Evaluation of Neutralization Potential of Naja naja and Daboiarusselii Snake Venom by Root Extract of Cyanthillium cinereum.

Aim: One of the main reasons for the death due to snake bites is the non-availability of antivenoms in the regions where they are needed. The use of medicinal plants and plant-based natural products as an alternative to antivenom will become a milestone in snake bite envenomation. The present study investigates the in vitro antivenom properties of Cyanthillium cinereum root extracts. Materials and methods: The C. cinereum root's aqueous extract was prepared by the Soxhlet extraction method, and phytochemical screening was performed to detect the presence of various bioactive compounds. Thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) analysis were performed for the detection and identification of phytochemical constituents. In this study, an in vitro model is used to assess the antivenom capability of aqueous extract. Venom toxicity and neutralization assays were as follows: An in vitro pharmacological evaluation was performed by direct hemolysis assay, indirect hemolytic assay, proteolytic activity, neutralization of procoagulant activity, and gelatin liquefaction method. Results: Qualitative analysis of phytochemicals by the standard method showed the presence of various phytochemical constituents. Also, GC-MS analysis showed the presence of three major compounds that possess antivenom activity from the obtained 60 bioactive compounds, and their chemical structures were also determined. Venom protein profiling was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The plant extract was able to neutralize the Naja naja (N. naja) and Daboia russelii (D. russelii) venom induced hemolysis and it was reduced below 50 and 40%, respectively and the extract was also able to reduce the hemolytic halo produced by venoms. Procoagulant activity and gelatin liquefaction assay showed that venom-induced clotting was neutralized by increasing the root extract concentration sufficiently. Conclusion: The aqueous extract of the root of C. cinereum showed potent in vitro venom-neutralizing activity, and it can be used as a formidable therapeutic agent against N. naja and D. russelii envenomation. How to cite this article: Suji S, Dinesh MD, Keerthi KU, Anagha KP, Arya J, Anju KV. Evaluation of Neutralization Potential of Naja naja and Daboia russelii Snake Venom by Root Extract of Cyanthillium cinereum. Indian J Crit Care Med 2023;27(11):821-829.

Snakebites from the standpoint of an indigenous anthropologist from the Brazilian Amazon.

Conflicting attempts between indigenous caregivers trying to exercise their healing practices in hospitals have been recorded in the Brazilian Amazon. In this work, we present an interview with the Baniwa indigenous anthropologist Francy Baniwa. In an external and colonial interpretation, it was previously stated that indigenous people attribute the origin of snakebites as supernatural and that indigenous medicine, when it saves a patient from complications and death, has symbolic efficacy. In this interview, we observed that this form of interpretation is asymmetric because, for indigenous people, their understanding of nature is broader than ours, with more possibilities of ways of existence, including non-human entities as well or ill-intentioned as humans. The interaction of humans with these identities produces a form of existence with its own clinical reality, which is full of symbolism. Effective communication between health agents and indigenous patients and caregivers must undergo this exercise of otherness and interculturality.

Broadening the research landscape in the field of snakebite envenoming: Towards a holistic perspective.

Snakebite envenoming (SBE) is a neglected tropical disease that kills and maims hundreds of thousands of people yearly, particularly in impoverished rural settings of the Global South. Understanding the complexity of SBE and tackling this disease demands a transdisciplinary, One Health approach. There is a long-standing research tradition on SBE in toxinology and human medicine. In contrast, other disciplines, such as veterinary medicine or social sciences, still need to be better developed in this field, especially in countries with a high incidence of SBE. Broadening the disciplinary landscape, connecting various research approaches, methods, and data across disciplines and sectors, and engaging with communities affected by SBE in implementing evidence-based solutions are needed. This review summarizes areas that require strengthening to better understand the complexity of SBE and to generate a robust body of knowledge to be translated into effective public health interventions.

Medicinal plants from Mexico used in the treatment of scorpion sting.

