Background Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus. Methodology/Principal Findings Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki. Conclusions/Significance Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa. This suggests that this monospecific antivenom has potential to treat envenoming by most, perhaps all, African Echis species.
References
[1]
Harrison RA, Hargreaves A, Wagstaff SC, Faragher B, Lalloo DG (2009) Snake envenoming: a disease of poverty. PLoS Negl Trop Dis 3(12): e569. doi: 10.1371/journal.pntd.0000569
[2]
Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, et al. (2008) The global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med 5(11): e218. doi: 10.1371/journal.pmed.0050218
[3]
Theakston RDG, Warrell DA (2000) Crisis in snake antivenom supply for Africa. Lancet 356: 2104–2104. doi: 10.1016/S0140-6736(05)74319-1
[4]
Gutiérrez JM, Theakston RDG, Warrell DA (2006) Confronting the neglected problem of snake bite envenoming: The need for a global partnership. PLoS Medicine 3: e150. doi: 10.1371/journal.pmed.0030150
[5]
Stock RP, Massougbodji A, Alagón A, Chippaux J-P (2007) Bringing antivenoms to sub-Saharan Africa. Nature Biotechnology 25: 173–177. doi: 10.1038/nbt0207-173
[6]
Williams D, Gutiérrez JM, Harrison R, Warrell DA, White J, Winkel KD (2010) Viewpoint: an antidote for snake bite. The Global Snake Bite Initiative. Lancet 375: 89–91. doi: 10.1016/S0140-6736(09)61159-4
[7]
Gutiérrez JM, Rojas E, Quesada L, León G, Nú?ez J, et al. (2005) Pan-African polyspecific antivenom produced by caprilyic acid purification of horse IgG: an alternative to the antivenom crisis in Africa. Trans R Soc Trop Med Hyg 99(6): 468–475. doi: 10.1016/j.trstmh.2004.09.014
[8]
Abubakar SB, Abubakar IS, Habib AG, Nasidi A, Durfa N, et al. (2010) 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. doi: 10.1016/j.toxicon.2009.10.024
[9]
Abubakar IS, Abubakar SB, Habib AG, Nasidi A, Durfa N, et al. (2010) 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(7): e767. doi: 10.1371/journal.pntd.0000767
[10]
Warrell DA, Arnett C (1976) 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 Tropica 33: 307–341.
[11]
Pugh RN, Theakston RD (1980) Incidence and mortality on snake bite in savanna Nigeria. Lancet 2: 1181–1183. doi: 10.1016/S0140-6736(80)92608-2
[12]
Habib AG, Gebi UI, Onyemelukwe GC (2001) Snake bite in Nigeria. Afr J Med Med Sci 30: 171–178.
[13]
Warrell DA, Ormerod LD, Davidson NM (1975) Bites by puff-adder (Bitis arietans) in Nigeria, and value of antivenom. Brit Med J 4: 697–700. doi: 10.1136/bmj.4.5998.697
[14]
Warrell DA, Greenwood BM, Davidson NM, Ormerod LD, Prentice CRM (1976) Necrosis, haemorrhage and complement depletion following bites by the spitting cobra (Naja nigricollis). Q J Med 45: 1–22.
[15]
Casewell NR, Harrison RA, Wüster W, Wagstaff SC (2009) Comparative venom gland transcriptome surveys of the saw-scaled vipers (Viperidae: Echis) reveal substantial intra-family gene diversity and novel venom transcripts. BMC Genomics 10: 564. doi: 10.1186/1471-2164-10-564
[16]
Pook CE, Joger U, Stümpel N, Wüster W (2009) When continents collide: phylogeny, historical biogeography and systematics of the medically important viper genus Echis (Squamata: Serpentes: Viperidae). Mol Phylogenet Evol 53: 792–807. doi: 10.1016/j.ympev.2009.08.002
[17]
WHO (2010) Guidelines for the Production, Control and Regulation of Snake Antivenom Immnoglobulins. Geneva: World Health Organisation. Available: http://www.who.int/bloodproducts/snake_a?ntivenoms/snakeantivenomguide/en/. Accessed 2010 August 3.
[18]
Cook DAN, Owen T, Wagstaff SW, Kinne J, Wernery U, Harrison RA (2010) Analysis of camelid antibodies for antivenom development: Neutralisation of venom-induced pathology. Toxicon 56: 373–380. doi: 10.1016/j.toxicon.2010.04.005
[19]
Finney DJ (1971) Probit analysis. London: Cambridge University Press: Third Edition.
