Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE)
Phase: PHASE4
Conditions: Malaria,Falciparum
Sponsor: Duke University

1 
 
Enhancing Preventive Therapy of Malaria In children 
with Sickle cell anemia in East Africa (EPiTOMISE) 
 
 
A randomized trial of daily Proguanil, monthly Sulfadoxine/Pyrimethamine-
Amodiaquine, or monthly Dihydroartemsinin-Piperaquine for the prevention 
of malaria in children with sickle cell anemia in Homa Bay, Kenya 
 
Protocol Identifying Number: 1R01HL134211 
 
 
Principal Investigators:  
Festus Njuguna MBChB MMed PhD 
(Pediatrics) 
 
 
 
 
 
Moi University School of Medicine 
 
Steve M Taylor MD MPH 
Duke Clinical Research Institute 
Duke University School of Medicine 
 
 
Co-Investigator: 
 
Wendy P O’Meara PhD 
 
 
 
 
 
Duke Global Health Institute 
 
 
 
Funded by: The U.S. National Institutes of Health/ National Heart, 
Lung and Blood Institute (NIH/NHLBI) 
 
 
Version Number:    
v10.0 
April 14, 2020 
 
 
 
 

2 
 
 
Table of Contents 
LIST OF ABBREVIATIONS .......................................................................................... 5 
STATEMENT OF COMPLIANCE ................................................................................. 7 
PROTOCOL SUMMARY .............................................................................................. 9 
SCHEMATIC OF STUDY DESIGN ............................................................................ 10 
AMENDMENT HISTORY ........................................................................................... 11 
1 
INTRODUCTION: BACKGROUND & SCIENTIFIC RATIONALE ................ 12 
1.1 
Background Information ................................................................ 12 
1.1.1 
Epidemiology of sickle cell anemia and malaria in Africa .............. 12 
1.1.2 
Chemoprevention of malaria in high-risk groups ........................... 13 
1.1.3 
Study site ...................................................................................... 14 
1.1.4 
Potential efficacy of chemoprevention agents ............................... 15 
1.2 
Rationale ....................................................................................... 16 
1.3 
Potential Risks and Benefits ......................................................... 17 
1.3.1 
Known potential risks .................................................................... 17 
1.3.2 
Known potential benefits ............................................................... 18 
2 
OBJECTIVES AND PURPOSE ................................................................... 19 
3 
STUDY DESIGN AND ENDPOINTS............................................................ 20 
3.1 
Description of the Study Design .................................................... 20 
3.2 
Primary Endpoint ........................................................................... 20 
3.3 
Secondary Endpoints .................................................................... 20 
4 
STUDY ENROLLMENT AND WITHDRAWAL ............................................. 23 
4.1 
Participant Inclusion Criteria ......................................................... 23 
4.2 
Participant Exclusion Criteria ........................................................ 23 
4.3 
Strategies for Recruitment and Retention ..................................... 23 
4.4 
Participant Withdrawal or Termination .......................................... 24 
4.4.1 
Reasons for withdrawal or termination .......................................... 24 
4.4.2 
Handling of participant withdrawals or termination ........................ 24 
4.5 
Premature Termination or Suspension of Study ........................... 24 
5 
STUDY AGENT ........................................................................................... 26 
5.1 
Study Agents and Control Description .......................................... 26 
5.1.1 
Acquisition ..................................................................................... 26 
5.1.2 
Formulation, appearance, packaging, and labeling ....................... 26 
5.1.3 
Product storage and stability ......................................................... 27 
5.1.4 
Dosing and administration ............................................................. 27 
5.1.5 
Route of administration ................................................................. 28 
5.1.6 
Duration of therapy ........................................................................ 28 
5.1.7 
Tracking of dose ............................................................................ 28 
5.2 
Study Agent Accountability Procedures ........................................ 28 
6 
STUDY PROCEDURES AND SCHEDULE ................................................. 29 
6.1 
Study Procedures/Evaluations ...................................................... 29 
6.1.1 
Study specific procedures ............................................................. 29 
6.1.2 
Standard of care study procedures ............................................... 29 
6.2 
Laboratory Procedures/Evaluations .............................................. 29 
6.2.1 
Clinical laboratory evaluations....................................................... 29 

3 
 
6.2.2 
Other assays or procedures .......................................................... 30 
6.2.3 
Specimen preparation, handling, and storage ............................... 30 
6.2.4 
Specimen shipment ....................................................................... 31 
6.3 
Study Schedule ............................................................................. 31 
6.3.1 
General screening procedures ...................................................... 31 
6.3.2 
Enrollment ..................................................................................... 32 
6.3.3 
Routine follow-up visits ................................................................. 33 
6.3.4 
Final study visit.............................................................................. 34 
6.3.5 
Early termination visit .................................................................... 34 
6.3.6  
Acute-care visits through month 12 ............................................... 34 
6.3.7 
Schedule of events table through month 12 .................................. 34 
6.4 
Concomitant Medications, Treatments, and Procedures ............... 35 
6.4.1 
Precautionary medications, treatments, and procedures .............. 35 
6.5 
Prohibited Medications, Treatments, and Procedures ................... 35 
6.6  
Rescue Medications, Treatments, and Procedures....................... 36 
6.7 
Participant Access to Study Agent at Study Closure ..................... 36 
7 
ASSESSMENT OF SAFETY ....................................................................... 37 
7.1 
Specification of Safety Parameters ............................................... 37 
7.1.1 
Definition of Suspected Unexpected Serious Adverse Reaction 
(SUSAR) 
37 
7.1.2 
 Ascertainment of SUSARs ........................................................... 37 
7.1.3 
Time Period and Frequency for Event Assessment and Follow-Up
 
37 
7.2 
Reporting Procedures ................................................................... 38 
7.2.1 
Reporting of SUSARs ................................................................... 38 
7.2.2  
Reporting of Participant Deaths .................................................... 38 
7.2.3 
Reporting of Unanticipated Problems ............................................ 38 
7.2.4 
Summary of Event Reporting ........................................................ 38 
7.3 
Study Halting Rules ....................................................................... 38 
7.4 
Safety Oversight ............................................................................ 39 
8 
CLINICAL MONITORING ............................................................................ 40 
9 
STATISTICAL CONSIDERATIONS ............................................................. 41 
9.1 
Statistical and Analytical Plans ..................................................... 41 
9.2 
Statistical Hypotheses ................................................................... 41 
9.3 
Analysis Datasets .......................................................................... 41 
9.4 
Description of Statistical Methods ................................................. 42 
9.4.1 
General approach ......................................................................... 42 
9.4.2 
Analysis of the primary efficacy endpoint ...................................... 42 
9.4.3 
Analysis of the secondary endpoints ............................................. 43 
9.4.4 
Data and safety analyses .............................................................. 43 
9.4.5 
Adherence and retention analyses ................................................ 44 
9.4.6  
Baseline descriptive statistics ....................................................... 44 
9.4.7 
Planned interim analyses .............................................................. 44 
9.4.8 
Additional sub-group analyses ...................................................... 44 
9.4.9 
Tabulation of individual response data .......................................... 45 
9.4.10 
Exploratory analyses ..................................................................... 45 

4 
 
9.5 
Sample Size .................................................................................. 45 
9.6 
Measures to Minimize Bias ........................................................... 47 
9.6.1 
Enrollment/Randomization ............................................................ 47 
10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS
 
48 
11 
QUALITY ASSURANCE AND QUALITY CONTROL ................................... 49 
12 
ETHICS/PROTECTION OF HUMAN SUBJECTS ....................................... 50 
12.1 
Ethical Standard ............................................................................ 50 
12.2 
Institutional Review Board ............................................................. 50 
12.3 
Informed Consent Process ............................................................ 50 
12.3.1 
Consent and other informational documents provided to 
participants 
50 
12.3.2 
Consent procedures and documentation ...................................... 51 
12.4 
Participant and Data Confidentiality .............................................. 51 
12.4.1 
Research use of stored human samples, specimens or data ........ 52 
12.5 
Potential Future Use of Stored Specimens ................................... 52 
13 
DATA HANDLING AND RECORD KEEPING .............................................. 54 
13.1 
Data Collection and Management Responsibilities ....................... 54 
13.2 
Study Records Retention .............................................................. 54 
13.3 
Protocol Deviations ....................................................................... 54 
13.4 
Publication and Data Sharing Policy ............................................. 54 
13.5 
Data and Safety Monitoring Plan................................................... 55 
14 
STUDY ADMINISTRATION ......................................................................... 56 
14.1 
Coordinating Center ...................................................................... 56 
15 
CONFLICT OF INTEREST POLICY ............................................................ 57 
16  
LITERATURE REFERENCES ..................................................................... 58 
APPENDIX A: STUDY INFORMATION SHEET (ENGLISH) ...................................... 63 
APPENDIX B: STUDY INFORMATION SHEET (KISWAHILI) ................................... 64 
APPENDIX C: STUDY INFORMATION SHEET (KISWAHILI TO ENGLISH) ............ 65 
APPENDIX D: STUDY INFORMATION SHEET (DHOLUO) ...................................... 66 
APPENDIX E: STUDY INFORMATION SHEET (DHOLUO TO ENGLISH) ............... 67 
APPENDIX F: INFORMED CONSENT (ENGLISH) ................................................... 68 
APPENDIX G: INFORMED CONSENT (KISWAHILI) ................................................ 79 
APPENDIX H: INFORMED CONSENT (KISWAHILI TO ENGLISH) .......................... 91 
APPENDIX J: INFORMED CONSENT (DHOLUO) .................................................. 102 
APPENDIX K: INFORMED CONSENT (DHOLUO TO ENGLISH) ........................... 112 
APPENDIX L: MEDICATIONS THAT PROLONG THE QT INTERVAL .................... 123 
 

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LIST OF ABBREVIATIONS 
 
ACT 
Artemisinin-combination therapy 
ACS 
Acute chest syndrome 
AE 
Adverse event 
AL 
Artemether-lumefantrine 
ALT 
Alanine aminotransferase 
AMPATH 
Academic Model Providing Access to Healthcare 
AP 
Atovaquone-proguanil 
AT 
As-treated 
ATP 
According-to-protocol 
BABY-HUG 
Pediatric hydroxyurea Phase 3 clinical trial (NCT00006400) 
BID 
Bis in die (twice a day) 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CC 
Coordinating center 
CFR 
Code of Federal Regulations (United States) 
CQ 
Chloroquine 
DBS 
Dried blood spot 
DCRI 
Duke Clinical Research Institute 
DP 
Dihydroartemisinin-piperaquine 
DSMB 
Data and Safety Monitoring Board 
DSMP 
Data and Safety Monitoring Plan 
DUMC 
Duke University Medical Center 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
EPiTOMISE 
Enhancing Preventive Therapy of Malaria In children with Sickle cell 
anemia in East Africa 
FDA 
Food and Drug Administration (United States) 
GCP 
Good clinical practice 
GLP 
Good laboratory practice 
GMP 
Good manufacturing practice 
HO 
Null hypothesis 
HA 
Alternative hypothesis 
HBCH 
Homa Bay County Hospital 
HbF 
Hemoglobin F 
HbSS 
Hemoglobin SS 
HIV 
Human Immunodeficiency Virus 
HPLC 
High Performance Liquid Chromatography 
IATA 
International Air Transportation Association 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 

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ICMJE 
International Council of Medical Journal Editors 
IPT 
Intermittent preventative therapy 
IR 
Incidence rate 
IRB 
Institutional Review Board 
IREC 
Institutional Research Ethics Committee (Moi University) 
ITN 
Insecticide-treated bednet 
ITT 
Intention-to-treat 
LAR 
Legally Authorized Representative 
LM 
Light microscopy 
MOP 
Manual of procedures 
MTRH 
Moi Teaching and Referral Hospital 
MQ 
Mefloquine 
MQAS 
Mefloquine-artesunate 
MSM 
Medical Safety Monitor 
NHIF 
National Hospital Insurance Fund (Kenya) 
NHLBI 
National Heart, Lung, and Blood Institute (United States) 
NIH 
National Institutes of Health (United States) 
PCR 
Polymerase chain reaction 
PfPR2-10 
Plasmodium falciparum prevalence rate in children 2-10 years old 
PI 
Principal investigator 
PO 
Per os 
PPB 
Pharmacy and Poisons Board (Kenya) 
PROMOTE 
Prevention of Malaria and HIV Disease in Tororo trial (NCT00948896) 
PYR 
Pyrimethamine 
QTcF 
Fridericia’s Corrected QT Interval 
RDT 
Rapid diagnostic test 
RTS,S/AS01 Recombinant protein-based P. falciparum vaccine (aka “Mosquirix”) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCA 
Sickle cell anemia 
SD 
Standard deviation 
SMC 
Seasonal malaria chemoprevention 
SNP 
Single nucleotide polymorphism 
SOC 
Standard of care 
SOP 
Standard operating procedure 
SP-AQ 
Sulfadoxine/pyrimethamine-amodiaquine 
SPC 
Summary of product characteristics 
SUSAR 
Suspected, Unexpected Serious Adverse Reaction 
UP 
Unanticipated Problem 
UPIRTSO 
Unanticipated Problem Involving Risk to Subjects or Others 
WHO 
World Health Organization 
 
 
 

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STATEMENT OF COMPLIANCE 
This trial will be carried out in accordance with Good Clinical Practice (GCP), as 
required by the International Conference on Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use (ICH) E6.  All personnel involved in 
the conduct of this trial will complete prior to their involvement Human Subjects 
Protection Training. 
 
I agree to ensure that all staff members involved in the conduct of this study are 
informed about their obligations in meeting the above commitments.  
 
 
 
________________________________  
Principal Investigator 
 
 
________________________________  
Signed 
 
 
______________ 
Date 
________________________________  
Principal Investigator 
 
 
________________________________  
Signed 
 
 
______________ 
Date 
 
 
 
 
 
 
 
 
 
 
                                                                                                                                           
 

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PROTOCOL SUMMARY 
Title: 
Enhancing Preventive Therapy of Malaria In children with 
Sickle cell anemia in East Africa (EPiTOMISE) 
Precis: 
This is a randomized, three-arm, open-label, clinical trial of 
malaria chemoprevention in children with sickle-cell anemia 
(SCA) at a single site in Homa Bay, Kenya. The study will 
enroll 246 children under 10 years of age, randomize 
participants 1:1:1 to one of three malaria chemoprevention 
regimens, and follow participants monthly for 12 months in 
order to record clinical episodes of malaria or SCA-related 
morbidity. Analyses will compare the efficacy of each regimen 
to prevent malaria and SCA morbidity. 
Objectives: 
 
Primary: To compare the efficacy of daily proguanil with 
monthly sulfadoxine/pyrimethanine-amodiaquine (SP-AQ) and 
with monthly dihydroartemisinin-piperaquine (DP) on the 
incidence of falciparum malaria in children with SCA.  
 
Secondary: To compare the efficacy of these malaria 
chemoprevention strategies on the incidence of major 
complications of SCA. 
Endpoints: 
Primary: incidence of malaria over 12 months. 
 
Secondary: incidence of SCA-related morbidity (pain crises, 
transfusions, acute chest syndrome), all-cause hospitalization 
or deaths, severe malaria, drug-resistant malaria parasites 
Population: 
Children of both genders between 1 and 10 years of age with 
laboratory-confirmed SCA living in malaria-endemic portions of 
Homa Bay or Migori Counties, Kenya 
Phase: 
4 
Number of Sites 
Enrolling 
Participants: 
1: Homa Bay County Hospital, Homa Bay, Kenya 
Description of Study 
Agents : 
Proguanil administered daily at a dosage determined by 
participant weight; or, sulfadoxine/pyrimethamine-amodiaquine 
administered orally over 3 days monthly at a dosage 
determined by participant age; or, dihydroartemisinin-
piperaquine administered orally over 3 days monthly at a 
dosage determined by participant weight. 
Study Duration: 
Approximately 48 months 
Participant Duration: 12 months  
 
 
 
 
 

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Enrollment/ 
Baseline Visit 
Prior to  
Enollment  
Routine  
Follow-up  
Visits  
(monthly) 
Acute-care 
Visits
Final Study 
Visit 
SCHEMATIC OF STUDY DESIGN 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* If temperature of > 37.5C or history of objective or subjective fever in the preceding 24 
hours. 
Screen potential participants by inclusion and exclusion 
criteria; obtain history, document. Obtain informed consent. 
Randomize 246 subjects 
Arm 1 
82 subjects 
Daily 
Structured medical history and physical exam 
Administer immunizations (if applicable); Enrollment in 
Kenyan NHIF 
Venous blood draw, ECG 
Dispense study medications 
Structured medical history and physical exam 
Outcome, AE, and adherence assessments 
Venous blood draw (every third visit) 
Test for malaria parasites with RDT* 
ECG (in subset of monthly DP participants) 
Dispense study medications 
Structured medical history and 
physical exam 
Outcome, AE, and adherence 
assessments 
Venous blood draw 
Test for malaria parasites with 
RDT* 
Arm 2 
82 subjects 
Monthly SP-
Arm 3 
82 subjects 
Monthly DP 
Structured medical history and physical exam 
Outcome assessment 
Test for malaria parasites with RDT* 

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AMENDMENT HISTORY 
Amendm
ent No. 
Protocol 
Version No. 
Date 
Issued 
Author(s) of 
Changes 
Details of Changes Made 
1 
V1.0 
 
Sheila Clapp 
Changing approved protocol from 
V0.4 to V1.0 
2 
V2.0 
 
Sheila Clapp 
Added in new exclusion criteria 
removed the assent for children  
>7, and other minor changes 
3 
V3.0 
 
Sheila Clapp 
Removed the provision of the 
Pneumococcal vaccine at 
enrollment 
4 
V4.0 
 
Sheila Clapp 
Removed sentence regarding 
distributing the study medications 
package inserts; added dose 
categories for dihydroartemisinin-
piperaquine for children > 25kg; 
clarified severe malaria 
language, and other minor 
corrections. 
5 
V5.0 
 
Steve Taylor 
Sheila Clapp 
Removed co-investigator; 
clarified safety event 
classification and reporting 
6 
V6.0 
 
Steve Taylor 
Further clarified safety event 
classification, reporting, and 
study halting procedures; 
clarified hemoglobin 
electrophoresis testing lab; 
added HPLC as an alternate to 
electrophoresis for HbSS 
confirmation and HbF 
quantification.Revised study 
eligibility criteria, moved 
enrollment blood tests to 
screening, and increased 
hemoglobin blood tests to 
monthly. 
7 
V7.0 
 
Steve Taylor 
Revised section 7.2 and added to 
Section 7.3 study halting 
guideline 
8 
V8.0 
 
Cindy Green 
Angie Wu 
Revised section 9.4.1, 9.4.2, 
9.4.3 and 9.4.4 regarding data 
analysis. 
9 
V9.0 
 
Ernest Ojwang Revised the Dholuo and Dholuo 
to English informed consent. 
10.0 
V10.0 
 
Sheila Clapp 
Minor language change to 
Dholuo ICF after v9.0 submitted 

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1 
INTRODUCTION: BACKGROUND & SCIENTIFIC RATIONALE  
1.1 
Background Information  
1.1.1 Epidemiology of sickle cell anemia and malaria in Africa 
Over 240,000 children with sickle cell anemia (SCA) are born in Africa annually.1 This 
number will increase to over 350,000 annual births of children with SCA by the year 
2050.2 Without sophisticated medical care, SCA patients in African settings die at young 
ages: in a Western Kenya cohort of newborns, 25% of SCA children died before their 
3rd birthday.3 Caring effectively for these children will be a major challenge for 
developing medical and public health systems in Africa including Kenya (Figure 1), and 
modeling studies suggest that the adequate provision of effective preventive care can 
substantially reduce the mortality of these children.2 Preventive care for SCA children 
must be evidence-based and tailored to the unique epidemiology of comorbidities in 
African settings.  
 
Children under 5 years of age in sub-Saharan Africa also suffer the majority of the 
annual 350 million infections and 500,000 deaths globally.4 Reducing this burden is a 
global public health priority, particularly in areas of high transmission like Western 
Kenya (Figure 1).  In the absence of an effective vaccine, global malaria control 
requires effective treatments and a suite of preventive measures that act upon the 
parasite, environment, and host. Among these preventive strategies is the 
administration of prophylactic antimalarials to high risk groups, including pregnant 
women, infants, and children 
exposed to seasonal malaria 
transmission. In these high-risk 
groups malaria morbidity is 
substantially reduced by routine 
periodic intake of effective 
antimalarials.  
 
Children with SCA are at high 
risk of life-threatening malaria. In 
East Africa,5,6 children with SCA 
admitted to the hospital with 
malaria parasites were more 
likely to die than those without 
parasites. Malaria is also a 
precipitant of sickle-cell pain 
crises, by unclear 
mechanisms.7,8 It remains 
unclear how SCA influences the 
overall risk of malaria, because 
most studies have been hospital based and therefore unsuited to capture mild 
episodes.5,6,9 The twin observations that malaria is more severe in SCA children and 
Figure 1. Allele prevalence of HbS (left; lighter is 
larger) and transmission intensity of P. falciparum 
(right; darker is greater) in Kenya. Study site is 
Homa Bay, and study administration is shared 
with team members in Eldoret. Images from the 
Malaria Atlas Project. 

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precipitates painful crises in these children indicate that the prevention of P. falciparum 
infections is critical to prolong the survival of SCA children in malaria-endemic areas.10 
 
1.1.2 Chemoprevention of malaria in high-risk groups 
Across Africa, children and pregnant women constitute high-risk groups for malaria and 
are specifically targeted by prevention programs. These programs include intermittent 
preventive therapy (IPT) with antimalarials. Among children, IPT for infants (IPTi) with 
sulfadoxine-pyrimethamine (SP) for and children (IPTc) with SP+amodiaquine (SP-AQ) 
have been studied widely. Both approaches are safe and reduce the risk of severe 
malaria by 38% (IPTi-SP)11 and 69-87% (IPTc-SP+AQ).12,13 Both strategies have been 
recommended by WHO for malaria control,14,15 though IPTc, implemented as seasonal 
malaria chemoprophylaxis (SMC) in West Africa, has been implemented more quickly. 
These approaches demonstrate that chemoprevention of high-risk groups to prevent 
malaria morbidity is feasible and effective. 
 
Children with SCA are higher-risk subsets of infants and children that are targeted by 
IPTi and ITPc programs, and it is unclear if these regimens that are effective in the 
general pediatric population are also suitable for children with SCA. Additionally, 
because the efficacy of chemoprevention programs is critically dependent on the 
epidemiology of drug resistance, both IPTi14 and IPTc15 are recommended by WHO 
only when resistance is below a threshold which is exceeded throughout East Africa. 
Therefore, current malaria chemoprevention regimens will not protect many children in 
Africa with SCA. 
 
Six published clinical trials have compared regimens to prevent malaria in people with 
SCA (Table 1). Two randomized studies from Nigeria in the early 2000s investigated 
the efficacy of daily Proguanil, compared with weekly mefloquine in older children16 or 
placebo and weekly pyrimethamine in younger children.17 In the former, the incidence of 
malaria was comparable between groups; in the latter, there were no differences 
between groups in the prevalence of parasites during active followup or in the incidence 
of painful crises, but children receiving proguanil had lower parasite densities. On the 
basis of this finding, daily Proguanil is recommended by the guidelines promulgated by 
Ministries of Health across Africa, including Kenya.18 Subsequent studies by Nakibuuka 
et al.19 and Diop et al.20 were suboptimal owing to short followup or older participants. 
Most recently, Olaosebikan et al.21 randomized 270 Nigerian children and young adults 
to daily Proguanil or every other month administration of SP-AQ or mefloquine-
artesunate (MQAS). In this study, SP-AQ and MQAS were well-tolerated, but the study 
was not powered to detect clinically-significant differences in malaria incidence. 
Therefore, there is a lack of adequately-powered studies of monthly treatment in SCA 
children with extended followup to prevent outcomes with clear clinical impact in East 
Africa. 
 
 
 
Study 
Site 
Follo
wup 
N 
Age 
Intervention 
Results 

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Table 1. Published studies of malaria chemoprevention in SCA patients. CQ: 
chloroquine; PCN: penicillin; PRO: proguanil; MQ: mefloquine; PYR: pyrimethamine; 
SP: sulfadoxine-pyrimethamine; AQ: amodiaquine; MQ: mefloquine; AS: artesunate; m: 
months. 
 
1.1.3 Study site 
Homa Bay, Kenya, is holoendemic for P. falciparum: in 2009, the entire population 
within the catchment area of Homa Bay County Hospital (HBCH) was at risk of P. 
falciparum, and over 20% lived in areas in which the P. falciparum parasite rate in 
children aged 2-10years (PfPR2-10, a standard index of malaria transmission intensity) is 
predicted to exceed 40%.23 From 2006-08, an estimated 9 children per 1000 under 14 
years were admitted to HBCH annually for malaria, twice the rate of non-malaria 
admissions and similar to other lakeside cities.24 In the outpatient setting, in a 2013 
study in the HBCH of 677 febrile children, 46% had falciparum malaria.25 Therefore, the 
transmission of falciparum malaria in and around Homa Bay is substantial. 
 
The SCA clinic in Homa Bay, Kenya, is operated by a collaboration between Academic 
Model Providing Access to Health Care (AMPATH) HematoOncology and Moi Teaching 
and Referral Hospital (MTRH). Established in 2013, the SCA clinic at Homa Bay County 
Hospital (HBCH) currently provides regular care to 1,400 SCA patients, of whom 67% 
are ≤ 10 years old. Despite comprehensive supportive care, the burden of disease in 
these SCA children is substantial. All 1,400 patients are enrolled in an electronic 
registry; clinical enrollment questionnaires indicated substantial morbidity in the 
preceding 12 months: 49% reported 3 or more hospitalizations, 45% reported at least 3 
painful episodes, and 25% reported at least 3 blood transfusions. No malaria-specific 
datapoints are currently routinely gathered, but 56% of enrollees also reported at least 3 
febrile episodes, which, in areas of intense malaria transmission like Homa Bay (see 
above), are likely to comprise many episodes of falciparum malaria. Because of this, on 
followup visits, 86% endorsed receipt of Proguanil or other antimalarial prophylaxis and 
Warley et al., 
196522 
Ugand
a 
6-12m 
126 
75% < 
6y 
weekly CQ + 
monthly PCN 
Decreased parasite prevalence 
with CQ+PCN 
Nwokolo et 
al.,16 2001 
Nigeri
a 
6m 
113 
>5y 
weekly MQ v. daily 
Pro 
No difference in malaria 
Eke et al., 
200317 
Nigeri
a 
9m 
101 
1-16y 
weekly PYR v. daily 
Pro v. placebo 
* No difference in P. falciparum 
or SCA events 
* Reduced parasite densities in 
Pro group 
* Reduced RBC transfusions in 
Pro & PYR groups 
Nakibuuka et 
al., 200919 
Ugand
a 
1m 
242 
6m-
12y 
monthly SP v. 
weekly CQ 
* 50% reduction in P. 
falciparum malaria in SP group 
* non-significant reduction in 
hospitalizations in SP group 
Diop et al., 
201120 
Mali 
5m 
60 
Mean 
23y 
monthly SP v. 
placebo 
* non-significant reductions in 
transfusions and parasite 
prevalence in SP group 
Olaosebikan et 
al., 201521 
Nigeri
a 
14m 
270 
63% 
<10y 
Daily Pro v. q2mo 
SP-AQ or MQAS 
* SP-AQ and MQAS well-
tolerated 
* reduced malaria in SP-AQ 
and MQAS 

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48% endorsed penicillin prophylaxis. This SCA clinic’s patient population, disease 
burden, and existing infrastructure allow immediate, direct testing of new strategies to 
prevent malaria in SCA children in Africa. 
1.1.4 Potential efficacy of chemoprevention agents 
Studies of the efficacy of Proguanil prophylaxis are detailed above (Table 1). Notably, 
molecular genetic studies indicate that parasite susceptibility to Proguanil is significantly 
reduced by mutations in the parasite’s dhfr gene.26,27 These mutations are very common 
in Western Kenya,28 and it is unclear if the clinical prophylactic effect of Proguanil is 
retained in areas of East Africa where these parasite mutations are prevalent. 
 
Is SP-AQ likely to be effective against P. falciparum in Western Kenya? The prevalence 
of parasite molecular markers of SP resistance is high in Western Kenya,28 but SP-AQ 
has retained appreciable activity against parasites in therapy studies. In a 2003 study in 
Mbita,29 adequate clinical response was achieved in 87% of children with uncomplicated 
falciparum malaria that were treated with SP-AQ. AQ, when coupled with artesunate as 
AS-AQ, is an effective partner drug for uncomplicated malaria therapy.30 For 
prophylaxis, few studies of SP-AQ have been conducted in areas with parasite 
resistance similar to contemporary Kenya. In a study of intermittent preventive therapy 
in schoolchildren aged 5-18 years in Western Kenya, thrice-yearly SP-AQ reduced 
anemia and improved school performance.31 This study was conducted in 2005-6 when 
the prevalence of markers of SP resistance had reached nearly 100%, indicating that, 
despite the high prevalence of molecular SP resistance in Kenyan parasites, SP-AQ 
was effective as chemoprevention. 
 
DP is an artemisinsin-combination therapy (ACT) that is highly effective as both therapy 
and chemoprevention. In over 1,000 children in West, Central, and Eastern Africa, the 
day 28 PCR-corrected efficacy of DP for uncomplicated malaria in a per-protocol 
population was 95%; this efficacy was non-inferior to the first-line therapy artemether-
lumefantrine (AL), and the reduced incidence of new infections in the DP group during 
the 42-day followup also indicated a substantial post-treatment prophylactic effect.32 
This latter effect was confirmed in a Cochrane review, in which DP reduces the number 
of new infections after treatment by 30%.33 In chemoprevention studies, monthly DP has 
reduced the incidence of malaria by 58% to 77%.34,35 DP’s high parasiticidal efficacy of 
DP and prolonged post-treatment prophylaxis make it an attractive candidate for 
intermittent preventive therapy. 
 
SP-AQ has a favorable safety profile. Agranulocytosis or hepatotoxicity were reported in 
travelers receiving weekly AQ,36 but recent use of SP-AQ in large trials of seasonal 
malaria chemoprevention (SMC) has enabled a comprehensive accounting of adverse 
effects in African children. In over 100,000 courses of SP-AQ administered as SMC to 
over 35,000 children,37 there were no cases of Stevens-Johnson Syndrome, serious 
blood dyscrasias, or hepatic damage; the most common AE was vomiting after SP-AQ 
(5.9%). In over 1,000 Gambian children allocated to receive SP-AQ, SP-Piperaquine, or 
DP for three monthly doses38 and who were actively queried for AEs after each dose, 
the most common symptoms after SP-AQ were cough (15%), diarrhea (13%), and 

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anorexia (8%), but these frequencies were similar to those receiving the other regimens 
and lower than controls who had received no drug regimen, suggesting that they were 
not attributable to SP-AQ itself.  
 
