Operational Evaluation of Mass Screening and Treatment Using Ultrasensitive Rapid Detection Tests to Reduce P. Falciparum Incidence in a Malaria Elimination Program in Eastern Kayin State, Myanmar
Phase: NA
Conditions: Plasmodium Falciparum Malaria
Sponsor: University of Oxford

 
 
 
 
 
 
 
Study Title:  Operational evaluation of Mass Screening and Treatment using 
ultrasensitive rapid detection tests to reduce P. falciparum incidence in a malaria 
elimination program in Eastern Kayin State, Myanmar. 
 
Internal Reference Number / Short title: MAL 17011 / Mass Screening and Treatment 
for reduction of falciparum malaria 
Date and Version No: 20 Feb 2018 – v2.0 
Trial registration number: NCT04093765 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 28 
 
 
Mass Screening and Treatment for reduction of falciparum malaria  
Operational research study protocol 
 
Study Title:  Operational evaluation of Mass Screening and Treatment using ultrasensitive rapid detection 
tests to reduce P. falciparum incidence in a malaria elimination program in Eastern Kayin State, Myanmar. 
Internal Reference Number / Short title: MAL 17011 / Mass Screening and Treatment for reduction of 
falciparum malaria 
OxTREC Ref: 4-18 
Date and Version No: 20 Feb 2018 – v2.0 
 
Chief Investigator: 
François Nosten 
Investigators: 
Khin Maung Lwin, Aung Myint Thu, Jordi Landier, Gilles Delmas 
Sponsor:  
Oxford University 
Funder: 
The Bill and Melinda Gates Foundation, The Global Fund, The Wellcome 
Trust 
Chief Investigator Signature:   
 
The investigators declare no conflict of interest. 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
authorised individuals from the University of Oxford, the Investigator Team and members of the Oxford 
Tropical Research Ethics Committee (OxTREC), unless authorised to do so. 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 2 of 28 
TABLE OF CONTENTS 
 
1. 
SYNOPSIS ............................................................................................................................................... 4 
2. 
ABBREVIATIONS ..................................................................................................................................... 5 
3. 
BACKGROUND AND RATIONALE ............................................................................................................ 6 
4. 
OBJECTIVES AND OUTCOME MEASURES ............................................................................................. 10 
5. 
STUDY DESIGN ..................................................................................................................................... 11 
6. 
PARTICIPANT IDENTIFICATION AND RECRUITMENT ........................................................................... 11 
6.1. 
Study villages selection ................................................................................................................ 11 
6.1.1. 
Group 1: sustained high incidence villages ............................................................................. 12 
6.1.2. 
Group 2: seasonal focal transmission villages/locations ......................................................... 12 
6.2. 
Study Participants ........................................................................................................................ 12 
6.3. 
MSAT intervention....................................................................................................................... 13 
6.3.1. 
Inclusion criteria ...................................................................................................................... 13 
6.3.2. 
Exclusion criteria...................................................................................................................... 13 
6.3.3. 
Specific treatment regimen ..................................................................................................... 13 
6.4. 
Follow-up at 12 months (group 1 only) ....................................................................................... 13 
6.4.1. 
Inclusion criteria ...................................................................................................................... 13 
6.4.2. 
Exclusion criteria...................................................................................................................... 13 
7. 
STUDY PROCEDURES ........................................................................................................................... 14 
7.1. 
Recruitment ................................................................................................................................. 14 
7.2. 
Informed Consent ........................................................................................................................ 14 
7.3. 
Screening and Eligibility Assessment ........................................................................................... 15 
7.4. 
Randomisation, blinding and code-breaking ............................................................................... 15 
7.5. 
Baseline Assessments .................................................................................................................. 15 
7.6. 
Subsequent Visits ........................................................................................................................ 16 
7.6.1. 
Treatment administration follow-up visits (visit 2, visit 3) ...................................................... 16 
7.6.2. 
Malaria incidence monitoring ................................................................................................. 16 
7.6.3. 
Follow-up prevalence survey (group 1) ................................................................................... 16 
7.7. 
Sample Handling .......................................................................................................................... 16 
7.8. 
Discontinuation/Withdrawal of Participants from Study ............................................................ 17 
7.9. 
Definition of End of Study ........................................................................................................... 17 
8. 
INTERVENTIONS / INVESTIGATIONS .................................................................................................... 18 
9. 
STATISTICS AND ANALYSIS ................................................................................................................... 18 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 3 of 28 
9.1. 
Description of Statistical Methods .............................................................................................. 18 
9.2. 
The Number of Participants (group 1 only) ................................................................................. 19 
9.2.1. 
Sample size for stepped-wedge comparison of incidence decrease following MSAT ............ 19 
9.2.2. 
Sample size for prevalence comparison .................................................................................. 19 
9.2.3. 
Sample size for retrospective incidence comparison between MSAT and MDA .................... 19 
9.3. 
Analysis of Outcome Measures ................................................................................................... 20 
10. 
DATA MANAGEMENT ...................................................................................................................... 20 
10.1. 
Access to Data ......................................................................................................................... 20 
10.2. 
Data Handling and Record Keeping ......................................................................................... 20 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES ........................................................ 20 
12. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................... 21 
12.1. 
Declaration of Helsinki............................................................................................................. 21 
12.2. 
Guidelines for Good Clinical Practice ...................................................................................... 21 
12.3. 
Approvals ................................................................................................................................. 21 
12.4. 
Participant Confidentiality ....................................................................................................... 21 
12.5. 
Expenses and Benefits ............................................................................................................. 21 
12.6. 
Reporting ................................................................................................................................. 21 
13. 
FINANCE AND INSURANCE .............................................................................................................. 21 
13.1. 
Funding .................................................................................................................................... 22 
13.2. 
Insurance ................................................................................................................................. 22 
14. 
PUBLICATION POLICY ....................................................................................................................... 22 
15. 
REFERENCES .................................................................................................................................... 23 
16. 
APPENDIX A:  STUDY FLOW CHART ................................................................................................. 24 
17. 
APPENDIX B:  SCHEDULE OF STUDY PROCEDURES .......................................................................... 25 
18. 
APPENDIX C:  AMENDMENT HISTORY ............................................................................................. 26 
19. 
APPENDIX D:  UNPUBLISHED DATA ON URDT PERFORMANCE ....................................................... 27 
 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 4 of 28 
1. SYNOPSIS 
Study Title 
Operational evaluation of Mass Screening and Treatment using ultrasensitive 
rapid detection tests to reduce P. falciparum malaria incidence and 
prevalence in a malaria elimination program in Eastern Kayin State, 
Myanmar. 
Internal ref. no.  
MAL 17011 
Study Design 
Stepped wedge intervention 
Study Participants 
Populations of villages with high P. falciparum incidence located in Eastern 
Kayin State, Myanmar. 
Planned Sample Size 
60 villages (group 1) 60 villages (group 2) 
Planned Study Period 
3 years 
 
