________________________________________
______ 
DBS collected  Yes   No 
 Not Done 
If DBS not done, why? Patient refused   Other _______________________________ 
 
Thank you for our participation in this study. 
 
 
 

 
 
 
120
Appendix Q. DP weight-based dosing guidelines 
 

 
 
 
121
Appendix R. Modified DOT dosing schedule 
 
Day 1 DOT only arm 
  
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Present all 3 days 
Rx 1 (DOT) 
Rx 2  
(self-admin) 
Rx 3 
(self-admin) 
Absent day 1 
Rx 1 (DOT) 
Rx 2  
(self-admin) 
Rx 3  
(self-admin) 
Absent days 1 & 2 
Rx 1 (DOT) 
Rx 2  
(self-admin) 
Rx 3  
(self-admin) 
 
If needed to improve coverage, study staff will visit neighborhoods on Days 2 and 3.  On these days, they may 
document that the dose that day was taken, remind subjects to take their medication, or directly observe 
ingestion. 
 

 
 
 
122
Appendix S. Serious adverse event report form 
To be completed by Study Physician 
 
 
1 
 
MINISTRY OF HEALTH 
 
Adverse Drug Reactions (ADR) Report Form 
 
Report can be returned to Central Medical Stores by fax 25186279 or 25186642 
Email swazilandpharmacovigilance@gmail.com or cms@realnet.co.sz or  
Post to: Adverse Drug Reaction, Central Medical Stores, P. O. Box 72, Kwaluseni 
For Further inquiries, please contact the Pharmacist (Pharmacovigilance) at Central Medical Stores at 25184111 or 25187255 
 
Section (A): Patient Information    
Patient initials or ref. no.: ------------------Sex: □ M □ F: Pregnant? No □ Yes □ Unknown □ 
Weight (if known): _____ kg Date of birth: (dd/ mm/ yyyy)  /   /   or age (at last birthday):_____ 
 
Section (B): Medication History 
Allergies or other relevant history (including medical history, liver/ kidney problems, smoking, alcohol use etc) 
______________________________________________________________________________ 
 
Section (C): About the Adverse Drug Reaction 
Date of onset of ADR: (dd/ mm/ yyyy)     /      /  
Description of event: -------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------------- 
Category of ADR (please tick) 
□ Suspect minor/ major reaction from a drug (e.g. allergic reaction) 
□ Adverse Event (e.g. congenital defects) 
□ Product Use Error (e.g. use of antibiotic instead of NSAID) 
 
Severity (can tick more than one if appropriate): 
□Life threatening  
□ Hospitalized   (dd/ mm/ yyyy)      /   / 
□Hospitalization NOT required 
 
Relevent Laboratory result:______________________________________________________________ 
 
Section (D): Treatment & Outcome 
All Drug Therapies/ Vaccines 
Prior to ADR 
(Please use trade names and circle the 
suspected drug.) 
Batch 
number 
 
Daily 
Dosage 
Route 
 
Date 
Begun 
 
Date 
Stopped 
 
Indication  for Use 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
123
 
Additional questions (also completed by study physician): 
20) Maximum severity (See WHO Grading) |_|_| 
1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening 
21) Suspected relationship |_|_| 
 
0=None, 1=Unlikely, 2=Possible, 3=Probable, 4=Definite 
22) If the event occurred in association with medication, was the event listed on the medication package 
insert?  |_|_| 
1=Yes, 2=No, 3=N/A 
 
 

 
 
 
124
Appendix T.WHO Grading for Determining Severity of Adverse 
Events 
 
Appendix:
WHO TOXICITY GRADING SCALE FOR DETERMINING 
THE SEVERITY OF ADVERSE EVENTS
Section VIII: 
Appendices
132
February 6, 2003 
WHO Toxicity Grading Scale for Determining The Severity of Adverse Events
HEMATOLOGY
 
