A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil.

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

Evaluation of Haemophilus influenzae type b carrier status among children 10 years after the introduction of Hib vaccine in Brazil.

The aim of the present study was to assess the prevalence of Haemophilus influenzae type b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010.

During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.

Accuracy of yellow fever case definition of epidemiologic surveillance, São Paulo, 2018.

OBJECTIVE: To evaluate the accuracy of yellow fever (YF) suspected case definitions from the Brazilian Ministry of Health (BMH) and World Health Organization (WHO), as well as propose and evaluate new definitions of suspected cases, considering confirmed and discarded cases. METHODS: The retrospective study was conducted at the Instituto de Infectologia Emílio Ribas (IIER), using the Epidemiologic Surveillance Form of YF cases. From the confirmed and discarded cases of YF, a logistic regression model was developed. The independent variables were used in a proposed definition of a suspected case of YF and its accuracy was evaluated. RESULTS: In total, 113 YF suspect cases were reported, with 78 confirmed (69.0%). The definitions by BMH and WHO presented low sensitivity, 59% and 53.8%, and reduced accuracy, 53.1% and 47.8%, respectively. Predictive factors for YF were thrombocytopenia, leukopenia, and elevation of transaminases greater than twice normal. The definition including individual with acute onset of fever, followed by elevation of ALT or AST greater than twice the reference value AND leukopenia OR thrombocytopenia presented high sensitivity (88.3%), specificity (62.9%), and the best accuracy (80.4%), as proposed in the model. CONCLUSION: The YF suspected case definitions of the BMH and the WHO have low sensitivity. The inclusion of nonspecific laboratory tests increases the accuracy of YF definition.

Early response to COVID-19 in Brazil: The impact of a targeted approach to suspected cases and on epidemiological surveillance efforts.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entered Brazil before travel restrictions and border closures were imposed. This study reports the characteristics of suspected and confirmed coronavirus disease 2019 (COVID-19) cases among symptomatic international travelers in Brazil and their contacts. Methods: The REDCap platform developed by the Brazilian Ministry of Health was analyzed to identify and investigate suspected cases of COVID-19 recorded during the period January 1 to March 20, 2020. The impact of Brazil's targeted approach to suspected cases from specific countries on epidemiological surveillance efforts during the early stages of the COVID-19 pandemic were analyzed. Results: Based on molecular RT-PCR tests, there were 217 (4.2%) confirmed, 1030 (20.1%) unconfirmed, 722 (14.1%) suspected, and 3157 (61.6%) non-investigated cases among travelers returning from countries included on the alert list for surveillance, as defined by the Ministry of Health. Among the 3372 travelers who went to countries not included on the alert list, there were 66 (2.0%) confirmed, 845 (25.3%) unconfirmed, 521 (15.6%) suspected, and 1914 (57.2%) non-investigated cases. A comparison of the characteristics of confirmed cases returning from alert and non-alert countries did not reveal a statistically significant difference in symptoms. Almost half of the hospitalized travelers with known travel dates and hospitalization status (53.6%) were inbound from countries not included on the alert list, and RT-PCR tests were reported for only 30.5%. Conclusions: Policies adopted at entry points to contain the introduction of SARS-CoV-2 in Brazil were not ideal. An analysis of the early response shows that surveillance of travelers, including testing strategies, data standards, and reporting systems, was insufficient.

Social inequalities and COVID-19 mortality in the city of São Paulo, Brazil.

BACKGROUND: Heterogeneity in COVID-19 morbidity and mortality is often associated with a country's health-services structure and social inequality. This study aimed to characterize social inequalities in COVID-19 mortality in São Paulo, the most populous city in Brazil and Latin America. METHODS: We conducted a population-based study, including COVID-19 deaths among São Paulo residents from March to September 2020. Age-standardized mortality rates and unadjusted rate ratios (RRs) [with corresponding 95% confidence intervals (CIs)] were estimated by race, sex, age group, district of residence, household crowding, educational attainment, income level and percentage of households in subnormal areas in each district. Time trends in mortality were assessed using the Joinpoint model. RESULTS: Males presented an 84% increase in COVID-19 mortality compared with females (RR = 1.84, 95% CI 1.79-1.90). Higher mortality rates were observed for Blacks (RR = 1.77, 95% CI 1.67-1.88) and mixed (RR = 1.42, 95% CI 1.37-1.47) compared with Whites, whereas lower mortality was noted for Asians (RR = 0.63, 95% CI 0.58-0.68). A positive gradient was found for all socio-economic indicators, i.e. increases in disparities denoted by less education, more household crowding, lower income and a higher concentration of subnormal areas were associated with higher mortality rates. A decrease in mortality over time was observed in all racial groups, but it started earlier among Whites and Asians. CONCLUSION: Our results reveal striking social inequalities in COVID-19 mortality in São Paulo, exposing structural inequities in Brazilian society that were not addressed by the governmental response to COVID-19. Without an equitable response, COVID-19 will further exacerbate current social inequalities in São Paulo.