Objectives 
Outcome Measures 
Primary 
 
To measure the impact of URDT-based 
MSAT on P. falciparum incidence at 
village-level (group 1 & 2) 
Adjusted incidence rate ratio 
before/after MSAT 
 
Secondary 
 
1) To measure the impact of MSAT on 
prevalence of P. falciparum infection in 
malaria hotspots (group 1) 
1) Prevalence of P. falciparum 
infection measured in the village by 
URDT and by reference method 
 
2) To measure the impact of reactive 
MSAT on incidence of seasonal 
malaria peaks / outbreaks (group 2) 
2) Change in the incidence 
dynamics over the transmission 
season 
 
3) Feasibility of MSAT as a 
programmatic tool and as a reactive 
strategy (group 1 and 2) 
3) Coverage of village population 
with intervention 
 
 
4) % of infections treated compared to 
infections detected by reference 
method (group 1 only) 
4) % of P. falciparum positive 
samples by reference method 
which were positive by URDT and 
treated; % of P. falciparum 
negative samples by reference 
method which were positive by 
URDT and treated 
 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 5 of 28 
 
2. ABBREVIATIONS 
ACT 
Artemisinin Combination Therapy 
AL 
Artemether Lumefanthrin 
CE 
Community engagement 
DP 
Dihydroartemisin-Piperaquin 
ELISA 
Enzyme Linked Immuno Sorbent Assay 
GCP 
Good Clinical Practice 
GMS 
Greater Mekong Subregion 
HRP2 
Histidin Rich Protein 2 (Plasmodial antigen detected by lateral flow assays: RDT or URDT) 
ICF 
Informed Consent Form 
MDA 
Mass drug administration 
METF 
Malaria Elimination Task Force 
MP 
Malaria Post 
MSAT 
Mass Screening and Treatment 
NMCP 
National Malaria Control Program 
OxTREC 
Oxford Tropical Research Ethics Committee 
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
PMQ 
Primaquine 
Q7C7 
Quinine 7 days; Clindamycine 7 days 
RDT 
Rapid Diagnostic Test 
sld PMQ 
single low dose Primaquine 
SOP 
Standard Operating Procedure 
uPCR 
Ultrasensitive quantitative polymerase chain reaction 
URDT 
Ultrasensitive Rapid Diagnostic Test 
 
 
 
 
 
 
 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 6 of 28 
3. BACKGROUND AND RATIONALE 
Malaria elimination has been undertaken in the Western Greater Mekong Subregion (Western Thailand, 
Eastern Myanmar) in an attempt to prevent the spread of artemisinin- and multidrug resistant falciparum 
parasites.  
The malaria elimination task force (METF) has been operating in Eastern Kayin State since April 2014. METF 
is present in the four townships of Hpapun, Hlaingbwe, Myawaddy and Kawkareik, in a total of 158 village 
tracts. METF is providing access to early diagnosis and treatment of malaria in 1200 villages through 
community-based facilities “Malaria Posts” (MP) [1]. The monitoring of falciparum malaria incidence in the 
villages after the opening of a MP showed that incidence decreases quickly in most locations 
(approximately by 25% per quarter of MP activity, Figure 1A). As a result in April 2017 a total of 965 villages 
out of 1,222 villages (79%) corresponding to 104 village tracts were free of P. falciparum malaria for at 
least 6 months.  
However the activity of the MP had more limited impact in villages with high prevalence of asymptomatic 
infections: a slower or no decrease of falciparum was observed, even after >24 months of MP activity 
(Figure 1B). 
 
Figure 
1: 
Malaria 
incidence 
(falciparum in red and vivax in 
black) since MP opening in the 
townships of Hpapun (n=468 MP) 
and Myawaddy (n=100) where 
hotspots were identified (52/69 
located in Hpapun Township, 7/69 
in Myawaddy). Different y-scales 
are used in each graph.  
A: 
non-hotspot 
villages. 
The 
widening confidence intervals after 
24 months indicate that fewer MP 
have been active for 2 years or 
more. The oscillations in P. vivax 
incidence are related to seasonal 
peaks occurring in the same 
locations in Myawaddy Township.  
B: 
hotspot 
villages, 
without 
intervention. Only 16 hotspots 
contribute 
to 
follow-up 
for 
durations of MP activity above 18 
months. These high incidence 
locations were only identified 
during the final campaign of 
baseline surveys (Nov. 2016 to Jan. 
2017) and had not been addressed 
by April 2017. The median duration 
of MP activity before intervention 
was 12 months (IQR=5-16). Over 
the period corresponding to a 
duration of MP activity between 0 
and 18 months, a decrease can be 
observed in hotspots which is 
captured by the statistical model. 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 7 of 28 
Following a successful pilot study initiated in 4 villages in 2013 [2], METF has conducted surveys to measure 
the prevalence of asymptomatic malaria infections. Villages with high prevalence of malaria (>40%) in 
which falciparum represented at least 20% of malaria infections, were defined as hotspots and treated 
with a 3-month mass drug administration campaign. These campaigns were very successful at depleting 
the reservoir of asymptomatic carriage of P. falciparum (Figure 2), which translated in a significant 
decrease in clinical episode incidence (Figure 3). In spite of its success, this strategy is difficult to scale up 
due to numerous constraints and was not considered by the Myanmar NMCP. However, the successful 
decrease in case incidence obtained by treating the reservoir of asymptomatic carriers sparks interest for 
a simpler and faster intervention, relying on mass screening and treatment (MSAT) rather than MDA (Table 
1). Such approach was previously impossible due to the lack of sensitivity of standard RDT to detect 
asymptomatic infections. A newly available ultrasensitive RDT (URDT) shows a 50% sensitivity and 99% 
specificity compared to uPCR. This sensitivity is sufficiently high to allow accurate detection of high 
prevalence villages, and to warrant evaluation of the impact of a URDT-based screening and treatment 
intervention. MSAT is a method approved by the Myanmar NMCP and recommended by the WHO. 
 
