The fuzzy system ensembles entomological, epidemiological, demographic and environmental data to unravel the dengue transmission risk in an endemic city.

BACKGROUND: The effectiveness of dengue control interventions depends on an effective integrated surveillance system that involves analysis of multiple variables associated with the natural history and transmission dynamics of this arbovirus. Entomological indicators associated with other biotic and abiotic parameters can assertively characterize the spatiotemporal trends related to dengue transmission risk. However, the unpredictability of the non-linear nature of the data, as well as the uncertainty and subjectivity inherent in biological data are often neglected in conventional models. METHODS: As an alternative for analyzing dengue-related data, we devised a fuzzy-logic approach to test ensembles of these indicators across categories, which align with the concept of degrees of truth to characterize the success of dengue transmission by Aedes aegypti mosquitoes in an endemic city in Brazil. We used locally gathered entomological, demographic, environmental and epidemiological data as input sources using freely available data on digital platforms. The outcome variable, risk of transmission, was aggregated into three categories: low, medium, and high. Spatial data was georeferenced and the defuzzified values were interpolated to create a map, translating our findings to local public health managers and decision-makers to direct further vector control interventions. RESULTS: The classification of low, medium, and high transmission risk areas followed a seasonal trend expected for dengue occurrence in the region. The fuzzy approach captured the 2020 outbreak, when only 14.06% of the areas were classified as low risk. The classification of transmission risk based on the fuzzy system revealed effective in predicting an increase in dengue transmission, since more than 75% of high-risk areas had an increase in dengue incidence within the following 15 days. CONCLUSIONS: Our study demonstrated the ability of fuzzy logic to characterize the city's spatiotemporal heterogeneity in relation to areas at high risk of dengue transmission, suggesting it can be considered as part of an integrated surveillance system to support timely decision-making.

Bed demand and occupancy within the Brazilian National Health System for the most common types of cancer in Brazil, from 2018 to 2021: a cross-sectional study.

OBJECTIVE: To analyze bed demand and occupancy within the Brazilian National Health System (Sistema Único de Saúde - SUS) for the main types of cancer in Brazil, from 2018 to 2021. METHODS: This was a descriptive cross-sectional study, using data from the Hospital Information System. Queuing theory model was used for calculating average admission rate, average hospitalization rate, probability of overload, and average number of people in the queue. RESULTS: The Southeast and South regions showed the highest average hospitalization rates, while the North region showed the lowest rates. The Southeast region presented a high probability of surgical bed overload, especially in the states of São Paulo (99.0%), Minas Gerais (97.0%) and Rio de Janeiro (97.0%). São Paulo state showed an overload above 95.0% in all types of beds analyzed. CONCLUSION: There was a high probability of oncology bed occupancy within the Brazilian National Health System, especially surgical and medical beds, and regional disparities in bed overload. MAIN RESULTS: The study found a high demand for hospital admissions to oncological bed in the Southeast region and a high probability of system overload in the states of the Southeast and Northeast regions of Brazil, thus highlighting the inequities in access to healthcare services in the country. IMPLICATIONS FOR SERVICES: This study presents a methodology for the improved allocation of resources and management of surgical and medical bed flows in areas with the highest bed overload and regions with low service availability. PERSPECTIVES: It is necessary to promote public policies that ensure the equitable supply of beds for oncological treatment within the SUS, especially in states with bed overload and healthcare service gaps.

SARS-CoV-2 transmission in a highly vulnerable population of Brazil: a household cohort study.

