The Intransigence of Malaria in Malawi—Understanding Hidden Reservoirs, Successful Vectors, and Prevention Failures
Lead Institution: Michigan State University
The overall goal of the Malawi ICEMR is to identify why the standard malaria control and prevention efforts in Malawi have not had significant impacts on malaria disease incidence and parasite prevalence. Multiple inter-related research projects in two adjoining districts with generally high malaria prevalence, diverse eco-environments, different exposures to bed nets (piperonyl butoxide (PBO) vs traditional long lasting insecticidal nets (LLINs)) and anti-malaria vaccination (RTS,S vs routine vaccines only), are addressing the following factors:
- Barriers to bed net use (including the role of bed bugs)
- Effect of insecticide resistance and the impact of PBO nets on bed net efficacy
- Sources of continued human-to-mosquito transmission in the context of current interventions
- Impact of the RTS,S malaria vaccine on infection prevalence and transmission
- Significance of local environmental features (land use/land cover, climate variability, elevation) to risk of transmission
- Non-random contact between human hosts and Anopheles vectors, permitting ready access of mosquitoes to gametocyte infected reservoirs, especially school age children
- Human and parasite determinants of developing asymptomatic infection vs. life-threatening malaria illness
The study designs of the Malawi ICEMR projects involve prospectively observing human cohorts over time – either as individuals or as households – for infection prevalence (using PCR-based assays) and for disease incidence (from passive case detection in rural health centers). Qualitative studies are conducted in the villages around the cohorts to understand barriers and enablers to using malaria interventions in the area.
Vector studies within the cohorts include entomological surveys using CDC light traps, mechanical aspiration, and pyrethrum spray catches (PSC) to track vector abundance and distribution. Sampling is carried out periodically, and mosquitoes are analyzed using molecular assays to determine species, sporozoite infection, and blood meal source. The team’s insectary is used for studies of insecticide resistance and membrane feeding, and researchers work closely with village-based volunteers to identify key mosquito behaviors (indoor vs outdoor biting, peak biting times, etc.).
Finally, in a case-control study, children with stringently defined cerebral malaria are compared to controls (age-and location-matched children), to detect host and parasite differences to understand why most malaria infections do not progress to a life-threatening illness.
School-age children are an important and underappreciated reservoir of P. falciparum infection in Malawi
Cross-sectional surveys conducted between 2010-2017 showed that school-age children (6-15 years of age) were at higher risk of Plasmodium parasite infection in general, and at higher risk of asymptomatic infection, in particular, than younger children. In comparison with younger children, they also were less likely to be brought in for treatment, and less frequently used insecticide-treated bed nets (ITNs). School-age children acquire new infections at the same rate as younger children, but they maintain infections for longer periods of time, like adults.
Detailed molecular studies showed that the odds of carrying gametocytes, the stage of Plasmodium that infects vector mosquitoes, are significantly higher in school-age children than in adults or younger children. Researchers developed a model of malaria transmission using these findings and suggested that school age children (who represent 30 percent of Malawi's overall population) were likely responsible for 60 percent of new mosquito infections.
Studies on school-age children are new, in part because this age group is less likely to develop life-threatening disease than younger children. The contribution of school-age children to transmission of malaria parasites may be very important, which is why quantifying their role in population infection is a major focus of the Malawi ICEMR.
Plasmodium transmission dynamics are highly heterogeneous over a fine spatial scale
Across the ICEMR network, malaria parasite transmission rates vary hugely among sites, from locations approaching elimination, to settings like Malawi, where transmission remains robust. In Malawi, ICEMR investigators found a heterogeneous distribution of Plasmodium infections within study sites and household-level variation in Anopheles mosquito abundance. Small-scale agriculture near dwellings, whether in the urban center or the more sparsely settled areas extending beyond the city limits, was strongly associated with indoor abundance of both An. funestus and An. gambiae, the primary vectors in Malawi.
Human behavior also contributes to the observed heterogeneity. In the same peri-urban setting, a case-control study evaluating malaria risk showed that travel within the previous month was the main factor influencing the incidence of malaria illness.
Researchers are conducting studies to identify which factors (host, vector, environmental) contribute in what ways to this local heterogeneity, as insights could impact policy decisions concerning malaria control and prevention programs. Findings will allow more tailored approaches that should be more successful than broader, “one size fits all” strategies.
The Malawi ICEMR is situated in a region of high malaria transmission intensity. Working in partnership with Malawi's National Malaria Control Programme in the Ministry of Health, the World Health Organization, the US Centers for Disease Control, and academic partner the University of Malawi College of Medicine, researchers aim to build capacity (particularly in terms of data management, biostatistics, entomology, and molecular parasitology) and to generate new scientific insights, which can be promptly incorporated into more effective prevention and control strategies that are responsive to the changing nature of malaria infection and disease in Malawi.
View Associated sites for the Malawi ICEMR in a larger map
Map description: Associated sites for the Malawi ICEMR—Blantyre, Chikhwawa, Karonga, Phalombe
Co-Principal Investigators: Don Mathanga, M.D., M.P.H., Terrie Taylor, D.O.
- Don Mathanga, Malaria Alert Centre, University of Malawi College of Medicine
- Karl Seydel, College of Osteopathic Medicine, Michigan State University
- Clarissa Valim, Boston University School of Public Health
- Boston University School of Public Health, Boston MA, USA
- University of Malawi College of Medicine, Blantyre, Malawi
- University of Maryland School of Medicine, Baltimore MD, USA
- University of Michigan, Ann Arbor MI, USA