Silent Intruder: Unusual Presentation of Neurocysticercosis in an HIV-Infected Patient from the Far Northern Brazilian Amazon.

Neurocysticercosis, a parasitic infection of the central nervous system (CNS), is a significant public health issue globally, including in Brazil. This article presents a case report of a 44-year-old male patient residing in the rural area of Roraima, the northernmost region of Brazil within the Amazon Forest. The patient, with chronic HIV infection, acquired the Taenia solium helminth, resulting in neurocysticercosis development. Remarkably, the diagnosis of neurocysticercosis was not initially apparent but emerged through meticulous analysis following a motorcycle accident. The absence of seizures, a common clinical manifestation, complicated the diagnostic process, making it an uncommon case of NCC, which may be related to co-infection. As the patient's condition progressed, multiple complications arose, requiring additional medical attention and interventions. This case underscores the immense challenges faced by healthcare teams in managing neurocysticercosis effectively. It emphasizes the critical need for a comprehensive, multidisciplinary approach to provide optimal care for such complex cases. The study's findings underscore the importance of raising awareness and implementing improved strategies for tackling neurocysticercosis, particularly in regions where it remains a prevalent concern.

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.

Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper.

Improved therapies are needed against snakebite envenoming, which kills and permanently disables thousands of people each year. Recently developed neutralizing monoclonal antibodies against several snake toxins have shown promise in preclinical rodent models. Here, we use phage display technology to discover a human monoclonal antibody and show that this antibody causes antibody-dependent enhancement of toxicity (ADET) of myotoxin II from the venomous pit viper, Bothrops asper, in a mouse model of envenoming that mimics a snakebite. While clinical ADET related to snake venom has not yet been reported in humans, this report of ADET of a toxin from the animal kingdom highlights the necessity of assessing even well-known antibody formats in representative preclinical models to evaluate their therapeutic utility against toxins or venoms. This is essential to avoid potential deleterious effects as exemplified in the present study.

Unveiling the Pain Relief Potential: Harnessing Analgesic Peptides from Animal Venoms.

The concept of pain encompasses a complex interplay of sensory and emotional experiences associated with actual or potential tissue damage. Accurately describing and localizing pain, whether acute or chronic, mild or severe, poses a challenge due to its diverse manifestations. Understanding the underlying origins and mechanisms of these pain variations is crucial for effective management and pharmacological interventions. Derived from a wide spectrum of species, including snakes, arthropods, mollusks, and vertebrates, animal venoms have emerged as abundant repositories of potential biomolecules exhibiting analgesic properties across a broad spectrum of pain models. This review focuses on highlighting the most promising venom-derived toxins investigated as potential prototypes for analgesic drugs. The discussion further encompasses research prospects, challenges in advancing analgesics, and the practical application of venom-derived toxins. As the field continues its evolution, tapping into the latent potential of these natural bioactive compounds holds the key to pioneering approaches in pain management and treatment. Therefore, animal toxins present countless possibilities for treating pain caused by different diseases. The development of new analgesic drugs from toxins is one of the directions that therapy must follow, and it seems to be moving forward by recommending the composition of multimodal therapy to combat pain.

Snakebite Clinics and Pathogenesis: From Preclinical to Resource Mapping Studies.

Amidst the global healthcare landscape, the menace of snakebite envenoming (SBE) has persisted, silently afflicting millions and annually claiming tens of thousands of lives [...].

Acute mesenteric ischemia following lancehead snakebite: an unusual case report in the Northernmost Brazilian Amazon.