ITEM 
Grade 1 Toxicity
Grade 2 Toxicity
Grade 3 Toxicity
Grade 4 Toxicity
Hemoglobin
9.5 - 10.5 gm/Dl
8.0  - 9.4 gm/Dl
6.5 - 7.9 gm/Dl
< 6.5 gm/Dl
Absolute Neutrophil
Count
1000-1500/mm3
750-999/mm3
500-749/mm3
<500/mm3
Platelets
75000-99000/mm3
50000-74999/mm3
20000-49000/mm3
<20000/mm3
Prothrombin
Time (PT) 
1.01 - 1.25 x ULN
1.26-1.5 x ULN
1.51 -3.0 x ULN
>3 x ULN
Activated Partial
Thromboplastin
(APPT)
1.01 -1.66 x ULN
1.67 - 2.33 x ULN
2.34 - 3 x ULN
> 3 x ULN
Fibrinogen
0.75 - 0.99 X LLN
0.50 - 0.74 x LLN
0.25 - 0.49 x LLN
< 0.25 x LLN
Fibrin Split Product
20-40 mcg/ml
41-50 mcg/ml
51-60 mcg/ml
> 60 mcg/ml
Methemoglobin
5 - 9.9 %
10.0 - 14.9 % 
15.0 - 19.9%
> 20 % 
LIVER ENZYMES
AST (SGOT)
1.25 - 2.5 x ULN
2.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
ALT (SGPT)
1.25 - 2.5 x ULN
2.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
GGT
1.25 -2.5 x ULN
1.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
Alkaline Phosphatase
1.25 - 2. 5 x ULN
1.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
Amylase
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.1 - 5.0 x ULN
> 5.1 x ULN
CHEMISTRIES
Hyponatremia
130-135 mEq/L
 123-129 mEq/L
116-122 mEq/L
< 116 or mental
status changes or
seizures
Hypernatremia
146-150 mEq/L
151-157 mEq/L
158-165 mEq/L
> 165 mEq/L or
mental status 
changes or seizures
Hypokalemia
3.0 - 3.4 mEq/L
2.5 - 2.9 mEq/L
2.0 - 2.4 mEq/L
or intensive
replacement Rx 
required or
hospitalization
required.
< 2.0 mEq/L
or paresis or ileus
or life-threatening 
arrhythmia
Hyperkalemia
5.6 - 6.0 mEq/L
6.1 - 6.5 mEq/L
6.6 - 7.0 mEq/l
> 7.0 mEq/L
or life-threatening 
arrhythmia
Hypoglycemia
55-64 mg/dL
40-54 mg/dL
30-39 mg/dL
<30 mg/dL or
mental status 
changes or coma
Monitoring and Reporting Adverse Events

 
 
 
125
 
 
 
 
 
 
 
 
 
Appendix:
WHO TOXICITY GRADING SCALE FOR DETERMINING 
THE SEVERITY OF ADVERSE EVENTS
Section VIII: 
Appendices
133
February 6, 2003 
CHEMISTRIES (continued)
Hyperglycemia
(note if fasting)
116 - 160 mg/dL
161- 250 mg/dL
251 - 500 mg/dL
> 500 mg/dL
or ketoacidosis
 or seizures
Hypocalcemia
(corrected for albumin)
8.4 - 7.8 mg/dL
7.7 - 7.0 mg/dL
6.9 - 6.1 mg/dL
< 6.1 mg/dL
or life threatening 
arrhythmia or tetany
Hypercalcemia
(correct for albumin)
10.6 - 11.5 mg/dL
11.6 - 12.5 mg/dL
12.6 - 13.5 mg/dL
> 13.5 mg/dL
life-threatening
arrhythmia
Hypomagnesemia
1.4 - 1.2 mEq/L
1.1 - 0.9 mEq/L
0.8 - 0.6 mEq/L
< 0.6 mEq/L or life-
threatening
arrhythmia
Hypophosphatemia
2.0 - 2.4 mg/dL
1.5 -1.9 mg/dL or
replacement Rx 
required
1.0 -1.4 mg/dL
intensive Rx or
hospitalization
required
< 1.0 mg/dL or life-
threatening
arrhythmia
Hyperbilirubinemia
1.1 - 1.5 x ULN
1.6 - 2.5 x ULN
2.6 - 5 x ULN
> 5 x ULN
BUN
1.25 - 2.5 x ULN
2.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
Creatinine
1.1 x 1.5 x ULN
1.6 - 3.0 x ULN
3.1 - 6 x ULN
> 6 x ULN or 
required dialysis
URINALYSIS
Proteinuria
1+ or < 0.3% or <3g/L
or 200 mg - 1 gm
loss/day
2 -3 + or 0.3 - 1.0% or
3-10 g/L
1- 2 gm loss/day
4+ or > 1.0% or > 10
g/L
2-3.5 gm loss/day
nephrotic syndrome
or > 3.5 gm loss/day
Hematuria
microscopic only 
gross, no clots
gross+ clots
obstructive or
required transfusion
CARDIAC DYSFUNCTION
Cardiac Rhythm
asymptomatic,
transient signs, no
Rx required
recurrent/persistent;
No Rx required
requires treatment 
Hypertension
transient inc. > 20 mm; 
no Rx
recurrent, chronic, > 
20 mm, Rx required
requires acute Rx; No
hospitalization
requires
hospitalization
Hypotension
transient orthostatic 
hypotension, No Rx
symptoms correctable 
with oral fluids Rx
requires IV fluids; no
hospitalization
required
requires
hospitalization
Pericarditis
minimal effusion
mild/moderate
asymptomatic
effusion, no Rx
symptomatic effusion;
pain; EKG changes
tamponade;
pericardiocentesis
or surgery required
Hemorrhage, Blood
Loss
microscopic/occult
mild, no transfusion
gross blood loss;
1-2 units transfused
massive blood loss;
> 3 units transfused
Monitoring and Reporting Adverse Events

