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.

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.

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.

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.

Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: A population-based serosurvey.

Background: COVID-19 serosurveys allow for the monitoring of the level of SARS-CoV-2 transmission and support data-driven decisions. We estimated the seroprevalence of anti-SARS-CoV-2 antibodies in a large favela complex in Rio de Janeiro, Brazil. Methods: A population-based panel study was conducted in Complexo de Manguinhos (16 favelas) with a probabilistic sampling of participants aged ≥1 year who were randomly selected from a census of individuals registered in primary health care clinics that serve the area. Participants answered a structured interview and provided blood samples for serology. Multilevel regression models (with random intercepts to account for participants' favela of residence) were used to assess factors associated with having anti-S IgG antibodies. Secondary analyses estimated seroprevalence using an additional anti-N IgG assay. Findings: 4,033 participants were included (from Sep/2020 to Feb/2021, 22 epidemic weeks), the median age was 39·8 years (IQR:21·8-57·7), 61% were female, 41% were mixed-race (Pardo) and 23% Black. Overall prevalence was 49·0% (95%CI:46·8%-51·2%) which varied across favelas (from 68·3% to 31·4%). Lower prevalence estimates were found when using the anti-N IgG assay. Odds of having anti-S IgG antibodies were highest for young adults, and those reporting larger household size, poor adherence to social distancing and use of public transportation. Interpretation: We found a significantly higher prevalence of anti-S IgG antibodies than initially anticipated. Disparities in estimates obtained using different serological assays highlight the need for cautious interpretation of serosurveys estimates given the heterogeneity of exposure in communities, loss of immunological biomarkers, serological antigen target, and variant-specific test affinity. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the European Union's Horizon 2020 research and innovation programme, Royal Society, Serrapilheira Institute, and FAPESP.

Citywide Integrated Aedes aegypti Mosquito Surveillance as Early Warning System for Arbovirus Transmission, Brazil.

Arbovirus epidemiology lacks efficient and timely surveillance systems with accurate outbreak alert signals. We devised a citywide integrated surveillance system combining entomologic, epidemiologic, and entomo-virologic data gathered during 2017-2020 in Foz do Iguaçu, Brazil. We installed 3,476 adult mosquito traps across the city and inspected traps every 2 months. We compared 5 entomologic indices: traditional house and Breteau indices for larval surveys and trap positivity, adult density, and mosquitoes per inhabitant indices for adult trapping. We screened for dengue, Zika, and chikungunya viruses in live adult Aedes aegypti mosquitoes collected from traps. Indices based on adult mosquito sampling had higher outbreak predictive values than larval indices, and we were able to build choropleth maps of infestation levels <36 h after each round of trap inspection. Locating naturally infected vectors provides a timely support tool for local public health managers to prioritize areas for intervention response to prevent virus outbreaks.

On multifactorial drivers for malaria rebound in Brazil: a spatio-temporal analysis.

BACKGROUND: Malaria incidence in Brazil reversed its decreasing trend when cases from recent years, as recent as 2015, exhibited an increase in the Brazilian Amazon basin, the area with the highest transmission of Plasmodium vivax and Plasmodium falciparum. In fact, an increase of more than 20% in the years 2016 and 2017 revealed possible vulnerabilities in the national malaria-control programme. METHODS: Factors potentially associated with this reversal, including migration, economic activities, and deforestation, were studied. Past incidences of malaria cases due to P. vivax and P. falciparum were analysed with a spatio-temporal Bayesian model using more than 5 million individual records of malaria cases from January of 2003 to December of 2018 in the Brazilian Amazon to establish the municipalities with unexpected increases in cases. RESULTS: Plasmodium vivax incidence surpassed the past trends in Amazonas (AM), Amapá (AP), Acre (AC), Pará (PA), Roraima (RR), and Rondônia (RO), implying a rebound of these states between 2015 and 2018. On the other hand, P. falciparum also surpassed the past trends in AM, AC, AP, and RR with less severity than P. vivax incidence. Outdoor activities, agricultural activities, accumulated deforestation, and travelling might explain the rebound in malaria cases in RR, AM, PA, and RO, mainly in P. vivax cases. These variables, however, did not explain the rebound of either P. vivax and P. falciparum cases in AC and AP states or P. falciparum cases in RR and RO states. CONCLUSION: The Amazon basin has experienced an unexpected increase in malaria cases, mainly in P. vivax cases, in some regions of the states of Amazonas, Acre, Pará, Amapá, Roraima, and Rondônia from 2015 to 2018 and agricultural activities, outdoor activities, travelling activities, and accumulated deforestation appear linked to this rebound of cases in particular regions with different impact. This shows the multifactorial effects and the heterogeneity of the Amazon basin, boosting the necessity of focusing the malaria control programme on particular social, economic, and environmental conditions.

