Multidisciplinary Research for Malaria Control and Prevention in West Africa
Lead Institution: University of Sciences, Techniques, and Technology of Bamako, Mali
Link to ICEMR website: http://icemr-waf.org/
Wide deployment of malaria control tools in the past decade has contributed to significant reductions in malaria incidence and deaths in sub-Saharan Africa. These tools include long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), intermittent presumptive treatment of pregnant women (IPTp), seasonal malaria chemoprevention (SMC) of children, and malaria case management with artemisinin-based combination therapies (ACTs).
These interventions are utilized in different combinations in different ecological settings. Depending on the level of transmission, the interventions have varying effects on different outcomes, such as infection, disease, immune response, response to drug treatments, and mosquito vector response to insecticides. Despite the widespread use of these interventions, sub-Saharan Africa continues to carry a disproportionately high share of the global burden of malaria deaths. Moreover, incidence remains high but stable in some settings while rebounding in others, after a long period of decrease associated with intensive deployment of malaria control tools.
The goal of this ICEMR is to study the variable effectiveness of malaria control interventions and their impact on the interactions between malaria parasites (genotypes, response to drug treatment), the vector (ecology, behaviors, and response to insecticides), and the human host (immune response and host genetics) in three different ecological settings of West Africa.
The ICEMR has four research projects:
- Project 1: Malaria Epidemiology - Study the effectiveness of control interventions and the changes in malaria epidemiological patterns (human & vector) in relation to control strategies.
- Project 2: Immuno-Genetics - Identify and examine the changes in genetic diversity of parasites, resistance to antimalarial drugs, and immunological aspects in relation to malaria control interventions.
- Project 3: Malaria Vector Ecology - Investigate the sources and survival strategies of malaria vector populations during the long dry season and their impact on malaria transmission.
- Supplement Project: Evaluate the effectiveness of three different treatment regimens for Seasonal Malaria Chemoprevention (SMC) with respect to implementation, malaria morbidity, protective immunity and cost-effectiveness.
Advancing malaria treatment and prevention through controlled cohort studies
Based on two annual cross-sectional surveys (beginning and end of transmission seasons) and passive case-detection approaches (PCD) for the study sites of Dangassa, Dioro, and Koulikoro, Mali, ICEMR researchers found a progressive decline in the prevalence rates of Plasmodium (P.) falciparum infections, gametocyte carriage, malaria-related anemia, and the incidence of clinical malaria. These declines may be attributed to the deployment of continuous interventions (free treatment of malaria cases with ACT, distribution of LLITNs, and SMC). Though clinical malaria incidence consistently peaked towards the end of the transmission season, there was a sharp reduction in its magnitude over the past two years.
Other significant changes documented in malaria epidemiology include: 1) A shift in the age-specific prevalence of P. falciparum infections and incidence of disease from children under 5 years of age to those aged 5-9 and 10-14 years. These findings suggest that target interventions, historically focusing on children under five years of age, need to be expanded to cover older children too. 2) Resurgence of malaria after withdrawal of malaria control intervention was observed following the termination of the Millennium Villages Project in Dioro, Mali. Resurgence was also found to be attributable to the withdrawal of indoor residual spraying (IRS) in Mali’s Koulikoro District following nearly 10 years of implementation.
To address the issues of age shift in the prevalence and incidence of malaria from younger to older children, ICEMR researchers have worked with the Mali National Malaria Control Program (NMCP) to perform pilot studies to assess the impact of extending SMC to children of 5-14 years old with five rounds of treatment as compared with standard SMC in Mali (monthly SMC to children under 5 with four rounds from July to October) in Dangassa. These studies have enrolled over 6,000 subjects as of July 2020. Significant reduction in malaria parasitemia was observed across all age groups (between 62 percent and 92 percent reduction), which suggests that SMC is suitable for children older than five years of age. No significant side effects were observed as a result of the administration of SMC to older children.
Advancing research on malaria vector ecology and resistance
The ICEMR studied seasonal variations in malaria transmission parameters using pyrethrum spray catch (PSC) at three study sites. Some of the key findings include:
- High entomological parameters of malaria transmission at the end compared to the start of the rainy season at three study sites.
- High outdoor transmission was observed, highlighting the need for additional strategies to combat outdoor malaria transmission to complement traditional indoor preventive approaches.
- The implication of G119S mutation in bendiocarb resistance in An. gambiae s.l. populations was assessed at Koulikoro and Dangassa sites. The G119S resistance allele was found in all the three species of the An. gambiae complex (i.e., An. arabiensis, An. coluzzii, and An. gambiae s.s.), with higher frequencies being observed in An gambiae s.s. at both study sites.
- The ICEMR determined the prevalence of different resistance mechanisms to pyrethroid insecticides in Anopheles gambiae s.l. populations at the Koulikoro and Dangassa study sites. Researchers found multiple resistance mechanisms to pyrethroids in Anopheles gambiae s.l. populations in Mali. Piperonyl butoxide (PBO) was found to be the most effective synergist for improving the efficacy of pyrethroids on An. gambiae s.l.
Identification and characterization of refugia distant to the River Niger
ICEMR researchers identified and defined small wetland pockets (mainly along small contributories to the River Niger) and some other low-lying habitats where water accumulates during the wet season that serve as dry season refugia for malaria vectors. Researchers characterized locations, size of the habitats, and how the suitable resting sites shrink during the dry season, while monitoring potential diurnal resting sites and sugar feeding sources.
Evaluation of the importance of honey dew as a sugar source for anophelines
According to the Malaise trap trials, there was no measurable attraction distance to these types of sugar sources. In the dry season about 20% of the sugar meals taken by local anophelines derived from different honeydews while in the rainy season less than 3% of the sugar meals derived from honeydews. The findings suggest that mosquitoes find honeydew by chance, by landing on soiled vegetation. More vegetation that is contaminated with honeydew or less alternative sugar sources that are available appear to coincide with higher the probabilities that mosquitoes will feed on honeydew.
These vector ecology studies have set the groundwork for conducting a larger cluster randomized trial in Mali to study Attractive Sugar Toxic Sugar Baits (ATSB), a new antimalaria vector control tool based on sugar feeding behavior of mosquitoes.
The ICEMR’s studies are being implemented at three field sites in Mali that represent three major eco-zones across West Africa that differ with regard to endemicity and current implementation of control strategies:
- Dangassa: A rural field site along the river Niger where malaria has been found to be stable over the past five years.
- Dioro: An irrigated site in the inland delta region of the Niger River where a sharp rebound of malaria was observed after withdrawal of 10 years of malaria control interventions.
- Koulikoro: Northern savanna area where IRS has been implemented for more than eight years and where increased insecticide resistance has been reported.
View Associated sites for the Mali ICEMR in a larger map
Map description: Associated sites for the Mali ICEMR: Dangassa, Dioro, Sirakorola
Principal Investigator: Seydou Doumbia, M.D., Ph.D.
- Nafomon Sogoba, University of Sciences, Techniques, and Technology of Bamako
- Mahamadou Diakite, University of Sciences, Techniques, and Technology of Bamako
- Sekou Fantamad Traore, University of Sciences, Techniques, and Technology of Bamako
- Tulane University, New Orleans, LA
- University of Georgia, Athens, GA
- University of Miami, Miami, FLA
- London School of Hygiene and Tropical Medicine, London, UK
- University of Copenhagen, Denmark
- Wellcome Trust Sanger Institute, Hinxton Cambridge, UK
- Malaria Immunology Section, Laboratory of Malaria and Vector Research, NIAID