Advancing malaria research, surveillance, and control through the implementation of applied genomics and translational systems biology approaches in an exigent malaria nexus of West and Central Africa.
Lead Institutions: University of Florida (USA), African Centre of Excellence for Genomics of Infectious Diseases (Nigeria), and the Centre for Research in Infectious Diseases (Cameroon)
Research Areas
The West-Central Africa Enhancing Malaria Epidemiology Research through Genomics and Translational Systems biology (EMERGENTS) ICEMR program leverages successful, well-established collaborations, unique research and training infrastructures, and an extensive Sub-Saharan Africa (SSA) research network to address emerging and challenging issues in malaria transmission in the region. Emergents ICEMR is built on a proven research platform and consortium, including the of World Bank, the Wellcome Trust, the African Academy of Sciences, research centers of excellence in Nigeria and Cameroon funded by the NIH and the Centers for Disease Control and Prevention. By leveraging existing infrastructure, the ICEMR team can launch directly into "advancing science", assuring implementation of rigorous and advanced approaches to tackling high-priority emerging and re-emerging issues in malaria that remain as significant impediments to achieving malaria elimination and eradication (MEE).
The Emergents ICEMR will tackle three major knowledge gaps and emerging obstacles to achieving MEE:
- Non-falciparum malaria. Expansion of Plasmodium vivax (Pv) cases (in Duffy-negative individuals), non-falciparum malaria (NFM), and low-density and submicroscopic malaria, either as mono- or mixed-infections with P. falciparum (Pf), is a considerable challenge to achieving MEE. Importantly, P. ovale (Po), representing two different species (P. ovale curtisi and P. ovale wallikeri), which like Pv has a dormant liver stage complicates control, impacts the understanding of clinical disease in Africa, and raises challenges for the understanding of parasite-parasite and parasite-host interactions. "Benign" NFM infections have now been recognized to be a significant cause of (severe) clinical illness and escalating morbidity and mortality.
- Expansion of the geographic range of Anopheles stephensi. This highly competent malaria vector for both Pf and Pv has expanded its distribution from the Horn of Africa into East and West Africa (Nigeria). This mosquito vector has adapted to the use of human-made or artificial containers as larval habitat. Therefore, sympatric Pf/Pv and An. stephensi will change the dynamics and effectiveness of malaria control programs. The application of standard malaria control measures in areas where Pv and Pf are syndemic, commonly outside of Africa, often results in reduction of Pf cases but a persistent dominance of Pv.
- Insecticide resistance (IR) of "primary" vectors and "secondary" mosquito vectors. In Cameroon, sixteen anopheline species vector malaria parasites, six of which are considered the "major" vectors: An. gambiae, An. coluzzii, An. arabiensis, An. funestus, An. nili, and An. moucheti. Widespread IR for An. gambiae, is well established but less is known for An. coluzzii, an emerging primary malaria vector, which has already developed pyrethroid resistance. An. funestus has also been shown to be the main vector not only for Pf mono-infections but also for Pf/NFM and Po/Pv/Pm mixed infections in this region. Broad generalizations with respect to distribution, abundance, species composition, zoophilic vs. anthropophilic and exophagic vs. endophagic behavior of funestus group members may in fact not hold true. Local temporal and spatial variations should be further explored to fully support MEE efforts.
To address these challenges, the ICEMR team will:
- Develop parasite genotyping platforms to create advanced genomic tools tailored for studying NFM transmission, including subsequent development of field- deployable genomic approaches to support parasite and vector surveillance as well as basic and applied research.
- Implement Artificial Intelligence (AI)-driven surveillance and detection system for tracking invasive An. stephensi emergence and establishment on the continent through a combination of citizen science and medical entomology team activities.
- Deploy a novel An. stephensi trap, baited with An. stephensi-specific adult lures, an integrated camera for image-based, AI-driven, cloud-based detection followed by rapid response deployment to targeted study sites.
- Implement field-deployable quantitative dried blood spot (DBS)-based collection systems that are test- integrated to increase testing speed, sensitivity, and accuracy for parasite infection status in samples from clinical and subclinical human subjects.
- Implement field-deployable laboratory techniques to increase testing speed, sensitivity, and accuracy of measurements for sporozoite infection status of mosquitoes.
- Test novel insecticide synergists and chemical actives in country that were designed to kill insecticide- resistant mosquitoes against sampled vector species in Cameroon and Nigeria.
- Establish an LMIC-suitable template for the application of Systems Translational Biology (metabolomics and proteomics) to understand the contribution of the human host to the unabated transmission of non-falciparum and falciparum malaria parasites across a region of heterogeneous malaria endemicity.
- Explore how subclinical and clinical malaria host metabolomic and proteomic profiles influence persistence and infectiousness to mosquitoes.
- Focus on translational outcomes that bridge basic and applied research to support MEE goals and ensures robust capacity building (and maintenance), community and stakeholder engagement, and ongoing research and training programs across the continent.
Regional Impact
The Emergents ICEMR is situated at the intersection of West and Central Africa, focused on two countries with differential malaria transmission intensities and disease risk. Nigeria is considered holoendemic for malaria; however, "endemicity" is heterogeneous across the various ecological zones of the country, complicating malaria control efforts. Whereas in Cameroon, malaria transmission is heterogeneous across the country, ranging from perennial transmission in the southern forested regions to seasonal and unstable transmission in the northern Soudano-savannah as well as Sahelian regions. Researchers work in close partnership with the Africa CDC, U.S. CDC, Nigeria Ministry of Health, Cameroon Ministry of Health and Nigerian and Cameroon National Malaria Control Programs, as well as regional research institutes, and have built the framework for genomics and translational research capacity from within, developing the next generation of malariologists and public health entomologists, and generating data that can then inform local malaria control policies. It is anticipated that the Emergents ICEMR program will lead to a deeper understanding of how decades of interventions designed to control malaria morbidity and mortality by eliminating Pf primarily can ultimately fail when other Plasmodium species are left unaddressed.
Study Sites
View Associated Sites for the Emergents ICEMR in Nigeria and Cameroon in a larger map
Collaborating Institutions
- Africa CDC, Ethiopia
- Brown University, USA
- Centre Pasteur du Cameroun, Cameroon
- CERMEL, Gabon
- DELGEME Plus, Mali
- Naval Medical Research Unit-3, Italy
- Pan African Mosquito Control Association, Kenya
- University of Dschang, Cameroon
- University of North Carolina at Chapel Hill, USA
- University of South Florida, USA
Staff
Principal Investigators: Rhoel Dinglasan Ph.D. M.P.H., Christian Happi, Ph.D., and Charles Wondji Ph.D.
Project Leads
- Onikepe Folarin, African Centre of Excellence for Genomics of Infectious Diseases
- Emmanuel Elanga, Centre for Research in Infectious Diseases
- Basile Kamgang, Centre for Research in Infectious Diseases
- Suleiman Ibrahim, Centre for Research in Infectious Diseases
- Timothy Garrett, University of Florida
- Sadie Ryan, University of Florida
- Jonathan Juliano, University of North Carolina at Chapel Hill
- Sriram Chellappan, University of South Florida
- Ryan Carney, University of South Florida