DISSEMINATED VISCERAL LEISHMANIASIS ( KALA AZAR )
Kala azar, which is caused by L. donovani, occurs in the tropical and subtropical areas of every continent except Australia. Its epidemiologic and clinical patterns vary from area to area. In Africa, rodents serve as the primary reservoir. Human cases occur sporadically, and the disease is often acute and highly lethal. In Eurasia and Latin America, the domestic dog is the most common reservoir. Human disease is endemic, primarily involves children, and runs a subacute to chronic course. In India, the human is the only known reservoir, and ransmission is carried out by anthropophilic species of sandflies. The disease recurs in epidemic form at 20-year intervals, when a new cadre of nonimmune children and young adults appears in the community. There appears to be a high incidence of visceral leishmaniasis in patients with HIV infection. Presumably, HIV-induced immunosuppression either facilitates acquisition of the disease and/or allows reactivation of latent infection.
After the host is bitten by an infected sandfly, the parasites disseminate in the bloodstream
and are taken up by the macrophages of the spleen, liver, bone marrow, lymph nodes, skin, and small intestine. Histiocytic proliferation in these organs produces enlargement with atrophy or replacement of the normal tissue.
The majority of infections are asymptomatic; these become symptomatic years later during periods of host immunocompromise. Symptomatic disease most commonly manifests itself 3 to 12 months after acquisition of the parasite. It is often mild and self-limited. A minority of infected individuals develop the classic manifestations of kala azar. Fever, which is usually present, may be abrupt or gradual in onset. It persists for 2 to 8 weeks and then disappears, only to reappear at irregular intervals during the course of the disease. A double-quotidian pattern (two fever spikes in a single day) is a characteristic but uncom-mon finding. Diarrhea and malabsorption are frequent in Indian cases, resulting in progres-sive weight loss and weakness. Physical findings include enlarged lymph nodes and liver, massively enlarged spleen, and edema. In light-skinned individuals, a grayish pigmentation of the face and hands is commonly seen, which gives the disease its name (kala azar, black disease). Anemia with resulting pallor and tachycardia are typical in advanced cases. Thrombocytopenia induces petechial formation and mucosal bleeding. The peripheral leukocyte count is usually less than 4000/mm3; agranulocytosis with secondary bacterial infections contributes to lethality. Serum immunoglobulin G levels are enormously ele-vated but play no protective role. Circulating antigen – antibody complexes are present and are probably responsible for the glomerulonephritis seen so often in this disease.
The diagnosis is made by demonstrating the presence of the organism in aspirates taken from the bone marrow, liver, spleen, or lymph nodes. In the Indian form of kala azar, L. donovani is also found in circulating monocytes. The specimens may be smeared,stained, and examined for the typical Leishman – Donovan bodies (amastigotes in mononuclear phagocytes) or cultured in artificial media and/or experimental animals. As described for cutaneous leishmaniasis, a limited number of reference laboratories can provide a rapid, direct, species-specific diagnosis through the use of the PCR and probes to kinetoplast DNA. Results of the leishmanin skin test are negative during active disease but become positive after successful therapy.
The mortality in untreated cases of kala azar is 75 to 90%. Treatment with pentavalent antimonial drugs lower this rate dramatically. Initial therapy, however, fails in up to 30% of African cases, and 15% of those that do respond eventually relapse. Resistant cases are treated with the more toxic pentamidine, amphotericin B, or liposomal amphotericin B. Allopurinol and interferon- γ have proven to be useful adjunctive therapies in resistant cases. Control measures are directed at the Phlebotomus vector, with the use of residual insecticides, and at the elimination of mammalian reservoirs by treating human cases and destroying infective dogs.
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