Proguanil safety has been investigated most closely when administered in combination 
with atovaquone (Malarone). In a meta-analysis of atovaquone-proguanil (AP) use for 
daily prophylaxis in travelers and residents of endemic areas, the rate of AEs was not 
higher than that for placebo,39 including data from a study of school-age children in 
Gabon in which rates were similar between AP (Proguanil dosing between 1.3 – 2.4 
mg/kg) and placebo groups.40 
 
DP is also well-tolerated. In two studies of DP administered monthly to children as 
prophylaxis in Burkina Faso,34 and in Gambia,38 the most common reported adverse 
events were cough, diarrhea, and vomiting, similar to those receiving SP-AQ. In a 
chemoprevention study in Ugandan children, there were fewer grade 3-4 adverse 
events in the monthly DP arm than in the placebo, monthly SP, or daily trimethoprim-
sulfadoxine arms.35 Piperaquine harbors the potential for QT prolongation,41 and a 
recent trial of DP as prophylaxis in healthy Thai adults was terminated early owing to 
QTc prolongation of 46ms.42 This phenomenon was not observed in a treatment study 
of over 1,500 African children under 5 years old.32 Few studies with repeated dosing 
have investigated this phenomenon: QTc intervals were reportedly normal in the 
PROMOTE study of SMC in Ugandan children,35 and trials of monthly DP prophylaxis in 
Thai adults43 and Ugandan,44 Gambian,38 and Senegalese children45 have indicated 
excellent tolerability of repeated DP, but not included formal QTc evaluations. Notably, 
however, sickle cell anemia itself may increase the risk of QTc prolongation:46 in one 
study of SCA patients between 10-24 years, the prevalence of a QTc interval > 
440msec was 38%,47 possibly owing to chronically-elevated pulmonary arterial 
pressures, recurrent acute chest syndrome, and hemolysis.48 
1.2 
Rationale  
The EPiTOMISE trial will evaluate the efficacy on malariologic and hematologic 
endpoints of two monthly malaria chemoprevention regimens compared with the 
standard of care. The rationale for this project is that intermittent therapy with highly-
active antimalarials is highly effective as malaria prevention in other high-risk groups. 
Therefore, intermittent therapy with more efficacious antimalarials may provide 
adequate protection from malaria and reduce the incidence of hematologic morbidity 
owing to SCA. Our hypotheses are that: 
1) both monthly SP-AQ and monthly DP will be superior to daily Proguanil at 
preventing falciparum malaria; 
2) both monthly SP-AQ and DP will be superior to daily Proguanil at preventing 
painful events; and  
3) receipt of chemoprevention will increase the prevalence of markers of resistance 
in breakthrough infections in recipients of SP-AQ or Proguanil but not DP. 

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1.3 
Potential Risks and Benefits  
1.3.1 Known potential risks  
Privacy. Care will be taken to protect the privacy of the participants and their guardians, 
but there is a risk that others may inadvertently see patient medical information and thus 
compromise privacy in the delivery of medical care. 
Blood drawing. Risks of venipuncture and heel- or fingerpricks include pain, self-limited 
bleeding, and infection of the soft tissues. 
 
Study medications. Proguanil is the current standard of care for chemoprevention of 
malaria in children with SCA in Kenya. Possible adverse reactions that are listed in the 
Summary of Product Characteristics (SPC) include allergic reactions, mild gastric 
intolerance including diarrhea or constipation, mouth ulceration, stomatitis, skin 
reactions, reversible hair loss, drug fever, cholestasis, or hematologic changes in 
recipients with renal insufficiency.49 In clinical studies using Proguanil alone or co-
formulated with Atovaquone, Proguanil has been well-tolerated. 
 
SP-AQ is a combination therapy comprised of sulfadoxine and pyrimethamine (two 
antifolate antimicrobials) co-administered with amodiaquine. Common adverse effects 
observed with amodiaquine include headache, vomiting, abdominal pain, diarrhea, 
pruritis, and fever, while rare but severe side effects include retinopathy and hepatitis. 
Common adverse effects observed with SP include abdominal pain, diarrhea, urticarial, 
pruritis, skin eruptions, headache, and fever.50 As noted above, large-scale deployment 
of SP-AQ as seasonal malaria chemoprevention in West Africa has suggested a 
favorable safety profile in children when used as preventive therapy. 
 
DP is an artemisinin-combination therapy consisting of the artemisinin derivative 
dihydroartemisinin and the bisquinoline piperaquine. DP is also well-tolerated. Common 
adverse effects in children after DP receipt include cough, anemia, thrombocytopenia, 
leukopenia, anorexia, QTc prolongation, vomiting, diarrhea, abdominal pain, dermatitis, 
rash, and asthenia.51 As noted above, in a chemoprevention study in Ugandan children, 
there were fewer grade 3-4 adverse events in the monthly DP arm than in the placebo, 
monthly SP, or daily trimethoprim-sulfadoxine arms.  
 
Alternative study medications. Other regimens have been studied as chemoprevention 
in various groups of children in Africa, including monthly dosing of mefloquine-
artesunate, mefloquine alone, SP-artesunate, or amodiaquine-artesunate, or daily 
trimethoprim-sulfamethoxazole. We selected DP as a treatment arm over these options 
owing to the protracted period of prophylaxis conferred by the prolonged half-life of 
piperaquine, the putative absence of resistance to either component, and emerging 
evidence that, in other high-risk groups, DP is very effective as prophylaxis. We 
selected SP-AQ as a treatment arm owing to abundant data indicating favorable safety 
and tolerability profiles, its low cost, and its effectiveness in prior studies of prevention 
despite prevalent parasite drug resistance.  

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1.3.2 Known potential benefits  
This study will potentially have immediate and long-range potential benefits to the 
human participants. Immediately, participants will receive free study medications to 
prevent malaria and treat malaria, free medications (for those under 5 years of age) to 
prevent bacterial infections, monthly comprehensive assessments and free testing for 
malaria parasites when they have subjective or objective fevers, a catch up routine 
immunization, and enrollment in the Kenya National Hospital Insurance Fund (NHIF). 
These services have the potential to reduce morbidity from both malaria and SCA. 
 
Long-range potential benefits include improved growth owing to reduced illness in the 
childhood period, improved school attendance and perhaps performance owing to 
reduced absenteeism, improved supportive care, and likely improved survival could 
result from the trial if the results of the trial enhance guidelines for care of children with 
SCA in Africa. 
 
 
 

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2 
OBJECTIVES AND PURPOSE 
The primary objective of the EPiTOMISE trial is to compare the efficacy of daily 
Proguanil with that of monthly SP-AQ or monthly DP to prevent P. falciparum malaria in 
children with SCA. 
 
The secondary objectives of this trial are to: 
1) compare the efficacy of daily Proguanil, monthly SP-AQ, and monthly DP to 
prevent painful events in children with sickle cell anemia, and 
2) compare the impact of malaria chemoprevention regimens on molecular markers 
of parasite drug resistance to Proguanil, SP-AQ, and DP. 
 
 
 
 

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3 
STUDY DESIGN AND ENDPOINTS 
3.1 
Description of the Study Design 
This study will be a three-arm, single-site, open-label randomized clinical trial in children 
with SCA of malaria chemoprevention comparing daily Proguanil (current standard of 
care), monthly SP-AQ, or monthly DP. The EPiTOMISE study is powered on the 
incidence of clinical malaria, and include as secondary outcomes other clinical and 
parasitologic endpoints as well as measures of SCA morbidity. 
3.2 
Primary Endpoint 
The primary endpoint is incidence of clinical malaria expressed as episodes per person-
year at risk.  Time at risk will begin when study participants are randomized and receive 
study drug (i.e. begin chemoprevention) and end when participants reach the end of the 
observation period. Clinical malaria will be detected by passive surveillance and will be 
defined as: 
• Uncomplicated malaria: 
o Presence of P. falciparum parasitemia of any density AND 
o Temperature of ≥ 37.5C or history of objective or subjective fever in the 
preceding 24 hours  
OR 
• Case meeting the definition of severe malaria according to WHO criteria (see 
Section 3.3 for definition)  
 
Those screening positive for fever or other signs or symptoms suggestive of severe 
malaria will be tested for malaria parasites by rapid immunochromatographic diagnostic 
test (RDT). The RDT will be used to guide clinical treatment. Only RDT-positive events 
will be recorded as primary endpoints; suspected malaria cases that are not confirmed 
by RDT will be recorded as secondary endpoints (see below).  
3.3 
Secondary Endpoints 
Multiple secondary endpoints of malaria- and sickle-cell-related morbidity will be 
captured. These secondary endpoints and their definitions and ascertainment are: 
1) Severe malaria, defined as a positive RDT AND one or more of the following:52 
● Impaired consciousness – Glasgow coma score <3 in children 
● Prostration – Generalized weakness so that the person is unable to sit, stand, 
or walk without assistance 
● Multiple convulsions – More than two episodes within 24 hours 
● Acidosis – A base deficit of >8 mEq/L, a plasma bicarbonate level of 
<15 mmol/L, or venous plasma lactate ≥5 mmol/L. Severe acidosis manifests 
clinically as respiratory distress (rapid, deep, labored breathing). 
● Hypoglycemia – Blood or plasma glucose <40 mg/dL (<2.2 mmol/L) 
● Severe malarial anemia – Hemoglobin concentration ≤5 g/dL or hematocrit ≤15 
percent in children with parasite count >10,000/mcL 
● Renal impairment – Plasma or serum creatinine >3 mg/dL (265 mcmol/L) or 
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● Jaundice – Plasma or serum bilirubin >50 mcmol/L (3 mg/dL) with a parasite 
count >100,000/mcL 
● Pulmonary edema – Radiographically confirmed or oxygen saturation <92 
percent on room air with respiratory rate >30/min, often with chest indrawing and 
crepitations on auscultation 
● Significant bleeding – Including recurrent or prolonged bleeding from the nose, 
gums, or venipuncture sites, hematemesis, or melena 
● Shock – Compensated shock is defined as capillary refill ≥3 seconds or 
temperature gradient on leg (mid to proximal limb) but no hypotension. 
Decompensated shock is defined as systolic blood pressure <70 mmHg in 
children, with evidence of impaired perfusion (cool peripheries or prolonged 
capillary refill). 
● P. falciparum parasitemia >10 percent (>500,000/mcL) 
Ascertainment: Signs of severe malaria will be captured during routine or acute 
care clinic visits. 
 
2) Hospitalization for malaria, defined as hospitalization at HBCH or other inpatient 
facility with admitting diagnosis of malaria and microbiologic confirmation of P. 
falciparum infection by RDT. 
Ascertainment: Review of HBCH pediatric ward admission logs and query of 
caregivers at followup visits. 
 
3) Light microscopy (LM)-positive malaria, defined as the reported presence of P. 
falciparum parasites detected by LM irrespective of RDT or other detection 
results. 
Ascertainment: Review of HBCH and other healthcare facility records. 
 
4) Unconfirmed malaria, defined as the receipt of antimalarials for suspected 
malaria episodes that were not confirmed by any objective diagnostic test. 
Ascertainment: Review of HBCH and other healthcare facility records. 
 
5) Fatal malaria, defined as death during hospitalization for malaria, as defined 
above. 
Ascertainment: Review of HBCH pediatric ward inpatient logs and query of 
caregivers at followup visits. 
 
6) Asymptomatic parasitization, defined as the presence of parasites during routine 
followup visits as detected by PCR in patients without fever or a history of recent 
fever. 
Ascertainment: Dried blood spots will be collected during routine visits from all 
participants and tested post-hoc for the presence of P. falciparum parasites using 
a real-time PCR assay. 
 
7) Painful events, defined as pain lasting 2 hours or more without obvious cause 
(either as inpatients or outpatients).53 
Ascertainment: Query using structured interview at each clinic visit. 

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8) Dactylitis, defined as pain or tenderness with or without swelling of the hands or 
feet.53 
Ascertainment: Query using structured interview at each clinic visit. 
 
9) Transfusions, defined as the receipt of red blood cells from any caregiver for any 
indication. 
Ascertainment: Query using structured interview at each clinic visit. 
 
10) Acute chest syndrome, defined as a new pulmonary infiltrate and at least 3 of 
the following findings: chest pain, temperature elevation > 38.5°C, tachypnea, 
wheezing, or cough. 
Ascertainment: Structured history and physical exam at each scheduled and 
acute care visit, or review of outside records. 
 
11) All-cause hospitalizations, defined as hospitalization at HBCH or other inpatient 
facility with any admitting diagnosis. 
Ascertainment: Query using structured interview at each clinic visit. 
 
12) All-cause deaths, defined as death by any cause. 
Ascertainment: Query using structured interview during followup. 
 
13) Molecular markers of parasite drug resistance, defined as the presence of single 
nucleotide polymorphisms (SNPs) in parasite genes that confer resistance to the 
study drugs. 
Ascertainment: Parasites detected in dried blood spots from asymptomatic or 
symptomatic individuals will be subjected to PCR amplification of the genes of 
interest followed by Sanger sequencing for gene mutations. 
 
 

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4 
STUDY ENROLLMENT AND WITHDRAWAL 
4.1 
Participant Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the 
following criteria: 
1) Age greater than 12 months and less than 10 years at enrollment; 
2) Current attendance at or willingness to attend the study SCA clinic at HBCH; 
3) Residence in either Homa Bay County or the Rongo or Awendo sub-counties of 
Migori County; 
4) Confirmed hemoglobin genotype of HbSS by electrophoresis or high-
performance liquid chromatography (HPLC); 
5) No immediate, apparent, or reported plans to relocate residence from Homa Bay 
County or the Rongo or Awendo sub-counties of Migori County in the next 2 
years; 
6) Ability to take oral medication and be willing to adhere to the medication regimen 
or caregiver willingness to give the medical regimen as prescribed; 
7) Ability and willingness of parent or legally authorized representative (LAR) to give 
informed consent;  
8) Hemoglobin concentration > 6.5 g/dL at screening; 
9) Alanine aminotransferase (ALT) <= 50 U/L at screening. 
4.2 
Participant Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation 
in this study: 
1) Taking routine antimalarial prophylaxis for another indication (including co-
trimoxazole for HIV infection); 
2) Known allergy or sensitivity to sulfadoxine, pyrimethamine, amodiaquine, 
proguanil, dihydroartemisinin, piperaquine, artemether, lumefantrine, penicillin (if 
under 5 years old), or derivatives of these compounds; 
3) Known chronic medical condition other than SCA (i.e. malignancy, HIV) requiring 
frequent medical attention; 
4) Currently participating in another clinical research study, or having participated in 
one in the prior 30 days; 
5) Living in the same household as a previously-enrolled study participant; 
6) Chronic use of medications known to prolong the QT interval in children (see 
Appendix L); 
7) Fridericia’s corrected QT interval (QTcF) interval > 450msec. 
8) Receipt of a transfusion of red blood cells in the 120 days prior to screening. 
4.3 
Strategies for Recruitment and Retention 
Potential participants will be screened for inclusion in the existing pediatric SCA clinic at 
HBCH. Currently, SCA patients are cared for in two parallel clinics: 1) the pediatric 
medical officer staffs a weekly SCA clinic, at which approximately 20 patients are 
evaluated once every 3 months, and 2) the AMPATH HematoOncology outreach team 
staffs a monthly 2-day SCA clinic at HBCH, during which they evaluate 120-140 
patients. 

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Potential participants will be screened for eligibility by study personnel when attending 
either clinic. If they meet all inclusion criteria and do not meet any exclusion criteria, 
they will be offered enrollment following informed consent. Children who do not meet 
inclusion criteria, or who meet exclusion criteria, or who do not want to participate in the 
trial, will receive subsequent care in the SCA clinic as determined by the standard of 
care at HBCH. For this study, only African children will be recruited. 
 
Retention will be enhanced by several methods. Participants will be compensated for 
each routine follow-up visits and the final study visit, including follow-up visits for repeat 
ECGs in the children that have been selected for ECG safety monitoring while allocated 
to DP; participants will not be compensated for acute-care visits. Compensation will be 
provided to participant’s guardian. In order to improve adherence to study visit 
schedule, study personnel will contact all study participants or their guardians in the 
week prior to their scheduled routine followup visit. 
4.4 
Participant Withdrawal or Termination 
4.4.1 Reasons for withdrawal or termination 
Participants are free to withdraw from participation in the study at any time upon 
request. In addition, an investigator may terminate participation in the study for any of 
the following reasons: 
1) Any clinical adverse event (AE), laboratory abnormality, or other medical 
condition or situation occurs such that continued participation in the study would 
be detrimental to the participant; 
2) The participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation; 
3) Movement out of the study area or inability to be located for > 60 consecutive 
days since the preceding clinic visit; 
4) Withdrawal of informed consent; 
5) Demonstrated or likely inability to comply with the study schedule or procedures; 
6) Participant or guardian requests to terminate participation in the study. 
4.4.2 Handling of participant withdrawals or termination 
Randomized subjects who withdraw from the study will not be replaced. If participants 
are withdrawn for reasons 3) or 4) above, no further study assessments will be 
performed. For withdrawals for other reasons above, follow-up testing will be at the 
discretion of the participant and their regular medical provider. All data collected prior to 
withdrawal will be retained and used in the study database. No further testing will be 
done if the participant withdraws informed consent or requests to terminate 
participation. 
4.5 
Premature Termination or Suspension of Study 
The study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. The decision to prematurely terminate the study will require the 
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suspension or termination, will be provided by the DCRI to the study investigators, 
partnering institutions, funding agency, and regulatory authorities, as applicable. If the 
study is prematurely terminated or suspended, the PI will promptly inform the Duke 
University IRB, the Kenya Pharmacy and Poisons Board (PPB), and the Moi University 
Institutional Research Ethics Committee (IREC), the DSMB (for suspensions) and the 
sponsor and will provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited 
to: 
1) Determination of unexpected, significant, or unacceptable risk to participants; 
2) Insufficient compliance to protocol requirements; 
3) Data that are not sufficiently complete and/or evaluable; 
4) Poor enrollment. 
 
The study may resume once concerns about safety, protocol compliance, data quality 
are addressed to the satisfaction of the DCRI and, as applicable, overseeing IRBs and 
regulatory agencies. 
 
 

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5 
STUDY AGENT 
5.1 
Study Agents and Control Description 
Participants will be randomized to one of 3 therapies: daily Proguanil, monthly SP-AQ, 
or monthly DP. The study agent is NOT to be used for any purpose other than that 
outlined in this protocol.  
 
1) Proguanil is the current standard of care for chemoprevention of malaria in 
children with SCA in Kenya. Proguanil is a dihydrofolate reductase inhibitor and 
therefore it interferes with the folic-folinic acid system of P. falciparum parasites. 
The active metabolite of Proguanil – cycloguanil -- binds to the enzyme 
dihydrofolate reductase in the malaria parasite and thereby prevents the 
completion of schizogony. 
 
2) SP-AQ consists of sulfadoxine, pyrimethamine, and amodiaquine. Amodiaquine 
is a synthetic 4-aminoquinoline antimalarial with schizonticidal action on P. 
falciparum by destroying intraerythrocytic forms. Its mechanism of action is 
incompletely understood. Pyrimethamine is a diaminopyrimidine with antimalarial 
activity that is mediated by the inhibition of plasmodial dihydrofolate reductase 
and thus the indirect blocking of the synthesis of nucleic acids in the malaria 
parasite. Sulfadoxine is a sulfonamide, and therefore a competitive antagonist of 
p-aminobenzoic acid, which results in competitive inhibition of dihydropteroate 
synthase, the enzyme in P. falciparum which is responsible for the incorporation 
of p-aminobenzoic acid in the synthesis of folic acid. 
 
3) DP consists of dihydroartemisinin and piperaquine. Dihydroartemisinin is a semi-
synthetic derivative of artemisinin and the active metabolite of all artemisinin 
compounds. The exact mechanism of action of dihydroartemisinin against P. 
falciparum parasites is incompletely understood, but appears to result in part 
from heme-mediated activation that causes pervasive free-radical damage to 
parasite membranes. Piperaquine is a bisquinoline antimalarial with an 
incompletely understood mechanism of action against malaria parasites. 
5.1.1 Acquisition 
Study medications are commercially available in Kenya and will be procured and 
packaged for use by the study participants. When possible, study medications will be 
acquired from manufacturers who have been prequalified by WHO to produce the 
antimalarial as a finished pharmaceutical product.  
 
Study medication will be provided to all consented and randomized participants free of 
charge.  
5.1.2 Formulation, appearance, packaging, and labeling 
All study agents are commercially-available oral medications and will not be modified in 
constitution from their manufactured state. Agents will be portioned to enable weight- or 
age-based dosing as described in Section 5.1.4. Agents will be packaged by study 

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pharmacists at the MTRH Investigational Pharmacy in monthly allotments. These 
allotments will be clearly coded to prevent potential mis-distribution to study 
participants. The package insert will be available for review at any time during the study. 
5.1.3 Product storage and stability 
 
Storage requirements will be per product label.  Each dose of study drug will be 
prepared according to the subject’s weight or age and treatment assignment by the 
pharmacist or other appropriately licensed and authorized personnel. Details on 
preparation and storage of study material will be provided in the Pharmacy Manual as a 
part of the study Manual of Procedures (MOP). 
5.1.4 Dosing and administration 
Administration of all study drugs will be open label. Study drugs will be administered at 
home by the study participant’s parents or guardians. Although this is an efficacy trial, it 
will not be practical to administer the study drugs utilizing a “directly observed therapy” 
approach, owing to the daily dosing of Proguanil and the multiple days of administration 
of both SP-AQ and DP; this asymmetry in dosing would result in potential bias if the 
initial doses were directly observed. Parents or guardians will be given pre-packaged 
study drugs along with dosing instructions. Study participants will be seen in the clinic for 
a final study visit at 12 months, at which time parents or guardians will be given clear 
instructions to return to their usual medical providers for ongoing care. Plans for the 
monitoring of safety of study drugs are detailed in Section 7. 
 
1) Dosing of daily proguanil will be approximately 3mg/kg/day, consistent with 
clinical practice and current recommendations in Kenya, rounded to the nearest 
25mg increment:18  
 
Weight (kg) 
No. of 100mg tabs 
Proguanil daily 
≤ 13 
¼ 
13-21 
½ 
21-29 
¾ 
> 29 
1 
 
 
2) Dosing of SP-AQ will be as follows: 
 
Age 
(y) 
Day 1 
Day 2 
Day 3 
1-5 
1 tablet 500/25mg SP 
1 tablet 150mg AQ 
 
1 tablet 150mg AQ 
 
1 tablet 150mg AQ 
6-10 
1.5 tablets 500/25mg 
SP 
1.5 tablets 150mg 
AQ 
 
1.5 tablets 150mg 
AQ 
 
1.5 tablets 150mg 
AQ 
 

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This is consistent with WHO recommendations for SMC with SP-AQ in West 
Africa.15 
  
3) The weight-based dosing of tablets of 40/320mg of DP is described below:  
 
Weight (kg) 
No. of 40/320mg 
tabs DP daily for 3 
days 
≤ 5 
¼ 
6-10 
½ 
11-14 
¾ 
15-19 
1 
20-23 
1 ¼ 
24-25 
1 ½ 
26-35 
2 
36-59 
3 
 
5.1.5 Route of administration 
All medications will be administered orally. 
5.1.6 Duration of therapy 
Participants will receive study drug for 12 consecutive months.  
5.1.7 Tracking of dose 
Proper dosing of Proguanil (based on weight), SP-AQ (based on age) and DP (based 
on weight) will be confirmed at each monthly study visit by measurement of weight and 
confirmation of age. Adherence to each of the study drugs will be assessed at each 
monthly evaluation by structured queries. Study drugs will be kept in a dedicated study 
pharmacy space maintained and accessed only by authorized study personnel. Study 
drugs will be dispensed by pharmacy staff to study nurses, and the study nurses will 
dispense the study medications to the subjects at the time they are seen for their routine 
monthly visits (scheduled approximately every 30 days). Detailed records will be kept on the 
amount of study drug distributed to each study participant. 
5.2 
Study Agent Accountability Procedures 
A registry of the study medication, current product labels, and Certificates of Analysis, 
provided by suppliers, will be maintained within the regulatory binder for the study. In 
addition, the study pharmacist will also maintain study drug accountability records in the 
pharmacy. The date received, lot number, expiration date, and date used will be 
recorded for each of the study medications, as well as the information pertaining to 
specific drug dispensed to each patient (e.g., lot number, amount dispensed). Monthly 
inventory of all study medications will be conducted and the information collected from 
those inventories will be documented in the pharmacy records.   
 
 

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6 
STUDY PROCEDURES AND SCHEDULE 
6.1 
Study Procedures/Evaluations 
6.1.1 Study specific procedures  
To ensure the proper timing of routine assessments, study participants will be 
scheduled to come to the study clinic 30 days (+/- 5 days) following the preceding 
routine followup visit. If a study participant is not seen in the study clinic within this time, 
study staff will contact by phone the participants parent/guardian and if necessary visit 
the home and ask the patient’s parent/guardian to come to the clinic.  
 
These routine assessments conducted during these monthly follow up visits will include: 
1) Queries regarding medical care obtained outside of the study site and 
medications taken outside study medications, including a request to review 
records and prescriptions; 
2) Assessment of adherence to study medications and to insecticide-treatment 
bednet (ITN) use; 
3) Routine interval medical history, review of systems, and physical examination 
(including vital signs and weight); 
4) Blood testing for routine laboratory tests:  
a. Venous blood will be collected for CBC, ALT, creatinine every 90 days and 
hemoglobin electrophoresis/HPLC for HbF quantitation every 180 days;  
b. Fingerprick blood will be collected at each visit for hemoglobin 
measurement and to be archived as a dried blood spot for post-hoc 
detection of malaria parasites and parasite genotyping by PCR. 
5) In the first 20 children allocated to the monthly DP regimen who live in Homa Bay 
town, ECG’s will be conducted 4-6 hours following the 3rd daily (and final) dose of 
monthly DP.  
 
In addition, all participants with a temperature > 37.5C or history of objective or 
subjective fever in the preceding 24 hours will be tested for malaria parasites using an 
RDT.   
6.1.2 Standard of care study procedures  
Clinical care for conditions other than SCA or possible malaria will be provided by non-
study clinicians. All efforts will be made to assist in prompt referral to additional care for 
participants as needed. In addition, diagnostic or therapeutic maneuvers during acute 
care or followup visits beyond those described below will be considered standard of 
care and not part of the clinical protocol. 
6.2 
Laboratory Procedures/Evaluations 
6.2.1 Clinical laboratory evaluations  
During screening, participants will have a blood sample taken for baseline 
measurements of CBC, ALT, and creatinine and confirmation and documentation of 

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their HbSS disease by electrophoresis or HPLC in order to determine eligibility for 
enrollment.  
 
At month 1, 2, 4, 5, 7, 8, 10, and 11, fingerprick blood will be tested for hemoglobin 
concentration.  
 
At month 3, 6, 9, and 12, we will collect venipuncture blood for the following clinical 
laboratory tests: 
1) Hematology: CBC; hemoglobin electrophoresis or HPLC for HbF quantification 
(only at month 6 and month 12 visits) 
2) Chemistry: creatinine, ALT. 
 
At baseline, followup, and acute-care visits through month 12 at which the participant 
has a temperature ≥37.5C or a history of subjective or objective fever in the preceding 
24 hours, blood will be collected by fingerprick for point-of-care testing for malaria 
parasites using an RDT. 
 
Hematology (exclusive of hemoglobin electrophoresis/HPLC) and chemistry tests will be 
performed by an accredited clinical laboratory in Western Kenya.  
 
Hemoglobin assessment by electrophoresis or HPLC will be performed by an 
established academic clinical or commercial laboratory. 
6.2.2 Other assays or procedures 
Venous blood will be collected and stored in a PAXgene tube in order to enable 
exploratory studies of biomarkers of severity of SCA, malaria, or other infections in 
children with SCA. This PAXgene tube sample will be collected only from participants 
who separately consent for this, and will be collected during a venous blood draw at a 
routine visit. 
 
At enrollment, monthly followup, and acute-care visits through month 12 (final visit), 
fingerprick blood will be stored as a dried blood spot (DBS) for post-hoc malaria parasite 
PCR detection and genotyping. This will be performed in Dr. Taylor’s research 
laboratory at Duke University in Durham, NC, USA. For detection, assays will be used 
that target P. falciparum gene targets.54 For genotyping, assays will be used to 
sequence parasite markers of drug resistance, vaccine-resistance, and other parasite 
gene markers for strain typing. 
6.2.3 Specimen preparation, handling, and storage 
For hemoglobin electrophoresis/HPLC (screening and 6-monthly routine visits), 1mL of 
blood will be collected by venipuncture into a vacutainer labeled with the participants 
screening or participant ID, transported to MTRH at room temperature in a cool box, 
and stored at room temperature for up to 1 week prior to testing. Procedures for 
hemoglobin electrophoresis or HPLC and HbF quantitation will be described in the study 
MOP. 
 

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PAXgene tubes will be labeled with participant ID, refrigerated for up to 5 days at 
HBCH, then transported and frozen at Moi University at -20C.  
 
DBS will be stored on standard chromatography filter paper as duplicate ~50 microliter 
blood spots. After drying at ambient temperature, these will be stored in sealed, 
individual plastic bags with desiccant on site. Each DBS will be labeled with a printed 
label with participant study ID and date of collection. The procedures will be detailed in 
the study MOP. 
6.2.4 Specimen shipment 
Whole blood specimens for hemoglobin electrophoresis/HPLC will be shipped on a 
regular basis for testing within 48 hours from the time of collection.  
 
DBS and PAXgene tubes will be shipped in IATA-approved containers without cooling 
using standard carriers (e.g. DHL) to Dr. Taylor’s lab at Duke University at the 
conclusion of the final followup visit for all patients. Included will be Dr. Taylor’s import 
permit from the US Centers for Disease Control and Prevention. The electronic 
inventory cataloging all shipped specimens will be transmitted electronically.  
 
Prior to shipping, export permission will be sought from the Kenyan Ministry of Health, 
and import permission sought from the US Centers for Disease Control and Prevention. 
6.3 
Study Schedule 
6.3.1 General screening procedures 
Potential study participants between 9 months and 10 years of age and their 
parents/guardians will be identified through the HBCH SCA clinic and, if necessary 
owing to poor enrollment, affiliated clinics in Homa Bay County. Parents/guardians will 
be approached about participating in the study and will be provided an information sheet 
about the requirements of the study (see Appendix A – English, Appendix B – Kiswahili, 
Appendix C – English back-translation from Kiswahili, Appendix D – Dholuo, Appendix 
E – English back translation from Dholuo). If the parents or guardians are agreeable to 
screening for participation in the study the child and parents will either be escorted to 
the study clinic or made an appointment to return at a later date. During the pre-
screening process, study physicians will assess for initial eligibility criteria through 
conversation with the parent/guardian (full Inclusion and Exclusion Criteria listed in 
Sections 4.2 and 4.3). All participants who pass pre-screening will be assigned a 
screening ID study number. 
 
Study personnel will conduct the informed consent discussion in the study clinic with the 
subjects’ parent(s) or guardian(s). Informed consent will be conducted in either English, 
Kiswahili, or Dholuo as appropriate, the consent forms will be translated into Kiswahili 
and Dholuo and back-translated into English to check for any loss or change of 
meaning. Following the informed consent discussion, parents or guardians will be asked 
by the study personnel to sign a written consent form approved by the Moi University 
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research study (Appendix F – English, Appendix G – Kiswahili, Appendix H – English 
back-translation from Kiswahili, Appendix J – Dholuo, Appendix K – English back-
translation from Dholuo). If the parent or guardian is unable to read or write, their 
fingerprint will substitute for a signature, and a signature from a witness to the informed 
consent discussion will be obtained. 
 
6.3.1.1 Screened children less than 12 months of age 
Potential study participants who pass pre-screening but are not yet 12 months of age 
will be given an appointment to the study clinic for a time after their first birthday for 
thorough assessment of study eligibility, informed consent, and potential enrollment.  
6.3.1.2 Screening procedures after informed consent 
Participants will first have eligibility assess by review of medical information and history. 
Those who meet criteria based on demographics and medical history will have an ECG 
performed to assess for baseline QTc interval length using Fridericia’s heart rate 
correction method (QTcF). Any QTcF interval > 450 msec will be confirmed by repeat 
ECG. Potential participants with QTcF intervals > 450 msec on this repeated ECG will 
be excluded from enrollment and therefore further screening procedures will be halted.  
 
Those with QTcF ≤ 450msec will have venipuncture blood drawn for CBC, ALT, 
creatinine, and hemoglobin electrophoresis or HPLC (see Section 6.2.1).  
6.3.1.3 Screened children with recent transfusion of red blood cells 
Potential study participants who are excluded from screening owing to the receipt of a 
transfusion of red blood cells in the 120 days prior to screening will be eligible to be re-
screened at a subsequent visit. 
6.3.2 Enrollment 
On the day of enrollment, all eligibility criteria will be confirmed.  
  
