RESUMO
The influenza-like illness (ILI) sentinel surveillance operates in Brazil to identify respiratory viruses of public health relevance circulating in the country and was first implemented in 2000. Recently, the COVID-19 pandemic reinforced the importance of early detection of the circulation of new viruses in Brazil. Therefore, an analysis of the design of the ILI sentinel surveillance is timely. To this end, we simulated a sentinel surveillance network, identifying the municipalities that would be part of the network according to the criteria defined in the design of the ILI sentinel surveillance and, based on data from tested cases of severe acute respiratory illness (SARI) from 2014 to 2019, we drew samples for each sentinel municipality per epidemiological week. The draw was performed 1,000 times, obtaining the median and 95% quantile interval (95%QI) of virus positivity by Federative Unit and epidemiological week. According to the ILI sentinel surveillance design criteria, sentinel units would be in 64 municipalities, distributed mainly in capitals and their metropolitan areas, recommending 690 weekly samples. The design showed good sensitivity (91.65% considering the 95%QI) for qualitatively detecting respiratory viruses, even those with low circulation. However, there was important uncertainty in the quantitative estimate of positivity, reaching at least 20% in 11.34% of estimates. The results presented here aim to assist in evaluating and updating the ILI sentinel surveillance design. Strategies to reduce uncertainty in positivity estimates need to be evaluated, as does the need for greater spatial coverage.
Assuntos
COVID-19 , Influenza Humana , Vigilância de Evento Sentinela , Humanos , Brasil/epidemiologia , Influenza Humana/epidemiologia , Influenza Humana/diagnóstico , COVID-19/epidemiologia , COVID-19/diagnóstico , SARS-CoV-2 , PandemiasRESUMO
The SARS-CoV-2 XBB is a group of highly immune-evasive lineages of the Omicron variant of concern that emerged by recombining BA.2-descendent lineages and spread worldwide during 2023. In this study, we combine SARS-CoV-2 genomic data (n = 11,065 sequences) with epidemiological data of severe acute respiratory infection (SARI) cases collected in Brazil between October 2022 and July 2023 to reconstruct the space-time dynamics and epidemiologic impact of XBB dissemination in the country. Our analyses revealed that the introduction and local emergence of lineages carrying convergent mutations within the Spike protein, especially F486P, F456L, and L455F, propelled the spread of XBB* lineages in Brazil. The average relative instantaneous reproduction numbers of XBB* + F486P, XBB* + F486P + F456L, and XBB* + F486P + F456L + L455F lineages in Brazil were estimated to be 1.24, 1.33, and 1.48 higher than that of other co-circulating lineages (mainly BQ.1*/BE*), respectively. Despite such a growth advantage, the dissemination of these XBB* lineages had a reduced impact on Brazil's epidemiological scenario concerning previous Omicron subvariants. The peak number of SARI cases from SARS-CoV-2 during the XBB wave was approximately 90%, 80%, and 70% lower than that observed during the previous BA.1*, BA.5*, and BQ.1* waves, respectively. These findings revealed the emergence of multiple XBB lineages with progressively increasing growth advantage, yet with relatively limited epidemiological impact in Brazil throughout 2023. The XBB* + F486P + F456L + L455F lineages stand out for their heightened transmissibility, warranting close monitoring in the months ahead. IMPORTANCE: Brazil was one the most affected countries by the SARS-CoV-2 pandemic, with more than 700,000 deaths by mid-2023. This study reconstructs the dissemination of the virus in the country in the first half of 2023, a period characterized by the dissemination of descendants of XBB.1, a recombinant of Omicron BA.2 lineages evolved in late 2022. The analysis supports that XBB dissemination was marked by the continuous emergence of indigenous lineages bearing similar mutations in key sites of their Spike protein, a process followed by continuous increments in transmissibility, and without repercussions in the incidence of severe cases. Thus, the results suggest that the epidemiological impact of the spread of a SARS-CoV-2 variant is influenced by an intricate interplay of factors that extend beyond the virus's transmissibility alone. The study also underlines the need for SARS-CoV-2 genomic surveillance that allows the monitoring of its ever-shifting composition.