 
 
 
126
Appendix U. Acceptability Assessment:  
Adult Informed Consent Form  
(Focus Group Discussions with Study Participants or the Malaria Surveillance Team) 
 
Introduction 
Greetings!  My name is _____________________________.  I would like to invite you to participate in a group discussion that is part of a research 
study about the acceptability of methods to eliminate malaria in the community. The study is organized by the National Malaria Control Program 
(NMCP) within the Ministry of Health.  Your participation is important, although entirely voluntary. Please take your time to make your decision about 
participating, and discuss your decision with your family and friends if you wish. If you have any questions, you may ask me. Funding for this study is 
provided by the Bill & Melinda Gates Foundation. 
 
Why am I being asked to be a part of this study? 
 
If a TPE community member who participated in the study intervention: You took part in a malaria elimination intervention 4 to 10 days ago 
and we would like to hear your impressions about malaria and the malaria intervention that was conducted. 
 
 
If a member of the malaria surveillance team: You have been part of the malaria surveillance team since the beginning of the study. In this 
capacity, you can provide us with valuable insight about the community’s perspectives on malaria and the malaria intervention that was 
conducted. 
 
Why is this study being done? 
The purpose of this study is to understand the experience with malaria ‘screening and treatment’ or ‘treatment without screening’ of residents who 
live within 500 meters of a confirmed malaria case. Communities have been selected at random to receive one of these two interventions. Specifically, 
we are interested in your experience with the malaria intervention offered to you after a malaria case was been identified in your community.  
 
How many people will take part in this study?  
If a TPE community member: About 150 people will take part in this study.  
If a member of the surveillance team: The entire surveillance team will be invited to participate. 
.  
 
What will happen if I take part in this research study? (NOTE TO STUDY STAFF: CIRCLE ONE OF THE BELOW) 
 
For Focus Group Discussions with  TPE Study Participants: I will conduct a group interview with you and your family and or neighbors in 
either the local health facility or at a location near your home. I will ask you to describe your experiences with the study intervention. 
Specifically, I will ask how your participation in the intervention affected you and or your family and community. 
 
 
For Focus Group Discussions with the Malaria Surveillance Team: I will conduct a group interview with you and other members of the 
malaria surveillance team. I will ask you to describe your experiences offering the study interventions to the community. 
 
I will make a sound recording of our conversation. After the group discussion, someone will type into a computer a transcription of what is on the tape 
and will remove any mention of names. The sound recording will then be destroyed.  
 
How long will I be in the study? 
Participation in the study will take a total of 1 hour.  
 
Can I stop being in the study? 
Yes, you can decide to stop at any time. Just tell me or the study staff right away if you wish to stop being in the study. Also, I may stop you from 
taking part in the study at any time if I believe it is in your best interest, if you do not follow the study rules, or if the study is stopped. 
 
What risk can I expect from being in the study? 
Some of the interview questions may make you uncomfortable. [For focus group interviews: There is a risk that other focus group members may 
mention that you participated in this study or may repeat what you said in the group to others outside of the group.] You are free to decline to answer 
any questions you do not wish to answer and we will not collect any names or personal identifiers during the interviews.  
 
Are there benefits to taking part in the study? 
There will be no direct benefit to you from participating in this study. However, the information that you provide may help the National Malaria 
Control Program better understand how to find and treat malaria cases in your community.  
 
What other choices do I have if I do not take part in the study? 
You are free to choose not to participate in the study. If you decide not to take part in the study, there will be no penalty to you.  
 
Will information from the records be kept private? 
We will not inform anyone of your participation in the study and your name will be removed from the transcribed recordings and the tape recordings 
will be destroyed.  The researchers will ask you not to say your name or other identifying information during the interview. Organizations that will 
examine the data are the National Malaria Control Program in Manzini, Swaziland, the Clinton Health Access Initiative in Mbabane, Swaziland and the 
University of California San Francisco, United States of America. Your name will not appear in any reports or publications. 
 
What are the costs of taking part in this study? 
You will not be charged for any of the study procedures. 
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study. 
 
 
What are my rights if I take part in this study? 

 
 
 
127
Taking part in this study is your choice. You may choose either to take part or not to take part in the study. If you decide to take part in the study, you 
may leave the study at any time. No matter what decision you make, there will be no penalty to you in any way. 
 