Scorpion sting envenomation is a major public health in Mexico. Rural communities rarely have antivenoms in the health centers, therefore, the people commonly resort to using medicinal plants to treat the symptoms of envenoming caused by scorpion venom, but this knowledge has not yet been reported in detail. In this review, we carry out a review of the medicinal plants used in Mexico against scorpion stings. PubMed, Google, Science Direct, and the Digital Library of Mexican Traditional Medicine (DLMTM) were used to collect data. The results showed the use of at least 48 medicinal plants distributed in 26 families, where Fabaceae (14.6%), Lamiaceae (10.4%), and Asteraceae (10.4%) have the maximum representation. The application of leaves (32%) was preferred followed by roots (20%), stem (17.3%), flowers (16%), and bark (8%). In addition, the most common method of use to treat scorpion stings is decoction (32.5%). The oral and topical routes of administration have similar percentages of use. In vitro and in vivo studies of Aristolochia elegans, Bouvardia ternifolia, and Mimosa tenuiflora were found, which showed an antagonistic effect on the contraction of the ileum caused by the venom of C. limpidus, likewise, they increased the LD50 of said venom and even B. ternofila showed reduced albumin extravasation. The results of these studies demonstrate the promising use of medicinal plants for future pharmacological applications; nevertheless, validation, bioactive compound isolation and toxicity studies are necessary to support and improve therapeutics.

A prospective study of snakebite in a tertiary care hospital in south-western Nepal.

BACKGROUND: Snakebite is a neglected public health issue in Nepal. We aimed to characterize patients with snake envenoming admitted to hospital in south-western Nepal. METHODS: This was a prospective cohort study of 476 snakebite patients admitted to Bheri Hospital from May to December 2017. Data were collected on patient demographics, bite circumstances, snake type, treatment-seeking behavior, clinical effects, complications and treatment. RESULTS: There were 139/476 (29%) patients with clinical features of envenomation and 10 deaths (8%), of which six were prehospital deaths; 325/476 (68%) patients used non-recommended prehospital first aid, including 278 (58%) who applied a tourniquet and 43 (9%) consulting traditional healers. Median time to hospital arrival was 1.5 (IQR: 0.8-4) h. Also, 127 envenomated patients (91%) developed neurotoxicity and 12 (9%) hemotoxicity, while 124 patients (89%) received antivenom, with a median dose of 10 (4-30) vials. Three patients developed anaphylaxis following antivenom administration; 111 of 139 (80%) cases were admitted to the ICU and 48 (35%) were intubated. Median length of hospital stay for all cases was 0.5 (IQR: 0.5-1.2) d, but it was 2.2 (IQR: 1.5-3.8) d for envenomated cases. CONCLUSIONS: The majority of snakebite patients used non-recommended first aid or attended traditional healers. Almost one-third of patients developed systemic envenomation and required antivenom. The case fatality rate was high, but many died prior to arriving in hospital.

Preliminary assessment of antivenom availability and management in the public health system of Costa Rica: An analysis based on a survey to pharmacists in public health facilities.

Availability and accessibility of safe and effective antivenoms are key elements for the successful treatment of snakebite envenoming (SBE). This study provides a preliminary analysis on the way antivenoms are managed by the public health system in Costa Rica and on the role played by pharmacists in the overall management of antivenoms. This was an observational, cross-sectional study based on an online survey sent to pharmacists working at Caja Costarricense de Seguro Social (Costa Rican Social Security System; CCSS) in different locations in Costa Rica. Characteristics and location of health facilities, as well as antivenom availability and management details, were analyzed. Responses from a total of 96 pharmacists, corresponding to 55 different healthcare facilities, were included in this study. Most respondents worked at pharmacies located in urban communities (69.0%) and in the secondary level of care, which includes clinics, and regional and peripheral hospitals (55.2%). Overall, participants reported antivenom availability at all levels of care and in centers having various operating schedules, although they were not available in some facilities in regions where SBE is uncommon or do not attend SBE cases because of the proximity of more complex health centers. On average, the stocks of anticoral and polyvalent antivenoms per health facility were compatible with the dose of antivenom required for treating a SBE case. More than half of participants reported knowing the availability of protocols for the management of SBE and the correct use of antivenom at their healthcare facilities. Of the total respondents, 49% agreed on possessing all the resources needed for the correct management of these medicines at their facilities, and 65.6% indicated that they know the procedures for antivenom storage and management. Our findings provide a first description of the availability of antivenoms in the public health system of Costa Rica, including the primary care level. Results also underscore the perceived role of participating pharmacists in the management of these life-saving drugs and the need to improve their knowledge on this topic.

The potential of Brazilian native plant species used in the therapy for snakebites: A literature review.

