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PLoS Neglected Tropical Diseases Apr 2024Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An estimated 1.2-5.5 million people are envenomed by snakebites annually. More than 125,000 of these bites are fatal, and 3-4 times as many results in disability/disfigurement. Despite its prevalence, collecting accurate epidemiological data on snakebite is challenging. This systematic review and meta-analysis collates global epidemiology data on snakebite morbidity and mortality.
METHODS
Medline, Embase, Cochrane and CINAHL Plus databases were searched for articles published between 2001-2022. Pooled incidence and mortality were obtained using random effects modelling, heterogeneity (I2) was tested, and sensitivity analyses performed. Newcastle-Ottawa Scale assessed study quality.
RESULTS
Out of the four databases, 5,312 articles were found. After removing duplicates, 3,953 articles were screened by title and abstract and 65 articles containing information on snakebite epidemiology, encompassing 663,460 snakebites, were selected for analysis. The people most at risk for snakebite were men (59%), engaged in agricultural labour (27.5%), and residing in rural areas (66.7%). More than half (57%) of the reported bites resulted in envenoming. Incidents occurred frequently in the summer season (38.5%), during daytime (56.7%), and bites were most often to the lower limb (56.4%). Envenoming severity was frequently mild (46.7%), treated in hospital (68.3%), and was treated with anti-venom (64.7%). The pooled global incidence and mortality was 69.4 /100,000 population (95%CI: 36.8 to 101.9) and 0.33/100,000 population (95%CI, 0.14 to 0.52) per year, respectively. Stratified by continents, Asia had the highest incidence of 130.7/100,000 population (95%CI: 48.3 to 213.1) while Europe has the lowest with 0.7/100,000 population (95%CI: -0.2 to 1.5). The highest mortality was reported in Asia at 0.96/100,000 population (95% CI: 0.22 to 1.70), and Africa 0.44/100,000 population (95%CI: -0.03 to 0.84). Incidence was highest among inhabitants of lower-middle-income countries 132.7/100,000 population (95%CI: 55.4 to 209.9) while mortality was highest in low-income countries at 0.85/100,000 population (95% CI: -0.06 to 2.31).
CONCLUSION
Incidence and mortality rates noted here highlight the global impact of snakebite and underscore the critical need to address the burden of snakebite envenoming. It also reveals that while reported snakebite incidence was higher in lower-middle-income countries, the burden of mortality was greatest among inhabitants of low-income countries, again emphasising the need for greater efforts to tackle this neglected tropical disease.
Topics: Male; Humans; Female; Snake Bites; Antivenins; Incidence; Asia; Prevalence
PubMed: 38574167
DOI: 10.1371/journal.pntd.0012080 -
PloS One 2023Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical...
BACKGROUND
Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to identify antivenoms' cross-neutralizing ability when clinical studies may not be considered ethical. Therefore, this study aimed to identify and summarize scattered evidence regarding the preclinical efficacy of antivenoms against Asian snakes.
METHODOLOGY/PRINCIPLE FINDINGS
In this systematic review, we searched for articles published until May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Preclinical studies that reported the available antivenoms' neutralizing ability against Asian snake lethality were included. Quality assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool and the adapted the Animal Research Reporting In Vivo Experiments guidelines. The availability of effective antivenoms against Asian snakes was analyzed by comparing data from included studies with snakebite-information and data platforms developed by the World Health Organization. Fifty-two studies were included. Most studies assessed the antivenom efficacy against snakes from Southeast Asia (58%), followed by South Asia (35%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability. Situation analyses of the availability of effective antivenoms in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Risk of bias assessment was limited in some domains because of unreported data.
CONCLUSIONS/SIGNIFICANCE
Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in novel antivenom development, especially in countries without local antivenom production. A database should be developed to aid the development of a snakebite-information system.
