Abstract
BackgroundAsymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC.MethodsQuantitative polymerase chain reaction (qPCR), loop-mediated isothermal amplification (LAMP), and the direct agglutination test (DAT) were carried out on blood samples, and the Leishmania antigen ELISA was carried out on urine samples collected from 720 household and neighbouring contacts of 276 VL and post–kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL or PKDL, in endemic regions of Bangladesh between September 2016 and March 2018.ResultsOf the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), and Leishmania antigen ELISA (3.3%). Only one (0.1%) participant was detected positive by all four diagnostic tests. Poor agreement between tests was calculated using Cohen’s kappa (κ) statistics; however, the Leishmania antigen ELISA and DAT in combination captured all participants as positive by more than one test. We find evidence for a moderately strong association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004), and being positive for at least one of the four tests.ConclusionsLeishmania antigen ELISA on urine detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in a rapid diagnostic test (RDT) format would be of benefit to the elimination campaign.Graphical
Highlights
Asymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic
Asymptomatic infection is of importance to visceral leishmaniasis (VL) endemic regions of the Indian subcontinent (ISC—India, Nepal, and Bangladesh), where the disease has been the target of an elimination campaign since 2005 [5, 6]
In this study, we assessed the utility of the direct agglutination test (DAT), Quantitative polymerase chain reaction (qPCR), loop-mediated isothermal amplification (LAMP), and Leishmania antigen enzyme-linked immunosorbent assay (ELISA) for detection of asymptomatic Leishmania infection in household or neighbouring contacts of VL and post–kala-azar dermal leishmaniasis (PKDL) index cases in endemic regions of Bangladesh
Summary
Asymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic. Progression from asymptomatic infection to symptomatic disease was estimated to be between 5.6 and 15.2% in individuals with high anti-Leishmania antibody titres, as measured by the direct agglutination test (DAT), in India and Nepal [2]. Asymptomatic infection is of importance to VL endemic regions of the Indian subcontinent (ISC—India, Nepal, and Bangladesh), where the disease has been the target of an elimination campaign since 2005 [5, 6]. A study in a small number of asymptomatically infected dogs showed that L. infantum parasites were transmittable to sand flies [9]; no human data with L. donovani have yet been recorded. Sixteen (8.2%) asymptomatic individuals who converted to VL within 2 years in a study in Bangladesh were found to have significantly higher anti-rK39 antibody titres than their counterparts who did not progress [10]
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