Browsing by Author "Shweta Srivastva"

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A subset of neutrophils expressing markers of antigen-presenting cells in human visceral leishmaniasis
(Oxford University Press, 2016) Smriti Sharma; Richard E. Davis; Shweta Srivastva; Susanne Nylén; Shyam Sundar; Mary E. Wilson
Background. Visceral leishmaniasis (VL) is a potentially fatal parasitic disease associated with fever, cachexia and impaired protective T-cell responses against the parasite. Methods. Peripheral blood leukocytes from 105 subjects with VL and healthy control subjects from the endemic region of Muzaffarpur, Bihar, India, were compared using flow cytometry and reverse-transcriptase quantitative polymerase chain reaction. Findings were correlated with clinical data. Results. An expanded population of low-density neutrophils that expressed HLA-DR, CD80 and CD86 was observed in subjects with VL. This neutrophil population contracted after successful treatment of disease. Plasma from patients with acute VL was able to induce similar high-level HLA-DR expression in neutrophils from healthy subjects. HLA-DR+ neutrophils from subjects with VL did not stimulate T-cell proliferation, but they did express higher programmed cell death ligand-1 (PDL1) than other neutrophils, and lymphocytes of the same subjects expressed high programmed cell death 1 (PD1). Conclusions. Patients with acute VL have expanded circulating low-density neutrophils expressing markers of antigen presentation, which diminish after treatment. Development of HLA-DR+ neutrophils is stimulated, at least in part, by components of plasma from patients with acute disease. Although we found no evidence that they act as antigen-presenting cells, these neutrophils expressed markers implicating a role in T-cell exhaustion. © 2016 Published by Oxford University Press for the Infectious Diseases Society of America.
Livestock and rodents within an endemic focus of Visceral Leishmaniasis are not reservoir hosts for Leishmania donovani
(Public Library of Science, 2022) Anurag Kumar Kushwaha; Ashish Shukla; Breanna M. Scorza; Tulika Kumari Rai; Rahul Chaubey; Dharmendra Kumar Maurya; Shweta Srivastva; Shreya Upadhyay; Abhishek Kumar Singh; Paritosh Malviya; Om Prakash Singh; Vivek Kumar Scholar; Puja Tiwary; Shakti Kumar Singh; Phillip Lawyer; Edgar Rowton; Scott A. Bernhardt; Christine A. Petersen; Shyam Sundar
Leishmaniasis on the Indian subcontinent is thought to have an anthroponotic transmission cycle. There is no direct evidence that a mammalian host other than humans can be infected with Leishmania donovani and transmit infection to the sand fly vector. The aim of the present study was to evaluate the impact of sand fly feeding on other domestic species and provide clinical evidence regarding possible non-human reservoirs through experimental sand fly feeding on cows, water buffalo goats and rodents. We performed xenodiagnosis using colonized Phlebotomus argentipes sand flies to feed on animals residing in villages with active Leishmania transmission based on current human cases. Xenodiagnoses on mammals within the endemic area were performed and blood-fed flies were analyzed for the presence of Leishmania via qPCR 48hrs after feeding. Blood samples were also collected from these mammals for qPCR and serology. Although we found evidence of Leishmania infection within some domestic mammals, they were not infectious to vector sand flies. Monitoring infection in sand flies and non-human blood meal sources in endemic villages leads to scientific proof of exposure and parasitemia in resident mammals. Lack of infectiousness of these domestic mammals to vector sand flies indicates that they likely play no role, or a very limited role in Leishmania donovani transmission to people in Bihar. Therefore, a surveillance system in the peri-/post-elimination phase of visceral leishmaniasis (VL) must monitor absence of transmission. Continued surveillance of domestic mammals in outbreak villages is necessary to ensure that a non-human reservoir is not established, including domestic mammals not present in this study, specifically dogs. © 2022 Kushwaha et al.
