Lead Institution: University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB)
Research Areas
The West Africa International Center of Excellence for Malaria Research (WA-ICEMR) program aims to conduct implementation research targeting residual malaria transmission and optimizing control interventions for interrupting malaria transmission. Leveraging research findings and capacity built over the past decade, this ICEMR seeks to investigate the determinants of residual malaria transmission during Mali’s long dry season, in rural and urban settings, to refine routine control interventions. Working in in close collaboration with the Malian National Malaria Control Program (NMCP) and its partners, the results of the findings are intended to guide malaria control policy in Mali. The program encompasses the epidemiology of residual malaria transmission and control project, studying the persistence of low-level residual P. falciparum infection in relation with malaria control interventions; and the urban-rural continuum of malaria transmission project studying malaria vector ecology and epidemiology in the rural-urban continuum and peri-urban settings of Bamako, Mali. Research will be conducted in diverse ecological field settings and include:
- Risk factors associated with the incidence of P. falciparum residual infections in the context of control interventions;
- Investigating breakthrough P. falciparum infections and clinical malaria among children under seasonal malaria chemoprophylaxis (SMC) by evaluating antimalaria drug metabolites and community compliance to the SMC intervention;
- Dynamics of malaria incidence during SMC intervention and during the first year after withdrawal from SMC;
- Changes in antibodies levels against both sexual and asexual stage antigens in the context of SMC;
- Studying urban malaria through school-based parasitemia surveys and health facility-based surveillance;
- Dry season malaria vector population structure, resting and biting behaviors in peri-urban and urban settings;
- Characterizing malaria parasite reservoirs in peri-urban and urban settings using reactive case detection;
- Contribution of endogenous and exogenous sources of malaria mosquitoes in urban settings;
- Spatial/temporal concentrations and survival of malaria mosquitoes in urban, peri-urban, and surrounding rural areas in relation to opportunistic indoor feeding on anthropogenic sugar sources (e.g. invasive plant species and garbage contaminated with sugar-containing food); and
- Planning implementation research in collaboration with the NMCP to optimize the season-specific combination of targeted control interventions (e.g. SMC, mass drug administration, larvicide, and community engagement).
The West Africa ICEMR program will conduct cohort studies to determine malaria incidence (passive case detection at community health centers and reactive case-detection) and changes in prevalence of sexual and asexual P. falciparum infection, using both microscopy and PCR-based assays.
To study the epidemiology of residual malaria transmission in rural areas, children participating in the cohort studies are followed to determine their compliance with SMC treatment, the risk of clinical malaria during the SMC season, and the risk of developing clinical malaria in months following SMC delivery. Four cohort-based surveys will be conducted in conjunction with entomological surveys during the dry season in November, January, March, and May each year to assess the changes in asymptomatic P. falciparum prevalence rates and changes in entomological parameters (vector species composition, density and EIR).
To study the urban-rural continuum of malaria transmission, baseline epidemiological and entomological surveys will be conducted to characterize local endemicity and risk gradient of malaria transmission in the urban and peri-urban areas of Bamako. To determine the changes in the prevalence of P. falciparum infection and malaria attributable fevers, investigators will carry out repeat school-based parasitemia surveys and health facility-based fever surveys in combination with health facility-based passive case-detection. To characterize urban malaria vector ecology and transmission, researchers will determine: the extent of larval habitats, diurnal resting sites and sugar sources in urban to rural continuum of Bamako using an integrated approach that includes ground searches, camera- mounted drones, and satellite imagery; and the contribution of endogenous and exogenous sources of malaria mosquitoes, and the spatiotemporal concentrations and survival of malaria mosquitoes (e.g, invasive flowering plants and sugar rich food contaminated garbage) in urban, peri-urban, and surrounding rural areas.
Past Achievements
Since 2010, the WA-ICEMR in collaboration with NMCP has performed longitudinal studies to monitor and assess the impact of malaria control interventions on space-time distributions, vector transmission indicators, and drug resistance markers. Key findings are highlighted below:
Trends in malaria epidemiology after scaling up of malaria control interventions. Significant declines in malaria burden among children under five years of age were noted following the introduction of SMC and universal net coverage in 2015. The West Africa ICEMR studies showed how school-aged children between 5-15 years of age became the age group more impacted by both asymptomatic and symptomatic malaria. In Dioro and Koulikoro, studies described the impact of the abrupt withdrawal of malaria interventions on the rebound of malaria in the community, with a 2- to 4-fold increase in prevalence and incidence within only six months of cessation of the control programs.
