A Poisson-multinomial spatial model for simultaneous outbreaks with application to arboviral diseases.

Dengue, Zika, and chikungunya are arboviral diseases (AVD) transmitted mainly by Aedes aegypti. Rio de Janeiro city, Brazil, has been endemic for dengue for over 30 years, and experienced the first joint epidemic of the three diseases between 2015-2016. They present similar symptoms and only a small proportion of cases are laboratory-confirmed. These facts lead to potential misdiagnosis and, consequently, uncertainty in the registration of the cases. We have available the number of cases of each disease for the n=160 neighborhoods of Rio de Janeiro. We propose a Poisson model for the total number of cases of Aedes-borne diseases and, conditioned on the total, we assume a multinomial model for the allocation of the number of cases of each of the diseases across the neighborhoods. This provides simultaneously the estimation of the associations of the relative risk of the total cases of AVD with environmental and socioeconomic variables; and the estimation of the probability of presence of each disease as a function of available covariates. Our findings suggest that a one standard deviation increase in the social development index decreases the relative risk of the total cases of AVD by 28%. Neighborhoods with smaller proportion of green area had greater odds of having chikungunya in comparison to dengue and Zika. A one standard deviation increase in population density decreases the odds of a neighborhood having Zika instead of dengue by 18% but increases the odds of chikungunya in comparison to dengue by 18% and by 43% in comparison to Zika.

Associations of human papillomavirus (HPV) genotypes and related risk factors in a cohort of women living with HIV in a Brazilian countryside city.

The human papillomavirus (HPV) is associated with cervical abnormalities. People living with HIV are more susceptible to HPV. Campos dos Goytacazes implemented the quadrivalent HPV vaccine (4vHPV) for women living with HIV (WLWH) in 2011, 4 years before the Brazilian public vaccination program. We aimed to characterize the genomic diversity and predictors of HPV infection in WLWH through a prospective cohort study. After the consent form was received, a questionnaire was applied and an endocervical sample was collected. For genotyping, a microarray HPV technique was performed. Two intervention moments were performed: T1, the initial moment, with collection and vaccination; T2 moment, 2 years after T1. Univariate and multivariate analyses were performed. The T1 moment cohort was formed by 146 women,107 belonging to Group 1(HPV-negative) and 39 to Group 2 (HPV-positive). The variables age, marital status, number of children, number of sexual partners, and CD4 count were protective against HPV. The variables number of sexual partners, marital status, and the number of children lost significance in multivariate analysis. Concerning T2 moment, 42 patients were followed with three positive cases. The use of 4vHPV is beneficial for this population and should also be recommended at an age from 26 to 45 years inside the public vaccination program.

Cohort-profile: Household transmission of SARS-CoV-2 in a low-resource community in Rio de Janeiro, Brazil.

PURPOSE: To better understand the household transmission of SARS-COV-2 in a low-resource community in Rio de Janeiro during the COVID-19 pandemic (2020-2022). PARTICIPANTS: This is an open prospective cohort study of children ≤12 years old and their household contacts. During home visits over 24 months, we collected data on sociodemographic characteristics, behavioural data, clinical manifestations of SARS-CoV-2, vaccination status, SARS-CoV-2 (reverse transcription-polymerase chain reaction) RT-PCR and anti-S antibody tests. Among adults, the majority of participants were women (62%). FINDINGS TO DATE: We enrolled 845 families from May 2020 to May 2022. The median number of residents per household was four. The median household density, defined as the number of persons per room, was 0.95. The risk of SARS-CoV-2 occurrence was higher in households with a high number of persons per room. Children were not the principal source of SARS-CoV-2 infections in their households during the first wave of the pandemic. FUTURE PLANS: Future studies will investigate cellular and humoral immune responses to locally circulating SARS-CoV-2 variants, which is relevant for the design of vaccines, antivirals and monoclonal antibodies. We will also engage in outreach to encourage vaccination as a means of limiting the transmission of novel SARS-CoV-2 variants and other emerging pathogens.

Assessing the spread of COVID-19 in Brazil: Mobility, morbidity and social vulnerability.