Modelling policy combinations of vaccination and transmission suppression of SARS-CoV-2 in Rio de Janeiro, Brazil.

COVID-19 vaccination in Brazil required a phased program, with priorities for age groups, health workers, and vulnerable people. Social distancing and isolation interventions have been essential to mitigate the advance of the pandemic in several countries. We developed a mathematical model capable of capturing the dynamics of the SARS-CoV-2 dissemination aligned with social distancing, isolation measures, and vaccination. Surveillance data from the city of Rio de Janeiro provided a case study to analyze possible scenarios, including non-pharmaceutical interventions and vaccination in the epidemic scenario. Our results demonstrate that the combination of vaccination and policies of transmission suppression potentially lowered the number of hospitalized cases by 380+ and 66+ thousand cases, respectively, compared to an absence of such policies. On top of transmission suppression-only policies, vaccination impacted more than 230+ thousand averted hospitalized cases and 43+ thousand averted deaths. Therefore, health surveillance activities should be maintained along with vaccination planning in scheduled groups until a large vaccinated coverage is reached. Furthermore, this analytical framework enables evaluation of such scenarios.

Entomo-Virological Aedes aegypti Surveillance Applied for Prediction of Dengue Transmission: A Spatio-Temporal Modeling Study.

Currently, DENV transmitted primarily by Aedes aegypti affects approximately one in three people annually. The spatio-temporal heterogeneity of vector infestation and the intensity of arbovirus transmission require surveillance capable of predicting an outbreak. In this work, we used data from 4 years of reported dengue cases and entomological indicators of adult Aedes collected from approximately 3500 traps installed in the city of Foz do Iguaçu, Brazil, to evaluate the spatial and temporal association between vector infestation and the occurrence of dengue cases. Entomological (TPI, ADI and MII) and entomo-virological (EVI) indexes were generated with the goal to provide local health managers with a transmission risk stratification that allows targeting areas for vector control activities. We observed a dynamic pattern in the evaluation; however, it was a low spatio-temporal correlation of Ae. aegypti and incidence of dengue. Independent temporal and spatial effects capture a significant portion of the signal given by human arbovirus cases. The entomo-virological index (EVI) significantly signaled risk in a few areas, whereas entomological indexes were not effective in providing dengue risk alert. Investigating the variation of biotic and abiotic factors between areas with and without correlation should provide more information about the local epidemiology of dengue.

Short-Time Recurrences of Plasmodium vivax Malaria as a Public Health Proxy for Chloroquine-Resistance Surveillance: A Spatio-Temporal Study in the Brazilian Amazon.

In Brazil, malaria caused by Plasmodium vivax presents control challenges due to several reasons, among them the increasing possibility of failure of P. vivax treatment due to chloroquine-resistance (CQR). Despite limited reports of CQR, more extensive studies on the actual magnitude of resistance are still needed. Short-time recurrences of malaria cases were analyzed in different transmission scenarios over three years (2005, 2010, and 2015), selected according to malaria incidence. Multilevel models (binomial) were used to evaluate association of short-time recurrences with variables such as age. The zero-inflated Poisson scan model (scanZIP) was used to detect spatial clusters of recurrences up to 28 days. Recurrences compose less than 5% of overall infection, being more frequent in the age group under four years. Recurrences slightly increased incidence. No fixed clusters were detected throughout the period, although there are clustering sites, spatially varying over the years. This is the most extensive analysis of short-time recurrences worldwide which addresses the occurrence of P. vivax CQR. As an important step forward in malaria elimination, policymakers should focus their efforts on young children, with an eventual shift in the first line of malaria treatment to P. vivax.

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.

Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax.

The spread of drug resistance of Plasmodium falciparum and Plasmodium vivax parasites is a challenge towards malaria elimination. P. falciparum has shown an early and severe drug resistance in comparison to P. vivax in various countries. In fact, P. vivax differs in its life cycle and treatment in various factors: development and duration of sexual parasite forms differ, symptoms severity are unequal, relapses present only in P. vivax cases and the Artemisinin-based combination therapy (ACT) is only mandatory in P. falciparum cases. We compared the spread of drug resistance for both species through two compartmental models using ordinary differential equations. The model structure describes how sensitive and resistant parasite strains infect a human population treated with antimalarials. We found that an early transmission,i.e., before treatment and low effectiveness of drug coverage, supports the prevalence of sensitive parasites delaying the emergence of resistant P. vivax. These results imply that earlier attention of both symptomatic cases and reservoirs of P. vivax are essential in controlling transmission but also accelerate the spread of drug resistance.

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.

Discrete time forecasting of epidemics.