Participants will be randomized 1:1:1 by block allocation to either daily Proguanil, 
monthly SP-AQ, or monthly DP. Randomization will be achieved using permuted blocks 
of undisclosed size using a random number generator in SAS version 9.4 or higher 
(SAS Institute, Cary, NC). 
 
Treatment assignments will be generated by computer as each participant is enrolled. 
The trial is open-label. 
 
At the enrollment visit, all children will receive: 
1) Meningococcal immunization with quadrivalent vaccine (if > 2y and no prior 
receipt); 
2) Enrollment in the Kenyan NHIF; 
3) If < 5 years old, a 30-day supply of daily penicillin prophylaxis, dosed as follows: 
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b. >3y-5y: Penicillin V 250mg PO BID. 
4) Allocated study medications, at dosages as listed in Section 5.1.4 above.  
 
At enrollment, the following will be collected from all children: 
1) Structured demographic and clinical questionnaire; 
2) Structured physical examination including vital signs; 
3) Fingerprick blood stored as DBS. 
6.3.3 Routine follow-up visits 
Participants will be scheduled for routine followup assessments at HBCH through month 
12. During these routine visits, data will be collected, as below. 
 
Routine follow-up visit (every 30 days, +/- 5 days): 
1) Performance of structured medical history, including: 
a. Adverse events potentially related to study medications, principally 
Suspected Unexpected Serious Adverse Reactions (SUSARs; see 
Section 7.4.1). 
b. Adherence to study medications; 
c. Study outcomes, including those recorded at an outside medical facility: 
i. Microbiologically-confirmed malaria since last visit; 
ii. Acute malaria treatments since last visit; 
iii. Painful events, transfusions, dactylitis, acute chest syndrome; 
iv. Hospitalization; 
2) Performance of structured physical examination, including: 
a. Vital signs with weight; 
b. Anthropomorphic measurements; 
c. General physical survey. 
3) Collection of blood for: 
a. Dried blood spot for PCR parasite detection (by fingerprick); 
b. Hemoglobin testing in month 1, 2, 4, 5, 7, 8, 10, and 11 (by fingerprick); 
c. CBC, creatinine, ALT in month 3, 6, 9, and 12 (by venous collection,); 
d. HbF quantitation by hemoglobin electrophoresis or HPLC in month 6 and 
12 (by venous collection,); 
e. PAXgene tube storage (for those who have separately consented for 
future unspecified research) in month 3, 6, 9, or 12 (by venous collection); 
f. RDT (by fingerprick, only in those with temperature ≥37.5C or a history of 
subjective or objective fever in the preceding 24 hours). 
4) Dispensing of 30-day supplies of: 
a. Study antimalarial prophylactic medication; 
b. Daily penicillin prophylaxis (for those < 5 years old). 
5) ECG assessment (only in the first 20 residents of Homa Bay town allocated to 
monthly DP): 4-6 hours following the 3rd (and final) dose of monthly DP (upon 
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6.3.4 Final study visit 
The final study visit procedures will be identical to those for routine study visits, except 
that prophylactic study agents will not be dispensed. The final study visit will be done at 
the month 12 visit or earlier if the participant is withdrawn earlier. 
6.3.5 Early termination visit 
If early termination occurs and the participant is willing, procedures will be identical to 
those for the final study visit. Participants who terminate the protocol early will not be 
replaced. 
6.3.6  Acute-care visits through month 12 
Unscheduled or acute-care visits will be arranged to be seen in the study clinic at HBCH 
within 1 working day of contact by the participant. These will be documented as acute-
care visits in the study database. Study clinicians will evaluate participants and 
complete the following procedures: 
1) Performance of structured medical history, including: 
a. Elicitation of chief complaint; 
b. Review of systems; 
c. Intake of non-study medications; 
2) Performance of structured physical examination, including: 
a. Vital signs with weight; 
b. Anthropomorphic measurements; 
c. General physical survey. 
Participants with temperature ≥37.5C, a history of subjective or objective fever in the 
preceding 24 hours, or other signs or symptoms potentially consistent with malaria will 
be tested for malaria parasites with an RDT. Those who test positive will be treated with 
either AL for uncomplicated malaria or referred for urgent evaluation to HBCH or 
another appropriate health care facility for potential severe malaria if adjudged as a 
concern by the study clinician. 
6.3.7 Schedule of events table through month 12 
 
Procedures 
Screening 
Enrollment 
Routine follow-up 
visits 
Acute-care 
visits 
Final visit 
Hemoglobin 
electrophoresis/HPLC 
X 
 
X1 
 
X 
Parent or LAR Consent 
X 
 
 
 
 
Medical History/Review of 
Systems 
 
X 
X 
X 
X 
Physical Exam 
 
X 
X 
X 
X 
Meningococcal Immunization (if 
needed) 
 
X 
 
 
 
Enrollment/maintenance in 
Kenyan NHIF 
 
X 
X 
 
 
Dispense study medications 
 
X 
X 
 
 
Study medication adherence 
assessment 
 
 
X 
 
X 
AE/SUSAR Assessment 
 
 
X 
 
X 

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Procedures 
Screening 
Enrollment 
Routine follow-up 
visits 
Acute-care 
visits 
Final visit 
Study outcome assessment 
 
 
X 
X 
X 
Fingerprick hemoglobin 
concentration 
 
 
X5 
 
 
Dried blood spot 
 
X 
X 
X 
X 
CBC, creatinine, ALT 
X 
 
X2 
 
X 
PAXgene venous blood 
 
 
X6 
 
 
Malaria parasite RDT testing3 
 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
ECG post-DP4 
 
X 
X 
 
 
1 At the month-6 visit. 
2 At the month-3, month-6, and month-9 visits. 
3 If temperature ≥37.5C or a history of subjective or objective fever in the preceding 24 
hours. 
4 In the first 20 residents of Homa Bay town allocated to monthly DP only. 
5 At the month 1, 2, 4, 5, 7, 8, 10, 11 visits. 
6 Collected at only one routine follow up visit for participants who have consented 
separately for future unspecified research. 
6.4 
Concomitant Medications, Treatments, and Procedures  
All children aged between 1 and 5 years, irrespective of study agent allocation, will 
receive daily penicillin prophylaxis with oral Penicillin V. The dosing is as follows: 
 
Age (y) 
No. of 125mg 
tabs BID 
1-3 
1 
>3-5 
2 
Other concomitant medications taken during study participation will be recorded on the 
case report forms (CRFs). For this protocol, a medication is defined as a manufactured 
pharmaceutical product that is obtained from a dispensary/pharmacy with or without a 
prescription from a medical provider. Therefore, medications to be reported in the CRF 
are concomitant prescription medications, over-the-counter medications, and non-
prescription medications. 
6.4.1 Precautionary medications, treatments, and procedures 
Antifolate antibiotics that are routinely used to empirically treat suspected bacterial 
infections (such as co-trimoxazole) are similar to both Proguanil and to SP. Participants 
will be cautioned against the use of these medications during the study. 
6.5 
Prohibited Medications, Treatments, and Procedures  
Prohibited medications include: 
1) Antimalarial drugs not prescribed within the trial protocol; 
2) Other drugs with antimalarial properties including co-trimoxazole; and 
3) Medications known to prolong the QT interval (see Appendix L). 
 

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Participants who take prohibited medications will remain in the trial and will be included 
in the primary, intention-to-treat analysis, but excluded from the per-protocol analysis. 
6.6  Rescue Medications, Treatments, and Procedures 
Participants who are diagnosed with malaria by RDT will be treated with first-line 
treatment as recommended by the Kenya Ministry of Public Health and Sanitation 
National Guidelines for the Diagnosis, Treatment, and Prevention of Malaria.18 
Artemether-lumefantrine (AL) is first-line treatment in Kenya for all age groups for 
uncomplicated falciparum malaria, 18 and will be used as treatment for malaria owing to 
any species of Plasmodium common in Kenya. The dosing of AL will be as follows: 
 
Weight 
(kg) 
No. of 20/120mg 
tabs BID for 3 
days 
5-14 
1 
15-24 
2 
25-34 
3 
>34 
4 
 
Participants diagnosed with or suspected of severe malaria will be referred for 
admission to HBCH, and treated at the discretion of the treating provider. 
6.7 
Participant Access to Study Agent at Study Closure  
Access to these medications are widely available and can be obtained by prescription 
from physicians providing care after the conclusion of the study, but will no longer be 
provided directly through the study protocol or by the study investigators. 
 
 

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7 
ASSESSMENT OF SAFETY 
7.1 
Specification of Safety Parameters 
Participants will have hemoglobin concentration measurements performed at screening 
and all followup visits. At screening, and month 3, 6, 9, and 12 visits, venous blood will 
be collected for testing by CBC. At month 1, 2, 4, 5, 7, 8, 10, and 11, fingerprick blood 
will be collected for point-of-care hemoglobin concentration measurement.  
 
For all study participants, venous blood drawn at screening and month 3, 6, 9, and 12 
visits, will also be used for creatinine and ALT measurements. 
 
A subset of patients randomized to DP (20 children) will have serial electrocardiograms 
performed each month 4-6 hours following their 3rd dose of monthly DP. 
 
Owing to the wide use of these antimalarials and their wide availability in Kenya, safety 
monitoring will focus on collection and reporting of SUSARS. 
7.1.1 Definition of Suspected Unexpected Serious Adverse Reaction 
(SUSAR) 
The definition of a SUSAR, as defined in ICH GCP, is: An adverse reaction, the nature 
or severity of which is not consistent with the applicable product information (e.g., for 
applicable product information include Investigator's Brochure for an unapproved 
investigational product or package insert/summary of product characteristics for an 
approved product). 
 
7.1.2  Ascertainment of SUSARs 
All SUSARs obtained via direct subject reporting and/or clinical staff observation will be 
captured within the SAE CRF and will be followed until resolution. 
 
The study clinician will complete a SAE CRF. All SAEs will be reviewed by a Medical 
Safety Monitor (MSM) who is independent of the study team. The MSM will review the 
SAE CRF and gather any necessary further primary information from the study team 
during their review of the event. The MSM will classify the SAE as either a SUSAR or 
simply an SAE. The MSM will participate in an SAE adjudication committee with the PI 
and the Site Coordinator. This committee will convene on a recurring basis to review 
SAEs. 
7.1.3 Time Period and Frequency for Event Assessment and Follow-
Up 
The occurrence of a SUSAR may come to the attention of study personnel during study 
visits and interviews of a study participant presenting for medical care, or upon review 
by a study monitor. Information regarding the potential SUSAR that will be collected 
includes SUSAR description, time of onset, clinician’s assessment of severity, 
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make a diagnosis), and time of resolution/stabilization of the reaction. All SUSARs will 
be followed to adequate resolution.  
7.2 
Reporting Procedures 
7.2.1 Reporting of SUSARs  
Confirmed SUSARs (see Section 7.1.2) will be reported to DCRI, the DSMB, NHLBI, the 
Moi University IREC, the Duke University IRB, and the Kenya PPB as soon as possible 
and no later than 7 calendar days. This initial report will be updated with further 
information on final disposition of the SUSAR. 
7.2.2  Reporting of Participant Deaths 
All participant deaths will be reported to the DCRI, the DSMB, NHLBI, the Moi University 
IREC, the Duke University IRB, and the Kenya PPB irrespective of the SUSAR 
classification. Participant deaths will be reported to NHLBI within 7 calendar days. 
7.2.3 Reporting of Unanticipated Problems 
Unanticipated Problems (UPs), which are also known as Unanticipated Problems 
Involving Risks to Subjects or Others (UPIRTSO), may occur during the course of the 
study. When an event or condition has occurred that is considered a UP or UPIRTSO 
by the IRB or IREC, the event will be reported to NHLBI within 14 calendar days. 
7.2.4 Summary of Event Reporting 
Organization 
SUSARs 
Deaths  
(non-SUSAR) 
UP/UPIRTSO 
DCRI 
X (7d) 
X 
 
Moi IREC 
X (7d) 
X 
 
Duke IRB 
X (7d) 
X 
 
DSMB 
X (7d) 
X 
 
Kenya PPB 
X (7d) 
X 
 
NHLBI 
X (15d) 
X (7d) 
X (14d) 
7.3 
Study Halting Rules  
All SUSARs and non-SUSAR participant deaths will be reported promptly to the DSMB 
(see Section 7.2.4). Study stopping guidelines are are designed to detect an imbalance 
of participant deaths in either intervention arm (monthly SP-AQ or monthly DP) 
compared to the standard of care (SOC) arm (daily Proguanil). For this purpose, 
sequential boundaries will be used to continuously monitor the rate of participant deaths 
in each treatment arm (monthly SP-AQ or monthly DP) compared to the standard-of-
care SOC arm (daily Proguanil). Accrual into a treatment arm will be considered for 
stopping if an excessive number of deaths is seen in that treatment arm compared to 
the SOC arm, that is, if the difference in the number of deaths between that treatment 
arm and SOC arm is equal to or exceeds bn out of n enrolled participants in the 
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that yields the probability of crossing the boundary when the difference in the rate of 
death is equal to or exceeds 5%. 
 
 
Assuming a maximum planned sample size of 82 in each of the three study arms and a 
desired probability of stopping owing to chance of 0.10, a treatment arm (SP-AQ or DP) 
will be considered for stopping if the difference in the number of deaths between the 
treatment arm and the SOC arm is equal to or exceeds bn out of n enrolled participants 
in each of the two arms.55  
 
The stopping rules assume an equal number of participants in the treatment and SOC 
arms being compared when a death occurs. If the numbers within the arms are 
imbalanced, the confidence interval should be verified by the study statistician prior to 
the final decision to stop a treatment arm. We should further consider the timing of 
events through Kaplan-Meier plots before the final decision is made. 
 
In addition, the DSMB will review in its regular meetings these data and all SAEs. Using 
these collective data or other concerns, the DSMB has the authority to recommend 
halting the study. If such concerns arise, the DSMB will convene an ad hoc meeting by 
teleconference or in writing as soon as possible. As a result of this ad hoc meeting, the 
DSMB will provide recommendations for proceeding with the study or halting the study 
to the NHLBI, who can follow or not follow the recommendations.  
7.4 
Safety Oversight 
Safety oversight will be under the direction of a DSMB organized by NHLBI composed 
of individuals with the appropriate expertise, including a 1) pediatric hematologist, 2) 
statistician, 3) bioethicist, and at least 1 other. At least one member will have 
experience with clinical care or research in Kenya. The DSMB will meet at least 
semiannually to assess safety and efficacy data on each arm of the study. The DSMB 
will operate under the rules of an approved charter that will be written and reviewed at 
the organizational meeting of the DSMB. At that time, each data element that the DSMB 
needs to assess will be clearly defined. 
 
 
n 
2-5 
6-14 
15-24 
25-36 
37-48 
49-61 
62-74 
75-82 
bn 
2 
3 
4 
5 
6 
7 
8 
9 

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 8 
CLINICAL MONITORING 
GCP guidelines will be followed when conducting routine monitoring for this study, to 
ensure protocol compliance, patient safety, and data integrity.  Experienced clinical 
research associates will be assigned to conduct these visits. Specific details related to 
the monitoring can be found in the study’s monitoring plan described in the study MOP. 
Key areas that will be reviewed include informed consent, eligibility criteria, endpoint 
components, SUSARs, and drug accountability. 
 
 

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9 
STATISTICAL CONSIDERATIONS  
9.1 
Statistical and Analytical Plans 
This section provides a general description of the statistical methods to be used in 
analyzing both effectiveness and safety data. The key statistical issues or 
considerations will be addressed.  A more detailed statistical analysis plan (SAP) will be 
provided in a separate document to be included in the study MOP.   
 
Unless otherwise specified, all statistical tests will be two-sided with a significance level 
of 0.05.  Summary statistics will be provided for all study variables with descriptive 
statistics (number of observations, mean, standard deviation (SD), median, 25th 
percentile, 50th percentile, minimum, and maximum) for numerical (or continuous) 
variables and with frequency and percentage for non-missing categorical variables. 
 
All statistical analysis will be conducted using SAS version 9.4 or higher (SAS Institute 
Inc., Cary, NC, USA).  
 
9.2 
Statistical Hypotheses 
The primary outcome of the study is clinical malaria, which will be expressed as an 
incidence rate (IR; the number of episodes per patient-year at risk of malaria) and will 
be evaluated through the 12-month follow-up visit for effectiveness.  
 
The null hypothesis for the primary endpoint is that there is no treatment difference 
between each of the experimental arms (monthly SP-AQ and monthly DP) compared to 
the standard-of-care (SOC) arm (daily Proguanil) from randomization to 12 months.  
The alternative hypothesis is that each of the experimental arms has a better treatment 
response (i.e., lower IR of malaria) compared to the SOC arm through 12 months of 
treatment and follow-up. 
 
Let IRSP and IRDP be the expected number of episodes per patient-year at risk 
(incidence rate) through 12-months for SP-AQ and DP arms, respectively, and IRC the 
rate for the SOC arm.  The null and alternative hypotheses are as follows: 
 
HO: IRSP = IRC  Vs. HA: IRSP ≠ IRC, and 
 
HO: IRDP = IRC  Vs. HA: IRDP ≠ IRC. 
 
9.3 
Analysis Datasets 
We will define three populations, including an as-treated (AT) population of all treated 
participants according to the treatment administered, an intention-to-treat (ITT) 
population of all randomized patients irrespective of confirmed receipt or administration 
of study drugs, and an according-to-protocol (ATP) population, consisting of those who 
completed 12 months of follow-up and confirmed receipt of study drugs at routine 
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9.4 
Description of Statistical Methods 
9.4.1 General approach 
Incidence rates for each experimental arm in the AT population will be compared to the 
control group using a generalized regression model that allows for interdependence 
between multiple episodes within the same participant that is unadjusted for potential 
covariates. Models considered for the count data will include the Poisson, 
negative-binomial and zero-inflated models with the final model determined by 
the smaller residual deviance.  Similar analyses for the ITT and ATP population will 
also be computed, as well as adjusted models which incorporate potential covariates, 
including age, baseline risk and bednet use.  Each regression model will provide 
incidence rate ratios with 95% confidence intervals for each experimental treatment 
group compared to the control arm. A two-sided p-value < 0.05 will be considered 
statistically significant unless otherwise stated.    
9.4.2 Analysis of the primary efficacy endpoint 
The primary outcome of malaria will be expressed as an IR, or the number of episodes 
per patient-year at risk through 12-months. IRs will be computed after subtracting two 
weeks from the time at risk for each episode, in order to avoid counting an episode 
more than once.  
 
IRs of malaria will be primarily compared between each experimental treatment group 
and the control arm using a generalized regression model. The model will be 
unadjusted and will utilize the AT population. The regression model will allow 
interdependence between episodes within the same individual (i.e., clustering by 
subject).  This will create robust standard errors for the parameter estimates, and also 
allow the use of actual follow-up time as the offset variable  
 
The treatment difference for each hypothesis test will be tested using the contrast 
between treatment groups under the regression model.  These differences will be 
presented as incidence rate ratios per patient-year at risk with 95% confidence intervals 
for each experimental treatment group compared to the control arm.  In order to control 
the nominal type-I error rate (α=0.05), each test and corresponding confidence interval 
will use an α=0.0269 per Dunnett’s test for multiple comparisons to the same control 
arm.56 
9.4.2.1 Special data considerations 
Subjects will be followed for up to 12 months for both the primary and secondary 
endpoints.  The sample size allows up to 20% of the subjects to be lost to follow-up and 
still maintain adequate statistical power.  Methods to reduce loss to follow-up will be 
employed by the study team, including telephone calls and, if necessary, home visits; 
however, not all subjects will be followed for the entire study period.  Subjects may have 
missing data during some of the follow-up time points; however, the generalized linear 
models used for the longitudinal primary and secondary endpoints will allow for any data 
collected to be utilized for analysis.  Thus, no imputation of endpoint data will be done.    

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9.4.3 Analysis of the secondary endpoints 
Secondary endpoints (defined in Section 3.3) will also be compared between arms and 
are: 
1) Severe malaria; 
2) Hospitalization for malaria; 
3) LM-positive malaria (unconfirmed by RDT); 
4) Unconfirmed malaria (receipt of antimalarials unconfirmed by any diagnostic 
test); 
5) Fatal malaria; 
6) Asymptomatic parasitization; 
7) Painful events; 
8) Dactylitis; 
9) Transfusions; 
10) Acute chest syndrome; 
11) All-cause hospitalization; 
12) All-cause deaths; 
13) Molecular markers of malaria parasite drug resistance. 
 
The secondary outcomes will each be expressed as a dichotomous response 
(yes/no) during follow-up and compared between treatment arms using a logistic 
regression model to estimate the unadjusted relative risk. Additionally, for 
outcomes in which more than one event is possible, event rates may be 
compared using a generalized regression model similar to that used for the 
primary outcome.  Since the event rates are likely to be very small, the following 
composite outcomes will also be compared: (1) dactylitis or painful events; (2) 
receipt of blood products, ACS, hospitalization, or death; and (3) any secondary 
outcome. 
9.4.4 Data and safety analyses 
The DSMB is an independent committee that oversees the safety of research subjects. 
It is anticipated that the DSMB will meet every 6 months to review the accumulating 
data. Prior to each meeting, the DCRI will conduct any requested statistical analyses 
and prepare a summary report along with the following information: patient enrollment 
reports, study status, demographics, serious adverse events, laboratory results, 
and counts of primary and secondary outcomes. The extracted data files and 
analysis programs for each DSMB report will be archived and maintained at the DCRI 
for the life of the study.  
 
The DSMB will weigh any trade-offs between short-term versus long-term results. The 
DSMB will play a valuable role in advising the study leadership on the relevance of 
advances in the diagnosis and treatment of patients with SCA and malaria. The DSMB 
would be asked to offer proper perspective on any therapeutic or diagnostic testing 
advances that may occur during the course of the trial. If protocol modifications are 
warranted, close consultation among the DSMB, the NHLBI staff and the study 
leadership will be required. A separate DSMB charter will outline the operating 
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created prior to patient randomization and agreed upon during the initial meeting of the 
DSMB.  
 
Minutes of all DSMB meetings will be prepared and distributed to committee members. 
DSMB reports will be distributed by the study sponsor to study investigators, who will 
then report these to the overseeing ethical review committees, including Moi University 
IREC and the Duke University IRB. 
9.4.5 Adherence and retention analyses 
Adherence to study medications will be assessed at each routine follow-up visit using a 
structured query. Adherence assessments will collect participant/guardian-reported 
adherence as both continuous and binary estimates of adherence, and include 
qualitative queries to address underlying reasons for suboptimal adherence. 
9.4.6  Baseline descriptive statistics 
At the time of randomization, we will compare between allocation arms: 
• Age (years, continuous); 
• Hemoglobin (g/dL, continuous) and other CBC red cell indices; 
• Anthropomorphic measurements (continuous); 
• Current use of malaria prophylaxis (dichotomous); 
• Current use of penicillin prophylaxis (dichotomous); 
• Current use of hydroxyurea (dichotomous); 
• History of transfusions (dichotomous); 
• HbF quantitation (continuous); 
• All-cause hospitalizations in the prior 12 months 
9.4.7 Planned interim analyses  
For ethical reasons, an interim examination of key safety data will be performed when 
the study has accrued approximately ½ of the estimated total person-time. The primary 
objective of this analysis will be to evaluate the accumulated data for high frequency of 
negative clinical outcomes in either of the three randomized arms. In addition, the 
periodic monitoring will review the standard-of-care arm event rates, patient recruitment, 
compliance with the study protocol, status of data collection, and other factors that 
reflect the overall progress, data quality, and integrity of the study. The results of the 
interim analysis and monitoring reports will be carefully and confidentially reviewed by 
the DSMB. The DSMB will then give their recommendations for continuing or stopping 
the study to the PIs. 
 
We have no plans for a formal analysis for either efficacy or futility, owing to both the 
short 12 month duration of the study as well as the provision of malaria 
chemoprevention to all participants. 
9.4.8 Additional sub-group analyses 
Malaria incidence rates, painful crises and dactylitis will also be analyzed by including 
baseline covariates into the regression models including, age, bednet use and their 

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receipt of hydroxyurea at baseline.  Both unadjusted and adjusted comparisons 
between the two experimental arms will be done.     
 
9.4.9 Tabulation of individual response data 
Individual participant data will be listed by measure and time point. 
9.4.10 
Exploratory analyses 
We will explore the relationship between HbF quantitation and neutrophil counts and the 
incidence of parasitological and hematological outcomes. 
9.5 
Sample Size 
Expected reductions in malaria incidence are imprecise of intermittent chemoprevention 
with SP-AQ or DP. In three West African studies, monthly SP-AQ in children aged up to 
5 years reduced the incidence of malaria (compared to placebo) by 70-83%.12,13,34 
Therefore, we anticipate more modest reductions in malaria incidence with SP-AQ 
owing to resistance to SP AQ in East Africa, the use of daily Proguanil as the 
comparator, and the inclusion of children up to 10 years. For DP, reductions relative to 
placebo of 45% (relative to placebo) in Ugandan children35 and 77% in Burkinabé 
children have been reported.34 Given the use of an active comparator (daily Proguanil), 
the higher prevalence of SP resistance in Kenya (compared with Burkina), and the 
inclusion of children aged up to 10 years, we anticipate more modest reductions with 
either study treatment, and a protective efficacy of SP-AQ that is approximately half of 
that of DP. 
 
To estimate sample sizes, we used as baseline incidence data the number of episodes 
of malaria in calendar year of 2011 by children enrolled in the RTS,S/AS01 vaccine trial 
in Siaya, Kenya.57 Siaya is located on the opposite shore of Lake Victoria from Homa 
Bay, and they have similar degrees of malaria risk.24 The Siaya cohort comprised 1,276 
children aged up to 17m who received either three doses of RTS,S/AS01 or a 
comparator vaccine; follow-up was passive and clinical malaria was defined as an 
illness with temperature ≥37.5C and P. falciparum parasites at a density >5,000 
parasites/μL. In Siaya, the overall annual incidence was 3.7 episodes per child, and the 
overall vaccine efficacy in children was 43%. See Figure 2A for the distribution of the 
number of clinical malaria episodes for all Siaya children in the year 2011. 
 
 

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To compute sample sizes for the 
EPiTOMISE trial, we assumed a similar 
expected distribution of episodes for the 
standard-of-care arm (daily Proguanil); 
that the monthly SP-AQ and monthly 
DP arms would also have similar 
distributions of episodes, but shifted left 
by effect factors; and that one treatment 
arm (DP) would have an effect size of 
twice that of the other (SP-AQ). We 
assumed that the test for each 
experimental arm would be made at the 
0.0269 level in order to preserve a 
nominal alpha level of 0.05.56 Assuming 
65 patients enrolled in each of three 
arms and followed for 12 months, we 
computed the power of each arm as a 
function of the expected reductions in 
episodes (Figure 2B). Power 
calculations were made using Compaq 
Visual Fortran,58 and were based on 
100,000 simulations per point on the 
curve. By enrolling 65 patients in each 
arm, we expect to have: 
1) >90% power to detect a 
reduction of 40% in the DP arm; 
2) ~40% power to detect a 
reduction of 20% in the 
Proguanil arm; and 
3) >90% power to detect a 
reduction of 40% in either 
arm.  
Given the reported efficacies of DP 
and SP-AQ in non-SCA children 
cited above, these expected 
reductions are reasonable when 
compared with an active 
comparator (Proguanil). Allowing for 
a drop-out rate of 20%, we propose 
to enroll 246 children and randomize 
1:1:1 to the treatment arms. 
 
The main secondary outcome is the 
incidence of painful events. The 
sample size for this aim is fixed at 
246 overall, or 65 participants in each arm allowing for 20% participant loss. Therefore, 
Counts of 
Painful 
Events 
Observed 
Counts 
Observed 
Fraction 
Predicted 
Fraction 
0 
22 
0.227 
0.204 
1 
15 
0.155 
0.169 
2 or 3 
19 
0.196 
0.243 
4+ 
41 
0.423 
0.384 
N o . o f e v e n ts
N o . o f c h ild re n
0
1
2
3
4
5
6
7
8
9
1 0
1 1
1 2
1 3
1 4
1 5
1 6
0
5 0
1 0 0
1 5 0
2 0 0
2 5 0
P e rc e n t re d u c tio n  (fu ll)
P o w e r
0
4 .0
8 .0
1 2 .2
1 6 .5
2 1 .0
2 5 .5
3 0 .2
3 4 .9
3 9 .9
4 5 .2
5 0 .6
5 6 .1
6 1 .8
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
E ith e r
Full
re d u c tio n
H alf
re d u c tio n
A
B
Table 2. Number of observed and predicted painful 
events. Observed counts are from BABY-HUG study, 
and predicted counts computed as described in 
Section 9.5. The chi-square goodness of fit is 2.22 for 
2 degrees of freedom, p = 0.330. 
Figure 2. A) Distribution of clinical malaria events in 
1,276 children enrolled in the RTS,S/AS01 vaccine 
trial in Siaya, Kenya, during the 2011 calendar year. B) 
Estimated power (y-axis) to detect reductions in 
malaria incidence at either the full (dotted) or half 
(dashed) listed degrees on the x-axis, assuming 65 
patients enrolled in each of 3 arms.  

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using this pre-specified size, we estimated the power of the EPiTOMISE study to detect 
various percent reductions in painful events. To do so, we used as baseline data the 
distribution of painful events (by the same definition proposed here) in the BABY-HUG 
study, a phase 3 multicenter clinical trial of hydroxyurea in infants with SCA in the USA 
(Table 2).53,59 For this endpoint we did not have the complete distribution as we did for 
the primary endpoint (Figure 2A). However, 
we found that a negative binomial distribution 
as described by Bartko60 provided an 
adequate fit: 
 
j
N  +  j
N  +  j  -  1
P[x = j] = 
  
  (1  +  p
 
p
)
N  -  1






 
Table 3 shows the fit to the observed data. 
We then used the predicted distribution based 
on the negative binomial as the expected 
distribution for the placebo arm and computed 
power estimates as above in order to estimate 
study power as a function of possible percent 
reductions in painful events in either treatment 
arm (Figure 3). Using this approach, we will 
have 80% power to detect a reduction of 35% in 
either treatment arm relative to the Proguanil 
arm. 
 
9.6 
Measures to Minimize Bias 
9.6.1 Enrollment/Randomization 
At enrollment, participants will be randomized in a 1:1:1 ratio to one of the study arms: 
1) daily Proguanil (standard-of-care), 2) monthly SP-AQ, or 3) monthly DP. After 
screening and informed consent is obtained, the site-investigator or research assistant 
will electronically randomize a patient to a study group intervention using the REDCap 
database (web-based secure database application maintained by the Duke 
Investigators).  The Duke Statistical Investigator (Department of Biostatistics and 
Bioinformatics, DUMC, Durham, NC) will provide the randomization scheme that will be 
used within the REDCap database to randomly assign patients to one of the three 
treatment groups.  A block randomization scheme will be used in order to preserve 
treatment group balance within the site.  The block size will be undisclosed.  Each 
patient who qualifies for entry into the study will be assigned a unique study number in 
chronological order within the participating site (i.e., site ID + patient ID).  
This study will be open-label, and therefore there will be no masking of study personnel 
or participants to the treatment allocation. In order to reduce bias in the recording of the 
primary outcome, objective measurement of malaria parasitemia by commercial RDT 
will be required as an endpoint criterion. 
P e rc e n t re d u c tio n  in  p a in fu l e v e n ts
P o w e r
0
5
1 0
1 5
2 0
2 5
3 0
3 5
4 0
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
Figure 3. Estimated power as a function of 
possible percent reductions in painful events. 
Distribution of painful events extracted from 
participants receiving placebo in the BABY-
HUG study. Power estimates assume 65 
patients in each treatment arm (Section 9.5). 

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10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Source documents include all recordings of observations or notations of clinical 
activities and all reports and records necessary for the evaluation and reconstruction of 
the clinical study.  
 
Whenever possible, the original recording of an observation will be retained as the 
source document; however, a photocopy is acceptable provided that it is a clear, legible, 
and exact duplication of the original document. 
 