Snakebite envenoming is a potentially fatal disease categorized as a neglected public health issue for not receiving the appropriate attention from national and international health authorities. The most affected people by this problem usually live in poor rural communities, where medical resources are often sparse and, in some instances, there is even a scarcity of serum therapy. The administration of the appropriate antivenom is the only specific treatment available, however it has limited efficacy against venom-induced local effects. In this scenario, various plant species are used as local first aid for the treatment of snakebite accidents in Brazil, and some of them can effectively inhibit lethality, neurotoxicity, hemorrhage, and venom enzymes activities. This review compiles a list of plants used in the treatment of snakebites in Brazil, focusing on the native Brazilian species registered in the databases Pubmed, Scielo, Scopus and Google Scholar. All these searches were limited to peer-reviewed journals written in English, with the exception of a few articles written in Portuguese. The most cited native plant species were Casearia sylvestris Sw., Eclipta prostrata (L.) L., Mikania glomerata Spreng., Schizolobium parahyba (Vell.) S.F.Blake and Dipteryx alata Vogel, all used to decrease the severity of toxic signs, inhibit proteolytic and hemorrhagic activities, thus increasing survival time and neutralizing myotoxicity effects. Different active compounds showing important activity against the snake venoms and their toxins include flavonoids, alkaloids and tannins. Although some limitations to the experimental studies with medicinal plants were observed, including lack of comparison with control drugs and unknown active extracts compounds, species with anti-venom characteristics are effective and considered as candidates for the development of adjuvants in the treatment of snake envenomation. Further studies on the chemistry and pharmacology of traditionally used plant species will help to understand the role that snakebite herbal remedies may display in local medical health systems. It might also contribute to the development of alternative or complementary treatments to reduce the number of severe disabilities and deaths.

A First Look at the Inhibitory Potential of Urospatha sagittifolia (Araceae) Ethanolic Extract for Bothrops atrox Snakebite Envenomation.

Bothrops atrox snakebites are a relevant problem in the Amazon basin. In this biodiverse region, the ethnomedicinal approach plays an important role as an alternative to antivenom therapy. Urospatha sagittifolia (Araceae) is a plant used for this purpose; however, its neutralizing properties have not been scientifically accessed. To fill this gap, we investigated the ability of U. sagittifolia to modulate the catalytic activity of Bothrops atrox venom, and their toxic consequences, such as local damage and lethality. The venom profile of B. atrox was assessed by chromatography and electrophoresis. Inhibition of the three main enzymatic and medically important toxins from the venom was evaluated using synthetic substrates and quantified by chromogenic activity assays. Additionally, the neutralization of lethality, hemorrhage and edema were investigated by in vivo assays. The possible interactions between venom proteins and plant molecules were visualized by polyacrylamide gel electrophoresis. Finally, the phytochemical constituents present in the ethanolic extract were determined by qualitative and quantitative analyses. The ethanolic extract reduced the activity of the three main enzymes of venom target, achieving ranges from 19% to 81% of inhibition. Our in vivo venom neuralizations assays showed a significant inhibition of edema (38.72%) and hemorrhage (42.90%). Additionally, lethality was remarkably counteracted. The highest extract ratio evaluated had a 75% survival rate. Our data support the biomedical value of U. sagittifolia as a source of natural enzyme inhibitors able to neutralize catalytically active B. atrox venom toxins and their toxic effects.

Hyperbaric oxygen therapy of soft tissue necrosis due to centipede bite in a patient with diabetes.

OBJECTIVE: The purpose of this study is to demonstrate that hyperbaric oxygen therapy (HBOT) is an option for the management of rapidly progressive tissue necrosis after centipede bites in patients with diabetes. METHOD: In this case report, we introduce a patient with diabetes with soft tissue necrosis and secondary infection due to a centipede bite, who was treated with a multidisciplinary approach including HBOT. RESULTS: In this case study, HBOT, applied in the treatment of rapidly developing cellulitis after a centipede bite in a patient with diabetes, accelerated wound healing. Deep soft tissue infection stopped progression to necrotising fasciitis and prevented possible amputation, and facilitated the patient's return to social life in a short time. CONCLUSION: HBOT can be used in combination with other local and systemic, due to its anti-venom effect and treatment of extremity-threatening infection.

Herbal Compounds as an Antidote Against Snake Bite.

Snakebites have been declared a neglected health problem that is considered a national disease by the WHO (world health organisation). Asian countries like India have high snakebite death rates due to short antidotes and poorly equipped doctors. In today's scenario, local resources like herbs need to be used to prepare cheap antidotes and are often available to victims. Snake bites should be viewed as an emergency problem and require additional national guidelines, doctor training, expertise, and human concentration for effective and timely treatment-measures to be taken to ensure the availability and mass production of antidotes. Currently available, antidotes have problems with storage, manufacture, and aspects of the results. Attention should be paid to the natural compound Gedunin with antitoxic effects. To determine Gedunin's therapeutic efficacy, well-designed clinical research is required. This article emphasizes and proves the therapeutic effectiveness of the herbal plant active ingredient Gedunin against snakebites.

