Addressing the global challenge of snake envenoming
Authors: Geoffrey K Isbister, Anjana Silva
Journal: The Lancet (2018)

Joshua Longbottom and colleagues1Longbottom J Shearer FM Devine M et al.Vulnerability to snakebite envenoming: a global mapping of hotspots.Lancet. 2018; (published online July 12.)http://dx.doi.org/S0140-6736(18)31224-8Summary Full Text Full Text PDF PubMed Scopus (170) Google Scholar highlight once again that snake envenoming is a major health issue affecting remote and rural regions of the tropics. They use information about venomous snake distribution, health-care access, and availability of antivenom to identify the most vulnerable populations to snakebite. This modelling study1Longbottom J Shearer FM Devine M et al.Vulnerability to snakebite envenoming: a global mapping of hotspots.Lancet. 2018; (published online July 12.)http://dx.doi.org/S0140-6736(18)31224-8Summary Full Text Full Text PDF PubMed Scopus (170) Google Scholar reported in The Lancet identified about 92·66 million people living in regions vulnerable to snakebite, including sub-Saharan Africa, southeast Asia, and Indonesia. The major limitation of Longbottom and colleagues' study1Longbottom J Shearer FM Devine M et al.Vulnerability to snakebite envenoming: a global mapping of hotspots.Lancet. 2018; (published online July 12.)http://dx.doi.org/S0140-6736(18)31224-8Summary Full Text Full Text PDF PubMed Scopus (170) Google Scholar is that they do not report actual snakebites—making a number of assumptions, such as different venomous snakes and different human populations living together. This assumption results in the same risk of snake envenoming across different geographical regions, which is unlikely to be true. They also used a Nigerian retrospective observational study,2Habib AG Abubakar SB Factors affecting snakebite mortality in north-eastern Nigeria.Int Health. 2011; 3: 50-55Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar with more than 90% of bites from Echis ocellatus (saw-scaled viper), in which deaths are due to coagulopathy and bleeding, to estimate the effect of delay to antivenom on mortality. The effectiveness of antivenom is highly species specific and different for neurotoxic envenoming,3Silva A Maduwage K Sedgwick M et al.Neuromuscular effects of common krait (Bungarus caeruleus) envenoming in Sri Lanka.PLoS Negl Trop Dis. 2016; 10: e0004368Crossref PubMed Scopus (50) Google Scholar and cannot be administered early enough to prevent early prehospital deaths from cardiac arrest.4Johnston CI Ryan NM Page CB et al.The Australian snakebite project, 2005–2015 (ASP-20).Med J Aust. 2017; 207: 119-125Crossref PubMed Scopus (65) Google Scholar Reassuringly, Longbottom and colleagues identified the same geographical regions as did a previously published global study of snakebites, which reported between 421 000 and 1 841 000 additional envenomings occurring annually, and 20 000–94 000 deaths.5Kasturiratne A Wickremasinghe AR de Silva N et al.The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths.PLoS Med. 2008; 5: e218Crossref PubMed Scopus (1172) Google Scholar 15 years ago, Lalloo and colleagues6Lalloo DG Theakston RD Warrell DA The African challenge.Lancet. 2002; 359: 1527Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar called for the global health community's attention to the problem of snake envenoming in Africa, highlighting the high cost and paucity of antivenom and the socioeconomic burden of snake envenoming. They stated the urgent need for research on the burden and economic effect of snake envenoming, and the need to improve antivenom development and supply to Africa. What progress has been made since then? In 2017, WHO categorised snakebite as a high-priority neglected tropical disease, and in May, 2018, WHO resolved to decrease the morbidity and mortality of snake envenoming, and "coordinate global efforts to control snakebite". Although acute effects of snakebites are relatively well understood, morbidity and cost associated with long-term effects are poorly studied globally. Many snakebite survivors, once treated for acute illness, are never followed up. Recent research has provided good evidence for the psychological and economic burden of snakebite.7Williams SS Wijesinghe CA Jayamanne SF et al.Delayed psychological morbidity associated with snakebite envenoming.PLoS Negl Trop Dis. 2011; 5: e1255Crossref PubMed Scopus (75) Google Scholar For example, patients with snakebites in Sri Lanka have symptoms of depression and post-traumatic stress disorder, and 10% did not return to work,7Williams SS Wijesinghe CA Jayamanne SF et al.Delayed psychological morbidity associated with snakebite envenoming.PLoS Negl Trop Dis. 2011; 5: e1255Crossref PubMed Scopus (75) Google Scholar which is a substantial economic burden to the country. Antivenom was first developed in the 1890s, along with the tetanus vaccine. Vaccines have been one of the greatest successes in public health, resulting in the eradication of some diseases and substantial reductions in morbidity and mortality.8Koff WC Burton DR Johnson PR et al.Accelerating next-generation vaccine development for global disease prevention.Science. 