Abstract. Russell's viper is the most important cause of life-threatening snake bite and acute renal failure in Sri Lanka. Only equine polyspecific antivenoms imported from India are available. They have not proved effective clinically or in clearing venom antigenemia and they frequently cause reactions. In an attempt to reduce mortality and morbidity, a new monospecific ovine Fab fragment antivenom (PolongaTab ; Therapeutic Antibodies, Inc., London, United Kingdom) was raised against Sri Lankan Russell's viper venom. In a preliminary dose-finding study in 35 patients, an initial dose of 3-4 g restored blood coagulability permanently and stopped systemic bleeding, even in severely envenomed patients. Venom antigenemia disappeared within 1 hr of antivenom treatment but recurred, probably as a result of continued absorption of venom from the site of the bite, after the rapid clearance of therapeutic antibody. Twelve patients (34%) experienced early reactions that were usually mild and always responded to epinephrine.

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Bothrops xanthogrammus/asper, B. atrox and Lachesis muta are probably responsible for most cases of severe envenoming in Ecuador. In recent years, the most widely used antivenom ('Myn' Ronti, imported from Mexico) has proved clinically ineffective. There is an urgent need to identify an effective alternative for clinical testing. Five antivenoms with activity against Bothrops venoms were compared using standard World Health Organization rodent and in vitro assays: (i) 'Myn', Ronti Mexico SA ('B. atrox', 'Crotalus terrificus'), (ii) Instituto Butantan (Bothrops polyvalent, Brazil), (iii) Instituto Nacional de Hygiene y Medicina Tropical (Bothrops polyvalent, Ecuador), (iv) Instituto Nacional de Salud (B. asper, C. durissus and Lachesis muta, Colombia), and (v) Laboratorios Probiol (Bothrops, Lachesis and Crotalus, Colombia). The venoms against which these antivenoms were tested were Ecuadorian B. atrox, B. asper and B. xanthogrammus. Brazilian antivenom proved to be the most effective, followed by the Ecudorian and Colombian antivenoms. Mexican antivenom was completely ineffective in neutralizing the lethal effects of Ecuadorian Bothrops venoms. Monospecific Brazilian L. muta antivenom (Instituto Butantan) proved effective against Ecuadorian L. muta venom, but the Colombian polyspecific antivenoms did not. Clinical trials of Brazilian and Ecuadorian antivenoms are planned in the Amazon region of Ecuador in the near future.

SUMMARYEnvenoming by the Brazilian pit viper, Bothrops jararaca, induces extensive local and systemic haemorrhage in humans. The severe and occasionally lethal outcome of envenoming is prevented only by administration of antivenom which is conventionally prepared by hyperimmunization of large animals with an individual venom or a range of venoms. Since snake venoms typically consist of numerous molecules, only some of which are toxic, antivenoms are antigenically crude preparations whose therapeutic value would theoretically be enhanced by restricting antibody specificity to toxic venom molecules. We report here that high-titre IgG antibody from mice immunized by the GeneGun with DNA encoding the carboxy-terminal JD9 domain of Jararhagin, a haemorrhage-inducing metalloprotease in B. jararaca venom, extensively neutralized the main lethal component of B. jararaca venom. This is to our knowledge the first study to apply DNA-based methods to preparation of antivenom; it represents a novel approach with greater immunological specificity and fewer hazards than conventional systems of antivenom production.

The New Guinea small-eyed or ikaheka snake, Micropechis ikaheka, which occurs throughout New Guinea and some adjacent islands, is feared by the indigenes. The first proven human fatality was in the 1950s and this species has since been implicated in many other cases of severe and fatal envenoming. Reliable attribution of envenoming to this species in victims unable to capture or kill the snake recently became possible by the use of enzyme immunoassay. Eleven cases of proven envenoming by M. ikaheka, with two fatalities, were identified in Papua New Guinea and Irian Jaya. Five patients showed no clinical signs of envenoming. The other six patients showed symptoms typical of envenoming by other Australasian elapids: mild local swelling, local lymphadenopathy, neurotoxicity, generalized myalgia, spontaneous systemic bleeding, incoagulable blood and passage of dark urine (haemoglobinuria or myoglobinuria). Two patients developed hypotension and two died of respiratory paralysis 19 and 38 h after being bitten. In vitro studies indicate that the venom is rich in phospholipase A2, is indirectly haemolytic, anticoagulant and inhibits platelets, but is not procoagulant or fibrinolytic. It shows predominantly post-synaptic neurotoxic and myotoxic activity. Anecdotally, Commonwealth Serum Laboratories' (CSL) death adder antivenom has proved ineffective whereas CSL polyvalent antivenom may be beneficial. Anticholinesterase drugs might prove effective in improving neuromuscular transmission and should be tested in patients with neurotoxic envenoming.