Assuntos
COVID-19 , Humanos , Brasil/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Abstract: The influenza-like illness (ILI) sentinel surveillance operates in Brazil to identify respiratory viruses of public health relevance circulating in the country and was first implemented in 2000. Recently, the COVID-19 pandemic reinforced the importance of early detection of the circulation of new viruses in Brazil. Therefore, an analysis of the design of the ILI sentinel surveillance is timely. To this end, we simulated a sentinel surveillance network, identifying the municipalities that would be part of the network according to the criteria defined in the design of the ILI sentinel surveillance and, based on data from tested cases of severe acute respiratory illness (SARI) from 2014 to 2019, we drew samples for each sentinel municipality per epidemiological week. The draw was performed 1,000 times, obtaining the median and 95% quantile interval (95%QI) of virus positivity by Federative Unit and epidemiological week. According to the ILI sentinel surveillance design criteria, sentinel units would be in 64 municipalities, distributed mainly in capitals and their metropolitan areas, recommending 690 weekly samples. The design showed good sensitivity (91.65% considering the 95%QI) for qualitatively detecting respiratory viruses, even those with low circulation. However, there was important uncertainty in the quantitative estimate of positivity, reaching at least 20% in 11.34% of estimates. The results presented here aim to assist in evaluating and updating the ILI sentinel surveillance design. Strategies to reduce uncertainty in positivity estimates need to be evaluated, as does the need for greater spatial coverage.
Resumen: La vigilancia centinela de la enfermedad tipo infuenza (ETI) funciona en Brasil para identificar los virus respiratorios de importancia para la salud pública que circulan en el país y comenzó a ser implementada en 2000. Recientemente, la pandemia de COVID-19 ha reforzado la importancia de la detección temprana de la circulación de nuevos virus en el territorio brasileño. Así, se hace oportuno un análisis del diseño de la vigilancia centinela de la ETI. Para ello, simulamos una red centinela identificando los municipios que formarían parte de la red según los criterios definidos en el diseño de la vigilancia centinela de la ETI y, a partir de los datos de casos testados de infección respiratoria aguda grave (IRAG) de 2014 a 2019, se extrajeron muestras para cada municipio centinela por semana epidemiológica. El sorteo se repitió 1.000 veces y se obtuvo la mediana y el intervalo cuantílico del 95% (IC95%) de la positividad por virus, por Unidad Federativa y semana epidemiológica. Según los criterios del diseño de la vigilancia centinela de la ETI, unidades centinelas estarían en 64 municipios, distribuidas principalmente en capitales y zonas metropolitanas de las capitales, preconizando 690 muestras semanales. El diseño presentó una buena sensibilidad (total de 91,65% considerando el IC95%) para la detección cualitativa de los virus respiratorios, incluso los de baja circulación. Sin embargo, hubo una importante incertidumbre en la estimación cuantitativa de la positividad, alcanzando al menos el 20% en el 11,34% de las estimaciones. Los resultados presentados aquí tienen como objetivo ayudar en la evaluación y actualización del diseño de la red centinela. Es necesario evaluar las estrategias para reducir la incertidumbre en las estimaciones de positividad, al igual que la necesidad de una mayor cobertura espacial.
Resumo: A vigilância sentinela de síndrome gripal atua no Brasil identificando os vírus respiratórios de importância para a saúde pública circulantes no país, e começou a ser implementada em 2000. Recentemente, a pandemia de COVID-19 reforçou a importância da detecção precoce de novos vírus em circulação no território brasileiro. Assim, se faz oportuna uma análise do desenho da vigilância sentinela de síndrome gripal. Para tal, simulamos uma rede sentinela, identificando os municípios que fariam parte da rede segundo os critérios definidos no desenho da vigilância sentinela de síndrome gripal, e, a partir dos dados de casos testados de síndrome respiratória aguda grave (SRAG) de 2014 a 2019, sorteamos amostras para cada município sentinela por semana epidemiológica. O sorteio foi repetido mil vezes, obtendo-se a mediana e intervalo quantílico de 95% (IQ95%) da positividade para cada vírus por Unidade Federativa e semana epidemiológica. Segundo os critérios do desenho da vigilância sentinela de síndrome gripal, unidades sentinelas estariam em 64 municípios, distribuídas principalmente em capitais e suas zonas metropolitanas, o que preconizou 690 amostras semanais. O desenho apresentou boa sensibilidade (total de 91,65%, considerando o IQ95%) para a detecção qualitativa dos vírus respiratórios, mesmo os de baixa circulação. Porém, houve importante incerteza na estimativa quantitativa de positividade, chegando a, pelo menos, 20% em 11,34% das estimativas. Os resultados aqui apresentados visam auxiliar a avaliação e a atualização do desenho da rede sentinela. Estratégias para reduzir a incerteza nas estimativas de positividade precisam ser avaliadas, assim como a necessidade de maior cobertura espacial.
