Prof David A Warrell , Emeritus Professor of Tropical Medicine at University of Oxford and Senior Editor of the Oxford textbook of Medicine and OTM: Infection in an interview with Dr. Soumyadeep B discusses various aspects of snakebite. Prof Warrell is a pioneer in research on the incidence, morbidity and mortality of snake bites as well as the clinical presentation, pathophysiology, treatment and prevention of envenoming by snakes and other venomous animals. In the interview he discusses various aspects of snakebite as a public health problem , issues with snake anti-venom and why more research is needed in this field .
Dr. Soumyadeep B: There is controversy over the incidence of snake bite and more so its mortality and morbidity. What your opinion on this issue? How important is snake bite as a clinical condition in India? In terms of public health how important is it?
Prof. Warrell : There is controversy because, until recently, there were no reliable data. Hospital returns to the Government of India in 2011 reported only 1440 snake-bites, while a much quoted WHO-sponsored study estimated between 11,000 and 15,000 deaths per year by extrapolating from hospital data. Because most snake-bite victims die outside hospital, and even hospital reporting is imperfect, these figures are bound to be underestimates. However, the Registrar General of India’s “Million Death Study” (MDS) has, for the first time, provided nationwide community-based data using “verbal autopsy” to identify snake-bite deaths (a structured interview of the relatives or close associates of the deceased by non-medical staff with central medical coding by at least two doctors). This technique is reliable for snake-bite because the event is distinctive, dramatic and therefore memorable. The result was that, in 2005, 46 000 people (99% CI 41 000–51 000) died of snake-bite in India, approximately 1 for every 2 HIV/AIDS deaths. Assuming that there are 100 non-fatal bites for each fatal bite (from results of a community-based study in Bangladesh) there could be as many as 4.6 million snake-bites in India each year. The MDS results indicate which states of India are worst affected: the highest numbers of deaths were in Uttar Pradesh (8,700), Andhra Pradesh (5,200), and Bihar (4,500). This is clearly a disease of major public health importance, affecting rural people predominantly (agricultural workers and their families including young children). Its clinical importance will become more obvious as villagers are educated to seek medical rather than traditional, ayurvedic treatment.
Dr. Soumyadeep B: Most snake bite victims in India go to traditional or faith healers instead of coming to doctors .Why is it so? How can this cultural aspect be suitably modified? Any notable programs being taken by govt/NGOs/corporates (in India or abroad) towards this direction that you are aware of? What steps do you recommend as an expert?
Prof Warrell : Rural people trust herbal and other traditional forms of treatment because that is what they are brought up to believe. Traditional practitioners are readily available in the village, their services are cheap and since the overall case-fatality of snake-bites is low (~1% see above) and only about 50% of bites by venomous snakes result in envenoming (injection of sufficient venom to cause local and/or systemic effects) even useless remedies will appear effective in a proportion of cases. However, these treatments have no scientifically demonstrable effectiveness, may be harmful and will delay the patients’ arrival in hospital. Alternative therapies should therefore be discouraged or the traditional practitioners educated to refer patients with definite symptoms of envenoming. Community education is the key to reducing the risk of snake-bite. There are several successful pilot projects, for example in West Bengal and Kerala. The main elements of the programmes are to emphasise where and when the risk of snake-bite is greatest (types of terrain, times of day and times of year) and to encourage safer working and walking by using adequate footwear and other protective clothing and carrying a light after dark; and safer sleeping by using a well tucked-in mosquito net. Victims of bites are encouraged to travel to hospital without delay, not wasting time with traditional treatments. The Australia-based charity “Global Snakebite Initiative” (GSI) http://www.snakebiteinitiative.org/ is committed to promoting preventive programmes for which it is actively seeking funding.
Dr. Soumyadeep B: Research in snakebite epidemiology, prevention, treatment and rehabilitation is important but neglected. Why do you think is reason behind this?
Prof Warrell : Snake-bite, as a subject for medical research, has suffered because, in comparison with other “neglected tropical diseases” (NTDs), it is not an infectious disease, cannot be prevented by vaccination and can never be eliminated. As a result, it has been overlooked by international charities and funding agencies. However, effective strategies for prevention and treatment are established but need to be deployed to the areas where they are most needed. More research is needed into all aspects of snake-bite, including studies of the snake species of greatest medical importance, community-based studies of incidence of bites and resulting mortality and persisting morbidity (an undetermined number of snake-bite survivors are left with permanent physical disabilities caused by the locally necrotic effects of some venoms).
