Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues

What are the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic

Indicação de cardioversor desfibrilador implantável após morte súbita por fibrilação ventricular em pré-operatório de catarata: relato de caso

Introdução: A fibrilação ventricular (FV) é um evento grave e fatal na maioria dos pacientes. Neste relato, descrevemos um caso de parada cardíaca durante pré-operatório de cirurgia de catarata em um paciente, com indicação subsequente de cardioversor desfibrilador implantável (CDI) para prevenção secundária de morte súbita cardíaca (MSC). Trata-se de um homem, 72 anos de idade, admitido para cirurgia de catarata com cardiomiopatia dilatada de etiologia desconhecida (DCM). O paciente apresentava hipertensão arterial, diabetes mellitus, hipotireoidismo e dislipidemia. Durante o período pré-operatório foi administrado, para realização de facectomia, colírio de tropicamida, fenilefrina e proximetacaína e, na sequência, o paciente desenvolveu FV e parada cardíaca. A parada foi revertida após 13 minutos de manobras de reanimação. O paciente foi encaminhado à Unidade de Estimulação Cardíaca de nossa instituição para avaliação. A ressonância magnética cardíaca não mostrou fibrose miocárdica e a coronariografia foi normal. Conclusão: Descrevemos um caso de FV intra-hospitalar, que acometeu paciente com DCM sem substrato anatômico arritmogênico. O mecanismo mais provável da arritmia ventricular foi hiperautomatismo induzido por estresse pré-operatório. O implante de CDI foi indicado para prevenção secundária de MSC, e afastadas causas reversíveis ou controláveis.Introduction: Ventricular fibrillation is a potentially fatal event. We describe herein a case of cardiac arrest during preoperative of cataract surgery in a patient, referred to implantable cardioverter defibrillator (ICD) for secondary prevention of sudden cardiac death (SCD) afterwards. A 72-year-old man was admitted for cataract surgery with dilated cardiomyopathy of unknown etiology (DCM). The patient presented hypertension, diabetes mellitus, hypothyroidism and dyslipidemia. Preoperative medication consisted of eyedrops of phenylephyne, proximetacaine and tropicamide. The patient developed ventricular fibrillation (VF) and cardiac arrest right after the administration of the eyedrops. which was reverted after 13 minutes of reanimate maneuvers. The patient was referred to the Cardiac Pacing Unit of our institution for evaluation. Cardiac MRI showed no myocardial fibrosis and coronary angiography was normal. Conclusion: We describe a case of in-hospital VF, in a patient without arrhythmogenic anatomical substrate. The most likely mechanism of ventricular arrhythmia was hyper automatism induced by preoperative stress. The ICD was implanted for secondary prevention SCD, considering controllable or reversible causes were ruled out

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Tattoos as indicators of transfusion-transmitted diseases in Brazil : a matched hospital-based cross-sectional study

Background. Evidence to date remains equivocal regarding the association between tattooing and various transfusion-transmitted diseases (TTDs).Objectives. To determine whether there is an association between the presence or specific characteristics of ornamental tattoos and one or more of the following infections: HBV, HCV, HIV, Chagas' disease, and syphilis.Methods. Type of study: Hospital-based cross-sectional pair-matched study. Setting: Teaching hospital and blood bank in a Brazilian town. Study population: Adults 18 years of age and over who were admitted to the hospital, attended the outpatient clinic or volunteered to donate blood. Exclusion criteria: medical conditions causing transitory or permanent intellectual impairment; physical impossibility to provide blood specimens or information. Exposure of interest: Having at least one permanent ornamental tattoo. Covariates: Several socio-demographic and behavioral characteristics. Outcomes of interest: Presence of serological markers for one or more of the following infections: HIV, HBV, HCV, Chagas' disease and syphilis. Matching variables: Individuals with tattoos (exposed group) were pair-matched to individuals without tattoos (unexposed group) on age, sex, and main clinical complaint. Assessment of the exposure: Interview and inspection of the tattoo(s). Assessment of the outcomes: Positive or negative laboratory findings as follows for each infection: HBV - HBsAg and anti-HBc (ELISA); HCV - anti-HCV (ELISA); HIV - anti-HIV (ELISA); Chagas' disease - anti-Trypanosoma cruzi (IFA, ELISA and/or IHA); syphilis - VDRL.Results. 345 subjects were included in the study, 182 with tattoos and 163 without tattoos. Having a tattoo was associated with HCV (adjusted OR: 6.41; 95% CI: 1.29, 31.84), and with having at least one positive test for any TTD (adjusted OR: 2.05; 95% CI: 1.11, 3.81). Among the subjects with tattoos associations were found between an increasing number of tattoos and HBV infection (adjusted OR: 2.04 (95% CI: 1.80, 9.97) for two tattoos and 3.48 (95% CI: 1.41, 8.58) for three or more tattoos), having a nonprofessional tattoo and testing positive for at least one TTD (adjusted OR: 3.25; 95% CI: 1.39, 7.59), and having three or more tattoos and testing positive for at least one TTD (adjusted OR: 2.98; 1.03, 8.64).Conclusion. The presence of tattoo(s) may be useful in certain settings for the screening of blood donors, mostly because tattoos are associated with good indicators of TTD such as intravenous drug use

Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues

In May 2005, the TB Vaccine Initiative of the World Health Organization (WHO) Initiative for Vaccine Research convened a working meeting of regulators, investigators, and clinicians from developing and developed countries involved in tuberculosis (TB) vaccine regulation and research (see Text S1 for a list of participants). The purpose of the meeting was to specifically discuss the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic. A particular focus of this meeting was a discussion among representatives of regulatory authorities from the Developing Countries Vaccine Regulators Network (DCVRN) with those of the United Kingdom and the United States about the important challenges that each regulatory agency will need to address if effective new TB vaccines are to be registered in their countries. The DCVRN is a new WHO initiative establishing a network of vaccine regulators from nine countries: Brazil, China, Cuba, the Republic of South Korea, India, Indonesia, the Russian Federation, South Africa, and Thailand. It provides a forum for discussion, advancement of knowledge, and exposure to policies and procedures pertaining to evaluation of clinical trial proposals and clinical trial data. In this article we describe key vaccine and regulatory issues arising during the meeting. We propose innovative recommendations that may be used to make important decisions for proceeding into various stages of clinical trials and for the final registration of new TB vaccines. We hope that this article will be particularly valuable to regulatory authorities of developing countries