Brazil detected community transmission of COVID-19 on March 13, 2020. In this study we identified which areas in the country were the most vulnerable for COVID-19, both in terms of the risk of arrival of cases, the risk of sustained transmission and their social vulnerability. Probabilistic models were used to calculate the probability of COVID-19 spread from São Paulo and Rio de Janeiro, the initial hotspots, using mobility data from the pre-epidemic period, while multivariate cluster analysis of socio-economic indices was done to identify areas with similar social vulnerability. The results consist of a series of maps of effective distance, outbreak probability, hospital capacity and social vulnerability. They show areas in the North and Northeast with high risk of COVID-19 outbreak that are also highly socially vulnerable. Later, these areas would be found the most severely affected. The maps produced were sent to health authorities to aid in their efforts to prioritize actions such as resource allocation to mitigate the effects of the pandemic. In the discussion, we address how predictions compared to the observed dynamics of the disease.

COVID-19 and hospitalizations for SARI in Brazil: a comparison up to the 12th epidemiological week of 2020. / COVID-19 e hospitalizações por SRAG no Brasil: uma comparação até a 12ª semana epidemiológica de 2020.

Surveillance of the severe acute respiratory illness (SARI) in Brazil aims to characterize the circulation of the Influenza A and B viruses in hospitalized cases and deaths, having been expanded in 2012 to include other respiratory viruses. COVID-19 was detected in Brazil for the time in the 9th epidemiological week of 2020, and the test for the SARS-CoV-2 virus was included in the surveillance protocol starting in the 12th epidemiological week. This study's objective was to investigate the pattern of hospitalizations for SARI in Brazil since the entry of SARS-CoV-2, comparing the temporal and age profiles and laboratory results to the years 2010 through 2019. In 2020, hospitalizations for SARI, compiled from the date of the first confirmed case of COVID-19 up to the 12th week, exceeded the numbers observed during the same period in each of the previous 10 years. The age bracket over 60 years was the most heavily affected, at higher than historical levels. There was a considerable increase in negative laboratory tests, suggesting circulation of a different virus from those already present in the panel. We concluded that the increase in hospitalizations for SARI, the lack of specific information on the etiological agent, and the predominance of cases among the elderly during the same period in which there was an increase in the number of new cases of COVID-19 are all consistent with the hypothesis that severe cases of COVID-19 are already being detected by SARI surveillance, placing an overload on the health system. The inclusion of testing for SARS-CoV-2 in the SARI surveillance protocol and the test's effective nationwide deployment are extremely important for monitoring the evolution of severe COVID-19 cases in Brazil.

A vigilância de síndrome respiratória aguda grave (SRAG) no Brasil visa a caracterizar a circulação dos vírus Influenza A e B em casos hospitalizados e óbitos, tendo sido ampliada em 2012 para incluir outros vírus respiratórios. A COVID-19 foi detectada no Brasil pela primeira vez na 9ª semana epidemiológica de 2020 e o teste para o vírus SARS-CoV-2 foi incluído no protocolo de vigilância a partir da 12ª semana epidemiológica. O objetivo deste estudo foi investigar o padrão de hospitalizações por SRAG no país após a entrada do SARS-CoV-2, comparando o perfil temporal, etário e de resultados laboratoriais com os anos de 2010 a 2019. Em 2020, a hospitalização por SRAG, contabilizada desde a data do primeiro caso de COVID-19 confirmado até a 12ª semana, superou o observado, no mesmo período, em cada um dos 10 anos anteriores. A faixa etária acima de 60 anos foi a mais acometida, em nível acima do histórico. Houve um aumento considerável de testes laboratoriais negativos, sugerindo a circulação de um vírus diferente dos presentes no painel. Concluímos que o aumento das hospitalizações por SRAG, a falta de informação específica sobre o agente etiológico e a predominância de casos entre idosos, no mesmo período de tempo em que cresce o número de casos novos de COVID-19, é coerente com a hipótese de que os casos graves da doença já estejam sendo detectados pela vigilância de SRAG com sobrecarga para o sistema de saúde. A inclusão da testagem para SARS-CoV-2 no protocolo de vigilância de SRAG e sua efetiva implementação são de grande importância para acompanhar a evolução dos casos graves da doença no país.

