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.

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.

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.

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.

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.

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.

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.

Crotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinology.

Crotalus durissus ruruima is a rattlesnake subspecies mainly found in Roraima, the northernmost state of Brazil. Envenomings caused by this subspecies lead to severe clinical manifestations (e.g. respiratory muscle paralysis, rhabdomyolysis, and acute renal failure) that can lead to the victim's death. In this review, we comprehensively describe C. d. ruruima biology and the challenges this subspecies poses for human health, including morphology, distribution, epidemiology, venom cocktail, clinical envenoming, and the current and future specific treatment of envenomings by this snake. Moreover, this review presents maps of the distribution of the snake subspecies and evidence that this species is responsible for some of the most severe envenomings in the country and causes the highest lethality rates. Finally, we also discuss the efficacy of the Brazilian horse-derived antivenoms to treat C. d. ruruima envenomings in Roraima state.

Crotalus durissus ruruima: current knowledge on natural history, medical importance, and clinical toxinology

Crotalus durissus ruruima is a rattlesnake subspecies mainly found in Roraima, the northernmost state of Brazil. Envenomings caused by this subspecies lead to severe clinical manifestations (e.g. respiratory muscle paralysis, rhabdomyolysis, and acute renal failure) that can lead to the victim’s death. In this review, we comprehensively describe C. d. ruruima biology and the challenges this subspecies poses for human health, including morphology, distribution, epidemiology, venom cocktail, clinical envenoming, and the current and future specific treatment of envenomings by this snake. Moreover, this review presents maps of the distribution of the snake subspecies and evidence that this species is responsible for some of the most severe envenomings in the country and causes the highest lethality rates. Finally, we also discuss the efficacy of the Brazilian horse-derived antivenoms to treat C. d. ruruima envenomings in Roraima state.

Pioneering Study on Rhopalurus crassicauda Scorpion Venom: Isolation and Characterization of the Major Toxin and Hyaluronidase.

Scorpionism is responsible for most accidents involving venomous animals in Brazil, which leads to severe symptoms that can evolve to death. Scorpion venoms consist of complexes cocktails, including peptides, proteins, and non-protein compounds, making separation and purification procedures extremely difficult and time-consuming. Scorpion toxins target different biological systems and can be used in basic science, for clinical, and biotechnological applications. This study is the first to explore the venom content of the unexplored scorpion species Rhopalurus crassicauda, which inhabits exclusively the northernmost state of Brazil, named Roraima, and southern region of Guyana. Here, we pioneer the fractionation of the R. crassicauda venom and isolated and characterized a novel scorpion beta-neurotoxin, designated Rc1, and a monomeric hyaluronidase. R. crassicauda venom and Rc1 (6,882 Da) demonstrated pro-inflammatory activities in vitro and a nociceptive response in vivo. Moreover, Rc1 toxin showed specificity for activating Nav1.4, Nav1.6, and BgNav1 voltage-gated ion channels. This study also represents a new perspective for the treatment of envenomings in Roraima, since the Brazilian scorpion and arachnid antivenoms were not able to recognize R. crassicauda venom and its fractions (with exception of hyaluronidase). Our work provides useful insights for the first understanding of the painful sting and pro-inflammatory effects associated with R. crassicauda envenomings.

Identification of cross-reactive human single-chain variable fragments against phospholipases A2 from Lachesis muta and Bothrops spp venoms.

Bushmasters (Lachesis spp) and lancehead vipers (Bothrops spp) are two of the most dangerous snakes found in Latin America. Victims of envenoming by these snakes require urgent administration of antivenom. Here, we report the identification of a small set of broadly neutralizing human monoclonal single-chain variable fragment (scFv) antibodies targeting key phospholipases A2 from Lachesis and Bothrops spp using phage display technology and demonstrate their in vitro efficacy using a hemolysis assay.

Scorpion Venom: Detriments and Benefits.

Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.

Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins.

Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects in prey and predators. Among the toxins that are known for interacting synergistically are cytotoxins from snake venoms, phospholipases A2 from snake and bee venoms, and melittin from bee venom. These toxins may derive a synergistically enhanced toxicity via formation of toxin complexes by hetero-oligomerization. Using a human keratinocyte assay mimicking human epidermis in vitro, we demonstrate and quantify the level of synergistically enhanced toxicity for 12 cytotoxin/melittin-PLA2 combinations using toxins from elapids, vipers, and bees. Moreover, by utilizing an interaction-based assay and by including a wealth of information obtained via a thorough literature review, we speculate and propose a mechanistic model for how toxin synergism in relation to cytotoxicity may be mediated by cytotoxin/melittin and PLA2 complex formation.

Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region.

BACKGROUND: Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The Bothrops (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. Bothrops spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied. CASE PRESENTATION: Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the Bothrops genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming. CONCLUSION: In Latin America, especially in Brazil, where there is a high prevalence of Bothrops envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.

Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region

Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The Bothrops (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. Bothrops spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied. Case presentation: Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the Bothrops genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming. Conclusion: In Latin America, especially in Brazil, where there is a high prevalence of Bothrops envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.(AU)

Current knowledge on snake dry bites

Snake ‘dry bites’ are characterized by the absence of venom being injected into the victim during a snakebite incident. The dry bite mechanism and diagnosis are quite complex, and the lack of envenoming symptoms in these cases may be misinterpreted as a miraculous treatment or as proof that the bite from the perpetrating snake species is rather harmless. The circumstances of dry bites and their clinical diagnosis are not well-explored in the literature, which may lead to ambiguity amongst treating personnel about whether antivenom is indicated or not. Here, the epidemiology and recorded history of dry bites are reviewed, and the clinical knowledge on the dry bite phenomenon is presented and discussed. Finally, this review proposes a diagnostic and therapeutic protocol to assist medical care after snake dry bites, aiming to improve patient outcomes.

Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy.

Honey bees can be found all around the world and fulfill key pollination roles within their natural ecosystems, as well as in agriculture. Most species are typically docile, and most interactions between humans and bees are unproblematic, despite their ability to inject a complex venom into their victims as a defensive mechanism. Nevertheless, incidences of bee stings have been on the rise since the accidental release of Africanized bees to Brazil in 1956 and their subsequent spread across the Americas. These bee hybrids are more aggressive and are prone to attack, presenting a significant healthcare burden to the countries they have colonized. To date, treatment of such stings typically focuses on controlling potential allergic reactions, as no specific antivenoms against bee venom currently exist. Researchers have investigated the possibility of developing bee antivenoms, but this has been complicated by the very low immunogenicity of the key bee toxins, which fail to induce a strong antibody response in the immunized animals. However, with current cutting-edge technologies, such as phage display, alongside the rise of monoclonal antibody therapeutics, the development of a recombinant bee antivenom is achievable, and promising results towards this goal have been reported in recent years. Here, current knowledge on the venom biology of Africanized bees and current treatment options against bee envenoming are reviewed. Additionally, recent developments within next-generation bee antivenoms are presented and discussed.

History of Envenoming Therapy and Current Perspectives.

Each year, millions of humans fall victim to animal envenomings, which may either be deadly or cause permanent disability to the effected individuals. The Nobel Prize-winning discovery of serum therapy for the treatment of bacterial infections (tetanus and diphtheria) paved the way for the introduction of antivenom therapies for envenomings caused by venomous animals. These antivenoms are based on polyclonal antibodies derived from the plasma of hyperimmunized animals and remain the only specific treatment against animal envenomings. Following the initial development of serum therapy for snakebite envenoming by French scientists in 1894, other countries with high incidences of animal envenomings, including Brazil, Australia, South Africa, Costa Rica, and Mexico, started taking up antivenom production against local venomous animals over the course of the twentieth century. These undertakings revolutionized envenoming therapy and have saved innumerous patients worldwide during the last 100 years. This review describes in detail the above-mentioned historical events surrounding the discovery and the application of serum therapy for envenomings, as well as it provides an overview of important developments and scientific breakthroughs that were of importance for antibody-based therapies in general. This begins with discoveries concerning the characterization of antibodies, including the events leading up to the elucidation of the antibody structure. These discoveries further paved the way for other milestones in antibody-based therapies, such as the introduction of hybridoma technology in 1975. Hybridoma technology enabled the expression and isolation of monoclonal antibodies, which in turn formed the basis for the development of phage display technology and transgenic mice, which can be harnessed to directly obtain fully human monoclonal antibodies. These developments were driven by the ultimate goal of producing potent neutralizing monoclonal antibodies with optimal pharmacokinetic properties and low immunogenicity. This review then provides an outline of the most recent achievements in antivenom research, which include the application of new biotechnologies, the development of the first human monoclonal antibodies that can neutralize animal toxins, and efforts toward creating fully recombinant antivenoms. Lastly, future perspectives in the field of envenoming therapies are discussed, including rational engineering of antibody cross-reactivity and the use of oligoclonal antibody mixtures.

Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression.

Scorpion venoms are natural sources of molecules that have, in addition to their toxic function, potential therapeutic applications. In this source the neurotoxins can be found especially those that act on potassium channels. Potassium channels are responsible for maintaining the membrane potential in the excitable cells, especially the voltage-dependent potassium channels (Kv), including Kv1.3 channels. These channels (Kv1.3) are expressed by various types of tissues and cells, being part of several physiological processes. However, the major studies of Kv1.3 are performed on T cells due its importance on autoimmune diseases. Scorpion toxins capable of acting on potassium channels (KTx), mainly on Kv1.3 channels, have gained a prominent role for their possible ability to control inflammatory autoimmune diseases. Some of these toxins have already left bench trials and are being evaluated in clinical trials, presenting great therapeutic potential. Thus, scorpion toxins are important natural molecules that should not be overlooked in the treatment of autoimmune and other diseases.