The cure rate after different treatments for mucosal leishmaniasis in the Americas: A systematic review.

BACKGROUND: Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and digestive tracts. The current treatment recommendations are based on low or very low-quality evidence, and pentavalent antimonial derivatives remain strongly recommended. The aim of this review was to update the evidence and estimate the cure rate and safety profile of the therapeutic options available for mucosal leishmaniasis (ML) in the Americas. METHODOLOGY: A systematic review was conducted in four different databases and by different reviewers, independently, to evaluate the therapeutic efficacy and toxicity associated with different treatments for ML. All original studies reporting cure rates in more than 10 patients from American regions were included, without restriction of design, language, or publication date. The risk of bias was assessed by two reviewers, using different tools according to the study design. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. The protocol for this review was registered at the International Prospective Register of Systematic Reviews, PROSPERO: CRD42019130708. PRINCIPAL FINDINGS: Twenty-seven original studies from four databases fulfilled the selection criteria. A total of 1,666 patients with ML were treated predominantly with pentavalent antimonials in Brazil. Other interventions, such as pentamidine, miltefosine, imidazoles, aminosidine sulfate, deoxycholate and lipidic formulations of amphotericin B (liposomal, lipid complex, colloidal dispersion), in addition to combinations with pentoxifylline, allopurinol or sulfa were also considered. In general, at least one domain with a high risk of bias was identified in the included studies, suggesting low methodological quality. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. It was confirmed that antimony is still the most used treatment for ML, with only moderate efficacy (possibly increased by combining with pentoxifylline). There is already evidence for the use of miltefosine for ML, with a cure rate similar to antimony, as observed in the only direct meta-analysis including 57 patients (OR: 1.2; 0.43-3.49, I2 = 0). It was possible to gather all descriptions available about adverse events reported during ML treatment, and the toxicity reflected the pattern informed in the manufacturers' technical information. CONCLUSIONS: This study provides an overview of the clinical experience in the Americas related to ML treatment and points out interventions and possible combinations that are eligible to be explored in future well-designed studies.

Monitoring the Establishment of VOC Gamma in Minas Gerais, Brazil: A Retrospective Epidemiological and Genomic Surveillance Study.

Since its first identification in Brazil, the variant of concern (VOC) Gamma has been associated with increased infection and transmission rates, hospitalizations, and deaths. Minas Gerais (MG), the second-largest populated Brazilian state with more than 20 million inhabitants, observed a peak of cases and deaths in March-April 2021. We conducted a surveillance study in 1240 COVID-19-positive samples from 305 municipalities distributed across MG's 28 Regional Health Units (RHU) between 1 March to 27 April 2021. The most common variant was the VOC Gamma (71.2%), followed by the variant of interest (VOI) zeta (12.4%) and VOC alpha (9.6%). Although the predominance of Gamma was found in most of the RHUs, clusters of Zeta and Alpha variants were observed. One Alpha-clustered RHU has a history of high human mobility from countries with Alpha predominance. Other less frequent lineages, such as P.4, P.5, and P.7, were also identified. With our genomic characterization approach, we estimated the introduction of Gamma on 7 January 2021, at RHU Belo Horizonte. Differences in mortality between the Zeta, Gamma and Alpha variants were not observed. We reinforce the importance of vaccination programs to prevent severe cases and deaths during transmission peaks.

Análise temporal, espacial e fatores associados à mortalidade por leishmaniose tegumentar no Brasil

A leishmaniose tegumentar (LT) está associada a uma morbidade significativa, mas, em geral, letalidade relacionada à doença não é esperada. No entanto, nos últimos anos número inesperado de óbitos relacionados à doença foram notificados ao sistema de vigilância epidemiológica do Brasil. Considerando a escassez de estudos abordando esta questão, o objetivo desta análise foi avaliar os fatores relacionados a mortalidade por LT e sua variabilidade no tempo e espaço. Com base nos dados do Sistema Nacional de Agravos de Notificação, no período entre 2007 e 2014, foram realizados três estudos: (i) análise da variação temporal e espacial das taxas de mortalidade e letalidade por LT (estudo ecológico); (ii) análise de banco individual de casos notificados de LT em busca de fatores associados ao óbito comparando os desfechos cura, óbito por LT e óbito por outras causas e (iii) estudo de série de casos de pacientes com LT que evoluíram para óbito. As taxas foram padronizadas pela distribuição etária da população brasileira no ano de 2010. No estudo ecológico, para a análise temporal, foram utilizados modelos lineares generalizados e series temporais. Sob um enfoque bayesiano, a dependência espacial foi verificada através de modelos de regressão ecológica e autocorrelação espacial foi avaliada pelo índice de Moran, global e local. No período analisado, as taxas de mortalidade e letalidade se mantiveram estáveis. Não foi encontrada dependência espacial global entre as taxas, mas um cluster local foi identificado para a taxa de letalidade unindo os estados de São Paulo, Paraná e Mato Grosso do Sul. Associação com indicadores de desenvolvimento revelaram que a gravidade da doença parece estar mais relacionada a fatores socioeconômicos e condições de acesso aos serviços de saúde. Entre o total de casos notificados, 125.129 evoluíram para cura e 974 evoluíram para óbito, nos dois grupos predominam homens, brancos ou pardos e com escolaridade até o ensino fundamental. A mediana de idade entre pacientes com evolução clínica para cura foi significativamente menor (30 anos) que a mediana de pacientes que evoluíram para óbito (70 anos). Fatores associados à letalidade foram: idade, sexo feminino, presença de lesão mucosa e deslocamento do município de residência para o diagnóstico e tratamento. Indícios de que a toxicidade ao antimonial pentavalente está associada ao óbito também foram encontrados. Especificamente, pacientes que receberam dose diária de antimônio maior ou igual a 20 mg/Kg tiveram maior chance de óbito. Os resultados sugerem que condições relacionadas à organização social e ao acesso e estrutura dos serviços de saúde, além da toxicidade secundária ao tratamento, agravada por algumas condições clínicas, sejam os principais determinantes do óbito entre pacientes com LT, e não a doença diretamente. O encontro de heterogeneidade espacial alerta para a importância de diferentes estratégias de vigilância para o controle da doença e redução de letalidade.