ABSTRACT The global reemergence of measles in 2018–2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

ABSTRACT Introduction: In the current standard of care (SoC) RT-PCR method for COVID-19, the patient’s swab was extracted in viral transport media (VTM). For the PanbioTM COVID-19 Ag Rapid Test, the patient swab is flushed out in extraction buffer, of which a small fraction is used for testing, leaving more than half the sample unused. This study was designed to show that RT-PCR results from the residual sample of the PanbioTM COVID-19 Ag Rapid Test (called Novel RT-PCR) are not worse than the SoC RT-PCR result. Methods: The study was performed using (1) dilution series of five patient samples, and (2) 413 patient samples comparing SOC versus Novel RT-PCR results. Results: For the dilution series samples, all tested positive by both methods. The bias between Ct values of Novel RT-PCR and SoC RT-PCR did not exceed 3.00 Ct using primers N1 and N2. A total of 413 COVID symptomatic patients seeking COVID testing were tested, of which 89 patients tested positive and 324 tested negative with SoC RT-PCR. In 324 patients who tested negative with SoC RT-PCR, 323 tested negative with Novel RT-PCR, and one (1) tested positive. Out of 89 who tested positive with SoC RT-PCR, 80 tested positive with the Novel RT-PCR, and nine patients showed a negative test result. The Overall Percent Agreement for the 413 valid patient sample pairs was 97.5 [95% CI 97 to 98]. Conclusion: The study demonstrated that the performance of the Novel RT-PCR method is acceptable compared to the SoC RT-PCR method and can be a useful tool to perform RTPCR without the need for new swab collections.

BACKGROUND During routine Coronavirus disease 2019 (COVID-19) diagnosis, an unusually high viral load was detected by reverse transcription real-time polymerase chain reaction (RT-qPCR) in a nasopharyngeal swab sample collected from a patient with respiratory and neurological symptoms who rapidly succumbed to the disease. Therefore we sought to characterise the infection. OBJECTIVES We aimed to determine and characterise the etiological agent responsible for the poor outcome. METHODS Classical virological methods, such as plaque assay and plaque reduction neutralisation test combined with amplicon-based sequencing, as well as a viral metagenomic approach, were performed to characterise the etiological agents of the infection. FINDINGS Plaque assay revealed two distinct plaque phenotypes, suggesting either the presence of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains or a productive coinfection of two different species of virus. Amplicon-based sequencing did not support the presence of any SARS-CoV-2 genetic variants that would explain the high viral load and suggested the presence of a single SARS-CoV-2 strain. Nonetheless, the viral metagenomic analysis revealed that Coronaviridae and Herpesviridae were the predominant virus families within the sample. This finding was confirmed by a plaque reduction neutralisation test and PCR. MAIN CONCLUSIONS We characterised a productive coinfection of SARS-CoV-2 and Herpes simplex virus 1 (HSV-1) in a patient with severe symptoms that succumbed to the disease. Although we cannot establish the causal relationship between the coinfection and the severity of the clinical case, this work serves as a warning for future studies focused on the interplay between SARS-CoV-2 and HSV-1 coinfection and COVID-19 severity.

RESUMO OBJETIVO Descrever o perfil clínico-epidemiológico dos casos confirmados de febre amarela internados em hospital geral de referência para doenças infecciosas no estado do Rio de Janeiro, Brasil, de 11 de março de 2017 a 15 de junho de 2018, durante recente surto e fatores associados ao óbito. MÉTODOS Estudo observacional retrospectivo, com análise de bases de dados secundários da vigilância epidemiológica local e coleta complementar de dados nas fichas de investigação epidemiológica e prontuários clínicos. As variáveis analisadas incluíram dados demográficos, epidemiológicos, clínicos e laboratoriais. Foi conduzida análise estatística descritiva bivariada e múltipla por regressão logística para estudo de fatores associados ao óbito. RESULTADOS Foram internados 52 casos confirmados, 86,5% deles homens, com mediana de idade de 49,5 anos e 40,4% trabalhadores rurais. Os sinais e sintomas mais frequentes foram: febre (90,4%), icterícia (86,5%), náuseas e/ou vômitos (69,2%), alterações de excreção renal (53,8%), hemorragias (50%) e dor abdominal (48,1%), com comorbidade em 38,5% dos casos. A letalidade foi de 40,4%. Os fatores associados significativamente à maior chance de óbito na análise bivariada foram: hemorragia, alterações de excreção renal e valores máximos de bilirrubina direta, aspartato aminotransferase (AST), alanina aminotransferase (ALT), ureia e creatinina. Na análise múltipla por regressão logística, apenas alterações de excreção renal e ALT permaneceram como preditores significativos de maior chance de óbito. Observou-se ainda efeito limítrofe para AST. Os pontos de corte identificados como de alto risco para óbito foram ALT > 4.000 U/L e AST > 6.000 U/L. CONCLUSÕES O estudo contribuiu para o conhecimento do perfil de casos confirmados de febre amarela com gravidade alta. Os principais fatores associados ao óbito foram a alteração da excreção renal e a elevação sérica de transaminases, sobretudo a ALT. A letalidade elevada reforça a necessidade de diagnóstico e tratamento precoces, e a importância do incremento da cobertura vacinal.