Background: Household transmission studies seek to understand the transmission dynamics of a pathogen by estimating the risk of infection from household contacts and community exposures. We estimated within/extra-household SARS-CoV-2 infection risk and associated factors in a household cohort study in one of the most vulnerable neighbourhoods in Rio de Janeiro city. Methods: Individuals ≥1 years-old with suspected or confirmed COVID-19 in the past 30 days (index cases) and household members aged ≥1 year were enrolled and followed at 14 and 28 days (study period November/2020-December/2021). RT-PCR testing, COVID-19 symptoms, and SARS-CoV-2 serologies were ascertained in all visits. Chain binomial household transmission models were fitted using data from 2024 individuals (593 households). Findings: Extra-household infection risk was 74.2% (95% credible interval [CrI] 70.3-77.8), while within-household infection risk was 11.4% (95% CrI 5.7-17.2). Participants reporting having received two doses of a COVID-19 vaccine had lower extra-household (68.9%, 95% CrI 57.3-77.6) and within-household (4.1%, 95% CrI 0.4-16.6) infection risk. Within-household infection risk was higher among participants aged 10-19 years, from overcrowded households, and with low family income. Contrastingly, extra-household infection risk was higher among participants aged 20-29 years, unemployed, and public transportation users. Interpretation: Our study provides important insights into COVID-19 household/community transmission in a vulnerable population that resided in overcrowded households and who struggled to adhere to lockdown policies and social distancing measures. The high extra-household infection risk highlights the extreme social vulnerability of this population. Prioritising vaccination of the most socially vulnerable could protect these individuals and reduce widespread community transmission. Funding: Fundação Oswaldo Cruz, CNPq, FAPERJ, Royal Society, Instituto Serrapilheira, FAPESP.

Disentangling the seasonality effects of malaria transmission in the Brazilian Amazon basin.

The evidence of seasonal patterns in malaria epidemiology in the Brazilian Amazon basin indicates the need for a thorough investigation of seasonality in this last and heterogeneous region. Additionally, since these patterns are linked to climate variables, malaria models should also incorporate them. This study applies wavelet analysis to incidence data from 2003 to 2020 in the Epidemiological Surveillance System for Malaria (SIVEP-Malaria) database. A mathematical model with climate-dependent parametrization is proposed to study counts of malaria cases over time based on notification data, temperature and rainfall. The wavelet analysis reveals marked seasonality in states Amazonas and Amapá throughout the study period, and from 2003 to 2012 in Pará. However, these patterns are not as marked in other states such as Acre and Pará in more recent years. The wavelet coherency analysis indicates a strong association between incidence and temperature, especially for the municipalities of Macapá and Manaus, and a similar association for rainfall. The mathematical model fits well with the observed temporal trends in both municipalities. Studies on climate-dependent mathematical models provide a good assessment of the baseline epidemiology of malaria. Additionally, the understanding of seasonality effects and the application of models have great potential as tools for studying interventions for malaria control.

Evaluation of the design of the influenza-like illness sentinel surveillance system in Brazil.

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.

Tafenoquine following G6PD screening versus primaquine for the treatment of vivax malaria in Brazil: A cost-effectiveness analysis using a transmission model.

BACKGROUND: Malaria transmission modelling has demonstrated the potential impact of semiquantitative glucose-6-phosphate dehydrogenase (G6PD) testing and treatment with single-dose tafenoquine for Plasmodium vivax radical cure but has not investigated the associated costs. This study evaluated the cost-effectiveness of P. vivax treatment with tafenoquine after G6PD testing using a transmission model. METHODS AND FINDINGS: We explored the cost-effectiveness of using tafenoquine after G6PD screening as compared to usual practice (7-day low-dose primaquine (0.5 mg/kg/day) without G6PD screening) in Brazil using a 10-year time horizon with 5% discounting considering 4 scenarios: (1) tafenoquine for adults only assuming 66.7% primaquine treatment adherence; (2) tafenoquine for adults and children aged >2 years assuming 66.7% primaquine adherence; (3) tafenoquine for adults only assuming 90% primaquine adherence; and (4) tafenoquine for adults only assuming 30% primaquine adherence. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life years (DALYs) averted. These were compared to a willingness to pay (WTP) threshold of US$7,800 for Brazil, and one-way and probabilistic sensitivity analyses were performed. All 4 scenarios were cost-effective in the base case analysis using this WTP threshold with ICERs ranging from US$154 to US$1,836. One-way sensitivity analyses showed that the results were most sensitive to severity and mortality due to vivax malaria, the lifetime and number of semiquantitative G6PD analysers needed, cost per malaria episode and per G6PD test strips, and life expectancy. All scenarios had a 100% likelihood of being cost-effective at the WTP threshold. The main limitations of this study are due to parameter uncertainty around our cost estimates for low transmission settings, the costs of G6PD screening, and the severity of vivax malaria. CONCLUSIONS: In our modelling study that incorporated impact on transmission, tafenoquine prescribed after a semiquantitative G6PD testing was highly likely to be cost-effective in Brazil. These results demonstrate the potential health and economic importance of ensuring safe and effective radical cure.