La vigilancia del síndrome respiratorio agudo grave (SRAG) en Brasil tiene como objetivo caracterizar la circulación de los virus de la Influenza A y B en casos y muertes hospitalizadas, y se expandió en 2012 para incluir otros virus respiratorios. La COVID-19 se detectó en Brasil por la primera vez en la 9ª semana epidemiológica de 2020, y el examen test para el virus SARS-CoV-2 se incluyó en el protocolo de vigilancia a partir de la 12ª semana epidemiológica. El objetivo de este estudio fue investigar el patrón de hospitalizaciones por SRAG en Brasil desde la entrada de SARS-CoV-2, comparando el perfil temporal y de edad y los resultados de laboratorio entre los años 2010 a 2019. En 2020, las hospitalizaciones por SRAG, compiladas a partir de la fecha del primer caso confirmado de COVID-19 hasta la 12ª semana, excedió los números observados durante el mismo período en cada uno de los 10 años anteriores. El grupo de edad mayor de 60 años fue el más afectado, a niveles superiores a los históricos. Hubo un aumento considerable en las pruebas de laboratorio negativas, lo que sugiere la circulación de un virus diferente de los que ya están presentes en el panel. Se concluye que el aumento de las hospitalizaciones por SRAG, la falta de información específica sobre el agente etiológico y el predominio de casos entre los ancianos en el mismo período en que hubo un aumento de casos nuevos de COVID-19 se entiende que con esta hipótesis de que los casos graves de COVID-19 ya estén siendo monitorados por la vigilancia de SRAG, lo que genera una sobrecarga en el sistema de salud. La inclusión de los exámenes para SARS-CoV-2 en el protocolo de vigilancia de SRAG y la eficacia de implementación son de grande importancia para monitorear la evolución de los casos graves de COVID-19 en Brasil.

COVID-19 e hospitalizações por SRAG no Brasil: uma comparação até a 12ª semana epidemiológica de 2020 / COVID-19 y las hospitalizaciones por el SRAG en Brasil: una comparación hasta la 12ª semana epidemiológica de 2020 / COVID-19 and hospitalizations for SARI in Brazil: a comparison up to the 12th epidemiological week of 2020

Resumo: A vigilância de síndrome respiratória aguda grave (SRAG) no Brasil visa a caracterizar a circulação dos vírus Influenza A e B em casos hospitalizados e óbitos, tendo sido ampliada em 2012 para incluir outros vírus respiratórios. A COVID-19 foi detectada no Brasil pela primeira vez na 9ª semana epidemiológica de 2020 e o teste para o vírus SARS-CoV-2 foi incluído no protocolo de vigilância a partir da 12ª semana epidemiológica. O objetivo deste estudo foi investigar o padrão de hospitalizações por SRAG no país após a entrada do SARS-CoV-2, comparando o perfil temporal, etário e de resultados laboratoriais com os anos de 2010 a 2019. Em 2020, a hospitalização por SRAG, contabilizada desde a data do primeiro caso de COVID-19 confirmado até a 12ª semana, superou o observado, no mesmo período, em cada um dos 10 anos anteriores. A faixa etária acima de 60 anos foi a mais acometida, em nível acima do histórico. Houve um aumento considerável de testes laboratoriais negativos, sugerindo a circulação de um vírus diferente dos presentes no painel. Concluímos que o aumento das hospitalizações por SRAG, a falta de informação específica sobre o agente etiológico e a predominância de casos entre idosos, no mesmo período de tempo em que cresce o número de casos novos de COVID-19, é coerente com a hipótese de que os casos graves da doença já estejam sendo detectados pela vigilância de SRAG com sobrecarga para o sistema de saúde. A inclusão da testagem para SARS-CoV-2 no protocolo de vigilância de SRAG e sua efetiva implementação são de grande importância para acompanhar a evolução dos casos graves da doença no país.

Resumen: La vigilancia del síndrome respiratorio agudo grave (SRAG) en Brasil tiene como objetivo caracterizar la circulación de los virus de la Influenza A y B en casos y muertes hospitalizadas, y se expandió en 2012 para incluir otros virus respiratorios. La COVID-19 se detectó en Brasil por la primera vez en la 9ª semana epidemiológica de 2020, y el examen test para el virus SARS-CoV-2 se incluyó en el protocolo de vigilancia a partir de la 12ª semana epidemiológica. El objetivo de este estudio fue investigar el patrón de hospitalizaciones por SRAG en Brasil desde la entrada de SARS-CoV-2, comparando el perfil temporal y de edad y los resultados de laboratorio entre los años 2010 a 2019. En 2020, las hospitalizaciones por SRAG, compiladas a partir de la fecha del primer caso confirmado de COVID-19 hasta la 12ª semana, excedió los números observados durante el mismo período en cada uno de los 10 años anteriores. El grupo de edad mayor de 60 años fue el más afectado, a niveles superiores a los históricos. Hubo un aumento considerable en las pruebas de laboratorio negativas, lo que sugiere la circulación de un virus diferente de los que ya están presentes en el panel. Se concluye que el aumento de las hospitalizaciones por SRAG, la falta de información específica sobre el agente etiológico y el predominio de casos entre los ancianos en el mismo período en que hubo un aumento de casos nuevos de COVID-19 se entiende que con esta hipótesis de que los casos graves de COVID-19 ya estén siendo monitorados por la vigilancia de SRAG, lo que genera una sobrecarga en el sistema de salud. La inclusión de los exámenes para SARS-CoV-2 en el protocolo de vigilancia de SRAG y la eficacia de implementación son de grande importancia para monitorear la evolución de los casos graves de COVID-19 en Brasil.

