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Abstract COVID-19 vaccination during pregnancy is safe and effective in reducing the risk of complications. However, the uptake is still below targets worldwide. This study aimed to explore the factors associated with COVID-19 vaccination uptake among pregnant women since data on this topic is scarce in low-to-middle-income countries. A retrospective cohort study included linked data on COVID-19 vaccination and pregnant women who delivered a singleton live birth from August 1, 2021, to July 31, 2022, in Rio de Janeiro City, Brazil. Multiple logistic regression was performed to identify factors associated with vaccination during pregnancy, applying a hierarchical model and describing odds ratio with 95% confidence intervals. Of 65,304 pregnant women included in the study, 53.0% (95% CI, 52–53%) received at least one dose of COVID-19 vaccine during pregnancy. Higher uptake was observed among women aged older than 34 (aOR 1.21, 95%CI 1.15–1.28), black (aOR 1.10, 1.04–1.16), or parda/brown skin colour (aOR 1.05, 1.01–1.09), with less than eight years of education (aOR 1.09, 1.02–1.17), living without a partner (aOR 2.24, 2.16–2.34), more than six antenatal care appointments (aOR 1.92, 1.75–2.09), and having a previous child loss (OR 1.06, 1.02–1.11). These results highlight the need for targeted educational campaigns, trustful communication, and accessibility strategies for specific populations to improve vaccination uptake during pregnancy.

Background: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. Objectives: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. Methods: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. Results: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. Conclusions: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. Trial registration: ClinicalTrials.gov: NCT00669643.

IntroductionLeprosy reactions (LR) are severe episodes of intense activation of the host inflammatory response of uncertain etiology, today the leading cause of permanent nerve damage in leprosy patients. Several genetic and non-genetic risk factors for LR have been described; however, there are limited attempts to combine this information to estimate the risk of a leprosy patient developing LR. Here we present an artificial intelligence (AI)-based system that can assess LR risk using clinical, demographic, and genetic data.MethodsThe study includes four datasets from different regions of Brazil, totalizing 1,450 leprosy patients followed prospectively for at least 2 years to assess the occurrence of LR. Data mining using WEKA software was performed following a two-step protocol to select the variables included in the AI system, based on Bayesian Networks, and developed using the NETICA software.ResultsAnalysis of the complete database resulted in a system able to estimate LR risk with 82.7% accuracy, 79.3% sensitivity, and 86.2% specificity. When using only databases for which host genetic information associated with LR was included, the performance increased to 87.7% accuracy, 85.7% sensitivity, and 89.4% specificity.ConclusionWe produced an easy-to-use, online, free-access system that identifies leprosy patients at risk of developing LR. Risk assessment of LR for individual patients may detect candidates for close monitoring, with a potentially positive impact on the prevention of permanent disabilities, the quality of life of the patients, and upon leprosy control programs.

BackgroundA vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.ObjectiveWe aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.MethodsWe performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.ResultsWe included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).ConclusionsOur study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.

Abstract Background Malaria causes 400 thousand deaths worldwide annually. In 2018, 25% (187,693) of the total malaria cases in the Americas were in Brazil, with nearly all (99%) Brazilian cases in the Amazon region. The Bolsa Família Programme (BFP) is a conditional cash transfer (CCT) programme launched in 2003 to reduce poverty and has led to improvements in health outcomes. CCT programmes may reduce the burden of malaria by alleviating poverty and by promoting access to healthcare, however this relationship is underexplored. This study investigated the association between BFP coverage and malaria incidence in Brazil. Methods A longitudinal panel study was conducted of 807 municipalities in the Brazilian Amazon between 2004 and 2015. Negative binomial regression models adjusted for demographic and socioeconomic covariates and time trends were employed with fixed effects specifications. Results A one percentage point increase in municipal BFP coverage was associated with a 0.3% decrease in the incidence of malaria (RR = 0.997; 95% CI = 0.994–0.998). The average municipal BFP coverage increased 24 percentage points over the period 2004–2015 corresponding to be a reduction of 7.2% in the malaria incidence. Conclusions Higher coverage of the BFP was associated with a reduction in the incidence of malaria. CCT programmes should be encouraged in endemic regions for malaria in order to mitigate the impact of disease and poverty itself in these settings.

Abstract Background Leprosy continues to be an important cause of physical disability in endemic countries such as Brazil. Knowledge of determinants of these events may lead to better control measures and targeted interventions to mitigate its impact on affected individuals. This study investigated such factors among the most vulnerable portion of the Brazilian population. Methods A large cohort was built from secondary data originated from a national registry of applicants to social benefit programs, covering the period 2001–2015, including over 114 million individuals. Data were linked to the leprosy notification system utilizing data from 2007 until 2014. Descriptive and bivariate analyses lead to a multivariate analysis using a multinomial logistic regression model with cluster-robust standard errors. Associations were reported as Odds Ratios with their respective 95% confidence intervals. Results Among the original cohort members 21,565 new leprosy cases were identified between 2007 and 2014. Most of the cases (63.1%) had grade zero disability. Grades 1 and 2 represented 21 and 6%, respectively. Factors associated with increasing odds of grades 1 and 2 disability were age over 15 years old (ORs 2.39 and 1.95, respectively), less schooling (with a clear dose response effect) and being a multibacillary patient (ORs 3.5 and 8.22). Protective factors for both grades were being female (ORs 0.81 and 0.61) and living in a high incidence municipality (ORs 0.85 and 0.67). Conclusions The findings suggest that the developing of physical disabilities remains a public health problem which increases the burden of leprosy, mainly for those with severe clinical features and worse socioeconomic conditions. Early diagnosis is paramount to decrease the incidence of leprosy-related disability and our study points to the need for strengthening control actions in non-endemic areas in Brazil, where cases may be missed when presented at early stages in disease. Both actions are needed, to benefit patients and to achieve the WHO goal in reducing physical disabilities among new cases of leprosy.