[20]
Segura A, Villalta M, Herrera M, León G, Harrison R (2010) Preclinical assessment of the efficacy of a new antivenom (EchiTAb-Plus-ICP) for the treatment of viper envenoming in sub-Saharan Africa. Toxicon 55: 369–374. doi: 10.1016/j.toxicon.2009.08.010
[21]
Cook DAN, Owen T, Wagstaff SC, Kinne J, Wernery U, Harrison RA (2010) Analysis of camelid IgG for antivenom developments: Serological responses of venom-immunised camels to prepare either monospecific or polyspecific antivenoms for West Africa. Toxicon 56: 363–372. doi: 10.1016/j.toxicon.2010.03.025
[22]
Pugh RN, Theakston RD, Reid HA (1980) Malumfashi endemic diseases research project, XIII. Epidemiology of human encounters with the spitting cobra, Naja nigricollis, in the Malumfashi area of northern Nigeria. Ann Trop Med Parasitol 74(5): 523–530.
[23]
Nasidi A (2007) Snakebite a serious public health problem for Nigeria and Africa. Available: http://www.who.int/bloodproducts/animal_?sera/A.Nasidi.pdf.
[24]
Warrell DA, Davidson NM, Greenwood BM, Ormerod LD, Pope HM, et al. (1977) Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria. Q J Med 46: 33–62. doi: 10.1016/0041-0101(75)90227-5
[25]
Sano-Martins IS, Fan HW, Castro SCB, Tomy SC, Franca FOS, et al. (1994) Reliability of the simple 20 minute whole blood clotting test (WBST20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Toxicon 32(9): 1045–1050. doi: 10.1016/0041-0101(94)90388-3
[26]
Kaboré J, Revault P (1996) Treatment of envenomation after Echis ocellatus bites in Burkina Faso. Toxicon 34(2): 164. doi: 10.1016/0041-0101(96)83724-x
[27]
Drame B, Diani N, Togo MM, Maiga M, Diallo D, et al. (2005) Envenomation accidents caused by snakebites in the surgical emergency unit of Gabriel-Toure Hospital, Bamako, Mali (1998–1999). Bulletin De La Societe De Pathologie Exotique 98: 287–289.
[28]
Chippaux JP (2002) Epidemiology of snakebites in Cote d'Ivoire. Bulletin De La Societe De Pathologie Exotique 95: 167–171. doi: 10.1007/13149.1961-9049
[29]
Swiecick AW (1965) Snakes and snake bite in Western Region Ghana. Journal of Tropical Medicine and Hygiene 68: 300.
[30]
Massougbodji A, Chobli M, Assouto P, Lokossou T, Sanoussi H, et al. (2002) Geoclimatology and severity of snakebite envenomations in Benin. Bulletin De La Societe De Pathologie Exotique 95: 175–177.
[31]
Chippaux JP, Kambewasso A (2002) Snake bites and availability of antivenom in the urban Community of Niamey. Bulletin De La Societe De Pathologie Exotique 95: 181–183.
[32]
Einterz EM, Bates ME (2003) Snakebite in northern Cameroon: 134 victims of bites by the saw-scaled or carpet viper, Echis ocellatus. Trans R Soc Trop Med Hyg 97: 693–696. doi: 10.1016/S0035-9203(03)80105-0
[33]
Kochar DK, Tanwar PD, Norris RL, Sabir M, Nayak KC, et al. (2007) Rediscovery of severe saw-scaled viper (Echis sochureki) envenoming in the Thar Desert region of Rajasthan, India. Wilderness Enviro Med 18: 75–85. doi: 10.1580/06-weme-or-078r.1
[34]
Visser LE, Kyei-Faried S, Belcher DW, Geelhoed DW, Schagen van Leeuwen J, et al. (2008) Failure of a new antivenom to treat Echis ocellatus snake bite in rural Ghana: the importance of quality surveillance. Trans R Soc Trop Med Hyg 102: 445–450. doi: 10.1016/j.trstmh.2007.11.006
[35]
WHO (2010) Venomous snake distribution database. Available: http://apps.who.int/bloodproducts/snakea?ntivenoms/database/. Accessed 2010 August 3.