Evaluation of the design of the influenza-like illness sentinel surveillance system in Brazil / Evaluación del diseño de la vigilancia centinela de la enfermedad tipo influenza en Brasil / Avaliação do desenho da vigilância sentinela de síndrome gripal no Brasil

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.

Bed demand and occupancy within the Brazilian National Health System for the most common types of cancer in Brazil, from 2018 to 2021: a cross-sectional study / Demanda y ocupación de camas en el Sistema Único de Salud de los principales tipos de cáncer en Brasil, de 2018 a 2021: estudio transversal / Demanda e ocupação de leitos do Sistema Único de Saúde para os principais tipos de câncer no Brasil, de 2018 a 2021: estudo transversal

ABSTRACT Objective To analyze bed demand and occupancy within the Brazilian National Health System (Sistema Único de Saúde - SUS) for the main types of cancer in Brazil, from 2018 to 2021. Methods This was a descriptive cross-sectional study, using data from the Hospital Information System. Queuing theory model was used for calculating average admission rate, average hospitalization rate, probability of overload, and average number of people in the queue. Results The Southeast and South regions showed the highest average hospitalization rates, while the North region showed the lowest rates. The Southeast region presented a high probability of surgical bed overload, especially in the states of São Paulo (99.0%), Minas Gerais (97.0%) and Rio de Janeiro (97.0%). São Paulo state showed an overload above 95.0% in all types of beds analyzed. Conclusion There was a high probability of oncology bed occupancy within the Brazilian National Health System, especially surgical and medical beds, and regional disparities in bed overload.

RESUMEN Objetivo Evaluar la demanda y ocupación de camas en el Sistema Único de Salud (SUS) de los principales tipos de cáncer en Brasil, de 2018 a 2021. Métodos Estudio descriptivo transversal, utilizando datos del Sistema de Información Hospitalaria. Se realizaron cálculos basados en el modelo de teoría de colas de: tasa promedio de ingreso por hospitalización, tasa promedio de hospitalización, probabilidad de sobrecarga y número promedio de personas en lista de espera. Resultados Las regiones Sur y Sureste presentaron las tasas promedio de hospitalización más altas, mientras que la región Norte tuvo las tasas más bajas. La región Sureste presentó alta probabilidad de sobrecarga de camas quirúrgicas, sobre todo San Pablo (99,0%), Minas Gerais (97,0%) y Río de Janeiro (97,0%). San Pablo presentó sobrecarga superior al 95,0% en todos los tipos de camas analizadas. Conclusión Hubo alta probabilidad de ocupación de camas de oncología en el SUS, mayormente en quirúrgicas y clínicas, además de disparidades regionales en la sobrecarga de camas.

RESUMO Objetivo Analisar a demanda e a ocupação de leitos do Sistema Único de Saúde para os principais tipos de câncer no Brasil, de 2018 a 2021. Métodos Estudo transversal, descritivo, com dados do Sistema de Informação Hospitalar. Por meio do modelo de teoria de filas, foram calculados: taxa média de entrada para internação, taxa média de internação, probabilidade de sobrecarga e número médio de pessoas em fila. Resultados As regiões Sudeste e Sul apresentaram as maiores taxas médias de internação, enquanto a região Norte obteve as menores taxas. A região Sudeste obteve alta probabilidade de sobrecarga de leitos cirúrgicos, principalmente São Paulo (99,0%), Minas Gerais (97,0%) e Rio de Janeiro (97,0%). São Paulo mostrou sobrecarga acima de 95,0% em todos os tipos de leitos analisados. Conclusão Constatou-se alta probabilidade de ocupação de leitos oncológicos no SUS, em especial os cirúrgicos e clínicos, e disparidades regionais na sobrecarga dos leitos.

Supplementation with Jatobá-do-cerrado flour (Hymenaea stigonocarpa Mart.) decreases hypothalamic inflammation and improves obesity parameters in rats on a high-fat diet.

