Capacity of community health centers to treat snakebite envenoming in indigenous territories of the Brazilian Amazon.

INTRODUCTION: The deaths from and morbidities associated with snakebites - amputations, loss of function in the limb, visible scarring or tissue damage - have a vast economic, social, and psychological impact on indigenous communities in the Brazilian Amazon, especially children, and represent a real and pressing health crisis in this population. Snakebite clinical and research experts have therefore proposed expanding antivenom access from only hospitals to include the community health centers (CHC) located near and within indigenous communities. However, there are no studies examining the capacity of CHCs to store, administer, and manage antivenom treatment. In response to this gap, the research team calling for antivenom decentralization developed and validated an expert-based checklist outlining the minimum requirements for a CHC to provide antivenom. METHODS: The objective of this study was thus to survey a sample of CHCs in indigenous territories and evaluate their capacity to provide antivenom treatment according to this accredited checklist. The checklist was administered to nurses and doctors from 16 CHCs, two per indigenous district in Amazonas/Roraima states. RESULTS: Our results can be conceptualized into three central findings: 1) most CHCs have the capacity to provide antivenom treatment, 2) challenges to capacity are human resources and specialized items, and 3) antivenom decentralization is feasible and appropriate in indigenous communities. CONCLUSION: Decentralization would provide culturally and contextually appropriate care accessibility to a historically marginalized and underserved population of the Brazilian Amazon. Future studies should examine optimal resource allocation in indigenous territories and develop an implementation strategy in partnership with indigenous leaders. Beyond the indigenous population, the checklist utilized could be applied to community health centers treating the general population and/or adapted to other low-resource settings.

Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings.

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.

Development and validation of a minimum requirements checklist for snakebite envenoming treatment in the Brazilian Amazonia.

BACKGROUND: Currently, antivenoms are the only specific treatment available for snakebite envenoming. In Brazil, over 30% of patients cannot access antivenom within its critical care window. Researchers have therefore proposed decentralizing to community health centers to decrease time-to-care and improve morbidity and mortality. Currently, there is no evidence-based method to evaluate the capacity of health units for antivenom treatment, nor what the absolute minimum supplies and staff are necessary for safe and effective antivenom administration and clinical management. METHODS: This study utilized a modified-Delphi approach to develop and validate a checklist to evaluate the minimum requirements for health units to adequately treat snakebite envenoming in the Amazon region of Brazil. The modified-Delphi approach consisted of four rounds: 1) iterative development of preliminary checklist by expert steering committee; 2) controlled feedback on preliminary checklist via expert judge survey; 3) two-phase nominal group technique with new expert judges to resolve pending items; and 4) checklist finalization and closing criteria by expert steering committee. The measure of agreement selected for this study was percent agreement defined a priori as ≥75%. RESULTS: A valid, reliable, and feasible checklist was developed. The development process highlighted three key findings: (1) the definition of community health centers and its list of essential items by expert judges is consistent with the Brazilian Ministry of Health, WHO snakebite strategic plan, and a general snakebite capacity guideline in India (internal validity), (2) the list of essential items for antivenom administration and clinical management is feasible and aligns with the literature regarding clinical care (reliability), and (3) engagement of local experts is critical to developing and implementing an antivenom decentralization strategy (feasibility). CONCLUSION: This study joins an international set of evidence advocating for decentralization, adding value in its definition of essential care items; identification of training needs across the care continuum; and demonstration of the validity, reliability, and feasibility provided by engaging local experts. Specific to Brazil, further added value comes in the potential use of the checklist for health unit accreditation as well as its applications to logistics and resource distribution. Future research priorities should apply this checklist to health units in the Amazon region of Brazil to determine which community health centers are or could be capable of receiving antivenom and translate this expert-driven checklist and approach to snakebite care in other settings or other diseases in low-resource settings.

Scaling up antivenom for snakebite envenoming in the Brazilian Amazon: a cost-effectiveness analysis.