Preclinical efficacy of African medicinal plants used in the treatment of snakebite envenoming: a systematic review protocol.

BACKGROUND: Snakebite envenoming (SBE) is a high-priority, neglected, tropical disease that affects millions of people in developing countries annually. The only available standard drug used for the treatment of SBE is antisnake venom (ASV) which consists of immunoglobulins that have been purified from the plasma of animals hyper-immunized against snake venoms. The use of plants as alternatives for treatment of poisonous bites particularly snakebites is important in remote areas where there might be limited, or no access to hospitals and storage facilities for antivenom. The pharmacological activity of some of the medicinal plants used traditionally in the treatment of SBE have also been scientifically validated. METHOD: A systematic review will be conducted according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist for study quality in animal/in vivo studies. The tool will be modified and validated to assess in vitro models and studies that combine in vivo and in vitro studies. The systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. English published articles on African medicinal plants used in the treatment of snakebite envenoming will be searched in Medline, Embase, and Scopus from 2000 to 2021. DISSEMINATION: The findings of the study will be communicated through publication in peer-reviewed journal and presentation at scientific conferences. Medicinal plants have been important sources for the development of many effective drugs currently available in orthodox medicine. Botanically derived medicines have played a major role in human societies throughout history. Plants components used in traditional medicine gained much attention by many toxinologists as a tool for designing potent antidotes against snake envenoming. Our systematic review will provide a synthesis of the literature on the efficacy of these medicinal plants. We will also appraise the prospects of African medicinal plants with pharmacologically demonstrated activity against snakebite and envenoming.

Refinement and Neutralization Evaluation of the F(ab')2 Type of Antivenom against the Deadly Jellyfish Nemopilema nomurai Toxins.

Jellyfish stings threaten people's health and even life in coastal areas worldwide. Nemopilema nomurai is one of the most dangerous jellyfish in the East Asian Marginal Seas, which not only stings hundreds of thousands of people every year but also is assumed to be responsible for most deaths by jellyfish stings in China. However, there is no effective first-aid drug, such as antivenoms, for the treatment of severe stings by N. nomurai to date. In this study, we prepared a N. nomurai antiserum from rabbits using inactivated N. nomurai toxins (NnTXs) and isolated the IgG type of antivenom (IgG-AntiNnTXs) from the antiserum. Subsequently, IgG-AntiNnTXs were refined with multiple optimizations to remove Fc fragments. Finally, the F(ab')2 type of antivenom (F(ab')2-AntiNnTXs) was purified using Superdex 200 and protein A columns. The neutralization efficacy of both types of antivenom was analyzed in vitro and in vivo, and the results showed that both IgG and F(ab')2 types of antivenom have some neutralization effect on the metalloproteinase activity of NnTXs in vitro and could also decrease the mortality of mice in the first 4 h after injection. This study provides some useful information for the development of an effective antivenom for N. nomurai stings in the future.

Biochemical evaluation and molecular docking assessment of glucosamines from Neocarya macrophylla fruits against Naja nigricollis venom.

Two new glucosamines, Microphyllose A and B were isolated from the chloroform fraction of Neocarya macrophylla fruit using flash column chromatography. The structures of these compounds were elucidated based on chemical tests and the analysis of their spectral data (IR, 1D- & 2D-NMR). The compounds have demonstrated significant (p < 0.05) antivenom activity against Naja nigricollis venom with 60 and 80% protection, respectively. When subjected to molecular docking, the compounds have demonstrated different binding affinities against three toxins (phospholipase A2, neurotoxin and cardiotoxin) from Naja nigricollis venom and they were further screened for ADMET analysis based on Lipinski's and Veber's rule and the compounds have failed absorptivity for oral medications. To the best of our knowledge, this is the first report of isolation and molecular docking analysis of these compounds from medicinal plants.

Dealing with snakebite in rural Cameroon: A qualitative investigation among victims and traditional healers.