RESUMO
BACKGROUND: Although several studies have reported attenuated influenza illness following influenza vaccination, results have been inconsistent and have focused predominantly on adults in the USA. This study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of influenza vaccine target groups across multiple South American countries. METHODS: We analysed data from four South American countries (Argentina, Brazil, Chile, and Paraguay) participating in REVELAC-i, a multicentre, test-negative design, vaccine effectiveness network including 41 sentinel hospitals. Individuals hospitalised at one of these centres with severe acute respiratory infection were tested for influenza by real-time RT-PCR, and were included in the analysis if they had complete information about their vaccination status and outcomes of their hospital stay. We used multivariable logistic regression weighted by inverse probability of vaccination and adjusted for antiviral use, duration of illness before admission, and calendar week, to calculate the adjusted odds ratios (aORs) of intensive care unit (ICU) admission and in-hospital death (and combinations of these outcomes) among influenza-positive patients by vaccination status for three target groups: young children (aged 6-24 months), adults (aged 18-64 years) with pre-existing health conditions, and older adults (aged ≥65 years). Survival curves were used to compare length of hospital stay by vaccination status in each target group. FINDINGS: 2747 patients hospitalised with PCR-confirmed influenza virus infection between Jan 1, 2013, and Dec 8, 2019, were included in the study: 649 children (70 [10·8%] fully vaccinated, 193 [29·7%] partially vaccinated) of whom 87 (13·4%) were admitted to ICU and 12 (1·8%) died in hospital; 520 adults with pre-existing medical conditions (118 [22·7%] vaccinated), of whom 139 (26·7%) were admitted to ICU and 55 (10·6%) died in hospital; and 1578 older adults (609 [38·6%] vaccinated), of whom 271 (17·2%) were admitted to ICU and 220 (13·9%) died in hospital. We observed earlier discharge among partially vaccinated children (adjusted hazard ratio 1·14 [95% CI 1·01-1·29]), fully vaccinated children (1·24 [1·04-1·47]), and vaccinated adults with pre-existing medical conditions (1·78 [1·18-2·69]) compared with their unvaccinated counterparts, but not among vaccinated older adults (0·82 [0·65-1·04]). Compared with unvaccinated individuals, lower odds of ICU admission were found for partially vaccinated children (aOR 0·64 [95% CI 0·44-0·92]) and fully vaccinated children (0·52 [0·28-0·98]), but not for adults with pre-existing conditions (1·25 [0·93-1·67]) or older adults (0·88 [0·72-1·08]). Lower odds of in-hospital death (0·62 [0·50-0·78]) were found in vaccinated versus unvaccinated older adults, with or without ICU admission, but did not differ significantly in partially vaccinated (1·35 [0·57-3·20]) or fully vaccinated young children (0·88 [0·16-4·82]) or adults with pre-existing medical conditions (1·09 [0·73-1·63]) compared with the respective unvaccinated patient groups. INTERPRETATION: Influenza vaccination was associated with illness attenuation among those hospitalised with influenza, although results differed by vaccine target group. These findings might suggest that attenuation of disease severity might be specific to certain target groups, seasons, or settings. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
Assuntos
Vacinas contra Influenza , Influenza Humana , Criança , Humanos , Pré-Escolar , Idoso , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estações do Ano , Estudos de Coortes , Mortalidade Hospitalar , Hospitalização , Vacinação , Brasil/epidemiologiaRESUMO
BACKGROUND: Widespread respiratory infections with high morbidity rates caused by respiratory viruses represent a significant global public health problem. Our objective was to describe cases and deaths from severe acute respiratory infection (SARI) in Brazil over the past 8 y as well as changes in the distribution and risk of illness and death from SARI before and in the first year of the coronavirus disease 2019 (COVID-19) pandemic (FYP). METHODS: We performed a descriptive epidemiological study of hospitalized SARI cases and deaths between 2013 and 2020 in Brazil, separated into pre-pandemic (2013 to 2019) and FYP (2020). We estimate the increase in SARI cases and deaths in the FYP as well as the mortality and infection risks attributable to the FYP (MRAP and IRAP, respectively). RESULTS: In 2020, an excess of 425 054 cases and 109 682 deaths was observed, with a significant increase in the risk of falling ill and dying from SARI, with an IRAP of 200.06 and an MRAP of 51.68 cases per 100 000 inhabitants. The increase in SARI cases and deaths was particularly prominent among patients with COVID-19, the elderly, males, those self-identifying as mixed race and patients with heart disease and diabetes. We conclude that an important increase in morbidity and mortality due to SARI was observed in the FYP. More vulnerable groups and those living in the Southeast, North and Center-West regions of the country suffered the most.
