Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review

Abouyannis, Michael; Aggarwal, Dinesh; Lalloo, David G.; Casewell, Nicholas R.; Hamaluba, Mainga; Esmail, Hanif

doi:10.1371/journal.pntd.0009589

Cited by 20 publications

(30 citation statements)

References 61 publications

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“…Although the frequency of severe allergic reactions was low, there was one case that died as a direct result of antivenom induced anaphylaxis. Despite local envenoming being the most frequent indication for administering antivenom in much of Africa, its effectiveness for this indication is unproven, particularly if it is given late, and clinical trials are urgently needed [19]. Novel oral small molecule therapeutics may hold promise, particularly if they can be administered in rural clinics and thus reduce the time to treatment [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

Paediatric snakebite in Kilifi County, Kenya: A 19-year observational study

Abouyannis

Boga

Amadi

et al. 2022

Preprint

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Introduction Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data describing the burden of paediatric snakebite. This study describes the clinical features, hospital management, population-incidence, and mortality of consecutive paediatric snakebite cases over a 19-year period. Methods Using the Kilifi Health and Demographic Surveillance System (KHDSS), all children with snakebite presenting to Kilifi County Hospital were identified. All cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. Results Between 2003 and 2021, there were 19,798 admissions to the paediatric HDU, of which 619 were due to snakebite. Amongst infants (<=5-years age) the population-incidence of hospital- attended snakebite was 9.8/100,000 person-years; for children aged 6-13-years this was 26.4/100,000 person-years. The number of children attending hospital with snakebite has increased over time. Children aged 8-11 years had the highest incidence. There were six snakebite associated deaths. At admission, low haemoglobin, raised white blood cell count, and an upper limb bite-site were associated with the development of severe local tissue damage. Conclusion There is a substantial burden of disease due to paediatric snakebite and this has increased in-line with population growth. Most cases present with local rather than systemic envenoming, and many of these receive antivenom. The mortality rate was low, which may reflect the quality of care delivered on the paediatric HDU. There is an urgent need to better define the burden of paediatric snakebite across Africa, to initiate community engagement to prevent snakebites, and to improve treatments for local tissue damage.

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Section: Discussionmentioning

confidence: 99%

Paediatric snakebite in Kilifi County, Kenya: A 19-year observational study

Abouyannis

Boga

Amadi

et al. 2022

Preprint

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“…When good quality antivenom directed against the relevant biting species is available, it has been shown to effectively reverse the consumption coagulopathy induced by SVMPs. However, few clinical trials of antivenom in sub-Saharan Africa have been conducted, and none have compared antivenom to placebo [6][7][8][9][10] . In Nigeria, ''EchiTAb Plus-ICP'' (ET-Plus) equine antivenom restored the 20-minute whole-blood clotting time (20WBCT) in 83% of trial participants 6 .…”

Section: Limitations Of Antivenommentioning

confidence: 99%

TRUE-1: Trial of Repurposed Unithiol for snakebite Envenoming phase 1 (safety, tolerability, pharmacokinetics and pharmacodynamics in healthy Kenyan adults)

et al. 2022

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Background: Snakebites affect over 5 million people each year, and over 100,000 per year die as a result. The only available treatment is antivenom, which has many shortcomings including high cost, intravenous administration, and high risk of adverse events. One of the most abundant and harmful components of viper venoms are the zinc-dependent snake venom metalloproteinases (SVMPs). Unithiol is a chelating agent which is routinely used to treat heavy metal poisoning. In vivo experiments in small animal models have demonstrated that unithiol can prevent local tissue damage and death caused by a certain viper species. This phase I clinical trial will assess the safety of ascending doses of unithiol with a view for repurposing for snakebite indication. Methods: This open label, single agent, phase I clinical trial of a repurposed drug has a primary objective to evaluate the safety of escalating doses of unithiol, and a secondary objective to describe its pharmacokinetics. In total, 64 healthy Kenyan volunteers from Kilifi County will be dosed in consecutive groups of eight, with dose escalation decisions dependent on review of safety data by an independent data safety monitoring board. Four groups will receive ascending single oral doses, two will receive multiple oral doses, and two will receive single intravenous doses. Follow-up will be for 6-months and includes full adverse event reporting. Pharmacokinetic analysis will define the Cmax, Tmax, half-life and renal elimination. Conclusions: This clinical trial will assess the safety and tolerability of a promising oral therapeutic in a relevant setting where snakebites are prevalent. Unithiol is likely to be safer than antivenom, is easier to manufacture, has activity against diverse snake species, and can be administered orally, and thus shows promise for repurposing for tropical snakebite. Pan African Clinical Trials Registry: PACTR202103718625048 (3/3/2021)

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“…If the cost of snakebite treatment was lower, it would not likely be argued that it is being overused. 1,3,6 To that end, it is essential to devise systematic and comparable methods for evaluating and reporting snakebite envenoming such that local, regional, and international data sets can be interpreted to their highest and best purpose to inform clinical decision-making.…”

Section: Acute Kidney Injury As a Complication Of Venomous Snakebite ...mentioning

confidence: 99%

“…5 In their recent review of snakebite envenoming, Abouyannis et al identified 14 published clinical trials in which acute kidney injury was one of the outcomes. 6 The findings of Bowden et al suggest the need for attention to acute kidney injury in clinical trials of snakebite envenoming, and, more specifically, suggest the possibility of modernizing the SSS to include acute kidney injury in order to optimize its utility in international trials testing traditional and novel snakebite envenoming therapeutics.…”

mentioning

confidence: 99%