The cytokine profile produced by peripheral blood mononuclear cells (PBMC) in response to leishmania antigens and the ability of interleukin-10 (IL-10) and transforming growth factor ␤ (TGF-␤) to modulate the immune response were evaluated in 21 mucosal leishmaniasis patients. Patients with mucosal disease exhibited increased gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) secretion and decreased IL-10 secretion compared to patients with classical cutaneous leishmaniasis. CD4 ؉ Th1 cells were the main source of IFN-␥ and TNF-␣ production in mucosal leishmaniasis patients. Evaluation of cytokine gene expression in PBMC of these patients showed that there was strong up-regulation of IFN-␥ transcripts upon stimulation with leishmania antigen, in contrast to the baseline levels of IL-10 mRNA. IL-10 suppressed IFN-␥ production by 48% in cell cultures from cutaneous leishmaniasis patients and by 86% in cell cultures from healthy subjects stimulated with purified protein derivative, whereas in similar conditions IL-10 suppressed IFN-␥ production by 19% in cell cultures from mucosal leishmaniasis patients stimulated with leishmania antigen. TGF-␤ suppressed IFN-␥ levels to a greater extent in healthy subjects than in mucosal leishmaniasis and cutaneous leishmaniasis patients. These data indicate that a poorly modulated T-cell response in mucosal leishmaniasis patients leads to production of high levels of proinflammatory cytokines, such as IFN-␥ and TNF-␣, as well as a decreased ability of IL-10 and TGF-␤ to modulate this response. These abnormalities may be the basis for the pathological findings observed in this disease.

It is important to realize that leishmaniasis guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The IDSA and ASTMH consider adherence to these guidelines to be voluntary, with the ultimate determinations regarding their application to be made by the physician in the light of each patient's individual circumstances.

During an epidemiological study of visceral leishmaniasis in an endemic region of Brazil, new perspectives emerged on a subclinical form of the disease. A group of 86 children with antibody to Leishmania were identified. None of these children had a history of leishmaniasis. The children were segregated into four groups: One group remained asymptomatic (n = 20), whereas another developed classic kala-azar within weeks of the index serology (n = 15). The remaining 51 patients initially had subclinical disease; 13 (25%) of these patients progressed to classic kala-azar (mean, five months). The others (75%) resolved their illness after a prolonged period (mean, 35 months). The initial illness in the subclinical group was characterized by hepatomegaly, frequent splenomegaly, intermittent cough, diarrhea, and low-grade fever. Malaise and poor weight gain were common. Giemsa-stained smears and cultures of bone marrow aspirates were usually negative for Leishmania in the absence of symptoms of classic kala-azar.