To evaluate the impact of jatobá-do-cerrado flour on nutritional, inflammatory, and oxidative stress markers, an study was conducted using male Wistar rats. These animals were allocated into four groups: a standard diet (Control), a high-fat diet (HFD), a diet with jatobá-do-cerrado flour (JCF), and a combination of high-fat diet and jatobá-do-cerrado flour (HFD + JCF). Comprehensive evaluations included food intake, cytokine concentrations, and redox status indicators. HFD group exhibited increased caloric intake and fat mass, elevated circulating IL-6, and heightened lipid peroxidation markers. This group also showed increased hypothalamic concentrations of IL-6, TNFα, and lipid peroxidation. In contrast, the HFD + JCF group showed reduced caloric intake, fat mass, and improvements in redox balance and inflammatory markers both in the blood and hypothalamus. SUMMARY: In the current study, we evaluated the potential of Jatobá-do-cerrado flour in mitigating the effects of a high-fat diet in adult Wistar rats. The addition of fat to the animals' diet for 63 days induced obesity, dyslipidemia, as well as an increase in inflammatory and lipid peroxidation markers, both in the blood and hypothalamus. Conversely, supplementation with Jatobá-do-Cerrado flour showed anti-obesogenic effects and these may be associated with the reduction of inflammation and oxidative stress. Therefore, supplementation with this flour has the potential to be a functional food for the treatment or prevention of obesity.

Covid-19 Fiocruz Observatory - an analysis of the evolution of the pandemic from February 2020 to April 2022. / Observatório Covid-19 Fiocruz - uma análise da evolução da pandemia de fevereiro de 2020 a abril de 2022.

The COVID-19 pandemic had a significant impact on the living and working conditions of the entire population of Brazil, having a different and more intense effect on groups considered to be vulnerable. The objective of this article is to present an overview of the evolution of the pandemic in the country according to the bulletins of the Covid-19 Fiocruz Observatory in the period between the declarations of the beginning and end of the Public Health Emergency of National Concern (ESPIN, in Portuguese), February 2020 to April 2022. Several of the indicators adopted in the 69 bulletins published for the analysis of the pandemic were used, such as cases and deaths due to SARIs and COVID-19, age groups, % of occupancy of ICU beds, and vaccination, among others. The evolution analysis was organized between years and phases of the pandemic, seeking to highlight what characterized each moment. The closing statement of ESPIN in Brazil coincides with the discussions on the transition from a pandemic to an endemic scenario, without this representing the elimination of the virus, infections, and disease, posing the challenges of advances in vaccination processes in Brazil and around the world, as well as living with scenarios that may require the adoption of temporary protection measures in epidemic periods and periods of greater risk for vulnerable groups.

A pandemia de COVID-19 teve um imenso impacto nas condições de vida e trabalho de toda a população do país, impactando de modo diferenciado e mais intenso os grupos considerados vulneráveis. O objetivo deste artigo é apresentar um panorama da evolução da pandemia no país segundo os boletins do Observatório Covid-19 Fiocruz, no período entre as declarações de início e de encerramento da Emergência em Saúde Pública de Importância Nacional (ESPIN), fevereiro de 2020 a abril de 2022. Foram utilizados diversos dos indicadores adotados nos 69 boletins publicados para a análise da pandemia, como casos e óbitos por SRAGs e COVID-19, grupos etários, taxas de ocupação de leitos UTI e vacinação, entre outros. A análise da evolução foi organizada entre anos e fases da pandemia, procurando destacar o que caracterizou cada momento. A declaração de encerramento da ESPIN no Brasil coincide com as discussões acerca da transição de pandemia para a endemia, sem que isso represente a eliminação do vírus, das infecções e da doença, colocando-se os desafios de avanços nos processos de vacinação no Brasil e no mundo e da convivência com cenários que poderão exigir a adoção de medidas de proteção temporárias em períodos epidêmicos e de maior risco para grupos vulneráveis.

