Calvete, J. J. Proteomic tools against the neglected pathology of snake bite envenoming. Expert Rev. Proteomics 8, 739–758 (2011).
Warrell, D. A. Snake bite. Lancet 375, 77–88 (2010).
Pyron, R., Burbrink, F. T. & Wiens, J. J. A phylogeny and revised classification of Squamata, including 4161 species of lizards and snakes. BMC Evol. Biol. 13, 93 (2013).
Hsiang, A. Y. et al. The origin of snakes: revealing the ecology, behavior, and evolutionary history of early snakes using genomics, phenomics, and the fossil record. BMC Evol. Biol. 15, 87 (2015).
Chippaux, J. P. Snake-bites: appraisal of the global situation. Bull. World Health Organ. 76, 515–524 (1998).
Mohapatra, B. et al. Snakebite mortality in India: a nationally representative mortality survey. PLoS Negl. Trop. Dis. 5, e1018 (2011). This nationally representative study of snakebite mortality in India demonstrates that the magnitude of the problem in terms of mortality is much higher than previously thought.
Chippaux, J.-P. Estimate of the burden of snakebites in sub-Saharan Africa: a meta-analytic approach. Toxicon 57, 586–599 (2011).
Gutiérrez, J. M., Williams, D., Fan, H. W. & Warrell, D. A. Snakebite envenoming from a global perspective: towards an integrated approach. Toxicon 56, 1223–1235 (2010).
Gutiérrez, J. M., Theakston, R. D. G. & Warrell, D. A. Confronting the neglected problem of snake bite envenoming: the need for a global partnership. PLoS Med. 3, e150 (2006).
Williams, D. et al. The Global Snake Bite Initiative: an antidote for snake bite. Lancet 375, 89–91 (2010). This paper describes the launch of the first organization to confront snakebite envenoming from a global perspective.
Harrison, R. A., Hargreaves, A., Wagstaff, S. C., Faragher, B. & Lalloo, D. G. Snake envenoming: a disease of poverty. PLoS Negl. Trop. Dis. 3, e569 (2009). This study highlights the relationship between snakebite envenoming and poverty.
Kasturiratne, A. et al. The global burden of snakebite a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med. 5, e218 (2008).
Habib, A. G. et al. Snakebite is under appreciated: appraisal of burden from West Africa. PLoS Negl. Trop. Dis. 9, e0004088 (2015). This study analyses the impact of snakebite envenoming in terms of disability-adjusted life years in 16 countries in West Africa.
Alirol, E., Sharma, S. K., Bawaskar, H. S., Kuch, U. & Chappuis, F. Snake bite in South Asia: a review. PLoS Negl. Trop. Dis. 4, e603 (2010).
Sankar, J., Nabeel, R., Sankar, M. J., Priyambada, L. & Mahadevan, S. Factors affecting outcome in children with snake envenomation: a prospective observational study. Arch. Dis. Child. 98, 596–601 (2013).
Stahel, E. Epidemiological aspects of snake bites on a Liberian rubber plantation. Acta Trop. 37, 367–374 (1980).
Warrell, D. A. et al. Randomized comparative trial of three monospecific antivenoms for bites by the Malayan pit viper (Calloselasma rhodostoma) in southern Thailand: clinical and laboratory correlations. Am. J. Trop. Med. Hyg. 35, 1235–1247 (1986).
Pierini, S. V., Warrell, D. A., De Paulo, A. & Theakston, R. D. G. High incidence of bites and stings by snakes and other animals among rubber tappers and Amazonian Indians of the Juruá Valley, Acre State, Brazil. Toxicon 34, 225–236 (1996).
Warrell, D. A. in Venomous Reptiles of the Western Hemisphere (eds Campbell, J. R. & Lamar, W. W.) 709–761 (Cornell Univ. Press, 2004).
Myint-Lwin et al. Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment. Lancet 326, 1259–1264 (1985).