Abstract: Surveillance of the severe acute respiratory illness (SARI) in Brazil aims to characterize the circulation of the Influenza A and B viruses in hospitalized cases and deaths, having been expanded in 2012 to include other respiratory viruses. COVID-19 was detected in Brazil for the time in the 9th epidemiological week of 2020, and the test for the SARS-CoV-2 virus was included in the surveillance protocol starting in the 12th epidemiological week. This study's objective was to investigate the pattern of hospitalizations for SARI in Brazil since the entry of SARS-CoV-2, comparing the temporal and age profiles and laboratory results to the years 2010 through 2019. In 2020, hospitalizations for SARI, compiled from the date of the first confirmed case of COVID-19 up to the 12th week, exceeded the numbers observed during the same period in each of the previous 10 years. The age bracket over 60 years was the most heavily affected, at higher than historical levels. There was a considerable increase in negative laboratory tests, suggesting circulation of a different virus from those already present in the panel. We concluded that the increase in hospitalizations for SARI, the lack of specific information on the etiological agent, and the predominance of cases among the elderly during the same period in which there was an increase in the number of new cases of COVID-19 are all consistent with the hypothesis that severe cases of COVID-19 are already being detected by SARI surveillance, placing an overload on the health system. The inclusion of testing for SARS-CoV-2 in the SARI surveillance protocol and the test's effective nationwide deployment are extremely important for monitoring the evolution of severe COVID-19 cases in Brazil.

A modelling approach for correcting reporting delays in disease surveillance data.

One difficulty for real-time tracking of epidemics is related to reporting delay. The reporting delay may be due to laboratory confirmation, logistical problems, infrastructure difficulties, and so on. The ability to correct the available information as quickly as possible is crucial, in terms of decision making such as issuing warnings to the public and local authorities. A Bayesian hierarchical modelling approach is proposed as a flexible way of correcting the reporting delays and to quantify the associated uncertainty. Implementation of the model is fast due to the use of the integrated nested Laplace approximation. The approach is illustrated on dengue fever incidence data in Rio de Janeiro, and severe acute respiratory infection data in the state of Paraná, Brazil.

The Zika Virus Epidemic in Brazil: From Discovery to Future Implications.

The first confirmed case of Zika virus infection in the Americas was reported in Northeast Brazil in May 2015, although phylogenetic studies indicate virus introduction as early as 2013. Zika rapidly spread across Brazil and to more than 50 other countries and territories on the American continent. The Aedesaegypti mosquito is thought to be the principal vector responsible for the widespread transmission of the virus. However, sexual transmission has also been reported. The explosively emerging epidemic has had diverse impacts on population health, coinciding with cases of Guillain-Barré Syndrome and an unexpected epidemic of newborns with microcephaly and other neurological impairments. This led to Brazil declaring a national public health emergency in November 2015, followed by a similar decision by the World Health Organization three months later. While dengue virus serotypes took several decades to spread across Brazil, the Zika virus epidemic diffused within months, extending beyond the area of permanent dengue transmission, which is bound by a climatic barrier in the south and low population density areas in the north. This rapid spread was probably due to a combination of factors, including a massive susceptible population, climatic conditions conducive for the mosquito vector, alternative non-vector transmission, and a highly mobile population. The epidemic has since subsided, but many unanswered questions remain. In this article, we provide an overview of the discovery of Zika virus in Brazil, including its emergence and spread, epidemiological surveillance, vector and non-vector transmission routes, clinical complications, and socio-economic impacts. We discuss gaps in the knowledge and the challenges ahead to anticipate, prevent, and control emerging and re-emerging epidemics of arboviruses in Brazil and worldwide.