Figure 2: Impact of MDA on P. falciparum prevalence (95% confidence interval) comparing baseline and 
12 months after MDA (n=40 villages) in villages equipped with MP and addressed with MDA between 
January 2015 and April 2016.  
 
By design, an MSAT intervention using a field test will not identify all carriers. However, it is likely to 
decrease village level prevalence by 50%, and parasite biomass by >97%, since 87% of infections with 
parasite densities >1000 parasite/mL are expected to be identified. This depletion of the reservoir could 
be sufficient to durably modify the village-level transmission and initiate or accelerate the MP-driven 
decrease. Additionally, a URDT-based MSAT strategy could be an extremely useful tool to respond to 
malaria outbreaks. Indeed, by rapidly screening the population of a village where the incidence has 
reached alarm thresholds, parasite carriers could be rapidly identified and treated, leading to a rapid 
decrease in the reservoir and an interruption of the transmission. 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 8 of 28 
 
 
 
Figure 3: Average P. falciparum and P. vivax incidence in hotspots before and after MDA, centered on 
date of MDA. A marked decrease in P. falciparum incidence after MDA can be observed, in spite of an 
increase in incidence around 15 months after MDA. This increase is related to 5 hotspots (out of 52 followed 
up to M18) showing an incidence above 50 case/1000 for 1 month during the second year after MDA. This 
increase did not persist further. 
 
In this project, we aim at an operational research deployment of URDT-based MSAT in the METF 
elimination program. This intervention will be tested in two types of setting, which correspond to two arms 
in this study. In group 1, MSAT will be used in a programmatic setting in order to decrease the reservoir of 
asymptomatic carriers in high incidence villages (following the same principles and objective as previously 
deployed MDA interventions). In group 2, we take advantage of the lighter framework of MSAT to use it 
as a reactive intervention in order to respond to malaria outbreaks in low to intermediate incidence 
villages. The MSAT intervention will be preceded with community-level consent and community 
engagement (CE) activities. MSAT will be conducted over a period of approximately 1 week in each hamlet, 
village or group of villages, and will consist in administering a P. falciparum URDT to all individuals agreeing 
to participate. A limited subgroup (expected 5-25%) will be found positive and receive supervised 
treatment over 3 days for the standard regimen (DP to cure asexual stage infection + single low-dose 
primaquine to destroy gametocytes). After this intervention, the incidence of clinical falciparum episodes 
will be monitored by the village MP. In group 1, a comparison of the prevalence at baseline and 12 months 
after MSAT intervention will be performed through a second URDT survey, in addition to which both 
baseline and 12-month surveys will include the collection of a 50µL capillary blood sample for reference 
detection in the laboratory. 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 9 of 28 
The intervention will be evaluated primarily on its ability to reduce yearly cumulative incidence of clinical 
falciparum malaria compared to year before intervention. Additional evaluations of the impact of MSAT 
will include: in group 1, comparison of asymptomatic infection prevalence; and in group 2, modifications 
of the shape of the incidence curve following intervention. 
Potential risks and benefits for participants 
This study has limited risks for participants. 75 to 95% of participants will only undergo a malaria rapid 
diagnostic test (URDT) requiring a finger prick and receive a negative result. 5 to 25% of participants are 
expected to be found URDT positive. The specificity of the test is high  compared to uPCR (99%) as well as 
predictive positive value (88%), ensuring that >9/10 of these positive individuals will be infected with P. 
falciparum and will benefit from the ACT treatment ([3], Appendix D). The safety of DP and single low dose 
primaquine are well-described, including among asymptomatic individuals [2,4]. The risk associated with 
treatment will be limited. All screening participants in group 1 will also be sampled for 50µL capillary blood 
using the same finger prick as used for the URDT, which does not aggravate the risk. All procedures on 
participants will be conducted by trained medical personal. 
Participants will benefit from this study by acquiring knowledge of their infection status as individuals and 
as a community. Infected individuals will be treated, which will decrease the potential negative 
consequences of a long-lasting infection [5,6] without increasing the risk of a subsequent clinical episode 
[7]. Households where positive participants will be identified will receive additional guidance on measures 
to protect against vectors and be reminded to consult the village MP within 24h in case of fever onset. At 
the community level, treatment of asymptomatic carriers is expected in reducing significantly the number 
of infective individuals, thus limiting the infection of mosquitoes and decreasing the overall village 
transmission and malaria burden. 
 
Interest of the research 
The METF target area in Eastern Kayin State, Myanmar, is piloting strategies with potential applications for 
>20 countries in the 2020 horizon, and many more countries by 2030 since elimination is one of the 
Sustainable Development Goals. It is also a region of significant artemisinin resistance, and under the 
threat of the expansion of a multidrug resistant falciparum lineage spreading in the GMS. Strategies 
developed and tested in a context of antimalarial resistance are therefore extremely valuable for this 
region. 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 10 of 28 
4. OBJECTIVES AND OUTCOME MEASURES 
 
 
Objectives 
Outcome Measures  
Timepoint(s) of 
evaluation of this 
outcome measure (if 
applicable) 
Primary Objective 
To measure the impact of URDT-
based MSAT on P. falciparum 
incidence at village-level. 
Adjusted incidence rate ratio 
before/after MSAT 
 
Follow-up from MP 
opening to end of 
study  
Secondary Objectives 
1) To measure the impact of MSAT 
on prevalence of P. falciparum 
infection in malaria hotspots 
 
1) Prevalence of P. falciparum infection 
measured in the village by URDT and by 
reference method (group 1) 
 
1) Comparison 
between M0 survey 
(during MSAT) and 
M12 survey (12 
months after) 
2) To measure the impact of 
reactive MSAT on incidence of 
seasonal malaria peaks / outbreaks. 
2) Change in the incidence dynamics 
over the transmission season (group 2) 
2) Duration and 
height of seasonal 
peak before, during 
and after reactive 
intervention 
3) Feasibility of MSAT as a 
programmatic tool and as a 
reactive strategy. 
3) Coverage of village population with 
intervention 
 
