Journal Article

Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study

Kansal, Sangeeta, Malaviya, Paritosh, Sacks, David, Chakravarty, Jaya, Fakiola, Michaela, Wilson, Mary E., Hasker, Epco, Blackwell, Jenefer M., Singh, Rudra Pratap, Singh, Akhil Pratap, Chourasia, Ankita, Sudarshan, Medhavi, Singh, Om Prakash, Picado, Albert, Singh, Bhawana, Sundar, Shyam, Singh, Toolika, Singh, Abhishek Kumar, Ostyn, Bart, Menten, Joris, Boelaert, Marleen

2019

Overview

Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Agglutination tests / Antibodies / Antibodies, Protozoan - blood / Antigens / Asymptomatic infection / Asymptomatic Infections - epidemiology / Biology and Life Sciences / Blood / Care and treatment / Cohort analysis / Cohort Studies / Cohorts / Converters / Development and progression / Disease Progression / DNA / Electric converters / ELISA / Endemic Diseases / Enzyme-Linked Immunosorbent Assay / Female / Filter paper / Genetic markers / Genotyping / Genètica molecular / Histocompatibility antigen HLA / Humans / Immunology / India - epidemiology / Infant / Infection / Infections / Leishmania / Leishmania donovani - genetics / Leishmania donovani - immunology / Leishmania donovani - isolation & purification / Leishmaniasis / Leishmaniasis, Visceral - epidemiology / Leishmaniasis, Visceral - parasitology / Leishmaniasis, Visceral - pathology / Leishmaniosi / Male / Medical research / Medicine / Medicine and Health Sciences / Molecular genetics / Nucleotide sequence / Observations / Parasitic diseases / PCR / People and Places / Polymerase chain reaction / Preventive medicine / Ratios / Research and Analysis Methods / Seroconversion / Single-nucleotide polymorphism / Studies / Tests / Tropical diseases / Vector-borne diseases / Virulence (Microbiology) / Visceral leishmaniasis