Chapman, Lloyd A. C., Dyson, Louise, Courtenay, Orin, Chowdhury, Rajib, Bern, Caryn, Medley, Graham and Hollingsworth, T. Déirdre (2015) Quantification of the natural history of visceral leishmaniasis and consequences for control. Parasites & Vectors, 8 (1). pp. 1-13. 521. doi:10.1186/s13071-015-1136-3 ISSN 1756-3305.

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Abstract

Background
Visceral leishmaniasis has been targeted for elimination as a public health problem (less than 1 case per 10,000 people per year) in the Indian sub-continent by 2017. However, there is still a high degree of uncertainty about the natural history of the disease, in particular about the duration of asymptomatic infection and the proportion of asymptomatically infected individuals that develop clinical visceral leishmaniasis. Quantifying these aspects of the disease is key for guiding efforts to eliminate visceral leishmaniasis and maintaining elimination once it is reached.

Methods
Data from a detailed epidemiological study in Bangladesh in 2002–2004 was analysed to estimate key epidemiological parameters. The role of diagnostics in determining the probability and rate of progression to clinical disease was estimated by fitting Cox proportional hazards models. A multi-state Markov model of the natural history of visceral leishmaniasis was fitted to the data to estimate the asymptomatic infection period and the proportion of asymptomatic individuals going on to develop clinical symptoms.

Results
At the time of the study, individuals were taking several months to be diagnosed with visceral leishmaniasis, leading to many opportunities for ongoing transmission. The probability of progression to clinical disease was strongly associated with initial seropositivity and even more strongly with seroconversion, with most clinical symptoms developing within a year. The estimated average durations of asymptomatic infection and symptomatic infection for our model of the natural history are 147 days (95 % CI 130–166) and 140 days (95 % CI 123–160), respectively, and are significantly longer than previously reported estimates. We estimate from the data that 14.7 % (95 % CI 12.6-20.0 %) of asymptomatic individuals develop clinical symptoms—a greater proportion than previously estimated.

Conclusions
Extended periods of asymptomatic infection could be important for visceral leishmaniasis transmission, but this depends critically on the relative infectivity of asymptomatic and symptomatic individuals to sandflies. These estimates could be informed by similar analysis of other datasets. Our results highlight the importance of reducing times from onset of symptoms to diagnosis and treatment to reduce opportunities for transmission.

Item Type:	Journal Article
Subjects:	R Medicine > RA Public aspects of medicine
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Science > Mathematics
Library of Congress Subject Headings (LCSH):	Leishmaniasis, Communicable diseases -- Prevention
Journal or Publication Title:	Parasites & Vectors
Publisher:	BioMed Central Ltd.
ISSN:	1756-3305
Official Date:	22 October 2015
Dates:	Date Event 22 October 2015 Published 3 October 2015 Accepted 2 September 2015 Submitted
Volume:	8
Number:	1
Number of Pages:	13
Page Range:	pp. 1-13
Article Number:	521
DOI:	10.1186/s13071-015-1136-3
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	31 December 2015
Date of first compliant Open Access:	31 December 2015
Funder:	Bill & Melinda Gates Foundation, Centers for Disease Control and Prevention (U.S.) (CDC)

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