Vicente Amato Neto

Treatment of New World cutaneous leishmaniasis: a systematic review with a meta-analysis

Background  New World leishmaniasis is an important endemic disease and public health problem in developing countries. The increase in ecologic tourism has extended this problem to developed countries. Few drugs have emerged over the past 50 years, and drug resistance has increased, such that the cure rate is no better than 80% in large studies. Despite these data, there has been no systematic review with a meta‐analysis of the therapy used in this important tropical disease. The aim of this study was to determine the best drug management in the treatment of cutaneous leishmaniasis (CL) in Latin America based on the best studies published in the medical literature.

Trypanosoma cruzi parasitemia in chronic Chagas disease : Comparison between human immunodeficiency virus (HIV)-positive and HIV-negative patients

This study evaluated Trypanosoma cruzi parasitemia in persons with chronic Chagas disease, compared the parasitemia in human immunodeficiency virus (HIV)-positive and -negative subjects, and, for HIV-positive subjects, analyzed the association between parasitemia and occurrence of acquired immunodeficiency syndrome-defining illnesses, CD4 cell counts, HIV loads, and antiretroviral therapy. In total, 110 adults with chronic Chagas disease (29 HIV positive, 81 HIV negative) were studied. T. cruzi parasitemia was evaluated by xenodiagnosis, blood culture, and direct microscopic examination of blood. T. cruzi parasitemia was detected significantly more frequently in HIV-positive than in HIV-negative subjects (odds ratio, 12.3; 95% confidence interval, 3.7-41.2). HIV-positive patients also had higher levels of parasitemia. No statistically significant association was seen between parasitemia and the variables of interest among the HIV-positive subjects.

Toll-like receptors and leishmaniasis

More than 10 million people around the world are currently affected by Leishmania sp. (33). Infection with this protozoan parasite continues to be a problem in underdeveloped countries and is a continuous worry in developed countries due to the possibility of the disease afflicting tourists returning from countries where the organism is endemic (82). Leishmaniasis is a neglected infectious disease, and it affects poor and marginalized populations. It is distributed, in its visceral, mucosal, and cutaneous forms, throughout more than 90 countries in Africa, the Americas, Asia, and Europe (5). It constitutes a serious public health problem and causes significant morbidity and mortality. In recent years, economic globalization and the increase in travel have extended the distribution of the disease to developed countries. Approximately 350 million people live in areas where there is active parasite transmission of zoonotic and anthroponotic leishmaniasis. Zoonotic transmission occurs in rural and periurban environments, whereas anthroponotic transmission occurs in urban environments (7). From a strictly biological point of view, de Almeida et al. described humans as just one of the actors in the leishmaniasis drama (23). Also involved are the parasite, the insect, and other hosts. Several immunological studies have increased our understanding of the adaptive response in leishmaniasis. Thus, this disease has been used as a model of Th1 and Th2 responses. Unfortunately, there are still several aspects of the initial steps of Leishmania infection in humans that are largely unknown.

Cutaneous leishmaniasis reactivation 2 years after treatment caused by systemic corticosteroids - first report.

American tegumentary leishmaniasis (ATL), an endemic anthropozoonosis in various countries in the world, is caused by parasites of the genus Leishmania. Despite reports on ATL reactivation as a result of immunosuppression, to the best of our knowledge, this paper describes the first case of ATL reactivation in its localized form (cutaneous leishmaniasis) associated with the administration of systemic corticosteroids. The possible action of corticosteroids on the host immune response to the parasite in patients with localized cutaneous leishmaniasis is discussed. This report demonstrates the possibility of ATL reactivation in patients using corticosteroids, an observation that should be considered in individuals treated with this medication.

Use of itraconazole in the treatment of mucocutaneous Leishmaniasis: A pilot study.

OBJECTIVE Mucocutaneous leishmaniasis is widely distributed in Brazil, with Leishmania (Viannia) braziliensis being the major etiologic agent. The currently recommended therapy is limited by its parenteral use, high toxicity, and variable efficacy. A clinical pilot study was conducted to analyze itraconazole as an oral alternative for the treatment of mucocutaneous leishmaniasis. METHODS Ten patients were enrolled to receive 4 mg/kg per day (up to 400 mg/d) itraconazole for 6 weeks on an outpatient regimen. Diagnosis was based on clinical otorhinolaryngologic examination, followed by a specific serologic reaction, the Montenegro test and pathologic analysis with immunohistochemical reaction. Healing of the lesions was confirmed by clinical otorhinolaryngologic examination. Side effects were monitored by general clinical assessment, hemoglobin determination, leukocyte counts, and liver function tests, all performed before, during, and 1 month after the end of treatment. RESULTS Six of 10 patients presented healed lesions 3 months after treatment, with a sustained therapeutic response for at least a median period of 14.5 months (range, 12-18 mo). Side effects were not observed. CONCLUSIONS This pilot study demonstrated that itraconazole can be an effective and well-tolerated alternative for the treatment of mucocutaneous leishmaniasis. Further randomized studies and double blind controlled trials are needed to assess the benefits of this drug in the treatment of mucocutaneous leishmaniasis.

