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Pathogen Page

Leishmania major

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Cutaneous leishmaniasis

3. Introduction

Leishmania parasites belonging to the order Kinetoplastida are the causative agents of a large spectrum of diseases, leishmaniasis, varying from localized cutaneous to visceral leishmaniasis, the later being often fatal if not treated. Leishmaniasis with a total number of 12 million cases, and 350 million at risk is a major health problem in several tropical and subtropical areas, and its control relies still most frequently on pentavalent antimony-containing drug chemotherapy. The effectiveness of these compounds however is eroded by the emergences of parasite resistance to the drug. Therefore, other strategies, such as vaccination, need to be developed for a better control of leishmaniasis. Mouse models of cutaneous leishmaniasis have been extensively used to explore the requirements for effective vaccination, namely vaccination which prevent at least the disease stage to be reached (Rafati et al., 2002).

4. Microbial Pathogenesis

The establishment of the primary leishmania infection and development of clinical disease depend on parasite, host, and sandfly factors; dose or route of inoculation; and the maintenance of macrophages in an inert, deactivated state. Pathogenesis follows a complex set of interactions between many factors triggered by the host's innate and acquired immune responses (eg, macrophages, neutrophils, natural killer cells, dendritic cells). These inflammatory responses mediate disease expression and may result in either symptomless or subclinical infection, self-healing LCL, or chronic leishmaniasis (eg, DCL, mucosal leishmaniasis, leishmaniasis recidivans). Clinical cure ensues when macrophages become activated to a leishmanicidal state.
When biting their hosts, infected sandflies regurgitate leishmania promastigotes into the skin, which invade or are phagocytosed by local or recruited host cells, mainly macrophages. Within the phagolysosomes of resident macrophages, promastigotes become amastigotes. Amastigotes replicate and may then infect additional macrophages, either locally or in distant tissues after dissemination. When blood-feeding on an infected host, naive sandflies become infected with amastigotes, which transform back into promastigotes in the sandfly's gut (depending on Leishmania spp, different regions of the gut will be parasitised. The parasites then migrate to the sandfly's proboscis, thus completing the leishmania life cycle (Reithinger et al., 2007).

5. Host Ranges and Animal Models

Leishmania major is vectored by the sandfly and can infect humans and other mammals. Natural leishmania infections are found in a range of non-human mammal hosts (mainly marsupials, rodents, edentates, and carnivores) (Reithinger et al., 2007).

6. Host Protective Immunity

The immune response to Leishmania infection is cell-mediated, and the clinical outcome is dependent on host-mediated T helper (Th)1 or Th2 responses. A Th1 response mediated by interferon (IFN)-γ, tumour necrosis factor and interleukin (IL)-12 is associated with disease resolution and resistance, and a Th2 IL-4-producing response confers disease susceptibility and progression (Ameen, 2010).

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