Forecasting in the domain of infectious diseases aims at estimating the number of cases ahead of time during an epidemic, hence fundamentally requires understanding its dynamics. In fact, estimates about the dynamics help to predict the number of cases in an epidemic, which will depend on determining a few of defining factors such as its starting point, the turning point, growth factor, and the size of the epidemic in total number of cases. In this work a phenomenological model deals with a practical aspect often disregarded in such studies, namely that health surveillance produces counts in batches when aggregated over discrete time, such as days, weeks, months, or other time units. This model enables derivation of equations that permit both estimating key dynamics parameters and forecasting. Results using both severe acute respiratory illness data and synthetic data show that the forecasting follows very well over time the dynamics and is resilient with statistical noise, but has a delay effect due to the discrete time.

Aedes aegypti insecticide resistance underlies the success (and failure) of Wolbachia population replacement.

Mosquitoes that carry Wolbachia endosymbionts may help control the spread of arboviral diseases, such as dengue, Zika and chikungunya. Wolbachia frequencies systematically increase only when the frequency-dependent advantage due to cytoplasmic incompatibility exceeds frequency-independent costs, which may be intrinsic to the Wolbachia and/or can be associated with the genetic background into which Wolbachia are introduced. Costs depend on field conditions such as the environmental pesticide load. Introduced mosquitoes need adequate protection against insecticides to ensure survival after release. We model how insecticide resistance of transinfected mosquitoes determines the success of local Wolbachia introductions and link our theoretical results to field data. Two Ae. aegypti laboratory strains carrying Wolbachia were released in an isolated district of Rio de Janeiro, Brazil: wMelBr (susceptible to pyrethroids) and wMelRio (resistant to pyrethroids). Our models elucidate why releases of the susceptible strain failed to result in Wolbachia establishment, while releases of the resistant strain led to Wolbachia transforming the native Ae. aegypti population. The results highlight the importance of matching insecticide resistance levels in release stocks to those in the target natural populations during Wolbachia deployment.

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.

Oscillatory regimes in a mosquito population model with larval feedback on egg hatching.

Understanding mosquitoes life cycle is of great interest presently because of the increasing impact of vector borne diseases in several countries. There is evidence of oscillations in mosquito populations independent of seasonality, still unexplained, based on observations both in laboratories and in nature. We propose a simple mathematical model of egg hatching enhancement by larvae which produces such oscillations that conveys a possible explanation. We propose both a theoretical analysis, based on slow-fast dynamics and Hopf bifurcation, and numerical investigations in order to shed some light on the mechanisms at work in this model.

Matching the genetics of released and local Aedes aegypti populations is critical to assure Wolbachia invasion.

BACKGROUND: Traditional vector control approaches such as source reduction and insecticide spraying have limited effect on reducing Aedes aegypti population. The endosymbiont Wolbachia is pointed as a promising tool to mitigate arbovirus transmission and has been deployed worldwide. Models predict a rapid increase on the frequency of Wolbachia-positive Ae. aegypti mosquitoes in local settings, supported by cytoplasmic incompatibility (CI) and high maternal transmission rate associated with the wMelBr strain. METHODOLOGY/PRINCIPLE FINDINGS: Wolbachia wMelBr strain was released for 20 consecutive weeks after receiving >87% approval of householders of the isolated community of Tubiacanga, Rio de Janeiro. wMelBr frequency plateued~40% during weeks 7-19, peaked 65% but dropped as releases stopped. A high (97.56%) maternal transmission was observed. Doubling releases and deploying mosquitoes with large wing length and low laboratory mortality produced no detectable effects on invasion trend. By investigating the lab colony maintenance procedures backwardly, pyrethroid resistant genotypes in wMelBr decreased from 68% to 3.5% after 17 generations. Therefore, we initially released susceptible mosquitoes in a local population highly resistant to pyrethroids which, associated with the over use of insecticides by householders, ended jeopardizing Wolbachia invasion. A new strain (wMelRio) was produced after backcrossing wMelBr females with males from field to introduce mostly pyrethroid resistance alleles. The new strain increased mosquito survival but produced relevant negative effects on Ae. aegypti fecundity traits, reducing egg clutche size and egg hatch. Despite the cost on fitness, wMelRio successful established where wMelBr failed, revealing that matching the local population genetics, especially insecticide resistance background, is critical to achieve invasion. CONCLUSIONS/SIGNIFICANCE: Local householders support was constantly high, reaching 90% backing on the second release (wMelRio strain). Notwithstanding the drought summer, the harsh temperature recorded (daily average above 30°C) did not seem to affect the expression of maternal transmission of wMel on a Brazilian background. Wolbachia deployment should match the insecticide resistance profile of the wild population to achieve invasion. Considering pyrethroid-resistance is a widely distributed phenotype in natural Ae. aegypti populations, future Wolbachia deployments must pay special attention in maintaining insecticide resistance in lab colonies for releases.