Quantification of the natural history of visceral leishmaniasis and consequences for control.
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.
School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK. L.Chapman.1@warwick.ac.uk.
Lloyd A C
LA
Chapman
School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
Louise
L
Dyson
School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
Orin
O
Courtenay
Country Programme Manager - Bangladesh, KalaCORE Programme, Dhaka, Bangladesh.|Department of Medical Entomology, National Institute of Preventive and Social Medicine (NIPSOM), Mohakhali, Dhaka, Bangladesh.
Rajib
R
Chowdhury
UCSF School of Medicine, 550 16th Street, San Francisco, CA, 94158, USA.
Caryn
C
Bern
London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Graham F
GF
Medley
School of Life Sciences, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
T Deirdre
TD
Hollingsworth
D000293:Adolescent; D000328:Adult; D000818:Animals; D001459:Bangladesh / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007893:Leishmania donovani / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000266:history / Q000517:prevention & control / Q000635:transmission*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D008962:Models, Theoretical; D016016:Proportional Hazards Models; D011576:Psychodidae / Q000469:parasitology; D055815:Young Adult