BACKGROUND: Snakebite is a neglected tropical disease (NTD) affecting rural and remote populations globally, who are additionally burdened by poverty and the lack of effective healthcare systems. Delayed healthcare and use of traditional treatments are very frequent. The purpose of our study was to explore perceptions of snakes, impact of snakebite, and knowledge and opinions of different snakebite treatments with the aim of identifying opportunities for improving snakebite management. METHODS: This is a qualitative descriptive study based on semi-structured interviews with 21 snakebite victims and 4 traditional healers in 4 villages of Akonolinga health district, Center Region, Cameroon. Analysis focused on describing participants' perceptions of snakes, the impact of snakebite on the victims' lives, and their opinions of different treatment options. RESULTS: Respondents were fearful of snakes and knowledgeable about envenoming symptoms and treatments. The experience of snakebite led to increased vigilance and avoidance behaviours, which sometimes resulted in financial loss for the victims. A range of traditional treatments were described, including tourniquets, black-stone application and medicinal plant decoctions. However, opinions were ambivalent regarding their efficacy, depending especially on previous personal experiences. Still, traditional treatments were said to be more available and cheaper than hospital care, and in particular, than antivenom. Nevertheless, most victims preferred hospital treatment if the financial and transportation barriers were lifted. Both snakebite victims and traditional healers were of the opinion that collaboration between health services and traditional healers could help to improve snakebite management and outcomes. CONCLUSION: Our study shows that snakebite victims are in favour of using antivenom for the treatment of snakebite and would welcome better access to it. However, its current unavailability and high cost pushes them to turn to traditional treatments. On the other hand, traditional healers are in favour of collaborating with health facilities. These results are very encouraging for the improvement of snakebite management in Cameroon along the lines of the WHO Snakebite Envenoming Strategy for Prevention and Control: ensuring access to safe and effective treatment, and increasing partnership and coordination between communities, traditional healers, and conventional caregivers.

Botanical treatments for snakebite in rural Ghana: A narrative review.

ETHNOPHARMACOLOGICAL RELEVANCE: In the countryside, there are some limitations with the use of venom antisera to manage snake bites. Due to poor access to healthcare and as a result of the difficulty in receiving treatment for cases of snake bites, most rural people in Ghana, a West African country, rely on plant medicine as a first aid to manage cases of venomous snakebite. This calls for more research into the species of plants used to medically manage snakebite envenomation. AIM OF THE STUDY: This review sought to present plants that are used in managing snakebite cases and also gather data supporting their use. METHODOLOGY: This is a systematic search and review of information obtained from textbooks and databases such as PubMed and ScienceDirect between January 1975 and August 2020. RESULTS: A search done identified 43 plant species and these were found to belong to 25 taxonomic families with the most frequent ones being, Fabaceae, Euphorbiaceae, Apocynaceae, and Solanaceae. Experimental data gathered indicate that among the many plants identified to be used to manage snakebites, only 5 were found with anti-venom in vitro and in vivo evidence-based data. CONCLUSION: Data collated hint that a few plant species identified namely Anacardium occidentale, Euphorbia hirta, Mimosa pudica, Musa paradisiaca and Mangifera indica, work by targeting diverse physiopathological and biochemical processes involved in the clinical manifestations of snakebites. This review has also unearthed knowledge gaps that can form the basis for broad investigations and development of these and other medicinal plants into useful anti-venom medications.

The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming.

A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at controlling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming.

What is the impact of snakebite envenoming on domestic animals? A nation-wide community-based study in Nepal and Cameroon.

Snakebite envenoming is a life-threatening disease in humans and animals and a major public health issue in rural communities of South-East Asia and sub-Saharan Africa. Yet the impact of snakebite on domestic animals has been poorly studied. This study aimed to describe the context, clinical features, treatment, and outcomes of snakebite envenoming in domestic animals in Nepal and Cameroon. Primary data on snakebite in animals were recorded from a community-based nation-wide survey on human and animal snakebite in Nepal and Cameroon (Snake-byte project). Mobile teams collected data on snakebite in humans and animals in 13,879 and 10,798 households in Nepal and Cameroon respectively from December 2018 to June 2019. This study included 405 snakebite cases (73 in Nepal and 332 in Cameroon) in multiple types of animals. An interview with a structured questionnaire collected specific information about the animal victims. Snake bites in animals took place predominantly inside and around the house or farm in Nepal (92%) and Cameroon (71%). Other frequent locations in Cameroon were field or pasture (12%). A large diversity of clinical features was reported in all types of envenomed animals. They showed either a few clinical signs (e.g., local swelling, bleeding) or a combination of multiple clinical signs. Only 9% of animal victims, mainly cattle and buffaloes and less frequently goats, sheep, and dogs, received treatment, predominantly with traditional medicine. The overall mortality of snakebite was 85% in Nepal and 87% in Cameroon. Results from this nationwide study show an important impact of snakebite on animal health in Nepal and Cameroon. There is a need for cost-effective prevention control strategies and affordable snakebite therapies in the veterinary field to save animal lives and farmer livelihood in the poorest countries of the world. The WHO global strategy to prevent and control snakebite envenoming supports a One Health approach, which may help develop integrated solutions to the snakebite problem taking into account human and animal health.