Background: Snakebite envenoming (SBE) affects nearly three million people yearly, causing up to 180,000 deaths and 400,000 cases of permanent disability. Brazil's state of Amazonas is a global hotspot for SBE, with one of the highest annual incidence rates per 100,000 people, worldwide. Despite this burden, snake antivenom remains inaccessible to a large proportion of SBE victims in Amazonas. This study estimates the costs, and health and economic benefits of scaling up antivenom to community health centers (CHCs) and hospitals in the state. Methods: We built a decision tree model to simulate three different antivenom scale-up scenarios: (1) scale up to 95% of hospitals, (2) scale up to 95% of CHCs, and (3) scale up to 95% of hospitals and 95% of CHCs. We consider each scenario with and without a 10% increase in demand for antivenom among SBE victims. For each scenario, we model the treatment costs averted, deaths averted, and disability-adjusted life years (DALYs) averted from a societal, health system, and patient perspective relative to the status quo and over a time horizon of one year. For each scenario and perspective, we also calculate the incremental cost per DALY averted and per death averted. We use a willingness to pay threshold equal to the 2022 gross domestic product (GDP) per capita of Brazil. Findings: Scaling up antivenom to 95% of hospitals averts up to 2022 DALYs, costs up to USD $460 per DALY averted from a health system perspective, but results in net economic benefits up to USD $4.42 million from a societal perspective. Scaling up antivenom to 95% of CHCs averts up to 3179 DALYs, costs up to USD $308 per DALY averted from a health system perspective, but results in net economic benefits up to USD $7.35 million from a societal perspective. Scaling up antivenom to 95% of hospitals and CHCs averts up to 3922 DALYs, costs up to USD $328 per DALY averted from a health system perspective, but results in net economic benefits up to USD $8.98 million from a societal perspective. Interpretation: All three antivenom scale up scenarios - scale up to 95% of hospitals, scale up to 95% of CHCs, and scale up to 95% of hospitals and 95% of CHCs - avert a substantial proportion of the SBE burden in Amazonas and are cost-saving from a societal perspective and cost-effective from a health system perspective. Funding: W.M. and J.S. were funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq productivity scholarships). W.M. was funded by Fundação de Amparo à Pesquisa do Estado do Amazonas (PRÓ-ESTADO, call n. 011/2021-PCGP/FAPEAM, call n. 010/2021-CT&I ÁREAS PRIORITÁRIAS, call n. 003/2022-PRODOC/FAPEAM, POSGRAD/FAPEAM) and by the Ministry of Health, Brazil (Proposal No. 733781/19-035). Research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number R21TW011944. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Snakebite envenomations and access to treatment in communities of two indigenous areas of the Western Brazilian Amazon: A cross-sectional study.

BACKGROUND: The indigenous populations of Brazil present poor health indicators and a disproportionate prevalence and case-fatality rate of neglected tropical diseases, including snakebite envenomations (SBEs). This study aims to estimate access to medical care for SBEs and analyze the barriers that prevent victims from accessing healthcare in indigenous communities in two health districts located in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study used semi-structured interviews to collect data from individuals who experienced SBEs in the Upper Rio Solimões and Upper Rio Negro indigenous health districts. Of the 187 participants, 164 (87.7%) reported that they had access to healthcare and received assistance in a hospital in the urban area of the municipalities. Frequency was 95.4% in the Upper Rio Solimões SIHD, and 69.6% in the Upper Rio Negro SIHD (P<0.0001). The study found that the availability of indigenous medicine as the only choice in the village was the main reason for not accessing healthcare (75%), followed by a lack of financial resources and means of transportation (28.1%). Four deaths were reported from SBEs, resulting in a case-fatality rate of 2.1%. CONCLUSIONS/SIGNIFICANCE: In the study areas, there are records of SBE patients who did not receive medical attention. Availability of pre-hospital emergency transport using motorboats, a greater number of hospitals and better navigability of the Solimões River and its tributaries would make access easier for indigenous people living in the region of the Upper Solimões River. The implementation of cross-cultural hospital care needs to be considered in order to reduce the resistance of indigenous populations in relation to seeking treatment for SBEs.