3) coverage based on 
census conducted 
before/during MSAT 
4) % of infections treated 
compared to infections detected by 
reference method  
4) % of P. falciparum positive samples 
by reference method which were 
positive by URDT and treated; % of P. 
falciparum negative samples by 
reference method which were positive 
by URDT and treated (group 1) 
Group 1 only 
Tertiary Objectives 
Retrospective comparison of MSAT 
versus MDA on prevalence and 
incidence of P. falciparum malaria 
 
Cumulative incidence of falciparum 
malaria episodes before and after 
MDA/MSAT; prevalence of falciparum 
infection before and after MDA/MSAT 
 
Entire incidence 
series 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 11 of 28 
5. STUDY DESIGN 
Stepped-wedge open-label, non-randomized, cluster intervention. 
This study will be performed in clusters (hamlet (isolated group of household, village, or group of village). 
The intervention will be conducted in two types of clusters, both corresponding to locations where an 
excess of case was detected. 
Group 1: Sustained high incidence clusters, characterized by a yearly cumulative incidence >84 
cases/1000/year 
Villages in group 1 will be attributed an intervention a given year based on the cumulative incidence over 
the previous 12 months (METF stratification January, including the last 2 transmission seasons). The order 
of intervention will be decided based on logistic constraints and highest incidence. 
Group 2: Focal transmission clusters, corresponding to locations where an epidemic alert has been 
signalled and confirmed (see definition of thresholds). 
Villages in group 2 will be attributed an intervention based on P. falciparum incidence in the previous 4 
weeks. In near-0 transmission area, an intervention will be conducted in each likely source location of 
transmission of a locally acquired case. In the other areas (METF1+METF2), the intervention will be 
triggered when the incidence is above the pre-defined epidemic threshold. 
In each cluster, all inhabitants will be invited to undergo an URDT test to identify their infection status, and 
will receive the appropriate treatment according to their characteristics. Information on village inhabitants 
absent during the MSAT activities will be obtained from village population lists provided by the village 
headman and from household member declarations. During the URDT screening, all individuals will receive 
a unique identifying number that will be used to record demographic data in the MSAT paper logbook and 
to label URDT and reference sample. 
Before and after MSAT intervention, incidence of clinical malaria episodes will be recorded at the MP (1 
or several) serving the cluster receiving the intervention. No individual data will be collected to link clinical 
case participation, infection status and incidence of clinical episodes. 
Participants from group 1 clusters will also be invited to participate in a prevalence survey during MSAT 
and 12 months after, in order to evaluate the impact of the MSAT campaign on the asymptomatic carriage 
prevalence. This will require collection of a 50µL sample during the MSAT campaign and a second round 
of URDT screening with the collection of a 50µL sample, 12 months after MSAT. 
6. PARTICIPANT IDENTIFICATION AND RECRUITMENT 
6.1. Study villages selection  
The study village selection is based on the definition of three main strata of P. falciparum incidence 
corresponding to different probabilities of rapid elimination. Based on 2017 data, the townships of 
Myawaddy, Hlaingbwe and Kawkareik have almost interrupted P. falciparum transmission (95% of villages 
with 0 incidence), while heterogeneity persists in Hpapun township with diverse transmission and 
incidence profiles.  

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 12 of 28 
6.1.1. Group 1: sustained high incidence villages 
Villages classified as high incidence, low probability of elimination (P. falciparum cumulative incidence >84 
cases/1000/year, in spite of >1 year of functioning malaria post) will be eligible to be included in group 1. 
Villages in this group will be addressed by MSAT waves of 10-15 villages.  
Villages will be included in a given wave based on accessibility to the team and proximity from each other, 
as well as requirements for the program impact. Wave 1 will include 5 villages and be conducted during 
first semester 2018, after which a maximum of two waves will be conducted per semester. 
6.1.2.  Group 2: seasonal focal transmission villages/locations 
This group will follow the NMCP case/and foci investigation guidelines, but use URDT instead of standard 
RDT for screening. MSAT group 2 locations will be cluster of houses, villages or clusters of villages selected 
based on the results of case or foci/outbreak investigation.  
6.1.2.1 Village inclusion after case investigation  
Case investigation will be performed systematically in the three townships of Myawaddy, Kawkareik and 
Hlaingbwe, upon notification of >1 P. falciparum clinical case. The aim will be to determine the most likely 
location of transmission. 
The village or cluster of houses corresponding to the most likely location of transmission will be included 
in group 2 it is located in Myawaddy, Kawkareik and Hlaingbwe. 
The most likely location of transmission will not be included in group 2 if it is located outside METF area, 
or in Hpapun township. 
However, upon evolution of the overall incidence, subdivisions of Hpapun township reaching 0-
transmission will be included in the case investigation activities and therefore eligible for case investigation 
and inclusion in group 2 MSAT. 
6.2.2.2 Village inclusion after outbreak investigation 
Outbreak alarms will be generated from Hpapun township by the analysis of weekly P. falciparum 
incidence data by METF surveillance system (e.g. following thresholds such as cases>90th percentile at the 
village or cluster level). An investigation will be conducted to determine the context of transmission and 
assess the contribution of imported case in this increase. 
The cluster will be included in group 2 if the investigation concludes to the existence of a local increased 
transmission episode.  
6.2. Study Participants 
Since the study will be performed at cluster/village level, the population of study villages will be included 
and monitored as a whole for the primary outcome on falciparum malaria incidence in the village. Likewise, 
change in prevalence will be measured by a follow-up survey at village level without matching individuals 
from MSAT screening to follow-up survey. 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 13 of 28 
MSAT intervention and follow-up surveys will be conducted on individual participants. All population of 
the cluster/village will be eligible for participation in the MSAT campaign. For the follow-up survey, only 
residents living in the village for >1 months will be considered in order to assess the reservoir in the village 
population and limit the contribution of imported carriage. 
6.3. MSAT intervention 
6.3.1. Inclusion criteria 
All persons living in the village or cluster of villages will be eligible for MSAT intervention. Individuals living 
in smaller settlements (permanent or temporary) within walking distance of a selected intervention village 
will also be eligible. 
Large “work-related” settlements in the vicinity of a targeted village (military camps, logging camp, mining 
site) will be approached by the team to be included in the screening and treatment activity. They will be 
included in the analysis as a unit within a cluster of villages if all the study information can be collected 
(including follow-up survey for Group 1). 
6.3.2. Exclusion criteria 
 
Individuals who do not provide informed consent for both URDT screening and treatment in case of 
positive result. Individuals will be given the possibility to refuse the collection of the 50µL reference 
sample or the DBS collection but participate to URDT screening and treatment. 
 
