Anti-inflammatory, healing and antiophidic potential of Jatropha mollissima (Pohl) Baill. (Euphorbiaceae): From popular use to pharmaceutical formulation in gel.

Jatropha mollissima (Pohl) Baill. (Euphorbiaceae) is widely used in traditional medicine to treat inflammatory disorders. So, a topical gel containing the hydroethanolic extract of its leaves was developed and evaluated for its anti-inflammatory, wound healing, and antiophidic properties in mice. First, the chemical profile of different parts of the plant was characterized by liquid chromatography coupled to mass spectrometry (LC-MS) using molecular networking. In the leaf extract, 11 compounds were characterized, with a particular emphasis on the identification of flavonoids. The gel efficiently inhibited carrageenan-induced paw edema, as well as acute and chronic croton oil-induced ear edema models, thereby reducing inflammatory and oxidative parameters in inflamed tissues. Besides anti-inflammatory activity, the herbal gel showed significant wound healing activity. The edematogenic, hemorrhagic and dermonecrotic activities induced by Bothrops jararaca snake venom were effectively inhibited by the treatment with J. mollissima gel. The association with the herbal gel improved in up to 90% the efficacy of commercial snake antivenom in reduce venom-induced edema. Additionally, while antivenom was not able to inhibit venom-induced dermonecrosis, treatment with herbal gel reduced in 55% the dermonocrotic halo produced. These results demonstrate the pharmacological potential of the herbal gel containing J. mollissima extract, which could be a strong candidate for the development of herbal products that can be used to complement the current antivenom therapy against snake venom local toxicity.

Phytochemical characterization and phospholipase A2 inhibitory effect of Vitex negundo L. root extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Snake bites are a critical health issue in many parts of the world particularly in Asian countries lacking efficient health facilities in rural areas. Cobra is the most common snake type in Asia and is responsible for a large number of mortalities particularly in rural areas. Plants are usually considered the most effective and easy-to-approach treatment for snake bites in rural areas of various countries. Vitex negundo L. is an important medicinal plant traditionally used to treat snake bite envenomation in many countries of Asia. AIM OF THE STUDY: From literature survey of plants traditionally used in the treatment of snake bites in Asian countries including India, Pakistan and Sri Lanka, roots of V. negundo were selected for the present study. Anti-snake venom potential of its roots was assessed through various in vitro assays targeting the phospholipase A2 enzyme. MATERIALS AND METHODS: V. negundo roots were sequentially extracted in different organic solvents to get fractions and in methanol to get total extract. The extracts were evaluated for phospholipase A2 (PLA2) inhibitory potential through inhibition of venom-induced hemolysis, ADP-induced platelet aggregation, PLA2-induced fatty acid hydrolysis and anticoagulant effect of cobra venom. Antioxidant power was determined using DPPH and superoxide radical scavenging assays. GC-MS and HPLC analysis was performed for the total methanol extract. RESULTS: Strong PLA2 inhibitory effect was observed for all the extracts. The ethyl acetate, acetone and methanol fractions significantly inhibited toxic effects of cobra venom under in vitro conditions. Radical scavenging potential of these fractions was also significantly high as compared to non-polar fractions in both DPPH and superoxide scavenging assays. Phytochemical analysis indicated high phenolic and flavonoid contents in these fractions. GC-MS and HPLC analysis of total methanol extract confirmed the presence of bis(2-ethylhexyl) phthalate, phenol, o-Guaiacol, palmitic acid-methyl ester, methyl stearate, quercetin and kaempferol in the plant. CONCLUSION: The study concluded that the roots of V. negundo, particularly their polar extracts, have strong PLA2 inhibitory effect against cobra venom confirming their traditional use to manage snake bites. The roots of this plant can be further studied for isolation of plant-based antisera.

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox: A Randomized Clinical Trial.

Importance: Bothrops venom acts almost immediately at the bite site and causes tissue damage. Objective: To investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations. Design, Setting, and Participants: This was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022. Intervention: The intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point. Main Outcomes and Measures: Feasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients' acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients' discharge. P values for outcomes were adjusted with Bonferroni correction. Results: A total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P < .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed. Conclusions and Relevance: The data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-4qw4vf.

Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors.

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.

"I sold my towel and shoes to pay the traditional healer": Care-seeking costs and productivity losses among snakebite victims in Eastern Province, Rwanda.

Snakebite envenomation (SBE) is endemic to sub-Saharan Africa and generally over-represented in rural, remote, and impoverished agricultural communities. While poverty is an established risk factor, little research has been done to investigate the economic consequences of SBE. This cross-sectional, quantitative study aimed to measure out-of-pocket spending and lost income when a household member was bitten by a snake. In 2020, 732 snakebite survivors from Eastern Province (Rwanda) agreed to complete a survey administered by telephone. The survey focused on participant demographics, income, direct medical and non-medical costs, care-seeking decisions, and lost work during convalescence. Our results suggested that patients incurred the highest mean expenses when they sought care from hospitals (11 307 RWF or 12 USD) or traditional healers (5 836 RWF or 6 USD) but that the highest maximum cost was incurred from traditional healers (300 000 RWF or 313 USD). Across all victims, the total amount paid to traditional healers (3.4 million RWF or 3 537 USD) was 4.7 times higher than all other care providers combined. On average, families lost 111 814 RWF (117 USD) per snakebite in direct treatment costs and indirect productivity losses. Many victims sought care from traditional healers despite being eligible for free medical care. Altogether, this study serves as a reminder of the serious physical and financial consequences associated with SBE and provides justification for new investments into SBE prevention and care.

Empowering Health care Systems and Communities for Snakebite Envenoming Control in India.

Snakebite envenoming (SBE) is a global health challenge, predominantly affecting economically disadvantaged regions. India contributes significantly to global snakebite mortality. Since 2013, the Indian Council of Medical Research (ICMR) has spearheaded efforts to combat SBE. A multi-sectoral engagement in the snakebite research projects and inputs from communities, traditional healers, and the health system have led to the creation of an Information Education and Communication (IEC) material suite, including management flowchart, information booklets, posters, and brochures, all available in local languages. These resources were broadly disseminated in high-burden regions in Maharashtra and Odisha, resulting in an approximately 10% increase in case reporting within a year. This holistic approach, engaging diverse stakeholders and addressing multiple facets of SBE, offers promise for alleviating the snakebite burden, not only in India but also in other low- and middle-income countries across South Asia, Africa, and South America, holding potential for broader positive global impact.

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.

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

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

Effects of Mauritia flexuosa L. f. buriti oil on symptoms induced by Bothrops moojeni snake envenomation.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, there are species of snakes that become involved in accidents and cause serious health problems to the inhabitants, highlighting the genus Bothrops for being responsible for approximately 90% of accidents reported annually. In the northern region of the country, this genus is responsible for the largest number of accidents, especially among rural dwellers. These populations invest in alternative treatments for with the purpose of improving the symptoms caused by snakebites. The species Mauritia flexuosa L. f., known as buriti, is traditionally used for the treatment of envenomation by snakes. AIM OF THE STUDY: This study aimed to evaluate the antiophidic potential of the oil of Mauritia flexuosa L. f. for Bothrops moojeni H. venom, confronting cultural and scientific knowledge. MATERIALS AND METHODS: The physicochemical properties were determined, and the components present in the oil, extracted from fruit pulp, were analyzed by Gas Chromatography Coupled with Mass Spectrometry. The in vitro inhibitory capacity of the oil for phospholipase, metalloprotease and serine protease activities was investigated. In the in vivo studies, male Swiss mice were used to evaluate the effect of oil on lethality and toxicity, and hemorrhagic, myotoxic and edematogenic activities were assessed. RESULTS: GC‒MS analysis identification of 90.95% of the constituents of the oil, with the main components being 9-eicosenoic acid, (Z)- (34.54%), n-hexadecanoic acid (25.55%) and (E)-9-octadecenoic acid ethyl ester (12.43%). For the substrates, the outcomes indicate that the oil inhibited the activity of the main classes of toxins present in Bothrops moojeni H. venom (VBm) at the highest dose tested (0.5 µL), with inhibition of 84% for the hydrolysis of the selective substrate for serine protease and inhibition of 60% for the hydrolysis of substrates for PLA2 and metalloproteases. The antiophidic activity in vivo was evaluated with two concentrations of the oil: 1.5 mg, the dosage the population, diluted in mineral oil to a volume of 1 tablespoon and 15 mg, administered by gavage 30 min before poisoning and at time zero (concomitant to poisoning), and both concentrations administered by gavage in combination with topical use at time zero. The bleeding time in the group treated with oil at a concentration of 15 mg administered at time zero was significantly lower than that in the control group (p < 0.05). However, a greater inhibition of bleeding time was observed when local application was combined with the gavage treatment at both concentrations tested at time zero (p < 0.05). In the myotoxicity test, oil was efficient in reducing the myotoxic effects induced by the venom at the two concentrations tested, with gavage administration at time zero and gavage plus topical administration at time zero (p < 0.05). CONCLUSIONS: The data obtained show that the oil is safe to use at the concentrations studied and contains fatty acids that may collaborate for cellular-level repair of the injuries caused by Bm poisoning. The in vitro and in vivo experiments showed that oil inhibits the main proteolytic enzymes present in the venom and that it has important activities to control the local effects caused by bothropic venom.

