Protocol > Research Study
de Wit MBK, Rao B, Lassovski M, Ouabo A, Badjo C, et al.
2018 July 1
Primary Objective: To measure the prevalence of molecular markers of SP resistant malaria in North and South Kivu, DRC.
Sulfadoxine/pyrimethamine (SP) forms the backbone of most malaria chemoprevention programmes in high endemicity settings, including intermittent preventative therapy in pregnancy and infants (IPTp and IPTi respectively) as well as seasonal malaria chemoprevention (SMC). P. falciparum parasite resistance to SP threatens recent triumphs preventing malaria infection in the most vulnerable risk groups. WHO guidance is that chemoprevention using SP may not be implemented when prevalence of the dhps K540E gene denoting SP resistance are greater than 50%. Simple, robust polymerase chain reaction (PCR) - based methods for molecular surveillance of resistance to SP have the potential to indicate whether SP-based chemoprevention programmes would be effective in areas where surveillance was conducted, but also to identify early stages of emerging resistance in order to advocate for alternative chemoprevention strategies.
A minimum of 750 samples will be collected per province. Three sites per province will provide 250 samples assuming an estimated prevalence of 50% prevalence of dhps K540E gene with 95% confidence and 5% precision. This is also sufficient for robust estimation of the prevalence of dhps 581, an alternative critical marker. This sample size is calculated to estimate regional prevalence, i.e. for both South Kivu and North Kivu, and hence this study requires samples from multiple MSF sites (including from different MSF Operating Centre missions) e.g. Baraka, Kimbi and Lulingu amongst others in South Kivu and Mweso, Rutsuru and Walikale in North Kivu with a minimum total of 750 per province. If estimating specific prevalence in only one limited site, a large sample size would be required.
Sulfadoxine/pyrimethamine (SP) forms the backbone of most malaria chemoprevention programmes in high endemicity settings, including intermittent preventative therapy in pregnancy and infants (IPTp and IPTi respectively) as well as seasonal malaria chemoprevention (SMC). P. falciparum parasite resistance to SP threatens recent triumphs preventing malaria infection in the most vulnerable risk groups. WHO guidance is that chemoprevention using SP may not be implemented when prevalence of the dhps K540E gene denoting SP resistance are greater than 50%. Simple, robust polymerase chain reaction (PCR) - based methods for molecular surveillance of resistance to SP have the potential to indicate whether SP-based chemoprevention programmes would be effective in areas where surveillance was conducted, but also to identify early stages of emerging resistance in order to advocate for alternative chemoprevention strategies.
A minimum of 750 samples will be collected per province. Three sites per province will provide 250 samples assuming an estimated prevalence of 50% prevalence of dhps K540E gene with 95% confidence and 5% precision. This is also sufficient for robust estimation of the prevalence of dhps 581, an alternative critical marker. This sample size is calculated to estimate regional prevalence, i.e. for both South Kivu and North Kivu, and hence this study requires samples from multiple MSF sites (including from different MSF Operating Centre missions) e.g. Baraka, Kimbi and Lulingu amongst others in South Kivu and Mweso, Rutsuru and Walikale in North Kivu with a minimum total of 750 per province. If estimating specific prevalence in only one limited site, a large sample size would be required.
Journal Article > Meta-AnalysisFull Text
Confl Health. 2019 November 21; Volume 13 (Issue 1); DOI:10.1186/s13031-019-0232-y
Robinson E, Crispino V, Ouabo A, Iballa F, Kremer R, et al.
Confl Health. 2019 November 21; Volume 13 (Issue 1); DOI:10.1186/s13031-019-0232-y
BACKGROUND
During humanitarian crises, health information systems are often lacking and surveys are a valuable tool to assess the health needs of affected populations. In 2013, a mortality and health survey undertaken by Médecins Sans Frontières (MSF) in the conflict affected Walikale territory of North Kivu, Democratic Republic of the Congo (DRC), indicated mortality rates exceeding humanitarian crisis thresholds and a high burden of mortality and morbidity due to malaria. In late 2017, after a period of relative stability, MSF reassessed the health status of the population through a second survey to guide ongoing operations.
METHODS
A two-stage cluster survey, selecting villages using probability proportional to size and households using random walk procedures, was conducted. Household members were interviewed on morbidity and mortality, healthcare use, vaccination status, and bednet availability.
RESULTS
The sample included 5711 persons in 794 households. The crude mortality rate (CMR) and under-five mortality rate (U5MR) were 0.98 per 10,000 persons/day (95% confidence interval (CI) 0.78–1.2) and 1.3 per 10,000 persons/day (95% CI): 0.82–2.0), respectively. The most frequently reported causes of death were fever/malaria (31%), diarrhoea (15%) and respiratory infections (8%). In 89% of households at least one person was reported as falling ill in the previous 2 weeks, and 58% sought healthcare. Cost was the main barrier amongst 58% of those who did not seek healthcare. Coverage of measles-containing-vaccine was 62% in under-fives. Sufficient bednet coverage (1 bednet/2 people) was reported from 17% of households.