O manejo clínico de pacientes com hanseníase apresenta um desafio particular que são as reações. O objetivo deste estudo de coorte não concorrente foi analisar o tempo e fatores associados à ocorrência da primeira reação durante e após o tratamento da poliquimioterapia (PQT). Avaliou-se 1.621 pacientes paucibacilares (PB = 8,9%) e multibacilares (MB = 91,1%) de 2008 a 2016 notificados no Sistema de Estados Reacionais em Hanseníase/Rondônia (SisReação/RO). Prevaleceu a ocorrência durante o tratamento da PQT = 997 (61,5%), e 624 (38,5%) somente após o PQT. A precocidade da reação, a partir do diagnóstico, foi analisada por meio de curvas de sobrevida de Kaplan-Meier e comparadas entre os grupos PB e MB, usando o teste de log-rank de Mantel-Cox; e foram construídos modelos de regressão de Cox univariada e multivariada para identificar os fatores associados à ocorrência da reação (hazard ratio) e os correspondentes IC95%. No modelo multivariado foram incluídas variáveis com valores de p < 0,2 na análise univariada. Os PB desenvolveram reação de forma mais precoce do que os MB. Outras características associaram-se à reação em menor tempo: sexo feminino e baciloscopia negativa. No período agregado (durante e após a PQT), os pacientes PB apresentaram risco 24% maior de reação do que os MB e aqueles com baciloscopia negativa aumentaram este risco em 40% comparado à baciloscopia positiva. Durante e após a PQT, os PB apresentaram 1,3 e 1,6 vezes maior risco de ocorrência da reação dos pacientes MB. Dessa forma, recomendamos priorizar ações de vigilância para reações hansênicas durante e após a PQT como medidas de prevenção de incapacidades físicas e de melhoria na qualidade de vida das pessoas acometidas pela hanseníase.

Abstract: Our study aims to describe trends in new case detection rate (NCDR) of leprosy in Brazil from 2006 to 2017 overall and in subgroups, and to analyze the evolution of clinical and treatment characteristics of patients, with emphasis on cases diagnosed with grade 2 physical disabilities. We conducted a descriptive study to analyze new cases of leprosy registered in the Brazilian Information System for Notificable Diseases (SINAN), from 2006-2017. We calculated the leprosy NCDR per 100,000 inhabitants (overall and for individuals aged < 15 and ≥ 15 years) by sex, age, race/ethnicity, urban/rural areas, and Brazilian regions, and estimated the trends using the Mann-Kendall non-parametric test. We analyzed the distributions of cases according to relevant clinical characteristics over time. In Brazil, there was a sharp decrease in the overall NCDR from 23.4/100,000 in 2006 to 10.3/100,000 in 2017; among children < 15 years, from 6.94 to 3.20/100,000. The decline was consistent in all Brazilian regions and race/ethnicity categories. By 2017, 70.2% of the cases were multibacillary, 30.5% had grade 1 (G1D) or 2 (G2D) physical disabilities at diagnosis and 42.8% were not evaluated at treatment completion/discharge; cases with G2D at diagnosis were mostly detected in urban areas (80%) and 5% of cases died during the treatment (leprosy or other causes). Although the frequency of leprosy NCDR decreased in Brazil from 2006 to 2017 across all evaluated population groups, the large number of cases with multibacillary leprosy, physical disabilities or without adequate evaluation, and among children suggest the need to reinforce timely diagnosis and treatment to control leprosy in Brazil.

[This corrects the article DOI: 10.1371/journal.pntd.0007714.].

Abstract: BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Abstract: In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.

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.

BackgroundAlthough leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil.Methodology/principal findingsUsing individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25-1.97) and Northeast (OR = 1.44; 95%CI 1.17-1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01-1.69), no income (OR = 1.41; 95%CI 1.07-1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13-1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28-1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10-1.66).ConclusionsThe findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control.

This original study describes the intra-urban distribution of cases of leprosy in residents under 15 years old in Salvador, Bahia, Brazil; the study also identifies the environment in which Mycobacterium leprae is being transmitted. The cases were distributed by operational classification, clinical forms, type of contact and the addresses were geo-referenced by neighborhood. Between 2007 and 2011, were reported 145 cases of leprosy in target population living in Salvador, corresponding to detection rates of 6.21, 6.14, 5.58, 5.41 and 6.88/100,000 inhabitants, respectively. The spatial distribution of the disease was focal. Of the 157 neighborhoods of Salvador, 44 (28.6%) notified cases of leprosy and in 22 (50%) of these were detected more than 10 cases per 100,000 inhabitants. The infectious forms were found in 40% of cases. Over 90% of cases had been living in Salvador for more than five years. Overall, 52.6% reported having had contact with another infected individual inside the household and 25% in their social circle. In Salvador, M. leprae transmission is established. The situation is a major concern, since transmission is intense at an early age, indicating that this endemic disease is expanding and contacts extend beyond individual households.

There is evidence that in southern US, leprosy is a zoonosis infecting wild Dasypus novemcinctus armadillos but the extent of this finding is unknown. This ecological study investigated leprosy in rural communities and in wild armadillos from the Brazilian Amazon. The study area was the Mamiá Lake of Coari municipality, Amazonas State, Northern region, a hyper endemic leprosy area where residents live on subsistence farming, fishing and armadillo hunting and its meat intake are frequent. The leprosy survey was conducted in sixteen communities by a visiting team of specialists. Local partakers provided wild armadillos to investigate M. leprae infection. Volunteers had complete dermato-neurological examination by a dermatologist with expertise in leprosy diagnosis, suspect skin lesions were biopsied for histopathology (Hematoxylin-eosin/HE, Fite-Faraco/FF staining); slit skin smears were collected. Armadillos' tissue fragments (skins, spleens, livers, lymph nodes, adrenal glands, others) were prepared for histopathology (HE/FF) and for M. leprae repetitive element-RLEP-qPCR. Among 176 volunteers, six new indeterminate leprosy cases were identified (incidence = 3.4%). Suspect skin sections and slit skin smears were negative for bacilli. Twelve wild D. novemcinctus were investigated (48 specimens/96 slides) and histopathological features of M. leprae infection were not found, except for one skin presenting unspecific inflammatory infiltrate suggestive of indeterminate leprosy. Possible traumatic neuroma, granuloma with epithelioid and Langhans cells, foreign-body granuloma were also identified. Granulomatous/non-granulomatous dermatitides were periodic-acid-Schiff/PAS negative for fungus. M. leprae-RLEP-qPCR was negative in all armadillos' tissues; no bacillus was found in histopathology. Our survey in rural communities confirmed the high endemicity for leprosy while one armadillo was compatible with paucibacillary M. leprae infection. At least in the highly endemic rural area of Coari, in the Brazilian Amazon region where infectious sources from untreated multibacillary leprosy are abundant, M. leprae infected armadillos may not represent a major source of infection nor a significant public health concern.

