Leishmania donovani: Life Cycle, Pathogenesis, Treatment Prevention and Diagnosis

  Leishmania donovani: The Causative Agent of Kalaazar (Visceral Leishmaniasis)

Lifecycle

Leishmania donovani's life cycle, relies on sandflies as vectors and various mammals, including dogs, foxes, and rodents, as reservoirs. Female sandflies, requiring blood meals for egg maturation, ingest macrophages containing amastigotes when feeding on an infected host Inside the sandfly, the amastigotes transform into promastigotes in the gut, multiply, and migrate to the pharynx and proboscis, ready to be transmitted during the next bite. This sandfly phase takes about 10 days.

Upon biting a human, the sandfly injects promastigotes, which are engulfed by macrophages and transform back into amastigotes (Figure 1). Amastigotes evade destruction by preventing the fusion of the vacuole with lysosomes, leading to the infection of other macrophages and reticuloendothelial cells. The cycle completes when another sandfly ingests macrophages containing amastigotes.

 

                                                              Figure 1 Life Cycle of Leishmaniasis

Pathogenesis & Epidemiology

In visceral leishmaniasis, the reticuloendothelial organs—liver, spleen, and bone marrow—are primarily affected. Bone marrow suppression, along with spleen cellular destruction, results in anemia, leukopenia, and thrombocytopenia, causing secondary infections and bleeding tendencies. Spleen enlargement is due to proliferating macrophages and sequestered blood cells, and increased IgG levels, though not specific or protective.

Kalaazar presents in three epidemiological patterns:

1. In the Mediterranean basin, Middle East, southern Russia, and parts of China, dogs and foxes are primary reservoirs.

2. In sub-Saharan Africa, rats and small carnivores (e.g., civets) serve as main reservoirs.

3. In India, neighboring countries, and Kenya, humans are the sole reservoir.

Clinical Findings

Symptoms begin with intermittent fever, weakness, and weight loss, progressing to massive spleen enlargement. Light skinned patients may exhibit hyperpigmentation (Kalaazar means black sickness). The disease can last months to years, with patients initially feeling relatively well despite persistent fever. As anemia, leukopenia, and thrombocytopenia worsen, weakness, infections, and gastrointestinal bleeding occur. Without treatment, severe disease is almost always fatal due to secondary infections.

Laboratory Diagnosis

Diagnosis is typically made by detecting amastigotes in bone marrow, spleen, or lymph node biopsies or "touch" preparations (see Figure 5215). Culturing the organisms and serologic tests (indirect immunofluorescence) are usually positive. High IgG levels indicate infection, although not diagnostic. A skin test using a crude promastigote homogenate (leishmanin) as the antigen is available, with negative results during active disease but positive in recovered patients.

Treatment & Prevention

Liposomal amphotericin B or sodium stibogluconate are the drugs of choice. Proper treatment reduces the mortality rate to nearly 5%, and recovery confers permanent immunity. Prevention focuses on avoiding sandfly bites through the use of netting, protective clothing, insect repellents, and insecticide spraying.