Target product profile for a diagnostic test to confirm cure of visceral leishmaniasis

Leishmaniasis is caused by protozoan parasites which are transmitted by the bite of infected female phlebotomine sandflies. The disease is poverty-related and is associated with poor housing, migration and population displacement of nonimmune people into areas with existing endemic or enzootic transmission cycles, environmental and climate changes, protein-energy malnutrition, weakness of the immune system and lack of resources.

There are three main forms, namely visceral leishmaniasis also known as kala-azar, which is the serious form because it is fatal if not treated timely, cutaneous leishmaniasis which is the most common form causing skin ulcers and mucocutaneous which affects the mouth, nose and throat.

Visceral leishmaniasis is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anaemia. Most cases occur in Brazil, Eastern Africa and India. It is estimated that 50 000–90 000 new cases of visceral leishmaniasis occur worldwide annually.

Early detection and appropriate treatment are key strategies for control of visceral leishmaniasis. Signs and symptoms of the infection are nonspecific; diagnosis is therefore confirmed by combining clinical signs with Leishmania-specific laboratory tests. Diagnostic policy for health services in endemic areas depends on the level of the health system. Two serological tests – the direct agglutination test and the rK39 antigen-based immunochromatographic tests – are developed for field use in most endemic areas (3). A rapid diagnostic test (RDT) detects antibodies and is a simple test that can be used at both peripheral and central levels. A scientific review of published studies estimates that the sensitivity of RDTs varies with the eco-epidemiological regions specially its low sensitivity in East Africa (4,5). Given the persistence of antibodies for long periods after cure, all serological tests have limitations because they cannot be used as a test of cure or to diagnose relapse. Also, a significant proportion of healthy people living in endemic areas with no history of visceral leishmaniasis test positive for antileishmanial antibodies as a result of asymptomatic infections. Therefore, antibody-based tests must therefore always be used in combination with a standardized clinical case definition for visceral leishmaniasis diagnosis.

Similarly, for monitoring treatment after cure, a non-invasive in vitro test of cure is needed, which should have good sensitivity and specificity and is reproducible and feasible to use.