Observatório Covid-19 Fiocruz - uma análise da evolução da pandemia de fevereiro de 2020 a abril de 2022 / Covid-19 Fiocruz Observatory - an analysis of the evolution of the pandemic from February 2020 to April 2022

Resumo A pandemia de COVID-19 teve um imenso impacto nas condições de vida e trabalho de toda a população do país, impactando de modo diferenciado e mais intenso os grupos considerados vulneráveis. O objetivo deste artigo é apresentar um panorama da evolução da pandemia no país segundo os boletins do Observatório Covid-19 Fiocruz, no período entre as declarações de início e de encerramento da Emergência em Saúde Pública de Importância Nacional (ESPIN), fevereiro de 2020 a abril de 2022. Foram utilizados diversos dos indicadores adotados nos 69 boletins publicados para a análise da pandemia, como casos e óbitos por SRAGs e COVID-19, grupos etários, taxas de ocupação de leitos UTI e vacinação, entre outros. A análise da evolução foi organizada entre anos e fases da pandemia, procurando destacar o que caracterizou cada momento. A declaração de encerramento da ESPIN no Brasil coincide com as discussões acerca da transição de pandemia para a endemia, sem que isso represente a eliminação do vírus, das infecções e da doença, colocando-se os desafios de avanços nos processos de vacinação no Brasil e no mundo e da convivência com cenários que poderão exigir a adoção de medidas de proteção temporárias em períodos epidêmicos e de maior risco para grupos vulneráveis.

Abstract The COVID-19 pandemic had a significant impact on the living and working conditions of the entire population of Brazil, having a different and more intense effect on groups considered to be vulnerable. The objective of this article is to present an overview of the evolution of the pandemic in the country according to the bulletins of the Covid-19 Fiocruz Observatory in the period between the declarations of the beginning and end of the Public Health Emergency of National Concern (ESPIN, in Portuguese), February 2020 to April 2022. Several of the indicators adopted in the 69 bulletins published for the analysis of the pandemic were used, such as cases and deaths due to SARIs and COVID-19, age groups, % of occupancy of ICU beds, and vaccination, among others. The evolution analysis was organized between years and phases of the pandemic, seeking to highlight what characterized each moment. The closing statement of ESPIN in Brazil coincides with the discussions on the transition from a pandemic to an endemic scenario, without this representing the elimination of the virus, infections, and disease, posing the challenges of advances in vaccination processes in Brazil and around the world, as well as living with scenarios that may require the adoption of temporary protection measures in epidemic periods and periods of greater risk for vulnerable groups.

AT2 receptor agonist LP2 restores respiratory function in a rat model of bleomycin-induced lung remodelling.

This study aimed to evaluate the prophylactic and therapeutic potential of angiotensin II type 2 receptor peptide agonist LP2 in bleomycin-induced airway and cardiac remodeling in rats. Male Wistar rats were intratracheally instillated with bleomycin. Animals of a prophylactic arm received LP2 from day 0 at intraperitoneal doses of 1, 3 or 10 µg/kg/d, whereas animals from a therapeutic arm received this LP2 treatment from day 7. On day 28 direct lung mechanics were determined and cardiac and lung tissues were collected and (histo)morphologically assessed. Prophylactic LP2 at 1 µg/kg/d with bleomycin, versus bleomycin alone, significantly improved the airway pressure responses at fixed inflation of 4 ml (p < 0.05) and 7 ml volume (p < 0.05), static compliance (p < 0.01), inspiratory capacity (p < 0.05), lung tolerance of increased volume (p < 0.0001), right to left ventricular hypertrophy (p < 0.05). Therapeutic regime showed a similar trend as the prophylactic arm but was less effective, mostly lacking significance. However, and importantly, therapeutic LP2 at 1 µg/kg/d significantly decreased mRNA expression of collagen 1A1 (p < 0.01), of Connective Tissue Growth Factor 1 (p < 0.05) and of Tissue MetalloPeptidase inhibitor 1 (p < 0.05). In conclusion, a very low dose of 1 µg/kg/d LP2 has capacity to counter bleomycin-induced impairment of lung functioning and consequent cardiac remodeling.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

The effectiveness of COVID-19 vaccines against severe cases and deaths in Brazil from 2021 to 2022: a registry-based study.

