Immunity certification for COVID-19: ethical considerations.

Restrictive measures imposed because of the coronavirus disease 2019 (COVID-19) pandemic have resulted in severe social, economic and health effects. Some countries have considered the use of immunity certification as a strategy to relax these measures for people who have recovered from the infection by issuing these individuals a document, commonly called an immunity passport. This document certifies them as having protective immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19. The World Health Organization has advised against the implementation of immunity certification at present because of uncertainty about whether long-term immunity truly exists for those who have recovered from COVID-19 and concerns over the reliability of the proposed serological test method for determining immunity. Immunity certification can only be considered if scientific thresholds for assuring immunity are met, whether based on antibodies or other criteria. However, even if immunity certification became well supported by science, it has many ethical issues in terms of different restrictions on individual liberties and its implementation process. We examine the main considerations for the ethical acceptability of immunity certification to exempt individuals from restrictive measures during the COVID-19 pandemic. As well as needing to meet robust scientific criteria, the ethical acceptability of immunity certification depends on its uses and policy objectives and the measures in place to reduce potential harms, and prevent disproportionate burdens on non-certified individuals and violation of individual liberties and rights.

Les restrictions imposées dans le cadre de la lutte contre la pandémie de maladie à coronavirus 2019 (COVID-19) ont eu de lourdes conséquences économiques, sociales et sanitaires. Certains pays ont envisagé la mise en place d'une stratégie visant à alléger ces restrictions pour les individus guéris en leur octroyant un document communément appelé «passeport d'immunité¼. Ce document atteste qu'ils ont développé une immunité protectrice contre le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2), le virus à l'origine de la COVID-19. L'Organisation mondiale de la Santé a déconseillé l'usage du certificat d'immunité pour l'instant, car l'incertitude demeure quant à l'existence réelle d'une immunité à long terme pour ceux qui se sont remis de la COVID-19. En outre, la fiabilité des tests sérologiques censés déterminer si l'individu est immunisé n'est pas avérée. Un tel certificat ne peut être instauré que si les seuils scientifiques en matière d'immunité sont respectés, qu'ils soient fondés sur les anticorps ou sur d'autres critères. Néanmoins, même si le certificat d'immunité est désormais bien accepté par la science, il s'accompagne de nombreuses questions d'ordre éthique en ce qui concerne la limitation des libertés individuelles et la mise en œuvre. Dans le présent document, nous examinons les principales considérations à prendre en compte pour garantir l'acceptabilité éthique du certificat d'immunité visant à lever les mesures de restriction pour certaines personnes durant la pandémie de COVID-19. Cette acceptabilité éthique dépend non seulement de son degré de conformité à des critères scientifiques stricts, mais aussi de son usage, des objectifs politiques ainsi que des mesures mises en place pour atténuer les préjudices potentiels et éviter d'imposer une charge disproportionnée sur les individus dépourvus de certificat, ou de bafouer les droits et libertés de tout un chacun.

Las medidas restrictivas impuestas a causa de la pandemia de la enfermedad coronavirus de 2019 (COVID-19) han tenido graves efectos sociales, económicos y sanitarios. Algunos países han considerado la posibilidad de utilizar la certificación de inmunidad como estrategia para flexibilizar dichas medidas para las personas que se han recuperado de la infección mediante la expedición a dichas personas de un documento, comúnmente denominado pasaporte de inmunidad. Este documento certifica que han desarrollado inmunidad protectora contra el coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2), el virus que causa la COVID-19. La Organización Mundial de la Salud ha desaconsejado la aplicación de la certificación de la inmunidad en la actualidad debido a la incertidumbre sobre si existe realmente una inmunidad a largo plazo para quienes se han recuperado de la COVID-19 y a las preocupaciones sobre la fiabilidad del método de prueba serológica propuesto para determinar la inmunidad. La certificación de la inmunidad solo puede considerarse si se cumplen los umbrales científicos para asegurar la inmunidad, ya sea que se basen en anticuerpos o en otros criterios. Sin embargo, incluso si la certificación de la inmunidad llegara a estar bien respaldada por la ciencia, tiene muchas cuestiones éticas en cuanto a las diferentes restricciones de las libertades individuales y su proceso de aplicación. Examinamos las principales consideraciones sobre la aceptabilidad ética de la certificación de la inmunidad para eximir a los individuos de las medidas restrictivas durante la pandemia de la COVID-19. Además de necesitar cumplir criterios científicos sólidos, la aceptabilidad ética de la certificación de inmunidad depende de sus usos y objetivos de política y de las medidas que se apliquen para reducir los posibles daños y evitar que se impongan cargas desproporcionadas a las personas que no cuenten con dicha certificación y se violen las libertades y derechos individuales.