Children <1 year old 
 
Individuals with a documented Pf-positive malaria RDT who received treatment (AL+sld PMQ) during 
the previous 7 days. 
NB: Individuals who were diagnosed infected with PF and received a treatment between 7 and 30 days 
before the intervention are still likely to be URDT positive due to the persistence of HRP2, and this will 
result in treatment of individuals who are likely uninfected. However, in a high prevalence area or in an 
outbreak context, previous infection signals exposure, and DP will provide a protection against a likely re-
infection.   
6.3.3. Specific treatment regimen 
Screening can be conducted on all village inhabitants but some specific population groups will require a 
specific treatment if they are found positive (see 8. Intervention) 
6.4. Follow-up at 12 months (group 1 only) 
6.4.1. Inclusion criteria 
Randomly sampled individuals living in the village. 
6.4.2. Exclusion criteria 
o Individuals who do not provide informed consent. 
o Individuals who have lived in the village for less than 4 weeks (newcomers residing elsewhere before) 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 14 of 28 
o Individuals who had a falciparum positive RDT and received a complete ACT-treatment course during 
the 3 weeks before the survey. 
 
6.4.3.  Follow-up MSAT 
A follow-up MSAT will be triggered if the estimated URDT prevalence of the M12 survey is >5%. It will 
follow the same procedures as the baseline MSAT. 
7. STUDY PROCEDURES 
7.1. Recruitment 
Villages will be allocated to group 1 (programmatic MSAT) based on incidence over the previous 12 
months. This list will be revised twice per year after each transmission season (February and August). 
Villages will be allocated to group 2 (reactive MSAT) based on weekly analysis of malaria surveillance data 
(see details in 6.1). 
Following the allocation of villages to a given group and the decision to conduct the intervention, the 
community engagement team will conduct meetings in the village/cluster to explain the purpose of the 
intervention and seek community approval, first with village and local authorities, then with the entire 
population. After the agreement from the community, a date will be set for the intervention and the 
mobilization and engagement of individuals will begin, involving CE team members and the MP worker 
from the village. 
The MSAT intervention will be conducted by visiting participants at home or by inviting them to a central 
location, depending on the lay-out of the village and the preferences of the populations. Participant 
information will be discussed individually and participant will be recruited in the MSAT intervention after 
informed consent. The same procedure will be followed for M12 follow-up survey in Group 1. 
7.2. Informed Consent 
The MSAT intervention will first be explained to the community, through meetings with leaders and 
authorities, public meetings with all individuals and meetings and activities for specific groups of 
participants (school-age children…). Seeking community consent first will allow time for the population 
invited to participate to discuss with field team members and with each other, to ask questions and 
address concerns. Participant information will be presented under different forms during these activities. 
At inclusion, written and verbal versions of the Participant Information and Informed Consent will be 
presented to the participants detailing: the exact nature of the study; what it will involve for the 
participant; the implications and constraints of the protocol; the known side effects and any risks involved 
in taking part. It will be clearly stated that the participant is free to withdraw from the study at any time 
for any reason without prejudice to future care, and with no obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the field team or other independent parties to decide whether they will participate in the 
study. Written Informed Consent will then be obtained by means of participant dated signature and dated 
signature of the person who presented and obtained the Informed Consent. The person who obtained the 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 15 of 28 
consent must be suitably qualified and experienced, and have been authorised to do so by the Chief 
Investigator. A copy of the signed Informed Consent will be given to the participant. The original signed 
form will be retained at the study site. 
For children ≥ 10 to < 18  years old t, an assent will be obtained in addition to the consent of their parent 
or guardian. For children below 10 years, the consent of the parent or guardian will be obtained. 
A second consent will be collected upon participation to the follow-up survey, 12 months after MSAT 
intervention. 
7.3. Screening and Eligibility Assessment 
All participants who consent to be tested and treated if falciparum positive will be eligible to participate 
in the MSAT intervention. 
7.4. Randomisation, blinding and code-breaking 
No randomization will be conducted. Villages with sustained high incidence will be assessed every 6 
months and prioritized based on accessibility/feasibility. As much as possible, all villages from a given area 
will be addressed at the same time in order to maximize impact of interventions. 
7.5. Baseline Assessments 
The baseline assessment (D0) will occur immediately after inclusion. Participants will be asked baseline 
demographic data (age, sex, visitor status, occupation and activities during the previous month) and 
baseline clinical data (temperature and history of fever over the previous week), which will be recorded in 
a logbook where each patient will be identified by a unique number printed on a sticker that will also be 
used to label the URDT, the sample(s) collected from the participant. 
In group 1 only, participants will undergo a finger-prick from which capillary blood will be collected using 
the lancet provided by the URDT manufacturer in order to realize the URDT. From the same finger-prick, 
50µL of capillary blood will also be collected on an EDTA microtube, labelled with a participant sticker. 
The URDT will be read by a trained field worker following the manufacturer’s instructions. If the test is 
positive, a second finger prick will be conducted in order to collect an additional blood sample on filter 
paper (3x 1cm blood spots), labelled with a participant sticker. 
If the test is positive, a physical and clinical examination will be conducted. Female participants of child-
bearing age will be asked if they are or could be pregnant and proposed to take a pregnancy test if unsure. 
History of malaria diagnosis and treatment during the previous week will be collected. The weight of the 
participant will be measured and history of previous allergies to drugs and specifically antimalarials will be 
collected. A curative treatment for P. falciparum malaria will be administered to falciparum-positive 
participant following a weight-adjusted dosage and according to each participant characteristics (see 8. 
intervention). 
The willingness and ability of eligible participants to take a complete treatment will be assessed by the 
fieldworker, and the importance of completing the treatment will be discussed with the participant if 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 16 of 28 
necessary. The first dose of treatment will be administered directly, and recorded in the logbook. An 
appointment will be set for the next dose on the following day. 
Participants who declare being unable to attend supervised treatment for the next takes will be given the 
remaining doses (expected <2.5% of treatments initiated). 
7.6. Subsequent Visits 
7.6.1. Treatment administration follow-up visits (visit 2, visit 3) 
Subsequent visits will be conducted on the second and third day of standard DP antimalarial treatment for 
individuals receiving the standard DP course (D1, D2). Before administering the next dose, a small 
questionnaire will be used to collect potential adverse events or other complaints.  
For 1st trimester pregnant women treated with Q/C, the village malaria post worker will be in charge of 
completing the follow-up of the 7-day treatment course as per his training. For patients receiving other 
types of treatment, a team medic will follow-up the completion of the treatment and monitor for AE daily. 
7.6.2. Malaria incidence monitoring 
Each village is equipped with a community-based malaria post, where a trained member of the community 
provides diagnosis and treatment to all fever cases occurring in the village. The MP records the result of 
all RDT conducted and reports weekly activity data, including number of fever consultations, number and 