Habib, A. G. et al. Envenoming after carpet viper (Echis ocellatus) bite during pregnancy: timely use of effective antivenom improves maternal and foetal outcomes. Trop. Med. Int. Health 13, 1172–1175 (2008).
Warrell, D. A. & Arnett, C. The importance of bites by the saw-scaled or carpet viper (Echis carinatus): epidemiological studies in Nigeria and a review of the world literature. Acta Trop. 33, 307–341 (1976).
Williams, D., Jensen, S., Nimorakiotakis, B. & Winkel, K. D. Venomous Bites and Stings in Papua New Guinea (Australian Venom Research Unit, 2005).
Warrell, D. A. & Ormerod, L. D. Snake venom ophthalmia and blindness caused by the spitting cobra (Naja nigricollis) in Nigeria. Am. J. Trop. Med. Hyg. 25, 525–529 (1976).
Smith, J. et al. Malignancy in chronic ulcers and scars of the leg (Marjolin's ulcer): a study of 21 patients. Skeletal Radiol. 30, 331–337 (2001).
Williams, S. S. et al. Delayed psychological morbidity associated with snakebite envenoming. PLoS Negl. Trop. Dis. 5, e1255 (2011).
GBD 2013 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: quantifying the epidemiological transition. Lancet 386, 2145–2191 (2015).
Fry, B. G. et al. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu. Rev. Genomics Hum. Genet. 10, 483–511 (2009).
Daltry, J. C., Wüster, W. & Thorpe, R. S. Diet and snake venom evolution. Nature 379, 537–540 (1996).
Chippaux, J.-P., Williams, V. & White, J. Snake venom variability: methods of study, results and interpretation. Toxicon 29, 1279–1303 (1991).
Olivera, B. M. Conus peptides: biodiversity-based discovery and exogenomics. J. Biol. Chem. 281, 31173–31177 (2006).
Durban, J. et al. Integrated ‘omics’ profiling indicates that miRNAs are modulators of the ontogenetic venom composition shift in the Central American rattlesnake, Crotalus simus simus. BMC Genomics 14, 234 (2013).
Casewell, N. R. et al. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. Proc. Natl Acad. Sci. USA 111, 9205–9210 (2014).
Sanz, L. & Calvete, J. Insights into the evolution of a snake venom multi-gene family from the genomic organization of Echis ocellatus SVMP genes. Toxins (Basel) 8, E216 (2016).
Dowell, N. L. et al. The deep origin and recent loss of venom toxin genes in rattlesnakes. Curr. Biol. 26, 2434–2445 (2016).
Calvete, J. J. Venomics: integrative venom proteomics and beyond. Biochem. J. 474, 611–634 (2017). A comprehensive review of the complexity of snake venoms and the biological and medical implications of this complexity.
Reeks, T. A., Fry, B. G. & Alewood, P. F. Privileged frameworks from snake venom. Cell. Mol. Life Sci. 72, 1939–1958 (2015).
Doley, R. & Kini, R. M. Protein complexes in snake venom. Cell. Mol. Life Sci. 66, 2851–2871 (2009).
Vonk, F. J. et al. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. Proc. Natl Acad. Sci. USA 110, 20651–20656 (2013).
Calvete, J. J. Snake venomics: from the inventory of toxins to biology. Toxicon 75, 44–62 (2013).
Rokyta, D. R., Wray, K. P., McGivern, J. J. & Margres, M. J. The transcriptomic and proteomic basis for the evolution of a novel venom phenotype within the timber rattlesnake (Crotalus horridus). Toxicon 98, 34–48 (2015).
Brahma, R. K., McCleary, R. J. R., Kini, R. M. & Doley, R. Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes. Toxicon 93, 1–10 (2015).
Pla, D., Gutiérrez, J. M. & Calvete, J. J. Second generation antivenomics: comparing immunoaffinity and immunodepletion protocols. Toxicon 60, 213–214 (2012).
Gutiérrez, J. M. et al. Assessing the preclinical efficacy of antivenoms: from the lethality neutralization assay to antivenomics. Toxicon 69, 168–179 (2013).