BACKGROUND:Leprosy is a chronic infectious disease neglected, caused by Mycobacterium leprae, considered a public health problem because may cause permanent physical disabilities and deformities, leading to severe limitations. This review presents an overview of the results of epidemiological studies on leprosy occurrence in childhood in Brazil, aiming to alert health planners and managers to the actual need to institute special control strategies. METHODOLOGY/PRINCIPAL FINDINGS:Data collection consisted of an electronic search for publications in eight databases: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), PuBMed, Biblioteca Virtual em Saúde (BVS), SciVerse Scopus (Scopus), CAPES theses database, CAPES journals database and Web of Science of papers published up to 2016. After apply selection criteria, twenty-two papers of studies conducted in four different regions of Brazil and published between 2001 and 2016 were included in the review. The leprosy detection rate ranged from 10.9 to 78.4 per 100,000 inhabitants. Despite affecting both sexes, leprosy was more common in boys and in 10-14-year-olds. Although the authors reported a high cure proportion (82-90%), between 1.7% and 5.5% of the individuals developed a disability resulting from the disease. CONCLUSIONS/SIGNIFICANCE:The findings of this review shows that leprosy situation in Brazilian children under 15 years is extremely adverse in that the leprosy detection rate remains high in the majority of studies. The proportion of cases involving disability is also high and reflects the difficulties and the poor effectiveness of actions aimed at controlling the disease. The authors suggest the development of studies in spatial clusters of leprosy, where beyond the routine actions established, are included news strategies of active search and campaigns and actions of educations inside the clusters of this disease. The new agenda needs to involve the precepts of ethical, humane and supportive care, in order to achieve a new level of leprosy control in Brazil.

Over 200,000 new cases of leprosy are detected each year, of which approximately 7% are associated with grade-2 disabilities (G2Ds). For achieving leprosy elimination, one of the main challenges will be targeting higher risk groups within endemic communities. Nevertheless, the socioeconomic risk markers of leprosy remain poorly understood. To address this gap we systematically reviewed MEDLINE/PubMed, Embase, LILACS and Web of Science for original articles investigating the social determinants of leprosy in countries with > 1000 cases/year in at least five years between 2006 and 2016. Cohort, case-control, cross-sectional, and ecological studies were eligible for inclusion; qualitative studies, case reports, and reviews were excluded. Out of 1,534 non-duplicate records, 96 full-text articles were reviewed, and 39 met inclusion criteria. 17 were included in random-effects meta-analyses for sex, occupation, food shortage, household contact, crowding, and lack of clean (i.e., treated) water. The majority of studies were conducted in Brazil, India, or Bangladesh while none were undertaken in low-income countries. Descriptive synthesis indicated that increased age, poor sanitary and socioeconomic conditions, lower level of education, and food-insecurity are risk markers for leprosy. Additionally, in pooled estimates, leprosy was associated with being male (RR = 1.33, 95% CI = 1.06-1.67), performing manual labor (RR = 2.15, 95% CI = 0.97-4.74), suffering from food shortage in the past (RR = 1.39, 95% CI = 1.05-1.85), being a household contact of a leprosy patient (RR = 3.40, 95% CI = 2.24-5.18), and living in a crowded household (≥5 per household) (RR = 1.38, 95% CI = 1.14-1.67). Lack of clean water did not appear to be a risk marker of leprosy (RR = 0.94, 95% CI = 0.65-1.35). Additionally, ecological studies provided evidence that lower inequality, better human development, increased healthcare coverage, and cash transfer programs are linked with lower leprosy risks. These findings point to a consistent relationship between leprosy and unfavorable economic circumstances and, thereby, underscore the pressing need of leprosy control policies to target socially vulnerable groups in high-burden countries.

Background: The importance of the social determinants of health (SDH) and barriers to the access and utilization of healthcare have been widely recognized but not previously studied in the context of universal healthcare coverage (UHC) in Brazil and other developing countries. Objective: To evaluate a set of proposed indicators of SDH and barriers to the access and utilization of healthcare – proposed by the SDH unit of the World Health Organization – with respect to their relevance in tracking progress in moving toward equitable population health and UHC in Brazil. Design: This study had a mixed methodology, combining a quantitative analysis of secondary data from governmental sources with a qualitative study comprising two focus group discussions and six key informant interviews. The set of indicators tested covered a broad range of dimensions classified by three different domains: environment quality; accountability and inclusion; and livelihood and skills. Indicators were stratified according to income quintiles, urbanization, race, and geographical region. Results: Overall, the indicators were adequate for tracking progress in terms of the SDH, equity, gender, and human rights in Brazil. Stratifications showed inequalities. The qualitative analysis revealed that many of the indicators were well known and already used by policymakers and health sector managers, whereas others were considered less useful in the Brazilian context. Conclusions: Monitoring and evaluation practices have been developed in Brazil, and the set of indicators assessed in this study could further improve these practices, especially from a health equity perspective. Socioeconomic inequalities have been reduced in Brazil in the last decade, but there is still much work to be done in relation to addressing the SDH.

