Vector-borne pathogen transmission

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The accomplishments of this project for FY2025 are: 1-We looked at the implications of vector transmission on the chronicity and pathogenesis of visceral leishmaniasis (VL) in high-risk populations. We investigated malnutrition which is a known risk factor in human VL. We found that sand fly transmission or malnutrition promote parasite dissemination by working in concert to drive IL1-β-driven acute inflammation, a significantly higher acute (P ≤ 0.001) and chronic (P ≤ 0.0001) splenic parasite burden, chronic clinical symptoms (P ≤ 0.0001), neutrophilia (P ≤ 0.001), lymphocytopenia (P ≤ 0.0001), increased heme oxygenase-1 (P ≤ 0.001) and IL17-A (P ≤ 0.0001) levels, dysregulation of liver enzymes, lymph node barrier dysfunction, and augmented dysbiosis, all associated with enhanced VL severity revealing new aspects of VL pathogenesis and host defense. Iniguez E, Doehl J, Cecilio P, Serafim TD, Percopo C, Rangel-Gonzalez Y, Dey S, Osorio EJ, Huffcutt P, Roitman S, Meneses C, Short M, Valenzuela JG, Melby PC, Kamhawi S (2025). Malnutrition exacerbates pathogenesis of Lutzomyia longipalpis sand fly-transmitted Leishmania donovani. Commun Biol 8(1):746. https://doi.org/10.1038/s42003-025-08106-8 2-In collaboration with Drs. Sanath Senanayake and Nadira Karunaweera, University of Colombo, Sri Lanka, we demonstrated that biomarker that we developed of vector exposure to Phlebotomus argentipes, the sand fly vector of Leishmania donovani, the causative agent of visceral leishmaniasis in the Indian subcontinent (ISC), is reliable for evaluating exposure to Phlebotomus argentipes in Sri Lanka, indicative of its effectiveness in another endemic setting. Piyasiri SB, Senanayake S, Smaranayake N, Doh S, Iniguez E, Valenzuela JG, Kamhawi S, Karunaweera ND (2024). Salivary antigens rPagSP02 and rPagSP06 are a reliable composite biomarker for evaluating exposure to Phlebotomus argentipes in Sri Lanka. Sci Rep 14(1):25863. https://doi.org/10.1038/s41598-024-77666-2 3-In collaboration with Drs. Sanath Senanayake and Nadira Karunaweera, University of Colombo, Sri Lanka, we are using our previously developed marker of vector exposure to Phlebotomus argentipes, the sand fly vector of Leishmania donovani, the causative agent of visceral leishmaniasis in the Indian subcontinent (ISC), to test the effectiveness of long-lasting insecticide impregnated bed nets (LLINs) to interrupt exposure to bites of this vector. This study demonstarted the efficacy or our biomarker as a tool to assess vector exposure and success of interventions. This collaboration is funded by a grant from the CRDFGLOBAL. The study was approved by the Ethics Review Committee of the Faculty of Medicine, University of Colombo, Sri Lanka (EC-21–074). Piyasiri SB, Senanayake S, Smaranayake N, Iniguez E, Valenzuela JG, Piyasiri NN, Kamhawi S, Karunaweera ND (2025). Effectiveness of Long-Lasting Insecticide-Impregnated Bed Nets in Controlling Phlebotomus argentipes in Sri Lanka: A Cluster Randomized Controlled Trial. J Infect Dis jiaf359. https://doi.org/10.1093/infdis/jiaf359 4- In collaboration with Seydou Doumbia, we reported on an epidemiological investigation of visceral leishmaniasis in the Lere district hospital in southwestern Chad, revealing its previously overlooked public health importance. Of a total of 40 serology positive patients, L. donovani DNA was found in 33 (82.5%), with 55% being male patients. The most affected age groups were 15–29 (47.5%) and 0–14 (32.5%) years. Fever, weight loss, and pallor were frequent symptoms. Notably, splenomegaly and hepatomegaly were uncommon clinical signs. Common comorbidities included malaria (25%) and hepatitis B (15%), followed by gastric ulcer (10%) and tuberculosis (7.5%). These comorbidities were concurrent with VL and were diagnosed