BackgroundCutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures. Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance.Methodology/Principal FindingsThis study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sbv) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sbv. Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sbv group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was more effective than Sbv in the age group of 13–65 years-old compared to 2–12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively). The incidence of adverse events was similar in the Sbv and miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sbv group.ConclusionsThis study demonstrates that miltefosine therapy is more effective than standard Sbv and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil.Trial RegistrationClinicaltrials.gov Identifier NCT00600548

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

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Este artigo apresenta os principais resultados da Pesquisa Nacional de Saúde do Escolar (PeNSE). Aplicou-se questionário em uma amostra de conglomerados de 60.973 estudantes do 9º ano do ensino fundamental de escolas públicas e privadas das capitais dos estados brasileiros e do Distrito Federal, entre março e junho de 2009. Analisam-se prevalências e intervalos de confiança de 95% (IC95%) das situações de violência envolvendo adolescentes. Foram identificadas as seguintes situações: insegurança no trajeto casa-escola (6,4%; IC95%: 6,1%-6,8%) e na escola (5,5%; IC95%: 5,2%-5,8%); envolvimento em brigas com agressão física (12,9%; IC95%: 12,4%-13,4%), com arma branca (6,1%; IC95%: 5,7%-6,4%) ou arma de fogo (4,0%; IC95%: 3,7%-4,3%); agressão física por familiar (9,5%; IC95%: 9,1%-9,9%). As situações de violência foram mais prevalentes entre estudantes do sexo masculino. Houve grande variação segundo as cidades estudadas. Os adolescentes estão expostos a diferentes manifestações de violência nas instituições que supostamente deveriam garantir sua proteção e desenvolvimento saudável e seguro - a escola e o lar. Esses resultados visam apoiar medidas de promoção à saúde e prevenção desses fatores de risco.

BackgroundSocial determinants can affect the transmission of leprosy and its progression to disease. Not much is known about the effectiveness of welfare and primary health care policies on the reduction of leprosy occurrence. The aim of this study is to evaluate the impact of the Brazilian cash transfer (Bolsa Família Program-BFP) and primary health care (Family Health Program-FHP) programs on new case detection rate of leprosy.Methodology/Principal FindingsWe conducted the study with a mixed ecological design, a combination of an ecological multiple-group and time-trend design in the period 2004–2011 with the Brazilian municipalities as unit of analysis. The main independent variables were the BFP and FHP coverage at the municipal level and the outcome was new case detection rate of leprosy. Leprosy new cases, BFP and FHP coverage, population and other relevant socio-demographic covariates were obtained from national databases. We used fixed-effects negative binomial models for panel data adjusted for relevant socio-demographic covariates. A total of 1,358 municipalities were included in the analysis. In the studied period, while the municipal coverage of BFP and FHP increased, the new case detection rate of leprosy decreased. Leprosy new case detection rate was significantly reduced in municipalities with consolidated BFP coverage (Risk Ratio 0.79; 95% CI  = 0.74–0.83) and significantly increased in municipalities with FHP coverage in the medium (72–95%) (Risk Ratio 1.05; 95% CI  = 1.02–1.09) and higher coverage tertiles (>95%) (Risk Ratio 1.12; 95% CI  = 1.08–1.17).ConclusionsAt the same time the Family Health Program had been effective in increasing the new case detection rate of leprosy in Brazil, the Bolsa Família Program was associated with a reduction of the new case detection rate of leprosy that we propose reflects a reduction in leprosy incidence.

BackgroundNew approaches and tools were needed to support the strategic planning, implementation and management of a Program launched by the Brazilian Government to fund research, development and capacity building on neglected tropical diseases with strong focus on the North, Northeast and Center-West regions of the country where these diseases are prevalent.Methodology/Principal FindingsBased on demographic, epidemiological and burden of disease data, seven diseases were selected by the Ministry of Health as targets of the initiative. Publications on these diseases by Brazilian researchers were retrieved from international databases, analyzed and processed with text-mining tools in order to standardize author- and institution's names and addresses. Co-authorship networks based on these publications were assembled, visualized and analyzed with social network analysis software packages. Network visualization and analysis generated new information, allowing better design and strategic planning of the Program, enabling decision makers to characterize network components by area of work, identify institutions as well as authors playing major roles as central hubs or located at critical network cut-points and readily detect authors or institutions participating in large international scientific collaborating networks.Conclusions/SignificanceTraditional criteria used to monitor and evaluate research proposals or R&D Programs, such as researchers' productivity and impact factor of scientific publications, are of limited value when addressing research areas of low productivity or involving institutions from endemic regions where human resources are limited. Network analysis was found to generate new and valuable information relevant to the strategic planning, implementation and monitoring of the Program. It afforded a more proactive role of the funding agencies in relation to public health and equity goals, to scientific capacity building objectives and a more consistent engagement of institutions and authors from endemic regions based on innovative criteria and parameters anchored on objective scientific data.

Summary Background Although leprosy is recognised as a disease of poverty, there is little evidence on the specific socioeconomic factors associated with disease risk. To inform targeted strategies for disease elimination, we investigated socioeconomic markers of leprosy risk in Brazil. Methods Socioeconomic data from the 100 Million Brazilian Cohort were linked to the Brazilian national disease registry (Sistema de Informação de Agravos de Notificação) for leprosy from Jan 1, 2007, to Dec 31, 2014. Using Poisson regression, we assessed the association of socioeconomic factors with risk of incident leprosy in the full cohort and in children (aged 0–15 years), by leprosy subtype and region of residence. Findings In an analysis of 23 899 942 individuals including 18 518 patients with leprosy, increased levels of deprivation were associated with an increased risk of leprosy in Brazil. Directions of effect were consistent in children younger than 15 years and across disease subtypes. Individuals residing in regions with the highest poverty in the country (central-west, north, and northeast regions) had a risk of leprosy incidence five-to-eight times greater than did other individuals. Decreased levels of income and education and factors reflecting unfavourable living conditions were associated with an up to two-times increase in leprosy incidence (incidence rate ratio 1·46, 95% CI 1·32–1·62, for lowest vs highest quartile of income per capita; 2·09, 95% CI 1·62–2·72, for lowest vs highest level of education). Interpretation Within the poorest half of the Brazilian population, the most deprived individuals have the greatest risk of leprosy. Strategies focusing on early detection and treatment in the poorest populations could contribute substantially to global disease control. Funding Medical Research Council, Wellcome Trust, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazil), the Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa, Economic and Social Research Council, Biotechnology and Biological Sciences Research Council, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundação de Apoio à Pesquisa do Distrito Federal.

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