Anti-Metalloproteases: Production and Characterization of Polyclonal IgG Anti-F2 Fraction Antibodies Purified from the Venom of the Snake Bitis arietans.

Bitis arietans is a medically important snake found in Sub-Saharan Africa. The envenomation is characterized by local and systemic effects, and the lack of antivenoms aggravates the treatment. This study aimed to identify venom toxins and develop antitoxins. The F2 fraction obtained from Bitis arietans venom (BaV) demonstrated the presence of several proteins in its composition, including metalloproteases. Titration assays carried out together with the immunization of mice demonstrated the development of anti-F2 fraction antibodies by the animals. The determination of the affinity of antibodies against different Bitis venoms was evaluated, revealing that only BaV had peptides recognized by anti-F2 fraction antibodies. In vivo analyses demonstrated the hemorrhagic capacity of the venom and the effectiveness of the antibodies in inhibiting up to 80% of the hemorrhage and 0% of the lethality caused by BaV. Together, the data indicate: (1) the prevalence of proteins that influence hemostasis and envenomation; (2) the effectiveness of antibodies in inhibiting specific activities of BaV; and (3) isolation and characterization of toxins can become crucial steps in the development of new alternative treatments. Thus, the results obtained help in understanding the envenoming mechanism and may be useful for the study of new complementary therapies.

Risks of snakebite and challenges to seeking and providing treatment for agro-pastoral communities in Tanzania.

BACKGROUND: Continuous occurrence of snakebite incidences and the vulnerability of some communities remain a critical problem in sub-Saharan Africa. Despite causing permanent disability to almost half a million people annually and numerous deaths, snakebite and associated complications are still largely neglected. This study aimed at elucidating risk factors associated with snakebite cases, treatment availability and case management practices for vulnerable agro-pastoralist communities in Northern Tanzania. METHODS: Data was collected in the Monduli (Arusha region) and the Simanjiro (Manyara region) districts in Tanzania. Interviews with 101 snakebite victims or their guardians and 13 health professionals from 3 health centers in the districts were conducted. Additionally, case records of patients admitted between 2007 and 2019 to the Meserani Snakebite Clinic were obtained. RESULTS: This study showed that appropriate treatment for snakebite including anti-venom, is difficult to access and that snakebite incidences were significantly linked to factors such as gender, age, socio-economic activity, season of the year, and whether being at home or out in the fields. Anti-venom and trained health professionals were only available at the Meserani Snake Park Clinic. Men were bitten most often (χ2 = 62.08, df = 4, p-value < 0.0001). Overall, adults between the ages of 18 and 60 years (χ2 = 62.08, df = 4, p-value < 0.0001) received most bites, usually while outdoors herding cattle in the dry season. A significant majority of victims looked for traditional treatment first (52.7%, χ2 = 29.541, df = 2, p-value = 0.0001). The results of this study present crucial information on what is needed to improve the accessibility to appropriate treatment after a snakebite among agro-pastoral communities. CONCLUSION: The situation regarding morbidity and mortality due to the inaccessibility of common treatment for snakebite in northern Tanzania is challenging. Reliance on traditional medicine exacerbates the situation. There is dire need to involve affected communities, researchers, the government, clinicians and the public in general, to work together and take part in the global snakebite initiative. Communities and health professionals recognise the underlying challenges and have valuable suggestions on how to improve the situation.