microscopically in blood and serum for malaria and tuberculosis, respectively, and by the rapid diagnostic test using serum for hepatitis B and gastric ulcer. Thirty-five percent of cases were treated with meglumine antimoniate, and three patients (7.5%), all with comorbidities, died. Sixty percent of patients lived close to the main town. Our data demonstrate that VL is endemic in the health district of Lere. Improving health education regarding L. donovani infection in endemic areas of Chad and providing training of health workers on early detection and management of VL are needed to help save lives. Israël DK, Coulibaly CA, Joël V, Fesuh Nono B, Vincent G, Kamhawi S, Doumbia S (2024). Demographic and Clinical Features of Visceral Leishmaniasis in Chad: A Prospective Cross-Sectional Survey. Am J Trop Med Hyg 111(6):1192–1197. https://doi.org/10.4269/ajtmh.23-0033 5- We continued to explore the potential of immunogenic sand fly salivary proteins as components of a Leishmania vaccines. In collaboration with Dr. Naomi Aronson, USUHS, we demonstrated that volunteers exposed to uninfected bites of Lutzomyia longipalpis sand flies developed a cellular immunity to salivary gland homogenate, and identified recombinant antigens, LJM19 and LJL143, that produce protective Th1-biased immunity, but with high co-expression of the Th-2 cytokine IL-13. This works demonstrates the immunogenicity of sand fly salivary proteins in humans reinforcing their potential as vaccine candidates. Abdeladhim M, Teixeira C, Ressner R, Hummer K, Dey R, Gomes R, de Castro W, de Araujo FF, Turiansky GW, Iniguez E, Meneses C, Oliveira F, Aronson N, Lacsina JR, Valenzuela JG, Kamhawi S (2025). Human sand fly challenge elicits saliva-specific innate and TH1-polarized immunity that promotes Leishmania killing. bioRxiv [Preprint]. 6-In collaboration with Caryn Bern and Sridhar Srikantiah, our work in India demonstrated the need for continued active surveillance of visceral leishmaniasis cases and Leishmania-infected sand flies in low transmission settings prevalent towards the end of elimination campaigns. Iniguez, E., Priyamvada, K., Dubey, P., Bindroo, J., Shahnawaz, M., Alam, A., Singh, S., Kumar, A., Kumar, G., Kumar, P., Pandey, S., Huffcutt, P., Meneses, C., Patra, D., Sukla, I., Ali, A., Mishra, P. K., Sinha, B., Mahapatra, T., Serafim, T. D., Kumar, A., Singh, B. K., Valenzuela, J. G., Hightower, A., Srikantiah, S., Sharma, S., Bern, C., & Kamhawi, S. (n.d.). High rK39 prevalence and capture of Leishmania donovani-infected sand flies in Bihar and Jharkhand emphasize the need for post-elimination surveillance of visceral leishmaniasis in India. SSRN. https://ssrn.com/abstract=5283105 or http://dx.doi.org/10.2139/ssrn.5283105.[Preprint] 7- We continue to maintain a thriving and working size sand fly colonies of important vector species that forms the basis of our research but is also a vital resource for the leishmaniasis research community at NIAID, nationally and internationally and are supporting BEI resources. Our colony manager, Claudio Meneses also provides links to protocols and videos of how to maintain and grow sand fly colonies. 8- We continue to explore the inflammatory response in host skin after Leishmania-infected sand fly bites with a focus on the role of inflammasomes in early parasite establishment. 9- We are in the final stages of developing a toolbox focused on in-depth analysis of DNA and RNA extracted from the midgut of individual field-collected females vector sand flies to facilitate the identification of animal reservoirs of Leishmania parasites, a major knowledge gap in the field central to planning of effective control strategies. Once completed, this could have a significant impact on how field work is conducted in active leishmaniasis foci to elucidate disease transmission and to guide a targeted control strategy.