result of RDT performed and number of clinical malaria episodes treated by sex and age-group of patient 
and by parasite species. 
7.6.3. Follow-up prevalence survey (group 1) 
Twelve months after the beginning of the MSAT campaign in group 1 villages (high incidence), a population 
list will be collected again and a prevalence survey will be conducted in a sample of village inhabitants to 
perform URDT and collect a sample of 50µL for reference testing (sample size based on ability to measure 
a 90% decrease from baseline, see 9.2).  
After the subsample of inhabitants has been surveyed, if the URDT prevalence is above 5%, the survey will 
shift to an MSAT round following the same protocol as baseline. If the URDT prevalence is below 5%, the 
positive individuals will be referred to MP for treatment and the survey will finish. 
This survey will identify households from the MSAT campaign, but not match individual identification 
codes. 
Since the procedures and interventions are similar to  
7.7. Sample Handling 
From the same finger-prick used to perform the URDT, 50µL of capillary blood will also be collected on an 
EDTA microtube, labelled with a participant sticker and transported to SMRU laboratories or stored 
immediately at -80°C in a dry-shipper liquid-nitrogen tank before transport. Upon reception at SMRU 
laboratories, the samples will be and stored at -80° C until processed for reference malaria detection by 
Quansys ELISA. 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 17 of 28 
If the test is positive, a second finger prick will be conducted in order to collect an additional blood sample 
on filter paper (3x 1cm blood spots), labelled with a participant sticker, dried and stored in a plastic blister 
with silica gel. The DBS will be sent to MORU laboratory in Bangkok for DNA extraction and analysis by 
GENRE Mekong (O. Miotto, Mahidol Oxford Research Unit & Sanger Institute, UK) or MIVS-ACT (M. 
Imwong, Faculty of Tropical Medicine, Mahidol University, Thailand and Mahidol Oxford Research Unit) 
projects. 
The follow-up survey 12 months after MSAT will follow the same procedures. The samples will be 
transported to SMRU laboratories and stored at -80°C until processed for reference malaria detection by 
Quansys ELISA. 
7.8. Discontinuation/Withdrawal of Participants from Study 
The follow-up and study outcomes are defined at the village-level and apply to village populations rather 
than individuals. An eligible village will be excluded from the study if: 
- 
the MSAT intervention can’t be conducted (refused by the community, impossible to access) 
- 
the population size changes by >50% between MSAT and follow-up survey. 
Each participant has the right to withdraw from the study at any time.  
In this study, systematic individual follow-up will occur during the MSAT intervention period and after the 
MSAT intervention to monitor demographics and clinical case incidence.  
During the MSAT intervention individual follow-up will be conducted to ensure that a complete treatment 
is taken by all individuals found infected with P. falciparum. In the light of the threats of artemisinin-
resistance, it will however be necessary to ensure that all falciparum-positive individuals are treated and 
that all individuals initiating a treatment take a complete curative course. Counselling will be provided to 
participants wishing to discontinue their participation. The counsellors will be members of the CE team 
with an extensive experience of interventions requiring the treatment of asymptomatic participants 
(filariasis and/or malaria mass drug administration campaigns in the region). In case the participant refuses 
to continue his/her antimalarial treatment course outside of the study, he/she will be offered to receive 
standard treatment for falciparum clinical malaria (AL+sld PMQ) from the village MP, or referred to the 
nearest health facility. The reason for withdrawal will be recorded in the MSAT logbook. 
Individuals or households moving in or out of the village will be assessed during the M12 follow-up. 
Newcomers will contribute to the village follow-up and be included in the prevalence survey if they match 
inclusion criteria.  
7.9. Definition of End of Study 
The end of the study will be 12 months after the MSAT campaign if the estimated prevalence measured 
by URDT in the field is <5%, with the upper limit of the confidence interval below 10%. If the estimated 
prevalence is >5%, a new round of MSAT will be triggered. The follow-up will be conducted until 12 months 
after the last MSAT or 36 months after the first MSAT. 
The threshold of 5% URDT prevalence corresponds to a 7.5% prevalence by uPCR, which was found to be 
indicating the presence of a substantial reservoir previously. 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 18 of 28 
The MP will remain to continue diagnosis and treatment of fever cases as per the general METF 
procedures. 
8. INTERVENTIONS / INVESTIGATIONS  
For all participants in the two groups, investigation will consist in 1 URDT (Malaria Ag P.f ultrasensitive, 
SD/Alere, Republic of Korea). 
For P. falciparum URDT positive individuals in the two groups:  
- 
collection of 3x1cm dried blood spots on filter paper  
- 
administration of a supervised antimalarial treatment course to individuals for which a P. 
falciparum will have been detected by URDT. 
Specifically in group 1, a population list will be collected in each village prior to MSAT campaign and all 
participants will undergo: 
- 
collection of a 50µL-aliquot of capillary blood for each participant to the screening during the 
MSAT intervention. 
- 
1 URDT + collection of a 50µL-aliquot of capillary blood for each participant to the follow-up survey 
at M12. 
A safe, recommended treatment of P. falciparum malaria will be administered to URDT positive individuals 
based on participant’s characteristics: 
o The standard regimen for participants without known antimalarial allergy, not pregnant and 
not breastfeeding, will be a 3-day supervised weight-adjusted DP course and a single low dose 
PMQ. The single low dose PMQ will be administered on the first day.  
o Pregnant women and in their 2nd or 3rd trimester, and breastfeeding mothers, will receive a DP 
course but no PMQ.  
o Pregnant women in their first trimester will receive an oral course of quinine+clindamycin (7 
days).  
o Individuals with known drug allergy to piperaquine will be treated with AL (+/- sld PMQ as per 
their pregnancy/breastfeeding status) 
o Specific/complex cases will be assessed by a medic and referred to a health facility for 
treatment if necessary. 
The treatment will be directly observed by the MSAT team. 
9. STATISTICS AND ANALYSIS 
9.1. Description of Statistical Methods 
Coverage of intervention: the coverage of the intervention will be defined as the proportion of individuals 
screened by URDT divided by the total number of individuals present in the village during the next 
Before/after MSAT yearly cumulative incidence and 95% Poisson confidence intervals will be calculated 
using: 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 19 of 28 
- 
Numerator: the total number of P. falciparum cases reported during the weeks with an MP report.  
- 
Denominator: the village population size measured during the MSAT * number of weeks with an 
MP report during the year (number of weeks of MP activity). 
Analysis including the entire follow-up available for malaria posts will be conducted in order to provide 
adjusted estimates on the 
9.2. The Number of Participants (group 1 only) 
The sample size can be calculated for group 1 only, since the baseline cumulative incidence in group 2 will 
depend on surveillance outcomes, and often correspond to responses to a single case. 
9.2.1. Sample size for stepped-wedge comparison of incidence decrease following 
MSAT  
MSAT will be implemented in 60 villages with high 1-year cumulative incidence of P. falciparum clinical 
cases in 6 waves of 10 villages (1 wave per semester). Assuming a baseline cumulative incidence of 250 
cases/1000/year, a population of 190 inhabitants per village with a 0.49 coefficient of variation in cluster 
size and an intra-cluster correlation coefficient of 0.12, the expected detectable difference between 
villages with and without intervention is <25 cases/1000/year for alpha=0.01 & beta=0.9. 
9.2.2. Sample size for prevalence comparison  
9.2.2.1. 
Sample size for prevalence decrease evaluation at village-level 
For each village, the sample size required for M12 survey will be calculated to measure a 90% prevalence 
decrease from baseline prevalence by reference method, with a 95%CI width of 200% of expected M12 
prevalence if its value is expected <2% and of 100% of expected M12 prevalence if its value is 
