Evaluation of rapid diagnostic tests: visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is a severe infectious disease caused by a protozoan parasite: Leishmania donovani in East Africa and the Indian subcontinent and Leishmania infantum in Latin America and the Mediterranean basin. Not all leishmanial infections lead to overt clinical disease, but in those infected persons who do develop the disease, multiplication of the parasite in the reticulo-endothelial system causes prolonged fever, anaemia, hepatosplenomegaly and weight loss. VL is fatal if it is not adequately treated. The drugs currently used to treat VL can have severe side effects and the clinical presentation of VL is not sufficiently specific to guide treatment. Highly accurate (both sensitive and specific), cheap and simple rapid diagnostic tests (RDTs) are therefore crucial for case-management of VL. Early case detection followed by adequate treatment is also central to control of VL because, as yet, no vaccine is available and the long-term impact of vector control is unclear. Although the need for accurate VL diagnostics is obvious, innovation in this field has been slow. Since the 1980s, the main objective of VL diagnostics development has been to replace the direct demonstration of parasites in tissue smears, a technique that is invasive and requires considerable expertise, by a ‘field test’ that is more appropriate for use in a VL-endemic context. Several serological tests have been developed, but none are specific for VL disease as such, although they have proved useful in combination with a clinical case definition. New diagnostic tools are needed for more than just the confirmation of VL disease. No alternatives to parasitological methods are yet available to establish test of cure in treated VL patients. Clinicians do not have the tools to distinguish re-infection from relapse in cases of recurrence, and control programmes do not have validated assays for the surveillance of drug resistance in parasites. Furthermore, in the context of the VL elimination initiative, it would be desirable to have better markers of leishmanial infection at the population level. Any evaluation of a new diagnostic device should carefully identify its intended purpose. Too often developers and researchers confuse a device for the detection of leishmanial infection with a device for the confirmation of VL disease, and this is particularly the case for nucleic-acidbased assays. PCR is usually highly sensitive for detection of leishmanial infection, but this does not mean PCR will be useful for the confirmation of acute VL disease in patients in endemic areas, as many carriers of the infection in these areas will be PCRpositive without developing VL disease. This article will focus specifically on the evaluation of RDTs for confirmation of VL disease.