Snakebites have a great impact in the Brazilian Amazon, being the lancehead Bothrops atrox the species responsible for most accidents, disabilities, and deaths. This study shows a case report of an indigenous patient from the Yanomami ethnicity, male, 33 years-old, envenomed by a B. atrox snake. Envenoming caused by B. atrox are characterized by local manifestations (e.g., pain and edema) and systemic manifestations, mainly coagulation disorders. The indigenous victim was admitted in the main hospital of Roraima and evolved with an unusual complication, an ischemia and necrosis of the proximal ileum, requiring segmental enterectomy with posterior side-to-side anastomosis. The victim was discharge after 27 days of hospitalization with no complaints. Snakebite envenomations may evolve with life-threatening complications, which can be treated by the antivenom following access to a healthcare unit, often late in indigenous population. This clinical case shows the need of strategies that aim improvement in the access to the healthcare by indigenous people, as well as demonstrates an unusual complication that may result from lancehead snakebites. The article also discusses the decentralization of snakebites clinical management to indigenous community healthcare centers to mitigate complications.

Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review.

Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs.

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.

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.

Multifaceted community health education programs as powerful tools to mitigate snakebite-induced deaths, disabilities, and socioeconomic burden.

Snakebite envenoming (SBE) predominantly affects rural impoverished communities that have limited access to immediate healthcare. These communities often hold numerous myths/misbeliefs about snakes and SBE. Moreover, healthcare professionals who practice in rural regions often work in unstable situations with limited medical infrastructure and therefore, lack sufficient knowledge/experience and confidence in the clinical management of SBE. Due to the lack of reliable statistics on the true burden of SBE, developing health policies for this condition by relevant authorities may be difficult. Hence, it is critical to improve awareness about SBE among rural communities, healthcare professionals and health authorities using robust multifaceted community health education approaches. Here, we describe the design, development, implementation, and impact of distinctive community health education approaches that we used in India and Brazil. A wide range of educational tools including information leaflets, posters, pocket guides, learning materials for healthcare professionals and short/long video documentaries were developed in local languages and used to engage with target communities through direct assemblies as well as mass/traditional and social media. Notably, we used diverse methods to determine the impact of our programs in improving awareness, treatment-seeking behaviour, and clinical practice. The people-centred approaches that we used were inclusive and highly impactful in instigating fundamental changes in the management of SBE among rural communities. The resources and approaches presented in this article can be easily adapted for wider use in other countries in order to collectively reduce SBE-induced deaths, disabilities and socioeconomic ramifications.

Snakebite clinics and pathogenesis: from preclinical to resource mapping studies

Amidst the global healthcare landscape, the menace of snakebite envenoming (SBE) has persisted, silently afflicting millions and annually claiming tens of thousands of lives. Indeed, in 2017, the World Health Organization (WHO) reclassified snakebite envenoming as a Category A Neglected Tropical Disease (NTD), finally prompting worldwide recognition of the profound health and economic devastation caused by these venomous encounters. Then, in 2019, WHO unveiled an ambitious strategy: to slash snakebite envenoming-related mortality and disability by 50% before 2030 [1,2]. This editorial marks the inception of our Special Issue, “Snakebite Clinics and Pathogenesis: From Preclinical to Resource Mapping Studies”, which stands as a guiding light in our collective effort to confront SBEs. Gathering insights from research on snakebite envenoming outcomes, diagnostic advancements, uncommon case reports, therapeutic strategies, and healthcare professional training, this Special Issue is dedicated to disseminating knowledge and charting a course towards a future where snakebite envenomings cease to be a neglected tragedy and evolve into a preventable and manageable challenge. In their pioneering study, Murta et al. [3] explored the experiences of healthcare professionals (HCPs) providing medical care to indigenous people with SBEs in the Brazilian Amazon. They conducted group discussions during a three-day training session for HCPs from the Indigenous Health Care Subsystem, involving 56 participants split between Boa Vista (Roraima) and Manaus (Amazonas), which are state capitals located in the Brazilian Amazon Forest. The study revealed three key findings: indigenous people are open to receiving antivenom but prefer not to leave their villages for hospitals; HCPs require antivenom and additional resources to improve patient care; and HCPs advocate for a collaborative, culturally sensitive approach to SBE treatment. To address these challenges, the study suggests decentralizing antivenom distribution to local health units. However, the diverse ethnicities in the Brazilian Amazon pose a challenge, necessitating further research on preparing HCPs for intercultural contexts. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. The study of Rocha et al. (2022) [4] aimed to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. Content validation was performed by a panel of expert judges with academic and/or technical expertise in SBE management, and semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon. 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. In the health system domain, this strategy involves ensuring the production and distribution of safe and effective antivenom treatment and strengthening local health systems. Bhatia et al. (2022) [5] highlight that there is an urgent need to replace the excessive use of animals in snake antivenom production. We tested the efficacy of a single batch of polyvalent antivenom from bioproducts limited to Echis carinatus venom collected from Tamil Nadu, Goa, and Rajasthan, using different in vitro assays. The use of both binding and functional assays allowed us to measure the efficacy of the antivenom. By normalizing the scale of measurements of the neutralization capacity of the Indian polyvalent antivenom using different in vitro assays, we were able to arrive at an efficacy score for Echis carinatus venoms that could be used to predict the ED50. This approach captures the variation in venom toxins shown by snake species and paves the way to replace the use of mice for evaluating antivenom potency. Protobothrops mucrosquamatus snakebites are frequent in Taiwan, and the species’ widespread distribution and diverse habitats drove Chiang et al. (2022) [6] to investigate envenoming effects and relevant venom variations. The results showed minor differences in the protein family, with variations in acidic phospholipases A2s, serine proteinases, metalloproteinases, C-type lectin-like proteins, and other less abundant components. Moreover, clinical manifestations of envenomed patients hospitalized in northern Taiwan revealed differences in local symptoms, such as ecchymosis and blistering. The mechanism of these local effects is probably related to the venom components’ geographical variability. These findings will help to improve the management of P. mucrosquamatus bites in Taiwan. Vera-Palacios et al. (2022) [7] investigated in vivo the ability of Urospatha sagittifolia (Araceae) to modulate the catalytic activity of Bothrops atrox venom, and their toxic consequences, such as edema, skin hemorrhage, and lethality. Ethanolic extract, which is rich in phenolics, alkaloids, coumarins, and flavonoids, reduced these three parameters. The authors concluded that these findings will support future studies with purified metabolites as new agents for the treatment of B. atrox snakebites, an important public health problem in the Amazon region. The study by Manson et al. [8] marks a groundbreaking leap forward in the realm of SBE treatment, with a particular focus on combating the toxicity of Three-Finger Toxins (3FTxs) of Naja ashei snake venom. These potent venom-derived toxins are prevalent in N. ashei venom and have posed a formidable challenge to effective antivenom therapy. What sets this research apart is the development of monoclonal antibodies (i.e., P4G6a, P6D9a, and P6D9b) meticulously designed to target these troublesome 3FTxs. Remarkably, the monoclonal antibodies demonstrated exceptional binding capabilities to the target 3FTxs, outperforming even the leading commercial antivenoms available in the Kenyan market. The true breakthrough lies in the combined use of these monoclonal antibodies, where their cocktail exhibited superior toxin inhibition compared to traditional antivenoms. Alsolaiss et al. [9] sheds essential light on the complex and diverse acute responses triggered by African snake venoms, a critical aspect of understanding the pathophysiology of SBEs. Using a well-designed murine model, the research systematically evaluated the acute-phase and inflammatory reactions induced by ten different African snake venoms, with a particular focus on sub-Saharan African species, including the spitting cobra (Naja nigricollis) and forest cobra (N. melanoleuca), as potent inducers of acute-phase and inflammatory responses, with N. nigricollis venom stimulating a remarkable 100-fold increase in systemic interleukin 6 (IL-6). Moreover, the study revealed species-specific changes in red blood cell morphology, lymphopenia, neutrophil leukocytosis, and marked hemolysis and platelet aggregation levels in response to these venoms. These findings underscore the intricate and diverse nature of acute responses to envenoming, paving the way for potential diagnostic and therapeutic advancements that could greatly benefit snakebite victims. A very interesting review was also presented in the Special Issue. Huang et al. [10] analyzes 35 cases of snakebites, primarily from front-fanged snakes, like vipers and cobras, as well as a few rare instances from rear-fanged snakes. Viper bites often result in severe complications, such as ischemic strokes and intracranial hemorrhages, leading to fatalities in some cases. In contrast, elapid bites are primarily manifested as neural, cardiac, and ophthalmic disorders. Remarkably, rear-fanged snakebites, characterized by shallow bites and minimal venom injection, rarely cause severe complications. An essential takeaway from the review is the pivotal role of antivenom (AV) treatment, although it also discusses various therapeutic agents that could potentially complement AV treatment for snakebite-induced complications. Furthermore, the Special Issue delved into two unconventional snakebite case reports, one conducted in Romania and the other in Brazil, subjecting them to comprehensive examination and discussion. Nitescu et al. [11] offers a unique perspective on snake envenomation, focusing on a specific exception within the European viper (Vipera berus) species. While most V. berus bites typically lack neurotoxic effects, their study highlights rare cases involving subspecies found in the Carpathian Basin of southeastern Europe that do induce such symptoms. The study presents a compelling case of a 5-year-old girl from southern Romania who experienced neurotoxicity, alongside systemic and local symptoms, following a bite from one of these Carpathian Basin V. berus subspecies. This case provides pivotal insights, affirming that venom from V. berus subspecies in the Carpathian Basin region can indeed induce neurotoxic effects. Additionally, it underscores the effectiveness of monospecific antivenom treatment in rapidly and completely mitigating the envenomation’s effects, offering valuable clinical guidance for the management of such rare cases. In contrast, Oliveira et al.’s [12] case report delves into the often-overlooked long-term musculoskeletal disabilities resulting from snakebites in indigenous communities in Brazil. The report focuses on a 32-year-old male indigenous patient envenomed by a Bothrops species (lancehead snake), highlighting the significant and enduring health challenges posed by snakebites. Over approximately 2 years and 6 months, the patient underwent various medical interventions, including debridement, tissue reconstruction, and physical therapy, resulting in improved mobility but a lasting impact on his gait. This case report emphasizes the need for a comprehensive healthcareapproach, including physiotherapy, plastic surgery, orthopedics, and social support, to aid in the reintegration of snakebite survivors into their communities. Antivenom treatments for SBE patients have existed for more than 130 years, remaining the only therapeutics available for this neglected problem. Remarkably, despite advances in the health system, access to antivenom treatment is poor in most areas of low-income countries. Better logistics for the transportation of antivenoms and other commodities is an issue to be addressed, as well as realistic and comprehensive health programs. In parallel, many investments are still needed for the research and development of more effective antivenoms for some species of snakes, as well as for the advance of small-molecule inhibitor-based drug therapies.

