Treatment of Visceral Leishmaniasis with Pentavalent Antimony and Interferon Gamma

Abstract

Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis.

Visceral leishmaniasis: clinical and laboratorial aspects

“…Badaró et al, em 1990, relataram a utilização de gamainterferon recombinante associado a antimoniato pentavalente em 17 pacientes com LV, com ou sem tratamento antimonial prévio, com falhas terapêuticas em 17% dos casos 27 .…”

Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2-like response to gp63 and Thl-like response to lipophosphoglycan- associated protein in cells from cured visceral leishmaniasis patients

“…First, in conditions with impaired T cell function the course of the disease is fulmitiant and refractory to medical treatment [26]. Second, patients with visceral leishmaniasis refractory to medieai treatment have been eured by pentavalent antimonial drugs in combination with IFN-7 [27], Third, in ehildren with serological signs of L. chagasi infection, IFN'7 production by Lci.shmania-?,i\m\.ilated PBMC was associated with subclinical infection, whereas weak IFN-7 response was a marker of disease progression [28], These findings contrasi the prominent DTH response and proliferative response of PBMC to Leishmania antigens in uncomplicated cutaneous leishtnaniasis [29.30].…”

Cytokines and their Role in Health and Disease: A Brief Overview

“…IFN-γ also has an immunomodulatory effect in other specific immunodeficiency syndromes. It is an effective adjunctive therapeutic agent in combination with other conventional antimicrobial agents in cutaneous and visceral leishmaniasis, disseminated atypical mycobacterial infection, or lepromatous leprosy patients [39][40][41]. It also activates alveolar macrophages and plays an effective role in host immunity against M. tuberculosis.…”