"I was afraid my baby would be upset with me" - women living with HIV's accounts going through non-breastfeeding in São Paulo, Brazil.

In Brazil prevention of mother to child HIV transmission guidelines recommend formula feeding. This qualitative study, carried out in a public clinic (CEADIPE/UNIFESP), aimed at exploring experiences of breastfeeding avoidance of women living with HIV living in São Paulo. Individual interviews were carried out with the support of a semi-structured questionnaire. Data was analyzed in a thematic approach with the support of AtlasTi®. During the months of January-February 2010, 25 women were interviewed, including women with (n = 12) and without previous breastfeeding experience (n = 13). Major themes identified were: Non-breastfeeding as a trigger for stigmatization, Non-breastfeeding, guilt and coping, Attitudes around non-breastfeeding for women with and without previous breastfeeding experience, and Women's support through non-breastfeeding. In conclusion women interviewed faced challenges related to HIV diagnosis, which got entangled with difficulties with breastfeeding avoidance. Different patterns of reaction and coping could be identified, regardless of mothers' previous breastfeeding experiences. Health systems were key in providing women living with HIV with tailored services and the necessary support.

WHO guidance on COVID-19 vaccine trial designs in the context of authorized COVID-19 vaccines and expanding global access: Ethical considerations.

While the degree of COVID-19 vaccine accessibility and uptake varies at both national and global levels, increasing vaccination coverage raises questions regarding the standard of prevention that ought to apply to different settings where COVID-19 vaccine trials are hosted. A WHO Expert Group has developed guidance on the ethical implications of conducting placebo-controlled trials in the context of expanding global COVID-19 vaccine coverage. The guidance also considers alternative trial designs to placebo controlled trials in the context of prototype vaccines, modified vaccines, and next generation vaccines.

Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.

BACKGROUND: Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults' infection, elite control has been rarely characterized in the pediatric population. DESIGN: We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents. RESULTS: PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B∗27/57/81. CONCLUSION: Pediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell mediated immune control of viremia, and in adult elite controllers, low immune activation is therefore the consequence of the rapid CD8+ T-cell mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in posttreatment controllers, in whom protective HLA-I molecules are not the main factor.

Dose-sparing effect of two adjuvant formulations with a pandemic influenza A/H7N9 vaccine: A randomized, double-blind, placebo-controlled, phase 1 clinical trial.

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15µg H7N9, 1B) IB160 + 7.5µg H7N9, 1C) IB160 + 3.75µg H7N9, 2A) SE + 15µg H7N9, 2B) SE + 7.5µg H7N9, 2C) SE + 3.75µg H7N9, 3) unadjuvanted vaccine 15µg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.

Top five ethical lessons of COVID-19 that the world must learn.

As the world reflects upon one year since the first cases of coronavirus disease 2019 (COVID-19) and prepare for and experience surges in cases, it is important to identify the most crucial ethical issues that might lie ahead so that countries are able to plan accordingly. Some ethical issues are rather obvious to predict, such as the ethical issues surrounding the use of immunity certificates, contact tracing, and the fair allocation of vaccines globally. Yet, the most significant ethical challenge that the world must address in the next year and beyond is to ensure that we learn the ethical lessons of the first year of this pandemic. Learning from our collective experiences thus far constitutes our greatest moral obligation. Appreciating that decision-making in the context of a pandemic is constrained by unprecedented complexity and uncertainty, beginning in June 2020, an international group of 17 experts in bioethics spanning 15 countries (including low-, middle-, and high-income countries) met virtually to identify what we considered to be the most significant ethical challenges and accompanying lessons faced thus far in the COVID-19 pandemic. Once collected, the group met over the course of several virtual meetings to identify challenges and lessons that are analytically distinct in order to identify common ethical themes under which different challenges and lessons could be grouped. The result, described in this paper, is what this expert group consider to be the top five ethical lessons from the initial experience with COVID-19 that must be learned.

Active pharmacovigilance of the seasonal trivalent influenza vaccine produced by Instituto Butantan: A prospective cohort study of five target groups.