The impact of the Brazilian Family Health Strategy and the conditional cash transfer on tuberculosis treatment outcomes in Rio de Janeiro: an individual-level analysis of secondary data.

Background: Unsuccessful tuberculosis outcomes are frequent; bold policies are needed to end the tuberculosis (TB) epidemic to attain the third Sustainable Development Goal (SDG) by 2030. We examined the effect of the Family Health Strategy (FHS) and its interactions with the conditional cash transfer programme (CTP) on TB outcomes in Rio de Janeiro, Brazil. Methods: We performed individual-based analyses of a database resulting from deterministic and probabilistic linkages of the TB information system, FHS registries and CTP payrolls. Patients ≥15 years old treated with the standard RHZE regimen were included. The rates of successful outcomes were analysed according to coverage by FHS. Effects from the CTP and its interactions with the FHS were examined among the poorest. Results: FHS coverage increased the likelihood for successful outcomes by 14% (12-17%) among 13 482 new cases, and by 35% (25-47%) among 1880 retreatment cases. The CTP had an independent effect but no interaction with the FHS among the poorest. Conclusions: This is the first individual-based study to show a relevant protection of poor urban communities regarding patient-important health outcomes by the Brazilian FHS and CTP. These findings support strategies of universal health coverage, primary care strengthening and social protection to achieve a major SDG.

Correction to: Socioeconomic and demographic characterization of an endemic malaria region in Brazil by multiple correspondence analysis.

After publication of the article [1], it has been brought to our attention that the y-axis of Fig. 6 has been labeled incorrectly. It should read "linear predictor". This has now been corrected in the original article.

Socioeconomic and demographic characterization of an endemic malaria region in Brazil by multiple correspondence analysis.

BACKGROUND: In the process of geographical retraction of malaria, some important endemicity pockets remain. Here, we report results from a study developed to obtain detailed community data from an important malaria hotspot in Latin America (Alto Juruá, Acre, Brazil), to investigate the association of malaria with socioeconomic, demographic and living conditions. METHODS: A household survey was conducted in 40 localities (n = 520) of Mâncio Lima and Rodrigues Alves municipalities, Acre state. Information on previous malaria, schooling, age, gender, income, occupation, household structure, habits and behaviors related to malaria exposure was collected. Multiple correspondence analysis (MCA) was applied to characterize similarities between households and identify gradients. The association of these gradients with malaria was assessed using regression. RESULTS: The first three dimensions of MCA accounted for almost 50% of the variability between households. The first dimension defined an urban/rurality gradient, where urbanization was associated with the presence of roads, basic services as garbage collection, water treatment, power grid energy, and less contact with the forest. There is a significant association between this axis and the probability of malaria at the household level, OR = 1.92 (1.23-3.02). The second dimension described a gradient from rural settlements in agricultural areas to those in forested areas. Access via dirt road or river, access to electricity power-grid services and aquaculture were important variables. Malaria was at lower risk at the forested area, OR = 0.55 (1.23-1.12). The third axis detected intraurban differences and did not correlate with malaria. CONCLUSIONS: Living conditions in the study area are strongly geographically structured. Although malaria is found throughout all the landscapes, household traits can explain part of the variation found in the odds of having malaria. It is expected these results stimulate further discussions on modelling approaches targeting a more systemic and multi-level view of malaria dynamics.

Clustering symptoms of non-severe malaria in semi-immune Amazonian patients.