Spatiotemporal pattern of COVID-19 spread in Brazil.

Brazil has been severely hit by COVID-19, with rapid spatial spread of both cases and deaths. We used daily data on reported cases and deaths to understand, measure, and compare the spatiotemporal pattern of the spread across municipalities. Indicators of clustering, trajectories, speed, and intensity of the movement of COVID-19 to interior areas, combined with indices of policy measures, show that although no single narrative explains the diversity in the spread, an overall failure of implementing prompt, coordinated, and equitable responses in a context of stark local inequalities fueled disease spread. This resulted in high and unequal infection and mortality burdens. With a current surge in cases and deaths and several variants of concern in circulation, failure to mitigate the spread could further aggravate the burden.

Splenic Infarction with Aortic Thrombosis in COVID-19.

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of venous and arterial thrombotic disease. Although pulmonary embolism has been the most common thrombotic complication, there have been recent reports of COVID-19-associated large-vessel ischemic stroke, acute upper- and lower-limb ischemia, as well as infarctions of the abdominal viscera, including renal, splenic, and small bowel infarctions. Here, we describe a case of splenic infarction (SI) associated with aortic thrombosis, which evolved despite the prophylactic use of low-molecular-weight heparin (LMWH), in a 60-year-old female patient with COVID-19. The patient was treated clinically with a therapeutic dose of LMWH, followed by warfarin, and eventually presented a favorable outcome. We also present a review of the literature regarding SI in patients with COVID-19.

Potential autoimmune encephalitis following yellow fever vaccination: A report of three cases.

Meningoencephalitis following yellow fever vaccination is considered a viral neuroinvasive disease. We describe three patients with typical autoimmune encephalitis syndromes that developed 1-27 days following yellow fever vaccination. Anti-N-methyl-d-aspartate-r antibodies were identified in the CSF and serum of two patients and the other case was associated with anti-neurexin-3 antibodies. One case was confirmed as vaccine-associated neurotropic disease due to reactive CSF yellow fever IgM, which suggested an infectious-autoimmune overlap mechanism. Two aditional cases of Anti-N-methyl-d-aspartate-r encephalitis were identified in the literature review. Antibody-positive autoimmune encephalitis should be included in the differential diagnosis of neurologic adverse events following yellow fever vaccination.

Intensive care unit staff preparedness as an independent factor for death of patients during COVID-19 pandemic: An observational cohort study.

The pandemic of COVID-19 brought to the world an unprecedented challenge. This single center observational study aimed to evaluate the impact of staff preparedness by comparing the outcomes between two intensive care units (ICUs) from a hospital that had to expand ICU beds to deal with an incremented volume of critical patients. Patients consecutively admitted to these ICUs with suspected COVID-19, from March 1st until April 30th, 2020, were included. Both ICUs attended a similar population and had the same facilities, what differed was the staff: one previously well-established (ICU-1) and another recently assembled (ICU-2). 114 patients with severe respiratory syndrome were included. In-hospital mortality was 40%. Compared with patients in the well-established ICU-1, patients in the recently assembled ICU-2 were older (54 versus 61.5, p=0.045), received more antibiotics (93% versus 98%, p=0.001) and chloroquine/hydroxychloroquine 6% versus 30%, p=0.001), had a higher proportion of invasive mechanical ventilation (44% versus 52%, p=0.008) and had greater in-hospital mortality (30% versus 50%, p=0.017). The proportion of patients considered at high risk for death according to PSI was similar between the two ICU populations. Age ≥ 60 years (adjusted OR 2.33; 95% CI 1.02-5.31), need of invasive mechanical ventilation (adjusted OR 2.79; 95% CI 1.22-6.37), and ICU type (recently assembled) (adjusted OR 2.38; 95% CI 1.04-5.44) were independently associated with in-hospital mortality . This finding highlights the importance of developing support strategies to improve preparedness of staff recently assembled to deal with emergencies.

