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.

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.

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.

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.

Functional assay for assessment of agonistic or antagonistic activity of angiotensin AT2 receptor ligands reveals that EMA401 and PD123319 have agonistic properties.

With the discovery of the protective arm of the renin-angiotensin system (RAS), interest has grown in protective RAS-related receptors such as the angiotensin AT2-receptor [AT2R] as potential new drug targets. While it is known that AT2R couple to Gi, it is also apparent that they do not signal via inhibition of adenylyl cyclase/decrease in cAMP, as do many Gi-coupled receptors. Thus, standard commercially-available assays cannot be applied to test for agonistic or antagonistic properties of AT2R ligands. This lack of standard assays has hampered the development of new drugs targeting the AT2R. Therefore, we aimed at developing a reliable, technically easy assay for the determination of intrinsic activity of AT2R ligands, primarily for distinguishing between AT2R agonists and antagonists. We found that measurement of NO release by DAF-FM fluorescence in primary human aortic endothelial cells (HAEC) or in AT2R-transfected CHO cells is a reliable assay for the characterization of AT2R ligands. While testing the assay, we made several novel findings, including: a) C21 is a full agonist at the AT2R (with the same efficacy as angiotensin II); b) C21 has no intrinsic activity at the receptor Mas; c) AT2R-transfected HEK-293 cells are unresponsive to AT2R stimulation; d) EMA401 and PD123319, which are commonly regarded as AT2R antagonists, are partial agonists at the AT2R. Collectively, we have developed and tested an assay based on the measurement and quantification of NO release in HAEC or in AT2R-CHO cells that is suitable for the characterisation of novel and established AT2R ligands.

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.

Big data technology in infectious diseases modeling, simulation, and prediction after the COVID-19 outbreak.

After the outbreak of COVID-19, the interaction of infectious disease systems and social systems has challenged traditional infectious disease modeling methods. Starting from the research purpose and data, researchers improved the structure and data of the compartment model or used agents and artificial intelligence based models to solve epidemiological problems. In terms of modeling methods, the researchers use compartment subdivision, dynamic parameters, agent-based model methods, and artificial intelligence related methods. In terms of factors studied, the researchers studied 6 categories: human mobility, nonpharmaceutical interventions (NPIs), ages, medical resources, human response, and vaccine. The researchers completed the study of factors through modeling methods to quantitatively analyze the impact of social systems and put forward their suggestions for the future transmission status of infectious diseases and prevention and control strategies. This review started with a research structure of research purpose, factor, data, model, and conclusion. Focusing on the post-COVID-19 infectious disease prediction simulation research, this study summarized various improvement methods and analyzes matching improvements for various specific research purposes.

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.

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.

Modelling: Understanding pandemics and how to control them.

New disease challenges, societal demands and better or novel types of data, drive innovations in the structure, formulation and analysis of epidemic models. Innovations in modelling can lead to new insights into epidemic processes and better use of available data, yielding improved disease control and stimulating collection of better data and new data types. Here we identify key challenges for the structure, formulation, analysis and use of mathematical models of pathogen transmission relevant to current and future pandemics.

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.

Challenges for modelling interventions for future pandemics.

Mathematical modelling and statistical inference provide a framework to evaluate different non-pharmaceutical and pharmaceutical interventions for the control of epidemics that has been widely used during the COVID-19 pandemic. In this paper, lessons learned from this and previous epidemics are used to highlight the challenges for future pandemic control. We consider the availability and use of data, as well as the need for correct parameterisation and calibration for different model frameworks. We discuss challenges that arise in describing and distinguishing between different interventions, within different modelling structures, and allowing both within and between host dynamics. We also highlight challenges in modelling the health economic and political aspects of interventions. Given the diversity of these challenges, a broad variety of interdisciplinary expertise is needed to address them, combining mathematical knowledge with biological and social insights, and including health economics and communication skills. Addressing these challenges for the future requires strong cross-disciplinary collaboration together with close communication between scientists and policy makers.