• Markers of sulfadoxine-pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention.

      van Lenthe, M; van der Meulen, R; Lassovski, M; Ouabo, A; Bakula, E; Badio, C; Cibenda, D; Okell, L; Piriou, E; Grignard, L; et al. (BioMed Central, 2019-12-18)
      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.
    • Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

      van Lenthe, M; van der Meulen, R; Okell, L; Piriou, E; Lassovski, M; Bakula, E; Badio, C; Roper, C; Bousema, T; Ouabo, A; et al. (Springer Science and Business Media LLC, 2019-12-18)
      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.
    • Mortality and health survey, Walikale, Democratic Republic of the Congo, 2017: an example of the use of survey data for humanitarian program planning

      Robinson, E; Crispino, V; Ouabo, A; Soung Iballa, F; Kremer, R; Serbassi, M; van Lenthe, M; Carrion Martin, A (Springer Science and Business Media LLC, 2019-11-21)
      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.
    • Mortality beyond emergency threshold in a silent crisis- results from a population-based mortality survey in Ouaka prefecture, Central African Republic, 2020.

      Robinson, E; Lee, L; Roberts, LF; Poelhekke, A; Charles, X; Ouabo, A; Vyncke, J; Ariti, C; Gbanzi, MCA; Ouakouma, MT; et al. (BioMed Central, 2021-06-30)
      Background: The Central African Republic (CAR) suffers a protracted conflict and has the second lowest human development index in the world. Available mortality estimates vary and differ in methodology. We undertook a retrospective mortality study in the Ouaka prefecture to obtain reliable mortality data. Methods: We conducted a population-based two-stage cluster survey from 9 March to 9 April, 2020 in Ouaka prefecture. We aimed to include 64 clusters of 12 households for a required sample size of 3636 persons. We assigned clusters to communes proportional to population size and then used systematic random sampling to identify cluster starting points from a dataset of buildings in each commune. In addition to the mortality survey questions, we included an open question on challenges faced by the household. Results: We completed 50 clusters with 591 participating households including 4000 household members on the interview day. The median household size was 7 (interquartile range (IQR): 4-9). The median age was 12 (IQR: 5-27). The birth rate was 59.0/1000 population (95% confidence interval (95%-CI): 51.7-67.4). The crude and under-five mortality rates (CMR & U5MR) were 1.33 (95%-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 were malaria/fever (16.0%; 95%-CI: 11.0-22.7), violence (13.2%; 95%-CI: 6.3-25.5), diarrhoea/vomiting (10.6%; 95%-CI: 6.2-17.5), and respiratory infections (8.4%; 95%-CI: 4.6-14.8). The maternal mortality ratio (MMR) was 2525/100,000 live births (95%-CI: 825-5794). Challenges reported by households included health problems and access to healthcare, high number of deaths, lack of potable water, insufficient means of subsistence, food insecurity and violence. Conclusions: The CMR, U5MR and MMR exceed previous estimates, and the CMR exceeds the humanitarian emergency threshold. Violence is a major threat to life, and to physical and mental wellbeing. Other causes of death speak to poor living conditions and poor access to healthcare and preventive measures, corroborated by the challenges reported by households. Many areas of CAR face similar challenges to Ouaka. If these results were generalisable across CAR, the country would suffer one of the highest mortality rates in the world, a reminder that the longstanding "silent crisis" continues.