Malaria is a disease that generates a broad spectrum of clinical features. The purpose of this study was to evaluate the clinical spectrum of malaria in semi-immune populations. Patients were recruited in Mâncio Lima, a city situated in the Brazilian Amazon region. The study included 171 malaria cases, which were diagnosed via the use of a thick blood smear and confirmed by molecular methods. A questionnaire addressing 19 common symptoms was administered to all patients. Multiple correspondence analysis and hierarchical cluster analysis were performed to identify clusters of symptoms, and logistic regression was used to identify factors associated with the occurrence of symptoms. The cluster analysis revealed five groups of symptoms: the first cluster, which included algic- and fever-related symptoms, occurred in up to 95.3% of the cases. The second cluster, which comprised gastric symptoms (nausea, abdominal pain, inappetence, and bitter mouth), occurred in frequencies that ranged between 35.1% and 42.7%, and at least one of these symptoms was observed in 71.9% of the subjects. All respiratory symptoms were clustered and occurred in 42.7% of the malaria cases, and diarrhea occurred in 9.9% of the cases. Symptoms constituting the fifth cluster were vomiting and pallor, with a 14.6% and 11.7% of prevalence, respectively. A higher parasitemia count (more than 300 parasites/mm(3)) was associated with the presence of fever, vomiting, dizziness, and weakness (P < 0.05). Arthralgia and myalgia were associated with patients over the age of 14 years (P < 0.001). Having experienced at least eight malaria episodes prior to the study was associated with a decreased risk of chills and fever and an increased risk of sore throat (P < 0.05). None of the symptoms showed an association with gender or with species of Plasmodium. The clinical spectrum of malaria in semi-immune individuals can have a broad range of symptoms, the frequency and intensity of which are associated with age, past exposure to malaria, and parasitemia. Understanding the full spectrum of nonsevere malaria is important in endemic areas to guide both passive and active case detection, for the diagnosis of malaria in travelers returning to non-endemic areas, and for the development of vaccines aimed to decrease symptom severity.

Sensitivity and specificity of the World Health Organization dengue classification schemes for severe dengue assessment in children in Rio de Janeiro.

BACKGROUND: The clinical definition of severe dengue fever remains a challenge for researchers in hyperendemic areas like Brazil. The ability of the traditional (1997) as well as the revised (2009) World Health Organization (WHO) dengue case classification schemes to detect severe dengue cases was evaluated in 267 children admitted to hospital with laboratory-confirmed dengue. PRINCIPAL FINDINGS: Using the traditional scheme, 28.5% of patients could not be assigned to any category, while the revised scheme categorized all patients. Intensive therapeutic interventions were used as the reference standard to evaluate the ability of both the traditional and revised schemes to detect severe dengue cases. Analyses of the classified cases (n = 183) demonstrated that the revised scheme had better sensitivity (86.8%, P<0.001), while the traditional scheme had better specificity (93.4%, P<0.001) for the detection of severe forms of dengue. CONCLUSIONS/SIGNIFICANCE: This improved sensitivity of the revised scheme allows for better case capture and increased ICU admission, which may aid pediatricians in avoiding deaths due to severe dengue among children, but, in turn, it may also result in the misclassification of the patients' condition as severe, reflected in the observed lower positive predictive value (61.6%, P<0.001) when compared with the traditional scheme (82.6%, P<0.001). The inclusion of unusual dengue manifestations in the revised scheme has not shifted the emphasis from the most important aspects of dengue disease and the major factors contributing to fatality in this study: shock with consequent organ dysfunction.

Infection by Brazilian and Dutch swine hepatitis E virus strains induces haematological changes in Macaca fascicularis.

BACKGROUND: Hepatitis E virus (HEV) has been described as an emerging pathogen in Brazil and seems to be widely disseminated among swine herds. An autochthonous human case of acute hepatitis E was recently reported. To obtain a better understanding of the phenotypic profiles of both human and swine HEV strains, a experimental study was conducted using the animal model, Macaca fascicularis. METHODS: Six cynomolgus monkeys (Macaca fascicularis) were inoculated intravenously with swine HEV genotype 3 that was isolated from naturally and experimentally infected pigs in Brazil and the Netherlands. Two other monkeys were inoculated with HEV genotype 3 that was recovered from Brazilian and Argentinean patients with locally acquired acute and fulminant hepatitis E. The haematological, biochemical, and virological parameters of all animals were monitored for 67 days. RESULTS: Subclinical hepatitis was observed in all monkeys after inoculation with HEV genotype 3 that was recovered from the infected swine and human patients. HEV RNA was detected in the serum and/or faeces of 6 out of the 8 cynomolgus monkeys between 5 and 53 days after inoculation. The mild inflammation of liver tissues and elevations of discrete liver enzymes were observed. Seroconversions to anti-HEV IgM and/or IgG were detected in 7 animals. Reactivities to anti-HEV IgA were also detected in the salivary samples of 3 animals. Interestingly, all of the infected monkeys showed severe lymphopenia and a trend toward monocytosis, which coincided with elevations in alanine aminotransferase and antibody titres. CONCLUSIONS: The ability of HEV to cross the species barrier was confirmed for both the swine (Brazilian and Dutch) and human (Argentinean) strains, thus reinforcing the zoonotic risk of hepatitis E in South America. Cynomolgus monkeys that were infected with HEV genotype 3 developed subclinical hepatitis that was associated with haematological changes. Haematological approaches should be considered in future studies of HEV infection.