Busca retrospectiva da transmissão maternal da infecção chagásica em pacientes na fase crônica

Maternal transmission of Trypanosoma cruzi from 278 children of 145 mothers, chronically infected with this protozoan, to their offspring was investigated. This study was based upon serological tests. In only two cases (2/278 = 0.70%), such mode of transmission was demonstrated to have occurred. However, as according to extant records both patients had also been breast-fed, and the contribution of this factor could not be ruled out. In any case, maternal transmission, an alternative mode of acquiring the infection with Trypanosoma cruzi, was demonstrated. The methodology used is a further contribution to the evaluation of the prevalence of this propagating mechanism of T. cruzi; in addition to those aimed at the main objective of the investigation, records were kept about pregnancy, parturition, puerperium, abortion, prematurity, perinatal deaths and breast-feeding, which might contribute to a better interpretation of the subject.

Análise da freqüência de recaídas de malária por Plasmodium vivax em região não endêmica (São Paulo, Brasil)

Very few well-established information is available about the frequency and timeliness of relapses in cases of Plasmodium vivax malaria acquired in Brazil. So, we analysed a series of correctly treated patients observed out of endemic areas. The rate of relapses seen in Sao Paulo, which may represent that of the parasitosis in the whole country, was high, ranging from 7.5% to 24.5%, and early in most cases, i.e. appearing by three months, what anticipates a high endemicity.

Mecanismos alternativos de transmissão do Trypanosoma cruzi no Brasil e sugestões para sua prevenção

INTRODUCTION: Following advances in the control of vector and blood transfusion transmission of Chagas disease, alternative mechanisms of transmission have become more relevant. This article discusses the importance of each one of these alternative mechanisms and the measures to prevent them. METHODS: A review was conducted of the scientific literature concerning alternative transmission mechanisms of Trypanosoma cruzi occurring in Brazil and the measures to prevent them. PubMed and BVS databases were consulted. RESULTS: Twenty-five publications describing alternative mechanisms of transmission of Chagas disease were identified. CONCLUSIONS: Oral transmission, through ingestion of contaminated food items has been the most frequent mode of transmission in Brazil in recent years. Other alternative mechanisms of transmission occur less frequently. It is important to understand these occurrences, especially now that vector transmission of the parasite is under control. Preventive measures have been presented, according to each of the situations considered, in line with current knowledge.

Leishmania: origin, evolution and future since the Precambrian

This brief review discusses the history of leishmaniasis, considering its origin from the Paleoartic, Neoartic or Neotropic. We reassess some of the theories of the likely origin of this protozoan since the beginning of life on Earth, passing through the Mesozoic and continuing to the appearance of humans. The relationship between this parasite or its ancestors, possible vectors and hosts with regard to ecological modifications is discussed. Recent molecular techniques have helped to elucidate some of the evolutionary questions regarding Leishmania, but have also brought doubts about the origin and evolution of this human parasite. PCR has been used for studies in the new discipline of paleoparasitology, helping to elucidate some of the remaining evolutionary questions. Understanding of this global condition is fundamental in determining the best approach to use against the parasite, specifically for the development of an efficient vaccine.

Local immunological factors associated with recurrence of mucosal leishmaniasis

Recurrence of mucosal leishmaniasis (ML) is frequent, but the causative mechanisms are unknown. Our aim was to compare cellular and cytokine patterns of lesions from ML that evolved to recurrence or cure in order to determine the risk factor associated with recurrence. Lesions were evaluated by immunohistochemistry before and after therapy, and patients were followed-up for five years. Higher levels of CD4(+) T and IFN-gamma-producing cells were detected in active lesions and decreased after therapy. Macrophages and IL-10 were markedly increased in cured patients. Conversely, CD8(+) T and NK cells were higher in relapsed than in cured cases. Notably, a decrease in these cells in addition to decreased IL-10 and IFN-gamma was also observed after therapy. These data suggest that exacerbated CD8(+) activity, in addition to a poor regulatory response, could underlie an unfavorable fate with regard to ML. These markers may be useful for predicting the prognosis of ML in lesion studies.