Dixon, R. W. & Harris, J. B. Myotoxic activity of the toxic phospholipase, notexin, from the venom of the Australian tiger snake. J. Neuropathol. Exp. Neurol. 55, 1230–1237 (1996).
Montecucco, C., Gutiérrez, J. M. & Lomonte, B. Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action. Cell. Mol. Life Sci. 65, 2897–2912 (2008). This paper reviews the mechanisms by which venom PLA2s induce myotoxicity and neurotoxicity.
Gutiérrez, J. M. & Ownby, C. L. Skeletal muscle degeneration induced by venom phospholipases A2: insights into the mechanisms of local and systemic myotoxicity. Toxicon 42, 915–931 (2003).
Gutiérrez, J. M., Rucavado, A., Chaves, F., Díaz, C. & Escalante, T. Experimental pathology of local tissue damage induced by Bothrops asper snake venom. Toxicon 54, 958–975 (2009).
Hernández, R. et al. Poor regenerative outcome after skeletal muscle necrosis induced by Bothrops asper venom: alterations in microvasculature and nerves. PLoS ONE 6, e19834 (2011).
Escalante, T., Rucavado, A., Fox, J. W. & Gutiérrez, J. M. Key events in microvascular damage induced by snake venom hemorrhagic metalloproteinases. J. Proteomics 74, 1781–1794 (2011). This review summarizes the mechanisms by which zinc-dependent SVMPs induce microvascular damage and haemorrhage.
Seo, T. et al. Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which disrupts cell–cell adhesions in vitro and induces haemorrhage in vivo. FEBS J. 284, 1657–1671 (2017).
Gutiérrez, J., Escalante, T., Rucavado, A., Herrera, C. & Fox, J. A comprehensive view of the structural and functional alterations of extracellular matrix by snake venom metalloproteinases (SVMPs): novel perspectives on the pathophysiology of envenoming. Toxins (Basel) 8, 304 (2016).
Jiménez, N., Escalante, T., Gutiérrez, J. M. & Rucavado, A. Skin pathology induced by snake venom metalloproteinase: acute damage, revascularization, and re-epithelization in a mouse ear model. J. Invest. Dermatol. 128, 2421–2428 (2008).
Rivel, M. et al. Pathogenesis of dermonecrosis induced by venom of the spitting cobra. Naja nigricollis: an experimental study in mice. Toxicon 119, 171–179 (2016).
Dubovskii, P. V. & Utkin, Y. N. Cobra cytotoxins: structural organization and antibacterial activity. Acta Naturae 6, 11–18 (2014).
Mora, J., Mora, R., Lomonte, B. & Gutiérrez, J. M. Effects of Bothrops asper snake venom on lymphatic vessels: insights into a hidden aspect of envenomation. PLoS Negl. Trop. Dis. 2, e318 (2008).
Teixeira, C., Cury, Y., Moreira, V., Picolo, G. & Chaves, F. Inflammation induced by Bothrops asper venom. Toxicon 54, 988–997 (2009).
Rucavado, A. et al. Viperid envenomation wound exudate contributes to increased vascular permeability via a DAMPs/TLR-4 mediated pathway. Toxins (Basel) 8, 349 (2016).
Zhang, C., Medzihradszky, K. F., Sánchez, E. E., Basbaum, A. I. & Julius, D. Lys49 myotoxin from the Brazilian lancehead pit viper elicits pain through regulated ATP release. Proc. Natl Acad. Sci. USA 114, E2524–E2532 (2017).
Barber, C. M., Isbister, G. K. & Hodgson, W. C. Alpha neurotoxins. Toxicon 66, 47–58 (2013).
Rossetto, O. & Montecucco, C. Presynaptic neurotoxins with enzymatic activities. Handb. Exp. Pharmacol. 184, 129–170 (2008).
Pungercar, J. & Križaj, I. Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A2. Toxicon 50, 871–892 (2007).