Detection of Wild-type Yellow Fever Virus in Breast Milk.

Yellow fever is an endemic disease in tropical areas in America and Africa. We report a case where the wild-type yellow fever virus was detected in a breast milk sample of a 33-year-old woman, from a rural area in the municipality of São Paulo, thus highlighting a potential risk for transmission of yellow fever virus through breast-feeding.

Yellow Fever: Factors Associated with Death in a Hospital of Reference in Infectious Diseases, São Paulo, Brazil, 2018.

Faced with the reemergence of yellow fever (YF) in the metropolitan region of São Paulo, Brazil, we developed a retrospective study to describe the cases of YF attended at the Institute of Infectology Emilio Ribas from January to March 2018 and analyze the factors associated with death, from the information obtained in the hospital epidemiological investigation. A total of 72 cases of sylvatic YF were confirmed, with 21 deaths (29.2% lethality rate). Cases were concentrated in males (80.6%) and in the age group of 30 to 59 years (56.9%). Two logistic regression models were performed, with continuous variables adjusted for the time between onset of symptoms and hospitalization. The first model indicated age (odds ratiosadjusted [ORadj]: 1.038; CI 95%: 1.008-1.212), aspartate aminotransferase (AST) (ORadj: 1.038; CI 95%: 1.005-1.072), and creatinine (ORadj: 2.343; CI 95%: 1.205-4.553) were independent factors associated with mortality. The second model indicated age (ORadj: 1.136; CI 95%: 1.013-1.275), alanine aminotransferase (ALT) (ORadj: 1.118; CI 95%: 1.018-1.228), and creatinine (ORadj: 2.835; CI 95%: 1.352-5,941). The risk of death in the model with continuous variables was calculated from the increase of 1 year (age), 1 mg/dL (creatinine), and 100 U/L for AST and ALT. Another logistic regression analysis with dichotomous variables indicated AST > 1,841 IU/L (ORadj: 12.92; CI 95%: 1.50-111.37) and creatinine > 1.2 mg/dL (ORadj: 81.47; CI 95%: 11.33-585.71) as independent factors associated with death. These results may contribute to the appropriate clinical management of patients with YF in health-care services and improve the response to outbreaks and public health emergencies.

Efficacy of sofosbuvir as treatment for yellow fever: protocol for a randomised controlled trial in Brazil (SOFFA study).

INTRODUCTION: An ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YF. This is a multicentre open-label randomised controlled trial with 1:1 individual allocation, stratified by severity and by recruiting centre. METHODS AND ANALYSIS: Adults with suspected or confirmed YF infection and symptoms lasting up to 15 days are screened. Eligible and consenting patients are randomised to receive oral sofosbuvir 400 mg daily for 10 days or to receive standard clinical care. Viral kinetics are measured daily and the reduction in YF plasma viral load from the sample at inclusion to 72 hours after randomisation will be compared between active and control groups. Clinical outcomes include severity meeting criteria for intensive care support, liver transplantation, in-hospital mortality and mortality within 60 days. ETHICS AND DISSEMINATION: Ethics approval was obtained at the participating sites and at the national research ethics committee (CAAE 82673018.6.1001.0068). The trial has been submitted for ethical approval at additional potential recruiting centres. Results of the study will be published in journals and presented at scientific meetings. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (RBR-93dp9n).

Accuracy of yellow fever case definition of epidemiologic surveillance, São Paulo, 2018

ABSTRACT OBJECTIVE To evaluate the accuracy of yellow fever (YF) suspected case definitions from the Brazilian Ministry of Health (BMH) and World Health Organization (WHO), as well as propose and evaluate new definitions of suspected cases, considering confirmed and discarded cases. METHODS The retrospective study was conducted at the Instituto de Infectologia Emílio Ribas (IIER), using the Epidemiologic Surveillance Form of YF cases. From the confirmed and discarded cases of YF, a logistic regression model was developed. The independent variables were used in a proposed definition of a suspected case of YF and its accuracy was evaluated. RESULTS In total, 113 YF suspect cases were reported, with 78 confirmed (69.0%). The definitions by BMH and WHO presented low sensitivity, 59% and 53.8%, and reduced accuracy, 53.1% and 47.8%, respectively. Predictive factors for YF were thrombocytopenia, leukopenia, and elevation of transaminases greater than twice normal. The definition including individual with acute onset of fever, followed by elevation of ALT or AST greater than twice the reference value AND leukopenia OR thrombocytopenia presented high sensitivity (88.3%), specificity (62.9%), and the best accuracy (80.4%), as proposed in the model. CONCLUSION The YF suspected case definitions of the BMH and the WHO have low sensitivity. The inclusion of nonspecific laboratory tests increases the accuracy of YF definition.

Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of Sao Paulo, Brazil, 2009.

To investigate the factors associated with death and describe the gestational outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case-control study (deaths and recovered) in hospitalized pregnant women with laboratory-confirmed influenza A(H1N1)pdm09 with severe acute respiratory illness (SARI) in the state of São Paulo from June 9 to December 1, 2009. All cases were evaluated, and four controls that were matched by the epidemiological week of hospitalization of the case were randomly selected for each case. Cases and controls were selected from the National Disease Notification System-SINAN Influenza-web. The hospital records from 126 hospitals were evaluated, and home interviews were conducted using standardized forms. A total of 48 cases and 185 controls were investigated. Having had a previous health visit to a healthcare provider for an influenza episode before hospital admission was a risk factor for death (adjusted OR (ORadj) of 7.93, 95% CI 2.19-28.69). Although not significant in the multiple analysis (ORadj of 2.13, 95% CI 0.91-5.00), the 3rd trimester deserves attention, with an OR = 2.22, 95% CI 1.13-4.37 in the univariate analysis. Antiviral treatment was a protective factor when administered within 48 hours of symptom onset (ORadj = 0.16, 95% CI 0.05-0.50) and from 48 to 72 hours (ORadj = 0.09, 95% CI 0.01-0.87). There was a higher proportion of fetal deaths and preterm births among cases (p = 0.001) and live births with low weight (p = 0.019), compared to control subjects who gave birth during hospitalization. After discharge, control subjects had a favorable neonatal outcome. Early antiviral treatment during the presence of a flu-like illness is an important factor in reducing mortality from influenza in pregnant women and unfavorable neonatal outcomes. It is important to monitor pregnant women, particularly in the 3rd trimester of gestation, with influenza illness for diagnosis and early treatment.

Educação permanente como estratégia para busca ativa dos sintomáticos respiratórios no território de uma unidade de saúde da família em Guarulhos - SP / Permanent education as a strategy for active search for respiratory symptoms in the territory of a family health unit in the city of Guarulhos - SP

OBJETIVO: analisar a efetividade da educação permanente na busca ativa dos sintomáticos respiratórios. MÉTODO: estudo descritivo e transversal com abordagem quantitativa realizada no ano de 2017. Os dados (total de interrogados e total de coletas de escarro) foram coletados dos registros laboratoriais e do livro de registro dos sintomáticos respiratórios por área da estratégia de saúde da família. Após a identificação da fragilidade, foi realizada a capacitação e reflexão crítica por meio de problematizações temáticas sobre tuberculose e busca ativa dos casos na população. RESULTADOS: mudanças consideráveis ocorreram nos indicadores da UBS, verificados com o aumento expressivo das coletas de escarro e do registro dos interrogados de sintomáticos respiratórios. CONCLUSÃO: com aumento de 241,8% no total de coletas na unidade, foi possível verificar a evolução na identificação dos sintomáticos, tratamento em tempo adequado dos portadores de tuberculose e promoção de saúde.

OBJECTIVE: to analyze the effectiveness of continuing education in the active search for respiratory symptoms. METHOD: a descriptive and cross-sectional study with a quantitative approach carried out in 2017. The data (total of respondents and total sputum collections) were collected from laboratory records and the respiratory symptomatic registry book by area of the family health strategy. After identifying the fragility, training and critical reflection were carried out through thematic problematizations about tuberculosis and active search for cases in the population. RESULTS: considerable changes occurred in the indicators of the Basic Health Unit, verified with the expressive increase in sputum collections and in the registration of respondents of respiratory symptoms. CONCLUSION: with an increase of 241.8% in the total collections in the unit, it was possible to verify the evolution in the identification of symptomatic patients, timely treatment of tuberculosis patients and health promotion.

Risk factors for death from Influenza A(H1N1)pdm09, State of São Paulo, Brazil, 2009.

This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28th and August 29th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31-4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11-3.57, if one or OR = 6.05, 95%CI: 2.76-13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28-5.83), immunosuppression (OR = 3.43, 95%CI: 1.28-9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75-6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08-0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11-0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.