Investigators will maintain information that corroborate data collected on the electronic 
CRF (eCRF). The following information will be maintained and made available as 
required by study monitors and/or inspectors: 
1) Medical history/physical condition of the study subject before involvement in 
the study sufficient to verify protocol entry criteria. 
2) Documentation that consent was obtained for the subject’s participation in the 
study. 
3) Dated and signed notes for each subject visit, including results of 
examinations. 
4) Notations on abnormal laboratory results and their resolution. 
5) Dated printouts or reports of special assessments (e.g., ECG reports). 
6) Description of SUSARS and follow-up (minimally: event description, severity, 
onset date, duration, relation to study drug/device, outcome, and treatment for 
SUSAR). 
7) Notes regarding concomitant medications taken during the study (including 
start and stop dates). 
8) Subject’s condition upon completion of or withdrawal from the study. 
 
 
 

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11 
QUALITY ASSURANCE AND QUALITY CONTROL 
Quality assurance personnel may conduct audits at the study sites. Audits will include, 
but not be limited to, examination of the audit trail of data handling and processes, 
standard operating procedures, drug supply, presence of required documents, the 
informed consent process, and comparison of eCRFs with source documents. The 
investigators agree to accommodate and participate in audits conducted at a 
reasonable time and in a reasonable manner. 
 
Regulatory authorities from Kenya or elsewhere may also inspect the study site during 
or after the study. The study site should contact the study leadership immediately if this 
occurs and must fully cooperate with governmental audits conducted at a reasonable 
time and in a reasonable manner. 
 
The study leadership and study site will provide access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the sponsor, 
and inspection by local and regulatory authorities. 
 
 
 

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12 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
12.1 Ethical Standard  
By signing this protocol, the PIs agree to conduct the study in compliance with the 
protocol; instructions given by the DCRI; International Council on Harmonisation 
guidelines on Good Clinical Practice (ICH E6, the principles of which have their origin in 
the Declaration of Helsinki); the Guidelines for Conduct of Clinical Trials In Kenya, 
Pharmacy and Poisons Board, September 2016; and all other applicable laws, rules, 
and regulations relating to the conduct of the clinical study. 
12.2 Institutional Review Board  
Before implementing this study, the protocol, the proposed informed consent form and 
other information to subjects, must be reviewed by the Moi University IREC and the 
Duke University IRB. A signed and dated statement that the protocol and informed 
consent have been approved by these ethical review boards will be given to the study 
investigators before study initiation. Any amendments to the protocol, other than 
administrative ones, must be approved by the Moi IREC and Duke IRB according to 
their procedures. All changes to consent form will be IRB-approved; a determination will 
be made subsequent to this regarding whether previously consented participants need 
to be re-consented. 
12.3 Informed Consent Process  
12.3.1 
Consent and other informational documents provided to 
participants 
The PIs have both ethical and legal responsibility to ensure that each subject being 
considered for inclusion in this study is given a full explanation of the study. Written 
informed consent will be obtained from all subjects (or their guardian or legally 
authorized representative [LAR]) before any study-related procedures (including testing 
for the purposes of determining final study eligibility during screening) are performed or 
given.  
 
Written informed consent will be documented on an informed consent form (ICF) 
approved by the same IRBs responsible for approval of this protocol. The ICF will 
conform to FDA regulations in 21 CFR Part 50 and to the institutional requirements for 
informed consent and applicable regulations.  
 
The ICF will be reviewed with the prospective study subject and his or her LAR, and the 
investigator or qualified designee will be available to answer questions regarding 
procedures, risks, and alternatives. 
 
Specific consent is required for blood samples to be stored for future studies in SCA, 
malaria, and other infections in children with SCA. Subjects who do not consent to such 
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consent for future use of these samples for this purpose. Participation in the study is not 
contingent upon a subject’s agreement to provide these blood samples. 
 
Once the appropriate essential information has been provided to the subject and fully 
explained by the investigators or qualified designee, and it is felt that the subject 
understands the implications of participating, the subject and the investigator or 
designee will sign and date the IRB-approved written ICF. The subject will receive a 
copy of the signed ICF. The original signed and dated ICF will be kept in the site’s 
regulatory file. Documentation of the subject’s informed consent for and participation in 
this trial will be noted in the subject’s medical record. 
 
If the parent or guardian is unable to read or write, their fingerprint will substitute for a 
signature, and a signature from a witness to the informed consent discussion will be 
obtained. 
 
The subject or his or her LAR will be informed in a timely manner if new information 
becomes available that may be relevant to the subject’s willingness to continue 
participation in the trial. The communication of this information to the subject will be 
documented. 
12.3.2 
Consent procedures and documentation 
Informed consent will be conducted in either English or Kiswahili or Dholuo, as 
appropriate, and a translator will be used if necessary. The informed consent form will 
describe the purpose of the study, all the procedures involved, and the risks and 
benefits of participation. Study physicians will ask parents/guardians of study 
participants to summarize the study and explain the reasons why they want to 
participate. The consent forms will be translated into Kiswahili and Dholuo and back-
translated into English to check for any loss or change of meaning. Either a signature or 
a thumbprint (for parents/guardians who cannot read) will be acceptable to confirm 
informed consent for participation in the study. 
 
The participant will sign the informed consent document prior to any procedures being 
done specifically for the study. The participants may withdraw consent at any time 
throughout the course of the trial. A copy of the informed consent document will be 
given to the participants for their records. The rights and welfare of the participants will 
be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
12.4 Participant and Data Confidentiality  
Participant confidentiality is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their agents. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information 
relating to participants. Therefore, the study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the 
study or the data will be released to any unauthorized third party without prior written 
approval of the sponsor. 

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The study monitor, other authorized representatives of the sponsor, representatives of 
the IRB may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will permit 
access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept 
in a secure location for at least 10 years from the conclusion of the study, in accordance 
with guidelines from the Kenyan Pharmacy and Poisons Board. 
  
Study participant research data, which is for purposes of statistical analysis and 
scientific reporting, will be transmitted to and stored at the DCRI. This will not include 
the participant’s contact or other identifying information. Rather, individual participants 
and their research data will be identified by a unique study identification number. The 
study data entry and study management systems used by clinical sites and by DCRI 
research staff will be secured and password protected. At the end of the study, all study 
databases will be de-identified and archived at the DCRI.  
12.4.1 
Research use of stored human samples, specimens or data 
 
Intended use. Samples and data collected under this protocol may be used to study 
SCA, malaria, or co-existing infectious diseases in children. No human genetic testing 
will be performed except to test for mediators of SCA or malaria severity.  
 
Storage. Access to stored samples will be limited using a locked laboratory. Samples 
and data will be stored using codes assigned by the investigators. Data will be kept in 
password-protected computers. Only investigators will have access to the samples and 
data. 
 
Tracking. Data will be tracked using a clinical trial informatics system. 
 
Disposition at the completion of the study. The stored PAXgene tubes and DBS will be 
maintained in a locked laboratory at Duke University. Study participants who request 
destruction of samples will be notified of compliance with such request and all 
supporting details will be maintained for tracking. 
12.5 Potential Future Use of Stored Specimens  
Data collected for this study will be analyzed and stored at the DCRI, in collaboration 
with co-investigators from Moi University. After the study is completed, the de-identified, 
archived data will be transmitted to and stored at the DCRI, under the supervision of Dr. 
Taylor, for potential use by other researchers, including those outside of the study. 
Permission to transmit data to the DCRI and allow use for future research will be 
included in the informed consent.  
 

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With the participant’s approval and as approved by local IRBs, de-identified DBS and 
PAXgene tubes will be stored at the Dr. Taylor’s laboratory at Duke University with the 
same goal as the sharing of data with the DCRI. These samples could be used for 
research into the causes of SCA or malaria, its complications and other conditions for 
which individuals with SCA are at increased risk, and to improve treatment. These 
samples may be shared by request with investigators outside of Duke or Moi 
Universities, but only for the same purposes as those described above. The DCRI will 
also be provided with a code-link that will allow linking the biological specimens with the 
phenotypic data from each participant, maintaining the masking of the identity of the 
participant. 
 
During the conduct of the study, an individual participant can choose to withdraw 
consent to have biological specimens stored for future research. When the study is 
completed, access to study data and/or samples will be provided through the DCRI. 
 
 
 

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13 
DATA HANDLING AND RECORD KEEPING  
13.1 Data Collection and Management Responsibilities  
Study sites will transcribe subject source data into eCRFs using a computerized 
electronic data capture (EDC) system. The EDC system has controls that enable 
compliance with all relevant aspects of GCP. Edit checks, electronic queries, and audit 
trails are built into the system to ensure accurate and complete data collection. Data will 
be transmitted via the Internet from the study site to servers hosted by DCRI. The EDC 
employs sophisticated encryption mechanisms to ensure security and confidentiality, 
including password protection that will prevent unauthorized access during 
transmission. 
 
Subject data will be entered in the eCRF at the time of or as soon as possible after the 
subject’s visit or the availability of test results. All completed eCRFs will be transmitted 
in real-time as the study proceeds, or uploaded in batch fashion in the event of network 
interruptions. 
13.2 Study Records Retention  
The site investigator will maintain the records of drug disposition, copies of final eCRFs, 
worksheets, and all other study-specific documentation (e.g., study file notebooks or 
documentation worksheet) for at least 10 years from the end of the study, in accord with 
the Guidelines for Conduct of Clinical Trials In Kenya, PPB, September 2016. In accord 
with these guidelines, these records will be archived in Kenya. To avoid error, the 
investigator will contact the sponsor or a sponsor designee, as well as the Kenya 
Pharmacy and Poisons Board, before the destruction of any records pertaining to the 
study to ensure they no longer need to be retained. In addition, if the site investigator 
plans to leave the institution, the investigator agrees to contact the sponsor or a sponsor 
designee so that arrangements can be made for the transfer of records. 
13.3 Protocol Deviations  
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP 
requirements. The noncompliance may be either on the part of the participant, the 
investigator, or the study site staff. As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. 
 
It is the responsibility of the site to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation, or within 5 
working days of the scheduled protocol-required activity. All deviations must be 
addressed in study source documents and reported to DCRI. Protocol deviations must 
be sent to the Moi University IREC and the Duke University IRB per their guidelines. 
The site PI/study staff is responsible for knowing and adhering to their IRB requirements 
13.4 Publication and Data Sharing Policy 
This study will comply with the NIH Public Access Policy, which ensures that the public 
has access to the published results of NIH-funded research. It requires scientists to 

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submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital 
archive PubMed Central upon acceptance for publication.  
 
The International Committee of Medical Journal Editors (ICMJE) member journals have 
adopted a clinical trials registration policy as a condition for publication. Therefore this 
study will be registered at ClinicalTrials.gov, which is sponsored by the National Library 
of Medicine, and the Pan African Clinical Trial Registry (www.pactr.org). 
 
Parasite gene sequences generated for drug resistance genotyping using next-
generation sequencing platforms will be deposited in the National Library of Medicine’s 
Short Read Archive at the time of publication of genotyping results or within 6 months of 
preliminary analysis of these data, whichever occurs first. 
 
13.5 Data and Safety Monitoring Plan 
Individual elements within this protocol collectively constitute the Data and Safety 
Monitoring Plan (DSMP) for the EPiTOMISE study. This DSMP comprises: 
 
1) Description of study monitoring (Section 8); 
2) Collection, reporting, and management of safety events (Section 7); 
3) Risks and benefits to participants (Section 1.3); 
4) Conflicts of interest among study personnel (Section 15); 
5) Data collection and analysis (Sections 9 and 13); 
6) Interim analyses (Section 9.4.7);  
7) Study halting rules (Section 7.4); and 
8) DSMB plan (Section 9.4.4). 
 
 

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STUDY ADMINISTRATION 
14.1 Coordinating Center 
The Coordinating Center (CC) will be at the DCRI. The CC functions as a clinical trial 
center and is responsible for all aspects of conducting this trial, including: clinical 
operations; oversight of all committees and working groups; development of the protocol 
and all amendments; quality control; site reimbursement; monitoring of study progress; 
and leadership in data analysis, presentations, and publications. Clinical Operations is 
the critical functional component of the CC, and will provide project management; 
development and preparation of study materials; site management; education of all site-
based personnel on the rationale, design, and execution of EPiTOMISE, and assistance 
with preparation of manuscripts and publications. 
 
CC staff will develop and implement educational and training plans, communication 
initiatives including phone and email contact, and conference calls. The CC staff will 
collaborate with the study site personnel to ensure their understanding of the protocol, 
the operationalization of the protocol, and the successful identification of eligible 
patients for screening and enrollment.  
 
 
 

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CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore any actual conflict of interest of persons 
who have a role in the design, conduct, analysis, publication, or any aspect of this trial 
will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to 
their participation in the trial. The DCRI in conjunction with the NHLBI has established 
policies and procedures for all study group members to disclose all conflicts of interest 
and will establish a mechanism for the management of all reported dualities of interest. 
 
 

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16  
LITERATURE REFERENCES  
 
1 
Piel, F. B. et al. Global epidemiology of sickle haemoglobin in neonates: a 
contemporary geostatistical model-based map and population estimates. Lancet 
381, 142-151, doi:10.1016/S0140-6736(12)61229-X (2013). 
2 
Piel, F. B., Hay, S. I., Gupta, S., Weatherall, D. J. & Williams, T. N. Global burden 
of sickle cell anaemia in children under five, 2010-2050: modelling based on 
demographics, excess mortality, and interventions. PLoS medicine 10, 
e1001484, doi:10.1371/journal.pmed.1001484 (2013). 
3 
Aidoo, M. et al. Protective effects of the sickle cell gene against malaria morbidity 
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4 
WHO. World Malaria Report 2014, 
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5 
McAuley, C. F. et al. High mortality from Plasmodium falciparum malaria in 
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6 
Makani, J. et al. Malaria in patients with sickle cell anemia: burden, risk factors, 
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7 
Konotey-Ahulu, F. I. Malaria and sickle-cell disease. British medical journal 2, 
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Fleming, A. F. The presentation, management and prevention of crisis in sickle 
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Komba, A. N. et al. Malaria as a cause of morbidity and mortality in children with 
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10 
Aneni, E. C., Hamer, D. H. & Gill, C. J. Systematic review of current and 
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11 
Aponte, J. J. et al. Efficacy and safety of intermittent preventive treatment with 
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12 
Konate, A. T. et al. Intermittent preventive treatment of malaria provides 
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13 
Dicko, A. et al. Intermittent preventive treatment of malaria provides substantial 
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Organization, W. H.     (2010). 

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15 
Organization, W. H. WHO Policy Recommendation: Seasonal Malaria 
Chemoprevention (SMC) for Plasmodium falciparum malaria control in highly 
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Nwokolo, C. et al. Mefloquine versus proguanil in short-term malaria 
chemoprophylaxis in sickle cell anaemia. Clin Drug Invest 21, 537-544, doi:Doi 
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17 
Eke, F. U. & Anochie, I. Effects of pyrimethamine versus proguanil in malarial 
chemoprophylaxis in children with sickle cell disease: a randomized, placebo-
controlled, open-label study. Current Therapeutic Research 64, 616 (2003). 
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 Vol. 3  (ed Ministry of Public Health and Sanitation & Ministry of Medical 
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Nakibuuka, V., Ndeezi, G., Nakiboneka, D., Ndugwa, C. M. & Tumwine, J. K. 
Presumptive treatment with sulphadoxine-pyrimethamine versus weekly 
chloroquine for malaria prophylaxis in children with sickle cell anaemia in 
Uganda: a randomized controlled trial. Malaria journal 8, 237, doi:10.1186/1475-
2875-8-237 (2009). 
20 
Diop, S. et al. Sickle-cell disease and malaria: evaluation of seasonal intermittent 
preventive treatment with sulfadoxine-pyrimethamine in Senegalese patients-a 
randomized placebo-controlled trial. Annals of hematology 90, 23-27, 
doi:10.1007/s00277-010-1040-z (2011). 
21 
Olaosebikan, R. et al. A randomized trial to compare the safety, tolerability, and 
effectiveness of three antimalarial regimens for the prevention of malaria in 
Nigerian patients with sickle-cell disease. in preparation (2014). 
22 
Warley, M. A. et al. Chemoprophylaxis of Homozygous Sicklers with 
Antimalarials and Long-Acting Penicillin. British medical journal 2, 86-88 (1965). 
23 
Project, M. A. Malaria Atlas Project, <http://www.map.ox.ac.uk/browse-
resources/> (2014). 
24 
Okiro, E. A. et al. Malaria paediatric hospitalization between 1999 and 2008 
across Kenya. BMC medicine 7, 75, doi:10.1186/1741-7015-7-75 (2009). 
25 
Onchiri, F. M. et al. Frequency and correlates of malaria over-treatment in areas 
of differing malaria transmission: a cross-sectional study in rural Western Kenya. 
Malaria journal 14, 97, doi:10.1186/s12936-015-0613-7 (2015). 
26 
Peterson, D. S., Milhous, W. K. & Wellems, T. E. Molecular basis of differential 
resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. 
Proceedings of the National Academy of Sciences of the United States of 
America 87, 3018-3022 (1990). 
27 
Foote, S. J., Galatis, D. & Cowman, A. F. Amino acids in the dihydrofolate 
reductase-thymidylate synthase gene of Plasmodium falciparum involved in 
cycloguanil resistance differ from those involved in pyrimethamine resistance. 
Proceedings of the National Academy of Sciences of the United States of 
America 87, 3014-3017 (1990). 
28 
Sridaran, S. et al. Anti-folate drug resistance in Africa: meta-analysis of reported 
dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant 
genotype frequencies in African Plasmodium falciparum parasite populations. 
Malaria journal 9, 247, doi:10.1186/1475-2875-9-247 (2010). 

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29 
Bousema, J. T. et al. Moderate effect of artemisinin-based combination therapy 
on transmission of Plasmodium falciparum. The Journal of infectious diseases 
193, 1151-1159, doi:10.1086/503051 (2006). 
30 
Thwing, J. I. et al. In-vivo efficacy of amodiaquine-artesunate in children with 
uncomplicated Plasmodium falciparum malaria in western Kenya. Tropical 
medicine & international health : TM & IH 14, 294-300, doi:10.1111/j.1365-
3156.2009.02222.x (2009). 
31 
Clarke, S. E. et al. Effect of intermittent preventive treatment of malaria on health 
and education in schoolchildren: a cluster-randomised, double-blind, placebo-
controlled trial. Lancet 372, 127-138, doi:10.1016/S0140-6736(08)61034-X 
(2008). 
32 
Bassat, Q. et al. Dihydroartemisinin-piperaquine and artemether-lumefantrine for 
treating uncomplicated malaria in African children: a randomised, non-inferiority 
trial. PloS one 4, e7871, doi:10.1371/journal.pone.0007871 (2009). 
33 
Zani, B., Gathu, M., Donegan, S., Olliaro, P. L. & Sinclair, D. Dihydroartemisinin-
piperaquine for treating uncomplicated Plasmodium falciparum malaria. 
Cochrane Database Syst Rev 1, CD010927, doi:10.1002/14651858.CD010927 
(2014). 
34 
Zongo, I. et al. Randomized Noninferiority Trial of Dihydroartemisinin-
Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for 
Seasonal Malaria Chemoprevention in Burkina Faso. Antimicrobial agents and 
chemotherapy 59, 4387-4396, doi:10.1128/AAC.04923-14 (2015). 
35 
Bigira, V. et al. Protective efficacy and safety of three antimalarial regimens for 
the prevention of malaria in young ugandan children: a randomized controlled 
trial. PLoS medicine 11, e1001689, doi:10.1371/journal.pmed.1001689 (2014). 
36 
Hatton, C. S. et al. Frequency of severe neutropenia associated with 
amodiaquine prophylaxis against malaria. Lancet 1, 411-414 (1986). 
37 
Wilson, A. L. A systematic review and meta-analysis of the efficacy and safety of 
intermittent preventive treatment of malaria in children (IPTc). PloS one 6, 
e16976, doi:10.1371/journal.pone.0016976 (2011). 
38 
Bojang, K. et al. A randomised trial to compare the safety, tolerability and efficacy 
of three drug combinations for intermittent preventive treatment in children. PloS 
one 5, e11225, doi:10.1371/journal.pone.0011225 (2010). 
39 
Nakato, H., Vivancos, R. & Hunter, P. R. A systematic review and meta-analysis 
of the effectiveness and safety of atovaquone proguanil (Malarone) for 
chemoprophylaxis against malaria. The Journal of antimicrobial chemotherapy 
60, 929-936, doi:10.1093/jac/dkm337 (2007). 
40 
Faucher, J. F. et al. Efficacy of atovaquone/proguanil for malaria prophylaxis in 
children and its effect on the immunogenicity of live oral typhoid and cholera 
vaccines. Clinical infectious diseases : an official publication of the Infectious 
Diseases Society of America 35, 1147-1154, doi:10.1086/342908 (2002). 
41 
Darpo, B. et al. Evaluation of the QT effect of a combination of piperaquine and a 
novel anti-malarial drug candidate OZ439, for the treatment of uncomplicated 
malaria. British journal of clinical pharmacology, doi:10.1111/bcp.12680 (2015). 
42 
Manning, J. et al. Randomized, double-blind, placebo-controlled clinical trial of a 
two-day regimen of dihydroartemisinin-piperaquine for malaria prevention halted 

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for concern over prolonged corrected QT interval. Antimicrobial agents and 
chemotherapy 58, 6056-6067, doi:10.1128/AAC.02667-14 (2014). 
43 
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. Antimicrobial agents and chemotherapy 56, 1571-1577, 
doi:10.1128/AAC.05877-11 (2012). 
44 
Nankabirwa, J. I. et al. Impact of intermittent preventive treatment with 
dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a 
randomized, placebo-controlled trial. Clinical infectious diseases : an official 
publication of the Infectious Diseases Society of America 58, 1404-1412, 
doi:10.1093/cid/ciu150 (2014). 
45 
Cisse, B. et al. Randomized trial of piperaquine with sulfadoxine-pyrimethamine 
or dihydroartemisinin for malaria intermittent preventive treatment in children. 
PloS one 4, e7164, doi:10.1371/journal.pone.0007164 (2009). 
46 
Mueller, B. U., Martin, K. J., Dreyer, W., Bezold, L. I. & Mahoney, D. H. 
Prolonged QT interval in pediatric sickle cell disease. Pediatric blood & cancer 
47, 831-833, doi:10.1002/pbc.20539 (2006). 
47 
Liem, R. I., Young, L. T. & Thompson, A. A. Prolonged QTc interval in children 
and young adults with sickle cell disease at steady state. Pediatric blood & 
cancer 52, 842-846, doi:10.1002/pbc.21973 (2009). 
48 
Akgul, F. et al. Increased QT dispersion in sickle cell disease: effect of pulmonary 
hypertension. Acta haematologica 118, 1-6, doi:10.1159/000100929 (2007). 
49 
Proguanil - Summary of Product Characteristics, 
<https://www.medicines.org.uk/emc/medicine/2293> ( 
50 
SP-AQ - Summary of Product Characteristics, 
<http://apps.who.int/prequal/WHOPAR/WHOPARPRODUCTS/MA098part4v1.pdf
> ( 
51 
DP- Summary of Product Characteristics, 
<http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/001199/WC500118113.pdf> ( 
52 
Severe falciparum malaria. World Health Organization, Communicable Diseases 
Cluster. Transactions of the Royal Society of Tropical Medicine and Hygiene 94 
Suppl 1, S1-90 (2000). 
53 
Thornburg, C. D. et al. Impact of hydroxyurea on clinical events in the BABY 
HUG trial. Blood 120, 4304-4310; quiz 4448, doi:10.1182/blood-2012-03-419879 
(2012). 
54 
Rantala, A. M. et al. Comparison of real-time PCR and microscopy for malaria 
parasite detection in Malawian pregnant women. Malaria journal 9, 269, 
doi:10.1186/1475-2875-9-269 (2010). 
55 
Ivanova, A., Qaqish, B. F. & Schell, M. J. Continuous toxicity monitoring in phase 
II trials in oncology. Biometrics 61, 540-545, doi:10.1111/j.1541-
0420.2005.00311.x (2005). 
56 
Hasselblad, V. & Allen, A. S. Power calculations for large multi-arm placebo-
controlled studies of dichotomous outcomes. Statistics in medicine 22, 1943-
1954, doi:10.1002/sim.1427 (2003). 

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Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after 
vaccination: a phase 3 randomized, controlled trial in children and young infants 
at 11 African sites. PLoS medicine 11, e1001685, 
doi:10.1371/journal.pmed.1001685 (2014). 
58 
Corportation, C. C. Compaq Fortran Language Reference Manual.  (Digital 
Equipment Corporation, 1999). 
59 
Wang, W. C. et al. Hydroxycarbamide in very young children with sickle-cell 
anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet 377, 
1663-1672, doi:10.1016/S0140-6736(11)60355-3 (2011). 
60 
Bartko, J. J. The negative binomial distribution: a review of properties and 
applications. Virginia journal of science 12, 18-37 (1961). 
 
 
 

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APPENDIX A: STUDY INFORMATION SHEET (ENGLISH) 
 
 
 

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APPENDIX B: STUDY INFORMATION SHEET (KISWAHILI) 
 
 
 

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APPENDIX C: STUDY INFORMATION SHEET (KISWAHILI TO 
ENGLISH) 
 

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APPENDIX D: STUDY INFORMATION SHEET (DHOLUO) 
BE NYATHINI NI GI TUO 
MAR SICKLE CELL?  
 
Onyalo bedo e nonro mitimo Homa Bay  
County Hospital. 
Nonroni bo ng’iyo yedhe adek  
mopogore ma gengo malaria kuom  
nyidhindo ma ningi sickle cell 
Gima Nyithindo ma biro bedo e nonro botimo: 
•
Duogo due ka due kuom hinga achiel e Klinic ma nonro Homa Bay County Hospital 
mondo orang’ ngimagi kedo giyud Yath. 
•
Onego gi duok e Klinic ma nonro orang-gi ka higni chuakrwa mar del. 
•
ibo pim remb gi kuom kinde ka kinde. 
•
Onego gi bed e kind dueche 12 nyaka gingini 10. To gi dak Homa Bay County, 
Rongo kata Awendo subcounties mar Migori County. 
 Kuom wach matut, coordinator mar nonro yudore ye +254719474231. 
Nonroni I timo gi jononro mosome wach yethe moae Moi University School of Medicine 
(Eldoret) gi Duke University School of Medicine(  United States) to pesa nonro a kuom US 
National Institutes of Health (R01HL134211) 
 
 Ibo chuli kuom bendo nyathini e nonro. 
 

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APPENDIX E: STUDY INFORMATION SHEET (DHOLUO TO ENGLISH) 
DOES YOUR CHILD HAVE  
A DISEASE CALLED  
SICKLE CELL? 
 
Can he be part of the research which is conducted in  
Homa Bay County Hospital? 
 
This research will look into three different  
types of drugs which prevents malaria  
from children suffering from sickle cell.  
 
•
What children who will be involved in research will do: Coming back every month 
for one year to the research clinic of Homa Bay County Hospital so that they can be 
checked up and given drugs. 
•
They should come back to the research clinic so that they can be checked if they 
have fever. 
•
Their blood will be tested from time to time 
•
They must be between 12 months to 10 years. They must be residents of Homa 
Bay County, Rongo or Awendo sub counties of Migori County 
For more information, you can reach the coordinator of the research through this No. 
254719474231 
 
This research is being conducted by researchers who have studied medicine from Moi 
University School of Medicine, Eldoret and Duke University School of Medicine, United 
States. Research grant is from US National Institute of Health. R01HL134211. 
 
You will be compensated for your child participation in this study.  
 

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APPENDIX F: INFORMED CONSENT (ENGLISH) 
 
Enrollment Consent to Participate in a Research Study 
 
Title of Study: Enhancing Preventive Therapy of Malaria in Children with Sickle Cell 
Anemia in East Africa (EPiTOMISE).  
Investigator: Dr. Festus Njuguna  
 
You are being asked to allow your child to take part in this research study because your 
child has sickle cell anemia (SCA). 
 
WHAT ARE SOME GENERAL THINGS TO KNOW ABOUT RESEARCH STUDIES? 
 
You are being asked to allow your child to participate in a clinical research study. Before 
agreeing to allow your child to participate in this clinical research study, it is important 
that you understand that studies like these only include people who choose to take part. 
Your child’s participation is voluntary.  Please read this consent form carefully and take 
your time making your decision. Your child’s study doctor or study staff will talk about 
this consent form with you.  Please ask about any words or information that you do not 
clearly understand.  
 
This consent form describes what will happen in this study.  This form describes the 
risks, inconveniences, discomforts, and other important information. It is important that 
you ask questions and understand what is required for participation in this research 
study. We encourage you to talk with your family and friends before you decide to allow 
your child to take part in this research study. You may take home a copy of the form to 
review, while you decide if you would like your child to participate in the study. If you 
agree to allow your child to participate and sign this form, you will be given a signed and 
dated copy of this form to keep.  
 
Please tell the study doctor or study staff if your child is taking part in another research 
study.  
 
WHO WILL BE MY STUDY DOCTOR? 
If you decide to participate, Dr. Njuguna will be your doctor for the study and will be in 
contact with your regular health care provider throughout the time that you are in the 
study and afterwards, if needed. 
 
A grant from the United States National Institutes of Health (NIH) will sponsor this study.  
Portions of Dr. Njuguna and his research team’s salaries will be paid by this grant. 
 
WHY IS THIS STUDY BEING DONE? 
You are being asked to allow your child to take part in this study because he/she is 
between the ages of 1 and 10 years of age, has SCA, and lives in an area with a lot of 
malaria. 
 

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We want to find better ways to prevent malaria in children with SCA. This study will help 
us identify the best medications that can be used to prevent malaria in children with 
SCA in parts of Africa that have malaria.   
 
In this study, we are going to compare three malaria drugs that are already available in 
your local pharmacy in order to see which of the medications, if any, is better at 
reducing the number of times your child has malaria.   
 
The study medications included in this research study are listed below. In this study, 
your child will take one of the following three medications by mouth as malaria 
prevention: 
• Proguanil (also known as Paludrine) is the current standard of care for prevention 
of malaria in children with SCA in Kenya. Your child may already be taking this 
medication to prevent malaria. This medication is taken daily.  
 
OR 
• Sulfadoxine/Pyrimethamine-Amodiaquine (SP-AQ) is a combination of 
medications comprised of sulfadoxine and pyrimethamine taken at the same time 
as amodiaquine. This medication is taken monthly.  
 
OR 
 
• Dihydroartemisinin-Piperaquine (DP) is a combination medicine of 
dihydroartemisinin and piperaquine. This medication is taken monthly. 
 
In addition, if your child does get malaria, he/she will be treated by mouth with a 
medication called Artemether-Lumefantrine (AL). All children under 5 years of age will 
also receive daily penicillin by mouth, which is intended to prevent bacterial infections 
and is standard of care for children with SCA. 
 
HOW MANY CHILDREN WILL TAKE PART IN THIS STUDY? 
About 246 children will complete this research study. This study will be done at Homa 
Bay County Hospital in Homa Bay, Kenya.  
 
WHAT IS INVOLVED IN THE STUDY? 
If you agree to allow your child to be in this study, you will be asked to sign this consent 
form.  Your child will have the following procedures to make sure that your child is 
eligible for the study: 
 
Screening Visit 
Before participating in the study, the study personnel need to determine if your child is 
eligible to participate. This helps to improve the safety of participating in the study. 
 
During the screening visit, the following procedures will be conducted and information 
recorded: 
• We will review your child’s medical history 

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• We will review medications that your child is taking  
• We will perform an electrocardiogram (ECG), in which the electrical activity of 
your child’s heart is measured through his/her skin 
• We will collect approximately 3 ½ milliliters (mL) of blood to test your child’s red 
blood cells for the proteins that cause SCA and to perform routine blood tests to 
determine if it is safe to enroll in the study. 
 