Who can answer my questions about the study? 
You can talk to the researcher about any questions, concerns, or complaints you have about this study during your interview. If you have any questions 
about this study or your participation, you can contact our Study Coordinator at +268 #### ####. If you wish to voice any problems or concerns you 
may have about how this study is being conducted, please call the office of the Swaziland Ministry of Health’s Ethics Committee at +268 2404 7253. 
 
CONSENT 
You have been given a copy of this consent form to keep. PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to be in this 
study, or to withdraw from it at any point without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this 
study, you should sign below. 
 
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                                        Name   
 
 
 
Signature or finger print  
 
 
 
                   
 
                    
                    
 
 
 
 
Date 
                  
Name of Person Obtaining Consent  
Signature of Person Obtaining Consent 
 
 
 
WITNESS (only necessary if consent conducted in language other than English or SiSwati) 
I witness that this consent form has been read to the participant in the language recorded below, and the participant has agreed to enroll in the study.  
Language that consent was conducted in:                                                            . 
 
 
 
 
 
 
                    
                    
 
 
 
 
Date 
                                    Name   
 
 
 
Signature or finger print of witness 
 
 
 

 
 
 
128
Appendix V. Qualitative questionnaires for the Acceptability Assessment 
– Individual Interviews with Refusers 
 
Barcode: ____________________ 
Auto populate this field as this questionnaire will be triggered by individual refusing to participate in RACD/TPE individual level 
questionnaire.  Grey-out (disable) so Agent cannot make changes. 
 
Capture GPS Coordinates: Latitude (______________) 
Longitude (__________) 
Distance from index case: ____________ 
Auto populate this field, after Surveillance Agent captures GPS coordinates, tablet should calculate distance from index case by 
comparing with GPS coordinates of index case 
 
Study arm (select one):  
 
 RACD  
TPE 
 
 
 
Participant age: ___________ 
Auto-populate based on information collected from household level questionnaire 
 
Participant gender: _____________ 
Auto-populate based on information collected from household level questionnaire 
 
Participant occupation (drop down list) 
Student  
 
 
 
Child or minor but not a student   
Unemployed   
Farming/Agriculture  
 
Manufacturing/Factory   
 
Other Manual Labor    
Small-market sales or trade  
 
Office or Clerical Work   
 
Other (specify ________) 
 
Surveillance Agent Name, check all that apply  
Calsile Sandile Khaya Mathokoza Mduduzi Mukelwe Nombuso 
Nomcebo Nolwazi Senzo Thulani Fanele  Other___________________ 
 
Thank you for answering a few questions for us. These questions will take approximately 5-10 minutes 
to answer. Your information will help us design interventions that are best for the community in future 
work to eliminate malaria. 
 
 
 
Do you mind telling me what your concerns are about participating in this intervention? 
__________________________________________________________________________________________________  
 
Have you ever been part of a malaria screening before?  Yes  No   
o If yes, when? ________________ (calendar pop up) 
 
Have you ever refused to take part in a malaria screening in the past?   Yes  No   
o If yes, why did you refuse?____________________ 
 
If you have been part of a malaria screening in the past (before this study), did you test positive 
for malaria?  Yes  No   
o If yes, did you take medication?  Yes  No   
 
Has anything in the past with medication influenced your decision not to participate in the 
intervention?  Yes  No   
o If yes, what was the problem?______________________  
 
Have you previously had malaria?  Yes  No   
 
If yes, when was the last time you had malaria? _____________yrs ________ months _____ days 
 
Were you informed about the intervention before the malaria nurses visited your household?  
Yes  No   
o If yes, how did that information influence your decision to refuse?  

 
 
 
129
___________________________________________________________________________ 
o If you were not informed earlier, how did the information you received on the day of the 
intervention influence your decision to refuse? 
____________________________________________________________________________ 
 
Is there anything that would make you decide differently in the future?  
_____________________________________________________________________________________ 
 
What do you think is the best way to get rid of malaria in Swaziland? 
_____________________________________________________________________________________ 

 
 
 
130
Appendix W. – Qualitative questionnaires for the Acceptability 
Assessment – Focus Groups with TPE Participants 
 
Semi-structured interview guide 
 
Focus Group ID #____________________ 
 
 
Number of participants: _______________  
 
 
Total number of women: ______________ 
 
Total number of men: ________________ 
 
Participant age range: ________________ 
 
List of participant occupations: ________________________________________________ 
 
Previous participant in this clinical trial?
 YES  
  NO 
 
Date of interview ___________________ 
 
Start time ________End time_________ 
 
Initials of interviewer _________________ 
 
Signed informed consent:  
 
These questions are loosely structured and meant to explore why community members choose to opt in or out of the 
clinical trial. The focus group discussion is intended to be 60 minutes. The researcher leading the focus group will 
describe the session, what topics will be discussed, expectations of member participation, and explain informed 
consent. Each participant will have to sign an individual informed consent that includes demographic information on 
a separate document. The demographic information and names will not be made public and are for the purpose of 
ensuring diversity in the focus group.  
 