From primary care to hospitalization: clinical warning signs of severe dengue fever in children and adolescents during an outbreak in Rio de Janeiro, Brazil.

We analyzed factors associated with severe cases of dengue in children and adolescents hospitalized during the 2007/2008 epidemic in Rio de Janeiro, Brazil. This is a retrospective case-control study that covers 88 cases of severe dengue in patients admitted to four tertiary care children's hospitals. Controls consisted of 22 children with non-severe dengue living in the same neighborhood as the patients with severe dengue. Differences in prevalence of the clinical signs - abdominal pain, breathing difficulty, drowsiness or irritability - emerged on the third day after the onset of symptoms, in the febrile stage. Cases and controls received first medical care at the same clinical stage of disease. However, hospital admission of severe cases occurred later, on average between the third and fourth day after the onset of the disease. Early discharge of patients with fever whose condition could have progressed to severe dengue may have been a consequence of the type of medical assistance provided by primary care units, suggesting deficiencies both in the use of the risk classification protocol and patient triage.

From primary care to hospitalization: clinical warning signs of severe dengue fever in children and adolescents during an outbreak in Rio de Janeiro, Brazil / Da atenção primária à hospitalização: sinais clínicos de alarme para dengue grave em crianças e adolescentes durante uma epidemia no Rio de Janeiro, Brasil / De la atención primaria a la hospitalización: señales clínicas de alarma del dengue grave en niños y adolescentes durante una epidemia en Río de Janeiro, Brasil

We analyzed factors associated with severe cases of dengue in children and adolescents hospitalized during the 2007/2008 epidemic in Rio de Janeiro, Brazil. This is a retrospective case-control study that covers 88 cases of severe dengue in patients admitted to four tertiary care children's hospitals. Controls consisted of 22 children with non-severe dengue living in the same neighborhood as the patients with severe dengue. Differences in prevalence of the clinical signs - abdominal pain, breathing difficulty, drowsiness or irritability - emerged on the third day after the onset of symptoms, in the febrile stage. Cases and controls received first medical care at the same clinical stage of disease. However, hospital admission of severe cases occurred later, on average between the third and fourth day after the onset of the disease. Early discharge of patients with fever whose condition could have progressed to severe dengue may have been a consequence of the type of medical assistance provided by primary care units, suggesting deficiencies both in the use of the risk classification protocol and patient triage.

Foram avaliados fatores associados à ocorrência de casos graves de dengue em crianças/adolescentes hospitalizados durante a epidemia de 2007/2008 no Rio de Janeiro, Brasil. Trata-se de estudo caso-controle retrospectivo com 88 casos graves de dengue, admitidos em quatro hospitais de atenção terciária infantil. Os controles foram 22 crianças com dengue não grave residentes na vizinhança dos casos. Foram observadas diferenças na prevalência de sinais clínicos - dor abdominal, dificuldade respiratória, sonolência/irritabilidade - a partir do terceiro dia do início dos sintomas, ainda na presença da febre. Casos e controles receberam o primeiro atendimento médico no mesmo estágio clínico da doença. Contudo, as hospitalizações dos casos graves ocorreram mais tardiamente, em média entre o terceiro e quarto dia da doença. A liberação precoce de pacientes com quadro febril e potencialmente graves pode ter sido consequência do atendimento médico prestado nas unidades de atenção primária, sugerindo deficiências na aplicação do protocolo de classificação de risco de dengue e triagem de pacientes.

Fueron evaluados factores asociados a la ocurrencia de casos graves de dengue en niños/adolescentes hospitalizados, durante la epidemia de 2007/2008 en Río de Janeiro, Brasil. Se trata de un estudio caso-control retrospectivo con 88 casos graves de dengue, admitidos en cuatro hospitales de atención terciaria infantil. Los controles se efectuaron con 22 niños con dengue no grave, residentes en los alrededores de los casos. Se observaron diferencias en la prevalencia de señales clínicas -dolor abdominal, dificultad respiratoria, somnolencia/irritabilidad- a partir del tercer día del inicio de los síntomas, todavía con presencia de fiebre. Casos y controles recibieron la primera atención médica en la misma fase clínica de la enfermedad. No obstante, las hospitalizaciones de los casos graves se produjeron más tardíamente, en media entre el tercer y cuarto día de la enfermedad. El alta precoz de pacientes con cuadro febril, y potencialmente graves, puede haber sido consecuencia de la atención médica prestada en las unidades de atención primaria, sugiriendo deficiencias en la aplicación del protocolo de clasificación de riesgo de dengue y selección de pacientes.