Children Growing Up with Severe Disabilities as a Result of Snakebite Envenomations in Indigenous Villages of the Brazilian Amazon: Three Cases and Narratives.

Snakebites are a major public health problem in the Brazilian Amazon and may lead to local complications and physical deficiencies. Access to antivenom treatment is poorer in indigenous populations compared to other populations. In this study, we report three cases of long-term severe disabilities as a result of Bothrops atrox snakebites in indigenous children, according to the narratives of the parents. The three cases evolved to compartment syndrome, secondary bacterial infection and extensive necrosis. The cases are associated with delayed antivenom treatment due to very fragmented therapeutic itineraries, which are marked by several changes in means of transport along the route. The loss of autonomy at such an early stage of life due to a disability caused by a snakebite, as observed in this study, may deprive children of sensory and social experiences and of learning their future roles in the community. In common to all cases, there was precarious access to rehabilitation services, which are generally centralized in the state capital, and which leads to a prolonged hospitalization of patients with severe snakebite, and distances them from their territory and family and community ties. Prospective studies should be conducted in the Amazon that estimate the burden of disabilities from snakebites in order to formulate public policies for the treatment and rehabilitation of patients through culturally tailored interventions.

Antivenom access impacts severity of Brazilian snakebite envenoming: A geographic information system analysis.

BACKGROUND: Snakebite envenoming (SBE) is a neglected tropical disease capable of causing both significant disability and death. The burden of SBE is especially high in low- and middle-income countries. The aim of this study was to perform a geospatial analysis evaluating the association of sociodemographics and access to care indicators on moderate and severe cases of SBE in Brazil. METHODS: We conducted an ecological, cross-sectional study of SBE in Brazil from 2014 to 2019 using the open access National System Identification of Notifiable Diseases (SINAN) database. We then collected a set of indicators from the Brazil Census of 2010 and performed a Principal Component Analysis to create variables related to health, economics, occupation, education, infrastructure, and access to care. Next, a descriptive and exploratory spatial analysis was conducted to evaluate the geospatial association of moderate and severe events. These variables related to events were evaluated using Geographically Weighted Poisson Regression. T-values were plotted in choropleth maps and considered statistically significant when values were <-1.96 or >+1.96. RESULTS: We found that the North region had the highest number of SBE cases by population (47.83/100,000), death rates (0.18/100,000), moderate and severe rates (22.96/100,000), and proportion of cases that took more than three hours to reach healthcare assistance (44.11%). The Northeast and Midwest had the next poorest indicators. Life expectancy, young population structure, inequality, electricity, occupation, and more than three hours to reach healthcare were positively associated with greater cases of moderate and severe events, while income, illiteracy, sanitation, and access to care were negatively associated. The remaining indicators showed a positive association in some areas of the country and a negative association in other areas. CONCLUSION: Regional disparities in SBE incidence and rates of poor outcomes exist in Brazil, with the North region disproportionately affected. Multiple indicators were associated with rates of moderate and severe events, such as sociodemographic and health care indicators. Any approach to improving snakebite care must work to ensure the timeliness of antivenom administration.

Spatiotemporal bayesian modelling of scorpionism and its risk factors in the state of São Paulo, Brazil.