Assuntos
COVID-19 , Influenza Humana , Infecções Respiratórias , Masculino , Humanos , Lactente , Idoso , Influenza Humana/epidemiologia , Pandemias , Brasil , Infecções Respiratórias/epidemiologia , HospitalizaçãoRESUMO
This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Adulto , Criança , Memória Imunológica , Linfócitos T CD8-Positivos , Nucleocapsídeo , AnticorposRESUMO
The influenza A virus (IAV) is of a major public health concern as it causes annual epidemics and has the potential to cause pandemics. At present, the neuraminidase inhibitors (NAIs) are the most widely used anti-influenza drugs, but, more recently, the drug baloxavir marboxil (BXM), a polymerase inhibitor, has also been licensed in some countries. Mutations in the viral genes that encode the antiviral targets can lead to treatment resistance. Worldwide, a low prevalence of antiviral resistant strains has been reported. Despite that, this situation can change rapidly, and resistant strain surveillance is a priority. Thus, the aim of this was to evaluate Brazilian IAVs antiviral resistance from 2017 to 2019 through the identification of viral mutations associated with reduced inhibition of the drugs and by testing the susceptibility of IAV isolates to oseltamivir (OST), the most widely used NAI drug in the country. Initially, we analyzed 282 influenza A(H1N1)pdm09 and 455 A(H3N2) genetic sequences available on GISAID. The amino acid substitution (AAS) NA:S247N was detected in one A(H1N1)pdm09 strain. We also identified NA:I222V (n = 6) and NA:N329K (n = 1) in A(H3N2) strains. In addition, we performed a molecular screening for NA:H275Y in 437 A(H1N1)pdm09 samples, by pyrosequencing, which revealed a single virus harboring this mutation. Furthermore, the determination of OST IC50 values for 222 A(H1N1)pdm09 and 83 A(H3N2) isolates revealed that all isolates presented a normal susceptibility profile to the drug. Interestingly, we detected one A(H3N2) virus presenting with PA:E119D AAS. Moreover, the majority of the IAV sequences had the M2:S31N adamantanes resistant marker. In conclusion, we show a low prevalence of Brazilian IAV strains with NAI resistance markers, in accordance with what is reported worldwide, indicating that NAIs still remain an option for the treatment of influenza infections in Brazil. However, surveillance of influenza resistance should be strengthened in the country for improving the representativeness of investigated viruses and the robustness of the analysis.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Antivirais/farmacologia , Antivirais/uso terapêutico , Brasil/epidemiologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Guanidinas/farmacologia , Guanidinas/uso terapêutico , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/metabolismo , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Neuraminidase/genética , Neuraminidase/metabolismo , Neuraminidase/uso terapêutico , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Prevalência , Estações do AnoRESUMO
Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.
Assuntos
COVID-19 , Adulto , Brasil/epidemiologia , COVID-19/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Obesidade/epidemiologia , Pacientes Ambulatoriais , Estudos Prospectivos , SARS-CoV-2RESUMO
Annual vaccination against influenza is the best tool to prevent deaths and hospitalizations. Regular updates of trivalent inactivated influenza vaccines (TIV) are necessary due to high mutation rates in influenza viruses. TIV effectiveness is affected by antigenic mismatches, age, previous immunity, and other host factors. Studying TIV effectiveness annually in different populations is critical. The serological responses to Southern-Hemisphere TIV and circulating influenza strains were evaluated in 2018−2020 among Brazilian volunteers, using hemagglutination inhibition (HI) assays. Post-vaccination titers were corrected to account for pre-vaccination titers. Our population achieved >83% post-vaccination seroprotection levels, whereas seroconversion rates ranged from 10% to 46%. TIV significantly enhanced antibody titers and seroprotection against all prior and contemporary vaccine and circulating strains tested. Strong cross-reactive responses were detected, especially between H1N1 subtypes. A/Singapore/INFIMH-16-0019/2016, included in the 2018 TIV, induced the poorest response. Significant titer and seroprotection reductions were observed 6 and 12 months after vaccination. Age had a slight effect on TIV response, whereas previous vaccination was associated with lower seroconversion rates and titers. Despite this, TIV induced high seroprotection for all strains, in all groups. Regular TIV evaluations, based on regional influenza strain circulation, should be conducted and the factors affecting response studied.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adulto , Anticorpos Antivirais , Brasil/epidemiologia , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Estações do Ano , Vacinas de Produtos InativadosRESUMO
ABSTRACT Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects and methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.