A Global Comparative Evaluation of Commercial Immunochromatographic Rapid Diagnostic Tests for Visceral Leishmaniasis

Visceral leishmaniasis (VL) is a parasitic disease transmitted through the bite of an infected phlebotomine sandfly [1]. The clinical syndrome is characterized by fever, weight loss, splenomegaly, and pancytopenia and is nearly always fatal if left untreated. Though visceral leishmaniasis is endemic in >60 countries, 90% of the 200 000–400 000 annual cases occur in just 6 countries: Bangladesh, Brazil, Ethiopia, India, Nepal, and Sudan [2]. Parasitological confirmation remains the reference standard for diagnosis but is not very sensitive unless a spleen puncture is performed. The invasiveness and potentially fatal complications associated with splenic aspiration has motivated the development of noninvasive serological tests such as direct agglutination test (DAT) [3] and lateral flow immunochromatographic tests (ICT), commonly referred to as rapid diagnostic tests (RDTs). To be useful, VL RDTs must have adequate (1) sensitivity to detect a high proportion of clinical cases, (2) specificity to accurately discriminate VL from other relevant disease conditions, (3) thermal stability for accuracy to be maintained after transport and storage in ambient conditions, and (4) ease of use to allow the correct interpretation of results. A meta-analysis [4] and a multicenter evaluation [5] corroborated earlier findings of high diagnostic accuracy of the rK39 ICT and led to its adoption as a diagnostic test in the Indian subcontinent VL Elimination Initiative. The enthusiasm and rapid uptake of RDTs for VL in the Asian region has prompted a surge of commercial tests targeting serum antibodies to rK39 and other antigens (eg, rKE16) [6]. However, in other endemic regions such as East Africa, reports of lower test sensitivity [7–9] have left the role of RDTs less clear. Moreover, there are few, if any, reports of diagnostic accuracy in the peer-reviewed literature for tests other than the Kalazar Detect (Inbios International) and DiaMed-IT LEISH (Bio-Rad Laboratories) and equally few head-to-head comparisons. Essential characteristics as heat stability are rarely assessed. As independent data on how well these assays meet criteria are lacking in countries without regulation by national testing authorities, the UNICEF/World Bank/United Nations Development Programme/World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) coordinated a multiregional head-to-head laboratory-based evaluation of 4 commercially available RDTs in 3 global regions of VL endemicity using well-characterized panels of human sera; a fifth RDT was included in the Indian subcontinent.