CONCLUSION
The second survey illustrates that although mortality is now just below crisis thresholds, the area still experiences excess mortality and has substantial health needs. The study results have supported the further expansion of integrated community case management to improve access to care for malaria, diarrhoea and respiratory infections. Such surveys are important to orient operations to the health needs of the population being served and also highlight the ongoing vulnerability of populations after humanitarian crises.
During humanitarian crises, health information systems are often lacking and surveys are a valuable tool to assess the health needs of affected populations. In 2013, a mortality and health survey undertaken by Médecins Sans Frontières (MSF) in the conflict affected Walikale territory of North Kivu, Democratic Republic of the Congo (DRC), indicated mortality rates exceeding humanitarian crisis thresholds and a high burden of mortality and morbidity due to malaria. In late 2017, after a period of relative stability, MSF reassessed the health status of the population through a second survey to guide ongoing operations.
METHODS
A two-stage cluster survey, selecting villages using probability proportional to size and households using random walk procedures, was conducted. Household members were interviewed on morbidity and mortality, healthcare use, vaccination status, and bednet availability.
RESULTS
The sample included 5711 persons in 794 households. The crude mortality rate (CMR) and under-five mortality rate (U5MR) were 0.98 per 10,000 persons/day (95% confidence interval (CI) 0.78–1.2) and 1.3 per 10,000 persons/day (95% CI): 0.82–2.0), respectively. The most frequently reported causes of death were fever/malaria (31%), diarrhoea (15%) and respiratory infections (8%). In 89% of households at least one person was reported as falling ill in the previous 2 weeks, and 58% sought healthcare. Cost was the main barrier amongst 58% of those who did not seek healthcare. Coverage of measles-containing-vaccine was 62% in under-fives. Sufficient bednet coverage (1 bednet/2 people) was reported from 17% of households.
CONCLUSION
The second survey illustrates that although mortality is now just below crisis thresholds, the area still experiences excess mortality and has substantial health needs. The study results have supported the further expansion of integrated community case management to improve access to care for malaria, diarrhoea and respiratory infections. Such surveys are important to orient operations to the health needs of the population being served and also highlight the ongoing vulnerability of populations after humanitarian crises.
Journal Article > ResearchFull Text
Malar J. 2024 May 15; Volume 23 (Issue 1); 146.; DOI:10.1186/s12936-024-04968-1
Robinson E, Ouabo A, Rose L, van Braak F, Vyncke J, et al.
Malar J. 2024 May 15; Volume 23 (Issue 1); 146.; DOI:10.1186/s12936-024-04968-1
BACKGROUND
In 2020, during the COVID-19 pandemic, Médecins Sans Frontières (MSF) initiated three cycles of dihydroartemisin-piperaquine (DHA-PQ) mass drug administration (MDA) for children aged three months to 15 years within Bossangoa sub-prefecture, Central African Republic. Coverage, clinical impact, and community members perspectives were evaluated to inform the use of MDAs in humanitarian emergencies.
METHODS
A household survey was undertaken after the MDA focusing on participation, recent illness among eligible children, and household satisfaction. Using routine surveillance data, the reduction during the MDA period compared to the same period of preceding two years in consultations, malaria diagnoses, malaria rapid diagnostic test (RDT) positivity in three MSF community healthcare facilities (HFs), and the reduction in severe malaria admissions at the regional hospital were estimated. Twenty-seven focus groups discussions (FGDs) with community members were conducted.
RESULTS
Overall coverage based on the MDA card or verbal report was 94.3% (95% confidence interval (CI): 86.3–97.8%). Among participants of the household survey, 2.6% (95% CI 1.6–40.3%) of round 3 MDA participants experienced illness in the preceding four weeks compared to 30.6% (95% CI 22.1–40.8%) of MDA non-participants. One community HF experienced a 54.5% (95% CI 50.8–57.9) reduction in consultations, a 73.7% (95% CI 70.5–76.5) reduction in malaria diagnoses, and 42.9% (95% CI 36.0–49.0) reduction in the proportion of positive RDTs among children under five. A second community HF experienced an increase in consultations (+ 15.1% (− 23.3 to 7.5)) and stable malaria diagnoses (4.2% (3.9–11.6)). A third community HF experienced an increase in consultations (+ 41.1% (95% CI 51.2–31.8) and malaria diagnoses (+ 37.3% (95% CI 47.4–27.9)). There were a 25.2% (95% CI 2.0–42.8) reduction in hospital admissions with severe malaria among children under five from the MDA area. FGDs revealed community members perceived less illness among children because of the MDA, as well as fewer hospitalizations. Other indirect benefits such as reduced household expenditure on healthcare were also described.