Background: Brazil started the COVID-19 mass vaccination in January 2021 with CoronaVac and ChAdOx1, followed by BNT162b2 and Ad26.COV2.S vaccines. By the end of 2021, more than 317 million vaccine doses were administered in the adult population. This study aimed at estimating the effectiveness of the primary series of COVID-19 vaccination and booster shots in protecting against severe cases and deaths in Brazil during the first year of vaccination. Methods: A cohort dataset of over 158 million vaccination and severe cases records linked from official national registries was analyzed via a mixed-effects Poisson model, adjusted for age, state of residence, time after immunization, and calendar time to estimate the absolute vaccine effectiveness of the primary series of vaccination and the relative effectiveness of the booster. The method permitted analysis of effectiveness against hospitalizations and deaths, including in the periods of variant dominance. Findings: Vaccine effectiveness against severe cases and deaths remained over 25% and 50%, respectively, after 19 weeks from primary vaccination of BNT162b2, ChAdOx1, or CoronaVac vaccines. The boosters conferred greater protection than the primary series of vaccination, with heterologous boosters providing marginally greater protection than homologous. The effectiveness against hospitalization during the Omicron dominance in the 60+ years old population started at 61.7% (95% CI, 26.1-86.2) for ChAdOx1, 95.6% (95% CI, 82.4-99.9) for CoronaVac, and 72.3% (95% CI, 51.4-87.4) for the BNT162b2 vaccine. Interpretation: This study provides real-world evidence of the effectiveness of COVID-19 vaccination in Brazil, including during the Omicron wave, demonstrating protection even after waning effectiveness. Comparisons of the effectiveness among different vaccines require caution due to potential bias effects related to age groups, periods in the pandemic, and eventual behavioural changes. Funding: Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).

Notification of malaria cases in the Brazilian Amazon Basin from 2010 to 2020: an analysis of the reporting times.

BACKGROUND: As controlling malaria transmission remains a public-health challenge in the Brazilian Amazon basin, the National Surveillance System for Malaria (SIVEP-MALARIA) has registered malaria notifications for over fifteen years helping in the decision-making on control and elimination. As a surveillance database, the system is prone to reporting delays, and knowledge about reporting patterns is essential in decisions. METHODS: This study contains an analysis of temporal and state trends of reporting times in a total of 1,580,617 individual malaria reports from January 2010 to December 2020, applying procedures for statistical distribution fitting. A nowcasting technique was applied to show an estimation of number of cases using a statistical model of reporting delays. RESULTS: Reporting delays increased over time for the states of Amazonas, Rondônia, Roraima, and Pará. Amapá has maintained a similar reporting delay pattern, while Acre decreased reporting delay between 2010 and 2020. Predictions were more accurate in states with lower reporting delays. The temporal evolution of reporting delays only showed a decrease in malaria reports in Acre from 2010 to 2020. CONCLUSION: Malaria notifications may take days or weeks to enter the national surveillance database. The reporting times are likely to impact incidence estimation over periods when data is incomplete, whilst the impact of delays becomes smaller for retrospective analysis. Short-term assessments for the estimation of malaria incidence from the malaria control programme must deal with reporting delays.

Estimated COVID-19 severe cases and deaths averted in the first year of the vaccination campaign in Brazil: A retrospective observational study.

Background: A nationwide Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination campaign was initiated in Brazil in January 2021 with CoronaVac (Sinovac Biotech) and ChAdOx1 nCoV-19 (AstraZeneca) followed by BNT162b2 mRNA (Pfizer-BioNTech) and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines. Here we provide estimates of the number of severe cases and deaths due to coronavirus disease (COVID-19) averted during the first year of the mass vaccination campaign in Brazil. Methods: Data on COVID-19 vaccination and COVID-19-related illness and death were obtained from the Brazilian Ministry of Health and used to estimate the direct effects of the vaccination campaign on the number of severe cases and deaths due to COVID-19 occurring between January 17, 2021 and January 31, 2022. To this end, we compared the daily age-specific rates between the unvaccinated population and the "at least partly vaccinated" population (received at least one dose of a two-dose vaccine), as well as other two vaccination subgroups, "fully vaccinated" (completed the one- or two-dose vaccine schedule), and "boosted-vaccinated" (fully vaccinated and recipients of booster dose) populations. Findings: We estimated that 74% (n = 875,846; 95% confidence interval, CI 843,383-915,709) of total expected cases of severe COVID-19 and 82% (n = 303,129; 95% CI 284,019-321,681) of total expected deaths due to COVID-19 were averted in the first year of the national vaccination campaign. The averted burden was heterogeneous between age groups and higher in the more populous states. However, outcome rate differences between vaccinated and unvaccinated groups were higher in the less populated states. Interpretation: The first year of the COVID-19 vaccination program in Brazil saved the lives of at least 303,129 adults. The results highlight the need for future vaccination campaigns, including those required in the current pandemic, to rapidly achieve high uptake, particularly among the elderly and residents of the least populous regions. Funding: Ministry of Health (Brazil).

