ABSTRACT Objective: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. Methods: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. Results: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. Conclusion: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics. Objective 201 Brazil region Methods 7000 7 000 7,00 2019 symptoms demographics status cases Results 95 decade presentation peaks 1 age discussed Additionally living Conclusion decisionmaking decision making epidemics 20 700 00 7,0 9 2 70 0 7,

Abstract Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and β), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil. Brazil fatalities modality effects T scorpions reproduction α β, β , β) channels Nevertheless metalloproteases proteases phospholipases hyaluronidases strategies

ABSTRACT Background: Climate change has significant implications on ecosystems. We verified the effects of climate change on the malaria vector Anopheles aquasalis using simulated climate change scenarios (SSCCs). Methods: An experimental model was designed for SSCCs, which composed of air-conditioned 25 m3 rooms. Results: The wing size was significantly different between SSCCs. A colony of Anopheles aquasalis could not be established in extreme scenarios. Conclusions: Increases in temperature and CO2 in the atmosphere may modify the global epidemiology of malaria, marking its emergence in currently malaria-free areas. Background ecosystems SSCCs . (SSCCs) Methods airconditioned air conditioned 2 m rooms Results Conclusions CO malariafree free areas (SSCCs

Abstract Identifying risk areas for envenomation by animals is relevant for public health, such as strategic distribution of antivenoms. Coral snakes are highly diverse in the Amazon, inhabit natural and human-modified environments, and the outcome of the cases tends to be serious and potentially lethal due to their neurotoxic venom. By integrating species’ geographical records and environmental variables, we used species distribution modeling to predict the distribution of coral snake species in the Brazilian Amazonia. We analyzed the relationship between the predicted distribution of coral snake species, along with envenomation data in the region, to propose actions to reduce the number of cases and to provide tools for a better policy of public health. We conclude that the entire Amazon shows high environmental suitability for coral snakes, and such suitability explains little about the incidence of cases. This is probably due to the low human density in the Amazon and to coral snake traits such as secretive habits and non-agressive behavior. Differently from other venomous snakes, the scenario regarding coral snakebites precludes the detection of prominent geographical areas of concern and demands a broad and equitable availability of health centers throughout Amazonia and along other areas of occurrence of the genus Micrurus. antivenoms humanmodified modified environments venom variables region nonagressive non agressive behavior Micrurus

ABSTRACT Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants’ perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials. Background worldwide treatment Methods crosssectional cross sectional study indepth depth interviews participants (SMS Results emerged forgetfulness tool easytounderstand easy understand language complaints Conclusions

ABSTRACT Background: Malaria is a serious problem in children because the immune system is less developed, thus, causing more severe symptoms. This study aimed to identify factors associated with malaria in indigenous and non-indigenous patients aged under 15 years in Amazonas, Brazil, from 2007 to 2018. Methods: An epidemiological, quantitative, cross-sectional study was conducted. Cases included patients aged under 15 years, using data from health system notifications between 2007 and 2018 in the state of Amazonas, Brazil. The variables included clinical-epidemiological, laboratory findings, and monitoring of cases. The outcome was ethnicity: indigenous, non-indigenous, and entries for which no ethnicity data were provided. A multivariable logistic regression model was used to compare the indigenous and non-indigenous populations. Results: Among malaria cases in patients aged under 15 years, there was a greater chance of being indigenous and having the following associated factors: female sex, children aged 0-4 years, passive case surveillance, a high load of parasitemia and the lack of data regarding the level of parasitemia, Plasmodium falciparum infections were more frequent, and timeliness of treatment, i.e., the interval between the onset of symptoms and time of treatment was within 48 hours. Conclusions: The factors associated with malaria are more frequent in indigenous populations and highlight differences according to ethnicity, suggesting that the severity of the disease is attributable to the increased number of malarial infections within this population. As a result, malaria has a greater impact on the health of indigenous people.

ABSTRACT Background: Malaria is curable. Nonetheless, over 229 million cases of malaria were recorded in 2019, along with 409,000 deaths. Although over 42 million Brazilians are at risk of contracting malaria, 99% percent of all malaria cases in Brazil are located in or around the Amazon rainforest. Despite declining cases and deaths, malaria remains a major public health issue in Brazil. Accurate spatiotemporal prediction of malaria propagation may enable improved resource allocation to support efforts to eradicate the disease. Methods: In response to calls for novel research on malaria elimination strategies that suit local conditions, in this study, we propose machine learning (ML) and deep learning (DL) models to predict the probability of malaria cases in the state of Amazonas. Using a dataset of approximately 6 million records (January 2003 to December 2018), we applied k-means clustering to group cities based on their similarity of malaria incidence. We evaluated random forest, long-short term memory (LSTM) and dated recurrent unit (GRU) models and compared their performance. Results: The LSTM architecture achieved better performance in clusters with less variability in the number of cases, whereas the GRU presents better results in clusters with high variability. Although Diebold-Mariano testing suggested that both the LSTM and GRU performed comparably, GRU can be trained significantly faster, which could prove advantageous in practice. Conclusions: All models showed satisfactory accuracy and strong performance in predicting new cases of malaria, and each could serve as a supplemental tool to support regional policies and strategies.

ABSTRACT In the Brazilian Amazon, envenomations by lancehead pit vipers prevail across the region, while bushmaster (Lachesis muta) envenomations are rarely confirmed. Here, we described a moderate snakebite, diagnosed as a lancehead pit viper envenomation upon admission and treated with four vials of Bothrops antivenom. Blood remained unclottable for 4 days of hospitalization. On day 4, after admission, the patient presented pictures of the perpetrating snake to the hospital staff, which was identified as a Lachesis muta specimen. After administering 10 vials of Lachesis antivenom, blood became clottable 12 hours after treatment. The patient was discharged without complaints.