A generalized framework for estimating snakebite underreporting using statistical models: A study in Colombia.

BACKGROUND: Snakebite envenoming is a neglected tropical disease affecting deprived populations, and its burden is underestimated in some regions where patients prefer using traditional medicine, case reporting systems are deficient, or health systems are inaccessible to at-risk populations. Thus, the development of strategies to optimize disease management is a major challenge. We propose a framework that can be used to estimate total snakebite incidence at a fine political scale. METHODOLOGY/PRINCIPAL FINDINGS: First, we generated fine-scale snakebite risk maps based on the distribution of venomous snakes in Colombia. We then used a generalized mixed-effect model that estimates total snakebite incidence based on risk maps, poverty, and travel time to the nearest medical center. Finally, we calibrated our model with snakebite data in Colombia from 2010 to 2019 using the Markov-chain-Monte-Carlo algorithm. Our results suggest that 10.19% of total snakebite cases (532.26 yearly envenomings) are not reported and these snakebite victims do not seek medical attention, and that populations in the Orinoco and Amazonian regions are the most at-risk and show the highest percentage of underreporting. We also found that variables such as precipitation of the driest month and mean temperature of the warmest quarter influences the suitability of environments for venomous snakes rather than absolute temperature or rainfall. CONCLUSIONS/SIGNIFICANCE: Our framework permits snakebite underreporting to be estimated using data on snakebite incidence and surveillance, presence locations for the most medically significant venomous snake species, and openly available information on population size, poverty, climate, land cover, roads, and the locations of medical centers. Thus, our algorithm could be used in other countries to estimate total snakebite incidence and improve disease management strategies; however, this framework does not serve as a replacement for a surveillance system, which should be made a priority in countries facing similar public health challenges.

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.

Morbidity survey of the history of snakebites in different communities in the alto Juruá, western Brazilian Amazon.

The Alto Juruá region has a rich diversity of venomous snakes, and snakebites represent an important cause of morbidity. The present study was carried out in five communities in the Alto Juruá region, and aimed to evaluate the history of snakebites in terms of which snakes were involved and what was the victims' conduct in relation to first aid and prevention. Between 2017 and 2019, semi-structured interviews were applied to 260 residents, 56 (21.53%) of whom had a history of snakebites. The profile of the victims is 73.2% male, a resident of rural areas who develops activities mainly in agriculture and extractivism and who has a low level of education. Just over half of the snakebites occurred during the rainy season (52.8%) and the majority during the day (77%). Bothrops bites were the most frequently reported (90.3%) and B. atrox was the most mentioned snake (jararaca and surucucu) for being responsible for snakebites (80.8%). Approximately 87.5% of the bites occurred to the lower limbs, and 48.2% of the victims were barefoot at the time of the bite. Inadequate first-aid procedures were reported, such as using tourniquets and consuming the drink known as "Específico Pessoa", not drinking water, and treatment with traditional therapy (phytotherapics, zootherapeutics and faith healers), as well as not seeking hospital care. Thus, the need to facilitate access to hospital units in these communities and health education (prevention and first aid) are essential in order to minimize this situation.

Pre-clinical efficacy of African medicinal plants used in the treatment of snakebite envenoming: A systematic review.

