allopurinol and Leishmaniasis--Diffuse-Cutaneous

A new treatment regimen was tested on patients with incurable diffuse cutaneous leshmaniasis (DCL) infected with Leishmania mexicana mexicana in Mexico. Two patients with advanced stages of the disease were treated with polychemotherapy (pentamidine and allopurinol) combined with recombinant human interferon-gamma (rIFN-gamma). For determination of the best medication, parasites isolated from patient lesions were exposed to available drugs both as promastigotes and as intracellular amastigotes. A synergistic effect was observed in vitro for the combination of pentamidine and allopurinol. Both patients were treated and recovered rapidly, but one of them developed insulin-dependent type I diabetes because of pentamidine toxicity. The complication was controlled and both patients were discharged with an apparent parasitologic cure, but after 3 months the two patients began to relapse. Our results suggest that allopurinol-pentamidine polychemotherapy, involving reduced dosage of pentamidine, combined with rIFN-gamma is an alternative for DCL patients infected with L. m. mexicana.

Topics: Adult; Allopurinol; Animals; Antiprotozoal Agents; Combined Modality Therapy; Diabetes Mellitus, Type 1; Drug Synergism; Humans; Interferon-gamma; Leishmania mexicana; Leishmaniasis, Diffuse Cutaneous; Mexico; Pentamidine; Recombinant Proteins

Two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexicana were treated with two leishmanicidal drugs (pentamidine and allopurinol) combined with recombinant interferon-gamma restoring Th-1 favouring conditions in the patients. Parasites decreased dramatically in the lesions and macrophages diminished concomitantly, while IL-12-producing Langerhans cells and interferon-gamma- producing NK and CD8 + lymphocytes increased in a reciprocal manner. The CD4+/CD8 + ratio in the peripheral blood normalized. During exogenous administration of interferon-gamma the parasites' capacity to inhibit the oxidative burst of the patients' monocytes was abolished. Even though Th-1-favouring conditions were restored, both patients relapsed two months after therapy was discontinued. We conclude that the tendency to develop a disease-promoting Th-2 response in DCL patients is unaffected by, and independent of, parasite numbers. Even though intensive treatment in DCL patients induced Th-1 disease restricting conditions, the disease-promoting immunomodulation of few persistent Leishmania sufficed to revert the immune response.

Topics: Allopurinol; Animals; Antimetabolites; Antiprotozoal Agents; CD4-CD8 Ratio; Drug Therapy, Combination; Humans; Interferon-gamma; Killer Cells, Natural; Langerhans Cells; Leishmania mexicana; Leishmaniasis, Diffuse Cutaneous; Pentamidine; Recombinant Proteins; Respiratory Burst; Treatment Outcome