BACKGROUND: Scorpion stings in Brazil represent a major public health problem due to their incidence and their potential ability to lead to severe and often fatal clinical outcomes. A better understanding of scorpionism determinants is essential for a precise comprehension of accident dynamics and to guide public policy. Our study is the first to model the spatio-temporal variability of scorpionism across municipalities in São Paulo (SP) and to investigate its relationship with demographic, socioeconomic, environmental, and climatic variables. METHODOLOGY: This ecological study analyzed secondary data on scorpion envenomation in SP from 2008 to 2021, using the Integrated Nested Laplace Approximation (INLA) to perform Bayesian inference for detection of areas and periods with the most suitable conditions for scorpionism. PRINCIPAL FINDINGS: From the spring of 2008 to 2021, the relative risk (RR) increased eight times in SP, from 0.47 (95%CI 0.43-0.51) to 3.57 (95%CI 3.36-3.78), although there has been an apparent stabilization since 2019. The western, northern, and northwestern parts of SP showed higher risks; overall, there was a 13% decrease in scorpionism during winters. Among the covariates considered, an increase of one standard deviation in the Gini index, which captures income inequality, was associated with a 11% increase in scorpion envenomation. Maximum temperatures were also associated with scorpionism, with risks doubling for temperatures above 36°C. Relative humidity displayed a nonlinear association, with a 50% increase in risk for 30-32% humidity and reached a minimum of 0.63 RR for 75-76% humidity. CONCLUSIONS: Higher temperatures, lower humidity, and social inequalities were associated with a higher risk of scorpionism in SP municipalities. By capturing local and temporal relationships across space and time, authorities can design more effective strategies that adhere to local and temporal considerations.

Prospecting Local Treatments Used in Conjunction with Antivenom Administration Following Envenomation Caused by Animals: A Systematic Review.

Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.

River dataset as a potential fluvial transportation network for healthcare access in the Amazon region.

Remote areas, such as the Amazon Forest, face unique geographical challenges of transportation-based access to health services. As transportation to healthcare in most of the Amazon Forest is only possible by rivers routes, any travel time and travel distance estimation is limited by the lack of data sources containing rivers as potential transportation routes. Therefore, we developed an approach to convert the geographical representation of roads and rivers in the Amazon into a combined, interoperable, and reusable dataset. To build the dataset, we processed and combined data from three data sources: OpenStreetMap, HydroSHEDS, and GloRiC. The resulting dataset can consider distance metrics using the combination of streets and rivers as a transportation route network for the Amazon Forest. The created dataset followed the guidelines and attributes defined by OpenStreetMap to leverage its reusability and interoperability possibilities. This new data source can be used by policymakers, health authorities, and researchers to perform time-to-care analysis in the International Amazon region.

Building an explanatory model for snakebite envenoming care in the Brazilian Amazon from the indigenous caregivers' perspective.

BACKGROUND: In the Brazilian Amazon, snakebite envenomings (SBE) disproportionately affect indigenous peoples. Communication between indigenous and biomedical health sectors in regards to SBEs has never been explored in this region. This study aims to build an explanatory model (EM) of the indigenous healthcare domain for SBE patients from the perspective of the indigenous caregivers. METHODOLOGY/PRINCIPAL FINDINGS: This is a qualitative study involving in-depth interviews of eight indigenous caregivers who are representatives of the Tikuna, Kokama and Kambeba ethnic groups, in the Alto Solimões River, western Brazilian Amazon. Data analysis was carried out via deductive thematic analysis. A framework was built containing the explanations based on three explanatory model (EM) components: etiology, course of sickness, and treatment. To indigenous caregivers, snakes are enemies and present conscience and intention. Snakebites have a natural or a supernatural cause, the last being more difficult to prevent and treat. Use of ayahuasca tea is a strategy used by some caregivers to identify the underlying cause of the SBE. Severe or lethal SBEs are understood as having been triggered by sorcery. Treatment is characterized by four components: i) immediate self-care; ii) first care in the village, mostly including tobacco smoking, chants and prayers, combined with the intake of animal bile and emetic plants; iii) a stay in a hospital, to receive antivenom and other treatments; iv) care in the village after hospital discharge, which is a phase of re-establishment of well-being and reintroduction into social life, using tobacco smoking, massages and compresses to the affected limb, and teas of bitter plants. Dietary taboos and behavioral interdictions (avoiding contact with menstruating and pregnant women) prevent complications, relapses, and death, and must be performed up to three months after the snakebite. Caregivers are in favor of antivenom treatment in indigenous areas. CONCLUSIONS/SIGNIFICANCE: There is a potential for articulation between different healthcare sectors to improve the management of SBEs in the Amazon region, and the aim is to decentralize antivenom treatment so that it occurs in indigenous health centers with the active participation of the indigenous caregivers.