INTRODUCTION: Active pharmacovigilance studies are pivotal to better characterize vaccine safety. METHODS: These are multicenter prospective cohort studies to evaluate the safety of the 2017 and 2018 seasonal trivalent influenza vaccines (TIVs) manufactured by Instituto Butantan, by means of active pharmacovigilance practices. Elderly, children, healthcare workers, pregnant women, and women in the puerperium period were invited to participate in the study during the 2017 and 2018 Brazilian national seasonal influenza vaccination campaigns. Following immunization, participants were observed for 30 minutes and they received a participant card to register adverse events information. All safety information registered were checked at a clinical site visit 14 days after immunization and by a telephone contact 42 days after immunization for unsolicited Adverse Events (AE) and Guillain-Barré Syndrome (GBS). RESULTS: A total of 942 volunteers participated in the two studies: 305 elderly, 109 children, 108 pregnant women, 32 women in the postpartum period, and 388 health workers. Overall, the median number of AR per participant ranged from 1 to 4. The lowest median number of AR per participant was observed among healthcare workers (1 AR per participant) and the highest among pregnant women (4 AR per participant). Overall, local pain (46.6%) was the most frequent solicited local AR. The most frequent systemic ARs were: headache (22.5%) followed by fatigue (16.0%), and malaise (11.0%). The majority of solicited ARs (96%) were mild, Grades 1 or 2), only 3% were Grade 3, and 1% was Grade 4. No serious AEs, including Guillain-Barré Syndrome, were reported up to 42 days postvaccination. CONCLUSION: The results from the two studies confirmed that the 2017 and 2018 seasonal trivalent influenza vaccines produced by Instituto Butantan were safe and that active pharmacovigilance studies should be considered, when it is feasible, as an important initiative to monitor vaccine safety in the post-marketing period.

Ethical Considerations for Restrictive and Physical Distancing Measures in Brazil During COVID-19: Facilitators and Barriers.

COVID-19 was recognized as a pandemic on March 11, 2020. Nine days later in Brazil, community transmission was deemed ongoing, and following what was already being put in place in various affected countries, restrictive and physical distancing measures that varied in severity across the different states were adopted. Adherence to restrictive and physical distancing measures depends on the general acceptance of public health measures as well as communities' financial leverage. This article aims to explore and discuss ethical facilitators and barriers to the implementation of physical distancing measures within three dimensions: political, socio-economic, and scientific. Furthermore, we would like to discuss ways to ethically promote restrictive and physical distancing measures in a large and unequal country like Brazil. There is an urgent need for transparent, consistent, and inclusive communication with the public, respecting the most vulnerable populations and attempting to minimize the disproportionate burden on them.

Adults at high-risk of severe coronavirus disease-2019 (Covid-19) in Brazil.

OBJECTIVE To estimate the proportion and total number of the general adult population who may be at higher risk of severe Covid-19 in Brazil. METHODS We included 51,770 participants from a nationally representative, household-based health survey (PNS) conducted in Brazil. We estimated the proportion and number of adults (≥ 18 years) at risk of severe Covid-19 by sex, educational level, race/ethnicity, and state based on the presence of one or more of the following risk factors: age ≥ 65 years or medical diagnosis of cardiovascular disease, diabetes, hypertension, chronic respiratory disease, cancer, stroke, chronic kidney disease and moderate to severe asthma, smoking status, and obesity. RESULTS Adults at risk of severe Covid-19 in Brazil varied from 34.0% (53 million) to 54.5% (86 million) nationwide. Less-educated adults present a 2-fold higher prevalence of risk factors compared to university graduated. We found no differences by sex and race/ethnicity. São Paulo, Rio de Janeiro, Minas Gerais, and Rio Grande do Sul were the most vulnerable states in absolute and relative terms of adults at risk. CONCLUSIONS Proportion and total number of adults at risk of severe Covid-19 are high in Brazil, with wide variation across states and adult subgroups. These findings should be considered while designing and implementing prevention measures in Brazil. We argue that these results support broad social isolation measures, particularly when testing capacity for SARS-CoV-2 is limited.

Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial.