CONCLUSION
The MDA achieved high coverage and community acceptance. While some positive health impact was observed, it was resource intensive, particularly in this rural context. The priority for malaria control in humanitarian contexts should remain diagnosis and treatment. MDA may be additional tool where the context supports its implementation.
In 2020, during the COVID-19 pandemic, Médecins Sans Frontières (MSF) initiated three cycles of dihydroartemisin-piperaquine (DHA-PQ) mass drug administration (MDA) for children aged three months to 15 years within Bossangoa sub-prefecture, Central African Republic. Coverage, clinical impact, and community members perspectives were evaluated to inform the use of MDAs in humanitarian emergencies.
METHODS
A household survey was undertaken after the MDA focusing on participation, recent illness among eligible children, and household satisfaction. Using routine surveillance data, the reduction during the MDA period compared to the same period of preceding two years in consultations, malaria diagnoses, malaria rapid diagnostic test (RDT) positivity in three MSF community healthcare facilities (HFs), and the reduction in severe malaria admissions at the regional hospital were estimated. Twenty-seven focus groups discussions (FGDs) with community members were conducted.
RESULTS
Overall coverage based on the MDA card or verbal report was 94.3% (95% confidence interval (CI): 86.3–97.8%). Among participants of the household survey, 2.6% (95% CI 1.6–40.3%) of round 3 MDA participants experienced illness in the preceding four weeks compared to 30.6% (95% CI 22.1–40.8%) of MDA non-participants. One community HF experienced a 54.5% (95% CI 50.8–57.9) reduction in consultations, a 73.7% (95% CI 70.5–76.5) reduction in malaria diagnoses, and 42.9% (95% CI 36.0–49.0) reduction in the proportion of positive RDTs among children under five. A second community HF experienced an increase in consultations (+ 15.1% (− 23.3 to 7.5)) and stable malaria diagnoses (4.2% (3.9–11.6)). A third community HF experienced an increase in consultations (+ 41.1% (95% CI 51.2–31.8) and malaria diagnoses (+ 37.3% (95% CI 47.4–27.9)). There were a 25.2% (95% CI 2.0–42.8) reduction in hospital admissions with severe malaria among children under five from the MDA area. FGDs revealed community members perceived less illness among children because of the MDA, as well as fewer hospitalizations. Other indirect benefits such as reduced household expenditure on healthcare were also described.
CONCLUSION
The MDA achieved high coverage and community acceptance. While some positive health impact was observed, it was resource intensive, particularly in this rural context. The priority for malaria control in humanitarian contexts should remain diagnosis and treatment. MDA may be additional tool where the context supports its implementation.
Journal Article > ResearchFull Text
Malar J. 2019 December 18; Volume 18 (Issue 1); 430.; DOI:10.1186/s12936-019-3057-7
van Lenthe M, van der Meulen R, Lassovsky M, Ouabo A, Bakula E, et al.
Malar J. 2019 December 18; Volume 18 (Issue 1); 430.; DOI:10.1186/s12936-019-3057-7
BACKGROUND
Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap.
METHODS
Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays.
RESULTS
Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample.
CONCLUSIONS
The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap.
METHODS
Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays.
RESULTS
Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample.
CONCLUSIONS
The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
Conference Material > Slide Presentation
Robinson E, Lee L, Roberts L, Poelhekke A, Charles X, et al.
MSF Scientific Days International 2021: Research. 2021 May 18
Conference Material > Abstract
Robinson E, Lee L, Roberts L, Poelhekke A, Charles X, et al.
MSF Scientific Days International 2021: Research. 2021 May 18
INTRODUCTION
The Central African Republic (CAR) has the second-lowest human development index globally and has long been described as being in a state of “silent crisis”. We planned a nationwide study to obtain reliable and comparable mortality data for CAR. Due to the COVID-19 pandemic, only the survey in Ouaka Prefecture proceeded.
METHODS
We conducted a two-stage cluster mortality survey between 9 March and 9 April 2020. We aimed to include 64 clusters of 12 households each, for a target sample size of 3,636 persons. We assigned clusters to communes proportional to population size and used systematic random sampling to identify cluster starting points from a dataset of buildings in each commune. We used a novel approach by: focusing on mortality only; adding an opening question about challenges experienced in the last year to build rapport and document general difficulties; and, for females aged 10-49 years, we included specific pregnancy-related questions to improve detection of neonatal and maternal deaths, and to estimate birth rate. The recall period ran from 26 May 2019 to the interview day (range 289-320 days). We coded reported challenges using a content analysis approach.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and the national ERB of CAR.