Leprosy is an ancient infectious disease caused by Mycobacterium leprae. According to comparative genomics studies, this disease originated in Eastern Africa or the Near East and spread with successive human migrations. The Europeans and North Africans introduced leprosy into West Africa and the Americas within the past 500 years. In Brazil, this disease arrived with the colonizers who disembarked at the first colonies, Rio de Janeiro, Salvador and Recife, at the end of the sixteenth century, after which it was spread to the other states. In 1854, the first leprosy cases were identified in State of Amazonas in the north of Brazil. The increasing number of leprosy cases and the need for treatment and disease control led to the creation of places to isolate patients, known as leprosaria. One of them, Colonia Antônio Aleixo was built in Amazonas in 1956 according to the most advanced recommendations for isolation at that time and was deactivated in 1979. The history of the Alfredo da Matta Center (AMC), which was the first leprosy dispensary created in 1955, parallels the history of leprosy in the state. Over the years, the AMC has become one of the best training centers for leprosy, general dermatology and sexually transmitted diseases in Brazil. In addition to being responsible for leprosy control programs in the state, the AMC has carried out training programs on leprosy diagnosis and treatment for health professionals in Manaus and other municipalities of the state, aiming to increase the coverage of leprosy control activities. This paper provides a historical overview of leprosy in State of Amazonas, which is an endemic state in Brazil.

BACKGROUND:Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY AND FINDINGS:An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year. CONCLUSION:Our results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide. TRIAL REGISTRATION:ClinicalTrials.gov: NCT00669643.

BACKGROUND:Leprosy reactions, reversal reactions/RR and erythema nodosum leprosum/ENL, can cause irreversible nerve damage, handicaps and deformities. The study of Mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil/U-MDT/CT-BR is suitable to evaluate its prognostic value for the development of reactions. METHODOLOGY:IgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time. PRINCIPAL FINDINGS:Among these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p

The aim of this article is to examine regional differences in mortality associated with influenza from 2006 to 2010 in Brazil. Syndromic surveillance, which includes deaths from pneumonia and influenza recorded in the Mortality Information System, only showed an increase in mortality during the pandemic in the South, Southeast, and Central, regions. In these regions, especially in the South, this increase occurred from July to September 2009. A review of deaths from confirmed influenza cases reported to the Information System for Notifiable Diseases showed different temporal patterns in the South/Southeast and the North/Northeast, with an increase from July to November 2009 for all regions and another peak, only for the latter, in March 2010, before the vaccination campaign. The results show regional differences in the intensity and temporal distribution of pandemic influenza and highlight the need for specific surveillance tools and control strategies for regions of the country.El objetivo de este artículo es examinar las diferencias regionales en la mortalidad asociada a la gripe, entre 2006 y 2010, en Brasil. La vigilancia de sindrómica, que incluye óbitos por neumonía y gripe, registrados en el Sistema de Información sobre Mortalidad, mostró un aumento en la mortalidad durante la pandemia sólo en las regiones Sur, Sudeste y Centro-Oeste. En esas regiones, principalmente en la Región Sur, ese aumento ocurrió entre julio y setiembre de 2009. Evaluándose los óbitos de casos confirmados de gripe, comunicados al Sistema de Información de Agravamientos por Notificación, se verificó un patrón temporal diferente entre las regiones Sur/Sudeste y las regiones Norte/Nordeste, con un aumento entre julio y noviembre de 2009 en todas las regiones y otro pico en marzo de 2010, antes de la campaña de vacunación, solamente en las últimas. Los resultados muestran diferencias regionales en la intensidad y en la distribución temporal de la pandemia de gripe, y apuntan a la necesidad de instrumentos de vigilancia y de control específicos para las regiones del país.O objetivo deste artigo é examinar as diferenças regionais na mortalidade associada à influenza entre 2006 e 2010 no Brasil. A vigilância sindrômica, que inclui óbitos por pneumonia e influenza registrados no Sistema de Informações sobre Mortalidade, mostrou aumento na mortalidade durante a pandemia apenas nas regiões Sul, Sudeste e Centro-Oeste. Nessas regiões, principalmente na Região Sul, esse aumento ocorreu entre julho e setembro de 2009. Avaliando-se os óbitos de casos confirmados de influenza notificados ao Sistema de Informações de Agravos de Notificação, verificou-se um padrão temporal diferente entre as regiões Sul/Sudeste e as regiões Norte/Nordeste, com aumento entre julho e novembro de 2009 para todas as regiões e outro pico em março de 2010, antes da campanha de vacinação, apenas para as últimas. Os resultados mostram diferenças regionais na intensidade e na distribuição temporal da pandemia de influenza e apontam para a necessidade de instrumentos de vigilância e de controle específicos para as regiões do país.

In 1991, the World Health Organization (WHO) committed to reducing the prevalence of leprosy to below 1 in 10,000 inhabitants by 2000. Significant improvements in leprosy control have occurred, but leprosy remains a public health problem in many countries due to its high incidence and rate of transmission. This paper reviews data published by the WHO in the years 2000, 2005 and 2010. These data sets included 148 countries or territories that reported to the WHO at least once. Only four countries reported higher prevalence rates in 2010 than in 2000 and eight reported higher case detection rate (CDR) in 2009 than in 1999. Prevalence rate reductions were greater for the first five-year period examined, while CDR reductions were greater in the second five-year period. Thirty-six countries and territories reported at least one prevalence value higher than 1 per 10,000 inhabitants and 32 reported at least one CDR value higher than 9 per 100,000 inhabitants. A total of 39 countries fit at least one of these criteria and all were located in tropical regions.

Leprosy will continue to be a public health problem for several decades. The World Health Organization (WHO) recommends that, for treatment purposes, leprosy cases be classified as either paucibacillary or multibacillary (MB). A uniform leprosy treatment regimen would simplify treatment and halve the treatment duration for MB patients. The clinical trial for uniform multidrug therapy (U-MDT) for leprosy patients (LPs) in Brazil is a randomised, open-label clinical trial to evaluate if the effectiveness of U-MDT for leprosy equals the regular regimen, to determine the acceptability of the U-MDT regimen and to identify the prognostic factors. This paper details the clinical trial methodology and patient enrolment data. The study enrolled 858 patients at two centres and 78.4% of participants were classified as MB according to the WHO criteria. The main difficulty in evaluating a new leprosy treatment regimen is that no reliable data are available for the current treatment regimen. Relapse, reaction and impaired nerve function rates have never been systematically determined, although reaction and impaired nerve function are the two major causes of nerve damage that lead to impairments and disabilities in LPs. Our study was designed to overcome the need for reliable data about the current treatment and to compare its efficacy with that of a uniform regimen.

The introduction, implementation, successes and failures of multidrug therapy (MDT) in all Hansen's disease endemic countries are discussed in this paper. The high efficacy of leprosy treatment with MDT and the global reduction of prevalence led the World Health Organization, in 1991, to establish the goal of elimination of Hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. Brazil, Nepal and East Timor are among the few countries that didn't reach the elimination goal by the year 2000 or even 2005. The implications of these aspects are highlighted in this paper. Current data from endemic and previously endemic countries that carry a regular leprosy control programme show that the important fall in prevalence was not followed by the reduction of the incidence. This means that transmission of Mycobacterium leprae is still an issue. It is reasonable to conclude that we are still far from the most important goal of Hansen's disease control: the interruption of transmission and reduction of incidence. It is necessary to emphasize to health managers the need of keeping Hansen's disease control activities to better develop control programmes in the future. The recent international proposal to interrupt the transmission of leprosy by the year 2020 seems to unrealistic and it is discussed in this paper. The possibility of epidemiological impact related to the human immunodeficiency virus/Hansen's disease coinfection is also considered.

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

A estruturação do Sistema Nacional de Vigilância Epidemiológica do Brasil, em 1975, tornou obrigatória a notificação de algumas doenças transmissíveis com o objetivo de reduzir a carga destes eventos no país. Entretanto, as alterações no perfil epidemiológico destas doenças, associadas a características da sociedade contemporânea, determinam a constante adequação das atividades de vigilância a este cenário. Neste manuscrito, são descritos epidemiologia, tendências e diagnóstico diferencial das seguintes doenças dermatológicas de notificação compulsória no Brasil: aids, dengue, hanseníase, leishmaniose tegumentar americana, sarampo, rubéola e síndrome da rubéola congênita e sífilis. Também são apresentados os principais desafios atuais para o controle e prevenção para cada uma dessas doenças no BrasilThe development of a Brazilian National Surveillance System in 1975 led to a compulsory reporting of selected infectious diseases aiming to reduce the burden of these events in the country. However, shifts in the epidemiology of these diseases associated with modern life style, demand constant revision of surveillance activities. In this manuscript we present the epidemiology, trends and differential diagnosis of the following compulsory notifiable diseases in Brazil: Aids, dengue fever, hanseniasis, American tegumentary leishmaniasis, measles, rubella and congenital rubella syndrome and syphilis. Additionally, the current challenges for control and prevention of each disease are presented

OBJETIVOS: Com o objetivo de estimar a prevalência da síndrome gripal em adultos das capitais e regiões do Brasil, realizou-se monitoramento da ocorrência de sinais e sintomas compatíveis por inquérito telefônico (VIGITEL) em 2010. MÉTODO: Estudo transversal que contou com 47.876 entrevistas nas capitais dos estados brasileiros e no Distrito Federal, com amostragem probabilística da população >18 anos, residente em domicílios com linha fixa de telefone. Foram analisadas as questões referentes à síndrome gripal e influenza pandêmica (H1N1) 2009, no período de 10 de janeiro a 30 de novembro de 2010. Os percentuais foram calculados para as regiões do país e para o Brasil e ponderados segundo a distribuição sociodemográfica da PNAD 2008. RESULTADOS: A prevalência de indivíduos, com algum sinal ou sintoma de gripe nos 30 dias anteriores à entrevista, foi de 31,2% (IC95% 30,2-32,2%). O relato de síndrome gripal foi mais frequente entre as mulheres, adultos jovens (18 a 29 anos) e aquelas pessoas com 9 a 11 anos de estudo. A maior prevalência de sinais ou sintomas gripais ocorreu na região Norte. Verificou-se tendência crescente com posterior decréscimo em todas as regiões, exceto na Nordeste. A procura pelo serviço de saúde foi relatada por 26,8% (IC95% 25,1-28,5) das pessoas que adoeceram. A suspeita médica de influenza pandêmica (H1N1) 2009 ocorreu em 2,6% (IC95% 1,8-3,4) dos entrevistados que relataram ter procurado o serviço de saúde. CONCLUSÃO: Os resultados deste inquérito forneceram informações oportunas e úteis, as quais não foram captadas pelo sistema de vigilância tradicional, como a ocorrência de sinal ou sintoma gripal e a procura pelo serviço de saúde.OBJECTIVES: In order to estimate the prevalence of influenza like illness (ILI) in adults from all state capitals and geographic regions in Brazil, a periodical monitoring of ILI cases by the national telephone survey (VIGITEL) was carried out in 2010. METHOD: A cross-sectional study with 47,876 telephone interviews in the state capitals and Federal District, a probabilistic sample of adult population (>18 years-old) with landline telephone. Questions concerning the results of ILI cases and pandemic influenza (H1N1) 2009, from January 10 to November 30, were analyzed. The proportion of cases stratified by sociodemographic characteristics and Brazilian geographic region was weighted with data from the National Survey with Household Sampling (PNAD) 2008. RESULTS: The prevalence of ILI cases in the last 30 days before interview was 31.2% (95%CI 30.2-32.2%) for all state capitals and the Federal District. This prevalence was higher among women, young adults (18 to 29 years-old) and individuals with 9 to 11 years of schooling. According to the geographic region analysis, Northern Brazil presented the highest prevalence of ILI cases. A tendency to increase with further decrease was observed among the geographic regions, except the Northeast. Need for health care assistance was reported by 26.8% (95%CI 25.1-28.5) from ILI cases. Among ILI cases that sought health care assistance, 2.6% (95%CI 1.8-3.4) reported pandemic influenza (H1N1) 2009 medical suspicion. CONCLUSION: The results of this survey supported influenza surveillance as it provided timeliness and useful surveillance information, which were not captured by the traditional surveillance system, as the occurrence of ILI and need of health care assistance.

Com o objetivo de analisar a proporção de adultos que dirigem alcoolizados nas capitais brasileiras e no Distrito Federal após instituição da Lei nº 11.705 foram analisados dados do sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL). Em 2008, 1,5% dos indivíduos entrevistados referiram em pelo menos uma ocasião ter conduzido veículo motorizado após consumo abusivo de bebida alcoólica. A freqüência de adultos que dirigiram após o consumo abusivo se manteve entre 1,8% e 2,2% nos oito meses anteriores à Lei, caindo no mês seqüente à promulgação da mesma, voltando a crescer dois meses depois, atingindo o máximo de 2,6% ao final de 2008 e retornando aos níveis iniciais nos primeiros meses de 2009.Con el objetivo de analizar la proporción de adultos que manejan alcoholizadas en las capitales brasileras y en el Distrito Federal posterior a la institución de la Ley nº 11.705 fueron analizados datos del sistema de Vigilancia de Factores de Riesgo y Protección para Enfermedades Crónicas por Pesquisa Telefónica (VIGITEL). En 2008, 1,5% de los individuos entrevistados refirieron en por lo menos una ocasión haber conducido vehículo motorizado posterior al consumo abusivo de bebida alcohólica. La frecuencia de adultos que manejaron posterior al consumo abusivo se mantuvo entre 1,8% y 2,2% en los ocho meses anteriores a la Ley, cayendo en el mes siguiente a la promulgación de la misma, volviendo a crecer dos meses después, alcanzando el máximo de 2,6% al final de 2008 y retornando a los niveles iniciales en los primeros meses de 2009.The present study aimed to analyze the proportion of adults who drive under the influence of alcohol in the Brazilian capitals and in the Federal District, after Law 11,705 was established. Data from the Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico System (VIGITEL - Surveillance System of Risk and Protective Factors for Chronic Diseases by Telephone Interview) were analyzed. In 2008, 1.5% of individuals interviewed reported having driven a motor vehicle after binge drinking in at least one occasion. The frequency of adults who drove after binge drinking remained between 1.8% and 2.2% in the eight months preceding the Law, decreased in the month following its establishment, and increased again two months later, reaching a maximum of 2.6% by the end of 2008 and returning to the initial levels in the first months of 2009.

Hansen's disease, also known as leprosy, is an infectious disease still prevalent in Brazil. It is a chronic illness with acute immunological phenomena known as leprosy reactions. In the Federal District of Brazil, the University Hospital of Brasília is the reference centre for leprosy care. The study aimed to characterize the clinical and epidemiological profile of Hansen's disease patients at the University Hospital of Brasília, by descriptive, retrospective analysis of 1,124 patients over the period from 1985 to 2005. The pattern of leprosy in this study demonstrated that type 2 leprosy reactions were common, especially in the lepromatous form and presented a direct correlation with the bacilloscopic index. The prevalence and frequency of severe complications, such as leprosy reactions, emphasize the importance of the ongoing study of leprosy and the need for continual improvement in the scope of knowledge concerning its treatment.Hanseníase, também conhecida como lepra, é doença infecciosa prevalente no Brasil. Caracteriza-se por curso crônico, com fenômenos imunológicos agudos denominados episódios reacionais. No Distrito Federal, o Hospital Universitário de Brasília é referência na assistência da hanseníase. O objetivo do estudo foi caracterizar o perfil clínico-epidemiológico dos doentes portadores de hanseníase do Hospital Universitário de Brasília. Foi realizada análise descritiva e retrospectiva de 1124 doentes portadores de hanseníase no período de 1985 a 2005. O padrão da hanseníase no nosso estudo concretizou-se por apresentar maior prevalência de reações do tipo 2, especialmente na forma lepromatosa e correlacionando-se diretamente com o índice baciloscópico. A significativa prevalência e freqüência de complicações graves como os episódios reacionais ressaltam a importância do estudo da doença e a necessidade de aprimoramento contínuo dos conhecimentos sobre a mesma.

Foram estudados 76 pacientes com paracoccidioidomicose, assistidos no Hospital Universitário de Brasília, entre 1984 e 2005. O gênero masculino representou 82,9% e a média de idade foi 42 anos. Atividades agropecuárias caracterizaram 54,9% dos pacientes. Entre pacientes com a forma crônica, 87% eram tabagistas e 55,3% etilistas. Em 71 pacientes sem co-infecção por HIV/aids: a) houve recidiva da paracoccidioidomicose em 21 (29,6%); b) a forma crônica ou mista acometeu 77,5% dos pacientes, com predominância de comprometimento orofaríngeo (70,9%) e pulmonar (67,3%), além de lesões linfonodais (29,8%), laríngeas (27,3%) e cutâneas (16,4%); c) na forma aguda/subaguda, predominou o comprometimento linfonodal (81,3%), seguido por lesões cutâneas (43,8%), resultando doença grave em 62,5% e moderada em 37,5%. Cinco pacientes tinham co-infecção por HIV/aids, dos quais três tiveram a infecção fúngica disseminada associada a acentuada imunodepressão.Seventy-six paracoccidioidomycosis patients attended at the university hospital of Brasília from 1984 to 2005 were studied. 82.9% were male and the mean age was 42 years. 54.9% of the patients were engaged in farming activities. Among the patients with the chronic form, 87% were smokers and 55.3% consumed alcohol. Among 71 patients without HIV/AIDS coinfection: a) paracoccidioidomycosis was recurrent in 21 (29.6%); b) the chronic or mixed form affected 77.5% of patients, predominantly in the oropharynx (70.9%) and lungs (67.3%), with lymph node lesions in 29.8%, laryngeal lesions in 27.3% and cutaneous lesions in 16.4%; c) in the acute/subacute form, lymph node lesions predominated (81.3%), followed by cutaneous lesions in 43.8%, which resulted in severe disease in 62.5% and moderate disease in 37.5%. Five patients had HIV/AIDS coinfection and three of them presented disseminated fungal infection together with marked immunosuppression.