 
Enrollment Visit 
During the enrollment visit, the following procedures will be conducted and information 
recorded:   
• We will review and record your child’s medical history, including any medical 
events that have occurred since the previous visit  
• We will record medicines your child is taking 
• We will conduct a physical examination, including height and weight 
• We will collect a fingerprick blood sample of less than ½ mL 
• If necessary, we will administer to your child a Meningococcal vaccine.  This 
vaccine will help protect your child against bacteria that causes meningitis. This 
may not be necessary if your child has already received this vaccine, which is 
routinely recommended in Kenya. 
• We will provide you with a 30-day supply of daily penicillin (if your child is less 
than 5 years old), which is a standard medication used to prevent bacterial 
infections in children with SCA 
• We will enroll your child into the Kenyan National Hospital Insurance Fund 
(NHIF); 
• We will provide you with your child’s malaria prevention study medication and 
instructions on how to take it. 
 
Also at this enrollment visit we will determine which malaria prevention study medication 
your child will receive. To do so, your child will be randomly assigned (like drawing 
numbers from a hat) to receive either daily Proguanil, monthly SP-AQ, or monthly DP. 
Your child has a 1 in 3 chance of receiving a particular study drug. Whichever drug that 
your child is assigned to receive through this process will be the malaria prevention drug 
that they receive throughout the study. All children will receive some type of malaria 
prevention medication. 
 
Routine Follow up Visits (monthly) 
At each monthly visit, the following procedures will be conducted: 
• We will review your child’s medical history, including medical events since the 
last visit 
• We will perform a physical exam, including height and weight 
• We will collect a fingerprick blood sample of less than ½ mL that will be used to 
test your child’s blood for anemia levels and for malaria parasites.  
• If your child has a fever or has had a fever within the last 24 hours, he/she will 
have an immediate test for malaria parasites; if your child has not had fever, then 
the blood will be saved for testing at the end of the study. 

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• Every third monthly visit, we will collect approximately 2½ mL of blood for routine 
testing 
• At the 6-month visit and final 12-month visit, we will collect an additional 1 mL of 
blood to test for sickle-cell red blood cells 
• If you sign the separate consent form agreeing to an additional blood collection, 
at either the 3, 6, 9, or 12 month visit we will collect an additional 2½ mL of blood 
for future research studies. 
• If necessary, we will perform an ECG;* 
• We will provide you with the study medication and instructions on how to take it; 
• We will provide you with a 30 day supply of daily penicillin (if less than 5 years 
old). 
 
*Approximately 20 children will be asked to return to clinic 2 days later to have repeat 
ECG done each month during the study; this will be to track the results of the ECG on 
an ongoing basis throughout the entire period.  This will only be some of the children 
assigned to the DP arm of the study. 
 
If your child has a positive blood test for malaria, he/she will be treated at that time with 
AL. 
 
Acute-Care Visits (as needed) 
For the study, if your child at home has a fever, either because they feel hot or because 
their temperature is measured above 37.5 degrees Celsius, we are asking that you call 
the study personnel in order to arrange to be evaluated by one of the study clinicians. At 
this visit, the following procedures will be conducted: 
• We will review your child’s medical history, including medical events since the 
last visit 
• We will perform a physical exam, including height and weight 
• We will collect a fingerprick blood sample of less than ½ mL.  
• If your child has a fever or has had a fever within the last 24 hours, he/she will 
have an immediate test for malaria parasites; if your child has not had fever, then 
the blood will be saved for testing at the end of the study. 
 
If your child has a positive blood test for malaria, he/she will be treated at that time with 
AL.  
 
HOW LONG WILL MY CHILD BE IN THIS STUDY? 
The expected duration of study participation is monthly for 12 months. Your child’s study 
participation will end after the month 12 final visit.  
 
You can choose to stop participating at any time without penalty. In that case, you will 
no longer receive medical care or benefits that are provided by the study, and your 
child‘s care would be transferred to clinicians who are not involved in the study, such as 
your pediatrician, hospital or clinic. However, if you decide to stop participating in the 
study, we encourage you to talk to your doctor first. 
 

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WHAT ARE THE RISKS OF THE STUDY? 
As a result of your participation in this study, your child is at risk for the following side 
effects. If you choose to participate, you should discuss these with the study doctor and 
your regular health care provider. 
 
It is possible for any drug to cause unwanted side effects.  You need to know about side 
effects that could occur in this study before you decide whether your child should 
participate.  There may be risks, discomforts, drug interactions or side effects that are 
not yet known. These risks include possible worsening of the complications of sickle cell 
anemia. If these complications are serious enough, they can be fatal. 
 
Proguanil may cause some, all or none of the side effects listed below. 
More likely: 
• Nausea   
 
 
 
Anemia 
• Vomiting   
 
 
 
Allergic reactions 
• Abdominal pain  
 
 
Depression  
• Abnormal dreams 
 
 
Cough 
• Headache  
 
 
 
Insomnia 
 
 
 
• Diarrhea   
 
 
 
Rash 
• Weakness 
 
 
 
Fever  
• Loss of appetite   
 
 
Dizziness 
• Itching 
Less Likely: 
• Nervousness 
• Rapid, strong, or irregular heartbeat 
• Mouth ulcers 
• Hair loss 
• Severe rash  
 
SP-AQ may cause some, all or none of the side effects listed below. 
More likely: 
• Headache 
 
 
 
Cough 
• Vomiting  
 
 
 
Nausea 
• Loss of appetite   
 
 
Abdominal Pain 
• Diarrhea  
 
 
 
Weakness 
• Fever 
 
 
 
 
Tiredness 
• Difficulty sleeping  
 
 
Rash/skin eruptions 
• Sleepiness  
 
 
 
Itching 
 
Less Likely 
• Eye Problems/Retinopathy 
• Liver Problems/Hepatitis 
• Anemia 
 
 

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DP may cause some, all or none of the side effects listed below. 
More likely:  
• Headache 
• Fever 
• Cough 
• Influenza 
• Diarrhea 
  
Less Likely:  
• Dizziness 
• Vomiting 
• Nausea 
• Loss of appetite 
 
OTHER RISKS 
As a result of drawing blood from your child’s arm or from a finger prick, your child may 
experience momentary discomfort and/or bruising.  Infection, excess bleeding, clotting, 
or fainting are also possible, although unlikely. To reduce the chances of these risks, we 
will hire only trained study staff and appropriate supplies for blood draws.  
 
In addition, your child may experience unforeseeable risks and inconveniences 
associated with the use of the study drug. These may include possible worsening of the 
complications of sickle cell anemia, which, when serious, can be fatal. You should 
report any problems you have to the study team. 
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
If you agree to allow your child to take part in this study, there may be direct medical 
benefit to your child.  Child participants will receive free study medications to prevent 
malaria and bacterial infections, monthly comprehensive assessments, free testing for 
malaria parasites when they have a fever and enrollment in the Kenyan National 
Hospital Insurance Fund. These services have the potential to reduce medical problems 
from both malaria and SCA. 
 
In the long-term, we hope that in the future the information learned from this study will 
benefit children in Africa with SCA, by finding better medications to prevent malaria. 
 
WHAT ALTERNATIVES ARE THERE TO PARTICIPATION IN THIS STUDY? 
Your child does not have to participate in this study. Even if you do not allow your child 
to participate, he/she can still receive regular medical treatment from their regular 
medical providers. 
 
WILL MY CHILD’S INFORMATION BE KEPT CONFIDENTIAL? 
Your child will not be identified by name, or any other facts that may point to him or her 
in study records shared outside of Homa Bay County Hospital.  For records disclosed 
outside of Homa Bay County Hospital, your child will be assigned a unique code 

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number.  The log or list which includes the code number and your child’s name and/or 
other personal identifier is confidential and will be kept secure by the research team. 
 
Every effort will be made to maintain the confidentiality of your child’s medical records. 
However, this cannot be guaranteed. There is the potential risk of loss of confidentiality. 
Certain offices and people other than the researchers may look at your child’s medical 
charts and study records.  These include people from: 
• The study teams at Moi University, Duke University, and the Duke Clinical 
Research Institute; 
• The Moi University Institutional Research & Ethics Committee and the Duke 
University Health System Institutional Review Board; 
• Representatives from the United States NIH. 
 
Study records will be retained for ten years after the end of the study per local 
regulations. Study information in your child’s medical records will be kept forever. 
 
During the course of this study, your doctor and the research team may share study 
information with certain individuals. These may include: 
• Study monitors, who verify the accuracy of the information;  
• Individuals with medical backgrounds who determine the effect that the drugs 
have on your child’s disease; and/or 
• Individuals who put all the study information together in report form.  
 
While your child is in this research study, research information collected about him/her 
might be put in his/her medical record. 
 
You have the right to stop participating in this study at any time. To stop participating, 
you should let your study doctor know that you want to stop it. If you want your child to 
participate in this research study, you must sign this consent form to give the study 
team permission to look at your child’s health information. If you refuse to allow us to 
review your child’s health information, your child will not be able to be in the research 
study. However, not signing this form will not affect you or your child’s access to 
medical care.  
 
While the information and data resulting from this study may be presented at scientific 
meetings or published in a scientific journal, your child’s identity will not be revealed and 
your child will not be mentioned by name. A description of this clinical trial will be 
available on http://www.ClinicalTrials.gov and the Pan African Clinical Trials Registry 
(http://www.pactr.org). These web sites will not include information that can identify you.  
At most, the web sites will include a summary of the results. You can search these web 
sites at any time. 
 
Your child’s records will not be used for any other purpose or shared with anyone else 
without your permission. 
 
WHAT ARE THE COSTS? 

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There will be no additional costs to you or your child as a result of being in this study. 
Any study procedures, study drugs, or study tests will be provided to your child free of 
charge. In addition, if your child participates in the study, we will enroll your child in the 
Kenya NHIF while they participate in the study. Some types of medical care may be 
paid by the NHIF.  
 
WHAT ABOUT COMPENSATION?   
There will be no money or compensation for your child’s participation in this study. 
However, you will receive KSh/500 for help with transportation to your scheduled follow 
up visits. This may not cover the full costs of transportation, but will help make it easier 
to fully participate in the study. 
 
WHAT IF MY CHILD IS INJURED?  
Immediate necessary medical care is available at Homa Bay County Hospital in the 
event that your child is injured as a result of participation in this research study. There is 
no commitment by Moi University, Duke University through its Duke Clinical Research 
Institute, Homa Bay County Hospital, or the NIH to provide any reimbursement or 
payment for any study-related injury costs, money or free medical care.     
 
For questions about the study or research-related injury, contact Dr. Njuguna at 
+254719474231 during regular business hours and at +254719474231 after hours and 
on weekends and holidays. 
 
WHAT ABOUT MY RIGHTS TO DECLINE MY CHILD’S PARTICIPATION OR 
WITHDRAW FROM THE STUDY? 
You may choose to not allow your child to be in the study.  You may also choose to 
allow your child to be in the study and you may withdraw him/her from the study at any 
time. If you withdraw your child from the study, no new data about your child will be 
collected for study purposes unless your child has a side effect related to the study 
drug.  If a side effect like this occurs, we may need to review your child’s entire medical 
record. All information collected for the study will be sent to the study sponsor, which is 
the United States’ NIH. 
 
Your decision not to allow your child to participate or to withdraw from the study will not 
involve any penalty, although you will no longer receive medical care or benefits that are 
provided by the study and your child‘s care would be transferred to clinicians who are 
not involved in the study, such as your pediatrician, hospital or clinic. This will not affect 
you or your child’s access to health care at through their regular medical providers.  
 
INVOLUNTARY REMOVAL FROM THE STUDY 
The study doctors may decide to take your child out of this study if:  
• your child’s condition gets worse, or  
• your child has a serious side effect, or  
• needs treatment not allowed in the study, or 
• the study doctors decide it is no longer in your child’s best interest to continue. 
 

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The NIH, Dr. Njuguna or other study doctors, or regulatory agencies may stop this study 
at any time without your consent. If this occurs, you will be told and your study doctor 
will talk to you about other options. 
 
WHAT IF THERE IS NEW INFORMATION? 
You will be given any new information learned during the course of the study that might 
affect you whether you agree to continue your child’s participation in the study.  
 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
For questions about the study or a research-related injury or if you have problems, 
concerns, or suggestions about the research, contact Dr. Njuguna at +254719474231 
during regular business hours, after hours, and on weekends and holidays. For 
questions about your child’s rights as a research participant, or to talk about problems, 
concerns, or suggestions related to the research, or to obtain information or offer input 
about the research, contact the Moi’s Institutional Research Ethics Committee (IREC) at 
+2540787723677.  The Duke University Health System Institutional Review Board has 
also reviewed this study, if you have any questions that those members can assist with 
please direct them to +1(919) 668-5111. 
 
STATEMENT OF CONSENT 
The purpose of this study, procedures to be followed, risks, and benefits have been 
explained to my child and me. I have been allowed to ask questions, and my questions 
have been answered to my satisfaction. I have been told whom to contact if I have 
questions, to talk about problems, concerns, or suggestions related to this research 
study. I have read this consent form and agree for my child to be in this study, with the 
understanding that I may withdraw my child at any time. I have been told that I will be 
given a signed and dated copy of this consent form. 
 
___________________________________ 
 
Printed Name of Parent or Legal Guardian 
 
 
____________________________________  
 
 
Signature of Parent or Legal Guardian   
Date                         Time: ___: ____ 
 
 
____________________________________   ______________________________ 
Signature of Witness (if applicable) 
 
Date  
 
Time 
 
 
I have fully explained the research study described by this form. I have answered the 
parent/guardian’s questions and will answer any future questions to the best of my 
ability. I will tell the family of any changes in the procedures or in the possible 
harms/possible benefits of the study that may affect parent/guardian’s willingness to 
have their child stay in the study. 
 

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____________________________________ ___________ 
 
Printed Name of Researcher Obtaining   
Date  
 
 
Parental Permission or Consent 
 
 
____________________________________ ___________ 
Signature of Researcher Obtaining  
  
 
Date  
 
 
Parental Permission or Consent    
 
 
 
 
 
 
 
 
 
 
 
 
WHAT WILL BLOOD SAMPLES BE USED FOR? 
During the course of this study, over 12 months your child will have blood collected in 
an amount specified above (this enrollment visit and then 12 monthly visits).  We will 
collect this blood to perform routine testing to monitor the effects of SCA, malaria, and 
the study medications. 
 
In addition, one blood sample will collected and used only for future research, if you 
agree to this request.  These samples will be stored for a long time at one of the 
universities or research organizations conducting this study, including Moi University or 
Duke University. Samples may also be shared with investigators at other institutions. 
Any use of these stored samples must be approved by an institutional review or ethics 
board. 
 
Here are a few important considerations for these samples: 
• We will collect and store approximately 2.5 mL of blood for future research during 
a visit at which we are collecting blood for routine care. This sample will only be 
used to study malaria, SCA, or other infectious diseases in children with SCA.  
• We will also store a blood spot on special paper from the blood we have 
collected from you. After the study is over, this will be used to test for malaria 
parasite genes. 
• The information that we get from these studies will not affect your child’s care. 
• These samples will not be sold or used for the production of commercial 
products.  
• We may perform research on the human or malaria genes in these samples, but 
no information will be placed in your child’s medical record, and samples will be 
coded so that nobody can figure out the identity of your child. 
• There is no direct benefit for your child if you allow us to use samples for these 
uses. However, if they can be used for future research studies, we hope that 
these will help us learn how to better prevent, treat, or cure medical problems in 
children with SCA. 
 
Every effort will be made to protect your confidential information, but this cannot be 
guaranteed. The information that may be obtained as a result of your participation in 
future research will not be included in your medical record.  
 

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IF I AGREE TO PROVIDE SAMPLES NOW, CAN I REQUEST THAT MY SAMPLES 
BE DESTROYED AT A LATER DATE?   
If you decide later that you would like your samples destroyed, you must inform Dr. 
Njuguna or his representatives on the study team that you are withdrawing your 
permission for your samples to be stored and used for future research.   
• During the main study, please contact the study coordinator Mr. Joseph Kipkoech 
at +254719474231.  
• After the main study, please contact the Moi’s Institutional Research Ethics 
Committee (IREC) at +2540787723677. 
If the information linking your coded samples to you has already been destroyed, your 
samples can no longer be linked to you and we will be unable to locate them for 
destruction. 
 
Also, even though your samples will be destroyed:  
• We cannot get back samples or information that we have already given out to 
researchers 
• You cannot withdraw your sample if it has already been analyzed or tested  
 
Please sign on one signature line below whether you agree to have your blood samples 
stored for possible future research, or if you do not agree to have your blood samples 
stored. 
 
I agree to allow my child’s blood samples to be stored for possible future research of 
SCA, malaria, and other infections in children with SCA. 
 
 
Parent or Legal Guardian Signature 
 
 
 
 
Date 
 
 
I DO NOT agree to allow my child’s blood samples to be stored for possible future 
research of SCA, malaria, and other infections in children with SCA. 
 
 
Parent or Legal Guardian Signature 
 
 
 
 
 Date 
 
 
 
______________________________________________________________________
Witness Signature (if applicable)  
 
 
 
 
Date 
 

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APPENDIX G: INFORMED CONSENT (KISWAHILI) 
Enrollment Consent to Participate in a Research Study 
 
Title of Study: Enhancing Preventive Therapy of Malaria in Children with Sickle Cell 
Anemia in East Africa (EPiTOMISE). 
Mtafiti:DaktariFestus Njuguna 
 
Unaulizwa kuruhusu mtoto wako ashiriki katika utafiti huu kwa sababu mtoto wako ako 
na Sickle Cell Anemia (SCA). 
 
NI MAMBO GANI YA JUMLA UNAYOSTAHILI KUJUA KUHUSU TAFITI ZA MASOMO? 
Unaulizawa kuruhusu mtoto wako ashiriki katika utafiti wa kimasomo ya kliniki.Kabla ya 
kukubali kumruhusu mtoto wako ashiriki katika huu utafiti wa kimasomo ya kliniki, ni 
muhimu uelewe kwamba tafiti kama hizi hujumuisha tu watu ambao huchagua kushiriki. 
Kushiriki kwa mtoto wako ni kwa hiari. Tafadhali soma fomu hii ya idhini kwa makini na 
uchukue muda wako kufanya uamuzi wako.Daktari wa utafiti wa mtoto wako au 
wafanyakazi wa utafiti watazungumza kuhusu hii fomu ya idhini na wewe. Tafadhali 
uliza kuhusu mambo yoyote au habari ambayo hauelewi kwa kina 
Hii fomu ya idhini inaeleza ni nini kitatendeka katika utafiti huu.Hii fomu inaelezea hatari, 
shida, ugumu na mambo mengine muhimu. Ni muhimu kwamba uulize maswali na 
uelewe kile  kinachohitajika kwa ajili ya kushiriki katika utafiti huu.Tunakuhimiza 
uzungumze na familia yako na marafiki kabla ya kuamua kumruhusu mtoto wako 
ashiriki katika utafiti huu. Unaweza kuenda nyumbani na nakala ya fomu hii uipitie huku 
ukiamua kama ungependa mtoto wako ashiriki katika utafiti. Ikiwa utakubali kumruhusu 
mtoto wako ashiriki na utie sahihi fomu hii, utapewa nakala ya fomu hii iliyotiwa sahihi 
na tarehe uweke. 
Tafadhali ambia daktari wa utafiti au wafanyakazi wa utafiti ikiwa mtoto wako anashiriki 
katika utafiti mwingine. 
 
NANI  ATAKUWA DAKTARI WANGU WA UTAFITI? 
Ikiwa utakubali kushiriki, Daktari Njuguna atakuwa daktari wako wa utafiti na 
atawasiliana na mhudumu wako wa afya wa kawaida katika wakati wote ambao wewe 
utakuwa kwenye utafiti na baada ya hapo, ikiwa itahitajika. 
 
Ruzuku kutoka kwa kwaTaasisi ya Taifa ya Afya ya Marekani (NIH) itadhamini utafiti 
huu. Sehemu ya mishahara ya Daktari Njuguna na timu yake ya utafiti italipwa na 
ruzuku hii. 
 
KWA NINI UTAFITI HUU UNAFANYWA? 
Unaulizwa kuruhusu mtoto wako ashiriki katika utafiti huu kwa sababu ako kati ya umri 
wa mwaka 1 na umri wa miaka 10, ako na SCA, na anaishi katiki eneo lililo na malaria 
mengi. 
 

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TUNATAKA KUTAFUTA NJIA BORA ZA KUZUIA MALARIA KWA WATOTO 
WALIO NA SCA. HUU UTAFITI UTATUSAIDIA KUTAMBUA DAWA BORA 
AMBAZO ZINAWEZA KUTUMIKA KUZUIA MALARIA KWA WATOTO WALIO NA 
SCA KATIKA MAENEO YA AFRIKA AMBAYO YANA MALARIA. 
Katika utafiti huu, tutalinganisha madawa matatu ya malaria ambayo tayari 
yanapatikana katika maduka ya madawa ya eneo lako ili kuona ni madawa gani, kama 
yapo, ni bora katika kupunguza idadi ya nyakati mtoto wako anakuwa na malaria. 
 
Dawa za utafiti zilizojumuishwa katika utafiti huu zimeorodheshwa hapo chini. Katika 
utafiti huu, mtoto wako atachukua moja ya dawa za aina tatu zifuatazo kwa kinywa ili 
kuzuia malaria: 
 
• Proguanil (pia inajulikana kama Paludrine) ni kipimo cha sasa cha utunzaji kwa 
ajili ya kuzuia malaria kwa watoto walio na SCA nchini Kenya. Mtoto wako 
anaweza kuwa tayari anatumia dawa hii kuzuia malaria. Dawa hii humezwa kila 
siku. 
 
AU 
 
• Sulfadoxine/Pyrimethamine-Amodiaquine (SP-AQ) ni mchanganyiko wa madawa 
zikiwemo za sulfadoxine na pyrimethamine zinazomezwa wakati mmoja kama 
amodiaquine. Dawa hizi humezwa kila mwezi. 
 
AU 
 
• Dihydroartemisinin-Piperaquine (DP) ni dawa mchanganyiko wa 
dihydroartemisinin na piperaquine.Dawa hii humezwa kila mwezi. 
 
Aidha, ikiwa mtoto wako atapata malaria, yeye atatibiwa kwa kinywa na dawa iitwayo  
Artemether-Lumefantrine (AL). Watoto wote chini ya umri wa miaka 5 pia watapokea 
penicillin kila siku kwa kinywa, ambayo inalengwa kuzuia maambukizi ya bacteria na ni 
kipimo cha matunzo kwa watoto walio na SCA. 
 
NI WATOTO WANGAPI WATASHIRIKI KATIKA UTAFITI HUU?  
Karibu watoto 246 watakamilisha utafiti huu. Utafiti huu utafanywa katika hospitali ya 
kaunti ya Homa Bay, katika Homa Bay, Kenya.  
 
NINI KINACHOHUSISHWA KATIKA UTAFITI HUU? 
Ikiwa utakubali kuruhusu mtoto wako ashiriki katika huu utafiti, utaulizwa kutia sahihi hii 
fomu ya idhini. Mtoto wako atafanyiwa  taratibu zifuatazo ili kuhakikisha kwamba 
anastahili kuwa kwa utafiti: 
 
Ziara ya Uchunguzi 

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Kabla ya kushiriki katika utafiti, wafanyakazi wa utafiti watahitaji kutambua ikiwa mtoto 
wako ana haki ya kushiriki. Hii husaidia kuboresha usalama wa kushiriki katika utafiti. 
Wakati wa ziara ya uchunguzi, taratibu zifuatazo zitafanywa na kurekodiwa: 
• Tutapitia historia ya matibabu ya mtoto wako 
• Tutapitia madawa ambayo mtoto wako anatumia 
• Tutafanya uchunguzi wa  electrocardiogram (ECG),ambapo shughuli za umeme 
katika moyo wa mtoto wako hupimwa kwa kupitia ngozi yake 
• Tutakusanya takriban mililita 31/2  (mL) za damu ili kupima seli nyekundu za 
damu za mtoto wako kuona protini zinazosababisha SCA na kufanya uchunguzi 
wa damu ili kubaini ikiwa ni salama kumhusisha katika utafiti.  
Ziara ya Kujiunga  
Wakati wa ziara ya kujiunga, taratibu zifuatazo zitafanywa na taarifa kurekodiwa:  
• Tutapitia na kurekodi  historia ya matibabu ya mtoto wako, ikiwa ni pamoja na 
matukio yoyote ya matibabu yaiyotokea tangu ziara iliyopita. 
• Tutarekodi madawa ambayo mtoto wako anatumia 
• Tutafanya uchunguzi wa mwili, ikiwa ni pamoja na urefu na uzito. 
• Tutakusanya sampuli ya damu kutoka kwa kidole chini ya mililita ½   
• Iwapo ni muhimu, tutampa mtoto wako chanjo ya Meningococcal.  Chanjo hii 
itasaidia kumkinga mtoto wako dhidi ya bakteria zinazosababisha meningitis. Hii 
haitakuwa muhimu ikiwa mtoto wako tayari ashapokea chanjo hii, ambyo kwa 
kawaida imependekezwa nchini Kenya. 
• Tutakupatia ugavi wa penicillin wa siku 30 (ikiwa mtoto wako ako chini ya umri 
wa miaka 5),  ambayo ni dawa  inayotumika kuzuia maambukizi ya bakteria 
katika watoto walio na SCA. 
• Tutaandikisha mtoto wako katika bima ya kitaifa ya hospitali ya Kenya (NHIF) 
• Tutakupatia madawa ya utafiti ya kuzuia uambukizaji wa malaria katika mtoto 
wako na maelekezo ya jinsi atakavyoyatumia.  
 
Pia katika ziara hii ya kujiunga  tutaamua ni dawa gani za utafiti za kuzuia malaria 
ambazo mtoto wako atapokea.Kufanya hivyo, mtoto wako, bila mpangilio (kama kutoa 
nambari kutoka kwa kofia) atawekwa kupokea  aidha Proguanil kila siku, SP-AQ kila 
mwezi, au DP kila mwezi. Mtoto wako ana fursa 1 kati ya 3 ya kupata dawa Fulani ya 
utafiti. 
 
Namna yeyote ya dawa ambayo mtoto wako atawekwa kupokea kupitia utaratibu huu, 
itakuwa dawa ya kuzuia malaria atakayoipokea katika utafiti wote. Watoto wote 
watapokea aina fulani ya dawa ya kuzuia malaria. 
 

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Ziara za kufuatilia zilizopangwa (kila mwezi) 
Katika kila ziara ya kila mwezi, taratibu zifutazo zitafanywa: 
• Tutapitia historia ya matibabu ya mtoto wako,  ikiwa ni pamoja na matukio ya 
matibabu tangu ziara iliyopita 
• Tutafanya uchunguzi wa mwili, ikiwa ni pamoja na urefu na uzito. 
• Tutakusanya sampuli ya damu iliyo chini ya mililita ½ kutoka kwa kidole 
kilichodungwa  ambayo itatumika kupima kiwango cha anemia kwa mtoto wako 
na vimelea vya malaria .  
• Ikiwa mtoto wako ana joto au amekuwa na joto ndani ya masaa 24 iliyopita, yeye 
atachunguzwa vijidudu vya malaria mara moja; ikiwa mtoto wako hajakuwa na 
joto, basi damu itahifadhiwa  kwa ajili ya uchunguzi mwishoni mwa utafiti. 
• Kila ziara ya kila mwezi wa tatu, tutakusanya takriban mililita 2 ½  ya damu kwa 
upimaji wa mara kwa mara. 
• Katika ziara ya mwezi wa 6 na ziara ya mwisho ya mwezi wa 12, tutakusanya 
ziada ya mililita 1 ya damu ili kuchunguza seli nyekundu za damu zilizo na 
selimundu.  
• Ikiwa utatia saini fomu tofauti itakayoidhinisha kukusanya damu zaidi katika ziara 
ya mwezi wa 3, 6, 9 ama 12, tutachukua mililita 2 ½ zaidi ya damu kwa ajili ya 
utafiti wa baadaye.  
• Ikiwa ni itahitajika, tutafanya ECG;* 
• Tutakupatia dawa za utafiti na maelekezo ya jinsi ya kuzitumia; 
• Tutakupatia ugavi wa siku 30 wa penicillin ya kila siku ( ikiwa ako chini ya umri 
wa miaka 5). 
 
*Takriban watoto 20 wataulizwa kurudi kwa kliniki siku 2 baadaye ili warudie kufanya 
ECG kila mwezi wakati wa utafiti; hii itakuwa kufuatilia matokeo ya ECG juu ya misingi 
endelevu katika kipindi chote.Hii itakuwa tu kwa baadhi ya watoto waliowekwa katika 
kikundi cha DP cha utafiti 
 
Ikiwa mtoto wako atapimwa damu na awe na malaria, yeye atatibiwa  wakati huo na AL.  
 
Ziara ya Huduma ya papo hapo (kama inahitajika) 
Katika huu utafiti, ikiwa mtoto wako yuko nyumbani na ana joto, aidha kwa sababu 
anahisi joto au kipimo cha joto la mwili kiko juu ya nyuzi 37.5, tunakuomba kwamba 
upigie simu wafanyakazi wa utafiti ili wapange aonwe na mmoja wa madaktari.Katika 
ziara hii, taratibu zifuatazo zitafanyika:  
• Tutapitia historia ya matibabu ya mtoto wako, ikiwa ni pamoja na matukio ya 
matibabu tangu ziara iliyopita. 
• Tutafanya uchunguzi wa kimwili, ikiwa ni pamoja na urefu na uzito. 
• Tutakusanya sampuli ya damu iliyo chini ya mililita ½. Ikiwa mtoto wako ana joto 
au amekuwa na joto ndani ya masaa 24 iliyopita, yeye atachunguzwa vijidudu 
vya malaria mara moja; ikiwa mtoto wako hajakuwa na joto, basi damu 
itahifadhiwa  kwa ajili ya uchunguzi mwishoni mwa utafiti. 
 
Ikiwa mtoto wako atapimwa damu na awe na malaria, yeye atatibiwa  wakati huo na AL.  
 

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MTOTO WANGU ATAKUWA KWA UTAFITI KWA MUDA GANI? 
Inatarajiwa muda wa kushiriki kwa utafiti ni wa kila mwezi kwa miezi 12. Kushiriki kwa 
mtoto wako katika utafiti kutaisha baada ya ziara ya mwisho ya mwezi wa 12.  
 
Unaweza kuchagua kuwacha kushiriki wakati wowote bila adhabu. Katika hali hiyo, 
hutaweza tena kupokea huduma ya afya au faida zinazotolewa na utafiti, na 
kuhudumiwa kwa mtoto wako kutahamishiwa madaktari wengine ambao hawahusiki 
katika utafiti, kama vile daktari wa mtoto wako, hospitali au kliniki. Hata hivyo, ikiwa 
utaamua kuacha kushiriki katika utafiti, tunakuhimiza uzungumze na daktari wako 
kwanza. 
 
HATARI ZA UTAFITI NI GANI? 
Kutokana na kushiriki kwako katika utafiti huu, mtoto wako ako katika hatari ya athari 
zifuatazo. Ikiwa utachagua kushiriki, unapaswa kujadili haya na daktari wa utafiti na 
mhudumu wako wa afya wa kawaida. 
 
Inawezekana  dawa yoyote kusababisha athari zisizotakikana. Unahitajika kujua kuhusu 
athari zinazoweza kutokea katika huu utafiti kabla hujaamua ikiwa mtoto wako 
anapaswa kushiriki. Kunaweza kuwa na hatari, usumbufu, mwingiliano wa madawa au 
athari ambazo bado hazijulikani. Athari hizi zaweza kuwa ni pamoja na kuongezeka kwa 
matatizo makubwa ya selimundu na anemia.Ikiwa matatizo haya ni makubwa, 
yanaweza yakasabisha kifo. 
 
