Mali International Center for Excellence in Research: Vectors and Hosts of Parasitic Infectious Diseases

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Note: The programs of Drs. Louis Miller and Carole Long were terminated and removed. Ecology of Disease Vector Program Mosquito-borne diseases such as malaria and dengue threaten billions of people and cause the death of hundreds of thousands annually, posing continued threat to Americans. 1) Our previous studies (Huestis et al. 2019: Nature, Yaro et al. 2022: Front. Epidemiol.) have revealed that mosquitoes regularly engage in high-altitude windborne migration. The hypothesis that high-flying mosquitoes spread pathogens over long distances has not been directly tested. In our new study we report that high-flying migrant mosquitoes are commonly infected with arboviruses, protozoans, and helminths affecting vertebrates and humans, and provide the first description of this pathogen-vector aerial network. Of 1,017 female mosquitoes intercepted on nets suspended from helium balloons at 120-290 m above ground over Mali and Ghana were screened for infection. They comprised 61 species, across 10 genera, dominated by Culex, Aedes, and Anopheles. Infection and infectiousness (capacity to transmit a pathogen to another host) rates of migrant mosquitoes were 7.2% and 4.4% with plasmodia, 1.6% and 0.6% with filariae, and 3.5% and 1.1% with flaviviruses, respectively. Twenty-one mosquito-borne pathogens were identified, including dengue, West Nile and M’Poko viruses, 15 avian plasmodia species, and three filariids. Confirmed disseminated infections of multiple pathogens in Culex perexiguus, Mansonia uniformis, and Anopheles squamosus reveal that pathogens carried by high-altitude windborne mosquitoes are capable of infecting hosts far from their departure location. This high-altitude traffic of sylvatic pathogens (circulating in wild animals) may be key to their maintenance among enzootic foci as well as initiating outbreaks at distant locations, as well as to disease prevention and control. 2) A collaboration with Drs. Dao (MRTC/UTTSB, Mali), Weaver (UTMB, USA) and Diallo (IPD, Senegal) to evaluate if arboviruses spread by windborne mosquitoes at altitude from enzootic sylvatic foci to distant sites where they cause outbreaks. We compare aerial sampling station in Kedougou, Senegal where they have ongoing virus surveillance for over 50 years with an aerial station in Mali near the border with Senegal. We also collect mosquitoes at ground level to compare vector and pathogen species at altitude with those near the ground at both sites. 3) Surveillance to detect the invasive Asian urban malaria vector in Mali. Anopheles stephensi spreads in from East to West Africa. As far as we know, we are the only ones who carry out surveillance in Mali targeting likely ports of entry (airport, truck main routes), etc. We incorporate identification of mosquitoes using AI visual system (IDx). So far An. stephensi was not detected in our collections in Mali. 4) In a new project (funded in part by the Science for Africa Foundation) with scientists from Mali, Burkina Faso, Ghana, USA, and Germany, we address regional and global vulnerabilities to epidemics. Our innovative approach for disease surveillance is based on harnessing mosquitoes as samplers of pathogens from humans, domestic and wild animals (e.g. monkeys, birds), including pathogens not transmitted by mosquitoes, e.g., Ebola. In this new project, we focus on the “urban-rural-forest continuum” and describe the species compositions of mosquitoes, vertebrate hosts, and pathogens along it. We analyze mosquito i) bloodmeals (from humans and animals) to identify the vertebrate host and its past exposure to pathogens using a multi-pathogen serological assay. The assays target antibodies to ≥10 pathogens with epidemic potential including Marburg, Lassa, Mpox, avian flu, Chikungunya, and dengue ii) employ metagenomics to detect pathogens in mosquitoes; and iii) integrate information to guide public health decisions that protect local, regional, and global interests. Understanding Hemoglobinopathies in Malian Children and Adults The CRLD is a clinic, day hospital, and research center in Bamako, Mali that provides specialized care for more than 12,000 children and adults with sickle cell disease. The LMVR has established a collaboration with the CRLD to conduct clinical observational studies into the pathophysiology of sickle cell disease and the underlying mechanisms by which genetic and acquired hemoglobinopathies such as HbS, HbC, alpha thalassemia, and iron deficiency protect against severe malaria. To support this goal, we are building capacity to conduct clinical and laboratory research at the CRLD. Our natural history protocol has enrolled >4,000 individuals with sickle cell disease. This includes 50% SS, 40% SC, and 10% SB genotypes. The exceptional diversity of hemoglobin genotypes provides unique opportunities to characterize its function in the vascular system. Effect of the microbiota on Anopheles gambiae malaria transmission and insecticide resistance. We are investigating the role of mosquito microbiota in malaria transmission and insecticide resistance. The Malian team collected adult Anopheles gambiae s.l. mosquitoes throughout the year and determined whether they were infected with Plasmodium falciparum. Subsequently, a microbiome analysis was conducted on infected and uninfected female mosquitoes, to examine how the microbiome affects malaria transmission. Additionally, the researchers collected mosquito larvae from various environments and raised them to adulthood in the laboratory. Studies are underway to investigate the effect of different larval habitats on adult microbiome composition and how the microbiome influences insecticide resistance. Cutaneous leishmaniasis (CL) We have been collecting sand flies from distinct biotopes within Fansira Dierobougou, collecting over 570 Phlebotomus sand flies. The gut of each female Ph. duboscqi was dissected, and DNA extracted. Molecular determination of infection status, blood meal source and gut microbial communities PCR and 16S sequencing is underway. We obtained IRB approval for the study of human skin microbiota from CL cases and have obtained swabs from multiple lesions and control uninfected skin of 7 CL cases. Extraction of DNA and 16S sequencing is underway.