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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Institute of Tropical Medicine, Antwerp, Belgium.
Epco
E
Hasker
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Paritosh
P
Malaviya
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India ; Department of Biotechnology, University of Turku, Turku, Finland.
Kamlesh
K
Gidwani
Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain.
Albert
A
Picado
Institute of Tropical Medicine, Antwerp, Belgium.
Bart
B
Ostyn
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Sangeeta
S
Kansal
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Rudra Pratap
RP
Singh
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Om Prakash
OP
Singh
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Ankita
A
Chourasia
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Abhishek
A
Kumar Singh
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Ravi
R
Shankar
University of Iowa and the Veterans' Affairs Medical Center, Iowa City, Iowa, United States of America.
Mary E
ME
Wilson
B.P. Koirala Institute of Health Sciences, Dharan, Nepal.
Basudha
B
Khanal
B.P. Koirala Institute of Health Sciences, Dharan, Nepal.
Suman
S
Rijal
Institute of Tropical Medicine, Antwerp, Belgium.
Marleen
M
Boelaert
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Shyam
S
Sundar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan; D002353:Carrier State / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009390:Nepal / Q000453:epidemiology; D011446:Prospective Studies; D018570:Risk Assessment; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan