Search

Introduction: The paediatric population represents a quarter of the world's population, and like adult patients, they have also suffered immeasurably from the SARS-CoV-2 pandemic. Immunisation is an effective strategy for reducing the number of COVID-19 cases. With the advancements in vaccination for younger age groups, parents or guardians have raised doubts and questions about adverse effects and the number of doses required. Therefore, systematic reviews focusing on this population are needed to consolidate evidence that can help in decision-making and clinical practice. This protocol aims to assess the safety of COVID-19 vaccines in paediatric patients and evaluate the correlation between the number of vaccine doses and side effects., Methods and Analysis: We will search the PubMed, ClinicalTrials.gov, Web of Science, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature, Scopus and Cochrane databases for randomised and quasi-randomised clinical trials that list the adverse effects of the COVID-19 vaccine and assess its correlation with the number of doses, without any language restrictions. Two reviewers will select the studies according to the inclusion and exclusion criteria, extract data and asses for risk of bias using the Cochrane risk-of-bias tool. The Review Software Manager (RevMan V.5.4.1) will be used to synthesise the data. We will use the Working Group's Grading of Recommendations Assessment, Development and Evaluations to grade the strength of the evidence of the results., Ethics and Dissemination: Formal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication., Prospero Registration Number: CRD42023390077., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Summarize the evidence on drug therapies for obstructive sleep apnea., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis., Results: 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]., Conclusion: The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed., Prospero Registration Number: CRD42022362639., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Obstructive sleep apnoea (OSA) is a common disorder that can affect the quality of life and increase the risk for psychiatric, neurological and cardiometabolic diseases. Despite the significant burden, it poses on health and well-being, there is a lack of evidence regarding the use of drug therapies in these patients. This work aims to evaluate the efficacy and safety of pharmacological treatment alternatives for patients with OSA., Methods and Analysis: Databases, including PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Register of Controlled Trials and ClinicalTrials.gov, will be used for the search. A search strategy was developed to retrieve clinical trials that have evaluated polysomnographic primary outcome (Apnoea-Hypopnoea index) and secondary outcomes (eg, daytime sleepiness, adverse events) of any drug therapy used for OSA. No date or language restrictions will be applied. Two authors will independently select the studies meeting the inclusion criteria by screening the title, abstract and full text. Data will be extracted, and the risk of bias will be evaluated using the Cochrane Risk of Bias Tool. Review Manager V.5.4.1 will be used for data synthesis. The Grading of Recommendation Assessment, Development and Evaluation will be used to assess the strength of the evidence., Ethics and Dissemination: As a review of published data, it is not necessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal., Prospero Registration Number: CRD42022362639., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT., Methodology: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC)., Results: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs., Conclusion: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 de Araujo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 ( NAT2 ) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states ( p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast ( p = 0.0396). The Southern region was significantly different from all other regions ( p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lopes, Teixeira, Cabello, Nery, Sales, Nahn J. R., Moreira, Stahlke, Possuelo, Rossetti, Rabahi, Silva, Leme, Woods, Nobre, Oliveira, Narahashi, Cavalcanti, Suffys, Boukouvala, Gallo and Santos.)

Introduction: Breast cancer survivors (BCSs) experience more severe symptoms of genitourinary syndrome of menopause (GSM) than healthy postmenopausal women. As hormonal therapy with oestrogen should be avoided in BCSs, finding an effective and safe therapy to address vaginal symptoms and sexual dysfunction is urgently needed. Physical methods may be promising alternatives for the specificities of this group of women. This review aims to evaluate the efficacy and safety of physical methods (laser and radiofrequency) for treating GSM in BCSs., Methods and Analysis: The PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases will be searched. A search strategy was developed to retrieve clinical trials that evaluate the efficacy and safety of any physical method (laser or radiofrequency) used for GSM in BCSs. No date or language restrictions will be imposed. Two authors will independently select studies by title, abstract and full text to meet the inclusion criteria. Data will be extracted, and the risk of bias will be evaluated using the Cochrane risk-of-bias tool (RoB 2). Review Manager 5.4.1 will be used for data synthesis. The Grading of Recommendations, Assessment, Development and Evaluation will be used to assess the strength of the evidence., Ethics and Dissemination: This study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal., Prospero Registration Number: CRD42023387680., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Collared and white-lipped peccaries are sympatric and are distributed in most of South America and in the humid tropical forests of Mexico and Central America. Historically, these species have been used as a source of protein by traditional and/or indigenous human communities, but currently they have been used for legal consumption in different countries. Thus, there has been greater interaction between these wild species and domestic animals and humans, enabling microbial interactions between different niches. The present study presents a systematic review of the literature on the microbial community of collared peccaries and white-lipped peccaries distributed throughout the world, focusing on experimental studies related to the detection of microorganisms as well as the prevalence of the animal species and its characterization of the studied population, in situ or ex situ. Seventy-two studies were selected, mainly in South American countries, related to different species of microorganisms isolated or serologically detected (viruses, bacteria, fungi, and parasites), either as microbiota, pathogens or commensals, many of which are of zoonotic interest, such as Leptospira, Toxoplasma, Brucella, among others. Therefore, these wild mammals are characterized as sentinel agents of anthropic action and require the implementation of studies in relation to their contribution to the spread of microorganisms, being a potential source of amplification and transmission of pathogens., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Leprosy is a debilitating, infectious, systemic or localized dermato-neurological disease caused by Mycobacterium lepra. In Brazil, the magnitude and high disabling power keep the disease as a public health problem. Skin spotting and numbness are pathognomonic signs and symptoms in leprosy. The Instituto Brasileiro de Geografia e Estatística (IBGE) 2019 National Health Survey (PNS-2019) considered the following question as a proxy to estimate its magnitude in the country. "Do you have a spot with numbness or part of the skin with numbness?". In Brazil, 1,921,289 adults reported having a patch or part of the skin with numbness, with no regional differences. As for the age group, the older, the higher the prevalence, for example, between 18 to 29 years old (235,445) and 30 to 39 years old (236,485), 0.7% had the condition, between 40 to 59 years old (827,887), 1.5% and among the elderly, 1.8% (621,472). Being able to estimate, in population-based surveys, with statistical representativeness, a reported morbidity such as leprosy is essential to support the formulation of public policies, notably those related to primary health care actions. In this way, the IBGE fulfills its constitutional role of portraying the reality of the Brazilian population and today it is the main external evaluator of the Unified Health System (SUS) and of public policies developed by the federal level.

Introduction: Endoscopic sinus surgery (ESS) is a current procedure for treating patients with chronic rhinosinusitis (CRS). Image-guided surgery (IGS) for ESS may help reduce complications and improve precision. However, it is uncertain in which cases IGS is beneficial. This work aims to compare ESS with and without IGS in patients with CRS., Methods and Analysis: PubMed, Embase, Scopus, Web of Science, Scielo, Cochrane Central Register of Controlled Trials, CINAHL, LILACS and Clinicaltrials.gov will be searched for reported clinical trials comparing the quality of life and perioperative outcomes of ESS with and without navigation. The search is planned for 20 April 2022. Three independent authors will select eligible articles and extract their data. The risk of bias will be assessed using the Cochrane Handbook for Systematic Reviews of Interventions. The Grading of Recommendation Assessment, Development and Evaluation method will evaluate the strength of the evidence. Data synthesis will be performed using the Review Manager software V.5.4.1. To assess heterogeneity, I 2 statistics will be computed. Additionally, meta-analysis will be performed if the included studies are sufficiently homogenous., Ethics and Dissemination: This study reviews published data, and thus it is not necessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal., Prospero Registration Number: CRD42020214791., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas., Methods and Findings: A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels., Conclusions: Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination., Competing Interests: The authors have declared that no competing interests exist.

Background: Leprosy causes a range of symptoms, and most diagnoses are established based on the clinical picture. Therefore, false negative and positive diagnoses are relatively common. We analyzed the spatial pattern of leprosy misdiagnosis and associated factors in Brazil., Method: Exploratory analyses of Kernel density of the new case detection rate (NCDR) and proportion of misdiagnosis in Brazil, 2003-2017. Factors associated with misdiagnosis were identified by logistic regression at the 5% significance level., Result: A total of 574,181 new leprosy cases were recorded in Brazil within the study period, of which 7,477 (1.3%) were misdiagnoses. No spatial correlation was observed between the proportion of misdiagnoses and the NCDR. The likelihood of misdiagnosis was elevated for females [OR: 1.58 (1.51-1.66)], children [OR: 1.49 (1.36-1.64)]; paucibacillary [OR: 1.08 (1.02-1.13)], indeterminate clinical forms [OR: 2.37 (2.15-2.62)], for cases diagnosed in the frame of mass screenings [OR: 3.36 (3.09- 3.73)] and contact examination [OR: 2.30 (2.13-2.49)] and for cases with affected nerves but no skin lesions [OR: 2.47 (2.19-2.77)] when compared with those presenting both skin lesion and affected nerves., Conclusion: Misdiagnosis of leprosy is not correlated with the endemicity level in Brazil but rather with personal, diagnosis-related and disease characteristics., (Copyright © 2020. Published by Elsevier B.V.)

The article aimed to describe epidemiological indicators and characteristics of new cases of leprosy in elderly Brazilians in 2016-2018, compared to other age groups. A descriptive cross-sectional cohort study was conducted with data from the Information System on Diseases of Notification (SINAN). New leprosy cases were categorized by age groups: 60 or more, 40-59, 15-39, and 15 years of age. Pearson's chi-square test was used to verify differences between groups. A total of 81,205 new leprosy cases were reported in Brazil. Of these, 24.1% were elderly, 37.7% from 40-59 years, 31.9% from 15-39 years, and 6.3% in individuals under 15 years of age. The elderly showed higher proportions (p < 0.001) of cases in males (60.1%), with multibacillary classification (81.3%), and with physical disability grade 2 (PDG2) (11.4%) when compared to the other groups. However, the proportion of new cases detected in the elderly based on contact testing (4.9%) was the lowest among all the age brackets (p < 0.001). The mean detection rate and rate of new cases with PDG2 at diagnosis were higher among the elderly (25.1/100,000 and 28.6/million inhabitants, respectively) compared to other age groups in Brazil as a whole and in the regions and states. Important differences were seen in the epidemiological and clinical profile of leprosy in the elderly compared to other age brackets, especially higher proportions of multibacillary cases, new cases with PDG2, and low detection by contact testing. The findings highlighted the need for leprosy control in this age group, aimed at contributing to interruption of transmission of the disease.

Objective: To describe the temporal trends of leprosy indicators among the elderly in Brazil in 2001 - 2018., Methods: This was an ecological time-series study of new leprosy cases in the elderly reported to the Notifiable Diseases Information System. Prais-Winsten generalized linear regression was used to estimate temporal variations., Results: There were 687 317 new leprosy cases in Brazil from 2001 - 2018, of which 129 214 (18.8%) were among elderly people. Overall detection rates in the elderly and of new cases with grade-2 disability showed a falling trend, with an annual percent change of -4.6% (95%CI = -5.1 to -4.0) and -3.9% (95%CI = -4.6 to -3.2). New case and new multibacillary case proportions showed an increasing trend, with an annual percent change of 2.9% (95%CI = 2.6 to 3.3) and 1.4% (95%CI = 1.0 to 1.7), respectively. Detection rates for new leprosy cases in elderly people in Brazil are decreasing, but the proportion of new cases and multibacillary cases are trending upwards., Conclusions: New cases are shifting to older age groups, and demographic transition and immunosenescence are an influence. Inadequate reduction of grade-2 disability indicates a high risk of physical disability persists. Improved contact tracing and more effective action are needed in this age group., Competing Interests: Conflicts of interests. None declared.

Objective: To analyze institutional/programmatic vulnerability of health services in the development of health care actions for people affected by leprosy and contact surveillance., Methods: This was a cross-sectional study conducted in 2017 based on primary data from a sample of leprosy cases notified between 2001-2014 with overlapping cases in household social networks (HSN) in municipalities in the states of Bahia, Piauí and Rondônia, Brazil., Results: A total of 233 leprosy cases were analyzed, 154 (66.1%) belonged to HSN with 3 or more leprosy cases. In 53.2% of cases, 2 or more generations were affected, this being an outcome associated with absence of dermato-neurological examination (prevalence ratio 1.32; confidence interval [95%CI 1.10;1.59]; p-value=0.004)., Conclusion: Operational failures in the surveillance of leprosy contacts in areas of high endemicity reinforce the character of institutional/programmatic vulnerability in HSN contexts with more than one case of leprosy in the three states analyzed.

Background: Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy., Methodology/findings: We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL., Conclusions: Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions., Competing Interests: The authors have declared that no competing interests exist.

Background: Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control., Methods: A national databank of cases reported in Brazil (2001-2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads., Results: A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65-69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33-2.38; OR = 1.99, CI95% = 1.96-2.02, respectively). Bacillary load was higher in male and in patients aged 20-39 and 40-59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country., Conclusion: Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.

Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. Challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. Although phenolic glycolipid (PGL)-I has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. The aim of this study was to evaluate the effectiveness of two related reagents, LID-1 and LID-NDO, for the detection of M. leprae infection. Sera from 98 leprosy patients, 365 household contacts (HHC) and 98 endemic controls from Rio Grande do Norte, Brazil, were evaluated. A subgroup of the HHC living in a hyperendemic area was followed for 7-10 years. Antigen-specific antibody responses were highest in multibacillary (MB) at the lepromatous pole (LL/BL) and lowest in paucibacillary (PB) at the tuberculoid pole (TT/BT). A positive correlation for both anti-LID-1 and anti-LID-NDO antibodies was found with bacterial burden (LID-1, r = 0.84, p<0.001; LID-NDO, r = 0.82, p<0.001), with higher sensitivity than bacilloscopy. According to Receiver Operating Curve, LID-1 and LID-NDO performed similarly. The sensitivity for MB cases was 89% for LID-1 and 95% for LID-NDO; the specificity was 96% for LID-1 and 88% for LID-NDO. Of the 332 HHC that were followed, 12 (3.6%) were diagnosed with leprosy in a median time of 31 (3-79) months after recruitment. A linear generalized model using LID-1 or LID-NDO as a predictor estimated that 8.3% and 10.4% of the HHC would become a leprosy case, respectively. Together, our findings support a role for the LID-1 and LID-NDO antigens in diagnosing MB leprosy and identifying people at greater risk of developing clinical disease. These assays have the potential to improve the diagnostic capacity at local health centers and aid development of strategies for the eventual control and elimination of leprosy from endemic areas., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following interests: IDRI (SGR and MSD) has provided antigen to companies for fabrication of rapid testes. All other authors have declared that they have no conflict of interest.

Introduction: Leprosy is a public health problem in Brazil where 31,044 new cases were detected in 2013. Rio Grande do Norte is a small Brazilian state with a rate of leprosy lower than other areas in the same region, for unknown reasons., Objectives: We present here a review based on the analysis of a database of registered leprosy cases in Rio Grande do Norte state, comparing leprosy's geographic distribution among municipalities with local socio-economic and public health indicators and with historical documents about human migration in this Brazilian region., Results: The current distribution of leprosy in Rio Grande do Norte did not show correlation with socio-economic or public health indicators at the municipal level, but it appears related to economically emerging municipalities 100 years ago, with spread facilitated by railroads and train stations. Drought-related migratory movements which occurred from this state to leprosy endemic areas within the same period may be involved in the introduction of leprosy and with its present distribution within Rio Grande do Norte., Conclusions: Leprosy may disseminate slowly, over many decades in certain circumstances, such as in small cities with few cases. This is a very unusual situation currently and a unique opportunity for epidemiologic studies of leprosy as an emerging disease.

Background: Leprosy morbidity is increased by 2 pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL)., Methods: To discover host factors related to immune reactions, global transcriptional profiles of peripheral blood mononuclear cells were compared between 11 RR, 11 ENL, and 19 matched control patients, with confirmation by quantitative polymerase chain reaction. Encoded proteins were investigated in skin biopsy specimens by means of immunohistochemistry., Results: There were 275 genes differentially expressed in RR and 517 differentially expressed in ENL on the microarray. Pathway analysis showed immunity-related pathways represented in RR and ENL transcriptional profiles, with the "complement and coagulation" pathway common to both. Interferon γ was identified as a significant upstream regulator of the expression changes for RR and ENL. Immunohistochemical staining of skin lesions showed increased C1q in both RR and ENL., Conclusions: These data suggest a previously underrecognized role for complement in the pathogenesis of both RR and ENL, and we propose new hypotheses for reaction pathogenesis., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The present study aimed at characterizing the oil extracted from Bertholletia excelsa H.B.K. almond, a native species from the Amazon region. Analytical methods used for oils and fats were employed through pharmacopoeia assays, AOCS (American Oil Chemists Society) standard methods as well as those recommended by ANVISA (National Health Surveillance Agency) such as acidity, peroxide value, saponification index, iodine value and refractive index, pH and relative density, and also thermoanalytical analyses (thermogravimetry, differential thermogravimetry and differential thermal analysis) as well as chromatographic analysis (gas chromatography). The characterization assessments of B. excelsa oil showed results indicating that the oil contains polyunsaturated fatty acids in large proportion. The termoanalytical tests indicated that B.excelsa oil showed thermal stability up to 220 °C, These results showed that the oil extracted from B. excelsa has acceptable characteristics and is of good quality.

Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. To determine whether polymorphisms at the ERBB2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from the state of Pará (PA). All three tag-SNPs were associated with leprosy per se [best SNP rs2517959 odds ratio (OR) = 2.22; 95% confidence interval (CI) 1.37-3.59; p = 0.001]. Lepromatous (LL) (OR = 3.25; 95% CI 1.37-7.70; p = 0.007) and tuberculoid (TT) (OR = 1.79; 95% CI 1.04-3.05; p = 0.034) leprosy both contributed to the association, which is consistent with the previous linkage to chromosome 17q11-q21 in the population from PA and supports the functional role of ErbB2 in disease pathogenesis. To attempt to replicate these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808) were genotyped in a population-based sample of 570 leprosy cases and 370 controls from the state of Rio Grande do Norte (RN) and the results were analysed using logistic regression analysis. However, none of the associations were replicated in the RN sample, whether analysed for leprosy per se, LL leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains unclear.

Objectives: The objective was to characterise and identify potential risk factors for intolerance to multi-drug leprosy therapy (MDT) which prompted a medication change in a leprosy referral centre in northeastern Brazil., Design: A retrospective chart review of leprosy patients treated at a state referral centre for leprosy in Natal, Rio Grande do Norte, Brazil was completed. Chart review focus was on adverse effects necessitating modification of MDT regimen., Results: Six hundred and twelve records were reviewed with detection of 91 (14.8%) adverse effects with associated change in MDT regimen. The most common recorded causes of medication intolerance were anemia (8.7%), headache (4.2%), cyanosis (1.8%), and gastrointestinal symptoms (1-6%). Both female gender (OR = 2.63) and age less than 42 years old (OR = 2.7) remained risk factors for MDT intolerance in a multivariate model including gender, age, and WHO regimen type. With intolerance due to anemia as the outcome, female gender (OR = 2.36) and age less than 42 years (OR = 1.86) were associated., Conclusions: In this study, female gender and younger age were associated with greater risk of medication intolerance and medication intolerance related to anemia. These findings have important operational implications for drug intolerance monitoring during therapy for leprosy.

Hansen's disease (leprosy) remains an important health problem in Brazil, where 34,894 new cases were diagnosed in 2010, corresponding to 15.3% of the world's new cases detected in that year. The purpose of this study was to use home visits as a tool for surveillance of Hansen's disease in a hyperendemic area in Brazil. A total of 258 residences were visited with 719 individuals examined. Of these, 82 individuals had had a previous history of Hansen's disease, 209 were their household contacts and 428 lived in neighboring residences. Fifteen new Hansen's disease cases were confirmed, yielding a detection rate of 2.0% of people examined. There was no difference in the detection rate between household and neighbor contacts (p = 0.615). The two groups had the same background in relation to education (p = 0.510), household income (p = 0.582), and the number of people living in the residence (p = 0.188). Spatial analysis showed clustering of newly diagnosed cases and association with residential coordinates of previously diagnosed multibacillary cases. Active case finding is an important tool for Hansen's disease control in hyperendemic areas, enabling earlier diagnosis, treatment, decrease in disability from Hansen's disease and potentially less spread of Mycobacterium leprae.

There are diverse skin manifestations of both leprosy and syphilis. These diseases can appear similar to many other dermatologic conditions as well as to systemic diseases with dermatologic signs. Nodular syphilis is an uncommon type of secondary syphilis. We present here a person from a leprosy-endemic area with diffuse nodular skin lesions of secondary syphilis who was initially suspected of having lepromatous leprosy.

Applied Spatial Statistics used in conjunction with geographic information systems (GIS) provide an efficient tool for the surveillance of diseases. Here, using these tools we analyzed the spatial distribution of Hansen's disease in an endemic area in Brazil. A sample of 808 selected from a universe of 1,293 cases was geocoded in Mossoró, Rio Grande do Norte, Brazil. Hansen's disease cases were not distributed randomly within the neighborhoods, with higher detection rates found in more populated districts. Cluster analysis identified two areas of high risk, one with a relative risk of 5.9 (P = 0.001) and the other 6.5 (P = 0.001). A significant relationship between the geographic distribution of disease and the social economic variables indicative of poverty was observed. Our study shows that the combination of GIS and spatial analysis can identify clustering of transmissible disease, such as Hansen's disease, pointing to areas where intervention efforts can be targeted to control disease.

There is a high incidence of leprosy in the municipality of Mossor6, Rio Grande do Norte state, where the detection coefficient has risen from 2.78/10,000 population in 1998 to 5.14 in 2004. While cases have been registered throughout the urban area, the disease is concentrated in select neighbourhoods. This study was undertaken using Geographical Information System (GIS) with the objective of defining low-cost, effective strategies to control leprosy. The land registry map of the city, Ikonos satellite images and the SINAN (National Morbidity Notification Information System) database were used as the cartographical basis for the study. The sample for the leprosy mapping was drawn from the 358 new cases of the disease diagnosed in the municipality between 1998 and 2002. The houses of 281 patients were located (78.5% of the total) and their addresses geo-referenced using a GPS handheld device. Subsequently, geographical analysis was carried out using ArcView 9.0 software showing predominant concentration of cases in the neighbourhoods of Barrocas, Santo Antônio, Bom Jardim and Paredões. This mapping served as the basis for four active case finding campaigns conducted in the most highly concentrated areas between March and September of 2005. Campaigns guided by spatial analysis led to the diagnosis of 104 new cases of the disease (50% of the total number of new cases detected in the municipality in 2005). The use of GIS in leprosy diagnosis has shown to be extremely effective, providing a clear visual understanding of the distribution of the disease in the municipality, which results in targeted interventions and important cost reductions in leprosy control activities.