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.

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.

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.

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.

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.

Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study.

BACKGROUND: Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness. Tafenoquine, a new single-dose treatment, offers an alternative option for preventing relapses and reducing transmission. In 2018, over 237,000 cases of malaria were reported to the Brazilian health system, of which 91.5% were due to P. vivax. METHODS AND FINDINGS: We evaluated the impact of introducing tafenoquine into case management practices on population-level transmission dynamics using a mathematical model of P. vivax transmission. The model was calibrated to reflect the transmission dynamics of P. vivax endemic settings in Brazil in 2018, informed by nationwide malaria case reporting data. Parameters for treatment pathways with chloroquine, primaquine, and tafenoquine with glucose-6-phosphate dehydrogenase deficiency (G6PDd) testing were informed by clinical trial data and the literature. We assumed 71.3% efficacy for primaquine and tafenoquine, a 66.7% adherence rate to the 7-day primaquine regimen, a mean 5.5% G6PDd prevalence, and 8.1% low metaboliser prevalence. The introduction of tafenoquine is predicted to improve effective hypnozoite clearance among P. vivax cases and reduce population-level transmission over time, with heterogeneous levels of impact across different transmission settings. According to the model, while achieving elimination in only few settings in Brazil, tafenoquine rollout in 2021 is estimated to improve the mean effective radical cure rate from 42% (95% uncertainty interval [UI] 41%-44%) to 62% (95% UI 54%-68%) among clinical cases, leading to a predicted 38% (95% UI 7%-99%) reduction in transmission and over 214,000 cumulative averted cases between 2021 and 2025. Higher impact is predicted in settings with low transmission, low pre-existing primaquine adherence, and a high proportion of cases in working-aged males. High-transmission settings with a high proportion of cases in children would benefit from a safe high-efficacy tafenoquine dose for children. Our methodological limitations include not accounting for the role of imported cases from outside the transmission setting, relying on reported clinical cases as a measurement of community-level transmission, and implementing treatment efficacy as a binary condition. CONCLUSIONS: In our modelling study, we predicted that, provided there is concurrent rollout of G6PDd diagnostics, tafenoquine has the potential to reduce P. vivax transmission by improving effective radical cure through increased adherence and increased protection from new infections. While tafenoquine alone may not be sufficient for P. vivax elimination, its introduction will improve case management, prevent a substantial number of cases, and bring countries closer to achieving malaria elimination goals.

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.

The top 1%: quantifying the unequal distribution of malaria in Brazil.

BACKGROUND: As malaria endemic countries strive towards elimination, intensified spatial heterogeneities of local transmission could undermine the effectiveness of traditional intervention policy. METHODS: The dynamic nature of large-scale and long-term malaria heterogeneity across Brazilian Amazon basin were explored by (1) exploratory analysis of Brazil's rich clinical malaria reporting database from 2004 to 2018, and (2) adapting Gini coefficient to study the distribution of malaria cases in the region. RESULTS: As transmission declined, heterogeneity increased with cases clustering into smaller subpopulations across the territory. In 2004, the 1% of health units with the greatest number of cases accounted for 46% of all reported Plasmodium vivax cases, whereas in 2018 52% of P. vivax cases occurred in the top 1% of health units. Plasmodium falciparum had lower levels of transmission than P. vivax, and also had greater levels of heterogeneity with 75% of cases occurring in the top 1% of health units. Age and gender stratification of cases revealed peri-domestic and occupational exposure settings that remained relatively stable. CONCLUSION: The pathway to decreasing incidence is characterized by higher proportions of cases in males, in adults, due to importation, and caused by P. vivax. Characterization of spatio-temporal heterogeneity and risk groups can aid stratification for improved malaria control towards elimination with increased heterogeneity potentially allowing for more efficient and cost-effective targeting. Although distinct epidemiological phenomena were clearly observed as malaria transmission declines, the authors argue that there is no canonical path to malaria elimination and a more targeted and dynamic surveillance will be needed if Brazil decides to adopt the elimination target.

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.

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.

Co-infection of human herpesvirus type 2 (HHV-2) and human immunodeficiency virus (HIV) among pregnant women in Rio de Janeiro, Brazil.

Pregnant women who are infected with the Human Immunodeficiency Virus (HIV) are particularly vulnerable to severe and recurrent infections with Human Herpesvirus 2 (HHV-2). Neonatal transmission of HHV-2 has been associated with malformations and neurological sequelae in infants, which makes it very important to perform antenatal monitoring for genital herpes. In the study, 134 pregnant women infected with HIV were tested for HHV-2 IgM and IgG using an enzyme-linked immunosorbent assay (ELISA) and had HHV-2 DNA analyzed by Real Time Polymerase Chain Reaction (qPCR). Fisher's exact test was applied to analyze the epidemiological dates (p < 0.05). A total of 59.7% of the pregnant women infected with HIV had HHV-2 IgG and 3.75% of them showed HHV-2 viremia. HHV-2 IgM was found in 6% of the pregnant women and 25% of them had HHV-2 viremia. The risk factors associated with HHV-2 seropositive were age under 20 and a CD4/CD8 ratio > 1. Our study found high HHV-2/HIV coinfection prevalence and HHV-2 viremia among patients with recurrent and primary genital infection, reinforcing the need of prevention and control of HHV-2 infection in order to avoid this virus transmission.