ABSTRACT OBJECTIVE Describe the clinical and epidemiological profile of confirmed cases of yellow fever whose patients were hospitalized in a general hospital for infectious diseases in the State of Rio de Janeiro, Brazil, from March 11, 2017 to June 15, 2018, during a recent outbreak and factors associated with death. METHODS This is a retrospective observational study with analysis of secondary databases of local epidemiological surveillance system, and complementary data collection from epidemiological investigation records and clinical records. Study variables included demographic, epidemiological, clinical, and laboratory data. A descriptive statistical analysis and a bivariate and multivariate analysis by logistic regression were performed to analyze factors associated with death. RESULTS Fifty-two patients diagnosed with yellow fever were hospitalized, 86.5% male patients, median age 49.5 years, 40.4% rural workers. The most frequent signs and symptoms were fever (90.4%), jaundice (86.5%), nausea and/or vomiting (69.2%), changes in renal excretion (53.8%), bleeding (50%), and abdominal pain (48.1%), with comorbidity in 38.5% of all cases. The lethality rate was 40.4%. Factors significantly associated with a higher chance of death in the bivariate analysis were: bleeding, changes in renal excretion, and maximum values of direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. In the multivariate analysis by logistic regression, only changes in renal excretion and ALT remained significant predictors of higher chance of death. A threshold effect was also observed for AST. The cutoff points identified as high risk for death were ALT > 4,000 U/L and AST > 6,000 U/L. CONCLUSIONS This study contributed to the knowledge on the profile of confirmed cases of high severity yellow fever. The main factors associated with death were changes in renal excretion and elevated serum transaminases, especially ALT. High lethality emphasizes the need for early diagnosis and treatment, and the importance of increasing vaccination coverage.

RESUMO OBJETIVO Descrever o perfil clínico-epidemiológico dos casos confirmados de febre amarela internados em hospital geral de referência para doenças infecciosas no estado do Rio de Janeiro, Brasil, de 11 de março de 2017 a 15 de junho de 2018, durante recente surto e fatores associados ao óbito. MÉTODOS Estudo observacional retrospectivo, com análise de bases de dados secundários da vigilância epidemiológica local e coleta complementar de dados nas fichas de investigação epidemiológica e prontuários clínicos. As variáveis analisadas incluíram dados demográficos, epidemiológicos, clínicos e laboratoriais. Foi conduzida análise estatística descritiva bivariada e múltipla por regressão logística para estudo de fatores associados ao óbito. RESULTADOS Foram internados 52 casos confirmados, 86,5% deles homens, com mediana de idade de 49,5 anos e 40,4% trabalhadores rurais. Os sinais e sintomas mais frequentes foram: febre (90,4%), icterícia (86,5%), náuseas e/ou vômitos (69,2%), alterações de excreção renal (53,8%), hemorragias (50%) e dor abdominal (48,1%), com comorbidade em 38,5% dos casos. A letalidade foi de 40,4%. Os fatores associados significativamente à maior chance de óbito na análise bivariada foram: hemorragia, alterações de excreção renal e valores máximos de bilirrubina direta, aspartato aminotransferase (AST), alanina aminotransferase (ALT), ureia e creatinina. Na análise múltipla por regressão logística, apenas alterações de excreção renal e ALT permaneceram como preditores significativos de maior chance de óbito. Observou-se ainda efeito limítrofe para AST. Os pontos de corte identificados como de alto risco para óbito foram ALT > 4.000 U/L e AST > 6.000 U/L. CONCLUSÕES O estudo contribuiu para o conhecimento do perfil de casos confirmados de febre amarela com gravidade alta. Os principais fatores associados ao óbito foram a alteração da excreção renal e a elevação sérica de transaminases, sobretudo a ALT. A letalidade elevada reforça a necessidade de diagnóstico e tratamento precoces, e a importância do incremento da cobertura vacinal.

ABSTRACT OBJECTIVE Describe the clinical and epidemiological profile of confirmed cases of yellow fever whose patients were hospitalized in a general hospital for infectious diseases in the State of Rio de Janeiro, Brazil, from March 11, 2017 to June 15, 2018, during a recent outbreak and factors associated with death. METHODS This is a retrospective observational study with analysis of secondary databases of local epidemiological surveillance system, and complementary data collection from epidemiological investigation records and clinical records. Study variables included demographic, epidemiological, clinical, and laboratory data. A descriptive statistical analysis and a bivariate and multivariate analysis by logistic regression were performed to analyze factors associated with death. RESULTS Fifty-two patients diagnosed with yellow fever were hospitalized, 86.5% male patients, median age 49.5 years, 40.4% rural workers. The most frequent signs and symptoms were fever (90.4%), jaundice (86.5%), nausea and/or vomiting (69.2%), changes in renal excretion (53.8%), bleeding (50%), and abdominal pain (48.1%), with comorbidity in 38.5% of all cases. The lethality rate was 40.4%. Factors significantly associated with a higher chance of death in the bivariate analysis were: bleeding, changes in renal excretion, and maximum values of direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. In the multivariate analysis by logistic regression, only changes in renal excretion and ALT remained significant predictors of higher chance of death. A threshold effect was also observed for AST. The cutoff points identified as high risk for death were ALT > 4,000 U/L and AST > 6,000 U/L. CONCLUSIONS This study contributed to the knowledge on the profile of confirmed cases of high severity yellow fever. The main factors associated with death were changes in renal excretion and elevated serum transaminases, especially ALT. High lethality emphasizes the need for early diagnosis and treatment, and the importance of increasing vaccination coverage.

Abstract This article reviews tuberculosis control actions performed over the last decade, at a global level. The perspectives for the fulfillment of the goals of the new Global Tuberculosis Elimination Plan are described, where the insertion of social protection (Pillar 2) and research (Pillar 3) will play an innovative and strategic role, especially in high-burden countries, like Brazil.