Paoli, M. et al. Mass spectrometry analysis of the phospholipase A2 activity of snake pre-synaptic neurotoxins in cultured neurons. J. Neurochem. 111, 737–744 (2009).
Harris, J. B., Grubb, B. D., Maltin, C. A. & Dixon, R. The neurotoxicity of the venom phospholipases A2, notexin and taipoxin. Exp. Neurol. 161, 517–526 (2000).
Prasarnpun, S., Walsh, J. & Harris, J. B. β-Bungarotoxin-induced depletion of synaptic vesicles at the mammalian neuromuscular junction. Neuropharmacology 47, 304–314 (2004).
Rigoni, M. et al. Snake phospholipase A2 neurotoxins enter neurons, bind specifically to mitochondria, and open their transition pores. J. Biol. Chem. 283, 34013–34020 (2008).
Harvey, A. & Robertson, B. Dendrotoxins: structure–activity relationships and effects on potassium ion channels. Curr. Med. Chem. 11, 3065–3072 (2004).
Harvey, A. L. in Handbook of Venoms and Toxins of Reptiles (ed. Mackessy, S. P.) 317–324 (CRC Press, 2010).
Fox, J. W. & Serrano, S. M. T. Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases. Toxicon 45, 969–985 (2005).
White, J. Snake venoms and coagulopathy. Toxicon 45, 951–967 (2005).
Del Brutto, O. H. & Del Brutto, V. J. Neurological complications of venomous snake bites: a review. Acta Neurol. Scand. 125, 363–372 (2011).
Kini, R. M. The intriguing world of prothrombin activators from snake venom. Toxicon 45, 1133–1145 (2005).
Kini, R. & Koh, C. Metalloproteases affecting blood coagulation, fibrinolysis and platelet aggregation from snake venoms: definition and nomenclature of interaction sites. Toxins (Basel) 8, 284 (2016).
Yamashita, K. M., Alves, A. F., Barbaro, K. C. & Santoro, M. L. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation. PLoS Negl. Trop. Dis. 8, e2814 (2014).
Rucavado, A. et al. Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom: toxins involved and their contribution to metalloproteinase-induced pulmonary hemorrhage. Thromb. Haemost. 94, 123–131 (2005).
Calvete, J. J. et al. Snake venom disintegrins: evolution of structure and function. Toxicon 45, 1063–1074 (2005).
Du, X. Y. & Clemetson, K. J. in Handbook of Venoms and Toxins of Reptiles (ed. Mackessy, S. P.) 359–375 (CRC Press, 2010).
Resiere, D., Mégarbane, B., Valentino, R., Mehdaoui, H. & Thomas, L. Bothrops lanceolatus bites: guidelines for severity assessment and emergent management. Toxins (Basel) 2, 163–173 (2010).
Than-Than et al. Contribution of focal haemorrhage and microvascular fibrin deposition to fatal envenoming by Russell's viper (Vipera russelli siamensis) in Burma. Acta Trop. 46, 23–38 (1989).
Hayashi, M. A. F. & Camargo, A. C. M. The bradykinin-potentiating peptides from venom gland and brain of Bothrops jararaca contain highly site specific inhibitors of the somatic angiotensin-converting enzyme. Toxicon 45, 1163–1170 (2005).
Höjer, J., Tran Hung, H. & Warrell, D. Life-threatening hyponatremia after krait bite envenoming — a new syndrome. Clin. Toxicol. 48, 956–957 (2010).
Sitprija, V. & Sitprija, S. Renal effects and injury induced by animal toxins. Toxicon 60, 943–953 (2012).
Pinho, F. M. O., Zanetta, D. M. T. & Burdmann, E. A. Acute renal failure after Crotalus durissus snakebite: a prospective survey on 100 patients. Kidney Int. 67, 659–667 (2005).
Warrell, D. A. in Venomous Snakes. Ecology, Evolution and Snakebite (eds Thorpe, R. S., Wuster, W. & Malhotra, A.) 189–203 (Clarendon Press, 1997).