I. 
Background and experience with malaria, perception of risk in the community 
 
 
How many of you have lived in this community for at least 5 years? If you have not, where else have you lived?  
 
How many of you have had malaria in the last 5 years? 
 
Has the number of times you have had malaria changed in those 5 years? If yes, how?  
 
If you have had malaria, were you tested? If not, why not?  
 
If you were tested and the test was negative, did you take medication?  
 
What about medication for malaria? Tell me about your experiences taking medication for malaria. What kinds, 
what happened, where did you obtain it? 
 
Do you know other people who have had malaria, other than the index case in this screening study? If yes, 
what is your relationship to them?  
 
Do you think you are at risk for malaria? Why or why not?  
 
Who do you think is at risk for malaria? What should they do to protect themselves?  
 
Do you sleep under a bed net? Why or why not? Tell me more about how you feel about a bed net. Do you 
think it works? What are some of the problems, if any, you have experienced with your bed net?  
 
What else do you do to prevent malaria?  
 
 
 

 
 
 
131
II. 
What experiences will most influence community uptake of the intervention? 
 
*These questions refer to any experiences in the past with malaria screening, NOT the focus group members experience 
during this clinical trial* 
 
 
Have you ever been part of the NMCPs screening for malaria in affected communities? (If no, STOP, ask 
whether they have refused in the past or not had the opportunity to be part of a screening and then go to 
questions about experience during this clinical trial) If YES, continue with other questions. 
 
When did you participate in screening? How was your experience with the screening test done by the NMCP 
officers? 
 
Did you know when you were tested that an index case (your family member or neighbor) was suffering from 
malaria? If yes, do you know if the index case was a family member or neighbor?  
 
How far from the index case did you live? What do you think were the reasons your family member or neighbor 
(index case) got malaria?  
 
Do you think you were at risk since someone living near you got malaria? How about the risk for your family 
members?   
 
Are there people in your household you believe are at greater risk for malaria? Why or why not? 
 
If you have been part of a malaria screening in the past (before this study), did you test positive for malaria? 
Did you believe the test results? Why or why not?  
 
Are you aware of people in your area who have been screened or tested for malaria before? Please share their 
experiences with me if they did inform you. 
 
*These questions refer to your experience during this clinical trial:  
 
Tell me about this malaria screening. How were you contacted? Who did you speak to and what was the 
message they gave you?  
 
What or who made you decide to participate? Tell me about your decision to be part of the screening.  
 
Are there other times or circumstances when you might decide not to accept medication if you have not been 
tested for malaria first?  
 
Do you feel differently or make different decisions about giving medication to your children? How? 
 
How did you learn about this intervention? Tell me what you thought when you first heard of it. 
 
Tell me about the time of day when you were contacted about the intervention, if you were home or work or 
elsewhere? Were you with family members? How far from the index case do you live?  
 
Why do you think your family member or neighbor (index case) got malaria? Do you think you are at risk since 
someone living near you got malaria? How about anyone in your family?  
 
Are there people in your village who you believe are at greater risk for malaria? Why or why not?  
 
Is this the first time you took malaria medication without being tested first? Would you do it again? 
 
What do you think about getting tested for malaria before you take medication? Is it important? Why or why 
not? Do you always get a malaria test when you have a fever? Why or why not? What do you do when the test 
is negative?  
 
Would you encourage others in your area to accept treatment before the start of the malaria season as 
prevention for malaria? 
 
 

 
 
 
132
III. 
Impact of the intervention on daily life 
 
 
Have you ever taken malaria medication before?  
 
If yes, how did malaria medication make you feel after taking it? Were there any uncomfortable side effects? If 
yes, what were they?  
 
How about any other medications for malaria? If yes, how was it the same or different from this one?  
 
Would you take this medication again? Why or why not?  
 
Did you finish your medication? Why or why not?  
 
If medication was not finished, please explain why you didn’t finish your medication.  
 
Do you think you can have malaria but not have symptoms?  
 
Do you think people should be tested before they take malaria medication? Why or why not?  
 
Do you believe giving malaria medication to everyone living near someone who has tested positive for malaria 
is a good way to get rid of malaria in Swaziland? Why or why not? 
 
 
FOR ALL PARTICIPANTS IN THE QUAL STUDY: 
 
Do you have any other suggestions on how the NMCP can keep you informed and protected from malaria?  
 
What do you think is the best way to completely eliminate malaria in Swaziland? 
 