Snakebite envenoming in Brazilian children: clinical aspects, management and outcomes.

Snakebite envenoming is currently considered a neglected tropical disease, which affects over 5 million people worldwide, and causes almost 150 000 deaths every year, as well as severe injuries, amputations and other sequelae. Snakebite envenoming in children, although proportionally less frequent, is generally more severe, and represents an important challenge for pediatric medicine, since they often result in worse outcomes. In Brazil, given its ecological, geographic and socioeconomic characteristics, snakebites are considered an important health problem, presenting approximately 30 000 victims per year, approximately 15% of them in children. Even with low snakebite incidence, children tend to have higher snakebite severity and complications due to the small body mass and same venom volume inoculated in comparison to adults, even though, due to the lack of epidemiological information about pediatric snakebites and induced injuries, it is difficult to measure the treatment effectiveness, outcomes and quality of emergency medical services for snakebites in children. In this review, we report how Brazilian children are affected by snakebites, describing the characteristics of this affected population, clinical aspects, management, outcomes and main challenges.

The Amazonian Tropical Bites Research Initiative, a hope for resolving zoonotic neglected tropical diseases in the One Health era.

BACKGROUND: Neglected tropical diseases (NTDs) disproportionately affect populations living in resource-limited settings. In the Amazon basin, substantial numbers of NTDs are zoonotic, transmitted by vertebrate (dogs, bats, snakes) and invertebrate species (sand flies and triatomine insects). However, no dedicated consortia exist to find commonalities in the risk factors for or mitigations against bite-associated NTDs such as rabies, snake envenoming, Chagas disease and leishmaniasis in the region. The rapid expansion of COVID-19 has further reduced resources for NTDs, exacerbated health inequality and reiterated the need to raise awareness of NTDs related to bites. METHODS: The nine countries that make up the Amazon basin have been considered (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Surinam and Venezuela) in the formation of a new network. RESULTS: The Amazonian Tropical Bites Research Initiative (ATBRI) has been created, with the aim of creating transdisciplinary solutions to the problem of animal bites leading to disease in Amazonian communities. The ATBRI seeks to unify the currently disjointed approach to the control of bite-related neglected zoonoses across Latin America. CONCLUSIONS: The coordination of different sectors and inclusion of all stakeholders will advance this field and generate evidence for policy-making, promoting governance and linkage across a One Health arena.

Perspectives on snakebite envenoming care needs across different sociocultural contexts and health systems: A comparative qualitative analysis among US and Brazilian health providers.

