Cure rates for American cutaneous leishmaniasis (ACL) range between 60% and 90%. Early evidence suggests lower cure rates for early ACL before the development of the ulceration. We evaluated risk factors for treatment failure in patients with early and classic ulcerative ACL. Patients (n = 136) were 13–60 years of age and had lesions with a duration of 15–90-days. Patients were treated with antimony (20 mg/kg/day for 20 days). The primary outcome was lesion cure by 90 days without recurrence. Patients with early ACL (n = 16) had papules, nodules, plaques, or superficial ulcerations with less than 30 days of illness. Patients with classic ulcerative ACL (n = 120) had ulcerated classic lesions, longer duration, larger lesions, and higher levels of interferon-γ and tumor necrosis factor-α (P ≤ 0.01 for all comparisons). Ulcerated lesions were associated with a lower treatment failure rate compared with early ACL (25.8% versus 75.0%; P < 0.001). Early treatment of ACL does not prevent lesion ulceration and is associated with higher rates of treatment failure.

O conhecimento dos principais mecanismos de defesa imune contra os diversos agentes infecciosos permite a compreensão da patogênese das doenças infectoparasitárias e das várias estratégias do hospedeiro e do parasita. O sistema imunológico atua numa rede de cooperação, envolvendo a participação de muitos componentes estruturais, moleculares e celulares. Nesse cenário encontra-se o delicado equilíbrio entre a saúde e a doença, em que tanto a deficiência quanto o exagero resultam em dano tecidual. Este artigo explora esses aspectos e algumas abordagens terapêuticas que surgem desse entendimento.

Disseminated leishmaniasis is a severe and emerging form of American tegumentary leishmaniasis. Disseminated leishmaniasis is defined by the presence of more than 10 polymorphic cutaneous lesions, distributed over more than two noncontiguous parts of the body. Nasal mucosal involvement is observed in almost half of cases. Disseminated leishmaniasis patients present with a decreased production of Th1 cytokines in the peripheral blood due to the attraction of leishmania- activated T cells to the multiple cutaneous lesions. Disseminated leishmaniasis development is poorly understood and is related to a complex network involving environmental, host immune response, and parasite factors, in which L. braziliensis polymorphism plays an important role. Disseminated leishmaniasis is a challenging disease to cure, presenting a high failure rate of 75% to pentavalent antimony therapy. Despite its importance and severity, this form of American tegumentary leishmaniasis has been poorly studied and documented, deserving greater attention from professionals working in endemic areas.

Mucosal leishmaniasis (ML) is observed only in about 3% of patients with American tegumentary leishmaniasis (ATL) but has a high potential for destructive, disfiguring, and disabling sequelae. Prior reports of clinical and epidemiologic features of ML are limited by small numbers of cases. In this study, we evaluated changes in the demographic features and clinical presentation of ML in an endemic area of Leishmania braziliensis transmission over a period of 20 years. The charts of 327 patients with ML diagnosed between 1995 and 2014 were reviewed. The majority of patients (67%) were male. Age ranged from 8 months to 103 years, with a median age of 38.5 years (interquartile range: 22–58 years). The greatest number of patients was between 19 and 39 years (31%). Over the study period, there was an increase in patients with ML more than 60 years of age, an increase in ML with concomitant cutaneous lesions, a decrease in the period of time between the documentation of cutaneous lesions and the diagnosis of mucosal disease, and an increase in the frequency of patients presenting with stage I and V of ML. Moreover, there was a positive correlation between severity of mucosal disease and both age and the period of time between cutaneous lesion and mucosal disease. Response to therapy of ML remained similar over a period of 20 years. Despite the improvement in medical care during the study period, the prevalence of ML did not change and severe disease continues to be a major challenge for the management of these patients.

Background. Disseminated leishmaniasis (DL) is a severe and emerging form of American tegumentary leishmaniasis, associated primarily with infection by Leishmania brasiliensis. DL is defined by the presence of ≥10 mixed-type lesions such as inflammatory papules and ulcers, located in ≥2 body parts. Most patients have hundreds of lesions all over the body, and mucosal involvement is detected in up to 44% of cases. DL is a difficult to cure disease and pentavalent antimony (Sb^v) is used as standard treatment, its highest dosage being 20 mg/kg/day, for 30 days. However, less than 25% of DL cases will be cured after standard therapy, and the majority of cases will require more than one course of Sb^v for a cure. In this context, new therapies are needed that offer a higher cure rate and a better safety profile, with convenience in drug administration. Methods. We have evaluated liposomal amphotericin B in 20 patients with DL in an open clinical trial. The total dose ranged from 17 to 37 mg/kg, used in 7 to 14 days of treatment. Results. Cure rate at 3 months after therapy was 70%. One relapse was documented 4 months after treatment, producing a final cure rate of 65%. Although liposomal amphotericin B was considered well tolerated, mild adverse events were documented in 75% of the patients. Conclusions. Liposomal amphotericin B is an effective therapy for DL, with a higher final cure rate of 75% observed when used in a total dose above 30 mg/kg. Clinical Trials Registration. NCT02025491.