 
 
Proguanil inaweza kusababisha baadhi, yote au isisababishe madhara 
yaliyoorodheshwa hapa chini.  
Uwezekano mkubwa:  
 
• Kichefuchefu 
 
 
Upungufu wa damu 
• Kutapika   
 
 
Athari mzio 
• Maumivu ya tumbo 
            majonzi 
• Ndoto zisizo za kawaida 
 
Kukohoa 
• Kuumwa na kichwa 
 
Kukosa usingizi 
 
 
 
• Kuhara 
 
 
 
Upele 
• Udhaifu  
 
 
Joto 
• Kupoteza hamu ya chakula 
Kizunguzungu 
• Kujikuna 
Uwezekano mdogo 
 
• Kuwa mwoga 
• Moyo kudunda kwa haraka, kwa nguvu au kusiko kwa kawaida 
• Vidonda mdomoni 
• Nywele kupotea 
• Upele mkali 
 

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SP-AQ inaweza kusababisha baadhi, yote au isisababishe madhara yaliyoorodheshwa 
hapa chini. 
Uwezekano mkubwa: 
• Kuumwa na kichwa 
 
 
Kukohoa 
• Kutapika  
 
 
 
Kichefuchefu 
• Kupoteza hamu ya chakula 
 
Maumivu ya tumbo 
• Kuhara 
 
 
 
            Udhaifu 
• Joto 
 
 
 
 
Uchovu 
• Ugumu katika kulala 
 
 
Upele/milipuko ya ngozi 
• Kuhisi usingizi 
 
 
 
Kujikuna 
 
 
Uwezekano mdogo 
• Matatizo ya macho/kuharibika kwa retina 
• Matatizo ya ini/hepatitis 
• Anemia 
 
 
DP inawza kusababisha baadhi, yote au isisababishe madhara yaliyotajwa hapa chini.. 
 
Uwezekano mkubwa: 
• Kuumwa na kichwa 
• Joto 
• Kukohoa 
• Homa ya mafua 
• Kuhara 
 
Uwezekano mdogo: 
• Kizunguzungu 
• Kutapika 
• Kichefuchefu 
• Kupoteza hamu ya chakula 
 
HATARI ZINGINE  
Kutokana na kutoa damu kutoka kwa mkono wa mtoto wako au kudunga kidole chake, 
mtoto wako anaweza kuwa na maumivu na/au kuchibuka. Maambukizi, kutoka damu 
kupita kiasi, kugandamana, au kuzirai pia kunawezekana, ijapokuwa kwa ugumu.Ili 
kupunguza uwezekano wa hizi hatari, tutaajiri tu wafanyakazi wa utafiti  waliohitimu na 
vifaa sahihi vya kutoa damu. 
 
Kwa kuongezea, mtoto wako anawezakumbwa na hatari zisizoweza kutabirika na kero 
linalohusishwa na matumizi ya dawa za utafiti. Hizi zinaweza kujumuisha kuongezeka 
kwa uwezekano wa matatizo ya selimundu na anemia ambayo ikiwa mbaya sana, 

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inaweza kusababisha maafa. Unapaswa kuripoti matatizo yoyote anayokuwa nayo kwa 
timu ya utafiti. 
 
KUNA MANUFAA YA KUSHIRIKI KATIKA UTAFITI?  
Ikiwa utaruhusu mtoto wako ashiriki katika utafiti huu, kunaweza kuwa na manufaa ya 
matibabu ya moja kwa moja kwa mtoto wako. Watoto washiriki watapata madawa ya 
bure ya utafiti ya kuzuia malaria na maambukizi ya bakteria, tathmini ya kina kila mwezi, 
kuchunguzwa bure kwa vijidudu vya malaria wanapokuwa na joto na usajili katika bima 
ya kitaifa ya afya ya Kenya. Huduma hizi zina uwezo wa kupunguza matatizo ya kiafya 
yatokayo kwa malaria na SCA.  
 
Katika muda mrefu, tunatumaini kwamba katika siku zijazo habari tuliyojifunza kutoka 
kwa utafiti huu utawafaidi watoto walio na SCA barani Afrika, kwa kupata dawa bora ya 
kuzuia malaria.   
 
NINI MBADALA WA KUSHIRIKI KATIKA UTAFITI HUU?  
Mtoto wako hahitaji kushiriki katika utafiti huu. Hata kama hautamruhusu mtoto wako 
ashiriki, yeye bado anaweza kupokea matibabu ya kawaida kutoka kwa watoa huduma 
ya matibabu wa kawaida. 
 
JE, HABARI YA MTOTO WANGU ITAWEKWA SIRI?  
Mtoto wako hatatambuliwa kwa jina, au mambo mengine yeyote ambayo yanaweza 
kumbainisha katika rekodi za utafiti zitakazoshirikiwa nje ya Hospitali ya Kaunti ya 
Homa Bay. Kwa rekodi zitakozofichuliwa  nje ya Hospitali ya Kaunti ya Homa Bay, 
mtoto wako atapewa nambari ya kificho ya kipekee. Logi au orodha ambayo ni pamoja 
na nambari ya kificho na jina la mtoto wako na/au kitambulisho kingine cha kibinafsi ni 
ya siri na itawekwa salama na timu ya utafiti. 
 
Kila juhudi zitafanywa kudumisha usiri wa rekodi za matibabu za mtoto wako. Hata hivyo, hii 
haiwezi kuwa ya uhakika. Kuna hatari ya uwezekano wa kupotea kwa usiri.Baadhi ya ofisi 
na watu wengine zaidi kuliko watafiti wanaweza kuangalia chati ya matibabu ya mtoto wako 
na rekodi za utafiti.Hawa ni pamoja na watu  kutoka: 
Timu za utafiti katika Chuo Kikuu cha Moi, Chuo Kikuu cha Duke, na Taasisi ya Utafiti wa 
kliniki ya Duke; 
• 
Taasisi ya utafiti na kamati ya maadili ya Chuo Kikuu cha Moi na Bodi ya Taasisi ya 
Kupitia Mfumo wa Afya ya Chuo Kikuu cha Duke;  
• 
Wawakilishi kutoka NIH ya nchi ya Marekani.  
 

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Rekodi za utafiti zitahifadhiwa kwa miaka kumi baada ya kukamilka kwa utafiti kwa 
taratibu za hapa. Habari za utafiti katika rekodi za matibabu za mtoto wako zitawekwa 
milele. 
 
Wakati wa kipindi cha utafiti huu, daktari wako na timu ya utafiti wanaweza shiriki  
habari yako ya utafiti na baadhi ya watu. Hawa ni pamoja na:   
 
• Wachunguzi wa utafiti, ambao huthibitisha usahihi wa taarifa;  
• Watu wenye asili ya matibabu ambao huamua athari za dawa zitakazokuwa kwa 
ugonjwa wa mtoto wako; na/au  
• Watu ambao huweka pamoja taarifa yote ya utafiti katika fomu ya ripoti.  
 
Wakati mtoto wako yuko katika huu utafiti, habari ya utafiti iliyokusanywa juu yake 
inaweza wekwa katika rekodi zake za matibabu. 
 
Una haki ya kuacha kushiriki katika utafiti huu wakati wowote. Kuacha kushiriki, ni 
lazima umjulishe daktari wako wa utafiti kwamba unataka kuacha.Ikiwa unataka mtoto 
wako ashiriki katika utafiti huu, ni lazma utie sahihi hii fomu ya adhini ili kuwapa timu ya 
utafiti ruhusa ya kuanagalia taarifa ya afya ya mtoto wako. Ikiwa utakataa kuturuhusu 
kupitia taarifa ya afya ya mtoto wako, mtoto wako hataweza kuwa katika utafiti. Hata 
hivyo, kutotia sahihi fomu hii hakutakuathiri wewe au mtoto wako kupata huduma ya 
matibabu.  
 
Ilhali taarifa inayotokana na utafiti huu inaweza kuwasilishwa katika mikutano ya 
kisayansi au kuchapishwa katika jarida ya kisayansi, utambulisho wa mtoto wako 
hautafunuliwa na mtoto wako hatatajwa kwa jina. Maelezo ya majaribio haya ya kliniki 
yatapatikana kwa http://www.ClinicalTrials.gov na sajili ya jaribio za kliniki ya Pan Afrika  
(http://www.pactr.org). Mitandao hii haitakuwa pamoja na taarifa inayoweza 
kukutambua wewe.  Kwa ukubwa, mitandao hii itajumuisha mukhtasari wa matokeo.  
 
Rekodi za mtoto wako hazitatumika kwa madhumuni mengine yeyote au kushirikiwa na 
mtu mwingine bila idhini yako.  
 
GHARAMA NI GANI?  
Hakutakuwa na gharama za ziada kwako wewe au mtoto wako kwa sababu ya kuwa 
katika utafiti huu. Taratibu zozote za utafiti, dawa za utafiti, au vipimo vya utafiti 
vitatolewa kwa mtoto wako bila malipo.Kwa kuongezea, ikiwa mtoto wako atashiriki 
katika utafiti, tutamsajili katika Bima ya Kitaifa ya Afya  ya Kenya (NHIF) wakati yeye 
anashiriki katika utafiti. Baadhi ya aina za huduma za matibabu zinaweza kulipwa kwa 
NHIF.  
 
NINI KUHUSU FIDIA?  
Hakutakuwa na fedha au fidia kwa ajili ya mtoto wako kushiriki katika utafiti huu. Hata 
hivyo, utapokea shilingi 500/= kwa ajili ya kukusaidia kwa usafiri wa ziara za ufuatiliaji 
zilizopangwa. Hii huenda isifidie gharama kamili ya usafiri, lakini itasaidia kufanya iwe 
rahisi kushiriki kikamilifu katika utafiti.  

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JE, KAMA MTOTO WANGU AMEJERUHIWA? 
Huduma ya matibabu ya haraka na ya muhimu inapatikana katika Hospitali ya Kaunti ya 
Homa Bay endapo mtoto wako atajeruhiwa kutokana na kushiriki katika huu utafiti. 
Hakuna dhamira kutoka kwa Chuo Kikuu cha Moi, Chuo Kikuu cha Duke kupitia Taasisi 
yake ya Duke ya Utafiti wa kliniki, Hospitali ya Kaunti ya Homa Bay, au NIH 
kukurudishia pesa au kulipa malipo ya gharama ya jeraha lolote linalohusiana na utafiti, 
pesa au huduma ya matibabu ya bure.  
 
Kwa maswali yoyote kuhusu utafiti au kuumia kunakohusiana na utafiti, wasiliana na 
Daktari Njuguna kupitia nambari +254719474231 wakati wa masaa ya kawaida ya kazi 
na nambari +254719474231baada ya masaa ya kazi, wikendi na likizo.  
 
JE, KUHUSU HAKI ZANGU NIKIMKATAZA MTOTO WANGU KUTOSHIRIKI AU 
KUJIONDOA KATIKA UTAFITI?  
Unawezachagua kutomruhusu mtoto wako asiwe katika utafiti. Pia unaweza chagua 
kumruhusu mtoto wako awe katika utafiti na unaweza kumwondoa katika utafiti wakati 
wowote. Kama utamwondoa mtoto wako kutoka kwa utafiti, hakuna habari yoyote mpya 
kuhusu mtoto wako  itakusanywa kwa madhumuni ya utafiti isipokuwa kama mtoto 
wako ana athari inayohusiana na dawa ya utafiti.Ikiwa athari kama hii itatokea, tutahitaji 
kupitia rekodi zote za matibabu za mtoto wako. Taarifa yote iliyokusanywa kwa ajili ya 
utafiti itatumwa kwa mdhamini wa utafiti, ambaye ni NIH ya nchi ya Marekani.  
 
Uamuzi wako kutomruhusu mtoto wako ashiriki au kumwondoa kutoka kwa utafiti 
hakutahusisha adhabu yoyote, ingawa hautapokea tena huduma ya matibabu au faida 
zinazotolewa na utafiti na huduma ya mtoto wako itahamishwa kwa madaktari ambao 
hawashiriki katika utafiti, kama vile daktari wa mtoto wako, hospitali au kliniki. Hii 
haitakuthuru  wewe au mtoto wako kupata huduma ya afya kupitia watoa huduma wa 
afya wako wa kawaida.  
 
KUONDOLEWA KUTOKA KWA UTAFITI BILA HIARI  
Daktari wa utafiti anaweza amua kumwondoa mtoto wako kutoka kwa utafiti ikiwa: 
• Hali ya mtoto wako itakuwa mbaya Zaidi , au  
• Mtoto wako ana athari mbaya sana, au  
• Anahitaji matibabu ambayo hayaruhusiwi katika utafiti, au  
• Daktari wa utafiti akiamua si bora kwa maslahi ya mtoto wako kuendelea katika 
utafiti.  
 
NIH, Daktari Njuguna au madaktari wengine wa utafiti, mashirika ya udhibitishaji  
wanaweza simamisha huu utafiti wakati wowote bila idhini yako. Ikiwa hili litatokea, 
utafahamishwa na daktari wako wa utafiti atakueleza kuhusu chaguo zingine. 
 
IKIWA KUNA HABARI MPYA?  
Utapewa habari yoyote mpya tutakayojifunza wakati wa kipindi cha utafiti ambayo 
inaweza kuathiri wewe iwapo utakubali kuendeleza ushirikishi wa mtoto wako katika 
utafiti.  

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NITAPIGIA NANI SIMU IKIWA NINA MASWALI AU TATIZO?  
Kwa maswali kuhusu utafiti au kuumia kunakohusiana na utafiti au ikiwa una TATIZO, 
wasiwasi au mapendekezo kuhusu utafiti, wasiliana na Daktari Njuguna kwa nambari 
+254719474231wakati wa masaa ya kazi,baada ya masaa ya kazi, na wikendi na likizo. 
Kwa maswali kuhusu haki za mtoto wako kama mshiriki katika utafiti, au kuongea 
kuhusu tatizo, wasiwasi au mapendekezo kuhusiana na utafiti, au kupata taarifa au 
kutoa mchango kuhusu utafiti, wasiliana na Taasisi ya utafiti na kamati ya maadili ya 
Moi (IREC) kwa nambari +2540787723677.  Bodi ya kupitia mifumo ya afya ya Taasisi 
ya Chuo Kikuu cha Duke pia imefanya mapitio ya utafiti huu, ikiwa una maswali yoyote 
ambayo wanachama hao wanaweza kukusaidia tafadhali yaelekeze kwa +1(919) 668-
5111. 
 
TAARIFA YA IDHINI  
Madhumuni ya utafiti huu, taratibu zitakazofuatwa, hatari, manufaa yameelezwa kwa 
mtoto wangu na mimi.Nimeruhusiwa kuuliza maswali, na maswali yangu yamejibiwa 
kwa kuridhika kwangu. Nimeambiwa ni nani wa kuwasiliana naye ikiwa nina maswali, 
kuongea kuhusu tatizo, wasiwasi au mapendekezo kuhusiana na huu utafiti. Nimesoma 
fomu hii ya idhini na kukubali kuwa mtoto wangu awe katika huu utafiti, kwa kuelewa 
kwamba naweza kumwondoa mtoto wangu wakati wowote. Nimeambiwa kwamba 
nitapewa nakala ya fomu hii ya idhini iliyotiwa sahihi na tarehe.  
 
 
___________________________________ 
 
Jina la mzazi au mlezi wa kisheria lililochapishwa  
 
 
____________________________________  
 
 
Sahihi ya mzazi au mlezi wa kisheria  
 
Tarehe                  Wakati: ___: ____ 
 
____________________________________  
 
        Wakati: ___: ____ 
Sahihi ya shahidi (ikiwa inafaa) 
 
 
Tarehe                    
 
 
Nimeeleza kwa kikamilifu huu utafiti kama ulivyofafanuliwa kwa fomu hii. Nimejibu 
maswali ya mzazi/mlezi na nitajibu maswali yoyote ya siku za usoni kadri ya uwezo 
wangu. Nitaiambia familia mabadiliko yoyote katika taratibu au katika uwezekano wa 
madhara/uwezekano wa faida za utafiti zinazoweza kuathiri nia ya  mzazi/mlezi ya 
kutaka mtoto wake aendelee kuwa katika utafiti. 
 
 
 
____________________________________                                     ___________ 
 
Jina lililochapishwa la mtafiti anayepokea ruhusa au idhini ya mzazi. 
 
Tarehe 
 
 
 
 

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____________________________________                                     ___________ 
Sahihi ya mtafiti anayepokea ruhusa au idhini ya mzazi. 
 
 
           
Tarehe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAMPULI ZA DAMU ZITATUMIKA VIPI?  
Wakati wa kipindi cha utafiti huu, kwa zaidi ya miezi 12, damu ya mtoto wako 
itachukuliwa katika kiasi Fulani kilichotajwa hapo juu (katika ziara hii ya kujiunga na 
kisha kila ziara ya kila mwezi kwa miezi 12). Tutakusanya hii damu ili kuipima mara kwa 
mara kufuatilia athari za SCA, malaria na dawa za utafiti.  
 
Aidha, sampuli moja ya damu itakusanywa na kutumika tu kwa ajili ya utafiti wa siku 
zijazo, kama wewe utakubaliana na ombi hili. Sampuli hizi zitahifadhiwa kwa muda 
mrefu katika moja ya vyuo vikuu au mashirika ya utafiti yanayofanya utafiti huu, ikiwa ni 
pamoja na Chuo kikuu cha Moi au Chuo Kikuu cha Duke. Sampuli pia zinaweza 
kushirikiwa na wachunguzi katika taasisi zingine. Matumizi yoyote ya hizi sampuli 
zilizohifadhiwa lazima iidhinishwe na  taasisi ya kupitisha au bodi ya maadili.  
 
Yafuatayo ni mazingatio kadhaa muhimu kwa ajili ya sampuli hizi 
• Tutakusanya na kuhifadhi takriban mililita 2.5 ya damu kwa ajili ya utafiti wa siku 
za usoni wakati wa ziara ambapo tunakusanya damu kwa ajili ya huduma ya 
kawaida  Sampuli hii itatumiwa tu kujifunza malaria, SCA, au magonjwa mengine 
ya kuambukiza katika watoto walio na SCA.  
• Tutahifadhi pia doa la damu katika karatasi maalum kutoka kwa damu 
tuliyochukua kutoka kwako. Baada ya utafiti kukamilika, hii damu itatumiwa 
kupima jeni za vijidudu vya malaria.  
• Taarifa  tutakayoipata kutoka kwa tafiti hizi haitaathiri kuhudumiwa kwa mtoto 
wako.  
• Sampuli hizi hazitauzwa au kutumika kwa uzalishaji wa bidhaa za kibiashara.  
• Tunaweza kufanya utafiti kwa jeni za binadamu au malaria katika sampuli hizi, 
lakini hakuna taarifa itakayowekwa katika rekodi za matibabu za mtoto wako, na 
sampuli zitawekwa kwa kificho ili kwamba hakuna mtu atakayeweza 
kumtambulisha mtoto wako.  
• Hakuna faida ya moja kwa moja kwa mtoto wako ikiwa utaturuhusu kutumia  
sampuli kwa matumizi haya. Hata hivyo, kama zinaweza kutumika kwa utafiti wa 
siku za usoni, tunatumai kwamba zitatusaidia kujifunza jinsi ya kuzuia vyema, 
kutibu, au kutibu matatizo ya kiafya katika watoto walio na SCA.  
 
Kila jitihada zitafanywa kulinda habari yako ya siri, lakini hii haiwezi kuwa na uhakika. 
Habari inayoweza kupatikana kutokana na kushiriki kwako katika utafiti wa siku za usoni 
haitawekwa pamoja na rekodi zako za matibabu. 
 
 
IKIWA NITAKUBALI KUTOA SAMPULI SASA, NAWEZA KUTOA OMBI KWAMBA 
SAMPULI ZANGU ZIHARIBIWE KATIKA TAREHE YA BAADAYE?  

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Ikiwa utaamua baadaye kwamba ungependa sampuli zako ziharibiwe, lazima umuarifu 
Daktari Njuguna au wawakilishi wake katika timu ya utafiti kwamba unaondoa ruhusa 
yako kwamba sampuli zako zihfadhiwe na kutumika kwa utafiti wa siku zijazo 
• Wakati wa utafiti mkuu, tafadhali wasiliana na mratibu wa utafiti Bwana. Joseph 
Kipkoech kwa nambari +254719474231. 
• Baada ya utafiti mkuu, tafadhali wasiliana na Taasisi ya utafiti na kamati ya 
maadili ya Moi kwa nambari +2540787723677. 
Ikiwa taarifa inayounganisha sampuli zako fiche na wewe tayari zimeharibiwa, sampuli 
zako haziwezi tena kuhusishwa nawe na hatutaweza kuzipata kwa ajili ya kuziharibu. 
 
Pia, hata kama sampuli zako zitaharibiwa:  
• Hatuwezi kupata tena sampuli au taarifa ambayo tayari tumeshapatia watafiti.  
• Hauwezi kuondoa sampuli yako ikiwa tayari imeshachambuliwa au kupimwa.  
 
Tafadhali tia sahihi kwenye mstari mmoja wa sahihi hapo chini kama unakubali kuwa 
sampuli zako za damu zihifadhiwe kwa uwezekano wa utafiti wa siku zijazo, au ikiwa 
haukubali sampuli zako za damu zihifadhiwe.  
 
Ninakubali kuruhusu sampuli zangu za damu zihifadhiwe kwa ajili ya uwezekano wa 
utafiti wa siku zijazo wa SCA, malaria na maambukizi mengine katika watoto walio na 
SCA.  
 
 
 
Sahihi ya mzazi au mlezi wa kisheria 
 
 
 
 
Tarehe 
 
 
Sahihi ya shahidi (ikiwa inafaa) 
 
 
 
 
 
Tarehe                   
 
 
 
Mimi sikubali kuruhusu sampuli za damu yangu kuhifadhiwa kwa uwezekano wa utafiti 
wa siku zijazo wa SCA, malaria, na maambukizi mengine katika watoto walio na  SCA.  
 
 
Sahihi ya mzazi au mlezi wa kisheria 
 
 
 
 
Tarehe 
 
 
 
 
 

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APPENDIX H: INFORMED CONSENT (KISWAHILI TO ENGLISH) 
 
Enrollment Consent to Participate in a Research Study 
 
Title of Study: Enhancing Preventive Therapy of Malaria in Children with Sickle Cell 
Anemia in East Africa (EPiTOMISE). 
Researcher: Dr. Festus Njuguna 
 
We are seeking your consent to allow your child to take part in this research because 
your child has Sickle Cell Anemia (SCA). 
 
WHAT DO YOU NEED TO KNOW IN GENERAL ABOUT RESEARCH STUDIES? 
We are seeking your consent to allow your child to take part in a clinical trial research. 
Before you consent to allow your child to participate in this clinical trial research study, it 
is important for you to understand that a research like this includes only those people 
who choose to participate. Your child’s participation is optional. Please read this 
consent form keenly and take your time to make your decision. Your child’s research 
doctor or research assistants will discuss about this consent form with you. Please ask 
about anything or any information that you do not understand well. 
This consent form explains what will happen in this research. The form explains the 
dangers, problems, challenges and any other thing of importance. It is important that 
you ask questions and understand what is needed for your child’s participation in this 
study. We encourage you to discuss with your family and friends before you decide to 
allow your child to take part in this research. You can go home with a copy of this form 
to go through as you decide whether you would like your child to participate in the 
research. If you will agree that your child participates and you sign on this form, you will 
be given a copy of this form that has a signature and date for you to keep. 
 
Please inform the research doctor or research assistants in case your child is 
participating in another research. 
 
WHO WILL BE MY RESEARCH DOCTOR? 
If you agree to participate, Dr. Njuguna will be your doctor for this research and he will 
communicate with your normal health officer at all times that you will be in the study and 
even after, if need be. 
 
The NIH grant will fund this research. Part of Dr. Njuguna’s salary and his research 
team will be paid from this grant. 
 
WHY IS THIS RESEARCH BEING DONE? 
We are seeking your consent for your child to participate in this research because your 
child is between 1 and 10 years of age, has SCA and lives in a malaria endemic area. 
 
We are looking for the best way to prevent malaria in children with SCA. This research 
will help us discover the best drugs that can be used to prevent malaria in children with 
SCA in malaria endemic areas in Africa. 

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Below is a list of drugs included in this study. In this research, your child will take one 
out of the following three types of oral drugs to prevent malaria: 
 
• Proguanil (also known as Paludrine) is the current drug used in Kenya that helps 
to prevent malaria in children with SCA. Your child could already be using this 
drug to prevent malaria. This drug is taken daily. 
 
OR 
• Sulfadoxine/Pyrimethamine-Amodiaquine (SP-AQ) is a combination of drugs that 
constitute sulfadoxine and pyrimethamine that are taken at the same time like 
amodiaquine. These drugs are taken monthly. 
 
OR 
• Dihydroartemisinin-Piperaquine (DP) is a combination of dihydroartemisinin and 
piperaquine.These drugs are taken monthly. 
 
In case your child gets malaria, he/she will be given an oral drug that is called 
Artemether-Lumefantrine (AL). All the children below 5 years of age will also be given 
Penicillin orally every day, whereby it is aimed at preventing bacterial infection and is a 
maintenance dose for children with SCA. 
 
HOW MANY CHILDREN WILL PARTICIPATE IN THIS RESEARCH? 
About 246 children will complete this research. The research will take place in Homa 
Bay county hospital in Homa Bay, Kenya.  
 
WHAT IS ASSOCIATED WITH THIS RESEARCH? 
If you agree that your child takes part in this study, you will be asked to sign on this 
consent form. Your child will go through the following procedures to make sure that 
he/she is suitable for this study: 
 
Examination Visit 
Before enrolling in the research, the research assistants will need to verify if your child 
is suitable to participate. This helps in improving the safety of participating in the study. 
 
During the examination visit, the following procedures will be performed and recorded: 
• We will go through your child’s medical history 
• We will go through the drugs that your child is using 
• We will perform an electrocardiogram (ECG) test, whereby the electrical activity 
in your child’s heart is measured through the skin. 
We will draw approximately 1milliliters (mL) of blood to measure the red blood cells of 
your child to see proteins that cause SCA and perform a blood test to determine if it 
safe to enroll him/her in the research. 
Enrollment visit 
 During the visit for enrollment, the following procedures will be done and the 
information recorded:  

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• We will go through and record your child’s medical history, together with any 
other medical treatment that came up since the previous visit. 
• We will record the drugs that your child is using 
• We will do physical examination which will include height and weight. 
• We will collect a blood sample from a finger prick less than 1/2ml 
• If necessary, we will administer to your child a Meningococcal vaccine.  This 
vaccine will help protect your child against bacteria that causes meningitis. This 
may not be necessary if your child has already received this vaccine, which is 
routinely recommended in Kenya. 
• We will give you a supply of penicillin for 30 days (if your child is below 5 years of 
age) which is a drug used to prevent bacterial infection in children with SCA. 
• We will register your child with the National Health Insurance Fund (NHIF) 
• We will give you drugs for research that will prevent your child from getting 
malaria and instructions on how to take the drugs. 
 
In this enrolment process also, we will decide on which drugs your child will receive that 
prevents malaria. To do so, your child, without any order (like getting a number), will 
receive either Proguanil every day, SP-AQ every month, or DP every month. Your child 
has a chance of 1 out of 3 of getting a particular research drug. 
 
Whichever drug that your child will receive through this procedure will be the preventive 
drug for malaria that your child will receive all through the study. All the children will 
receive a particular type of drug that prevents malaria. 
 
Follow up visits (monthly) 
In every monthly visit, the following procedures will be done: 
• We will go through your child’s medical history, together with the outcomes of the 
previous visit  
• We will do physical examination including height and weight 
• We will draw a sample of blood less than ½ mL from a finger prick. which will be 
tested for anaemia level and malaria parasites in your child 
•  If your child has fever or has had a fever within the past 24 hours, he/she will 
immediately undergo a test for malaria parasites; if your child has not had a 
fever, then the blood will be preserved for testing at the end of the study. 
• Every three months, we will draw approximately 2 ½ ml of blood for frequent/ 
regular testing. 
• On the 6th month and the 12th month which will be the last, we will collect blood 
samples of 1 ml to check for red blood cells that are sickled. 
• If you sign a separate form to consent for additional blood collections for the 
visits after 3,6,9 or 12 months, we will collect additional 2 ½ml of blood for future 
research studies. 
• If need be, we will do an ECG*. 
• We will give you study drugs and prescriptions on how to take them; 
• We will give you a 30-day supply of penicillin to be taken daily (if below the age 
of 5) 

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*Approximately 20 children will be asked to return to the clinic two days later so as to 
repeat the ECG test every month during the study; this will be a follow up of ECG 
results as a sustainable basis through the whole period. This will only be among the 
children in the DP group of study.                                                 
 
If your child will have a blood test for malaria and it turns out positive, he/she will be 
treated at that moment with AL. 
 
Emergency Visit (If needed) 
In this research, if your child is at home and has a fever either because he/she feels it or 
the temperature reading is above 37.5 degrees Celsius, we kindly request you to call 
the research workers so that they can arrange for the child to be seen by one of the 
doctors. In this process, the following will be done: 
 
• We will go through your child’s medical history including all the results from the 
previous visit. 
• We will do physical examination including height and weight. 
• We will draw a sample of blood less than ½ Ml from a finger prick. If your child 
has fever or has had a fever within the past 24 hours, he/she will immediately 
undergo a test for malaria parasites; if your child has not had a fever, then the 
blood will be preserved for testing at the end of the study. 
 
If your child will have a blood test for malaria and it turns out positive, he/she will be 
treated at that moment with AL. 
 
HOW LONG WILL MY CHILD BE IN THE STUDY? 
It is expected that the period of participation in the study will be every month for 12 
months. Your child’s participation in the study will end at the last visit at 12 months. 
 
You can choose to stop participation at any point without any penalty. In that state, you 
will not be able to receive any health services or benefits provided by the study and the 
services given to your child will be handed over to other doctors who are not in the 
study like your child’s doctor, hospital or clinic. Even so, we encourage you to speak 
with your doctor first if you decide to stop participation in the study. 
 
WHAT ARE THE RISKS IN THE STUDY? 
Your participation in the study exposes your child to the following risks. If you choose to 
participate, you are required to discuss these with the study doctor as well as your 
normal health officer. 
 
It is possible for any drug to cause unwanted side effects. You are required to know 
about the effects that can arise from this research before you decide if your child will 
take part. There ca be risks, disruption, drug interactions or other effects that are not 
known. These risks can be as a result of worsening of the complications of sicke cell 
anaemia. If these complications are worse they can cause death. 

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Proguanil can cause some, all or none of the effects listed below. 
 
Most likely: 
 
• Nausea  
 
Anemia 
• Vomiting  
 
Allergic reactions 
• Stomach ache   
Depression 
• Abnormal dreams 
 
Coughing 
• Headache 
 
 
Lack of sleep  
 
 
• Diarrhea  
 
Rashes 
• Weakness 
 
 
Fever 
• Loss of appetite  
Dizziness 
• Skin itching 
Less likely: 
 
• Being scared 
• Fast, hard or unusual heartbeat 
• Mouth sores 
• Hair loss 
• Severe rash 
 
SP-AQ can cause some, all or none of the effects listed below: 
 
Most likely: 
• Headache  
 
Coughing 
• Vomiting  
 
Nausea 
• Loss of appetite  
Stomachache 
• Diarrhea  
 
Weakness 
• Fever 
 
 
Fatigue 
• Difficulty in sleeping 
Rash 
• Feeling sleepy  
Scratching/Itching 
 
Less likely 
• Eye problems/retinopathy 
• Hepatitis 
• Anaemia 
 
 
DP can cause some, all or none of the effects listed below 
 
Most likely: 
• Headache 
• Fever 
• Coughing 

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• Flu 
• Diarrhea 
 
Less likely: 
• Dizziness 
• Vomiting 
• Nausea 
• Lack of appetite 
 
OTHER RISKS 
Your child can feel pain and/ or discomfort during the process of finger prick or drawing 
blood. Infection, abnormal bleeding, freeze-up and fainting can hardly occur. In order to 
reduce these risks, we will employ research workers who are qualified and know how to 
draw blood correctly. 
 