RESULTS
We reached 50 clusters, including 591 participating households with a total of 4,272 individuals. We identified 160 deaths. Crude and under-five mortality rates (CMR, U5MR) were 1.33 (95% confidence interval, CI, 1.09-1.61) and 1.87 (95%CI 1.37-2.54) deaths/10,000 persons/day, respectively. The most common specified causes of death (COD) for individuals aged >5 years were violence (16.7%; n=20; 95%CI 7.7-32.5) and malaria/fever (9.9%; n=11; 95%CI 5.9-16.2). Amongst children aged <5 years, the most common causes were malaria/fever (30.5%;n=15; 95%CI 17.8-47.1), diarrhoea/vomiting (24.0%; n=11;95%CI 11.9-42.7), neonatal deaths (11.9%; n=6; 95%CI 5.3-24.7), and respiratory infections (6.8%; n=3; 95%CI 2.1-20.1).Amongst females aged 10-49 years, 29.1% (95%CI 26.4-31.9%) were pregnant during the recall period. The birth rate was 59/1,000 population (95%CI 51.7-67.4), and the maternal mortality ratio was 2,525/100,000 live births (95%CI 825-5,794). Reported challenges included concerns about specific illnesses, access to healthcare, bereavement, lack of safe drinking water, insufficient means of subsistence, food insecurity, and violence.
CONCLUSION
Mortality indicators seen here exceed previous estimates, and the CMR is above the humanitarian emergency threshold. New methods used in this study may have improved data completeness and quality. Violence is a leading COD, while other causes highlight poor living conditions and difficulties accessing healthcare and preventive measures; these findings are consistent with reported challenges. The high MMR, despite its lack of precision, alongside the high neonatal death rate and birth rate, call for accessible reproductive healthcare. If our results are generalisable to other regions of CAR, national mortality rates would be among the highest globally. The planned nationwide study should proceed as soon as feasible.
CONFLICTS OF INTEREST
None declared.
The Central African Republic (CAR) has the second-lowest human development index globally and has long been described as being in a state of “silent crisis”. We planned a nationwide study to obtain reliable and comparable mortality data for CAR. Due to the COVID-19 pandemic, only the survey in Ouaka Prefecture proceeded.
METHODS
We conducted a two-stage cluster mortality survey between 9 March and 9 April 2020. We aimed to include 64 clusters of 12 households each, for a target sample size of 3,636 persons. We assigned clusters to communes proportional to population size and used systematic random sampling to identify cluster starting points from a dataset of buildings in each commune. We used a novel approach by: focusing on mortality only; adding an opening question about challenges experienced in the last year to build rapport and document general difficulties; and, for females aged 10-49 years, we included specific pregnancy-related questions to improve detection of neonatal and maternal deaths, and to estimate birth rate. The recall period ran from 26 May 2019 to the interview day (range 289-320 days). We coded reported challenges using a content analysis approach.
ETHICS
This study was approved by the MSF Ethics Review Board (ERB) and the national ERB of CAR.
RESULTS
We reached 50 clusters, including 591 participating households with a total of 4,272 individuals. We identified 160 deaths. Crude and under-five mortality rates (CMR, U5MR) were 1.33 (95% confidence interval, CI, 1.09-1.61) and 1.87 (95%CI 1.37-2.54) deaths/10,000 persons/day, respectively. The most common specified causes of death (COD) for individuals aged >5 years were violence (16.7%; n=20; 95%CI 7.7-32.5) and malaria/fever (9.9%; n=11; 95%CI 5.9-16.2). Amongst children aged <5 years, the most common causes were malaria/fever (30.5%;n=15; 95%CI 17.8-47.1), diarrhoea/vomiting (24.0%; n=11;95%CI 11.9-42.7), neonatal deaths (11.9%; n=6; 95%CI 5.3-24.7), and respiratory infections (6.8%; n=3; 95%CI 2.1-20.1).Amongst females aged 10-49 years, 29.1% (95%CI 26.4-31.9%) were pregnant during the recall period. The birth rate was 59/1,000 population (95%CI 51.7-67.4), and the maternal mortality ratio was 2,525/100,000 live births (95%CI 825-5,794). Reported challenges included concerns about specific illnesses, access to healthcare, bereavement, lack of safe drinking water, insufficient means of subsistence, food insecurity, and violence.
CONCLUSION
Mortality indicators seen here exceed previous estimates, and the CMR is above the humanitarian emergency threshold. New methods used in this study may have improved data completeness and quality. Violence is a leading COD, while other causes highlight poor living conditions and difficulties accessing healthcare and preventive measures; these findings are consistent with reported challenges. The high MMR, despite its lack of precision, alongside the high neonatal death rate and birth rate, call for accessible reproductive healthcare. If our results are generalisable to other regions of CAR, national mortality rates would be among the highest globally. The planned nationwide study should proceed as soon as feasible.
CONFLICTS OF INTEREST
None declared.