Harris, J. B. et al. Snake bite in Chittagong division, Bangladesh: a study of bitten patients who developed no signs of systemic envenoming. Trans. R. Soc. Trop. Med. Hyg. 104, 320–327 (2010).
WHO Regional Office for Africa. Guidelines for the prevention and clinical management of snakebite in Africa. WHO http://apps.who.int/medicinedocs/documents/s17810en/s17810en.pdf (2010). These are the WHO guidelines for snakebite envenoming in Africa, which are to be used in the training of health staff on the correct diagnosis and management of envenomings.
WHO Regional Office for South-East Asia. Guidelines for the management of snakebites. WHO http://apps.searo.who.int/PDS_DOCS/B5255.pdf?ua=1 (2016).
Sutherland, S. K. & Tibballs, J. Australian Animal Toxins: The Creatures, their Toxins and Care of the Poisoned Patient2nd edn (Oxford Univ. Press, 2001).
White, J. A Clinician's Guide to Australian Venomous Bites and Stings (bioCSL, 2013).
Weinstein, S., Warrell, D. A., White, J. & Keyler, D. ‘Venomous’ Bites from Non-Venomous Snakes: A Critical Analysis of Risk and Management of ‘Colubrid’ Snake Bites (Elsevier, 2011).
Weinstein, S. A., White, J., Keyler, D. E. & Warrell, D. A. Non-front-fanged colubroid snakes: a current evidence-based analysis of medical significance. Toxicon 69, 103–113 (2013).
Warrell, D. A. et al. Severe neurotoxic envenoming by the Malayan krait Bungarus candidus (Linnaeus): response to antivenom and anticholinesterase. BMJ 286, 678–680 (1983).
Ariaratnam, C. A., Sheriff, M. H. R., Theakston, R. D. G. & Warrell, D. A. Distinctive epidemiologic and clinical features of common krait (Bungarus caeruleus) bites in Sri Lanka. Am. J. Trop. Med. Hyg. 79, 458–462 (2008).
Russell, F. E. Snake Venom Poisoning (JB Lippincott, 1980).
Ariaratnam, C. A., Sheriff, M. H. R., Arambepola, C., Theakston, R. D. G. & Warrell, D. A. Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes. Am. J. Trop. Med. Hyg. 81, 725–731 (2009).
Warrell, D. A. et al. Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria. QJ Med. 46, 33–62 (1977).
Sano-Martins, I. S. et al. Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Toxicon 32, 1045–1050 (1994).
Wood, D., Sartorius, B. & Hift, R. Ultrasound findings in 42 patients with cytotoxic tissue damage following bites by South African snakes. Emerg. Med. J. 33, 477–481 (2016).
Theakston, R. & Laing, G. Diagnosis of snakebite and the importance of immunological tests in venom research. Toxins (Basel) 6, 1667–1695 (2014).
Ho, M., Warrell, M. J., Warrell, D. A., Bidwell, D. & Voller, A. A critical reappraisal of the use of enzyme-linked immunosorbent assays in the study of snake bite. Toxicon 24, 211–221 (1986).
Dong, L. Immunogenicity of venoms from four common snakes in the south of Vietnam and development of ELISA kit for venom detection. J. Immunol. Methods 282, 13–31 (2003).
Kulawickrama, S. et al. Development of a sensitive enzyme immunoassay for measuring taipan venom in serum. Toxicon 55, 1510–1518 (2010).
Sutherland, S. K. Rapid venom identification: availability of kits. Med. J. Aust. 2, 602–603 (1979).
Chen, T. et al. Unmasking venom gland transcriptomes in reptile venoms. Anal. Biochem. 311, 152–156 (2002).
Sharma, S. K. et al. Use of molecular diagnostic tools for the identification of species responsible for snakebite in Nepal: a pilot study. PLoS Negl. Trop. Dis. 10, e0004620 (2016).