Topics: Animals; Antivenins; Snake Bites; Snakes; Sri Lanka; Asia, Eastern
PubMed: 37467278
DOI: 10.1371/journal.pone.0288723 -
Toxins Apr 2023Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to... (Review)
Review
Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.
Topics: Animals; Antivenins; Snakes; Scorpions; Insecta; Spiders; Snake Bites
PubMed: 37235348
DOI: 10.3390/toxins15050313 -
PLoS Neglected Tropical Diseases Feb 2023Snakebite envenoming is a serious and life-threatening medical condition that predominantly affects people living in rural communities across Africa, Asia, and Latin... (Meta-Analysis)
Meta-Analysis Review
Assessing knowledge and awareness regarding snakebite and management of snakebite envenoming in healthcare workers and the general population: A systematic review and meta-analysis.
BACKGROUND
Snakebite envenoming is a serious and life-threatening medical condition that predominantly affects people living in rural communities across Africa, Asia, and Latin America. As our climate changes, there is a growing concern that negative human-snake interactions will increase. Our ability to prevent and manage snakebite requires effective antivenoms as well as knowledge regarding the prevention and management of snakebite among healthcare workers and affected communities across the globe. This systematic review aims to assess existing levels of knowledge regarding snakebite prevention and management in both healthcare workers and affected communities.
METHODS
This review was conducted on studies reporting quantitative measurements to evaluate knowledge and practice regarding snakebite prevention and management published in major databases between 1 January 2000 and 31 December 2021. Random effects modelling was used to obtain the pooled proportion. Heterogeneity (I2) was tested, and sensitivity analyses performed.
RESULTS
Out of 3,697 records, 16 studies from 12 countries assessing 7,640 participants were included. Four of the studies were ranked as good quality studies, 9 as fair, and 3 as poor. This study results demonstrated that 56% of the study population answered the knowledge question correctly (95% CI 48% to 63%, p < 0.001). High heterogeneity was observed (I2 = 97.29%), with marginal publication bias (Egger's regression test, p = 0.0814). Participants had relatively higher knowledge concerning use of antivenom as preferred treatment, followed by snakebite prevention, knowledge of signs and symptoms of snakebite, knowledge of first-aid, and knowledge of treatment. Participants had lower knowledge relating to types of snakes and the identification of snakes.
CONCLUSION
Adequate knowledge about snakebites and its management among the general population and healthcare workers was 56%. Healthcare workers and communities across Asia showed higher relative knowledge compared to those in Africa and the Middle East. These data suggest that further education is needed in both the general population and among healthcare workers to ensure that appropriate preventative and patient management techniques are being utilised in snakebite endemic regions. Greater local awareness of the risks and appropriate management of snakebite is required to reduce the burden of snakebite mortality and morbidity.
Topics: Animals; Humans; Snake Bites; Snakes; Antivenins; Health Personnel; Africa
PubMed: 36757933
DOI: 10.1371/journal.pntd.0011048 -
Pharmaceutical Biology Dec 2022Snake 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...
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%). Pers. (Annonaceae), (L.) (Fabaceae), Baill. (Euphorbiaceae), E.Mey. ex Tul. (Phyllanthaceae), L. (Menispermaceae) and 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.
Topics: Antivenins; Ethnobotany; Medicine, Traditional; Phytotherapy; Plants, Medicinal; Snake Bites; Tanzania
PubMed: 36205572
DOI: 10.1080/13880209.2022.2123942 -
PLoS Neglected Tropical Diseases Aug 2021The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming.
METHODS AND FINDINGS
Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity.
CONCLUSIONS
In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.
Topics: Antivenins; Blood Coagulation; Blood Coagulation Tests; Fibrinogen; Humans; International Normalized Ratio; Sensitivity and Specificity; Snake Bites
PubMed: 34375338
DOI: 10.1371/journal.pntd.0009657 -
Frontiers in Immunology 2020There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological...
There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between toxicity tests and surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A), (d) coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity , (g) use of hens' eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more 'humane' protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new alternatives and more 'humane' experimental designs will emerge in this field.
