Asymptomatic Leishmania infection: a new challenge for Leishmania control

Abstract

Visceral leishmaniasis (VL) is a serious parasitic disease, causing high morbidity and mortality in the developing world. The pathogenesis of VL is complex, and the clinical presentation ranges from asymptomatic infection to severe and fatal disease. Despite a wealth of research on the full-blown "clinical VL" syndrome, asymptomatic leishmania infections remain poorly understood. Asymptomatic infection could present a major challenge for control programs if its infectiousness is confirmed. In this viewpoint, we highlight the crucial knowledge gaps as well as the obstacles in research on asymptomatic leishmanial infection. Research in this area is essential for the development of more-effective VL control strategies.

Keywords: asymptomatic infection; immunity; visceral leishmaniasis.

Figure 1.

Generalized scheme of immune status and interplay of factors that affect risk of visceral leishmaniasis (VL) and asymptomatic Leishmania donovani infection. Infection with the Leishmania parasite causing visceral disease leads to different pathological conditions. A considerable percentage of the infected population undergoes asymptomatic or subclinical infection and remains immune to symptomatic disease, whereas some infected individuals develop symptomatic VL. There is a balance between effector responses, which control the parasites, and regulatory cytokines, which limit collateral tissue damage. As a result of combinations of genetic and environmental factors, L. donovani infection ensues when innate or acquired immune responses are inadequate to clear or control the infection. Infection risk is increased by exposure to infected sand flies, by proximity to the infectious reservoir host (eg, untreated post–kala-azar dermal leishmaniasis and kala-azar patients) and host factors such as nutrition that affect the immune response, but may be decreased by behaviors such as bed-net use that interrupt human–sand fly contact. Cattle may affect risk in complex ways, through their effect on sand fly abundance, breeding, infection rates, and feeding frequency on humans. Abbreviations: +ve, positive; CMI, cell-mediated immunity; DAT, direct agglutination test; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus; IFN-γ, interferon gamma; IGRA, interferon-γ release assay; IL, interleukin; LST, leishmanin skin test; PKDL, post–kala-azar dermal leishmaniasis; qPCR, quantitative polymerase chain reaction; SLA, soluble leishmania antigen; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor alpha; VL, visceral leishmaniasis.