Tun-Pe et al. in Management of Snakebite and Research (ed. WHO) 7–11 (WHO, 2002).
Chappuis, F., Sharma, S. K., Jha, N., Loutan, L. & Bovier, P. A. Protection against snake bites by sleeping under a bed net in southeastern Nepal. Am. J. Trop. Med. Hyg. 77, 197–199 (2007).
Sharma, S. K. et al. Effectiveness of rapid transport of victims and community health education on snake bite fatalities in rural Nepal. Am. J. Trop. Med. Hyg. 89, 145–150 (2013). This study describes a successful intervention at the community level aimed at improving the access of patients with a snakebite to health facilities.
Tun-Pe, Aye-Aye-Myint, Khin-Ei-Han, Thi-Ha & Tin-Nu-Swe. Local compression pads as a first-aid measure for victims of bites by Russell's viper (Daboia russelii siamensis) in Myanmar. Trans. R. Soc. Trop. Med. Hyg. 89, 293–295 (1995).
Avau, B., Borra, V., Vandekerckhove, P. & De Buck, E. The treatment of snake bites in a first aid setting: a systematic review. PLoS Negl. Trop. Dis. 10, e0005079 (2016).
Faiz, M. A. et al. Bites by the monocled cobra, Naja kaouthia, in Chittagong division, Bangladesh: epidemiology, clinical features of envenoming and management of 70 identified cases. Am. J. Trop. Med. Hyg. 96, 876–884 (2017).
Watt, G., Theakston, R. D. G., Padre, L., Laughlin, L. W. & Tuazon, M. L. Tourniquet application after cobra bite: delay in the onset of neurotoxicity and the dangers of sudden release. Am. J. Trop. Med. Hyg. 38, 618–622 (1988).
Audebert, F., Sorkine, M. & Bon, C. Envenoming by viper bites in France: clinical gradation and biological quantification by ELISA. Toxicon 30, 599–609 (1992).
Bucher, B. et al. Clinical indicators of envenoming and serum levels of venom antigens in patients bitten by Bothrops lanceolatus in Martinique. Trans. R. Soc. Trop. Med. Hyg. 91, 186–190 (1997).
World Health Organization. Guidelines for the production, control and regulation of snake antivenom immunoglobulins. WHO http://www.who.int/bloodproducts/snake_antivenoms/en (2010). These guidelines provide a detailed account on the main aspects related to the production and control of antivenoms, and contain valuable information for manufacturers, researchers and regulatory agencies.
Gutiérrez, J. M., León, G. & Lomonte, B. Pharmacokinetic–pharmacodynamic relationships of immunoglobulin therapy for envenomation. Clin. Pharmacokinet. 42, 721–741 (2003).
Habib, A. G. & Warrell, D. A. Antivenom therapy of carpet viper (Echis ocellatus) envenoming: effectiveness and strategies for delivery in West Africa. Toxicon 69, 82–89 (2013).
Theakston, R. D. G. & Warrell, D. A. Crisis in snake antivenom supply for Africa. Lancet 356, 2104 (2000).
Warrell, D. A. et al. Bites by the saw-scaled or carpet viper (Echis carinatus): trial of two specific antivenoms. Br. Med. J. 4, 437–440 (1974).
Cardoso, J. L. et al. Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil. QJ Med. 86, 315–325 (1993).
Smalligan, R. Crotaline snake bite in the Ecuadorian Amazon: randomised double blind comparative trial of three South American polyspecific antivenoms. BMJ 329, 1120–1129 (2004).
Abubakar, S. B. et al. Pre-clinical and preliminary dose-finding and safety studies to identify candidate antivenoms for treatment of envenoming by saw-scaled or carpet vipers (Echis ocellatus) in northern Nigeria. Toxicon 55, 719–723 (2010).
Abubakar, I. S. et al. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria. PLoS Negl. Trop. Dis. 4, e767 (2010). An example of a randomized controlled, double-blind clinical trial for the evaluation of efficacy and safety of antivenoms in the treatment of snakebite envenomings.
de Silva, H. A. et al. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial. PLoS Med. 8, e1000435 (2011).