Topics: Animals; Antivenins; Humans; In Vitro Techniques; Neutralization Tests; Snake Venoms
PubMed: 33505403
DOI: 10.3389/fimmu.2020.617429 -
PLoS Neglected Tropical Diseases Dec 2020Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication...
Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication of snakebite associated with acute kidney injury (AKI). Numerous treatments have been attempted based on limited evidence. We conducted a systematic review of TMA following snakebite using a pre-determined case definition of blood film red cell schistocytes or histologically diagnosed TMA. The search strategy included major electronic databases and grey literature. We present a descriptive synthesis for the outcomes of AKI, dialysis free survival (DFS), other end-organ damage, overall survival, and interventions with antivenom and therapeutic plasmapheresis (TPE). This study was prospectively registered with PROSPERO (CRD42019121436). Seventy-two studies reporting 351 cases were included, predominantly small observational studies. Heterogeneity for study selection, design, reporting and outcomes were observed. The commonest envenoming species were hump-nosed vipers (Hypnale spp.), Russell's viper (Daboia russelii) and Australian brown snakes (Pseudechis spp.). The prevalence of TMA was at least 5.4% in proven and probable Hypnale bites, and 10-15% of Australian elapid envenomings, AKI occurred in 94% (293/312) of TMA cases, excluding case reports. The majority of cases with AKI required dialysis. Included prospective and retrospective cohort studies reporting interventions and renal outcomes showed no evidence for benefit from antivenom or TPE with respect to DFS in dialysis dependant AKI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment for quality of accumulated evidence for interventions was low. The major complication of TMA following snakebite is AKI. AKI improves in most cases. We found no evidence to support benefit from antivenom in snakebite associated TMA, but antivenom remains the standard of care for snake envenoming. There was no evidence for benefit of TPE in snakebite associated TMA, so TPE cannot be recommended. The quality of accumulated evidence was low, highlighting a need for high quality larger studies.
Topics: Acute Kidney Injury; Animals; Antivenins; Australia; Female; Humans; Male; Plasmapheresis; Prevalence; Prospective Studies; Retrospective Studies; Daboia; Snake Bites; Thrombotic Microangiopathies; Viper Venoms
PubMed: 33290400
DOI: 10.1371/journal.pntd.0008936 -
PLoS Neglected Tropical Diseases Jun 2019Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality...
Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial.
BACKGROUND
Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa.
METHODOLOGY/PRINCIPAL FINDINGS
Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness.
CONCLUSIONS/SIGNIFICANCE
Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.
Topics: Africa South of the Sahara; Antivenins; Clinical Trials as Topic; Humans; Multicenter Studies as Topic; Snake Bites; Treatment Outcome
PubMed: 31233536
DOI: 10.1371/journal.pntd.0007551 -
Toxins Apr 2017Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results... (Review)
Review
Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of mild to moderate latrodectism is primarily supportive while severe cases have variously been treated with intravenous calcium, muscle relaxants, widow-spider antivenom and analgesic opioids. The object of this systematic review is to examine the literature on the clinical effectiveness of past and current treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched from 1946 to December 2016 to identify clinical studies on the treatment of latrodectism. Studies older than 40 years and not in English were not reviewed. There were only two full-publications and one abstract of placebo-controlled randomised trials on antivenom use for latrodectism. Another two randomised comparative trials compared the route of administration of antivenom for latrodectism. There were fourteen case series (including two abstracts), fourteen case reports and one letter investigating drug treatments for latrodectism with the majority of these also including antivenom for severe latrodectism. Antivenom with opioid analgesia is often the major treatment reported for latrodectism however; recent high quality evidence has cast doubt on the clinical effectiveness of this combination and suggests that other treatments need to be investigated.
Topics: Animals; Antivenins; Humans; Spider Bites; Treatment Outcome
PubMed: 28430165
DOI: 10.3390/toxins9040148