BACKGROUND: The Butantan Institute has manufactured a lyophilised tetravalent live-attenuated dengue vaccine Butantan-DV, which is analogous to the US National Institutes of Health (NIH) TV003 admixture. We aimed to assess the safety and immunogenicity of Butantan-DV. METHODS: We did a two-step, double-blind, randomised placebo-controlled phase 2 trial at two clinical sites in São Paulo, Brazil. We recruited healthy volunteers aged 18-59 years; pregnant women, individuals with a history of neurological, heart, lung, liver or kidney disease, diabetes, cancer, or autoimmune diseases, and individuals with HIV or hepatitis C were excluded. Step A was designed as a small bridge-study between Butantan-DV and TV003 in DENV-naive participants. In step A, we planned to randomly assign 50 dengue virus (DENV)-naive individuals to receive two doses of Butantan-DV, TV003, or placebo, given 6 months apart. In step B, we planned to randomly assign 250 participants (DENV-naive and DENV-exposed) to receive one dose of Butantan-DV or placebo. Participants were randomly assigned, by computer-generated block randomisation (block sizes of five); participants in step A were randomly assigned (2:2:1) to receive Butantan-DV, TV003, or placebo and participants in step B were randomly assigned (4:1) to receive Butantan-DV or placebo. Participants and study staff were unaware of treatment allocation. The primary safety outcome was the frequency of solicited and unsolicited local and systemic adverse reactions within 21 days of the first vaccination, analysed by intention to treat. The primary immunogenicity outcome was seroconversion rates of the DENV-1-4 serotypes measured 91 days after the first vaccination, analysed in the per-protocol population, which included all participants in step A, and all participants included in step B who completed all study visits with serology sample collection. This trial is registered with ClinicalTrials.gov, NCT01696422. FINDINGS: Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received placebo. Butantan-DV and TV003 were both immunogenic, well-tolerated, and no serious adverse reactions were observed. In step A, rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4. INTERPRETATION: Butantan-DV and TV003 were safe and induced robust, balanced neutralising antibody responses against the four DENV serotypes. Efficacy evaluation of the Butantan-DV vaccine is ongoing. FUNDING: Intramural Research Program US NIH National Institute of Allergy and Infectious Diseases, Brazilian National Bank for Economic and Social Development, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Fundação Butantan.

Pharmacovigilance capacity strengthening for WHO prequalification: The case of the trivalent influenza vaccine manufactured by Instituto Butantan.

Instituto Butantan is a biomedical research center and vaccine manufacturer affiliated with the São Paulo State Secretary of Health in Brazil. In 2013, Instituto Butantan successfully licensed its trivalent influenza vaccine, in order to support the Brazilian National Immunization Program's influenza vaccination strategy, which was introduced in 1999. In order to respond to the increasing influenza vaccine demand worldwide, Instituto Butantan is undergoing prequalification of its trivalent influenza vaccine by the World Health Organization (WHO). A key requirement of the prequalification review was the submission of a pharmacovigilance plan, including an active surveillance evaluation, for the trivalent influenza vaccine, and proof of a functional pharmacovigilance system at Instituto Butantan. The aim of this paper is to describe the capacity strengthening process of the pharmacovigilance system at Instituto Butantan for the WHO prequalification of the trivalent influenza vaccine. This process was supported by PATH and the U.S. Federal Government Biomedical Advanced Research and Development Authority (BARDA). The key strategic axes for this capacity strengthening process included the improvement of organizational structure, human resources training, internal processes and procedures, appropriate documentation, and acquisition of an E2B compliant pharmacovigilance database. The project led to the establishment of a functional pharmacovigilance system compliant with international regulatory requirements.

Strong sex bias in elite control of paediatric HIV infection.

BACKGROUND: Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection. METHODS: We describe 11 ART-naive elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe. RESULTS: All but one of the elite controllers (91%) are females. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age of 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4 cell counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5-10-fold lower than in adults. CONCLUSION: Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females.

Research ethics and resource allocation in times of covid-19 / Ética de investigación y asignación de recursos en tiempos de covid-19 / Ética em pesquisa e alocação de recursos em tempos de covid-19

Abstract The purpose of this reflection is to include ethical principles in the discussion on resource allocation in times of covid-19. This study presents recent news and documents on the use of resources in the pandemic and principles such as justice, autonomy and beneficence. The comprehension that all human beings are worthy of respect, solidarity and protection can help pave the way for accelerating pandemic control for all.

Resumen El propósito de esta reflexión es incluir principios éticos en la discusión sobre la asignación de recursos en tiempos de covid-19. Se trata de un estudio que presenta noticias y documentos recientes sobre el uso de recursos en la pandemia y sobre principios como justicia, autonomía y beneficencia. La comprensión de que todos los seres humanos son dignos de respeto, solidaridad y protección puede ayudar a allanar el camino para acelerar el control de la pandemia para todos.

Resumo O objetivo desta reflexão é incluir princípios éticos na discussão sobre alocação de recursos em tempos de covid-19. Este estudo apresenta notícias e documentos recentes sobre uso de recursos na pandemia, e princípios como justiça, autonomia e beneficência. A compreensão de que todos os seres humanos merecem respeito, solidariedade e proteção pode ajudar a trilhar caminhos que acelerem o controle da pandemia para todos.

Outcomes Among Children Enrolled in HIV Care in Mozambique 2009-2013.

BACKGROUND: Scale-up of HIV care and antiretroviral therapy (ART) services for children has expanded access, but significant gaps and challenges remain. We examined lost to follow-up (LTF) and mortality in a large cohort of children enrolled in HIV care in Mozambique. METHODS: Routinely collected medical data on children 0-14 years enrolled in care 2009-2013 at ICAP-supported health facilities in 5 provinces of Mozambique were used. Children not receiving ART (pre-ART) were considered LTF if they did not a have a visit within 12 months of the end of data collection; for those receiving ART, LTF was no visit within 6 months. Competing risk and Kaplan-Meier estimators were used, respectively, to estimate pre-ART and on ART LTF and mortality. RESULTS: A total of 13,695 children enrolled in HIV care at 64 health facilities (48.6%, <2 years), and 7733 (56.5%) initiated ART during follow-up. Cumulative incidence of pre-ART LTF was 32.9% [95% confidence interval (CI): 32.1-33.7] and 34.4% (95% CI: 33.6-35.2) by 12 and 24 months, respectively, and was highest in children <5 years (12-month LTF in children 2-4 years, 34.2%, 95% CI: 32.6-35.9). Pre-ART mortality at 12 months was 3.3% (95% CI: 3.0-3.6) and was highest in children <2 years (4.1%, 95% CI: 3.6-4.6). On ART, LTF was 28.6% (95% CI: 27.6-29.7) and 37.6 (95% CI: 36.4-38.8) at 12 and 24 months, and 12 months mortality after ART was 8.0% (95% CI: 7.3-8.7). CONCLUSIONS: High rates of LTF were observed in this large cohort of HIV-infected children accessing care in Mozambique both before and after ART initiation highlighting the urgent need for interventions to improve retention in routine care settings.

Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine.

Butantan Institute is a public Brazilian biomedical research-manufacturer center affiliated to the São Paulo State Secretary of Health. Currently, Butantan is one of the main public producers of vaccines, antivenoms, and antitoxins in Latin America. The partnership between Butantan and the National Institutes of Health (NIH) of the United Sates has been one of the longest and most successful partnerships in the development and manufacturing of new vaccines. Recently, Butantan Institute has developed and manufactured a lyophilized tetravalent live attenuated dengue vaccine with the four dengue viruses attenuated and licensed from the Laboratory of Infectious Diseases at The National Institutes of Allergy and Infectious Diseases (LID/NIAID/NIH). The objective of this paper is to describe the clinical evaluation strategies of a live attenuated tetravalent dengue vaccine (Butantan-DV) developed and manufactured by Butantan Institute. These clinical strategies will be used to evaluate the Butantan-DV Phase III trial to support the Butantan-DV licensure for protection against any symptomatic dengue caused by any serotype in people aged 2 to 59 years.

Adults at high-risk of severe coronavirus disease-2019 (Covid-19) in Brazil

ABSTRACT OBJECTIVE To estimate the proportion and total number of the general adult population who may be at higher risk of severe Covid-19 in Brazil. METHODS We included 51,770 participants from a nationally representative, household-based health survey (PNS) conducted in Brazil. We estimated the proportion and number of adults (≥ 18 years) at risk of severe Covid-19 by sex, educational level, race/ethnicity, and state based on the presence of one or more of the following risk factors: age ≥ 65 years or medical diagnosis of cardiovascular disease, diabetes, hypertension, chronic respiratory disease, cancer, stroke, chronic kidney disease and moderate to severe asthma, smoking status, and obesity. RESULTS Adults at risk of severe Covid-19 in Brazil varied from 34.0% (53 million) to 54.5% (86 million) nationwide. Less-educated adults present a 2-fold higher prevalence of risk factors compared to university graduated. We found no differences by sex and race/ethnicity. São Paulo, Rio de Janeiro, Minas Gerais, and Rio Grande do Sul were the most vulnerable states in absolute and relative terms of adults at risk. CONCLUSIONS Proportion and total number of adults at risk of severe Covid-19 are high in Brazil, with wide variation across states and adult subgroups. These findings should be considered while designing and implementing prevention measures in Brazil. We argue that these results support broad social isolation measures, particularly when testing capacity for SARS-CoV-2 is limited.