Progression of asymptomaticLeishmaniainfection to visceral leishmaniasis in HIV-positive individuals in Bihar, India
Authors: Mahajan Raman , Owen Sophie I. , Kumar Shiril , Pandey Krishna , Kazmi Shahwar , Kumar Vikash , Adams Emily R. , Harshana Amit , Burza Sakib 
Published: October 2022

AbstractThere are no data on rate and risk factors for progression from asymptomaticLeishmaniainfection (ALI) to visceral leishmaniasis (VL) in people living with HIV (PLHIV) on the Indian subcontinent. In this prospective cohort study, we aim to establish the rate and risk factors for progression of ALI to VL in a cohort of PLHIV in Bihar, India. We identified 108 PLHIV having ALI at baseline (rK39 enzyme-linked immunosorbent assay (ELISA) and/or rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR); in addition, the urinaryLeishmaniaantigen ELISA was evaluated). The cohort was followed up every three months for 18 months in person; four (3.7%) participants developed VL. All four progressors to VL were positive by a minimum of three of the four tests in combination and had high levels of antigenuria and anti-Leishmaniaantibody titers compared to ALI non-progressors. The overall risk of developing VL in ALI diagnosed by rK39 ELISA, rK39 RDT, qPCR, andLeishmaniaantigen ELISA was 3.7% (4/108), 40% (2/5), 57% (4/7) and 50% (4/8), respectively. A secondary analysis was conducted on a cohort of 1198 PLHIV without ALI at baseline residing in the same areas, who were followed up by telephone for 18 months. All-cause mortality was higher in ALI compared to non-ALI (odds ratio (OR)=2.7; 95% confidence intervals (CI): 1.1-6.1). In multivariate modelling combining both cohorts, low CD4 counts, being clinical stage III for HIV infection as per World Health Organization (WHO) classification, and not being on anti-retroviral therapy (ART) at baseline were significantly associated with mortality, while ALI was not. There is a low rate of progression from ALI to VL in PLHIV. Individuals with ALI have higher mortality than those without, however, ALI was not a statistically significant factor for mortality after adjusting for other factors in a multivariate model.Author summaryPeople living with HIV (PLHIV) are at higher risk of developing visceral leishmaniasis (VL) and poor associated outcomes. We followed a cohort of 108 PLHIV in India with asymptomaticLeishmaniainfection (ALI) identified at baseline for 18 months to establish the rate and risk factors for progression of ALI to VL. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA) and/or rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinaryLeishmaniaantigen ELISA was evaluated. Within the 18-month follow-up period, four (3.7%) individuals developed VL, all positive by at least three of the four tests in combination at baseline and had high levels of antigen in the urine and anti-Leishmaniaantibody titers compared to ALI non-progressors. As a secondary analysis, we followed up a cohort of 1198 PLHIV without ALI from the same area by telephone over the same 18-month period. Mortality associated with any cause was higher in those with ALI compared to non-ALI. Across both ALI and non-ALI cohorts, low CD4 counts, being clinical stage three for HIV infection according to the World Health Organization (WHO) classification (one to four), and not being on anti-retroviral therapy (ART) at baseline were significantly associated with mortality.