 
 

 
 
 
133
Appendix X. Qualitative questionnaires for the Acceptability Assessment 
– Focus Groups with Malaria Surveillance Team (RACD & TPE Arms) 
 
Semi-structured interview guide 
 
Study participant ID #____________________ 
 
 
 
Participant age: ___________ 
 
Participant sex: _____________ 
 
 
Date of interview ________________________ 
 
Start time ________End time_________ 
 
Initials of interviewer ______________________ 
 
Signed informed consent:  
 
 
 
What is your overall opinion of this study?  
 
Do you feel that one of these interventions may be better than the other? If yes, how? If not, why not? 
 
How does offering TPE affect your job? Is it more or less difficult to implement than RACD? Describe how one 
intervention differs from the other in terms of implementation 
 
What do you think is working well? Please elaborate. 
 
What should be changed in terms of offering the interventions? Please elaborate. 
 
What do you think should be scaled up? Why? 
 
What do you think should be scaled back? Why?  
 
What sort of barriers did you encounter during your involvement with the study? Please describe them, particularly 
with whom you encountered barriers. (after 1st FGD, ask if this has changed over time and if so, how) 
 
Were there any particular groups who did not want to participate? Who and why? 
 
Why do you think those barriers were present?  
 
How do you think those barriers could be addressed? 
 
Did you do anything to overcome those barriers? If yes, what did you do? 
 
Were there any particular groups that were receptive to the interventions? Who and why? (after 1st FGD, ask if this has 
changed over time and if so, how) 
 
What effect do you think this study is having the community? Please elaborate. Do you notice a change in the effect 
over time?  
 
Do you think the community members you encounter understand this study and why it is being done?  
 
What do you think will define success in this trial?  
 
Is there anything else you would like to add? 
 
 

 
 
 
134
Appendix Y.   Swaziland Malaria Elimination Advisory Group 
(SMEAG) 
 
Swaziland Malaria Elimination Advisory Group (SMEAG) 
Terms of Reference 
 
Swaziland Ministry of Health 
National Malaria Control Program 
June 2010 
 
Background 
In 2007, the Swaziland government established the goal of malaria elimination by 2015 in alignment with the Southern 
African Development Community (SADC) vision of a malaria-free southern Africa. Since then, the National Malaria 
Control Program (NMCP), along with its key technical and implementation partners, has mobilized resources to fund an 
elimination campaign, strategically planned the implementation of key elimination interventions, and begun to 
implement critical components of the elimination program. Major areas of focus include strengthening malaria 
diagnosis, establishing an active surveillance program, scaling up vector control coverage, expanding a health promotion 
campaign, and increasing monitoring and evaluation (M&E) activities. 
 
Purpose 
As Swaziland continues to target its goal of malaria elimination, the NMCP and its implementing partners require 
additional technical support and guidance to assure steady progress toward elimination. The Swaziland Malaria 
Elimination Advisory Group (SMEAG) is established to serve this purpose – to establish policy, to provide technical 
guidance on implementation of policies, and to monitor policy implementation and progress toward elimination. 
 
Responsibilities 
The Swaziland Malaria Elimination Advisory Group (SMEAG) has three major responsibilities. 
 
1. POLICY ESTABLISHMENT – The SMEAG meets regularly to review malaria elimination policies in surveillance, case 
management, and vector control and prevention. Where applicable, the group provides recommendations to the 
Ministry of Health on new policies and revision of existing policies. As the members of SMEAG are experts in their 
respective fields, they base policy recommendations on current research and regional and global best practices. 
 
2. TECHNICAL SUPPORT AND GUIDANCE FOR IMPLEMENTATION – In addition to recommending malaria policy changes, SMEAG is 
responsible for providing regular support and guidance to the NMCP and its partners on technical issues related to 
implementation of policies or interventions. The SMEAG works with the NMCP and its partners to identify key 
challenges and bottlenecks, discuss solutions, and offer recommendations on overcoming impediments to elimination. 
Identified challenges are reviewed on a regular basis to ensure effective resolution of all issues. 
 
3. MONITORING AND EVALUATION OF PROGRESS TOWARD ELIMINATION  –The SMEAG regularly reviews M&E indicators on the 
implementation of malaria policies and Swaziland’s progress toward elimination. When necessary, the SMEAG 
recommends reorientation in policies, practices, and interventions to the NMCP and partners to ensure achievement of 
Swaziland’s elimination goal. 
 