Evaluating SMC in diverse ecological settings. Numerous studies were conducted to evaluate the target age-groups that need SMC and identifying potential alternative regimens to the standard of care (sulfadoxine-pyrimethamine plus amodiaquine [SP-AQ]). Studies compared two SMC regimens (standard of care SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) for preventing uncomplicated P. falciparum malaria in children 3 months to 9 years of age. The studies showed that DHA-PQ may be a plausible second-line or alternative SMC regimen with fewer side effects and better acceptance than SP-AQ.
Monitoring malaria drug resistance molecular markers and P. falciparum genetic diversity. The diversity and the prevalence of P. falciparum drug-resistance molecular markers were assessed using next-generation sequencing (NGS) strategies to track drug-resistant malaria parasites. The analysis of anti-malarial drug resistance molecular markers revealed a low prevalence of amodiaquine resistance-associated Pfmdr1_86Y mutant parasite and a high prevalence of Pfmdr1_Y184F, the lumefantrine-reduced susceptibility mutation (39.9%). These results suggest that the current antimalaria drugs used for control interventions in Mali are relevant and highlight the need for routine drug resistance monitoring.
Impact of SMC on molecular markers of P. falciparum antimalarial drug resistance in Koulikoro, Mali. As part of SMC effectiveness study, researchers examined potential changes in P. falciparum genes related to SP+AQ and DHA+PQ resistance using 2019 and 2020 SMC data in Koulikoro region, Mali. Despite minor variations of prevalence of drug resistance alleles from year to year, deploying SMC using either SP+AQ or DHA-PQ does not appear to select for molecular markers of drug resistance in the tested population in Mali.
Malaria vector ecology studies, a neglected aspect of malaria vector control. The ICEMR deployed ground searches, camera-mounted drones, and satellite imagery to identify and define the extent of dry season vector habitats. WA-ICEMR studies characterized dry season refuges for A. coluzzi and A. gambiae and demonstrated their dispersal at the onset of the rainy season. Sugar sources were identified to determine factors associated with malaria vector survival during the dry season, showing that flowering plants favored female populations. Migration patterns of mosquitoes during the dry season showed that large numbers of marked mosquitoes were able to cross over the Niger River (over 1-2 km wide). These factors could likely represent sources for dry season malaria transmission and could be targeted by vector control interventions.
Increased outdoor transmission rates and widespread insecticide resistance threaten conventional malaria vector control approaches. Findings demonstrated that active indoor and outdoor residual malaria transmission were comparable across different ecological settings. The variable endophilic behavior of Anopheles gambiae s.l. relative to human outdoor nocturnal behavior and more extended outdoor dwelling periods could explain the high observed outdoor biting rates and EIRs. Notable challenges to vector control include the multiple resistance mechanisms to pyrethroids observed in A. gambiae s.l., displaying widespread and high phenotypic resistance to deltamethrin and permethrin (Keita et al. 2022). The high outdoor transmission patterns and widespread insecticide resistance highlight the need for additional strategies to combat outdoor malaria transmission.
Regional Impact
The WA-ICEMR’s studies are being implemented at three field sites in Mali that represent three distinct eco-zones across West Africa that differ with regard to endemicity:
- Dangassa: A rural field site along the Niger River where malaria remained 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 interventions against malaria.
- Urban and peri-urban areas of Bamako with low but persistent heterogenous malaria transmission.
The WA-ICEMR is based at the University Clinical Research Center (UCRC) of USTTB at Point G teaching Hospital, working closely with the NMCP, the Mali PMI/USAID, Population Services International, and Catholic Relief Services.
Study Sites
View Associated sites for the Mali ICEMR in a larger map
Collaborative Institutions
- Tulane University (USA)
- University of South Florida (USA)
- University of Copenhagen (Denmark)
- University of Deakin (Austria)
- University of Miami (USA)
- Southeast Asia ICEMR
- LMVR/NIAID/NIH
Staff
Principal Investigators: Doumbia Seydou, M.D.
Project Leads
- Epidemiology of residual malaria transmission and control: Mahamadou Diakite, Ph.D. ; Mahamoudou Toure, Ph.D.
- Urban-rural continuum of malaria transmission: Nafomon Sogoba, Ph.D.; Gunter Muller, Ph.D.; Tovi Lehmann, Ph.D.
- Data Management and Biostatistics Core: Jeffrey Shaffer, Ph.D.; Fousseyni Kane, M.D.