Leishmaniasis Overview and Lifecycle

Leishmaniasis: Overview

• Leishmania is a parasite belonging to the Phylum Kinetoplastida
• Four morphological forms:
  • Amastigote: Ovoid, develops in vertebrate hosts, single nucleus, short flagellum
  • Promastigote: Elongate, found in insect vectors, longer flagellum than amastigote
  • Epimastigote: Kinetoplast posterior to nucleus, undulating membrane present
  • Trypomastigote: Various forms, longer body, undulating membrane, kinetoplast anterior to nucleus
• Endemic in tropical and subtropical regions, with two main vector genera:
  • Phlebotomus: Eastern hemisphere (Africa, Asia, Europe)
  • Lutzomyia: Western hemisphere (South and Central America)
• Sandflies feed on blood and lymph, transmitting the parasite
• Leishmania species are difficult to distinguish morphologically
• Parasite life cycle includes asexual multiplication in the fly gut, and recent evidence suggests sexual reproduction as well

Leishmania Life Cycle

• Initial infection comes from the sandfly's regurgitation of promastigotes into the host wound
• Leishmania does not invade host cells but relies on host cell phagocytosis, specifically targeting phagolysosomes
• The parasite suppresses reactive oxygen species (ROS) production in macrophages
• Distinct forms of leishmaniasis exist based on the clinical manifestation:

Types of Leishmaniasis

• Cutaneous Leishmaniasis (CL):
  • New World (e.g., L. mexicana, L. braziliensis) and Old World (e.g., L. tropica, L. major, West Central Africa, Middle East, India, Asia) strains, with varying transmission routes
  • Often self-healing, producing dry skin lesions (papules, nodules, ulcers) on exposed body parts.
  • Pentavalent antimony is a treatment for diffuse cutaneous leishmaniasis (DCL)
  • Leishmania recidivans (recurrent form) involves parasite elimination but not complete cure
• Mucocutaneous Leishmaniasis (MCL):
  • Primarily caused by L. braziliensis and L. tropica
  • Can develop from CL, causing progressive damage to mucous membranes (nose, mouth, lips, palate, throat)
  • Two forms: ulcerative (rapid mutilation) and non-ulcerative (edema and hypertrophy)
  • Treated with amphotericin B or antimony drugs
• Visceral Leishmaniasis (VL; Kala-azar):
  • Most severe form, often asymptomatic, high fatality rate without treatment, targeting reticuloendothelial system (systemic)
  • Characterized by fever, weight loss, hepatosplenomegaly (enlarged liver and spleen), anemia, and enlarged lymph nodes.
  • Severe cases involve protruding abdomen and muscle wasting.
  • Post kala-azar dermal leishmaniasis (PKDL) is a possible complication, with varying prevalence in different regions (50% in Sudan, 5-10% in India). PKDL is usually self-healing in Africa, but not in India
  • High IL-10 levels during VL are predictive of PKDL development.
• Lipophosphoglycan (LPG):
  • Protects the parasite from digestive enzymes in the sandfly gut.
  • Important for evading the host immune response, including macrophages and NKT cells.

Host Immune Response & Diagnosis

• Strong Th1 response: Associated with resistance to infection, localizing the infection and facilitating healing; influenced by INF-gamma and cytotoxin T cells
• Strong Th2 response: Associated with susceptibility to developing DCL or VL
• Diagnosis:
  • CL: Lesion sampling, biopsy, or in-vivo culture
  • VL: Bone marrow, lymph nodes, or spleen aspirate
  • Serological tests: Detect antibodies to the parasite using serum samples (DAT, ELISA)
• Leishmanin skin test (LST): A delayed-type hypersensitivity (DTH) test based on detecting a T-cell mediated immune response. Cannot distinguish between past/current infections though.

Explore the fascinating world of Leishmaniasis, an infection caused by the Leishmania parasite. This quiz covers the different morphological forms of Leishmania, its life cycle, and the vectors responsible for its transmission across tropical and subtropical regions. Test your knowledge on this disease and enhance your understanding of parasitology.