The Malaria Reservoir: Micro-scale studies of human to mosquito malaria transmission
Biting heterogeneity and infectiousness
Although anyone is theoretically at risk of contracting malaria where the parasite and the vector are present, research shows that infection and disease burden are unevenly distributed in the population. As few as 20% of individuals suffer 80% of malaria episodes. This highly over-dispersed burden of malaria may enhance persistence and also suggests that onward transmission may originate from a small subpopulation of infected humans. It should be possible to identify and characterize this group of individuals responsible for the majority of onward transmission. Targeting this group of transmitters – also called the malaria ‘reservoir’ – would have the largest impact on transmission in a population.
The objective of our work is to investigate, under natural conditions, which humans are bitten by mosquito vectors, and which humans transmit malaria infections to mosquitoes. To do this, we have established a longitudinal cohort in western Kenya where we collect mosquitoes each week and monitor individuals for malaria infection. By matching mosquito bloodmeals to individual household members, we can learn about mosquito behavior and whether mosquitoes bite randomly or prefer certain individuals. Biting preference could have a substantial impact on malaria persistence. Going further, by matching malaria infections in mosquitoes to those in the human hosts, we can understand who is infecting mosquitoes and directly characterize the reservoir of infection.
Matching infections between mosquitoes and people requires advanced parasite genotyping methods that are being developed and refined in collaboration with Dr. Steve Taylor’s lab. By combining intensive human and entomological sampling with sequence-based, high-resolution parasite genotyping techniques, we can directly track individual parasite infections between mosquitoes and humans and identify which human hosts are most infectious.
Spatial scales of transmission
The science of identifying ‘hotspots’ of malaria infection or foci of transmission is a growing area that promises to help target interventions more effectively. However, it has not been shown whether infected individuals in close physical proximity (i.e. in the same household) are jointly infected due to simply living in a risky place, or because an infected household member is a risk factor for nearby susceptible individuals. If the latter is true, then interventions to identify and treat ‘transmitters’ and ‘hotspots’ will reduce transmission and the incidence of new cases.
We are using two approaches to understand this important issue. First, we measure the genetic relatedness of infections within the same household compared to the relatedness of infections at further distances. We have sequenced P. falciparum infections from households in our study area at a moderately polymorphic gene using deep sequencing techniques. We are using spatial and population genetics approaches to determine the spatial scale of ‘mixing’ of infections. Our second objective is to trap malaria mosquito vectors and identify infected mosquitoes. We will determine the source of the mosquito’s infection by sequencing parasites in the mosquito salivary glands and comparing to parasite genotypes in humans. Using these two approaches, we can find out whether infections are being transmitted at a household scale or transmission is ‘well mixed’ geographically and only limited by the range of the mosquito. The ability to track infections from human to mosquito and back again would allow us to understand the dynamics and scale of transmission in a way that has not previously been possible.
Collaborators: Steve Taylor, Andrew Obala (Moi University), Judith Mangeni (Moi University)
- C. S. Nelson, K. M. Sumner, B. Freedman, A. A. Obala, J. N. Mangeni, S. M. Taylor, W. Prudhomme O’Meara “Children with clinical Plasmodium falciparum infection have enhanced sharing of haplotypes with household members and temporally-proximal symptomatic peers” Nature Communications Dec 9;10(1):5615 (2019)
- W. Prudhomme O’Meara, R. Simmons, P. Bullins, B. Freedman, L. Abel, J. Mangeni, S. M. Taylor, A. A. Obala “Mosquito exposure and malaria morbidity; a micro-level analysis of household mosquito populations and malaria in a population-based longitudinal cohort in western Kenya” Journal of Infectious Diseases 30 October jiz561 (2019)
- S. M. Taylor, K. Sumner, B. Freedman, J. Mangeni, A. A. Obala, W. Prudhomme O’Meara “Direct estimation of sensitivity of Plasmodium falciparum rapid diagnostic test for active case detection in a high-transmission community setting” American Journal of Tropical Medicine and Hygiene Volume 101, Issue 6, 4 Dec. p. 1416 – 1423 (2019)
- The malERA Consultative Group on Characterising the Reservoir and Measuring Transmission, “Characterising the reservoir and measuring transmission: The malERA Refresh research agenda for malaria elimination and eradication” PLoS Medicine 14(11):e1002452 (2017)
- B. Levitt, A. Obala, S. Langdon, D. Corcoran, W. Prudhomme-O’Meara, S .Taylor, “Overlap Extension Barcoding for the Next Generation Sequencing and Genotyping of Plasmodium Falciparum in Individual Patients in Western Kenya” Scientific Reports 7:41108 (2017) PMC5259759