As not all infections with lead to disease, the impact of control programs should not only be measured in numbers of VL cases, but also in number of new infections. asymptomatic contamination in VL high-endemic foci in India and Nepal is usually nine times more frequent than incident VL disease. About 1 in 50 of these new but latent infections led to VL within the next 18 months. Author Summary Visceral Leishmaniasis is well known as a public health problem in North-Indian Bihar state and adjacent districts in Nepal, with about 300.000 new cases per year. As not all infections with lead to disease, the impact of control programs should not only be measured in numbers of VL cases, but also in number of new infections. So far there have been little or no data around the infectiondisease ratio for this region, and the evolution of these latent infections. Using DAT seroconversion as a marker of contamination, we found MK-2894 incident asymptomatic contamination to be nine times more frequent than incident VL disease in high-endemic villages in India and Nepal, and about 1 in 50 of these latent infections lead to VL in the next 18 months, while over 80% turn seronegative again within a year. Asymptomatic DAT-positivity detected through screening in a person with no history of VL, and Rabbit Polyclonal to ATG4D especially in case of documented recent seroconversion, is usually a risk factor for ultimately developing MK-2894 VL. Further studies on transient and persistent asymptomatic contamination are needed to better understand their immunological patterns and serokinetics, their level of infectivity, and their potential for later progression to VL. Introduction In the Indian subcontinent 200 million people are estimated to be at risk of developing Visceral Leishmaniasis (VL). VL, also known as kala-azar is usually a fatal parasitic disease caused by infections remain asymptomatic [4]. Cross-sectional surveys based on serological testing by Direct Agglutination Test (DAT) [5]C[9] or ELISA [9] and/or positive delayed-type hypersensitivity (DTH) reaction to a leishmanin skin test (LST) [10]C[12] show high proportions of MK-2894 positive persons who never reported clinical disease. It is unclear whether these asymptomatic infected persons are infectious to the sandfly vector, whether they acquire persistent immunity or develop VL later on. The proportion of infections that result in VL disease is usually poorly documented as this requires large prospective epidemiological studies. In Brazil the ratio of incident contamination to incident disease ranged between 6.51 and 18.51 [13]C[15], whereas in Africa ratios ranging from 12.4 to 111 have been reported [16]C[19]. In the only population-based longitudinal study in South-East Asia published so far Bern found a 41 ratio of incident contamination versus disease in Bangladesh [20]. Comparable estimates are not yet available for India and Nepal, two other countries affected by VL in the Indian subcontinent. The objective of this study was to examine the relationship between contamination and clinical disease, and to estimate the probability of progressing to clinical VL in recently infected persons in India and Nepal. Materials and Methods a. Ethical issues A large community intervention study to measure effectiveness of long-lasting insecticide treated bednets (LN) for prevention of VL in India and Nepal (KALANET, ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT00318721″,”term_id”:”NCT00318721″NCT00318721) provided the opportunity to document incident contamination and disease in Nepal and in India. Consent for the Kalanet study was sought at three levels: community, household and individual. Communities were duly informed about the purpose of the trial and consent was sought from village leaders for inclusion of the cluster in the trial. Written informed consent was obtained from all participants or their guardians for those under 18 years old. A literate witness signed on behalf of illiterate participants who added their thumbprint to the informed consent form..