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.

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 Amazonian kambô frog Phyllomedusa bicolor (Amphibia: Phyllomedusidae): Current knowledge on biology, phylogeography, toxinology, ethnopharmacology and medical aspects.

Phyllomedusa bicolor (Phyllomedusidae), popularly known as the kambô in Brazil, is a tree frog that is widely distributed in South American countries and is known for producing a skin secretion that is rich in bioactive peptides, which are often used in indigenous rituals. The biological effects of the skin secretion were observed in the first studies with indigenous communities. Over the last six decades, researchers have been studying the chemical composition in detail, as well as the potential pharmacological applications of its constituents. For this reason, indigenous communities and health agents fear the misuse of the kambô, or the inappropriate use of the species, which can result in health complications or even death of users. This article seeks to provide a transdisciplinary review that integrates knowledge regarding the biology of P. bicolor, ethnoknowledge about the ritual of the kambô, and the chemistry and pharmacology of the skin secretion of this species, in addition to medical aspects of the indiscriminate use of the kambô. Furthermore, this review seeks to shed light on perspectives on the future of research related to the kambô.

Medical Management after Lancehead Snakebite in North Amazon: A Case Report of Long-Term Disability.

Snakebites are a major public health problem in indigenous communities in Brazil, leading to acute local and systemic damage with resulting deficiencies. Long-term musculoskeletal disabilities related to snakebites have been a neglected area of research. Bothrops (lancehead) snakes are responsible for most of the permanent sequelae related to snakebites in Latin America. Here, we present a case report of a 32-year-old male indigenous patient who was envenomed by a Bothrops species. The patient was clinically followed for a period of approximately 2 years and 6 months, during which time he experienced a loss of musculoskeletal tissue and required several medical procedures such as debridement, tissue reconstruction, and physical therapy, which resulted in a recovery of mobility, though with a permanent sequelae in gait. This case report shows how snakebites have a significant impact on health systems, as victims require physiotherapy, plastic surgery, and orthopedics services, as well as social support for reintegration into their local communities.

Plant-Derived Toxin Inhibitors as Potential Candidates to Complement Antivenom Treatment in Snakebite Envenomations.

Snakebite envenomations (SBEs) are a neglected medical condition of global importance that mainly affect the tropical and subtropical regions. Clinical manifestations include pain, edema, hemorrhage, tissue necrosis, and neurotoxic signs, and may evolve to functional loss of the affected limb, acute renal and/or respiratory failure, and even death. The standard treatment for snake envenomations is antivenom, which is produced from the hyperimmunization of animals with snake toxins. The inhibition of the effects of SBEs using natural or synthetic compounds has been suggested as a complementary treatment particularly before admission to hospital for antivenom treatment, since these alternative molecules are also able to inhibit toxins. Biodiversity-derived molecules, namely those extracted from medicinal plants, are promising sources of toxin inhibitors that can minimize the deleterious consequences of SBEs. In this review, we systematically synthesize the literature on plant metabolites that can be used as toxin-inhibiting agents, as well as present the potential mechanisms of action of molecules derived from natural sources. These findings aim to further our understanding of the potential of natural products and provide new lead compounds as auxiliary therapies for SBEs.

Lower levels of CXCL-8 and IL-2 on admission as predictors of early adverse reactions to Bothrops antivenom in the Brazilian Amazon.

Snakebite envenomings are considered a global health problem. The specific therapy for these envenomings consists of administering animal-derived antivenoms aiming to neutralize the venom toxins. Antivenoms have been used effectively to treat snakebites for more than a century; however, their administration may result in early and/or late adverse reactions. The present study presents the prevalence of early adverse reactions (EARs) towards Bothrops antivenom therapy in a health tertiary unit in the Brazilian Amazon and explores if specific plasma cytokines and chemokines from envenomed patients could be used as predictors of EARs. A cohort of patients bitten by Bothrops atrox was followed-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), from 2014 to 2016. Patients were treated with the Brazilian Bothrops antivenom and CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-y, IL-4, and IL-17A were evaluated in patients' plasma samples before and after antivenom administration. From the total of patients (n = 186), mostly were male (82.3%), inhabiting rural areas (87.1%), with an average age of 35 years. Most of the patients (83.8%) were admitted to the hospital within 6 h after the accident, 26 (14%) reported having suffered a previous snakebite, and 97 (52.1%) received between 7 and 9 antivenom vials. The frequency of antivenom-induced EARs was 11.8% (22), resulting mostly of mild reactions. Urticaria was the major EAR manifestation (46.4%). Interestingly, CXCL-8 and IL-2 showed significantly lower levels in patients who progressed to EARs, although IL-2 levels might not represent biological relevance due the small magnitude difference between groups. This study reveals that CXCL-8 and IL-2 could play a role in the onset of EARs in pit viper envenomings.