Determinants for the Development of Visceral Leishmaniasis Disease

Abstract

Leishmaniasis is a vector-borne neglected tropical disease associated with a spectrum of clinical manifestations, ranging from self-healing cutaneous lesions to fatal visceral infections. Among the most important questions in Leishmania research is why some species like L. donovani infect visceral organs, whereas other species like L. major remain in the skin. The determinants of visceral leishmaniasis are still poorly understood, although genomic, immunologic, and animal models are beginning to provide important insight into this disease. In this review, we discuss the vector, host, and pathogen factors that mediate the development of visceral leishmaniasis. We examine the progression of the parasite from the initial site of sand fly bite to the visceral organs and its ability to survive there. The identification of visceral disease determinants is required to understand disease evolution, to understand visceral organ survival mechanisms, and potentially to develop better interventions for this largely neglected disease.

Cross-species genetic exchange between visceral and cutaneous strains of Leishmania in the sand fly vector

“…Although there is strong evidence that A2 genes influence the ability of Leishmania to disseminate to and/or grow in the viscera (23), there were no apparent differences between the hybrids in A2 gene inheritance or inducible expression in vitro (Fig. S1).…”

“…We included in our nuclear DNA genotyping an analysis of the A2 loci because the expression of these amastigote-specific genes is associated with the capacity of L. donovani and L. infantum to visceralize (23). In these species, multiple copies of the A2 genes are arranged in tandem on Chr 22, whereas in L. major, the corresponding sequences have been found functionally expressed as a single copy gene (24).…”

Diagnosis of leishmaniasis

“…When selective antigenic molecules were used (with molecular weights of 116 kDa, 72 kDa, and 66 kDa), the specificity approached 100%, while the sensitivity was very low (37%) [31,52]. Other purified antigens used were a 36-kDa glycoprotein [53], metabolic antigens released by L. donovani [54], and A2 proteins implicated in the development of visceral disease [55][56][57].…”

Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent

“…There are few well-conducted studies to describe the natural history of visceral leishmaniasis, which is multifactorial 18 , and hence the risks for an infected individual to become diseased are not quantified. Owing to the localized epidemics that are seen surrounding index cases it is reasonable to assume that patients with kala-azar are the main reservoir of infection for sand flies.…”