Phytochemical composition, antisnake venom and antibacterial activities of ethanolic extract of Aegiphila integrifolia (Jacq) Moldenke leaves.

Snakebites are considered a major neglected tropical disease, resulting in around 100,000 deaths per year. The recommended treatment by the WHO is serotherapy, which has limited effectiveness against the toxins involved in local tissue damage. In some countries, patients use plants from folk medicines as antivenoms. Aegiphila species are common plants from the Brazilian Amazon and are used to treat snakebites. In this study, leaves from Aegiphila integrifolia (Jacq) Moldenke were collected from Roraima state, Brazil and its ethanolic extract was evaluated through in vitro and in vivo experiments to verify their antiophidic activity against Bothrops atrox crude venom. The isolated compounds from A. integrifolia were analyzed and the chemical structures were elucidated on the basis of infrared, ultraviolet, mass, 1H and 1³C NMR spectrometry data. Among the described compounds, lupeol (7), betulinic acid (1), ß-sitosterol (6), stigmasterol (5), mannitol (4), and the flavonoids, pectolinarigenin (2) and hispidulin (3), were identified. The ethanolic extract and flavonoids (2 and 3) partially inhibited the proteolytic, phospholipase A2 and hyaluronidase activities of B. atrox venom, and the skin hemorrhage induced by this venom in mice. Antimicrobial activity against different bacteria was evaluated and the extract partially inhibited bacterial growth. Thus, taken together, A. integrifolia ethanolic extract has promising use as an antiophidic and antimicrobial.

An exploratory focus group study on experiences with snakebites: health-seeking behaviour and challenges in rural communities of Kenya.

BACKGROUND: Snakebite envenoming is a long-hidden public health threat in the rural communities of Kenya. This study aimed to shed light on the health-seeking behaviour of people bitten by snakes, views on prevention measures and community needs and the consequences for snakebite patients in these areas. METHODS: Six focus group interviews were conducted in communities in the Kajiado (n=3) and Kilifi (n=3) counties. RESULTS: Traditional first-aid practices such as the use of a tourniquet and/or cutting the wound, use of a black stone and a variety of other traditional remedies were common. Challenges with transportation to health facilities and inadequately resourced facilities complicated accessing medical care. Community members voiced a need to improve access to trained healthcare workers and snakebite treatments at health facilities. CONCLUSION: While communities had high trust in evidence-based medical care, traditional treatment was often sought, causing delays in timely medical attention. Traditional practices were often used in the home environment and these were not usually administered by a traditional healer. The findings illustrate the need to combine improving the availability of effective snakebite treatment and healthcare worker training on snakebite with community education to reduce the impact of snakebite.

Single-Arm, Multicenter Phase I/II Clinical Trial for the Treatment of Envenomings by Massive Africanized Honey Bee Stings Using the Unique Apilic Antivenom.

We evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach Africanized honeybee (Apis mellifera) Antivenom (AAV) in a phase I/II, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. Participants received 2 to 10 vials of AAV depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. The primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. Preliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. ELISA assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. Twenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m2 (median = 1.93 m2) were recruited. The number of stings ranged from 7 to > 2,000, with a median of 52.5. Symptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of AAV as per the protocol. None of the patients had late reactions (serum sickness) within 30 d of treatment. There was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. One patient had a moderate adverse event, transient itchy skin, and erythroderma. All participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. ELISA assays showed venom (melittin and PLA2) concentrations varying between 0.25 and 1.479 ng/mL prior to treatment. Venom levels decreased in all patients during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. Mass spectrometry showed melittin in eight participants, 30 d after treatment. Considering the promising safety results for this investigational product in the treatment of massive Africanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the AAV has shown to be safe for human use. Clinical Trial Registration: UTN: U1111-1160-7011, identifier [RBR-3fthf8].