Safer treatment snakebite study

Classified as a neglected tropical disease by the WHO, snakebite is a major public health problem in Sri Lanka. Annual snakebite incidence in Sri Lanka is about 400 per 100,000 population, one of the highest in the world. Although there are more than 90 species of snakes in the country, much of the morbidity and about 95% of the mortality associated with snakebites are due to the highly venomous Cobra, Russell’s viper, and Kraits.

Sri Lanka is an agricultural country whose agricultural activities are mainly carried out around two monsoon seasons, May to September and November to January. Snakebite is considered as an occupational hazard by farmers; high incidences of snakebites have been reported during the periods of high rains and agricultural activity. The farming community, especially those living in North-Central and North-Western provinces, are seriously challenged by this problem.

Polyvalent antivenom is the most effective, if not the only effective treatment available for snakebite envenomation. Unfortunately, in the South Asian countries including Sri Lanka where snakebites are common, antivenoms are often of poor quality, and acute allergic reactions to them occur frequently. Many studies have shown approximately 80% of snakebite victims who receive antivenom, develop acute reactions; up to 40% of these are life-threatening anaphylactic reactions. As a result, the management of acute adverse reactions to antivenom is an important part of the management of snake envenoming. Increasing the safety of treatment with antivenom for snakebite victims is therefore a matter of high priority.

Crisscrossing the country at least once a month during three long years, from March 2005 to April 2008, one of the largest clinical trials on snakebite was conducted at five different sites by Principal Researcher Prof. Asita de Silva and his team from the Clinical Trials Unit of the Faculty of Medicine, University of Kelaniya. Undertaken in collaboration with the University of Oxford and the- Liverpool School of Tropical Medicine, the research was funded by small grants from the University of Kelaniya and the Clinical Trial Service Unit of the University of Oxford. The researchers randomised 1,007 patients who had been admitted to secondary referral hospitals in Sri Lanka after snakebite to receive low-dose adrenaline, promethazine, hydrocortisone, or placebo alone and in all possible combinations immediately before treatment with antivenom. The patients were monitored for at least 96 hours for adverse reactions to the antivenom; patients who reacted badly were given adrenaline, promethazine, and hydrocortisone as ‘rescue medication’. Three-quarters of the patients had acute reactions mostly ‘moderate’ or ‘severe’ to the antivenom. Most of the acute reactions occurred within an hour of receiving the antivenom, and nearly half of all the patients were given rescue.

medication during the first hour. Compared with placebo, pretreatment with adrenaline, reduced severe reactions to the antivenom by 43% at one hour and by 38% over 48 hours. In contrast, neither hydrocortisone nor promethazine given alone reduced the rate of adverse reactions to the antivenom. Moreover, adding hydrocortisone negated the beneficial effect of adrenaline. The findings were published in PLoS Medicine in 2011. Since then, pre-treatment with adrenaline has been used widely by physicians in Sri Lanka and other countries in the region. In 2015, this intervention before antivenom infusion was included into WHO snakebite management guideline.

This pivotal study was the starting point of our journey into the world of international, multi-centre clinical trials and paved the way to establishing the public-private partnership between University of Kelaniya and RemediumOne. This fired our imagination and determination to find simple and cost-effective solutions to major public health problems, which remains our ethos to this day.