Organization 
SMEAG is composed of a general committee as well as four sub-committees in surveillance, case management, vector 
control and prevention. A global technical advisory committee, composed on regional and global experts on malaria 
elimination, provides additional remote technical assistance. 
SMEAG General Committee 

 
 
 
135
Chairperson: Rejoice Nkambule, Deputy Director of Health Services – Public Health 
NMCP Secretariat: Simon Kunene, NMCP, Program Manager 
 
The Swaziland Ministry of Health, including the Directorate of Health Services and the National Malaria Control 
Program (NMCP) 
 
The World Health Organization (WHO) 
 
United Nations Children’s Fund (UNICEF) 
 
The Southern Africa Malaria Elimination Support Team (SAMEST) – a collaboration between the Clinton Health 
Access Initiative (CHAI) and the Global Health Group (GHG) of the University of California – San Francisco (UCSF) 
 
The Swaziland National Association 
 
The Swaziland Medical and Dental Association 
 
Swaziland Nurses Association 
 
Red Cross 
 
Traditional Healers Organization 
 
University of Swaziland (UNISWA) 
 
Chairpersons from each subcommittees 
 
Sub-Committees 
 
1. SURVEILLANCE SUBCOMMITTEE – 
Chairperson: Nhlanhla Nhlabatsi, Epidemiology Unit, Ministry of Health 
NMCP Secretariat: Zulisile Zulu, Nyasatu, Sabelo Dlamini, Bongani Dlamini 
 
Meteorological Services, Ministry of Works 
 
Department of Immigration, Ministry of Home Affairs 
 
Health Management Information Systems (HMIS), Ministry of Health 
 
Epidemic Preparedness and Response (EPR), Ministry of Health 
 
Epidemiology Unit, Ministry of Health 
 
2. CASE MANAGEMENT SUBCOMMITTEE – 
Chairperson: Doctor from Good Shepherd Hospital 
NMCP Secretariat: Nolwazi Sibusani, Sarah Adra-Dartey, Steven Mthethwa 
 
Nurse matrons from major hospitals and health centers 
 
Doctor representatives from major hospitals and health centers 
 
Pharmacy Department, Ministry of Health 
 
National Laboratory Services, Ministry of Health 
 
Swaziland Medical and Dental Association 
 
3. VECTOR CONTROL AND PREVENTION SUBCOMMITTEE – 
Chairperson: Edmund Dlamini, Principal Health Inspector, Ministry of Health 
NMCP Secretariat: Quinton Dlamini, Zandie Dlamini 
 
Environmental Science Department, UNISWA 
 
Entomology Department, UNISWA 
 
Ministry of Agriculture 
 
Environmental Health, Ministry of Health 
 
Environmental Authority, Ministry of Health 
 
4. HEALTH PROMOTION SUBCOMMITTEE – 
Chairperson: Nokuthula Mahlalela, Senior Health Educator, Ministry of Health 
NMCP Secretariat: Teclar Maphosa, Mancoba Mabuza 
 
Health Promotion Unit, Ministry of Health 
 
Media Institutes of South Africa 
 
Department of Health Promotion, UNISWA 
 
Rural Health Motivator Program, Ministry of Health 
 
School Health Teams 
 
Global Technical Advisory Committee 

 
 
 
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The Global Technical Advisory Committee is composed of global and regional experts in malaria elimination, 
epidemiology, case management, vector control, surveillance, health promotion, and M&E. These experts are drawn 
from regional and global academic and research institutions, UN agencies, NGOs, and other organizations. 
 
Meetings and Deliverables 
 
The SMEAG General Committee meets biannually in November and May (the beginning and end of the malaria season) 
to review policies, implementation of policies and interventions, and progress toward elimination. Meetings may include 
the following agenda topics. 
 
1. Introduction 
2. Review of minutes 
3. Review of policies 
a. Surveillance 
b. Case management 
c. 
Vector control and prevention 
4. Review of elimination policy and intervention implementation – review of key indicators, identification of key 
challenges, discussion of problems, and recommendations for implementation 
a. Surveillance 
b. Case management 
c. 
Vector control and prevention 
d. Health promotion 
e. Project management and M&E 
5. Evaluation of progress toward elimination 
6. Conclusion 
 
The SMEAG Subcommittees meet biannually prior to the meeting of the General Committee (and more frequently if 
needed) to identify issues and discuss preliminary solutions, which then are presented to the general committee. The 
Global Technical Advisory Committee provides ongoing support whenever requested by members of the General 
Committee or Sub-Committees. 
 
At the conclusion of each meeting, the secretary of the meeting produces a set of minutes that include detailed account 
of all discussions and recommendations. After the meetings, the NMCP and relevant partners will then incorporate 
recommendations into existing work plans. 
 
 
 

 
 
 
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Appendix Z.   TPE Safety Monitoring Committee 
 
 
Terms of Reference (TOR) 
Targeted Parasite Elimination (TPE) Pharmacovigilance and Adverse Drug Reactions Committee  
(Data and Safety Monitoring Committee) 
for approval at December 2014, Committee Meeting 
 
This TOR provides the framework for the responsibilities and activities of the Targeted Parasite Elimination 
Pharmacovigilance and Adverse Drug Reactions Committee (Data and Safety Monitoring Committee). The committee 
shall oversee the safety of the study drug – dihydroartemisinin-piperaquine (DP) or artemether-lumefantrine (AL) as an 
alternative to DP, and shall perform this function by receiving and reviewing all data on DP or AL administered to study 
participants and by providing appropriate advice to the Ministry of Health which includes the National Malaria Control 
Program (NMCP) and the Swaziland Ethics Committee (SEC). 
 