ABSTRACT Background: Bothrops envenomations can often lead to complications, such as secondary infections. Methods: This cross-sectional study analyzed the medical records of all patients diagnosed with snakebite. Results: A total of 127 patients were included. Clindamycin was the most commonly prescribed antibiotic, with 105 patients (82.7%) receiving it as the primary antibiotic regimen. In 31 (24.4%) individuals, the first-choice antibiotic did not cease the infection. Conclusions: Secondary infection is an important complication resulting from snakebites, and evidence-based management of this complication can contribute to better clinical outcomes.

ABSTRACT Over the years, vaccinations have provided significant advances in public health, because they substantially reduce the morbimortality of vaccine-preventable diseases. Nevertheless, many people are still hesitant to be vaccinated. Brazil is a region of many anti-vaccine movements, and several outbreaks of vaccine-preventable diseases, such as yellow fever and measles, have occurred in the country during the last few years. To avoid new outbreaks, immunization coverage must be high; however, this is a great challenge to achieve due to the countless anti-vaccine movements. The World Health Organization has suggested new actions for the next decade via the Immunization Agenda 2030 to control, reduce, or eradicate vaccine-preventable diseases. Nonetheless, the vaccination coverage has decreased recently. To resolve the anti-vaccine issue, it is necessary to propose a long-term approach that involves innovative education programs on immunization and critical thinking, using different communication channels, including social media. Cooperation among biology and health scientists, ethicists, human scientists, policymakers, journalists, and civil society is essential for an in-depth understanding of the social action of vaccine refusal and planning effective education measures to increase the vaccine coverage.

ABSTRACT Background: Snakebites are a major problem in developing countries owing to their high morbidity rates, severity, and sequelae. In Brazil, most cases of envenomation are caused by Bothrops and Lachesis snakes. The present study aimed to evaluate variables associated with death, systemic complications, and amputations in victims of envenomation due to Bothrops or Lachesis snake. Methods: An analytical epidemiological study was performed with data from the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação [SINAN]) relating to the Brazilian Amazon for the period 2010-2015. A hierarchical Poisson regression analysis was performed with three aspects, namely, individual characteristics, sociodemographic characteristics, and clinical conditions. Results: The following associations were observed: i) advanced age (>65 years), sepsis, renal failure, and hemorrhagic manifestations were related to two outcomes - death due to snakebite and death from all causes; ii) more advanced age (≥46 years), time to health care longer than 6 hours, renal and hemorrhagic manifestations, and region of occurrence being rural areas were associated with systemic complications; and iii) children (up to 12 years old) were associated with amputations. Conclusions: Knowledge of the characteristics associated with severe outcomes in snakebites may help identify patients who will require more intensive care or longer follow-up and may provide the physician with counseling rationale for their possible prognosis.

Abstract Introduction: The efficacy of 20-minute whole blood clotting (WBCT20) and the Lee-White clotting time (LWCT) tests in diagnosing coagulation alterations from snakebites were compared. Methods: We evaluated 89 snakebite cases treated at the Hospital Regional do Juruá em Cruzeiro do Sul, Acre, Brazil. Results: WBCT20 results were normal in 33.7% and unclottable in 66.3% of cases, while LWCT results were normal in 23.6% and altered (prolonged or unclottable) in 76.4% of cases, with no significant differences. Conclusions: The WBCT20 is important for rapidly diagnosing coagulation alterations from snakebites. Furthermore, it is efficient, inexpensive, and can be deployed in isolated hospitals.

BACKGROUND Different strategies for improvement of malaria control and elimination are based on the blockage of malaria parasite transmission to the mosquito vector. These strategies include the drugs that target the plasmodial sexual stages in humans and the early developmental stages inside mosquitoes. OBJECTIVES Here we tested Malaria Box compounds in order to evaluate their activity against male and female gametocytes in Plasmodium berghei, mosquito infection in P. vivax and ookinete formation in both species. METHODS/FINDINGS The membrane feeding assay and the development of ookinetes by a 24 h ex vivo culture and the ookinete yield per 1000 erythrocytes were used to test transmission-blocking potential of the Malaria Box compounds in P. vivax. For P. berghei we used flow cytometry to evaluate male and female gametocyte time course and fluorescence microscopy to check the ookinete development. The two species used in this study showed similar results concerning the compounds’ activity against gametocytes and ookinetes, which were different from those in P. falciparum. In addition, from the eight Malaria Box compounds tested in both species, compounds MMV665830, MMV665878 and MMV665941 were selected as a hit compounds due the high inhibition observed. CONCLUSION Our results showed that P. berghei is suitable as an initial screening system to test compounds against P. vivax.

Abstract Bee venom is a natural toxin composed of several peptides. Massive envenoming causes severe local and systemic reactions. We report two cases of severe bee envenomation, of which one was fatal. We also describe clinical characteristics and immune markers. Both victims suffered from respiratory distress, renal failure, rhabdomyolysis, and shock. They required invasive mechanical ventilation, vasoactive drugs, and renal replacement therapy. Moreover, serum levels of chemokines, cytokines, and cell-free circulating nucleic acids demonstrated an intense inflammatory process. Massive envenoming produced systemic injury in the victims, with an uncontrolled inflammatory response, and a more significant chemotactic response in the fatal case.

Abstract INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.