In addition, your child can have unpredictable side effects and problems related to the 
use of the research drugs. These can combine with possible increase in the 
complications of sicke cell anaemia which if more serious can be fatal. You should 
report any problems you may have to the study team. 
 
ARE THERE ANY BENEFITS IN PARTICIPATION IN THE RESEARCH? 
If you will allow your child to participate in this research, there can be direct benefits of 
treatment to your child. The participating children will get study drugs for free that will 
prevent malaria and bacterial infection, monthly comprehensive evaluation, free malaria 
test whenever they have fever and registration to NHIF. These services are able to 
reduce health problems resulting from malaria and SCA. 
 
In the end, we are hopeful that the lessons we learnt from this study will benefit children 
with SCA in Africa by getting the best drugs that prevent malaria. 
 
BY CHOSING NOT TO PARTICIPATE, WHAT IS THE OTHER ALTERNATIVE? 
It is not necessary that your child take part in this study. Even if you do not allow 
him/her to participate, your child will still get the normal medical care from the 
healthcare workers. 
 
WILL MY CHILD’S INFORMATION BE KEPT CONFIDENTIALLY? 
Your child will not be identified by name or by any other way that will reveal him/her in 
the study records that will be used outside of Homa Bay county hospital. Your child will 
be given a code for all records that will be outside of Homa Bay county hospital. The list 
that includes the code and your child’s name and/or any other personal identity is a 
secret and will be kept safe by the study team. 
 
We will put all effort to maintain confidentiality of your child’s medical records. However, 
this cannot be guaranteed. There is a risk of breach of confidentiality. People in other 
offices other than the study team can look at your child’s medical charts and study 

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records. These includes; research teams from Moi University, Duke University and 
Duke Medical Research Institute 
 
• Moi University – Institutional Review and Ethics Committee and Duke 
University’s Institutional Review Board. 
• Representatives from NIH in USA 
 
Study records will be kept for 10 years after completion of the study as per the 
procedure here. Your child’s research information in the medical records will be kept 
forever. 
 
During the period of this study, your doctor and the research team can share your 
research information with other people including: 
 
• Research investigators who confirm the accuracy of the information 
• Individuals with medical backgrounds who know the effect that the drugs have 
on your child’s disease; and/or 
• People who put together all the research information in the report form. 
 
At the time that your child will be in this study, any research information relating to 
him/her can be put in his/her medical records. 
 
You have the right to stop participation in this research at any point. You must inform 
your research doctor when you want to withdraw from the study. If you want your child 
to take part in this study, you must sign on this consent form to allow the research team 
to look at your child’s information. If you will not allow us to go through your child’s 
health information, then your child will not be in the study. However, your not signing on 
the form will not prevent you or your child from getting health services. 
 
While the information resulting from this study can be presented in scientific 
conferences or published in scientific journals, your child’s identity will not be revealed 
and will not be mentioned by name. Explanations of these clinical trials will be found in 
http://www.ClinicalTrials.gov and registers of clinical trials of Pan Africa 
(http://www.pactr.org). These websites will not have information that can identify you. In 
general, these websites will include summary of findings. 
 
Your child’s records will not be used for other purposes or shared with any other person 
without your consent. 
 
WHAT IS THE COST? 
There will be no additional costs on you or your child because of being in this research. 
Any study procedure, study drugs or tests will be provided to your child at no charge. In 
addition, if your child will participate in this research, we will enroll him/her to NHIF 
during the period that the child will be in the study. Some of the health services can be 
paid through NHIF. 
 

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WHAT ABOUT COMPENSATION? 
There will be no funds or compensation for your child’s participation in this study. 
However, you will receive Ksh. 500 to help you travel for follow-up visits as planned. 
This may not completely compensate for your travel cost, but it will help to make it 
easier for you to participate in the study. 
 
WHAT IF MY CHILD HAS BEEN INJURED? 
Health emergency services are available at Homa Bay county hospital whenever your 
child is injured while participating in this research. There is no commitment from Moi 
University, Duke University through its medical research institute, Homa Bay county 
hospital or NIH to give you back money or pay for any injury costs related to the study 
or to give you free treatment. 
 
For any questions about the study or injury related to the study, get in touch with Dr. 
Njuguna through this number +254719474231 at normal working hours and this number 
+254719474231 after working hours, on weekends or public holidays. 
 
WHAT ABOUT MY RIGHTS WHEN I DO NOT ALLOW MY CHILD TO PARTICIPATE 
OR WITHDRAW FROM THE STUDY? 
You can decide not to allow your child to participate in the research. You can also allow 
your child to be in the study and you can remove him/her from the study at any time. If 
you will remove your child from the study, there will be no more collection of new 
information about your child for purposes of the study unless if your child has side 
effects related to the study drugs. If such effects come up, we will need to go through all 
of your child’s medical records. All information collected for this study will be sent to the 
funding agency that is NIH in the USA. 
 
Your decision not to allow your child to participate or withdrawal from the research will 
not result in any punishment although you will no longer receive medical services or 
benefits given by the study. Services to your child will be transferred to other doctors 
who are not in the study like your child’s doctor in the hospital or clinic. This will not 
affect you or your child from getting health services from your normal health service 
provider. 
 
REMOVAL FROM THE STUDY INVOLUNTARILY  
The research doctor can decide to remove your child from the study if: 
• Your child’s condition will be worse, or 
• Your child has very bad side effects, or 
• Requires treatment that is not allowed in the study, or 
• If the study doctor decides that it is not in your child’s best interest to continue in 
the study 
 
NIH, Dr. Njuguna or any other study doctors and regulatory agencies are able to stop 
this research at any time without your consent. If this happens, your study doctor will 
inform you and he will explain to you about other options.  
 

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WHAT IF THERE IS NEW INFORMATION? 
You will be informed of any new thing that we will learn during the period of study that 
can affect you in case you will agree that your child continues participation in the study. 
 
WHO CAN I CALL WHEN I HAVE A QUESTION OR PROBLEM? 
For questions about the research or injury related to the study or if you have a problem, 
worries or recommendations about the research, get in touch with Dr. Njuguna on this 
number +254719474231 during working hours, after working hours, on weekends and 
public holidays. For questions about your child’s rights as a participant in the study, or to 
talk about any problems, worries or recommendations about the research, get in touch 
with Moi’s Institutional Review and Ethics Committee (IREC) on this number: 
+254787723677. Duke University’s Institutional Review Board of health systems has 
also done a review for this study and if you have any questions that the members can 
help you with, please direct them to +19196685111. 
 
STATEMENT OF CONSENT 
The purpose of this research, procedures to be followed, risks and benefits have been 
explained to my child and I have been allowed to ask questions, and the questions have 
been answered to my satisfaction. I have been told whom to communicate with if I have 
questions, problems to discuss, worries and recommendations related to this study. I 
have read this consent form and agreed that my child be in this research, with the 
understanding that I can remove my child at any time. I have been told that I will be 
given a copy of this consent form that has a signature and date. 
 
 
___________________________________ 
 
Name of parent or legal guardian 
 
____________________________________  
 
 
___:___ 
Signature of parent or legal guardian 
 
Date  
 
Time 
 
____________________________________   ______________________________ 
Signature of Witness (if applicable) 
 
Date  
 
Time 
 
I have explained this study in detail as outlined on this form. I have answered the 
questions from the parent/guardian and I will answer any future questions to my best. I 
will tell the family about any changes to the procedures or potential hazards/benefits of 
the study that can affect the interest of the parent/guardian to want to have the child 
continue with the study. 
 
____________________________________                                     ___________ 
 
Name of the researcher receiving permission or approval from the parent  
Date 
 
 
 
 
____________________________________                                     ___________ 

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Signature of the researcher receiving permission or approval from the parent  
Date 
 
 
 
 
 
 
 
 
HOW WILL THE BLOOD SAMPLES BE USED? 
During this study period of over 12 months, your child’s blood will be taken in quantities 
as mentioned above (in the enrollment visit and thereafter monthly for 12 months). We 
will collect this blood so as to test regularly to check on the effects of SCA, malaria and 
the study drugs. 
 
If you will agree, one blood sample may be collected and used by the study at a later 
date. These samples will be stored for a long period of time in one of the universities or 
institutions of research conducting this study, including Moi University and Duke 
University. The samples can also be used by researchers from other institutions. Any 
use of these preserved samples must be authorized by the institutional review board. 
 
The following are some important factors about these samples: 
 
• We will collect and preserve approximately 2.5ml of blood for future research use 
during the visits which we will collect blood for routine care.. This sample will only 
be used to learn about malaria, SCA, or any other infectious diseases in children 
with SCA. 
• We will also preserve a drop of blood on a special paper from the sample of 
blood we took from you. This blood will be used to test microbial genes of malaria 
after the research is finished. 
• The findings from this study will not affect the services given to your child. 
• These samples will not be sold or used for production of goods for business. 
• We can use this samples to do research on human genes or malaria, but no 
report will be put in your child’s record, and the samples will be coded so that no 
one can identify your child.  
• There will be no direct benefits to your child if you will allow us to use the 
samples for this purpose. However, if they can be used in future research, we 
hope that they will help us learn how to properly prevent, treat and manage 
health problems related to children with SCA. 
 
All effort will be put to protect your confidential information, but this cannot be 
guaranteed. Any information related to your future participation in the research will not 
be put together with your medical records. 
 
IF I AGREE TO GIVE MY SAMPLE NOW, CAN I REQUEST THAT MY SAMPLE BE 
DESTROYED AT A LATER DATE? 
If you decide later that you want your sample to be destroyed, you must inform Dr. 
Njuguna or his representatives in the study team that you are withdrawing and that your 
sample will not be preserved and used by the study in future. 
• At the time of the main study, please communicate with the study coordinator Mr. 
Joseph Kipkoech on this number - +254719474231. 

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• After the main study, please communicate with the Moi Institute of Research and 
Ethics Committee on this number - +2540787723677. 
 
If the report linking your coded sample to you has been destroyed, then the sample 
cannot be linked to you and we cannot find them since they are destroyed. 
 
Also, even if your samples will be destroyed:  
 
• You cannot get the sample or report that we have already given to the 
researchers/investigators. 
 
• You cannot remove your sample if it has already been analyzed or tested. 
 
Please sign on one line below if you agree to give your sample of blood to be preserved 
for future use by the study, or if you disagree. 
 
I agree to give my blood sample to be preserved for future study testing for SCA, 
malaria and any other infection in children with SCA.  
 
 
Signature of parent or legally authorized representative 
 
Date 
 
 
Signature of Witness (if applicable) 
 
 
 
 
Date  
 
 
 
 
I do not agree to give my blood sample to be preserved for future study testing for SCA, 
malaria and any other infection in children with SCA 
 
 
 
Signature of parent or legally authorized representative 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX J: INFORMED CONSENT (DHOLUO) 
Wi Nonro: Choro nyime chenro mar geng’o malaria e nyithindo mankod tuo mar remo ei 
Afrika mamilambo.  
 
Janonro: Daktari Festus Njuguna   
 
Ikwayi mondo iyie ni nyathini obed enonroni nikech nyathini nigi tuo mar remo. 
 
GIN GIGO MAGE MOROMO ING’E ENONRO? 
Ikwayi mondo miiyie ne nyathini obedie enonro mar thieth. Kapok iyie mimondo nyathini 
obed enonro mar thieth ni, ber mondo mi ing’e ni nonro kaka magi dwaro mana jogo 
moyiero bedo eachiel. Bedo mar nyathini en mana kachiuruok. Koyie some otasni 
eyomakare to ikau thuoloni mar yiero pachi. Daktach nyathini mar nonro kata jalo 
matimone nonro bowuoyo ewi otasni kachiel kodi. Koyie penje ewi wach moramora ma 
okiwinj maler. 
Otasni nyiso matut gimabiro timore enonroni. Otasni nyiso matut ewi ahinye, gigo 
mamiyi pek, winjo marach, kod weche moko mapek. Ber mondo mi ipenj penjo kendo 
iwinj makare gigo maidwaro enonroni. Wajiwi mondo mi ilos gi anyuolani kata gi 
osiepeni kapok iyie mimondo nyathini odonj enonroni. Inyalotero otas achiel mar wachni 
edala kapodi iparo kabe nyathini onego donj enonroni. Kaponiyie mimondo nyathini oyie 
odonj enonroni to ogoyo seyi eotasni, ibomiyi otas mar wachni mogoye seyi kachielgi 
tarik mimondo ikan. 
Koyie nyis dactari mar nonro kata ng’at matimo nonro kopo ni nyathini nitiere enonro 
machielo. 
 
NG’ANO MABOBEDO DAKTARINA MAR NONRO? 
Kapo ni iyie donjo e nonro, daktari Njuguna bobedo daktachi enonro to obobedo koloso 
gi jalno marango ngimani endalo duto ma ibobedo enonro to kata bang’e kapo ni 
idwaro. 
Chiwo kowuok kar puonjre mar United States National Institute of Health (NIH) bo 
chung’ne nonroni. Kanmoro mar daktari Njuguna kod joge mag timo nonroni pesagi 
ibiro chul kod chiwoni. 
 
ANG’O MOMIYO ITIMO NONRONI? 
Ikwayi ni mimondo iyie nyathini odonj enonroni nikech en ekind higni mar 1 kod 10, en 
kod tuo mar remo, to odak e aluora ma malaria ng’enye. 
Wadwayudo yore mabeyo mag geng’o malaria kuom nyithindo mankod tuo mar remo. 
Nonroni bomiyo wang’e kit thieth maber ma inyalo tikodo egeng’o malaria kuom 
nyithindo mangi tuo mar remo ekuonde mag Afrika man kod malaria.   
Enonroni wadhi pimo kind yiedhi adek mag malaria mabede yudore e ute yiedhe mi 
mondo wane ni thieth mane kaponi nitie moramora ber eduoko chien kuan mar ndalo 
ma nyathini bedo gi malaria. 
Thieth mag nonro manitie e nonroni gin mochiu piny gi. Enonroni nyathini birokawo 
thieth achiel kuom thieth adekgi kod dhoge kaka yoo mar geng’o malaria: 

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• Proguanil (mabende ong’e kaka Paludrine) enie sani rang’iny mamalo mar 
geng’o tuo mar malaria e nyithindo mankod tuo mar remo ei Kenya. Sechemoko 
nyathini osegabet nimuonyo yadhni mimondo ogeng’ malaria. Yadhni imuonyo 
pile. 
KATA 
• Sulfadoxine/Pyrimethamine-Amodiaquine (SP-AQ) en riuruok mar yiedhe 
moting’o sulfadoxine kod pyrimethamine mimuonyo karachiel kaka amodiaquine. 
Yadhni imuonyo edwe. 
KATA 
• Dihydroartemisinin-Piperaquine (DP) enriuruok mar yiedhi mar 
dihydroartemisinin kod piperaquine. Yadhni imuonyo edwe. 
 
Kamedo, kapo ni nyathini oyudo malaria, ibiro thiedhe gi dhoge gi yath ma iluongo ni 
Artemether-Lumefantrine (AL). Nyithindo duto man piny mar higni 5 bende boyudo 
penicillin pile ka pile eyor dhok ma idwaro ni ogeng’ landruok mar bakteria to enyie 
rang’iny mamalo kuom nyithindo mankod tuo mar remo. 
 
NYITHINDO ADI MABOBEDO ETIMO NONRONI? 
Maromo nyithindo 246 botieko nonroni. Nonroni ibirotimo e osubtal mar County ma 
Homabay ei Homabay, Kenya. 
 
ANG’O MA IDWARO ETIMO NONRONI? 
Kaiyie mimondo nyathini odonj enonroni, ibokwayi mimondo igoseyi e otasni. Nyathini 
bokalo e okengegi mimondo onyis ni nyathini oromo enonroni. 
 
Pimo elimbe 
Kapok idonjo enonro, janonro nyaka ng’e kapo ni nyathini owinjore donji. Maye konyo e 
okang’ mar donjo enonroni. 
Epimo mar limbe, okangegi ibiroluwo to kendo ndiko piny gigo duoko mabiro yudore: 
• Wabiro nuoyo rang’o chal mar ngima nyathini 
• Wabiro nuoyo rang’o yiedhi ma nyathini tiyogo 
• Wabotimo electrocardiogram ma gocho mar dhochuny nyathini ipimo edende gi 
rapim 
• 
Wabokawo maromo milliliter3.5 mar remb nyathini mimondo wapim bath remo 
malosore ei odhundo makowo muya kendo golo muya maricho mare nikech 
proteins makelo tuo mar remo Kendo timo pim ma kinde ka kinde mar remo 
mondo one kowinjore donjo e nonro 
 
Donjo ni mokuong’o 
E seche mar ndiko jii ma okwongo’, yore ma chalo kame ibiro luu bange kae to bange’ 
weche ibiro maki: 
• Wabiro ng’iyo kod ndiko piny duoko mar nyathini kaka osebet e hospital, nyaka 
duoko ma osebedo ka timre chakre biro ne mokuongo. 
• Wabiro ndiko yedhe ma nyathini osetiyo go. 
• Wabotimo nono del mar del, ka achiel gi bor ne gi pek ne. 
• Wabirokao remo koae lith lwet nyathi maok rom ½ ml. 

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• Ka nyalore, wabomiyo nyathini chanjo mar Meningococcal. Chanjoni bokonyo 
nyathini mondo kik yud bakteria makelo meningitis. Mae ok ochuno ka bed ni 
nyathini oseyudo chanjoni, ma owach e Kenya.  
• Wabiro miyo u penicillin kuom odiechienge’ piero adek (ka nyathini pok ochopo 
higni abich), ma en chendro mar thieth ma itiyo go mondo ogeng’ bacterial 
infections kuom nyithindo man tiere gi tuo mar remo. 
• Wabondiko nyithindu e Kenyan National Insurance Fund  
             (NHIF); 
• Wabiro miyo u kaka nyathini inyalo kingo kod kaka inyalo kawe. 
 
Kod chendro mar limbe ni, wanong’eyo ni en nonro mane mar malaria ma nyathini biro 
yudo. To mondo mano timre, nyathini ibiro mana mi (kwanyo nembni) modo giyud 
Proguani pile, SP-AQ e due, kata DP e due. Nyathini ni gi atamalo mar achiel kuom 
adek mar yudo yath ma ochan. Yath moro amora ma nyathini onego oyud e nondro ni 
biro bedo mar kingo malaria ma giyudo e nondro no. Nyithindo tee boyudo aina moro 
magengo malaria biro yudo yath machalre. 
 
Limbe ma iluo (e due) 
E limbe mar due ka due, magi e gik ma ibiro luu: 
• Wabiro nono chal mar nyathini mar hospital, ka achiel gi weche mek thieth ka 
lure gi limbe ge ma ogik. 
• Wabotimo penj, ka achiel gi  pek mare gi bor ne. 
• Wabiro kao remo ka ochuo lwete ma ok kal ½ ml maa ibiro tiyo go epimo romb 
rumo  remo kod kute makelo malaria  
• Ka nyathini ni gi liet, kata ka osebet gi liet ma okchop seche 24, obobedo gi pim 
mar malaria sano sano; ka nyathini pok ne dende ochwakre ga, koro rembe ibiro 
kan mar pim ka nondro orumo.Bang thuolo mar duech a dek ka dueche adek, 
wabiro kao gimoro 2 ½ ml mar remo mar pim. 
• Ka ochopo due mar auchiel e limbe kod due mae apar gi ariyo, wabiro kao remo 
moro ma 1 ml ma ibiro pim ne tuo mar remo. 
• Ka iketo sei e oboke mar yie machielo kendo, ka iyie ni remo inyalo kaw kendo e 
limbe dweye mar 3, 6, 9, kata 12 wabro kao kendo 2 1/2 ml mar remo ne nonro 
ma biro mbele 
• Ka ochuno,wabiro timo ECG. 
• Wabiro miyo u nondro mar thieth kod kaka itiyo kode. 
• Kuom odiechieng’e piero adek, wabiro miyo u penicillin pile (ka pok ochopo higni 
abich) 
 
Nyithindo maromo 20 ibokwa mondo odok e klinik band odiechienge ariyo mondo onuo 
ECG ma itimo due ka due seche mar nondro; mae ibiro tim mondo oyud duoko mar 
ECG mar chendro ma dhi mbele kuom seche go tee. Mae bobedo mana kuom nyithindo 
ma oyier kod DP mar nondro. 
Ka nyathini oyud ni nitiere gi malaria bang’ pim, ibiro thiedhe seche mar AL. 
 
 
 

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Limbe ma opoya (Kaka dwarre) 
Ka lure gi nonro, ka nyathini mantie ot dende ochwakre, nyalo bedo ni giwinjo liet kata 
nyalo nikech liet mar del osepim ma okalo 37.5, wakwayo ni ugochne jatend nonro 
mondo opang kaka inyalo kony gi jik ma timo nonro. E limbe ni, gik ma chalo kamae 
ibiro luu: 
• Wabiro nono chal mar nyathini mar hospital, ka achiel gi weche mek thieth ka 
lure gi limbe ge ma ogik. 
• Wabotimo penj, ka achiel gi  pek mare gi bor ne. 
• Wabiro kao remo ka ochuo lwete ma ok kal ½ ml.  
• Ka nyathini ni gi liet, kata ka osebet gi liet ma okchop seche 24, obobedo gi pim 
mar malaria sano sano; ka nyathini pok ne dende ochwakre ga, koro rembe ibiro 
kan mar pim ka nondro orumo. 
Ka remb nyathini oyud ni ni gi malaria, ibiro thiedhe e saa ma AL. 
 
Nyathina biro kao seche adi e nonro? 
Onego bed ni okao seche ma room dueche apar gi ariyo to itime due ka due. Nonro mar 
nyathini biro rumo bang’ due mar apar gi ariyo bang’ limbe. 
 
Inyalo yiero weyo bedo e nonro saa moro amora maong’e saa ma ibong’adi. Kuom 
mano, okibochak iyud thieth moro amora kata ber ma nonro chiwo, to nyathini be ibiro 
ter laktar ma ok oriwre gi nonro, kaka laktar mar nyithindo matindo, osipital kata klinik. 
To be kata ka iseyiero ni okidwa riwri e nonro ni, wanyalo nyisi ni ikuong’ iwuo gi laktar 
mari mondi. 
 
Ang’o ma en ahinye  mar nonro? 
Ka lure kod kaka isebedo kanyakla e nonro ni, nyathini  yalo bedo gi gik ma nyalo wuok 
bange’. Ka iyiero ni idwaro riwri, onego obed ni iwacho weche gi  laktar kod nga’t ma 
ngiyo ga chalni ma konyi ga. 
 
Nyalre ni mondo omi yath moro amora nyalo bedo gi gima wuok bange. Onego bed ni 
ingeyo gik manyalo wuok mayalo biro e nonro ni ka pok iyie ka nyathini nyalo riwre. Gik 
machalo kaka ahinye, winjo marach, yedhe ma okwinyre gi del, kata gik moko mayalo 
wuoke ma kiaree. Andong’egi nyalo riwo koda ka medruok marach moloyo mar midekre 
motudre gi tuo mar remo. Midekre marach gi ka rach moloyo to, ngima nyalo lal. 
 
Proguanil nyalo omo moko, magi tee kata oknyal omo gik ma nyalo wuok ma ondk piny 
kae. 
 
Machalo kama: 
• Chuny ma wire          
nyamuoda 
• Ng’ok                                             
• Ich kach 
 
• Lek ma ok beyo 
ahonda 
• Wich bar                  Puodruok 
• Diep                         Pudhno 

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• Yom                         Del moolre 
• Ketho dhok              Wich marundre 
• Guon ruok 
 
Ma ok nyal timo ahinya 
• Buogrok 
• Piyo, matek, kata adundo magocho mok kare 
• Adhola mar dhok 
• Wich ma lal 
• Pudno marach 
 
SP-AQ nalo kelo gikmoko, tee kata mok achel ma kelo chanroke mo ket pin gi.       
• Ma nyalo bedo ahinya: 
• Wich bar                       
Ahonda 
• Ng’ok                            
Chuny ma wire 
• Dhok marach  
 
            Ich kach 
• Diep                                       Yom yom   
• Del maolre                             Olo 
• Chandruok e nido                  Del ma pudno 
• Tho nido                                 Ilo 
        
Ma ok nyal timo ahinya 
• Chandok mar wang/tuo wang 
• Chandork mar chuny/ tuo chuny 
• .Rumo mar remo 
 
DP nyalo kelo moko, tee kata tee kata mok achel ma kelo chanroke mo ket pin gi. 
 
Ma nyalo bedo ahinya:  
• Wich bar 
• Del maorle 
• Ahoda 
• Yamo 
• Diep 
 
Ma konyalo bedo ahinya:  
• Wich ma luore 
• Ngok 
• Chuny ma wire 
• Dhok ma kethre 
 
AHINYE MOKO: 
 
Kak duoko mar golo remo kuom lut nyathini kata chonyolich, mar nyathini nyalo yudo  
okobibedo gi kue matin kata kol matin. Yamo, golo remo magen, poto mar lemo kata 

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podho be nyalore, kata gik mok nyare. Duok piny nyalo mar yudo gik ma hinyo, wa  diko 
mana gi mo puojire gi golo remo makare.   
 
Ewi mano, yathini nyalo bedo gi ahinye kod gik ma ok winjre ma oluwore gi tiyo gi 
yedhe mag nonro ma nyalo ting’o medruok marach mar midekre e tuo mar remo, ma 
karach, ngima nyalo lal. Onego iwach chandruok moramora ma ingo ne jotim nonro. 
 
BE NITIERE BER E BEDO KAKA JA TIM NONRO? 
Ka iyie mar weyo nyathini mondo obed e nonro ni, Nyathini nyalo yudo ber mar thieth, 
Nyithindo ma odonjo e nonro biro yudo thieth ma nono mondo ogeng’ malaria kod kute 
ma makelo tuo, rengo matut mar dwe ka dwe, pim ma nono mar kute mag malaria ka 
gin gi liet mar del kendo donjo e Kenyan National Hospital Insurance Fund. Kony gi nigi 
nyalo mar duoko chien chandruok mag thieth ka oa kuom malaria kod SCA. 
 
kuom ndalo mang’eny, wageno ni ndalo mabiro weche ma ji opuonjore kuom nonro ni 
biro konyo nyithindo ma nie Africa gi SCA ka iyudo thieth ma ber mar geng’o malaria.  
 
YORE MAGE MAMOKO MA NITIERE KA MAR BEDO E NONRO NI? 
Ok ochuno ni nyathini nyaka bed e nonro ni. Kata ka ok iyie ne nyathini mondo otime, 
pod onyalo yudo thieth ma kinde ka kinde ka owuok kuom jo chiw thieth ma kinde ka 
kinde.  
 
BE WECHE NYATHINA IBIRO KAN E YO MA OPANDI? 
Nyathini ok bi hul gi nyinge kata wach moramora ma biro chome e andike mag nonro 
ma ioro ne joma ni oko mar kar thieth mar Homa Bay County. Ne andike ma wuok oko 
mar kar thieth mar homa Bay county, nyathini ibiro mi namba ma opondo. Otas ma 
oting’o nembni ma opondo kod nying nyathini gi/kata weche mamoko ma wuoyo kuome 
opandi kendo ibiro kan kama irito gi oganda ma timo nonro. 
 
Teko duto te ibiro ti godo mondo ondike mag nyathini mag thieth osik e yo ma opondo. 
Kata kamano, ma ok nyal yie. Nitiere ahinya mar fwenyruok mag weche ma opandi gi 
nyalore. Ofise moko gi jok mamoko ma opogore gi jo nonro nyalo neon goro mag thieth 
mag nyathini kod andike mag nonro. Ma oting’o ji ma wuok: 
 
• Jo nonro man e mbalariany mar moi, mbalariany mar Duke, kod  kar nonro mar 
thieth mar Duke; 
• Kar nonro mar mbalariany mar Moi kod Ethics Committee and the Duke 
University Health System Institutional Review Board; 
• Jok ma ochung’ ne NIH  ma wuok e piny amerika.Representatives. 
 
Andike mag nonro biro ibiro kan mar higni apar bang’ nonro kaluwore gi chike ma piny. 
Weche mag nonro ma ni e andike mag thieth mag nyathini ibiro kan nyaka chieng. 
 
E saa ma nonro ni dhi mbele, ja thieth mari kod jo tim nonro nyalo ng’iyo weche mag 
nonro kanyakla gi jok mamoko. Ma nyalo riwo: 
• Jok marango research, marango adieri mar wach; 

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• Jok man gi weche manyiso chakruok mag thieth ma hulo chandruok ma yedhe 
kelo kuom tuo mar nyathini kod/kata. 
• Jok maketo wech te mag nonro kanyakla e yor andike. 
E saa ma nyathini ni e nonro ni, weche mag nonro ma okaw kuome inyalo ndiki e 
andike mare mar thieth. 
 
In gi ratiro mar weyo bedo e nonro ni samoramora. Mar mondo iwe, onego inyis ja thieth 
mari mar nonro ni idwa weyo. Ka idwaro mondo nyathini odonji e nonro ni, nyaka igo sei 
e andike ni manyiso ni iyiene mar mondo mi jo kanyakla ma timo nonro thuolo mar 
ng’iyo ngima nyathini korka thieth mare. Ka itamori yienwa mondo wang’i ma tut weche 
mag ngima nyathini korka thieth to nyathini ok binyalo bedo e nonro.Kata kamano weyo 
mar goyo sei e andikeni ok bi chandi kata nyathini e yudo kony mar thieth. 
 
E saa ma duoko ma oa kuom nonro inyalo ter e nyim bura matimo nonro kata ondiki e 
oboke mag jo nonro, gima wuoyo kuom nyathini ok bi nyisi kendo Nyathini ok bi luong gi 
nyinge. Weche ma wuoyo kuom thieth biro yudore e http://www.ClinicalTrial.gov kod pan 
african clinical trials registry (http://www.pactr.org). Mbui ni ok bi ting’o weche ma nyalo 
fuli. Di mang’eny, mbui biro ting’o duoko e yo ma chiek. Inyalo manyo mbui gi saa 
moramora. 
 
Weche nyathini ok bi ti godo e yo moramora kata nyiso ng’atang’ata ka ok ichiwo 
thuolo. 
 
NENGO GIN ANG’O? 
Onge nengo ma biro medore ne in kata ne nyathini kuom bedo e nonro ni. Yor nonro 
moramora, yedhe mag nonro kata pim mag nonro ibiro chiw ne nyathini nono ma onge 
chudo. Ewi manos, ka nyathini obedo e nonro, wabiro piko nyathini e NHIF mar Kenya 
ka gin e puonj. Gund thieth mamoko inyalo chul gi NHIF. 
 
 
TO CHUDO? 
Onge pesa ma biro bedo kata chudo ne nyathini kuom bedo e nonro. Kata kamano ibiro 
yudo omenda mar Kenya maromo mia abich mar konyi e yor wuoth mar lao chienro 
magi ma idhie. Ma samoro ok nyal romo nengo te mar wuoth to biro konyo kete ma yot 
mar bedo enonromalong’o. 
 
TO KA NYATHINA OHINYORE? 
Thieth ma nyalo duarore e sechego yudore e kar thieth mar Homa Bay county ka dibed 
ni nyathini ohinyore nikech bedo e nonroni. Onge andika moro gi mbalariany mar Moi, 
mbalariany mar Duke kokalo kuom kar puonjruok mar nonro mar thieth mar Duke, kar 
thieth mar Homa Bay county kata NIH mondo ochiw chudo moramora kata chudo mar 
hinyruok moramora ma otudore gi nonro, pesa kata thieth ma nono. 
 
Ne penjo kuom nonro kata hinyruok ma otudore gi nonro, tudri gi Dr. Njuguna e 
+254719474231 e seche mag tich kod e +254719474231 bang’ seche mag tich kod 
giko juma kod ndalo yweyo. 
 

