Fredrick Kateera

Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance

BackgroundDaily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS.Materials and methodsSubjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance.ResultsSixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of dhfr 51I, 108N, and 59R and dhps 437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the dhfr 164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the dhfr and dhps genes identified only one additional polymorphism, dhps 581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children.ConclusionDespite high prevalence of known anti-folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of dhfr 164L mutation.

Malaria Prevalence, Spatial Clustering and Risk Factors in a Low Endemic Area of Eastern Rwanda: A Cross Sectional Study

Background Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda. Methods A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted. Results Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5–15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5–15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed. Conclusions Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.

Community mobilization for malaria elimination: application of an open space methodology in Ruhuha sector, Rwanda

BackgroundDespite the significant reduction of malaria transmission in Rwanda, Ruhuha sector is still a highly endemic area for malaria. The objective of this activity was to explore and brainstorm the potential roles of various community stakeholders in malaria elimination.MethodsHorizontal participatory approaches such as ‘open space’ have been deployed to explore local priorities, stimulate community contribution to project planning, and to promote local capacity to manage programmes. Two open space meetings were conducted with 62 and 82 participants in years 1 and 2, respectively. Participants included purposively selected community and local organizations’ representatives.ResultsMalaria was perceived as a health concern by the respondents despite the reported reduction in prevalence from 60 to 20% for cases at the local health centre. Some misconceptions of the cause of malaria and misuse of preventive strategies were noted. Poverty was deemed to be a contributing factor to malaria transmission, with suggestions that improvement of living conditions for poor families might help malaria reduction. Participants expressed willingness to contribute to malaria elimination and underscored the need for constant education, sensitization and mobilization towards malaria control in general. Active diagnosis, preventative strategies and prompt treatment of malaria cases were all mentioned by participants as ways to reduce malaria. Participants suggested that partnership of stakeholders at various levels could speed up programme activities. A community rewards system was deemed important to motivate engaged participants, i.e., community health workers and households. Establishment of malaria clubs in schools settings was also suggested as crucial to speed up community awareness and increase skills towards further malaria reduction.ConclusionsThis bottom-up approach was found useful in engaging the local community, enabling them to explore issues related to malaria in the area and suggest solutions for sustainable malaria elimination gains.

Malaria parasite carriage and risk determinants in a rural population: a malariometric survey in Rwanda

BackgroundBased on routine health facility case data, Rwanda has achieved a significant malaria burden reduction in the past ten years. However, community-based malaria parasitaemia burden and reasons for continued residual infections, despite a high coverage of control interventions, have yet to be characterized. Measurement of malaria parasitaemia rates and evaluation of associated risk factors among asymptomatic household members in a rural community in Rwanda were conducted.MethodsA malariometric household survey was conducted between June and November 2013, involving 12,965 persons living in 3,989 households located in 35 villages in a sector in eastern Rwanda. Screening for malaria parasite carriage and collection of demographic, socio-economic, house structural features, and prior fever management data, were performed. Logistic regression models with adjustment for within- and between-households clustering were used to assess malaria parasitaemia risk determinants.ResultsOverall, malaria parasitaemia was found in 652 (5%) individuals, with 518 (13%) of households having at least one parasitaemic member. High malaria parasite carriage risk was associated with being male, child or adolescent (age group 4–15), reported history of fever and living in a household with multiple occupants. A malaria parasite carriage risk-protective effect was associated with living in households of, higher socio-economic status, where the head of household was educated and where the house floor or walls were made of cement/bricks rather than mud/earth/wood materials. Parasitaemia cases were found to significantly cluster in the Gikundamvura area that neighbours marshlands.ConclusionOverall, Ruhuha Sector can be classified as hypo-endemic, albeit with a particular ‘cell of villages’ posing a higher risk for malaria parasitaemia than others. Efforts to further reduce transmission and eventually eliminate malaria locally should focus on investments in programmes that improve house structure features (that limit indoor malaria transmission), making insecticide-treated bed nets and indoor residual spraying implementation more effective.

Molecular surveillance of Plasmodium falciparum drug resistance markers reveals partial recovery of chloroquine susceptibility but sustained sulfadoxine-pyrimethamine resistance at two sites of different malaria transmission intensities in Rwanda

Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda replaced CQ with amodiaquine (AQ)+sulfadoxine-pyrimethamine (SP) in 2001, and subsequently with artemether-lumefantrine (AL) in 2006, as first-line treatments for uncomplicated malaria. Following years of discontinuation of CQ use, re-emergence of CQ-susceptible parasites has been reported in countries including Malawi, Kenya and Tanzania. In contrast, high levels of SP resistant mutant parasites continue to be reported even in countries of presumed reduced SP drug selection pressure. The prevalence and distributions of genetic polymorphisms linked with CQ and SP resistance at two sites of different malaria transmission intensities are described here to better understand drug-related genomic adaptations over time and exposure to varying drug pressures in Rwanda. Using filter paper blood isolates collected from P. falciparum infected patients, DNA was extracted and a nested PCR performed to identify resistance-mediating polymorphisms in the pfcrt, pfmdr1, pfdhps and pfdhfr genes. Amplicons from a total of 399 genotyped samples were analysed by ligase detection reaction fluorescent microsphere assay. CQ susceptible pfcrt 76K and pfmdr1 86N wild-type parasites were found in about 50% and 81% of isolates, respectively. Concurrently, SP susceptible pfdhps double (437G-540E), pfdhfr triple (108N-51I-59R), quintuple pfdhps 437G-540E/pfdhfr 51I-59R-108N and sextuple haplotypes were found in about 84%, 85%, 74% and 18% of isolates, respectively. High-level SP resistance associated pfdhfr 164L and pfdhps 581G mutant prevalences were noted to decline. Mutations pfcrt 76T, pfdhfr 59R and pfdhfr 164L were found differentially distributed between the two study sites with the pfdhfr 164L mutants found only at Ruhuha site, eastern Rwanda. Overall, sustained intense levels of SP resistance mutations and a recovery of CQ susceptible parasites were found in this study following 7 years and 14 years of drug withdrawal from use, respectively. Most likely, the sustained high prevalence of resistant parasites is due to the use of DHFR/DHPS inhibitors like trimethoprim-sulfamethoxazole (TS) for the treatment of and prophylaxis against bacterial infections among HIV infected individuals as well as the continued use of IPTp-SP within the East and Central African regions for malaria prevention among pregnant women. With regard to CQ, the slow recovery of CQ susceptible parasites may have been caused partly by the continued use of CQ and/or CQ mimicking antimalarial drugs like AQ in spite of policies to withdraw it from Rwanda and the neighbouring countries of Uganda and Tanzania. Continued surveillance of P. falciparum CQ and SP associated polymorphisms is recommended for guiding future rational drug policy-making and mitigation of future risk of anti-malaria drug resistance development.