expected>2%. This should result in a sample size of 60 to 120 samples per village, depending on village 
size. 
9.2.2.2. 
Number of villages required for prevalence comparison 
We assume an average P. falciparum prevalence of 16% in group 1 villages using reference assay. 
Before/after comparison at village level will use samples from the same village but not necessarily the 
same individuals (correlation between paired observations set to 0). The sample size was calculated 
assuming 60 samples per cluster (the minimal number of samples collected at M12), an intra-cluster 
correlation coefficient of 0.15, the sample size required to identify a 50% decrease 12 months after 
intervention compared to baseline is 43 clusters for alpha=0.05 and 1-beta=0.8. 
9.2.3. Sample size for retrospective incidence comparison between MSAT and MDA 
If comparing 50 MSAT villages and 50 MDA, we will be able to differentiate MSAT from MDA efficacy if 
MSAT achieves around 50% of MDA impact on incidence or less.  
The average village size was 190 inhabitants (coefficient of size variation=0.64) with an intra-cluster 
correlation coefficient of 0.12 (estimated using incidence series) and MDA was already completed in 60 
villages. The 10 villages in which MDA was conducted based on prevalence values that will be the furthest 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 20 of 28 
from what will be measured during the MSAT campaign will be excluded. Villages receiving MSAT after 
MDA will be excluded from MSAT group. With a comparison of 50 MSAT, it will be possible to detect a 
difference in incidence rate of 50/1000/year between the two groups (with alpha=5% and power=80%). 
This would correspond to a reduction of incidence by only 40% after MSAT (70 cases/1000/year after 
compared to 125 before). With MDA, 80% incidence reduction was achieved: the average cumulative 
incidence during the first year after MDA was 20 case/1000/year, compared to 125 before. 
9.3. Analysis of Outcome Measures 
Primary outcome: stepped-wedge comparison of incidence. 
The incidence comparison will be conducted over a 2-year series of weekly incidence data, corresponding 
to 12 months before and 12 months after MSAT intervention. A generalized additive multilevel mixed 
model will be used to adjust for location, season, and temporal trend due to MP activity using uni- 
(seasonality, duration of MP activity in the village) or bivariate (latitude and longitude) splines, including 
random intercept and slopes at village level. MSAT intervention will be included in the model as a 0-1 
variable. The incidence rate ratio obtain for this variable will quantify the average decrease in incidence 
after MSAT campaign compared to before.  
Secondary outcome: before-after comparison of prevalence 
For each village, the fractional change in prevalence before MSAT and 12 months after will be calculated 
and compared to 0% change.  This change will be compared to the fractional change observed after MDA. 
10. DATA MANAGEMENT 
10.1. 
Access to Data 
Direct access will be granted to authorised representatives from the Shoklo Malaria Research 
Unit/Mahidol Oxford Research Unit and any host institution for monitoring and/or audit of the study to 
ensure compliance with regulations.  
10.2. 
Data Handling and Record Keeping 
All data collected specifically for the study (MSAT logbook, AE forms and where appropriate, follow-up 
survey logbook, demographic follow-up and individual falciparum clinical case data) will be recorded on 
paper forms in the field and entered in a secure Access database managed by SMRU data management 
team. 
Laboratory results will be merged to this database using patient unique identifier which will be used to 
label the samples. 
Analysis will be conducted on anonymized data. 
11. QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
The study will be conducted in accordance with relevant regulations and standard operating procedures. 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 21 of 28 
12. ETHICAL AND REGULATORY CONSIDERATIONS 
12.1. 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki.  
12.2. 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
12.3. 
Approvals 
The protocol, informed consent form, and participant information sheet will be submitted to the Ethics 
Review Committee on Medical Research Involving Human Subjects from the Republic of the Union of 
Myanmar, Ministry of Health and Sports, Department of Medical Research (Lower Myanmar), OXTREC for 
written approval. Furthermore, the protocol, informed consent form, and participant information sheet 
will be reviewed by community-based committees assembling members of the communities in which the 
study will be performed: the Karen Department of Health and Welfare and the Tak Community Advisory 
Board [8]. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
amendments to the original approved documents. 
12.4. 
Participant Confidentiality 
The study staff will ensure that the participants’ anonymity is maintained. The participants will be 
identified only by a participant ID number on all study documents and any electronic database, with the 
exception of the MSAT logbook, where participant name will be added to allow identification.  All 
documents will be stored securely and only accessible by study staff and authorised personnel. The study 
will comply with the Data Protection Act, which requires data to be anonymised as soon as it is practical 
to do so. 
12.5. 
Expenses and Benefits 
No payments will be given to participants for their participation in the study.  
12.6. 
Reporting 
The CI shall submit an Annual Progress Report to OxTREC on the anniversary of the date of approval of the 
study. In addition, the CI shall submit an End of Study Report to OxTREC within 12 months of completion 
of the study. 
13. FINANCE AND INSURANCE 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 22 of 28 
13.1. 
Funding 
This project is funded by a grant from the Bill & Melinda Gates Foundation to the Shoklo Malaria Research 
Unit, via Oxford University and the Mahidol Oxford Research Unit. 
13.2. 
Insurance 
The project is covered under the Oxford University sponsorship. 
The University has a specialist insurance policy in place which would operate in the event of any participant 
suffering harm as a result of their involvement in the research (Newline Underwriting Management Ltd, at 
Lloyd’s of London).   
14. PUBLICATION POLICY 
The results of this study will be published in peer-reviewed journal, following the standard policy of the 
Mahidol-Oxford University Research Unit. 
The results will be communicated to the communities, by the Community Engagement team of the Malaria 
Elimination Task Force. 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 23 of 28 
15. REFERENCES 
1. Parker DM, Landier J, Thu AM, Lwin KM, Delmas G, Nosten FH. Scale up of a Plasmodium falciparum 
elimination program and surveillance system in Kayin State, Myanmar. Wellcome Open Res. 2017;2:98.  
2. Landier J, Kajeechiwa L, Thwin MM, Parker DM, Chaumeau V, Wiladphaingern J, et al. Safety and 
effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum 
malaria: A pilot trial in four villages of Eastern Myanmar. Wellcome Open Res. 2017;2:1–14.  
3. Das S, Jang IK, Barney B, Peck R, Rek JC, Arinaitwe E, et al. Performance of a High-Sensitivity Rapid 
Diagnostic Test for Plasmodium falciparum Malaria in Asymptomatic Individuals from Uganda and 
Myanmar and Naive Human Challenge Infections. Am. J. Trop. Med. Hyg. 2017;  
4. Bancone G, Chowwiwat N, Somsakchaicharoen R, Nyo N, Ling CL, Wiladphaingern J, et al. Single Low 
Dose Primaquine ( 0 . 25mg / kg ) does not cause clinically significant haemolysis in G6PD deficient 
subjects. PLoS One. 2016;11:e0151898.  
5. Cottrell G, Moussiliou A, Luty AJF, Cot M, Fievet N, Massougbodji A, et al. Submicroscopic Plasmodium 
falciparum Infections Are Associated With Maternal Anemia, Premature Births, and Low Birth Weight. 
Clin. Infect. Dis. 2015;60:1481–8.  
6. Sifft KC, Geus D, Mukampunga C, Mugisha JC, Habarugira F, Fraundorfer K, et al. Asymptomatic only at 
first sight: malaria infection among schoolchildren in highland Rwanda. Malar. J. BioMed Central; 
2016;15:553.  
7. Portugal S, Tran TM, Ongoiba A, Bathily A, Li S, Doumbo S, et al. Treatment of Chronic Asymptomatic 
Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection. Clin. 
Infect. Dis. 2017;64:645–53.  
8. Cheah PY, Lwin KM, Phaiphun L, Maelankiri L, Parker M, Day NP, et al. Community engagement on the 
Thai-Burmese border: rationale, experience and lessons learnt. Int. Health. 2010;2:123–9.  
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 24 of 28 
16. APPENDIX A:  STUDY FLOW CHART  
– by village 
 
