The visceral leishmaniasis (VL) elimination strategy in the Indian subcontinent, that has a current goal of reducing the incidence of VL to below 1/10,000 people by 2017, consists of rapid detection and treatment of VL cases to reduce the number of human infection reservoirs, and vector control using indoor residual spraying (IRS). To achieve sustained elimination of VL, an appropriate surveillance program is needed to detect the emergence of insecticide resistant populations of P. argentipes, as well as studies to define the contribution of individuals from across the infection spectrum, and of possible non-human reservoirs, to the maintenance of the L. donovani transmission cycle. To address these issues, we have proposed a series of cutting edge studies that will exploit the exceptional resources now available to carry out vector related research in Bihar. These resources include 1) a new, fully functional insectary that will permit containment, rearing, infection, and manipulation of field caught sand flies, 2) an established working colony of P. argentipes that has been certified for use in xenodiagnostic procedures, and 3) an entomological field team that has extensive experience in the capture, taxonomic identification, and colonization of sand flies in Bihar. Studies are proposed to survey insecticide resistance in field populations of P. argentipes, establish a pyrethroid resistant colony, and develop biomarker-based assays to quickly identify emergent populations of insecticide resistant sand flies in Bihar. Vector competency studies will be conducted on wild caught P. argentipes captured from different peridomestic settings and associated to their midgut microbiota profiles. Methods for metagenomic sequencing and analysis will interface with the studies of the human gut microbiome proposed in Project 1. Cultivable bacterial flora that appear to negatively or positively impact Leishmania development will be used in bacterial feeds in attempts to manipulate vector competence in colonized flies. The colonized flies will also be used in xenodiagnostic assays to identify possible non-human reservoirs that may be playing a greater role in the maintenance of the L. donovani transmission cycle as a consequence of IRS. Finally, the metabolic and immunologic profiling approaches proposed in Projects 1 & 3 will be applied to the ongoing human xenodiagnostic surveys sponsored by the Gates Foundation in attempts to identify biomarkers in plasma and localized sand fly bite sites that are associated with transmission potential in infected people.

Public Health Relevance

The studies proposed in the vector biology project will contribute to the visceral leishmaniasis elimination effort in India by addressing the potential obstacles to its long range success. These obstacles include the emergence of insecticide resistant sand flies, and the roles played by human and non-human infection reservoirs in the persistence of the L. donovani transmission cycle in Bihar.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Banaras Hindu University
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Sundar, Shyam; Singh, Om Prakash (2018) Molecular Diagnosis of Visceral Leishmaniasis. Mol Diagn Ther :
Sundar, Shyam; Singh, Bhawana (2018) Emerging therapeutic targets for treatment of leishmaniasis. Expert Opin Ther Targets 22:467-486
Sundar, Shyam; Singh, Bhawana (2018) Understanding Leishmania parasites through proteomics and implications for the clinic. Expert Rev Proteomics 15:371-390
Sundar, Shyam; Agarwal, Dipti (2018) Visceral Leishmaniasis-Optimum Treatment Options in Children. Pediatr Infect Dis J 37:492-494
Singh, Neetu; Sundar, Shyam (2018) Combined neutralization of interferon gamma and tumor necrosis factor alpha induces IL-4 production but has no direct additive impact on parasite burden in splenic cultures of human visceral leishmaniasis. PLoS One 13:e0199817
Singh, Neetu; Kumar, Rajiv; Chauhan, Shashi Bhushan et al. (2018) Peripheral Blood Monocytes With an Antiinflammatory Phenotype Display Limited Phagocytosis and Oxidative Burst in Patients With Visceral Leishmaniasis. J Infect Dis 218:1130-1141
Hasker, Epco; Malaviya, Paritosh; Cloots, Kristien et al. (2018) Visceral Leishmaniasis in the Muzaffapur Demographic Surveillance Site: A Spatiotemporal Analysis. Am J Trop Med Hyg 99:1555-1561
Singh, Toolika; Fakiola, Michaela; Oommen, Joyce et al. (2018) Epitope-Binding Characteristics for Risk versus Protective DRB1 Alleles for Visceral Leishmaniasis. J Immunol 200:2727-2737
Kansal, S; Chakravarty, J; Kumar, A et al. (2017) Risk Factors associated with defaulting from visceral leishmaniasis treatment: analysis under routine programme conditions in Bihar, India. Trop Med Int Health 22:1037-1042
Singh, Neetu; Sundar, Shyam (2017) Inflammatory chemokines and their receptors in human visceral leishmaniasis: Gene expression profile in peripheral blood, splenic cellular sources and their impact on trafficking of inflammatory cells. Mol Immunol 85:111-119