Project 1 """"""""Determinants of disease progression and role of latent infection in transmission"""""""" will study a series of factors that will help understanding why only a limited number of individuals infected with Leishmania donovani develop Visceral Leishmaniasis (VL) on the Indian subcontinent. Project 1 will also contribute to assess the role of asymptomatically infected individuals (those who do not progress to disease) in L. donovani transmission. This project will combine field and laboratory work. Two serological surveys of leishmaniasis infection will be done in high transmission areas to identify recent asymptomatic seroconvertors and controls in the study area (see Core C for details). Similariy, VL cases and controls (i.e healthy household contacts) will also be identified and included in the different studies. Project 1 is divided in 4 specific aims.
Aim 1 will examine the association of HLA-type with seroconversion and disease progression controlling for several confounders identified in the previous risk factor studies.
Aim 2 will use a recently developed quantitative PCR to assess parasite load in different subpopulations (i.e.seroconvertors and seronegative individuals) and assess its influence in progression to VL taking into account genetic and environmental factors.
Aim 3 will examine the association between co-infections with other Neglected Tropical Diseases (NTD) and VL in two case-control studies. (1) An unmatched case-control study comparing Leishmania seropositives with the general population and (2) a matched case-control study comparing VL cases to community controls will be used to assess the effect of filaria- or geo-helminths-L. donovani co-infection on progression to VL. Finally, Aim 4 will contribute to study the role of asymptomatically infected persons by (1) validating a modified SLA-based Quantiferon to detect cellular immune response in asymptomatic individuals and (2) selecting individuals (peripheral blood mononuclear cells (PBMC) culture positive) to be included in the xenodiagnosis experiments (see Project 2 for details) .
Results generated in this project will be of importance for individual as well as for public health. Identifying risk factors for progression from VL infection to disease may allow for secondary prevention. Evidence on the potential role of asymptomatic infections in L. donovani transmission may have major implications for the current VL control strategy.
|Sundar, Shyam; Singh, Anup (2018) Chemotherapeutics of visceral leishmaniasis: present and future developments. Parasitology 145:481-489|
|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|
|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|
|Kelly, Patrick H; Bahr, Sarah M; Serafim, Tiago D et al. (2017) The Gut Microbiome of the Vector Lutzomyia longipalpis Is Essential for Survival of Leishmania infantum. MBio 8:|
|Sharma, Smriti; Srivastva, Shweta; Davis, Richard E et al. (2017) The Phenotype of Circulating Neutrophils during Visceral Leishmaniasis. Am J Trop Med Hyg 97:767-770|
|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|
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