The World Health Organization has listed Snakebite Envenoming (SBE) as a priority neglected tropical disease, with a worldwide annual snakebite affecting 5.4 million people and injuring 2.7 million lives. In many parts of rural areas of Africa and Asia, medicinal plants have been used as alternatives to conventional antisnake venom (ASV) due in part to inaccessibility to hospitals. Systemic reviews (SR) of laboratory-based preclinical studies play an essential role in drug discovery. We conducted an SR to evaluate the relationship between interventional medicinal plants and their observed effects on venom-induced experiments. This SR was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Modified collaborative approach to meta-analysis and review of animal data from experimental studies (CAMARADES) and SYRCLE's risk of bias tools were used to appraise the included studies. Data were searched online in Medline via PubMed, Embase via OVID, and Scopus. Studies reporting in vivo and in vitro pharmacological activities of African medicinal plants/extracts/constituents against venom-induced pathologies were identified and included for screening. Data from the included studies were extracted and synthesized. Ten studies reported statistically significant percentage protection (40-100%) of animals against venom-induced lethality compared with control groups that received no medicinal plant intervention. Sixteen studies reported significant effects (p ≤ 0.05) against venom-induced pathologies compared with the control group; these include hemolytic, histopathologic, necrotic, and anti-enzymatic effects. The plant family Fabaceae has the highest number of studies reporting its efficacy, followed by Annonaceae, Malvaceae, Combretaceae, Sterculiaceae, and Olacaceae. Some African medicinal plants are preclinically effective against venom-induced lethality, hematotoxicity, and cytotoxicity. The evidence was extracted from three in vitro studies, nine in vivo studies, and five studies that combined both in vivo and in vitro models. The effective plants belong to the Fabaceae family, followed by Malvaceae, and Annonaceae.

Attitudes, knowledge and practices of traditional snakebite healers in Nepal: implications for prevention and control of snakebite.

BACKGROUND: Traditional healers are a valuable source of information about community-level treatment of snakebite. Snakebite victims in Nepal depend on traditional healers for treatment, but their practices have not been well-documented. METHODS: This was a cross-sectional study of 50 traditional snakebite healers (TSHs) who were selected using a snowball sampling method representing eight districts and four provinces of Nepal. Data were collected using face-to-face-interviews and semi-structured questionnaires. RESULTS: About half of the respondents liked to gain knowledge on modern care for snakebite management and nearly all respondents (94%) wished to cooperate closely with the local healthcare system to support snakebite management. People's ingrained faith in traditional healing of snakebite (84%), unaffordable modern care of snakebite (60%) and wishes for early treatment of snakebites (44-48%) were the main causes of their dependency on TSHs. Rauvolfia serpentina, Piper nigrum, Momordica charantia and Tinospora cordifolia were commonly used plants in traditional treatment of snakebite. CONCLUSIONS: Easily accessible and affordable healthcare facilities provided by TSHs, public beliefs in traditional healing and inadequate knowledge of antivenom therapy caused dependency on TSHs. The introduction of snakebite treatment centres in snakebite-prone regions and educational interventions are essential to minimize this kind of dependency and associated deaths and disabilities.

Snakebite incidence in rural sub-Saharan Africa might be severely underestimated.

Snakebites in sub-Saharan Africa account for 20,000 to 32,000 annual deaths. But since most data is retrieved from hospital or incomplete central databases, and many victims do not seek hospital treatment or prefer traditional remedies, the current numbers are likely underestimated. In order to reduce snakebite incidence by 50% by 2030 as targeted by World Health Organization, it is crucial to accurately quantify and understand the current rates of snakebite incidence, which can only be reliably measured through household surveys. In this study, we interviewed 1037 households in nine communities in Cabo Delgado, northern Mozambique. Our aim was to quantify true snakebite incidence and under-reporting, by comparing the total number of snakebites reported to our team during household surveys with the subset of reports that reached health centers. We additionally quantified snakebite incidence in terms of species, location of the attack, type of treatment, season, and gender of the victims. These data allow us to propose conservative extrapolations of snakebite incidence and mortality for the province of Cabo Delgado and for Mozambique. Of all snakebites reported in the surveys (N = 296), most incidents were treated exclusively by traditional doctors (N = 174; 59%) and 25% were not seen by any doctor. Most bites occurred on farms and during the rainy season. Using a conservative estimation where we assume our results to be extrapolatable for the whole of rural Mozambique, but considering snakebites in urban areas to be inexistent, we propose that in Cabo Delgado, every year at least 6124 people are victims of snakebites, of which at least 791 result in deaths. In Mozambique, we extrapolated that every year at least 69,261 people are victims of snakebite, of which at least 8950 result in death (one in eight snakebites is fatal). Our estimates are the first for Mozambique based on data retrieved in the country, and despite being an underestimation they increase snakebite incidence levels ten-fold and the number of deaths by 30-fold. Urgent and widespread surveys are needed to further assess the full extent of snakebites in sub-Saharan Africa, explore regional patterns and develop mitigation plans.