 
- by participant 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 25 of 28 
17. APPENDIX B:  SCHEDULE OF STUDY PROCEDURES 
 
Procedures 
Visits (insert visit numbers as appropriate) 
Day 0 
 
 
 
 
 
Informed consent 
Day 0 
 
 
 
 
 
Demographics 
Day 0 
 
 
 
 
 
Malaria history over previous 3 
weeks 
Day 0 
 
 
 
 
 
Temperature 
Day 0 
 
 
 
 
 
Falciparum URDT (+50µL sample 
collection in group 1) 
Day 0 
 
 
 
 
 
Falciparum positive participant 
 
 
 
 
 
 
Clinical examination 
Day 0 
 
 
 
 
 
Treatment 
Day 0 
Day 1 
Day 2 
* 
 
 
Passive AE follow-up 
(study team/MPW) 
Day 0 
Day 1 
Day 2 
Day 3 
Day 4 
 
All participants 
 
 
 
 
 
 
Passive incidence data collection 
Day 0 
 
 
 
Daily 
Day 
365 
Group 1 villages 
 
 
 
 
 
 
Demographic data collection  
Day 0 
 
 
 
 
Day 
365 
M12 follow-up survey in group 1: 
URDT+50µL sample collection 
 
 
 
 
 
Day 
365 
*a longer follow-up may be required for patients receiving specific regimen other than standard 
MDA treatment (DP3+sldPMQ) or standard first-line treatment for clinical cases (AL3+sldPMQ).  
 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 26 of 28 
18. APPENDIX C:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made 
 
 
 
 
 
 
List details of all protocol amendments here whenever a new version of the protocol is produced.  This is 
not necessary prior to initial Ethics Committee submission. 
 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 27 of 28 
19. APPENDIX D:  UNPUBLISHED DATA ON URDT PERFORMANCE 
This data was presented as a poster at the ASTMH Conference in November 2017. 
 

METF MSAT v2.0 – 20 Feb 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 28 of 28