Long-term treatment outcome and mutational analysis of patients on third-line antiretroviral therapy in programmatic conditions
(Oxford University Press, 2023) Jaya Chakravarty; Shweta Srivastva; Anurag Kumar Kushwaha; Arijit Pal
Background: In low- and middle-income countries where most patients receive standardized third-line ART through national programmes, real-world data are scarce. This study was done to assess the long-term survival, and virological and mutational outcomes of people living with HIV receiving third-line ART between July 2016 and December 2019 in an ART centre in India. Methods: Eighty-five patients were started on third-line ART. Genotypic resistance testing to identify drug resistance mutations in the integrase, reverse transcriptase and protease genes was done at the start of third-line therapy, as well as in those who did not attain virological suppression after 12 months of therapy. Results: Survival was 85% (72/85) at 12 months and 72% (61/85) at the end of follow-up in March 2022. Virological suppression was present in 82% (59/72) and 88% (59/67) at 12 months and at the end of followup, respectively. Five out of 13 patients who had virological failure at 12 months showed virological suppression at the end of the study. At the start of third-line therapy, 35% (14/40) and 45% (17/38) of patients had major integrase- and protease-associated mutations, respectively, even though they had never been on integrase inhibitor-based regimens. At 1 year follow-up, among those failing third-line therapy, 33% (4/12) of patients had major integrase mutations, but none had major protease mutations. Conclusions: This study demonstrates good long-term outcome in patients on standardized third-line ART in programmatic conditions with very few mutations in those failing the therapy. © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved.
Prevalence of HIV Drug Resistance Mutations among Treatment-Naive People Living with HIV in a Tertiary Care Center in India
(American Society of Tropical Medicine and Hygiene, 2024) Shweta Srivastva; Jaya Chakravarty; Anurag Kumar Kushwaha
India has the third-largest number of people living with HIV (PLHIV) in the world. A national program provides free access to standard uniform antiretroviral therapy. However, the program is not monitored by comprehensive drug resistance surveys. The aim of this study was to determine the prevalence of HIV drug resistance mutations (DRMs) among treatment-naive PLHIV in a large antiretroviral treatment center of the national program. This cross-sectional study was done in 2017 and involved 200 consecutive treatment-naive PLHIV. A target fragment of 1,306 bp in the reverse transcriptase and protease regions was amplified. Identification of mutations and drug resistance interpretation was done by HIV Genotypic Resistance Interpretation and International Antiviral Society-USA list. Sequencing was successful in 177 samples. The majority (98.8%; 175/177) belonged to subtype C. Nineteen of 177 patients (10.7%; 95% CI: 6.2%–15.3%) had at least one major DRM. The prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations was 10.2% (18/177). The most frequent mutations were E138A/K, A98G, K103N, V179D, and K101H/E. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI) mutations was 1.1% (2/177). None of the samples had major protease inhibitor resistance mutations. The prevalence of NNRTI mutations in this study was .10%, crossing the threshold recommended by the WHO to change the NNRTI-based first-line regimen to non–NNRTI based. In 2021, the national program replaced efavirenz with dolutegravir in the first-line regimen of tenofovir, lamivudine, and efavirenz. As the majority (64%) of PLHIV in India are accessing free ART from the national program, this study highlights the need for regular nationally representative drug resistance surveys for optimizing antiretroviral regimens in the program. © 2024 American Society of Tropical Medicine and Hygiene. All rights reserved.
The phenotype of circulating neutrophils during visceral leishmaniasis
(American Society of Tropical Medicine and Hygiene, 2017) Smriti Sharma; Shweta Srivastva; Richard E. Davis; Siddharth Sankar Singh; Rajiv Kumar; Susanne Nylén; Mary E. Wilson; Shyam Sundar
Visceral leishmaniasis (VL) is a chronic parasitic disease associated with suppressed T cell responses. Although parasites reside intracellularly in macrophages during chronic VL, neutrophils are the first host cell to in filtrate the infection site and phagocytose the parasite. Subsets of neutrophils with unusual characteristics have been documented in human VL, but whether the total neutrophil population is a berrant during disease is not known. Therefore, we examined phenotypic characteristics of unfractionated polymorphonuclear leukocyte (neutrophils) from subjects with active VL, and compared these with neutrophils from healthy controls or subjects who have been treated for VL. The data showed decreased mRNA and diminished amounts of the neutrophil chemoattractant CXCL8 (interleukin [IL]-8), increased IL-10 mRNA and protein, and elevated transcripts encoding arginase-1, which is involved in suppressing T cell responses. Neutrophils from VL subjects showed enhanced capacity to phagocytose Leishmania spp. promastigotes. The results suggest that neutrophils may contribute to immunosuppression in subjects with active VL. © Copyright 2017 by The American Society of Tropical Medicine and Hygiene.