2013; 340: 1232910Crossref PubMed Scopus (208) Google Scholar By contrast, there is a crisis in antivenom supply, and technology not dissimilar from early vaccines is still used to manufacture antivenom.9Wagstaff SC Laing GD Theakston RD Papaspyridis C Harrison RA Bioinformatics and multiepitope DNA immunization to design rational snake antivenom.PLoS Med. 2006; 3: e184Crossref PubMed Scopus (84) Google Scholar Human monoclonal antibodies are the future for cancer treatment,10Yang Y Cancer immunotherapy: harnessing the immune system to battle cancer.J Clin Invest. 2015; 125: 3335-3337Crossref PubMed Scopus (760) Google Scholar but poorly purified equine polyclonal antibodies to treat snake envenoming still exists with high rates of adverse reactions.11Stone SF Isbister GK Shahmy S et al.Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation.PLoS Negl Trop Dis. 2013; 7: e2326Crossref PubMed Scopus (65) Google Scholar There continues to be a paucity of evidence to support antivenom effectiveness for snake envenoming. This doesn't mean antivenoms are ineffective as they bind to snake toxins in vitro.12Maduwage K Buckley NA de Silva HJ Lalloo DG Isbister GK Snake antivenom for snake venom induced consumption coagulopathy.Cochrane Database Syst Rev. 2015; 6 (CD011428.)Google Scholar, 13Isbister GK Antivenom efficacy or effectiveness: the Australian experience.Toxicology. 2010; 268: 148-154Crossref PubMed Scopus (54) Google Scholar However, research must provide scientific and clinical trial evidence that antivenoms are clinically effective, because they can cause anaphylaxis and are expensive. More importantly, there is a need to identify for which snakes, what types of toxin effects, and what period of time antivenom will be effective. It is clear that the earlier antivenom is administered, the more effective it is in preventing toxin effects and potentially reversing some effects.2Habib AG Abubakar SB Factors affecting snakebite mortality in north-eastern Nigeria.Int Health. 2011; 3: 50-55Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 3Silva A Maduwage K Sedgwick M et al.Neuromuscular effects of common krait (Bungarus caeruleus) envenoming in Sri Lanka.PLoS Negl Trop Dis. 2016; 10: e0004368Crossref PubMed Scopus (50) Google Scholar To make early administration possible, there must be immediate access to antivenom, requiring increased production, and bedside diagnostic testing to identify envenomed patients. With training and standardisation, whole blood clotting testing appears to identify coagulopathy in 80% of viper-envenomed patients.14Ratnayake I Shihana F Dissanayake DM Buckley NA Maduwage K Isbister GK Performance of the 20-minute whole blood clotting test in detecting venom induced consumption coagulopathy from Russell's viper (Daboia russelii) bites.Thromb Haemost. 2017; 117: 500-507Crossref PubMed Scopus (29) Google Scholar Simpler tests with greater diagnostic accuracy, which can also identify all forms of envenoming (eg, neurotoxicity), are required. Testing for common snake enzyme activity is one potential way forward, and the almost ubiquitous group of snake toxins, phospholipase A2, might prove useful.15Maduwage K O'Leary MA Isbister GK Diagnosis of snake envenomation using a simple phospholipase A2 assay.Sci Rep. 2014; 4: 4827Crossref PubMed Scopus (30) Google Scholar 15 years on and progress is being made to improve the treatment of snake envenoming. As the Longbottom and colleagues' study confirms, there is a clearer picture of the most vulnerable regions and the overall social and economic burden. Going forward, there is a need to increase research efforts and funding into improved, safer, and more universally available antivenoms. Finally, research must also now focus on prevention of snakebite, a neglected aspect of decreasing snakebite burden. For the 71st World Health Assembly see http://www.who.int/news-room/detail/25-05-2018-seventy-first-worldhealth-assembly-update-25-may For the 71st World Health Assembly see http://www.who.int/news-room/detail/25-05-2018-seventy-first-worldhealth-assembly-update-25-may We declare no competing interests. Vulnerability to snakebite envenoming: a global mapping of hotspotsIdentifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. Full-Text PDF Open Access