Entomo-virological surveillance followed by serological active survey of symptomatic individuals is helpful to identify hotspots of early arbovirus transmission.

Arboviruses transmitted by Aedes aegypti in urban environments have spread rapidly worldwide, causing great impacts on public health. The development of reliable and timely alert signals is among the most important steps in designing accurate surveillance systems for vector-borne diseases. In July and September 2017, we conducted a pilot study to improve an existing integrated surveillance system by using entomo-virological surveillance to prioritize areas to conduct active searches for individuals with arbovirus infection symptoms. Foz do Iguaçu City has a permanent entomo-virological surveillance system with approximately 3,500 traps to capture Aedes sp. in the adult stage. The Aedes aegypti females are captured alive and human samples are submitted to RT-qPCR (real-time qPCR) screening for DENV, ZIKV, and CHIKV diagnosis. Of the 55 Ae. aegypti mosquitoes tested in July 2017, seven (12.7%) were considered positive for DENV-2 and three (5.4%) for CHIKV. In September, we tested a sample of 54 mosquitoes, and 15 (27.7%) were considered infected by DENV-2. We created 25 circumferences with 150-m radius each to perform an active survey to identify symptomatic householders. In July, we selected one circumference, and five (35.7%) patients were positive for DENV, whereas two (14.3%) for CHIKV. In September, we selected four circumferences, and, from the 21 individuals sampled, nine (42.8%) were positive for DENV-2. A statistical model with a binomial response was used to estimate the number of cases in areas without active surveys, i.e., 20 circumferences. We estimated an additional 83 symptomatic patients (95% CI: 45-145) to be found in active searches, with 38 (95% CI: 18-72) of them confirming arbovirus infection. Arbovirus detection and serotyping in mosquitoes, but also in symptomatic individuals during active surveys, can provide an alert signal of early arbovirus transmission.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

Occurrence of yellow fever outbreaks in a partially vaccinated population: An analysis of the effective reproduction number.

BACKGROUND: Yellow fever is endemic in Africa and the Americas, occurring in urban or sylvatic environments. The infection presents varying symptoms, with high case-fatality among severe cases. In 2016, Brazil had sylvatic yellow fever outbreaks with more than 11 thousand cases, predominantly affecting the country's Southeast region. The state of Minas Gerais accounted for 30% of cases, even after the vaccine had been included in the immunization calendar for at least 30 years. METHODOLOGY AND PRINCIPAL FINDINGS: We applied parameters described in the literature from yellow fever disease into a compartmental model of vector-borne diseases, using namely generation time intervals, vital host and vector parameters, and force of infection, using macroregions as the spatial unit and epidemiological weeks as the time interval. The model permits obtaining the reproduction number, which we analyzed from reported cases of yellow fever from 2016 to 2018 in residents of the state of Minas Gerais, Brazil. Minas Gerais recorded two outbreak periods, starting in EW 51/2016 and EW 51/2017. Of all the reported cases (3,304), 57% were men 30 to 59 years of age. Approximately 27% of cases (905) were confirmed, and 22% (202) of these individuals died. The estimated effective reproduction number varied from 2.7 (95% CI: 2.0-3.6) to 7.2 (95% CI: 4.4-10.9], found in the Oeste and Nordeste regions, respectively. Vaccination coverage in children under one year of age showed heterogeneity among the municipalities comprising the macroregions. CONCLUSION: The outbreaks in multiple parts of the state and the estimated Re values raise concern since the state population was partially vaccinated. Heterogeneity in vaccination coverage may have been associated with the occurrence of outbreaks in the first period, while the subsequent intense vaccination campaign may have determined lower Re values in the second period.