1. Background and scope of the Committee 
Swaziland is currently aiming for malaria elimination by 2015. A major part of the approach has been reactive case 
detection (RACD), or the testing of individuals around index cases as a way to identify and treat secondary infections.  
Although the approach is useful for finding infected individuals and hotspots, there are some technical and logistical 
challenges relating to the test and treat approach.  Presumptive treatment without testing, also known as targeted 
parasite elimination (TPE), has potential to be more effective and feasible. The goal of TPE is to critically evaluate this 
approach versus RACD as a surveillance and response strategy for malaria elimination in Swaziland.  The TPE 
Pharmacovigilance and Adverse Drug Reactions Committee Committee was established in December 2014 to monitor 
the safe use of DP or AL in the study.  Members of the committee are representatives of institutions overseeing 
pharmacovigilance and adverse drug reactions in Swaziland. The committee includes individuals from the Swaziland 
Malaria Elimination Advisory Group (General Committee), the Ministry of Health (pharmacovigilance), the World Health 
Organization (WHO) and non-governmental organizations such as Management Sciences for Health (MSH).  
 
2. Roles and Responsibilities 
The purpose of the committee is to provide drug safety surveillance for the use of DP or AL in TPE in Swaziland. The 
committee will 1) periodically review and evaluate the accumulated study data for participant safety, study conduct and 
progress, and, when appropriate, efficacy, and 2) make recommendations to the study investigators concerning the 
continuation, modification, or termination of the study. The committee will consider study-specific data as well as 
relevant background knowledge about the disease, test agent, or patient population under study.  
 
The Committee is responsible for defining its deliberative processes, including event triggers that would call for an 
unscheduled review, stopping guidelines, and voting procedures prior to initiating any data review. The Committee is 
also responsible for maintaining the confidentiality of its internal discussions and activities as well as the contents of 
reports provided to it. 
 
The Committee will review the protocol for any major concern prior to implementation. During the trial, the Committee 
should review cumulative study data to evaluate safety, study conduct, and scientific validity and integrity of the trial. As 
part of this responsibility, Committee members must be satisfied that the timeliness, completeness, and accuracy of the 
data submitted to them for review are sufficient for evaluation of the safety and welfare of study participants. The 
Committee should also assess the performance of overall study operations and any other relevant issues.  
 
3. Membership of the Monitoring Committee 
Members of the committee will be comprised of staff from the Ministry of Health and its partners conversant on drug 
safety and field drug studies and will be from the following institutions  
 
The Swaziland Ministry of Health – Central Medical Stores 
 
The Swaziland Ministry of Health – Scientific and Ethics Committee 
 
Measurement Sciences for Health (MSH) 
 
World Health Organization (WHO) 
Each institution will be represented by one member, and one or more observers invited should there be need. Members 
will include experts in statistics, epidemiology, clinical trial design, and include at least one local clinician. Core members 
should have decision-making power from their institution as well as good knowledge of drug safety and random control 
trial research studies. In case of decisions to be made by the committee, which are not agreed by unanimity, core 

 
 
 
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members will vote for the majority.  Other institutions and members to the committee may be added as seen fit by the 
committee.  
 
Minutes from the committee meetings will be made available for review to the group.  The committee will be led by a 
Chairperson and Secretary whose functions are briefly outlined below: 
 
Chairperson: 
The chair position will be assigned by vote among committee members at the inaugural meeting and 
revisited each year. 
 
Secretary: 
The secretary position will be assigned by vote among committee members at the inaugural meeting 
and revisited each year.  The secretary will be responsible for arranging the committee meetings, 
including agenda and recording and sharing minutes.  
 
4. Meetings 
An initial meeting will be held in December 2014 to introduce the project to committee members. Following this 
introductory meeting, the committee will meet every quarter or more frequently if required. These meetings will be 
planned around observed and regular reports of suspected adverse drug reactions. Committee members are expected 
to attend meetings and should not rely upon substitute representatives. Members will participate in email discussions as 
necessary and will be updated regularly on TPE progress and activities. However, the busy schedules of members will be 
respected and meetings convened their availability. Depending on the agenda, independent advisors or experts can be 
invited to the meeting, upon approval by the chair and secretary.  
 
5. Terms of Service 
Committee members will be invited to commit to two years of service. If a member is unable to meet the terms of 
membership, another member of that institution may be nominated with the approval of committee members.