Ethnomedicinal plants used for treatment of snakebites in Tanzania - a systematic review.

CONTEXT: Snake envenomation is one of the neglected health problems in Tanzania. Since most people, especially in rural areas, suffer from its burden, their cases are not documented due to reliance on medicinal plants. Despite the pivotal role of medicinal plants in treating snakebites, there is a paucity of information. OBJECTIVE: This review documents medicinal plants used to treat snakebites in Tanzania. MATERIALS AND METHODS: A systematic search using electronic databases such as PubMed, Google Scholar, Scopus, Science Direct and grey literature was conducted to retrieve relevant information on medicinal plants used to treat snakebites in Tanzania. The review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The obtained information from 19 published articles was organized and analysed based on citation frequency. RESULTS: A total of 109 plant species belonging to 49 families are used as snakebite antivenom in Tanzania. Fabaceae had the highest number of medicinal plants (19.3%). The dominant plant growth forms were trees (35%) and shrubs (33%). Roots were the most frequently used plant part (54%), followed by leaves (26%) and bark (11%). Annona senegalensis Pers. (Annonaceae), Dichrostachys cinerea (L.) (Fabaceae), Suregada zanzibariensis Baill. (Euphorbiaceae), Antidesma venosum E.Mey. ex Tul. (Phyllanthaceae), Cissampelos pareira L. (Menispermaceae) and Dalbergia melanoxylon Guill. & Perr. (Fabaceae) were the most cited medicinal plants. CONCLUSIONS: Tanzania has diverse plants used for snakebite treatment; a few have been analysed for their bioactive components. Further study of the phytochemicals may provide scientific information to develop snakebite drugs.

Topical gel containing phenolic-rich extract from Ipomoea pes-capre leaf (Convolvulaceae) has anti-inflammatory, wound healing, and antiophidic properties.

The growing use of phytotherapy in clinical practice arouses interest in studies using medicinal plants as active ingredients for new medicines. Ipomoea pes-caprae has a wide medicinal use in the treatment of inflammatory disorders, skin wounds, stings, and painful rheumatic processes. Assayed in this study are the physicochemical characterization of a gel developed with this extract and the evaluation of its anti-inflammatory and healing efficacy, in addition to its antiedematogenic action on Bothrops snake envenoming in mice. The qualitative and quantitative analyses of the hydroethanolic extract by mass spectrometry showed 18 phenolic compounds, highlighting a high content of chlorogenic acid (0.92 µg/g), neochlorogenic acid (6.07 µg/g), and isochlorogenic acid (0.80 µg/g) compounds. The formulation was stable in relation to the physical-chemical characteristics during the time of analysis and was considered safe for topical treatment in animals, causing no skin irritation. Although the results have shown an absence of activity in the model of ear edema induced by croton oil (acute inflammation), the herbal gel efficiently inhibited carrageenan paw edema and chronic ear edema induced by multiple applications of croton oil, which may indicate the possible performance under the kinin pathway such as bradykinin, histamine, and serotonin. Wound healing in the group treated with the I. pes-caprae gel was accelerated compared with the placebo group, also confirmed through histological data. Edema induced by Bothrops erythromelas snake venom was efficiently reduced in the treatment with I. pes-caprae gel associated with the antibothropic-crotalic serum, whereas the antivenom alone was not effective. This approach presents a promising formulation based on I. pes-caprae with potential therapeutic use for inflammatory disorders.