Diagnosis of Visceral Leishmaniasis in an Elimination Setting: A Validation Study of the Diagnostic Algorithm in India.

Kristien Cloots,Abhishek Kumar Singh,Shyam Sundar,Paritosh Malaviya,Epco Hasker,Sangeeta Kansal,Anurag Kumar Kushwaha,Om Prakash Singh

doi:10.3390/diagnostics12030670

Abstract

Visceral leishmaniasis (VL) is on the verge of elimination on the Indian subcontinent. Nonetheless, the currently low VL-incidence setting brings along new challenges, one of which is the validity of the diagnostic algorithm, based on a combination of suggestive clinical symptoms in combination with a positive rK39 Rapid Diagnostic Test (RDT). With this study, we aimed to assess the positive predictive value of the diagnostic algorithm in the current low-endemic setting in India by re-assessing newly diagnosed VL patients with a qPCR analysis on venous blood as the reference test. In addition, we evaluated the specificity of the rK39 RDT by testing non-VL cases with the rK39 RDT. Participants were recruited in Bihar and Uttar Pradesh, India. VL patients diagnosed based on the diagnostic algorithm were recruited through six primary health care centers (PHCs); non-VL cases were identified through a door-to-door survey in currently endemic, previously endemic, and non-endemic clusters, and tested with rK39 RDT, as well as—if positive—with qPCR on peripheral blood. We found that 95% (70/74; 95% CI 87–99%) of incident VL cases diagnosed at the PHC level using the current diagnostic algorithm were confirmed by qPCR. Among 15,422 non-VL cases, 39 were rK39 RDT positive, reflecting a specificity of the test of 99.7% (95% CI 99.7–99.8%). The current diagnostic algorithm combining suggestive clinical features with a positive rK39 RDT still seems valid in the current low-endemic setting in India.

Highlights

Visceral leishmaniasis (VL), called kala-azar on the Indian subcontinent, is a parasitic, vector-borne, Neglected Tropical Disease that is fatal if not treated in a timely fashion
Out of the 74 VL patients, 70 tested positive with quantitative polymerase chain reaction (qPCR), yielding a positive predictive value (PPV) of 95% (70/74 = 95%; 95% CI 87–99%) of the diagnostic algorithm
We found the PPV of the diagnostic algorithm to be 95% when using a qPCR analysis on peripheral blood as a reference test

Summary

Introduction

Visceral leishmaniasis (VL), called kala-azar on the Indian subcontinent, is a parasitic, vector-borne, Neglected Tropical Disease that is fatal if not treated in a timely fashion. Since the kala-azar elimination initiative was launched on the Indian subcontinent in 2005, an important reduction in the number of VL cases has been observed in the region. In India, reported cases of VL dropped from 32,803 in 2005 to 2033 in 2020, translating into an annual incidence below the elimination threshold of 1 per 10,000 population in 98%. This low-incidence setting brings along new challenges, one if which is the validity of the current diagnostic algorithm [2,3]. Visceral leishmaniasis usually presents with a spectrum of rather non-specific clinical symptoms. The National Guidelines in India state that a diagnosis of VL should be based on a combination of suggestive clinical signs (mainly fever for more than two weeks and hepatosplenomegaly) and a positive serological and/or parasitological test [4]

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