Watt, G. et al. Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja philippinensis). N. Engl. J. Med. 315, 1444–1448 (1986).
Golnik, K. C., Pena, R., Lee, A. G. & Eggenberger, E. R. An ice test for the diagnosis of myasthenia gravis. Ophthalmology 106, 1282–1286 (1999).
Jorge, M. T. et al. Failure of chloramphenicol prophylaxis to reduce the frequency of abscess formation as a complication of envenoming by Bothrops snakes in Brazil: a double-blind randomized controlled trial. Trans. R. Soc. Trop. Med. Hyg. 98, 529–534 (2004).
Darracq, M. A., Cantrell, F. L., Klauk, B. & Thornton, S. L. A chance to cut is not always a chance to cure — fasciotomy in the treatment of rattlesnake envenomation: a retrospective poison center study. Toxicon 101, 23–26 (2015).
Jayawardana, S., Gnanathasan, A., Arambepola, C. & Chang, T. Chronic musculoskeletal disabilities following snake envenoming in Sri Lanka: a population-based study. PLoS Negl. Trop. Dis. 10, e0005103 (2016).
Hasan, S. M. K., Basher, A., Molla, A. A., Sultana, N. K. & Faiz, M. A. The impact of snake bite on household economy in Bangladesh. Trop. Doct. 42, 41–43 (2012).
Vaiyapuri, S. et al. Snakebite and its socio-economic impact on the rural population of Tamil Nadu, India. PLoS ONE 8, e80090 (2013). This paper describes the socioeconomic consequences of snakebites in an impoverished rural setting.
Aye, K.-P. et al. Clinical and laboratory parameters associated with acute kidney injury in patients with snakebite envenomation: a prospective observational study from Myanmar. BMC Nephrol. 18, 92 (2017).
Krishnamurthy, S., Gunasekaran, K., Mahadevan, S., Bobby, Z. & Kumar, A. P. Russell's viper envenomation-associated acute kidney injury in children in southern India. Indian Pediatr. 52, 583–586 (2015).
Muhammed, A. et al. Predictors of depression among patients receiving treatment for snakebite in General Hospital, Kaltungo, Gombe State, Nigeria: August 2015. Int. J. Ment. Health Syst. 11, 26 (2017).
Pawade, B. S. et al. Rapid and selective detection of experimental snake envenomation — use of gold nanoparticle based lateral flow assay. Toxicon 119, 299–306 (2016).
Maduwage, K., O’Leary, M. A. & Isbister, G. K. Diagnosis of snake envenomation using a simple phospholipase A2 assay. Sci. Rep. 4, 4827 (2014).
Harrison, R. A. et al. Research strategies to improve snakebite treatment: challenges and progress. J. Proteomics 74, 1768–1780 (2011). This review discusses some of the main research areas that need to be developed to generate novel diagnostic and therapeutic tools to confront snakebite envenoming.
Harrison, R. & Gutiérrez, J. Priority actions and progress to substantially and sustainably reduce the mortality, morbidity and socioeconomic burden of tropical snakebite. Toxins (Basel) 8, 351 (2016).
Wagstaff, S. C., Laing, G. D., Theakston, R. D. G., Papaspyridis, C. & Harrison, R. A. Bioinformatics and multiepitope DNA immunization to design rational snake antivenom. PLoS Med. 3, e184 (2006).
Casewell, N. R., Wüster, W., Vonk, F. J., Harrison, R. A. & Fry, B. G. Complex cocktails: the evolutionary novelty of venoms. Trends Ecol. Evol. 28, 219–229 (2013).
Ramos, H. R. et al. A heterologous multiepitope DNA prime/recombinant protein boost immunisation strategy for the development of an antiserum against Micrurus corallinus (coral snake) venom. PLoS Negl. Trop. Dis. 10, e0004484 (2016).