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TO RATIRO MARA MAR TAMO NYATHINA DONJO KATA WUOK E NONRO? 
Inyalo yiero mar tamo nyathini bedo e nonro. Bende inyalo yiero mar yie ne nyathini 
mondo obed e nonro kendo inyalo gole e nonro samoramora. Ka igolo nyathini e nonro, 
onge weche manyien kuom nyathini ma ibiro kaw mag nonro mak mana ka nyathini nigi 
chandruok ka otudore gi yedhe mag nonro. Ka chandruok ma kama otimore, wanyalo 
dwaro mondo wachak warang andike mag nyathini mag thieth te. Weche te ma oyudi 
mag nonro ibiro or ne jatelo mar nonro ma en NIH mar America. 
Yiero mari mar tamo nyathini mondo kik donji kata wuok e nonro ok bi kelo kum 
moramora, kata kamano ok ibi yudo thieth moramora kata ohala ma nitie ei nonro 
kendo rit mar nyathini ibiro ter ne jo thieth ma onge e nonro kaka jathieth mar nyithindo 
kar thieth maduong’ kata matin. Ma ok bi moni kata nyathini yudo rit e yor thieth kuom 
dakteche gi ma kinde ka kinde. 
 
GOLO NG’ATO E NONRO GI ACHUNE. 
Ja thieth mar nonro nyalo ng’ado mar golo nyathini oko mar nonro ka: ngima mar 
nyathini ni e okang’ marach, kata. Nyathini obedo gi chandruok ka oa kuom gik ma 
itiyogo, kata dwaro thieth ma ok dwarore e nonro, kata Jo thieth mag nonro ong’ado ni 
ok en dwaro maber moloyo mar nyathini mar dhi mbele. 
 
NIH, Dr. Njuguna kata jothieth mag nonro ma moko, kata oganda ma keto chuke nyalo 
chungo nonro ni samoramora ka ok ing’eyo. Ka ma otimore, ibiro wachni kendo ja thieth 
mar nonro ma mari biro wuoyo kodi kuom yore ma moko. 
 
TO KA NITIE WACH MA NYIEN? 
Ibiro miyi wach moramora manyien ma ji opuonjore e seche mag nonro ma nyalo 
chandi kata iyie mar dhi mbele gi bedo mar nyathini e nonro. 
 
NG’A MA ANYALO GOCHONE KA AN GI PENJO KATA CHANDRUOK? 
Ne penjo man kuom nonro kata hinyruok ma otudore gi nonro kata ka in gi chandruok, 
wach moramora kata paro kuom nonro, tudri gi Dr. Njuguna e +254719474231 e seche 
mag tich, bang’ seche mag tich kendo nyaka giko juma kod ndalo yueyo. Ne penjo 
kuom ratiro mag nyathini kaka jatim nonro, kata wuoyo kuom chandruoge, weche ma in 
go, kata paro ma otudore gi nonro, kata yudo weche moko kata wuoyo kuom 
chandruoge, dwaro, kataparo ma otudore gi nonro, kata yudo weche moko, kata chiwo 
kony ne nonro, tudri gi jo bura mar nonro e wi timbe ma opuodhi mar Moi e 
+2540787723677. Jogo ma puodho weche mag ngima man e mbalariany mar Duke 
bende oseng’iyo puojni, ka in gi penjo moramora ma jo kanyo go nyalo konyo go akwayi 
ni kel gi e +1(919) 668-5111. 
 
WACH MAR YIE 
Dwaro mar nonro ni, yore ma iluwo,ahinye, kod berose ler ne nyathina kod an. Oyiena  
mondo apenj penjo kendo penjoga ose duoki e yo ma adwaro. Osenyisa ng’ama 
agochone ka an gi penjo, wuoyo kuom chandruok, dwaro, kata paro ma otudore gi 
nonro ni. Ase somo andike mayiena kendo yie mondo nyathina obed e nonro ni, kod 
winjo ni anyalo golo nyathina samoramora. Osenyisa  ni ibiro miya andike mar yie 
machielo maket,  ma ogoe sei kendo ondike tarik. 

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___________________________________ 
 
Nying janyuol ma ogo chapa kata jar it ma opuodhi. 
 
 
____________________________________  
 
 
Sei mar janyuol kata jar it ma opuodhi.  
Tarik                         Saa: ___: ____ 
 
 
 
____________________________________  
 
 
Saa: ___: ____ 
Sei mar janeno (ka dwarore) 
 
 
 
 
Tarik                          
Ase lero malong’o nonro ma owuoe gi andike ni. Ase dwoko penjo mag ja nyuol/ja 
ritkendo abiro duoko penjo moramora ma biro mbele maber kar nyalona. Abiro nyisojo 
ot kuom lokruok moramora e yore kata e ber ma nyalore mag nonro ma nyalo chando 
gombo mar janyuol mar miyo nyathine mondo obed e nonro. 
 
____________________________________ ___________ 
 
Nying jatim nonro ma kwayo  
 
                   Tarik  
 
 
Mondo janyuol oyie ne. 
 
_____________________________________ ___________ 
Sei mar jatim nonro ma kwayo    
            Tarik  
 
 
Mondo janyuol oyie ne. 
 
 
 
 
 
 
 
 
 
 
 
REMO MAR RANYISI IBIRO TIM GO ANG’O? 
E kinde ma nonro dhi nyime, ma ohingo dweche 12 nyathi biro kao remo e kiwango ma 
owachi malo kanyo ( ka idonjokendo kaibiro bng’ dweche 12). Wabiro kao remo ni 
mondo watim pim ma pile mondo wang’i duoko mar SCA, tuo ma ikelo gi suna kod 
thieth mag punj. Ewi mano, remo mar ranyisi moro ibiro kaw kendo kendo ti godo mana 
e nonro ma biro mbele,ka iyie gi kwayoni. Gik ranyisi gi ibiro kan kuom ndalo mang’eny 
e achiel kuom mbalariany kata kuonde riwruok mag timo nonro ma timo nonro ni, ka 
oting’o mbalariany mar Moi kata mbalariany mar Duke.Ranyisi gi bende inyalo tang’ne 
jotim nonro e kar puonjruok mamako. Tich moramora ma itimo gi gik ranyisi ma okan gi 
nyaka puodhi gi jok ma opuodhi ma nono kata jo bura ma puodho timbe. 
 
Magi e moko matin kuom gik ma nigi nengo ma ing’iyo kuom gik ranyisi gi: 
• Wabiro choko remo manyalo romomilliliter ariyo gi nusmondo okan ne nonro 
mabiro mbele elimbe ma ikawe remo ma  kinde ka kinde mar rit makare. Ranyisi 
ni ibiro ti godo mana e nonro mar malaria, SCA, kata touché ma makoji mamoko 
kuom nyithindo man gi SCA. 
• Bende wabiro kano remo ma ondong’ e kalatas ma opuodhi ka oa kuom remo 
ma wayudo kuomi. Ka nonro oserumo, ma ibiro ti godo mar pimo kute ma kelo 
malaria. 
• Weche ma wayudo kuom nonro gi ok bi chando rit mar nyathini. 
• Ranyisi gi ok bi usi kata tiyo godo mar loso mwandu mamoko mag ohala. 
• Wanyalo timo nonro kuom dhano kata koth malaria ma nitiere e mag ranyisi gito 
onge wachmoro maibiro keti e andika mag thieth mag nyathini kendo ranyisi gi 
ibiro mi number ma opondo mondo ng’ato kikng’e gik ma hulo nyathini. 

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• Onge ber ma aching’ ma nyathini yudo ka iyienwa mondo wati gi ranyisi e tijegi. 
To kata kamano, ka inyalo ti kodgi e nonro ma biro mbele, wageno ni mae biro 
konyowa mondo wapuonjre kaka imedo bero geng’o, thiedho kata tieko 
chandruok mag thieth ma kuom nyithindo man kodSCA. 
 
Ibiro tem matek mondo orit weche ma korka kori to ma ok nyal kony.Weche ma inyalo 
yud kuomi ka owuok kuom nonro ma ibiri timo ndalo ma biro ok bi ket e andikemari mar 
thieth. 
 
TO KA AYIE MAR CHIWO RANYISI SANI, BE ANYALO KWAYO MONDO RANYISI 
MA ACHIWO OKETHI BANG’E? 
Ka ing’ado bang’e ni diher mondo mi ranyisi magi okethi, nyaka ikon jathieth ma 
Njuguna kata jok ma ochung’ne e kanyakla mar nonro niigolo yie mane iyie godo 
mondo ranyisi magi okan kendo oti godo e research mabiro mbele. 
 
Seche ma nonro maduong’ dhi nyime, ikwayi ni itudri gi ja ta nonro Mr.Joseph Kipkoech 
e +254719474231. Bang’ nonro maduong’, ikwai ni itudri gi jo bura matimo nonro mar 
kar puonjruok mar Moi e +2540787723677. Ka weche weche ma tudo number mar 
ranyisi mari kod in ose kethi, ranyisi magi ok nyal chak tud kodi kendo ok wabinyalo 
yudo gi mondo oketh gi. Kendo, kata obedo ni ranyisi magi ibiro kethi: 
 
Ok wanyal yudo kendo ranyisi kata weche ma wasechiwo ne jotim nonro. 
Okinyal golo ranyisi mari ka osetimne nonro matut kata ka osepime. 
 
Yieigo sei e kar go sei achiel piny ka iyie mondi rembi ma itiyogo ka ranyisi okan ne 
nonro manyalo biro mbele, kata ka ok iyie mondo rembi ma itiyogo kaka ranyisi mondo 
okan.  
 
Ayie mondo  okaw remb  nyathina mar ranyisi okan ne nonro manyalo biro mbele mar 
SCA, malaria, kod touché moko ma mako nyithindo ma nigi SCA. 
 
______________________________ 
 
 
__________________________ 
Sei mar ja nyuol 
 
 
 
 
 
Tarik 
 
____________________________________  
 
 
 
________ 
Sei mar janeno (ka dwarore) 
 
 
 
 
Tarik                          
 
 
OK AYIE mondo okaw remb nyathina mar ranyisi okan ne nonro manyalo biro mbele 
mar SCA, malaria, kod touché mamoko mag nyithindo man kod SCA. 
 
______________________________ 
 
 
__________________________ 
Sei mar jatuo  
 
 
 
 
 
 Tarik 
 
 

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APPENDIX K: INFORMED CONSENT (DHOLUO TO ENGLISH) 
 
LETTER FOR JOINING STUDY 
 
Study heading: Strengthening Plans for Malaria Prevention in Children with a Blood 
Disease in East Africa 
 
Researcher: Doctor Festus Njuguna   
 
You are requested to allow your child to be in study because your child has a blood 
disease  
 
WHAT ARE THE THINGS YOU NEED TO KNOW IN STUDY? 
You are requested to allow your child be in study. Before you accept to allow your child 
to be in this study for treatment, it is good you know that this like studies requires only 
those who have decided to be part of it. Your child’s being in the study voluntary. If you 
accept to read from this paper properly then take your time to make up your mind. Your 
child’s Dr. for the study or whoever is doing the study on his behalf/ for him will be 
speaking regarding this paper together with you. If you agree ask any question that you 
don’t understand properly   
This paper gives us detailed information of what will take place in this study. This paper 
tells us in details over injuries, difficulties, discomfort, and other difficult issues. It is 
important that you ask question and you clearly understand what is required in this 
study. We encourage you to talk with your family or your friends before you allow your 
child in this study. You can take one of these papers at home while you are still thinking 
as to whether your child should join the study. If you accept to allow your child to join 
this study then sign on this paper. You will be given a paper containing this issues that 
is signed and dated for you. If she/he accepts tell study doctor or a researcher if your 
child is in another study. 
 
WHO WILL BE MY STUDY DOCTOR? 
If you accept to be in the study Doctor Njuguna will be the study doctor and will be 
talking with or your regular health worker during the period you will be in the study and 
later if you need. Donation from learning institution of United States National Institute of 
Health (NIH) will support this study. Doctor Njuguna and his people doing the study will 
be paid from this donation. 
 
WHY IS THIS STUDY DONE? 
You are requested to allow your child to join this study because she/he is between the 
age of 1 and 10 years, she/he has a blood disease and lives in an area that has high 
prevalence of malaria. 
We would wish to get better ways of preventing malaria in children with blood disease. 
This study will enable us know better treatment that can be used to prevent malaria in 
children with blood disease in areas of Africa with malaria. In this study we will compare 
among the three malaria drugs available in chemist so that we can find out which 
treatment if any that is better in reducing number of days of your child having malaria. 

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Study treatment available in this study are as below. Your child will be examined, your 
child will receive one of the three treatments per oral as a way of preventing malaria: 
  
• Proguanil (also known as Paludrine) it is the current highest standard in 
prevention of malaria in children with blood disease in Kenya. Sometimes your 
child has been on this drug so as to prevent malaria. This drug is taken daily. 
 
OR 
• Sulfadoxine/Pyrimethamine-Amodiaquine (SP-AQ) is a combination of drug 
containing sulfadoxine and pyrimethamine taken together with amodiaquine. This 
drug is taken monthly 
OR 
• Dihydroartemisinin-Piperaquine (DP) it’s a combination of dihydroartemisinin and 
piperaquine. This drug is taken monthly. 
I would wish to add that, if your child gets malaria, s/he will be treated through the 
mouth by Artemether-Lumefantrine (AL). All children below the age of 5 will receive 
penicillin everyday through the mouth this will prevent spread of bacteria which is 
highest in children with blood disease. 
 
HOW MANY CHILDREN WILL BE IN THIS STUDY? 
About 246 will complete this study. This study will be done at Homabay county hospital 
in Homabay, Kenya. 
 
WHAT IS REQUIRED IN THIS STUDY? 
If you allow your child to be in this study you will be requested to sign this paper. Your 
child will go through the following steps to show that she/he qualifies for enrolment 
 
Examination at visit 
In case you get in to the study, researcher has to know if your child qualifies. This helps 
in enrollment step. 
In the examination visit you will go through these steps and documentation of the 
findings: 
• We shall examine your health 
• We shall again check treatment that your child receives. 
• We will perform electrocardiogram this measure heart bit over the body using a 
machine 
• We will collect about 1Ml of your child’s blood so that we test some the protein 
that causes blood disease. If either you or your child has had blood made in the 
marrow that collects gases and removes unwanted gases because results for 
sickle cell test, some of the blood made in the marrow that collects and removes 
unwanted gases you can give us documents for the result, this test shall not be 
done in  examination visit 
• We shall collect about 1Ml your child’s blood so that we test part of the blood 
made in the bone marrow that collects gases and removes unwanted gases 
because of the protein that causes blood disease and will perform routine blood 
test to determine if it is safe to be enrolled into the study. Here your child needs 

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to complete test, that shows that your child is not prescribed for test that you 
know, However after that he/she can be enrolled  in the study when  she comes 
is when we can now if she/he qualifies. 
 
Your first entry 
During your first registration, the following procedure will be followed, then recorded 
• We shall document results for your child how it has been in the hospital, and 
result that has been since the first coming. 
• We shall document the drugs that your has used 
• We shall  do body examination together with height and weight. 
• We shall collect about 5ml of blood 
• We will collect the blood less than ½ ml from a finger prick of your child. 
• If necessary, we will administer to your child a Meningococcal vaccine.  This 
vaccine will help protect your child against bacteria that causes meningitis. This 
may not be necessary if your child has already received this vaccine, which is 
routinely recommended in Kenya. 
• We shall give you penicillin for 30 days ( if your child is under  the age of 5 
years),  this is a treatment plan to prevent bacterial infection for children with 
blood  disease 
• We shall register your child in Kenyan National Insurance Fund (NHIF) 
• We shall show how to protect and register your child 
Also with this visit plan, we shall know which malaria study your child will get. For that to 
happen, your child will be given (picking numbers) so that they get daily Proguani, SP-
AQ  monthly, or DP monthly. Your child has one in three chance of getting drug that is 
in plan. Any drug that a child should get in the study will be to protect against malaria in 
that study. All children will get some kind of malaria prevention drug.. 
Subsequent visit (monthly visit) 
In the monthly visit, these are what will be followed: 
• We shall study how your child is doing hospital wise, together with his/her 
treatment issues as per her/his last visit. 
• We shall ask questions, together with weight and height. 

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•  We shall collect less than 1/2ml of blood after pricking his/her finger to   
test for sickle cell anaemia and malaria parasites. If your child has a 
headache, or has had a headache that has lasted less than 24 hours, 
he/she will have a malaria test immediately; if your child has had no fever, 
his/ her blood will be stored for test when the study is over. 
• After every three months, we shall take about 2 ½ ml of blood for test. 
• When it reaches sixth month of visit and twelfth month we shall collect 
some blood of about 1ml to test blood disease. 
• If you sign a different form to consent for blood collection for visits after 
3,6,9 an 12 months will collect 2 ½ of blood for future research studies. 
• If we have to, we shall do ECG. 
• We shall give you study treatment and how it is used 
• For 30 days we shall give you daily penicillin (if he/she is less than 5 
years) 
• About 20 children will be selected to go back to clinic after two days for a 
repeat ECG this is done every month during study. This will be done so as 
to get results for ECG for study during the whole time. This will be for 
children who are selected for the DP of the study 
• If your child is found to be having malaria after, will be treated at that time 
with AL. 
Scheduled Visits (as required) 
According to the study, if your child who is at home has fever, it could be because they 
are feeling hot, or body hotness that is over 37.5, we request you call the study leader 
to organize how you can be assisted with the people doing the study. In this visit, the 
following will be followed: 
• We shall investigate your child health status, alongside other treatment 
issues in regards to the last visit. 
• We shall enquire, together with weight and height 
• We shall collect not more than ½ mL of blood after pricking his/her finger. 
If your child has fever or has had fever that has not lasted 24 hours, 

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he/she will be tested for malaria at that particular time; if your child has not 
had fever, his/her blood will be stored to be tested at the end of the study. 
If your child’s blood is found to be having malaria he/she will be treated immediately 
with AL  
 
How long will your child be in the study? 
He/She should be taking about 12 months, but it’s done monthly. Your child’s study will 
be completed after the 12th month after visits  
You can choose to avoid being in the study any time and there is no particular time that 
will be decided. For that, you will not receive treatment or study benefit, and your child 
will be taken to a doctor who is not in the study such as peadiatrician, hospital or clinic. 
And even if you have chosen not to be in the study, we will encourage you talk with your 
doctor before  
 
What is it harm of the study? 
According to how you have been in this study team, your child can have certain things 
that may occur later, if you decide that you can join, you need to discuss these issues 
with doctor and those who always help you  
It is possible that every drug to have something that follows. You should know some of 
the things that follows which may come in the study before you allow your child to join 
the study. Things like injuries, feel bad, drugs that do not agree with the body, and other 
things that may come that are not known.These injuries can be as a result of increased 
complication associated with the sicke cell anaemia, if the complications are very 
serious they can be fatal. 
 Proguanil may cause this, some of this, all of this, may not cause, some of the things 
that may come that are written here. 
Like these: 
Nausea                                          
Anemia 
• Vomiting                                           
• Abdominal pain 
 
• Bad dreams                                                  Cough 
• Head ache                                                    Restlessness 

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• Diarrhea                                                      Rash 
• Weakness                                                     Fever 
• Loss of appetite                                             Dizziness 
• Itchiness 
• These are less likely 
• Anxiety 
• Fast, strong, or abnormal heart beat 
• Mouth wounds 
• Forgetfulness 
• Excessive rash 
SP-AQ may cause, all or some or not one of the following problems. 
That which is likely to happen: 
• Headache                      Cough 
• Vomiting                                       Nausea 
• Loss of appetite                           Abdominal pain 
• Diarrhea                                     Weakness   
• Fever 
 
 
       Tiredness 
• Sleep  problems                           Rash 
• Sleep sickness                             Itchiness 
These are not common 
• Eye problems 
• Liver diseases 
• Anaemia 
DP may cause, all or some or not one of the listed problems below. 
Most common:  
• Head ache 
• Fever 
• Cough 
• Boils 
• Diarrhoea 
The most less likely:  
• Dizziness 
• Vomiting 
• Nausea 
•  Loss of appetite 
Some Injuries: 
Such as collection of blood from your child, discomfort. Boil, bleeding in excess, blood 
clotting, falling. For reducing chances of injuries, we only employ those who are trained 
and proper equipment. In addition to that, your child can get some injuries and some 
undesired effect due to the study drugs which can increase serious complications of the 
sickle cell disease and can be fatal. Its better you share any problems with the 
researchers  
 
ISTHERE BENEFIT AS A RESEACHER? 

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If you allow your child in this study. Your child can get treatment benefit. Children who 
join the study will get free malaria prevention drug and for other disease causing 
organism, free thorough monthly assessment, free malaria test if they have fever, and 
put on Kenyan National Hospital Insurance Fund. This assistance has the benefit of 
reducing problems related to treatment emanating from malaria and SCA  
 
For a long period, we hope that in coming days what has been learnt from this study will 
help children from Africa with sickle SCA by getting better treatment for malaria 
prevention 
 
WHAT ARE SOME OTHER WAYS AVAILABLE HERE FOR BEING IN THIS STUDY? 
It is not a must your child be in this study. Even if you don’t allow your child to be in it, 
he/she can still get treatment from to time to time from regular health providers. 
 
WILL INFORMATION OF MY CHILD BE KEPT CONFIDENTIAL? 
Your child will not be identified by her/his name or by reports sent to people outside 
Homa bay county hospital. For any writings leaving Homa bay county hospital your child 
will be given a number that  is secret, document containing the secret numbers together 
with the names of the children and other information that talks about her/him are kept 
secret and be kept by the team that does research.  
 
All will be done to ensure that all that’s written about your child are kept permanently 
confidential. However there is a possibility of your child’s information being known. 
Some offices and other people who are not part of the study may be able to see your 
child’s information about treatment and study information 
 
Among them are people from: 
• 
Researchers from Moi and Duke university and research institute of Duke; 
• 
Research institution of Moi and Ethics committee and the Duke University of Health 
System institutional Review Board  
• 
The overseers for NIH from the American  
 The documentation for the study shall be kept for 10 years after the study in accordance 
with the regulations, research information that are in the treatment documents shall be kept 
for ever  
 
During the study period your health worker and researchers may go through research 
matter together with other people. This may consist of: 
• Those who check the research, those checking about honesty of the study 
• Those who have information showing beginning of treatment, those who tell 
problems drugs brings to sickness of a child and also. 
• The people who compile all research matters in writings. 
 
When your child is in this study, information collected from him can be documented in 
his/her medical records. 
 

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You have a right to decline to be in this study any time. So as to stop, it is better you tell 
your health care provider for the study that you would like to stop. If you want your child 
to join this study, you must sign to show that you allow the research team to examine 
your child in relations to her/his treatment. If you refuse to allow us examine your child’s 
health in details then your child shall not be in the study. However, declining to sign in 
this form will not hinder you or your child in getting medical help. 
 
Sometimes the result for study can be taken to a board that does research or be written 
in research papers, anything about your child will not be shared and your child will not 
be identified by name.  Information about treatment shall be found at 
http://www.ClinicalTrial.gov and pan African clinical trials registry (http://www.pactr.org). 
This website shall not contain information that will reveal your identity.  Most of the time 
this website will carry results in summery. You can visit this website anytime. 
Information about your child shall not be used in anyway or be shown anybody without 
your permission.  
 
WHAT IS THE COST? 
There is no additional charge that shall be added to your child for being in this study. 
Any study, drug for the study or tests will be offered to your child free of charge. In 
addition to that, if your child is put in the study we shall put her/him in KNHIF. All sought 
of treatment can be paid by NHIF  
  
HOW ABOUT COMPENSATION? 
There is no money that will be available or compensation for child’s participation in the 
study. However you shall get five hundred Kenya shilling that will assist you in transport 
to access these treatment programs. Sometimes this may not cater for full transport but 
this will facilitate being in the study. 
 
WHAT IF MY CHILD GETS INJURED? 
Any treatment that may be required at that time will be found at Homa Bay county 
Hospital. If your child gets injured as a result of being in the study. There is no 
agreement with Moi University, university of Duke from the medical research of Duke, 
Homa Bay County or NHIF to offer any compensation for injuries related to this 
research. There is no agreement with the University of Moi, University of Duke through 
medical school of medical research, Homa bay county hospital or NHIF to offer any 
compensation or compensation for any injury related to this study, money or free 
treatment. 
For question about the study or injuries in connection with the study get in touch with Dr. 
Njuguna at +254719474231 during working hours and on +254719474231 after working 
hours, weekend and holidays. 
 
WHAT ABOUT MY RIGHT TO REFUSE TO ALLOW MY CHILD BE IN OR LEAVE THE 
STUDY? 
You can decide to refuse to allow your child be in the study. You can also decide to 
allow your child to be in the study or leave the study anytime. If you decide to stop your 
child from being in the study there are no new information that will be collected from 

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your child unless he/she has drug related problems, if such problems occur  we may 
want  to check again all his/her treatment records. All research information will be sent 
to the research lead which is American NIH. 
Your decision to refuse to allow your child be in or leave the study will not attract any 
punishment, however, you will not receive any treatment or profit in the study, and care 
of your child will be transferred to health care providers who are not in the study such as 
pediatrician major or small health facilities. This will not prevent you or your child from 
receiving from the regular doctors from time to time.  
 
FORCEFUL REMOVAL OF A PERSON FROM THE STUDY. 
Study health care provider may decide to remove your child from the study when: 
• Life of your child is in danger or 
• Your child develops problems from some of the things used. Or 
• Treatment requirement is not offered in the study  or 
• When study health care providers decide that it is not the best thing for the child 
to continue. 
 
NIH, Dr. Njuguna or   other study health care providers, or law implementers may 
decide to stop this study anytime without you knowing. If this happens you will be told 
and your study health care provider will talk to you about other ways 
 
WHAT IF THERE IS NEW INFORMATION? 
You will be informed of any new information that people have learnt during the study 
that may affect you or that may require your child to continue being in the study. 
 
WHOM CAN I CALL IF I HAVE QUESTION OR PROBLEM? 
For questions about the study or injuries in connection with the study or you have a 
problem, any issues get in touch with Dr. Njuguna on +254719474231 during working 
hours, after the working hours, weekends and holidays. For questions about your child’s 
rights as a researcher, or talking about problems, any issues you have, or ideas related 
to the study, or getting information or talking about problems, desire, or idea in 
connection with the study or getting other information, or supporting the study, get in 
touch with study board over approved behavior of Moi at +2540787723677.  Those who 
approve health matter at Duke University has also studies this study, if you have any 
questions for the members that may assist forward them to +1(919) 668-5111. 
 
ABOUT CONSENT 
Requirements for this study, steps to be followed, injuries, has been explained to me 
and my child. Am allowed to ask questions, and my questions have been answered 
satisfactorily. I have been told whom to call when I have questions, talks about 
problems, desires, or ideas in connection with the study. I have read about being 
allowed and allowing my child to be in the study and understanding that I can stop my 
child from the study anytime. I have been told that I will be given a copy to keep which is 
signed and dated. 
 
___________________________________ 
 

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Printed name of the parent or legal guardian. 
 
 
____________________________________  
 
 
Signature of the parent or legal guardian. 
 
        Date                      Time: 
___: ____ 
 
 
____________________________________  
 
 
Signature of Witness (if applicable) 
 
Date  
 
  Time: ___: ____ 
 
I have explained properly about the study that is discussed in this paper. I have 
answered questions asked by the parent/ guardian and I will answer any questions to 
the best of my ability. I will tell family about any changes in ways or benefits from the 
study that may affect the desire of the parent to allow his/her child to be in the study.  
____________________________________  
 
 
___________ 
 
STUDY STAFF OBTAINING CONSENT  
                    
Date  
 
 
 
_________________________________ 
 
 
 
 
__________ 
SIGNATURE OF STUDY STAFF OBTAINING CONSENT 
 
 
Date  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WHAT WILL THE BLOOD SAMPLE BE USED FOR? 
During the study, after lasting more than 12 months blood will be collected from the 
child in the volumes shown above ( if you join or come after 12 months) we will collect 
blood to do regular tests to observe results for SCA, a disease that is caused by 
mosquitoes and treatment. 
In addition to that, blood sample will be collected and be used in the study in future if 
you accept this request. These samples will be stored for a long time in one of the 
universities or research organizations doing this research, this includes Moi University 
or Duke University. These samples may be shown to researchers in other learning 
institutions.  Anything that is done with the stored samples must be approved by 
relevant people who oversee studies or committee that regulates behavior. 
These are some of the most important things that you need to know the about the study: 
• We will collect about two and a half romomilliliter of blood to be stored for future 
study at registration during visits which we will collect blood for routine care. At 
enrollment this sample  will be used in malaria research, SCA or other diseases 
in children with sickle cell 
• We shall store the remaining sample in approved paper from blood that we 
collected from you this will be used to test malaria parasites,  
• Information we get from this study will not affect your child’s care.  
• These samples will not be sold  or be used for creating wealth or profit  
• We can do study human or malaria parasites present in the sample and there is 
nothing that will be documented about your child’s  care and these samples will 
be labeled by secret number so that someone does not identify your child. 

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• There is no direct benefit if you allow us use him/her sample in this work. 
However, they can be used for future study, we hope that this will help us to learn 
how to better prevent, treat, or complete problems of treatment of children with 
SCA. 
Great effort shall be done to protect your information but this cannot be guaranteed. 
Information that will be received from you from the study shall not be recorded in your 
treatment notes. 
 
IF I DECIDE TO GIVE SAMPLE NOW, CAN I REQUEST THAT THE SAMPLE BE 
DESTROYED LATER? 
If you later decide later that you would like your samples be destroyed, you must tell Dr. 
Njuguna or representatives for the study that you have withdrawn consent for your 
sample to be stored for future research.  
During the main study you are requested to get in touch with study Mr. Joseph Kipkoech 
at +254719474231. 
After the main study you are asked to get in touch with study committee members from 
Moi University at +2540787723677. 
If the numbers that link your sample and you have been destroyed, then your sample 
cannot be linked to you and we will not be able to get them for destruction.  
Even though your samples will be destroyed: 
• We will not be able to get back your samples or information that has been 
delivered to researchers. 
• You cannot get your samples after your sample has been studies in details or 
tested.  
Kindly sign down here in the space provided if you allow your sample to be stored for 
future use, or if you refuse to allow your blood sample to be stored  
 
I accept my sample that my child’s blood sample be stored for possible future research 
for SCA, malaria, and other diseases with SCA  
 
______________________________________________________________________ 
Signature of Parent  
 
 
 
 
 
 
 
Date  
 
 
______________________________________________________________________ 
Signature of Witness (if applicable) 
 
 
 
 
 
Date  
 
 
I DECLINE to allow my child’s blood sample be stored for future study about SCA, 
malaria, and other diseases in children with SCA.  
 
 
______________________________________________________________________ 
Parent ‘s Sign 
 
 
 
 
 
Date  
 
 
 
 

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APPENDIX L: MEDICATIONS THAT PROLONG THE QT INTERVAL 
 
The following medications are known to prolong the QT interval and are likely to be 
used in children: 
 
Azole antifungals 
Fluconazole 
 
Itraconazole 
 
Ketoconazole 
 
Posaconazole 
 
Voriconazole 
Fluoroquinolone antibiotics 
Ciprofloxacin 
 
Gatifloxacin 
 
Levofloxacin 
 
Moxifloxacin 
 
Ofloxacin 
 
Sparfloxacin 
HIV antiretrovirals 
Efavirenz 
 
Lopinavir 
 
Saquinavir 
Macrolide antibiotics 
Azithromycin 
 
Clarithromycin 
 
Roxithromycin 
 
Telithromycin 
Other antimicrobials 
Metronidazole 
 
Telavancin 
 
Pentamidine 
 
Foscarnet 
Psychotropics 
Haloperidol 
 
Tricyclic antidepressants 
 
Fluoxetine 
 
Escitalopram 
 
Citalopram 
 
Risperidone 
Bronchodilators 
Albuterol 
 
Levalbuterol 
 
Formoterol 
 
Salmeterol 
 
Terbutaline