Zika is not a reason for missing the Olympic Games in Rio de Janeiro: response to the open letter of Dr Attaran and colleagues to Dr Margaret Chan, Director - General, WHO, on the Zika threat to the Olympic and Paralympic Games.

Attaran and colleagues in an open letter to WHO expressed their concern about the upcoming Olympic and Paralympic Games in Rio de Janeiro and the threat posed by the Zika epidemic (Attaran 2016). We agree that Zika virus is of great public health concern and much remains to be known about this disease. Care should be taken to reduce the risk of infection, especially to pregnant women. However, we argue that this is not sufficient reason for changing the original plans for the Games, in particular because of the time of the year when they will take place. The present article outlines several scientific results related to Zika and mosquito-borne infectious diseases dynamics that we believe ratify the current position of WHO in not endorsing the postponing or relocation of the 2016 Olympic and Paralympic Games (WHO 2016).

Angiotensin type 2 receptor (AT2R) and receptor Mas: a complex liaison.

The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking similarities. Moreover, in some instances, antagonists for one receptor are able to inhibit the action of agonists for the respective other receptor. These observations suggest that there may be a functional or even physical interaction of both receptors. This article discusses potential mechanisms underlying the phenomenon of blockade of angiotensin-(1-7) [Ang-(1-7)] actions by AT2R antagonists and vice versa. Such mechanisms may comprise dimerization of the receptors or dimerization-independent mechanisms such as lack of specificity of the receptor ligands used in the experiments or involvement of the Ang-(1-7) metabolite alamandine and its receptor MrgD in the observed effects. We conclude that evidence for a functional interaction of both receptors is strong, but that such an interaction may be species- and/or tissue-specific and that elucidation of the precise nature of the interaction is only at the very beginning.

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice.

In the present study, we evaluated stimulation of the angiotensin type 2 receptor (AT2R) by the selective non-peptide agonist Compound 21 (C21) as a novel therapeutic concept for the treatment of multiple sclerosis using the model of experimental autoimmune encephalomyelitis (EAE) in mice. C57BL-6 mice were immunized with myelin-oligodendrocyte peptide and treated for 4 weeks with C21 (0.3 mg/kg/day i.p.). Potential effects on myelination, microglia and T-cell composition were estimated by immunostaining and FACS analyses of lumbar spinal cords. The in vivo study was complemented by experiments in aggregating brain cell cultures and microglia in vitro. In the EAE model, treatment with C21 ameliorated microglia activation and decreased the number of total T-cells and CD4+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords further revealed a significant reduction in EAE-induced demyelinated areas in lumbar spinal cord tissue after AT2R stimulation. C21-treated mice had a significantly better neurological score than vehicle-treated controls. In aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus interferon-γ (IFNγ), AT2R stimulation prevented demyelination, accelerated re-myelination and reduced the number of microglia. Cytokine synthesis and nitric oxide production by microglia in vitro were significantly reduced after C21 treatment. These results suggest that AT2R stimulation protects the myelin sheaths in autoimmune central nervous system inflammation by inhibiting the T-cell response and microglia activation. Our findings identify the AT2R as a potential new pharmacological target for demyelinating diseases such as multiple sclerosis.

Discovery and characterization of alamandine: a novel component of the renin-angiotensin system.

RATIONALE: The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1-7). OBJECTIVE: To characterize a novel component of the RAS, alamandine. METHODS AND RESULTS: Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1-7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1-7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein-coupled receptor, member D. Binding of alamandine to Mas-related G-protein-coupled receptor, member D is blocked by D-Pro(7)-angiotensin-(1-7), the Mas-related G-protein-coupled receptor, member D ligand ß-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/ß-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. CONCLUSIONS: The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.

Alamandine: a new member of the angiotensin family.

PURPOSE OF REVIEW: In this article, we review the recent findings regarding a new derivative of angiotensin-(1-7) [Ang-(1-7)], alamandine, and its receptor, the Mas-related G-coupled receptor type D (MrgD) with a special emphasis on its role and how it can be formed. RECENT FINDINGS: Over the last decade, there have been significant conceptual changes regarding the understanding of the renin-angiotensin system (RAS). A cardioprotective axis has been elucidated by the discovery of the Mas receptor for the biologically active Ang-(1-7), and the angiotensin-converting enzyme 2 (ACE2) that coverts Ang II into Ang-(1-7). In addition, several components of the system, such as Ang-(1-12), Angiotensin A (Ang A) and the newly discovered peptide, alamandine, have been identified. Alamandine is generated by catalysis of Ang A via ACE2 or directly from Ang-(1-7). SUMMARY: Alamandine is a vasoactive peptide with similar protective actions as Ang-(1-7) that acts through the MrgD and may represent another important counter-regulatory mechanism within the RAS.

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.

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.