A taxa de detecção da hanseníase no Brasil aumentou nas duas últimas décadas do século XX, sendo que a reforma sanitária ocorreu no mesmo período. A taxa de detecção é função da incidência real de casos e da agilidade diagnóstica do sistema de saúde. Utilizou-se a cobertura vacinal por BCG como uma variável procuradora do acesso à atenção primária em saúde. Uma regressão log-normal foi ajustada à taxa de detecção de 1980 a 2006, com o tempo, tempo ao quadrado e da cobertura do BCG como variáveis independentes, sendo positivo o coeficiente de regressão desta última variável, sugerindo que o comportamento da taxa de detecção da hanseníase refletiu a melhora de acesso à atenção primária no período estudado. A tendência de aumento da taxa de detecção se reverte em 2003, indicando o início de uma nova fase no controle da hanseníase.Brazilian Hansen's disease detection rate rose during the 80s and 90s of the 20th century. The Brazilian health system reform happened during the same period. Detection rate is a function of the real incidence of cases and the diagnostic agility of the health system. Coverage of BCG immunization in infants was used as a proxy variable for primary healthcare coverage. A log-normal regression model of detection rate as a function of BCG coverage, time and time square was adjusted to data. The detection rate presents an upward trend throughout the period and with a downturn beginning in 2003. The model showed a statistically significant positive regression coefficient for BCG coverage, suggesting that detection rate behavior reflects the improvement of access to health care. The detection rate began a trend towards decline in 2003, indicating a new phase of Hansen's disease control.

FUNDAMENTOS: A hanseníase persiste como problema de saúde pública, e episódios de ENH são eventos agudos que ocorrem antes, durante e após PQT. Na última década, o uso da talidomida como agente imunomodulador foi expandido a outras doenças. OBJETIVOS: realizar revisão sistemática dos ensaios clínicos publicados sobre a eficácia e efeitos colaterais da talidomida no ENH. Descrever metodologia e resultados da triagem para recrutamento de ensaio clínico visando avaliar dose-resposta da talidomida seguida de desmame no ENH moderado e grave, realizado no Brasil. MÉTODOS: Analisaram-se ensaios publicados sobre talidomida no ENH. Foi delineado um ensaio clínico duplo-cego randomizado para avaliar dose de 100 thalid 300mg/dia de talidomida durante fase aguda de ENH, seguida de desmame da talidomida, thalid placebo. Para este ensaio clínico descreve-se metodologia e dados de recrutamento de pacientes, com ênfase na gravidade dos episódios de ENH. RESULTADOS: Os seis ensaios clínicos publicados nas décadas de 1960 e 1970 apontam para o benefício da talidomida no ENH, embora diferenças metodológicas dificultem a comparação. Na fase de recrutamento do ensaio brasileiro, dos 143 pacientes de ENH triados, 65% eram potencialmente elegíveis. A associação com neurite em 56,4% dos ENH moderados e graves exigiu co-intervenção com corticosteróide. CONCLUSÃO: O padrão de recrutamento dos pacientes evidenciou alta freqüência de neurite nos episódios de ENH. O esquema de talidomida isolada no ENH foi avaliado como infreqüente na prática clínica brasileira. O desafio atual é acumular evidências sobre a eficácia e efeitos colaterais da talidomida em associação com corticosteróides.BACKGROUND: Leprosy remains a public health problem. Episodes of erythema nodosum leprosum (ENL) are acute events that occur before, during and after polychemotherapy. In the last decade, the use of thalidomide as an immunomodulating agent was expanded to other diseases. OBJECTIVES: To perform a systematic review of published clinical trials on efficacy and side effects of thalidomide in ENL. To describe the methodology and screening results of recruiting for a clinical trial performed in Brazil, which aimed to assess the dose-response of thalidomide followed by tapering regimen in severe and moderate cases of ENL. METHODS: Published clinical trials on the use of thalidomide in ENL were analyzed. A randomized, double-blind clinical trial was designed to evaluate the doses of 100mg versus 300mg/day thalidomide during the acute stage of ENL, followed by thalidomide tapering regimen versus placebo. For this clinical trial, the methodology and data for enrollment of patients were described, with an emphasis on severity of ENL episodes. RESULTS: Six clinical trials published in the 1960's and 1970's indicated the benefits of thalidomide in ENL, although methodological differences made comparison difficult. In the enrollment stage of the Brazilian trial, 65% of patients were potentially eligible out of 143 ENL patients screened. The association with neuritis in 56.4% of moderate and severe cases of ENL required the co-intervention with steroids. CONCLUSION: The patients' enrollment pattern demonstrated high frequency of neuritis in ENL episodes. The treatment regimen with thalidomide in monotherapy for ENL was considered infrequent in the clinical practice in Brazil. The current challenge is to accumulate evidence about efficacy and side effects of thalidomide in combination with steroids.

A endemia hansênica apresenta-se, na virada do milênio, no limiar da sua eliminação como problema global de saúde pública. O Brasil é o único país da América Latina onde a doença não foi eliminada, tendo sido a meta de eliminação postergada para 2005. Neste artigo discute-se o declínio da prevalência após a introdução da poliquimioterapia (PQT) para o tratamento da hanseníase, não acompanhada pela redução da incidência no mesmo período. Os progressos na área de imunologia, biologia molecular e seqüenciamento genômico do M. leprae são apresentados enquanto perspectivas de pesquisa e de aplicação potencial para diagnóstico, prognóstico e vigilância na hanseníase. Apesar do êxito das atuais estratégias de controle tem-se observado com preocupação a redução do interesse e do apoio financeiro em pesquisa na hanseníase e na desestruturação dos serviços de saúde frente ao atual cenário de eliminação. A exclusão da hanseníase da lista de doenças prioritárias é prematura, representando um perigo concreto de não se eliminar a doença, mas a pesquisa em hanseníase. Fica evidente a necessidade de investir na produção de conhecimentos de áreas básica e aplicada que viabilizem uma maior compreensão dos mecanismos de transmissão da infecção, da efetividade dos métodos de prevenção e controle, serão essenciais na "erradicação" da infecção pelo M. leprae.At the beginning of the millennium the elimination of leprosy as a public health problem was considered an attainable goal worldwide. Brazil is the only Latin American country where leprosy is still endemic and the elimination goal has been postponed to 2005. In this review, we discuss the currently declining prevalence after the implementation of multi-drug therapy (MDT), without the reduction in incidence in the same period. The progress in the fields of immunology, molecular biology and the recent accomplishment of M. leprae genomic sequence indicate the new tools potentially applicable to leprosy diagnosis, prognosis and surveillance. Despite the success of the current public health strategy there is a global concern about the lack of interest and financial support for leprosy research, for the maintenance and improvement of field expertise in public health. The exclusion of leprosy among public health priorities was premature and represents a real threat of not eliminating leprosy, but leprosy research. It is necessary to generate knowledge on basic and applied research for understanding the mechanism of transmission of the infection, and to test new preventive and therapeutic tools in order to achieve the "eradication" of the M. leprae infection. Maintenance and field expertise are essential for leprosy surveillance during and after its elimination.