With the advancements in therapeutics and available treatment options, almost all deaths and permanent disabilities from snakebite envenoming (SBE) are preventable. The challenge lies in implementing these evidence-based treatments and practices across different settings and populations. This study aims to compare data on provider perceptions of SBE care across health systems and cultural contexts to inform potential implementation science approaches. We hypothesize different health systems and cultural contexts will influence specific perceived needs to provide adequate snakebite care within central tenets of care delivery (e.g., cost, access, human resources). We previously conducted exploratory descriptive studies in the US and Brazil in order to understand the experience, knowledge, and perceptions of health professionals treating SBE. In the US, in-depth interviews were performed with emergency physicians from January 2020 to March 2020. In BR, focus group discussions were conducted with health professionals from community health centers at the end of June 2021. The focus group discussions (BR) were originally analyzed through an inductive thematic analysis approach. We conducted a secondary qualitative analysis in which this codebook was then applied to the interviews (US) in a deductive content analysis. The analysis concluded in August 2022. Brazil participants were physicians (n=5) or nurses (n=20) from three municipalities in the State of Amazonas with an average of three years of professional experience. US participants were emergency physicians (n=16) with an average of 15 years of professional experience. Four main themes emerged: 1) barriers to adequate care on the patient and/or community side and 2) on the health system side, 3) perceived considerations for how to address SBE, and 4) identified needs for improving care. There were 25 subthemes within the four themes. These subthemes were largely the same across the Brazil and US data, but the rationale and content within each shared subtheme varied significantly. For example, the subtheme "role of health professionals in improving care" extended across Brazil and the US. Brazil emphasized the need for task-shifting and -sharing amongst health care disciplines, whereas the US suggested specialized approaches geared toward increasing access to toxicologists and other referral resources. Despite similar core barriers to adequate snakebite envenoming care and factors to consider when trying to improve care delivery, health professionals in different health systems and sociocultural contexts identified different needs. Accounting for, and understanding, these differences is crucial to the success of initiatives intended to strengthen snakebite envenoming care. Implementation science efforts, with explicit health professional input, should be applied to develop new and/or adapt existing evidence-based treatments and practices for SBE.

Pregnancy outcomes after snakebite envenomations: A retrospective cohort in the Brazilian Amazonia.

Snakebite envenomations (SBEs) in pregnant women can result in adverse maternal or neonatal effects, such as abortion, placental abruption, preterm labor, fetal malformations, and maternal, fetal or neonatal deaths. Despite the high incidence of SBEs in the Brazilian Amazon, there is no literature on the impact of SBEs on pregnancy outcomes. The objective of this study was to describe clinical epidemiology and outcomes associated with SBEs in women of childbearing age and pregnant women in the state of Amazonas, Western Brazilian Amazon, from 2007 to 2021. Information on the population was obtained from the Reporting Information System (SINAN), Mortality Information System (SIM) and Live Birth Information System (SINASC) for the period from 2007 to 2021. A total of 36,786 SBEs were reported, of which 3,297 (9%) involved women of childbearing age, and 274 (8.3%) involved pregnant women. Severity (7.9% in pregnant versus 8.7% in non-pregnant women) (P = 0.87) and case-fatality (0.4% in pregnant versus 0.3% in non-pregnant women) rates were similar between groups (P = 0.76). Pregnant women who suffered snakebites were at higher risk for fetal death (OR: 2.17, 95%CI: 1.74-2.67) and neonatal death (OR = 2.79, 95%CI: 2.26-3.40). This study had major limitations related to the completeness of the information on the pregnancy outcomes. Although SBE incidence in pregnant women is low in the Brazilian Amazon, SBEs increased the risk of fetal and neonatal deaths.

The severity of acute kidney injury correlates with plasma venom levels in Bothrops atrox envenomings.

The Brazilian Amazon has high rates of snakebite envenomings (SBEs), with ∼90% caused by Bothrops atrox. Envenomings by this species can trigger local and systemic effects, such as acute kidney injury (AKI). Our aim was to identify predictors of AKI in Bothrops SBEs in patients from Manaus, Western Brazilian Amazon. A total of 127 patients were enrolled, with a predominance of men between 16 and 45 years old from rural areas. Of the 127 patients, 38.6% developed AKI, with 61.2% presenting stage I, 34.7% presenting stage II and 4.1% presenting stage III severity. The age groups 0-10 years and ≥60 years presented a significantly higher frequency of AKI compared to the 11-40 years group. Moderate/severe edema in the affeccted limb was significantly associated with lower risk of AKI [p = 0.01; OR = 0.11 (95%CI 0.02-0.53)]. Nausea [p = 0.01; OR = 54.44 (95%CI = 3.26-909.27)] and high blood urea levels [p = 0.01; OR = 5.38 (95%CI = 2.12-13.66)] were risk factors for AKI. There was a significant positive correlation between circulating venom levels and the highest creatinine serum values during the hospital stay (p = 0.03) and with the difference between the maximum creatinine levels and the creatinine levels on admission (p = 0.02). A positive correlation between serum venom concentrations and creatinine levels suggests a direct or indirect dose-dependent participation of the venom toxins in the pathogenesis of AKI.

