Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study

Jaya Chakravarty; Epco Hasker; Sangeeta Kansal; Om Prakash Singh; Paritosh Malaviya; Abhishek Kumar Singh; Ankita Chourasia; Toolika Singh; Medhavi Sudarshan; Akhil Pratap Singh; Bhawana Singh; Rudra Pratap Singh; Bart Ostyn; Michaela Fakiola; Albert Picado; Joris Menten; Jenefer M Blackwell; Mary E Wilson; David Sacks; Marleen Boelaert; Shyam Sundar

doi:10.1371/journal.pntd.0007216

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Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study

Journal article

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Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study

Jaya Chakravarty, Epco Hasker, Sangeeta Kansal, Om Prakash Singh, Paritosh Malaviya, Abhishek Kumar Singh, Ankita Chourasia, Toolika Singh, Medhavi Sudarshan, Akhil Pratap Singh, …

PLoS neglected tropical diseases, Vol.13(3), pp.e0007216-e0007216

03/27/2019

DOI: 10.1371/journal.pntd.0007216

PMCID: PMC6453476

PMID: 30917114

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Abstract

Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.

Details

Title: Subtitle: Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study
Creators: Jaya Chakravarty - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Epco Hasker - Institute of Tropical Medicine, Antwerp, Belgium
Sangeeta Kansal - Department of Community Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Om Prakash Singh - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Paritosh Malaviya - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Abhishek Kumar Singh - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Ankita Chourasia - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Toolika Singh - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Medhavi Sudarshan - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Akhil Pratap Singh - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Bhawana Singh - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Rudra Pratap Singh - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Bart Ostyn - Institute of Tropical Medicine, Antwerp, Belgium
Michaela Fakiola - Cambridge Institute for Medical Research, University of Cambridge, United Kingdom and Telethon Kids Institute, University of Western Australia, Crawley, Australia
Albert Picado - ISGlobal, Barcelona Ctr. Int.Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
Joris Menten - Institute of Tropical Medicine, Antwerp, Belgium
Jenefer M Blackwell - Cambridge Institute for Medical Research, University of Cambridge, United Kingdom and Telethon Kids Institute, University of Western Australia, Crawley, Australia
Mary E Wilson - University of Iowa and the Veterans Affairs Medical Centre, Iowa City, Iowa, United States of America
David Sacks - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland, United States of America
Marleen Boelaert - Institute of Tropical Medicine, Antwerp, Belgium
Shyam Sundar - Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Banaras, India
Resource Type: Journal article
Publication Details: PLoS neglected tropical diseases, Vol.13(3), pp.e0007216-e0007216
DOI: 10.1371/journal.pntd.0007216
PMID: 30917114
PMCID: PMC6453476
NLM abbreviation: PLoS Negl Trop Dis
ISSN: 1935-2735
eISSN: 1935-2735
Publisher: United States
Grant note: P50 AI074321 / NIAID NIH HHS U19 AI074321 / NIAID NIH HHS
Language: English
Date published: 03/27/2019
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001140802771

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