Dataset Information

Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal.

ABSTRACT:

Background

Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming.

Methodology/ principal findings

This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal. Participants received either low (two vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The primary composite outcome consisted of death, the need for assisted ventilation and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom treatment. Between April 2011 and October 2012, 157 snakebite victims were enrolled, of which 154 were analysed (76 in the low and 78 in the high initial dose group). Sixty-seven (43·5%) participants met the primary outcome definition. The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%) initial dose group (difference = 10·2%, 95%CI [-6·7 to 27·1], p = 0·264). The mean number of vials used was similar between treatment groups. Overall, patients bitten by kraits did worse than those bitten by cobras. The occurrence of treatment-related adverse events did not differ among treatment groups. A total of 19 serious adverse events occurred, including seven attributed to antivenom.

Conclusions

This first robust trial investigating antivenom dosage for neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal performs poorly. Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction. The development of new and more effective antivenoms that better target the species responsible for bites in the region will help improve future patients' outcomes.

Trial registration

The study was registered on clinicaltrials.gov (NCT01284855) (GJ 5/1).

SUBMITTER: Alirol E

PROVIDER: S-EPMC5446183 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal.

Alirol Emilie E Sharma Sanjib Kumar SK Ghimire Anup A Poncet Antoine A Combescure Christophe C Thapa Chabilal C Paudel Vijaya Prasad VP Adhikary Kalidas K Taylor Walter Robert WR Warrell David D Kuch Ulrich U Chappuis François F

PLoS neglected tropical diseases 20170516 5

<h4>Background</h4>Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming.<h4>Methodology/ principal findings</h4>This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai pl ...[more]

PMID: 28510574

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Project description:BackgroundDeath adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment.Methodology/principal findingsDefinite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom.Conclusions/significanceDeath adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.

Project description:Snakebite envenoming is a life-threatening disease in humans and animals and a major public health issue in rural communities of South-East Asia and sub-Saharan Africa. Yet the impact of snakebite on domestic animals has been poorly studied. This study aimed to describe the context, clinical features, treatment, and outcomes of snakebite envenoming in domestic animals in Nepal and Cameroon. Primary data on snakebite in animals were recorded from a community-based nation-wide survey on human and animal snakebite in Nepal and Cameroon (Snake-byte project). Mobile teams collected data on snakebite in humans and animals in 13,879 and 10,798 households in Nepal and Cameroon respectively from December 2018 to June 2019. This study included 405 snakebite cases (73 in Nepal and 332 in Cameroon) in multiple types of animals. An interview with a structured questionnaire collected specific information about the animal victims. Snake bites in animals took place predominantly inside and around the house or farm in Nepal (92%) and Cameroon (71%). Other frequent locations in Cameroon were field or pasture (12%). A large diversity of clinical features was reported in all types of envenomed animals. They showed either a few clinical signs (e.g., local swelling, bleeding) or a combination of multiple clinical signs. Only 9% of animal victims, mainly cattle and buffaloes and less frequently goats, sheep, and dogs, received treatment, predominantly with traditional medicine. The overall mortality of snakebite was 85% in Nepal and 87% in Cameroon. Results from this nationwide study show an important impact of snakebite on animal health in Nepal and Cameroon. There is a need for cost-effective prevention control strategies and affordable snakebite therapies in the veterinary field to save animal lives and farmer livelihood in the poorest countries of the world. The WHO global strategy to prevent and control snakebite envenoming supports a One Health approach, which may help develop integrated solutions to the snakebite problem taking into account human and animal health.

Dataset Information

Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal.

Background

Methodology/ principal findings

Conclusions

Trial registration

Publications

Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal.

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