Mapping of clinical management resources for snakebites and other animal envenomings in the Brazilian Amazon.

Snakebite envenomings (SBEs) and other envenomings triggered by venomous animals (VAEs) represent a significant disease burden in Brazil, with 29,152 SBEs reported in 2021 alone with nearly half of those occurring in the remote Brazilian Amazon. In 2021, Brazil recorded 240,294 envenomings from snakes, scorpions, spiders, and caterpillars. Therefore, there is an unequal distribution of SBEs with high morbidity and mortality in the Brazilian Amazon. The severity of SBEs increases when patients require more than 6 h to access antivenom treatment, a common issue for the rural and indigenous populations. Understanding currently available resources and practices in Amazon remote areas of Brazil can serve to inform future interventions and guide health care policies. This study aims to develop a resource map of existing healthcare resources for the Brazilian Amazon's clinical management of VAEs with emphasis in SBEs, which will aid future strategic interventions. Data collection included a literature review, secondary data collected by government departments and organizational records, GIS mapping activities, and expert input. Our framework was guided by the three levels of healthcare service ecosystem analysis (macro, meso, and micro). Our resource map lays out a comprehensive overview of antivenom access, the distribution landscape, differences in patient transportation, and barriers to access healthcare that face populations in the Brazilian Amazon.

Equine Anti-SARS-CoV-2 Serum (ECIG) Binds to Mutated RBDs and N Proteins of Variants of Concern and Inhibits the Binding of RBDs to ACE-2 Receptor.

The COVID-19 pandemic caused by the severe acute syndrome virus 2 (SARS-CoV-2) has been around since November 2019. As of early June 2022, more than 527 million cases were diagnosed, with more than 6.0 million deaths due to this disease. Coronaviruses accumulate mutations and generate greater diversity through recombination when variants with different mutations infect the same host. Consequently, this virus is predisposed to constant and diverse mutations. The SARS-CoV-2 variants of concern/interest (VOCs/VOIs) such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28/P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) have quickly spread across the world. These VOCs and VOIs have accumulated mutations within the spike protein receptor-binding domain (RBD) which interacts with the angiotensin-2 converting enzyme (ACE-2) receptor, increasing cell entry and infection. The RBD region is the main target for neutralizing antibodies; however, other notable mutations have been reported to enhance COVID-19 infectivity and lethality. Considering the urgent need for alternative therapies against this virus, an anti-SARS-CoV-2 equine immunoglobulin F(ab')2, called ECIG, was developed by the Butantan Institute using the whole gamma-irradiated SARS-CoV-2 virus. Surface plasmon resonance experiments revealed that ECIG binds to wild-type and mutated RBD, S1+S2 domains, and nucleocapsid proteins of known VOCs, including Alpha, Gamma, Beta, Delta, Delta Plus, and Omicron. Additionally, it was observed that ECIG attenuates the binding of RBD (wild-type, Beta, and Omicron) to human ACE-2, suggesting that it could prevent viral entry into the host cell. Furthermore, the ability to concomitantly bind to the wild-type and mutated nucleocapsid protein likely enhances its neutralizing activity of SARS-CoV-2. We postulate that ECIG benefits COVID-19 patients by reducing the infectivity of the original virus and existing variants and may be effective against future ones. Impacting the course of the disease, mainly in the more vulnerable, reduces infection time and limits the appearance of new variants by new recombination.

Validation of a Culturally Relevant Snakebite Envenomation Clinical Practice Guideline in Brazil.

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.