Laustsen, A. et al. From fangs to pharmacology: the future of snakebite envenoming therapy. Curr. Pharm. Des. 22, 5270–5293 (2016). A summary of novel therapeutic alternatives to approach snakebite envenomings, including recombinant antibodies and natural and synthetic venom inhibitors.
Engmark, M. et al. High-throughput immuno-profiling of mamba (Dendroaspis) venom toxin epitopes using high-density peptide microarrays. Sci. Rep. 6, 36629 (2016).
Laustsen, A. H., Johansen, K. H., Engmark, M. & Andersen, M. R. Recombinant snakebite antivenoms: a cost-competitive solution to a neglected tropical disease? PLoS Negl. Trop. Dis. 11, e0005361 (2017).
Lewin, M., Samuel, S., Merkel, J. & Bickler, P. Varespladib (LY315920) appears to be a potent, broad-spectrum, inhibitor of snake venom phospholipase A2 and a possible pre-referral treatment for envenomation. Toxins (Basel) 8, 248 (2016).
O’Brien, J., Lee, S.-H., Onogi, S. & Shea, K. J. Engineering the protein corona of a synthetic polymer nanoparticle for broad-spectrum sequestration and neutralization of venomous biomacromolecules. J. Am. Chem. Soc. 138, 16604–16607 (2016).
Saul, M. E. et al. A pharmacological approach to first aid treatment for snakebite. Nat. Med. 17, 809–811 (2011).
Rucavado, A. et al. Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA. Am. J. Trop. Med. Hyg. 63, 313–319 (2000).
Azofeifa, K., Angulo, Y. & Lomonte, B. Ability of fucoidan to prevent muscle necrosis induced by snake venom myotoxins: comparison of high- and low-molecular weight fractions. Toxicon 51, 373–380 (2008).
Prado, N. D. R. et al. Inhibition of the myotoxicity induced by Bothrops jararacussu venom and isolated phospholipases A2 by specific camelid single-domain antibody fragments. PLoS ONE 11, e0151363 (2016).
Richard, G. et al. In vivo neutralization of α-cobratoxin with high-affinity Llama single-domain antibodies (VHHs) and a VHH-Fc antibody. PLoS ONE 8, e69495 (2013).
Gutiérrez, J. M. Improving antivenom availability and accessibility: science, technology, and beyond. Toxicon 60, 676–687 (2012).
Lancet, T. Snake bite — the neglected tropical disease. Lancet 386, 1110 (2015).
King, G. F. (ed.) Venoms to Drugs: Venom as a Source for the Development of Human Therapeutics (Royal Society of Chemistry Publishing, 2015).
Eichberg, S., Sanz, L., Calvete, J. J. & Pla, D. Constructing comprehensive venom proteome reference maps for integrative venomics. Expert Rev. Proteomics 12, 557–573 (2015).
Petras, D., Heiss, P., Süssmuth, R. D. & Calvete, J. J. Venom proteomics of Indonesian king cobra, Ophiophagus hannah: integrating top-down and bottom-up approaches. J. Proteome Res. 14, 2539–2556 (2015).
Petras, D., Heiss, P., Harrison, R. A., Süssmuth, R. D. & Calvete, J. J. Top-down venomics of the East African green mamba, Dendroaspis angusticeps, and the black mamba, Dendroaspis polylepis, highlight the complexity of their toxin arsenals. J. Proteomics 146, 148–164 (2016).
Catherman, A. D., Skinner, O. S. & Kelleher, N. L. Top down proteomics: facts and perspectives. Biochem. Biophys. Res. Commun. 445, 683–693 (2014).
Fornelli, L. et al. Advancing top-down analysis of the human proteome using a benchtop quadrupole-orbitrap mass spectrometer. J. Proteome Res. 16, 609–618 (2016).
Calderón-Celis, F. et al. Elemental mass spectrometry for absolute intact protein quantification without protein-specific standards: application to snake venomics. Anal. Chem. 88, 9699–9706 (2016).