Morphometry of the wings of Anopheles aquasalis in simulated scenarios of climate change

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.

Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components

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 ß), 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.

Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon

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.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study

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.

Prediction of malaria using deep learning models: A case study on city clusters in the state of Amazonas, Brazil, from 2003 to 2018

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.

Snakebites caused by the genera Bothrops and Lachesis in the Brazilian Amazon: a study of factors associated with severe cases and death

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.

Anti-vaccination movements in the world and in Brazil

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.

When to think about a Lachesis muta envenomation in the Western Brazilian Amazon: Lessons from a case report

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.

Malaria in indigenous and non-indigenous patients aged under 15 years between 2007-2018, Amazonas state, Brazil

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.

Secondary infection profile after snakebite treated at a tertiary referral center in the Brazilian Amazon

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.

Bee sting envenomation severe cases in Manaus, Brazilian Amazon: clinical characteristics and immune markers of case reports

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.

Pathological findings and morphologic correlation of the lungs of autopsied patients with SARS-CoV-2 infection in the Brazilian Amazon using transmission electron microscopy

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.

Transmission-blocking compound candidates against Plasmodium vivax using P. berghei as an initial screening

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.

Severe tissue complications in patients of Bothrops snakebite at a tertiary health unit in the Brazilian Amazon: clinical characteristics and associated factors

Abstract INTRODUCTION: Snakebites in the Brazilian Amazon are caused mostly by snakes from the Bothrops genus and envenomated patients may suffer from tissue complications. METHODS: This study aimed to identify risk factors for severe tissue complications (STC) in patients with Bothrops snakebite in the Amazonas state, Brazil. RESULTS: Snakebites that were classified as severe and affected female patients with comorbidities presented greater risks of developing STCs. In addition, hospitalizations of patients with STC exceeded 5 days. CONCLUSIONS: Clinical and epidemiological characteristics can prove essential for assessing the evolution of STC and clinical prognosis of patients with Bothrops snakebites.

Efficacy of the 20-minute whole blood clotting test (WBCT20) in the diagnosis of coagulation alteration related to snakebites in a Western Brazilian Amazon hospital

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.

Epidemiological and clinical aspects of snakebites in the upper Juruá River region, western Brazilian Amazonia

This study addresses the clinical and epidemiological aspects of envenoming cases resulting from snakebites treated at a hospital in Cruzeiro do Sul, in the upper Juruá River region, western Brazilian Amazonia. The specific identity of snakes that caused the envenomings was inferred (a) from the diagnosis of patient symptoms and signs upon hospital admission, (b) by enzyme immunoassay for detection of Bothrops atrox and Lachesis muta venom from serum samples taken from patients before antivenom therapy, or (c) by direct identification of the snake, when it was brought along to the hospital or photographed. There were 133 snakebites (76.2 cases per 100,000 inhabitants) registered during one year (July 2017 to June 2018). Most snakebites (88.7%) were caused by Bothrops spp., and the rest by non-venomous snakes or dry bites. Snakebites tended to occur more often during the rainy season, coinciding with the period of greater reproductive activity of the snakes and greater availability of their prey. In addition, the increase in the water level of rivers and lakes during the rainy season tends to concentrate snakes in dry places and, thus, to increase encounters with humans. Information campaigns on prevention and first aid, specially among the most vulnerable groups (indigenous people, farmers, and children and teenagers in rural areas), and the importance of using protective equipment (boots, leggings, leather gloves) in certain high risk activities (e.g. agriculture and extractivism in forests) are fundamental for the reduction of snakebite morbidity. (AU)

Role of crotoxin in coagulation: novel insights into anticoagulant mechanisms and impairment of inflammation-induced coagulation

Snake venom phospholipases A2 (svPLA2) are biologically active toxins, capable of triggering and modulating a wide range of biological functions. Among the svPLA2s, crotoxin (CTX) has been in the spotlight of bioprospecting research due to its role in modulating immune response and hemostasis. In the present study, novel anticoagulant mechanisms of CTX, and the modulation of inflammation-induced coagulation were investigated. Methods: CTX anticoagulant activity was evaluated using platelet poor plasma (PPP) and whole blood (WB), and also using isolated coagulation factors and complexes. The toxin modulation of procoagulant and pro-inflammatory effects was evaluated using the expression of tissue factor (TF) and cytokines in lipopolysaccharide (LPS)-treated peripheral blood mononuclear cells (PBMC) and in WB. Results: The results showed that CTX impaired clot formation in both PPP and WB, and was responsible for the inhibition of both intrinsic (TF/factor VIIa) and extrinsic (factor IXa/factor VIIIa) tenase complexes, but not for factor Xa and thrombin alone. In addition, the PLA2 mitigated the prothrombinase complex by modulating the coagulation phospholipid role in the complex. In regards to the inflammation-coagulation cross talk, the toxin was capable of reducing the production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, and was followed by decreased levels of TF and procoagulant activity from LPS-treated PBMC either isolated or in WB. Conclusion: The results obtained in the present study recognize the toxin as a novel medicinal candidate to be applied in inflammatory diseases with coagulation disorders.(AU)

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

BACKGROUND Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1β and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.