Major areas of emphasis in the O’Meara lab include:
Micro-scale studies of malaria transmission
Malaria is highly heterogeneous in a population – 20% of individuals experience 80% of cases. This heterogeneity contributes to malaria persistence but is poorly understood. Our team is working on identifying individual transmission events from human to mosquito and mosquito to human by using cutting edge genetic approaches to identify biting events and transmission events in a natural system.
Matching infections between mosquitoes and people requires advanced parasite genotyping methods that are being developed and refined in Dr. Steve Taylor’s lab. Dr. Christine Markwalter is developing robust pipelines to resolve multi-source bloodmeals in individual mosquito bloodmeals. By combining intensive human and entomological sampling with sequence-based, high-resolution human and parasite genotyping techniques, we can directly track individual parasite infections between mosquitoes and humans and identify which human hosts are most infectious. We can also leverage clinical outcomes to understand which immune responses protect people when they have an exposure to an infectious bite. We are using this rich resource to directly observe the reservoir of infection, to identify high value targets for transmission blocking interventions, and to improve the design of the next generation of malaria vaccines.
- Reservoir of infection – 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.In our long-standing community-based cohort in western Kenya, we can investigate, under natural conditions, which humans are bitten by mosquito vectors, and which humans transmit malaria infections to mosquitoes. By matching mosquito bloodmeals to individual household members, we can learn about mosquito behavior and whether mosquitoes bite randomly or prefer certain individuals. 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.
- Next-generation vaccine design – Two malaria vaccines have been approved for use in children in malaria-endemic areas. Although this is a huge step forward for the field, both vaccines suffer limitations in effectiveness partly due to the incredible genetic diversity of the key target antigen, CSP. Through our innovative cohort design, we can identify individual mosquito to human transmission events. By observing the clinical outcomes in individuals exposed to an infectious bite, we can quantify the immune context that leads to protection from infection and disease. Using immunoinformatics approaches, we hope to identify a minimum set of CSP variants that confers ‘strain-transcendent’ immunity.
Emerging threats to malaria elimination
We are extending the use of genetic tools to understand transmission networks in areas where malaria is an emerging problem. Pastoral communities in the semi-arid regions of northern Kenya were historically considered outside of the malaria risk map. But these areas are rapidly changing and experiencing increased settlement, many more migrants from all over east Africa, and changing lifestyle, attributed in large part to oil discovery and the influx of people, money, and infrastructure that accompanies resource extraction.
Using reactive case detection and traveler surveillance, we confirmed a very high burden of malaria in both rural and peri-urban communities in Turkana County in northern Kenya. Using haplotype deep sequencing, we were able to show that infections imported by travelers are being transmitted locally, but are not contributing substantially to transmission networks. We have also shown that seasonal pastoralist movement increases risk of malaria infection and leads to importation of infections back to home villages.
We have also identified emerging threats to these communities which have the potential to disrupt malaria transmission in Kenya and beyond. First, we documented low but significant prevalence of Plasmodium vivax in people who had no recent travel, including children. This is the first time P. vivax has been confirmed in people in Kenya. Second, in January 2023, we identified An. stephensi in this region. WHO has declared the spread of An. stephensi in sub-Saharan Africa as a major emerging threat to malaria control. This finding has since been repeated in at least four other subcounties that border Turkana leading to deep concern about the future of malaria elimination in Kenya. We are now working with the Turkana County Health team to establish surveillance for P. vivax and An. stephensi across the county.
Because ITN ownership in these communities is low, partly due to lack of availability but also complicated by frequent migration and the practice of sleeping outdoors, they are in dire need of alternative malaria prevention approaches. In collaboration with Catholic Relief Services (CRS), we are working with the Turkana County Health Team to design and roll-out seasonal drug-based prevention approaches specifically targeted to children.
Implementation science to improve antimalarial stewardship
Antimicrobial resistance is a global threat that kills more people than car accidents every year in the U.S. Overuse of antimicrobials, including antimalarials, accelerates the spread of drug resistance and threatens the useful therapeutic life of these drugs. Improving access to diagnostic testing can reduce unnecessary consumption of antimalarials. Our group is testing innovative incentive strategies to try to increase uptake of, and adherence to, diagnostic testing in an effort to improve rational use of antimalarials and reduce the likelihood of spread of resistance. We are working in both the formal and the informal retail health sectors.
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Like any good scientific team, we sometimes explore new areas and important public health questions a bit outside of our main lane. Read about these other exciting projects:
