Effectiveness of Heterologous Coronavirus Disease 2019 (COVID-19) Vaccine Booster Dosing in Brazilian Healthcare Workers, 2021.

BACKGROUND: Little is currently known about vaccine effectiveness (VE) for either 2 doses of Oxford-AstraZeneca (ChAdOx1) viral vector vaccine or CoronaVac (Instituto Butantan) inactivated viral vaccine followed by a third dose of mRNA vaccine (Pfizer/BioNTech) among healthcare workers (HCWs). METHODS: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil from January to December 2021. VE was defined as 1 - incidence rate ratio (IRR), with IRR determined using Poisson models with the occurrence of laboratory-confirmed coronavirus disease 2019 (COVID-19) infection as the outcome, adjusting for age, sex, and job type. We compared those receiving viral vector or inactivated viral primary series (2 doses) with those who received an mRNA booster. RESULTS: A total of 11 427 HCWs met the inclusion criteria. COVID-19 was confirmed in 31.5% of HCWs receiving 2 doses of CoronaVac vaccine versus 0.9% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001) and 9.8% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 1% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). In the adjusted analyses, the estimated VE was 92.0% for 2 CoronaVac vaccines plus mRNA booster and 60.2% for 2 ChAdOx1 vaccines plus mRNA booster, when compared with those with no mRNA booster. Of 246 samples screened for mutations, 191 (77.6%) were Delta variants. CONCLUSIONS: While 2 doses of ChAdOx1 or CoronaVac vaccines prevent COVID-19, the addition of a Pfizer/BioNTech booster provided significantly more protection.

Dental vulnerability scale in primary health care: evidence of content and structure internal validity.

BACKGROUND: Access to oral health services remains a challenge in the Brazilian healthcare system, especially in the primary health care setting, where the use of a risk stratification tool that could identify individuals with higher dental vulnerability would be extremely valuable. However, there literature on this theme is scarce, and there is no validated instrument in Brazil that is capable of measuring dental vulnerability. Hence, this psychometric study aimed at the development and evaluation of content and internal structure validity of the Dental Vulnerability Scale for Primary Health Care (PHC). METHODS: The items were developed based on a qualitative exploratory analysis. A total of 172 items were prepared and submitted to a panel of specialists, with content validity analyzed with the Content Validity Ratio (CVR), resulting in an the initial version of the instrument composed by 41 items. Internal structure validity was analyzed by Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and by applying 3 reliability indicators (Cronbach's Alpha, McDonald's Omega and Greatest Lower Bound - GBL), with a sample of 1227 individuals. RESULTS: The final configuration indicated a scale of 15 items divided into 4 dimensions (overall health, oral health, infrastructure, and healthcare services) with explained variance of 72.11%. The factor loads varied from 0.37 to 0.96. The model adjustment indices were set at × 2/df(51) = 3.23, NNFI = 0.95, CFI = 0.98, GFI = 0.96, AGFI = 0.97, RMSEA = 0.04 and RMSR = 0.03. CONCLUSION: DVS presented satisfactory evidence of validity, indicating its suitability to be used by healthcare professionals, students and managers to plan oral health actions and services at PHC.

A prospective evaluation of inter-rater agreement of routine medical records audits at a large general hospital in São Paulo, Brazil.

BACKGROUND: The quality of patient medical records is intrinsically related to patient safety, clinical decision-making, communication between health providers, and continuity of care. Additionally, its data are widely used in observational studies. However, the reliability of the information extracted from the records is a matter of concern in audit processes to ensure inter-rater agreement (IRA). Thus, the objective of this study is to evaluate the IRA among members of the Patient Health Record Review Board (PHRRB) in routine auditing of medical records, and the impact of periodic discussions of results with raters. METHODS: A prospective longitudinal study was conducted between July of 2015 and April of 2016 at Hospital Municipal Dr. Moysés Deutsch, a large public hospital in São Paulo. The PHRRB was composed of 12 physicians, 9 nurses, and 3 physiotherapists who audited medical records monthly, with the number of raters changing throughout the study. PHRRB meetings were held to reach a consensus on rating criteria that the members use in the auditing process. A review chart was created for raters to verify the registry of the patient's secondary diagnosis, chief complaint, history of presenting complaint, past medical history, medication history, physical exam, and diagnostic testing. The IRA was obtained every three months. The Gwet's AC1 coefficient and Proportion of Agreement (PA) were calculated to evaluate the IRA for each item over time. RESULTS: The study included 1884 items from 239 records with an overall full agreement among raters of 71.2%. A significant IRA increase of 16.5% (OR = 1.17; 95% CI = 1.03-1.32; p = 0.014) was found in the routine PHRRB auditing, with no significant differences between the PA and the Gwet's AC1, which showed a similar evolution over time. The PA decreased by 27.1% when at least one of the raters was absent from the review meeting (OR = 0.73; 95% CI = 0.53-1.00; p = 0.048). CONCLUSIONS: Medical record quality has been associated with the quality of care and could be optimized and improved by targeted interventions. The PA and the Gwet's AC1 are suitable agreement coefficients that are feasible to be incorporated in the routine PHRRB evaluation process.

Risk assessment for oral urgent treatment in Primary Healthcare: a cross-sectional study.

BACKGROUND: The World Health Organization has advocated for the integration of dental care into the primary healthcare (PHC) setting, including oral urgent treatment (OUT). However, the knowledge necessary for OUT implementation in this setting is still limited. Thus, this study aimed to describe the impact of the implementation of oral disease risk assessment tools for oral health management in PHC. METHODS: This was a cross-sectional study that included individuals served by a single public PHC unit, with integrated oral healthcare teams, located in the south region of the city of São Paulo, Brazil, between April of 2015 and March of 2017. Data were collected from dental records. Three co-primary endpoints: same day treatment offered, first future appointment scheduled fulfilled, and treatment plan completed were compared before and after the implementation of oral disease risk assessment for OUT. RESULTS: A total of 1214 individuals that sought OUT, 599 before and 615 after the implementation of oral disease risk assessment for OUT were included in the study. All three co-primary endpoints had significant changes after the implementation of oral disease risk assessment for OUT. Individuals were significantly more likely to be offered same day treatment after (39.9%; 95% CI:36.0-43.9%) than before (9.4%; 95% CI: 7.2-12.0%), to fulfill their first future appointment scheduled after (34.9%; 95% CI:31.1-38.8%) than before (20.7%; 95% CI: 17.5-24.2%), and to have their treatment plan completed after (14.3%; 95% CI:11.6-17.4%) than before (10.0%; 95% CI: 7.7-12.7%) the intervention. CONCLUSIONS: This study provided evidence of the positive impact oral disease risk assessment tools could have in the organization of OUT in PHC settings.

Distance learning in antimicrobial stewardship: innovation in medical education.

BACKGROUND: This study aimed to analyse the impact that web-based distance learning has on knowledge gain in medical students, as well as student perceptions of the methodology. METHODS: This was an educational intervention study conducted at a tertiary teaching hospital in the city of São Paulo, Brazil. From 2008 to 2014, we offered a free web-based distance learning course, covering antimicrobial use and microbial resistance, to fifth-year medical students. The course encompassed 100 h of activities, with five theoretical modules, exercises and simulations, within a virtual learning environment. The students were tutored in their online activities, and some classes were conducted in real time for live discussions. In addition, students underwent face-to-face assessments of their knowledge of the topic before and after the course. Statistical analysis was performed and the means of the overall scores were obtained, as were the respective 95% confidence intervals (CIs). The means were compared by two-tailed paired t-tests and by the paired Wilcoxon test. RESULTS: Of 814 eligible medical students, 606 (74.45%) completed the entire course during the study period. The mean score for knowledge of the topic was significantly higher on the final assessment than on the initial assessment (p <  0.001). We found that dedication (in hours) was directly proportional to the level of participation, as reflected in the mean final score (p = 0.009) and in the proportion of students who passed (p = 0.028). All of the participants considered their knowledge adequate or insufficient before the course, stating that it is quite important or important to address the topic during medical education. Although dedication levels were low, 70.5% stated that they had learned "quite a lot" or "more than expected" about the topic and would dedicate more time to it if they could. CONCLUSIONS: The use of a virtual learning environment can promote teaching and learning in the infectious diseases field, specifically for antimicrobial stewardship, increasing knowledge significantly, and should be considered for inclusion in the final stages of medical education.

Factors associated with the quality of death certification in Brazilian municipalities: A data-driven non-linear model.

Studies evaluating the local quality of death certification in Brazil focused on completeness of death reporting or inappropriate coding of causes of death, with few investigating missing data. We aimed to use missing and unexpected values in core topics to assess the quality of death certification in Brazilian municipalities, to evaluate its correlation with the percentage of garbage codes, and to employ a data-driven approach with non-linear models to investigate the association of the socioeconomic and health infrastructure context with quality of death statistics among municipalities. This retrospective study used data from the Mortality Information System (2010-2017), and municipal data regarding healthcare infrastructure, socioeconomic characteristics, and death rates. Quality of death certification was assessed by missing or unexpected values in the following core topics: dates of occurrence, registration, and birth, place of occurrence, certifier, sex, and marital status. Models were fit to classify municipalities according to the quality of death certification (poor quality defined as death records with missing or unexpected values in core topics ≥ 80%). Municipalities with poor quality of death certification (43.9%) presented larger populations, lower death rates, lower socioeconomic index, healthcare infrastructure with fewer beds and physicians, and higher proportion of public healthcare facilities. The correlation coefficients between quality of death certification assessed by missing or unexpected values and the proportion of garbage codes were weak (0.11-0.49), but stronger for municipalities with lower socioeconomic scores. The model that best fitted the data was the random forest classifier (ROC AUC = 0.76; precision-recall AUC = 0.78). This innovative way of assessing the quality of death certification could help quality improvement initiatives to include the correctness of essential fields, in addition to garbage coding or completeness of records, especially in municipalities with lower socioeconomic status where garbage coding and the correctness of core topics appear to be related issues.

Longer-term effectiveness of a heterologous coronavirus disease 2019 (COVID-19) vaccine booster in healthcare workers in Brazil.

Objective: To compare the long-term vaccine effectiveness between those receiving viral vector [Oxford-AstraZeneca (ChAdOx1)] or inactivated viral (CoronaVac) primary series (2 doses) and those who received an mRNA booster (Pfizer/BioNTech) (the third dose) among healthcare workers (HCWs). Methods: We conducted a retrospective cohort study among HCWs (aged ≥18 years) in Brazil from January 2021 to July 2022. To assess the variation in the effectiveness of booster dose over time, we estimated the effectiveness rate by taking the log risk ratio as a function of time. Results: Of 14,532 HCWs, coronavirus disease 2019 (COVID-19) was confirmed in 56.3% of HCWs receiving 2 doses of CoronaVac vaccine versus 23.2% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001), and 37.1% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 22.7% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). The highest vaccine effectiveness with mRNA booster was observed 30 days after vaccination: 91% for the CoronaVac vaccine group and 97% for the ChAdOx1 vaccine group. Vacine effectiveness declined to 55% and 67%, respectively, at 180 days. Of 430 samples screened for mutations, 49.5% were SARS-CoV-2 delta variants and 34.2% were SARS-CoV-2 omicron variants. Conclusions: Heterologous COVID-19 vaccines were effective for up to 180 days in preventing COVID-19 in the SARS-CoV-2 delta and omicron variant eras, which suggests the need for a second booster.

Risk factors for long coronavirus disease 2019 (long COVID) among healthcare personnel, Brazil, 2020-2022.

OBJECTIVE: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP). METHODS: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. RESULTS: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID. CONCLUSIONS: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

Effectiveness of two coronavirus disease 2019 (COVID-19) vaccines (viral vector and inactivated viral vaccine) against severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in a cohort of healthcare workers.

OBJECTIVE: We investigated real-world vaccine effectiveness for Oxford-AstraZeneca (ChAdOx1) and CoronaVac against laboratory-confirmed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). METHODS: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil between January 1, 2021 and August 3, 2021, to assess vaccine effectiveness. We calculated vaccine effectiveness as 1 - rate ratio (RR), with RR determined by adjusting Poisson models with the occurrence of SARS-CoV-2 infection as the outcome and the vaccination status as the main variable. We used the logarithmic link function and simple models adjusting for sex, age, and job types. RESULTS: In total, 13,813 HCWs met the inclusion criteria for this analysis. Among them, 6,385 (46.2%) received the CoronaVac vaccine, 5,916 (42.8%) received the ChAdOx1 vaccine, and 1,512 (11.0%) were not vaccinated. Overall, COVID-19 occurred in 6% of unvaccinated HCWs, 3% of HCWs who received 2 doses of CoronaVac vaccine, and 0.7% of HCWs who received 2 doses of ChAdOx1 vaccine (P < .001). In the adjusted analyses, the estimated vaccine effectiveness rates were 51.3% for CoronaVac, and 88.1% for ChAdOx1 vaccine. Both vaccines reduced the number of hospitalizations, the length of hospital stay, and the need for mechanical ventilation. In addition, 19 SARS-CoV-2 samples from 19 HCWs were screened for mutations of interest. Of 19 samples, 18 were the γ (gamma) variant. CONCLUSIONS: Although both COVID-19 vaccines (viral vector and inactivated virus) can significantly prevent COVID-19 among HCWs, CoronaVac was much less effective. The COVID-19 vaccines were also effective against the dominant γ variant.

Short-term effectiveness of COVID-19 vaccines in immunocompromised patients: A systematic literature review and meta-analysis.

OBJECTIVES: We aimed to assess the short-term effectiveness of COVID-19 vaccines among immunocompromised patients to prevent laboratory-confirmed symptomatic COVID-19 infection. METHODS: Systematic review and meta-analysis. We calculated the pooled diagnostic odds ratio [DOR] (95% CI) for COVID-19 infection between immunocompromised patients and healthy people or those with stable chronic medical conditions. VE was estimated as 100% x (1-DOR). We also investigated the rates of developing anti-SARS-CoV-2 spike protein IgG between the 2 groups. RESULTS: Twenty studies evaluating COVID-19 vaccine response, and four studies evaluating VE were included in the meta-analysis. The pooled DOR for symptomatic COVID-19 infection in immunocompromised patients was 0.296 (95% CI: 0.108-0.811) with an estimated VE of 70.4% (95% CI: 18.9%- 89.2%). When stratified by diagnosis, IgG antibody levels were much higher in the control group compared to immunocompromised patients with solid organ transplant (pOR 232.3; 95% Cl: 66.98-806.03), malignant diseases (pOR 42.0, 95% Cl: 11.68-151.03), and inflammatory rheumatic diseases (pOR 19.06; 95% Cl: 5.00-72.62). CONCLUSIONS: We found COVID-19 mRNA vaccines were effective against symptomatic COVID-19 among the immunocompromised patients but had lower VE compared to the controls. Further research is needed to understand the discordance between antibody production and protection against symptomatic COVID-19 infection.

An Open-label Randomized Controlled Parallel-group Pilot Study Comparing the Immunogenicity of a Standard-, Double-, and Booster-dose Regimens of the 2014 Seasonal Trivalent Inactivated Influenza Vaccine in Kidney Transplant Recipients.

BACKGROUND: Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. METHODS: We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV), and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59), and BDTIIV regimens (58). Antibody titers were determined by hemagglutination inhibition at enrollment and 21 d postvaccination. Seroprotection rates (SPRs), seroconversion rates (SCRs), and geometric mean ratios (GMRs) were analyzed separately for participants with low (<1:40) and high (≥1:40) prevaccination antibody titers. RESULTS: Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided postvaccination blood samples. In the subgroup with high prevaccination antibody titers, all vaccination regimens induced SPR > 70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low prevaccination antibody titers, DDTIIV and BDTIIV regimens induced adequate SCR > 40% and GMR > 2.5 for all antigens, whereas SDTIIV achieved the same outcomes only for influenza B. SPRs were >70% only after DDTIIV (A/H1N1-77.8%) and BDTIIV (A/H3N2-77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR = 2.58; P = 0.021) and A/H3N2 (PR = 2.21; P = 0.004), whereas DDTIIV independently increased seroprotection to A/H1N1 (PR = 2.59; P = 0.021). CONCLUSIONS: Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

A seroprevalence survey of anti-SARS-CoV-2 antibodies among individuals 18 years of age or older living in a vulnerable region of the city of São Paulo, Brazil.

A second wave of COVID-19 has demonstrated how challenging it will be to achieve sustained control of the disease, even with vaccination underway in many countries. Therefore, it remains relevant to keep improving our understanding of the distribution of COVID-19, especially of asymptomatic individuals, among different populations, and particularly in vulnerable regions. Hence, this population-based serosurvey had the objective of estimating the prevalence of individuals 18 years of age or older infected by SARS-CoV-2, and the proportion of asymptomatic individuals, among a vulnerable population living in an urban setting. This was a cross-sectional single-stage cluster sampling serosurvey conducted between September and December of 2019, in a vulnerable region of the city of São Paulo, Brazil. Families covered by three public primary healthcare units represented the selected clusters. After study inclusion, participants were asked about signs and symptoms related to COVID-19, and had collected 10 mL of blood for serology testing. A total of 272 individuals from 185 families were included in the study, out of the 400 eligible individuals for inclusion, resulting in a non-response rate of 32%. The post stratified prevalence of individuals infected by SARS-CoV-2 was 45.2% (95% CI: 39.4-51.0%), with a proportion of asymptomatic cases of 30.2% (95% CI: 23.3-38.0%). This population-based serosurvey identified a greater prevalence of infected individuals by SARS-CoV-2 compared to data from the beginning of the pandemic, and from a recent citywide serosurvey, with a similar proportion of asymptomatic individuals. It demonstrated the value of primary healthcare services for disease surveillance activities, and the importance of more focused serosurveys, especially in vulnerable locations, and the need to evaluate new surveillance strategies to take into account asymptomatic cases.

Liver transplant from Anti-HBc-positive, HBsAg-negative donor into HBsAg-negative recipient: is it safe? A systematic review of the literature.

INTRODUCTION: After liver transplant (LT) from Anti-HBc+/HBsAg- donors into HBsAg- recipients, transmission of hepatitis B virus (HBV) may occur (de novo HBV infection). This study analyzes the incidence of de novo HBV infection in HBsAg- recipients of Anti-HBc+/HBsAg- LT with respect to: (i) the recipients' HBV serology and (ii) the type of preventive therapy adopted. METHODS: A systematic review of the literature using the electronic database Medline. RESULTS: Five hundred and fifty-two LT in 36 articles were selected. Lamivudine, Hepatitis B immune globulin (HBIG), revaccination, and combined therapies were employed in multiple strategies as preventive interventions. Naïve recipients had a high risk of de novo HBV infection, with smaller incidences when HBIG and lamivudine were used, either alone or in association. Vaccinated recipients or those with isolated hepatitis B core antibodies (Anti-HBc) and previous HBV infection had lower risks of viral transmission, additionally reduced by any prophylaxis adoption. DISCUSSION: LT from Anti-HBc+/HBsAg- donors into HBsAg- recipients is apparently safe, as long as the recipient is vaccinated or presents an isolated Anti-HBc or previous HBV infection and some prophylaxis is employed. Currently lamivudine seems the best alternative; other nucleoside analogs and revaccination strategies should be considered in future studies. Follow-up and preventive therapies should be maintained for five yr or preferably throughout the recipients' life span.

Frenetic, under-Challenged, and Worn-out Burnout Subtypes among Brazilian Primary Care Personnel: Validation of the Brazilian "Burnout Clinical Subtype Questionnaire" (BCSQ-36/BCSQ-12).

Primary healthcare personnel show high levels of burnout. A new model of burnout has been developed to distinguish three subtypes: frenetic, under-challenged, and worn-out, which are characterized as overwhelmed, under-stimulated, and disengaged at work, respectively. The aim of this study was to assess the psychometric properties of the long/short Brazilian versions of the "Burnout Clinical Subtypes Questionnaire" (BCSQ-36/BCSQ-12) among Brazilian primary healthcare staff and its possible associations with other psychological health-related outcomes. An online cross-sectional study conducted among 407 Brazilian primary healthcare personnel was developed. Participants answered a Brazil-specific survey including the BCSQ-36/BCSQ-12, "Maslach Burnout Inventory-General Survey", "Utrecht Work Engagement Scale", "Hospital Anxiety/Depression Scale", "Positive-Negative Affect Schedule", and a Visual Analogue Scale of guilt at work. The bifactor was the model with the best fit to the data using the BCSQ-36, which allowed a general factor for each subtype. The three-correlated factors model fit better to the BCSQ-12. Internal consistence was appropriate, and the convergence between the long-short versions was high. The pattern of relationships between the burnout subtypes and the psychological outcomes suggested a progressive deterioration from the frenetic to the under-challenged and worn-out. In sum, the Brazilian BCSQ-36/BCSQ-12 showed appropriate psychometrics to be used in primary healthcare personnel.

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.

The variation of the burden of hypertension and diabetes in two large districts of the city of São Paulo, Brazil, based on primary health care routinely-collected data.

BACKGROUND: Noncommunicable diseases (NCDs) were responsible for 72.3% of global deaths in 2016, with cardiovascular diseases accounting for almost half of those deaths and low- and middle-income countries carrying the biggest burden. As a result, the prevention and control of NCDs is recognized as urgent, while better surveillance at the country level could result in more effective policies. Hence, the objective of this study was to obtain more detailed information on the distribution of the prevalence of hypertension and diabetes among the population of two large districts of the city of São Paulo in Brazil, and to compare these findings to the results of a citywide health survey. METHODS AND FINDINGS: This cross-sectional study used primary health care (PHC) routinely-collected data. The study population included 187,110 individuals 20 years of age or older registered in 13 public PHC facilities at two districts of the city of São Paulo in 2015. Data extracted from SIAB, a primary care database, was used to calculate age and sex directly standardized prevalences for diabetes and hypertension for each PHC facility. The prevalence of hypertension among women was significantly higher than the prevalence among men in the entire study population, and in every PHC facility. There was great variation among PHC facilities that was more pronounced among women. The prevalence of diabetes among women was significantly higher than the prevalence among men in the entire study population, and in every PHC facility, but there was little variation among PHC facilities. CONCLUSIONS: This study provided information that could help with policy planning and allocation of resources, and demonstrated the use of PHC routinely-collected data to generate important insights that if replicated could have a substantial impact given the broad coverage of the national public PHC program in Brazil.

An open-label randomized controlled parallel-group pilot study comparing the immunogenicity of a standard-, double- and booster-dose regimens of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients

Background: Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. Methods: We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV) and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59) and BDTIIV regimens (58). Antibody titres were determined by hemagglutination inhibition at enrollment and 21 days post-vaccination. Seroprotection rates (SPR), seroconversion rates (SCR) and geometric mean ratios (GMR) were analyzed separately for participants with low (<1:40) and high (≥1:40) pre-vaccination antibody titres. Results: Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided post-vaccination blood samples. In the subgroup with high pre-vaccination antibody titres, all vaccination regimens induced SPR >70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low pre-vaccination antibody titres, DDTIIV and BDTIIV regimens induced adequate SCR >40% and GMR >2,5 for all antigens, while SDTIIV achieved the same outcomes only for influenza B. SPR were >70% only after DDTIIV (A/H1N1 - 77.8%) and BDTIIV (A/H3N2 - 77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR=2.58; p=0.021) and A/H3N2 (PR=2.21; p=0.004), while DDTIIV independently increased seroprotection to A/H1N1 (PR=2.59; p=0.021). Conclusion: Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

Campaign, counseling and compliance with influenza vaccine among older persons.

OBJECTIVES: Population aging raises concerns regarding the increases in the rates of morbidity and mortality that result from influenza and its complications. Although vaccination is the most important tool for preventing influenza, vaccination program among high-risk groups has not reached its predetermined aims in several settings. This study aimed to evaluate the impacts of clinical and demographic factors on vaccine compliance among the elderly in a setting that includes a well-established annual national influenza vaccination campaign. METHODS: This cross-sectional study included 134 elderly patients who were regularly followed in an academic medical institution and who were evaluated for their influenza vaccination uptake within the last five years; in addition, the demographic and clinical characteristics and the reasons for compliance or noncompliance with the vaccination program were investigated. RESULTS: In total, 67.1% of the participants received the seasonal influenza vaccine in 2009. Within this vaccination-compliant group, the most common reason for vaccine uptake was the annual nationwide campaign (52.2%; 95% CI: 41.4-62.9%); compared to the noncompliant group, a higher percentage of compliant patients had been advised by their physician to take the vaccine (58.9% vs. 34.1%; p<0.01). CONCLUSION: The education of patients and health care professionals along with the implementation of immunization campaigns should be evaluated and considered by health authorities as essential for increasing the success rate of influenza vaccination compliance among the elderly.

Prevalence, incidence density, and genotype distribution of GB virus C infection in a cohort of recently HIV-1-infected subjects in Sao Paulo, Brazil.

BACKGROUND: The results of previous studies elsewhere have indicated that GB virus C (GBV-C) infection is frequent in patients infected with the human immunodeficiency virus type 1 (HIV-1) due to similar transmission routes of both viruses. The aim of this study was to determine the prevalence, incidence density and genotypic characteristics of GBV-C in this population. METHODOLOGY/PRINCIPAL FINDINGS: The study population included 233 patients from a cohort primarily comprised of homosexual men recently infected with HIV-1 in São Paulo, Brazil. The presence of GBV-C RNA was determined in plasma samples by reverse transcriptase-nested polymerase chain reaction and quantified by real-time PCR. GBV-C genotypes were determined by direct sequencing. HIV viral load, CD4+ T lymphocyte and CD8+ T lymphocyte count were also tested in all patients. The overall prevalence of GBV-C infection was 0.23 (95% CI: 0.18 to 0.29) in the study group. There was no significant difference between patients with and without GBV-C infection and Glycoprotein E2 antibody presence regarding age, sex, HIV-1 viral load, CD4+ and CD8+T cell counts and treatment with antiretroviral drugs. An inverse correlation was observed between GBV-C and HIV-1 loads at enrollment and after one year. Also, a positive but not significant correlation was observed between GBV-C load and CD4+ T lymphocyte. Phylogenetic analysis of the GBV-C isolates revealed the presence of genotype 1 and genotype 2, these sub classified into subtype 2a and 2b. CONCLUSION/SIGNIFICANCE: GBV-C infection is common in recently HIV -1 infected patients in Sao Paulo, Brazil and the predominant genotype is 2b. This study provides the first report of the GBV-C prevalence at the time of diagnosis of HIV-1 and the incidence density of GBV-C infection in one year.