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Parabuthus granulatus identified as the most venomous scorpion in South Africa: Motivation for the development of a new antivenom GJ Muller, HT Modler, CA Wium, DJH Veale, JM van Zyl Division of Pharmacology, Stellenbosch University, Cape Town Campus, South Africa The currently available South African scorpion antivenom is manufactured from the venom of Parabuthus transvaalicus. The efficacy of this antivenom is questionable. At best, a moderate therapeutic effect is only seen 4 6 hours post administration. Objective Due to the questionable efficacy of the currently available antivenom a study was undertaken to identify the scorpion species responsible for cases of severe scorpionism in order to: facilitate and/or motivate for the development of a more effective and rapid-acting acting antivenom. Methods A study of all cases of scorpionism (scorpion sting associated with systemic toxicity) dealt with by the Tygerberg Poison Information Centre over a period 20 years (1990 to 2010) was undertaken. The geographical locations of all cases, were recorded. Where available scorpions were identified Results Geographical distribution of Parabuthus granulatus and P. transvaalicus Of the 148 cases studied, 90% occurred in the Western & Northern Cape provinces. In 38 of the 148 cases, the scorpion was available for identification. All of the 38 specimens were identified as Parabuthus granulatus.

Geographical distribution of 148 cases of severe scorpionism. Geographical distribution of the 38 identified scorpions. Red dots indicate incidence is which scorpion specimens were obtained and identified as. Discussion The syndrome of serious scorpion envenomation is characterized by copious oral and pharyngeal secretions and symptoms and signs of bulbar paralysis. The result is loss of protective laryngeal / upper airway reflexes, difficulty in swallowing, upper airway obstruction, aspiration and respiratory failure. Children are particularly vulnerable, with a mortality rate of 12 15%. Death may occur within 1 2 hours post envenoming often while the patient is on route to a medical facility. To reduce morbidity and mortality, prompt respiratory support and administration of an effective antivenom is crucial. If antivenom is not administered, the toxic syndrome may last days to a week before clearing up. Scorpions South Africa has a rich scorpion fauna with 127 species. Venomous scorpions Thin pincers & thick tail Less venomous scorpions Thick pincers & thin tail Most scorpions stings are relatively harmless and cause mild to moderate local pain only. (6 15 cm) Buthidae Scorpionidae

Four scorpion families occur in South Africa: Buthidae (34%) Scorpionidae (42%) Liochelidae (21%) Bothriuridae (2%) The potentially dangerous and medically important species belong to the family Buthidae. Seven Buthid genera occur in South Africa: Parabuthus Uroplectes Hottentotta Pseudolychas Lychas Karasbergia Afroisometrus Parabuthus is medically the most important. Of the Parabuthus species, 22 are endemic to southern Africa. Some of the larger species in this genus include: P. transvaalicus P. capensis P. raudus P. villosus P. kalaharicus P. schlechteri P. mossambicensis It was assumed until recently that all of the above larger Parabuthus species are equally venomous. However, we now know that only two spp, namely and P. transvaalicus, can cause serious envenoming. We now also know that, although P. transvaalicus may cause significant systemic envenomation, is the no 1 culprit, causing life-threatening scorpionism. This finding has also recently been supported by LD 50 experiments in mice. (Current PhD study) LD 50 values of the venom of 5 Parabuthus scorpion species. Experiments performed on adult Balb C mice. (Meier and Theakston, 1986) Scorpion Species Parabuthus granulatus LD 50 Values mg/kg 1,56 mg/kg P. transvaalicus 4,25 mg/kg P. schlechteri > 20 mg/kg P. capensis > 20 mg/kg P. mossambicensis > 20 mg/kg Centruroides noxius (control venom) 1,19 mg/kg 1 Geographical distribution of Parabuthus granulatus and P. transvaalicus

Parabuthus granulatus (6 15 cm) Unique morphological characteristics of P. transvaalicus 2 P. schlechteri Unique morphological characteristics of Habitat and Behaviour of P. transvaalicus 3 4

In Conclusion 5 has now for the first time been positively identified as the most venomous scorpion species in southern Africa. It is important to note that P. transvaalicus (the venom of which is used in the production of the current antivenom) does not occur in the Western and Northern Cape, regions known for a high incidence of scorpionism. The most probable reason for the suboptimal efficacy of the antivenom is that the venom of the wrong scorpion is used in its production In light of this, a strong case exists for the development of a specific antivenom, or the inclusion of both P. granulatus and P. transvaalicus venom in the production of a more effective polyvalent antivenom. Thank you