A hanseníase, cujo agente etiológico Mycobacterium Ieprae, é doença de amplo espectro clínico e imunopatológico. Suas apresentações clínicas estão correlacionadas com padrões imunológicos distintos, variando de uma vigorosa resposta imune mediada por células ao M. Ieprae, com padrão Th1 no pólo tuberculóide, a uma ausência de resposta celular específica aos antígenos do M. Ieprae no pólo lepromatoso, com predomínio da resposta Th2 e exacerbação da resposta humoral. É provável que a suscetibilidade ao M. Ieprae é determinada por diferentes genes polimórficos. Estudos adicionais são necessários para esclarecer os mecanismos das interações complexas entre as citocinas e a participação da diversidade fenotípica da rede de células que contribuem para a defesa do hospedeiro. O entendimento de tais mecanismos poderá oferecer novas abordagens para identificar agonistas e/ou antagonistas para os efeitos pró- ou anti-inflamatórios e em quais circunstâncias sua utilização seria apropriada para intervenções imunológicas e/ou imunoterapeuticas.

Social 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.We 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).At 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.

A gonorréia é uma infecção bacteriana freqüente, causada pela Neisseria gonorrhoeae, um diplococo Gram-negativo de transmissão quase que exclusiva através de contato sexual ou perinatal. Primariamente afeta membranas mucosas do trato genital inferior, e mais raramente, as mucosas do reto, orofaringe e conjuntiva. A infecção genital ascendente na mulher leva a uma complicação séria, a salpingite aguda, uma das principais causas de infertilidade feminina. A partir dos anos 90, deu-se início a um novo tempo no que se refere a descobertas sobre a patogenia da gonorréia e seu agente etiológico. O controle da gonorréia tem sido difícil na maioria das populações, e essa permanece um exemplo da influência que os fatores sociais, comportamentais e demográficos exercem na epidemiologia de uma doença infecciosa. O manejo da gonorréia e de outras doenças sexualmente transmissíveis requer tanto o tratamento do paciente e de seu parceiro sexual como medidas de saúde pública para interromper a transmissão da infecção e evitar complicações a longo prazo.Gonorrhea is a common bacterial infection caused by Neisseria gonorrhoeae, a Gram-negative diplococcus that is transmitted almost exclusively by sexual contact or perinatally. It primarily affects the mucous membranes of the lower genital tract and less frequently those of the rectum, oropharynx, and conjunctivae. Ascending genital infection in women leads to the predominant complication, acute salpingitis, one of the most common causes of female infertility in the world. Since the 1990s, a remarkable surge of information ensued regarding the pathogenesis of gonorrhea and its agent. Gonorrohea has proven difficult to control in most populations and remains a prime example of the influence that social, behavioral, and demographic factors can have on the epidemiology of an infectious disease. The management of gonorrhea and other sexually transmitted infections requires both treatment of the patient as an individual and of his or her sexual partner(s) as a public health measure to interrupt the onward spread of infection and prevent long-term complications.

BACKGROUND: New 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 FINDINGS: Based 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/SIGNIFICANCE: Traditional 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.

FUNDAMENTOS: A hanseníase permanece sério problema de saúde pública mundial. O conhecimento das características epidemiológicas da doença é importante ferramenta para o controle da endemia. OBJETIVO: Descrever as características clínicas e epidemiológicas dos pacientes diagnosticados com hanseníase no ano de 2004 em um centro de referência da Região Nordeste do Brasil. MÉTODO: Foram avaliados prontuários de pacientes que deram entrada no registro ativo do Centro de Dermatologia Dona Libânia, em Fortaleza, Ceará, no período de janeiro a dezembro de 2004. RESULTADOS: dos 967 casos que deram entrada nesse Centro naquele ano, 909 foram casos novos. Cerca de 7,7% eram pacientes entre zero e 14 anos de idade, e a distribuição por gênero foi de 483 (49,95%) homens e 484 (50,05%) mulheres. A maioria apresentava a forma clínica dimorfa (54,6%), sendo 82,2% dos pacientes provenientes de Fortaleza, CE. Foi realizada a avaliação do grau de incapacidades no diagnóstico em 94,2% dos pacientes, com 21,7% apresentando grau diferente de zero no diagnóstico. CONCLUSÃO: Com base nos resultados obtidos, constatou-se a presença de elevado percentual (7,7%) de casos detectados em menores de 15 anos, associado a baixo percentual (5,8%) de pacientes diagnosticados na forma indeterminada e elevado percentual (21,7%) de casos com incapacidade ao diagnóstico.BACKGROUND: Leprosy continues to represent a serious public health problem worldwide. Knowledge of epidemiological characteristics of the disease is an important tool for the endemy control. OBJECTIVES: To describe the clinical and epidemiological characteristics of patients diagnosed with leprosy during 2004, in a Reference Center in the Northeast of Brazil. METHODS: We analyzed the records referring to patients who entered de active register of the Center of Dermatology Dona Libânia, in Fortaleza, Ceará, from January to december 2004. RESULTS: Out of 967 cases that entered this Center in this year, 909 were new detected cases. About 7,7% were between zero e 14 years old, and distribution per gender was of 483(49,95%) men and 484(50,05%) women. Most of them presented the borderline clinical form (54,6%), and 82,2% resided in the city of Fortaleza/CE. Measurement of disabilities degree in diagnosis was made in 94,2% of the patients, and 21,7% of total showed a degree different from zero. CONCLUSION: Based in the results, we noted a high percentual (7,7%) of patients under fifteen years old, associated with low percentual of indeterminate forms and a high percentual of cases with disabilities at diagnosis. These factors are expressive enough to make the authorities consider the difficulties to reach the goal of eliminating leprosy by the end of 2005, and the necessity of new approaches and strategies to control leprosy endemy.