Traffic crashes and alcohol outlets in a Brazilian state capital.

OBJECTIVE: Restricting alcohol outlets is being considered as a measure for preventing alcohol-related crashes. However, in many developing countries, alcohol availability is not regulated and its influence on motor vehicle traffic crashes is unknown. This study explores the association between traffic crashes and alcohol outlets in a Brazilian city. METHOD: Data were geocoded and exploratory analysis was conducted using the kernel density estimator. Two generalized additive models (GAMs) were implemented to predict the factors associated with alcohol-related crashes. RESULTS: For 78 percent of the 3840 traffic crashes where the driver was a victim, there was at least one bar located within a 300-m radius. The median distances between an outlet were 124.4 and 130.7 m for a non-alcohol- and alcohol-related crashes, respectively (P =.13). The GAMs did not make evident any significant association between the outlet locations and alcohol-related crashes: the presence of at least one outlet was associated with alcohol-related crashes with an odds ratio (OR) of 0.94 (95% confidence interval [CI] = 0.75-1.17). Alcohol crashes are more likely to be observed among males (OR = 1.58; 95% CI = 1.21-2.06), young drivers vs. those aged 50 years+ (OR = 3.4; 95% CI = 1.79-6.43), and crashes with fatalities (OR = 1.73; 95% CI = 0.98-3.04). CONCLUSIONS: Density of alcohol outlets was high all over the city and both alcohol- and non-alcohol-related crashes occurred near an outlet. The study helps to better understand the relationship between alcohol availability and traffic crashes in a middle-income country where licensing/zoning is absent and suggests that measures for restricting the physical availability of alcohol are necessary, even though further studies are still needed.

Structural and topographic dynamics of pulmonary histopathology and local cytokine profiles in Paracoccidioides brasiliensis conidia-infected mice.

BACKGROUND: Paracoccidioidomycosis (PCM), an endemic systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb), usually results in severe lung damage in patients. METHODS AND FINDINGS: Considering the difficulties to sequentially study the infection in humans, this work was done in mice inoculated intranasally with infective Pb-conidia. Lungs of control and Pb-infected mice were studied after 2-hours, 4, 8, 12 and 16-weeks post-infection (p.i) in order to define histopathologic patterns of pulmonary lesions, multiplex-cytokine profiles and their dynamics during the course of this mycosis. Besides the nodular/granulomatous lesions previously informed, results revealed additional non-formerly described lung abnormalities, such as periarterial sheath inflammation and pseudotumoral masses. The following chronologic stages occurring during the course of the experimental infection were defined: Stage one (2-hours p.i): mild septal infiltration composed by neutrophils and macrophages accompanied by an intense "cytokine burst" represented by significant increases in IL-1α, IL-1ß, IL-4, IL-5, IL-6, IL-10, IL12p70, IL-13, IL-17, Eotaxin, G-CSF, MCP1, MIP1α, GM-CSF, IFN-γ, MIP1ß and TNFα levels. Stage two (4-weeks p.i): presence of nodules, evidence of incipient periarterial- and intense but disperse parenchymal- inflammation, abnormalities that continued to be accompanied by hyper-secretion of those cytokines and chemokines mentioned in the first stage of infection. Stages three and four (8 and 12-weeks p.i.): fungal proliferation, inflammation and collagenesis reached their highest intensity with particular involvement of the periarterial space. Paradoxically, lung cytokines and chemokines were down-regulated with significant decreases in IL-2,IL-3,IL-5,IL-9,IL-13,IL-15,GM-CSF,IFN-γ,MIP1ß and TNFα. Stage five (16-weeks p.i.): inflammation decreased becoming limited to the pseudotumoral masses and was accompanied by a "silent" cytokine response, except for PDGF, MIG, RANTES and IL12p40 which remained up-regulated for the duration of the experiment. CONCLUSIONS: Results of this study identified both classic and novel patterns corresponding to histopathologic and immunologic responses occurring during the course of experimental PCM.