Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal

Epco Hasker; Paritosh Malaviya; Kamlesh Gidwani; Albert Picado; Bart Ostyn; Sangeeta Kansal; Rudra Pratap Singh; Om Prakash Singh; Ankita Chourasia; Abhishek Kumar  Singh; Ravi Shankar; Mary E Wilson; Basudha Khanal; Suman Rijal; Marleen Boelaert; Shyam Sundar

doi:10.1371/journal.pntd.0002657

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Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal

Journal article

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Peer reviewed

Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal

Epco Hasker, Paritosh Malaviya, Kamlesh Gidwani, Albert Picado, Bart Ostyn, Sangeeta Kansal, Rudra Pratap Singh, Om Prakash Singh, Ankita Chourasia, Abhishek Kumar Singh, …

PLoS neglected tropical diseases, Vol.8(1), pp.e2657-e2657

2014

DOI: 10.1371/journal.pntd.0002657

PMCID: PMC3900391

PMID: 24466361

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Abstract

Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4-10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers. We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified. We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers. There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious for sand flies.

Carrier State - immunology

Leishmania donovani - immunology

Prospective Studies

Risk Assessment

Humans

Middle Aged

Child, Preschool

India - epidemiology

Male

Leishmaniasis, Visceral - immunology

Leishmaniasis, Visceral - pathology

Antigens, Protozoan

Young Adult

Antibodies, Protozoan - blood

Adolescent

Aged, 80 and over

Adult

Female

Aged

Child

Leishmaniasis, Visceral - epidemiology

Nepal - epidemiology

Cohort Studies

Details

Title: Subtitle: Strong association between serological status and probability of progression to clinical visceral leishmaniasis in prospective cohort studies in India and Nepal
Creators: Epco Hasker - Institute of Tropical Medicine, Antwerp, Belgium
Paritosh Malaviya - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Kamlesh Gidwani - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India ; Department of Biotechnology, University of Turku, Turku, Finland
Albert Picado - Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain
Bart Ostyn - Institute of Tropical Medicine, Antwerp, Belgium
Sangeeta Kansal - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Rudra Pratap Singh - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Om Prakash Singh - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Ankita Chourasia - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Abhishek Kumar Singh - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Ravi Shankar - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Mary E Wilson - University of Iowa and the Veterans' Affairs Medical Center, Iowa City, Iowa, United States of America
Basudha Khanal - B.P. Koirala Institute of Health Sciences, Dharan, Nepal
Suman Rijal - B.P. Koirala Institute of Health Sciences, Dharan, Nepal
Marleen Boelaert - Institute of Tropical Medicine, Antwerp, Belgium
Shyam Sundar - Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Resource Type: Journal article
Publication Details: PLoS neglected tropical diseases, Vol.8(1), pp.e2657-e2657
DOI: 10.1371/journal.pntd.0002657
PMID: 24466361
PMCID: PMC3900391
NLM abbreviation: PLoS Negl Trop Dis
ISSN: 1935-2727
eISSN: 1935-2735
Publisher: United States
Grant note: P50 AI074321 / NIAID NIH HHS R01 AI045540 / NIAID NIH HHS P50 AI-074321 / NIAID NIH HHS R01 AI076233 / NIAID NIH HHS
Language: English
Date published: 2014
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001217602771

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