Dr. Soumyadeep B: Use of snake anti-venom (SAV) in the healthcare set up is also associated with many problems. Why are some doctors averse to prescribing SAV ? Are SAV available in the primary healthcare scenario?
Prof Warrell :Antivenoms are the only effective antidotes for treating envenoming. India is fortunate in having national antivenom production for almost 100 years. However, these antivenoms have not been subject to formal clinical trials in India. They commonly cause adverse reactions, such as fever and anaphylaxis, which discourages some doctors from using these essential drugs. Antivenom must be given intravenously by medical staff trained to assess the clinical criteria justifying treatment and to identify and treat reactions. They are therefore unsuitable for use at primary health care facilities unless the staff can be trained to a sufficient level.
Dr. Soumyadeep B: What is the evidence for the use of SAV? Any potential gaps. What about the role of dialysis and
Prof Warrell: Research in countries outside India has provided evidence that specific antivenoms can correct bleeding and clotting disorders, shock, and cobra-bite paralysis. Their use early after the bite can prevent the development of life-threatening envenoming and local tissue destruction. However, they cannot reverse krait-bite paralysis and may not prevent acute kidney injury after Russell’s viper-bites. To be effective, antivenoms must be specific for the particular venom involved. They will neutralise only the venoms used in their production or those of some closely related species. Traditionally, Indian antivenoms have been raised against the venoms of only the four most important species: Russell’s viper, saw-scaled viper, spectacled cobra and common krait. They do not cover venoms of any of the Indian pit-vipers and may not be effective for bites by monocellate cobras (in the east), Oxus cobra (in the north), several other species of krait and the king cobra. Another problem is that venom composition in a single species such as Russell’s viper may vary throughout its wide geographical range. Yet 80% of the venom used to make Indian antivenoms comes from one small area in Tamil Nadu. As a result, the antivenom may not be equally effective in all parts of the country. It is reported that larger doses of antivenom are required to treat saw-scaled viper bites in Rajasthan and Russell’s viper bites in Northern Kerala.
There is an urgent need for India to review the design of its classic polyvalent antivenom covering the “big four species”, to take into account the expanded range of species now known to be important in some parts of the country and to address the problem of regional variations in venom composition and potency.
In addition to specific antivenom, snake-bite victims may need other emergency treatments to support failing systems: assisted ventilation for respiratory paralysis, dialysis for acute kidney injury, fluid replacement and vasoactive drugs for shock and surgical debridement and skin grafting to deal with the locally-necrotic effects of cobra and viper venoms. Patients may die on their way to hospital if transport is delayed and if early life-threatening events such as shock or airway obstruction are not prevented or treated.
Dr. Soumyadeep B: How safe are Indian SAV? Concerns over the product have been raised. Can you elaborate on this and give your opinion.
Prof Warrell: Indian antivenoms have a bad reputation for causing adverse events. In Sri Lanka, where only Indian antivenoms are available, up to 80% of patients develop early reactions. This risk can be reduced by using prophylactic adrenaline. Such high rates of reactions suggest flaws in production techniques, but there seems to be little commercial incentive for manufacturers to improve their products. Recently, WHO published guidelines to improve antivenom production. Unfortunately, a plan to provide expert technical advice for antivenom producers could not be funded.
Dr. Soumyadeep B:Overall would you agree that snake bite is a forgotten neglected tropical disease in India?
Prof Warrell: Worldwide, snake-bite has been neglected and forgotten and its victims abandoned by medical science and public health systems. This neglect is particularly surprising in India, which has long been regarded as the country that suffers the worst snake-bite problem in the world but whose doctors have the greatest experience and skill in dealing with this ancient scourge of mankind.
Dr. Soumyadeep B: Anything else you want to say in this issue.
Prof Warrell : Clinical research on snake-bite in India is urgently needed to answer questions about antivenom safety, dosage regimens and effectiveness and limitations in treating various types of envenoming. In the past, published studies from India have been disappointing because of flawed trial design (problems with case definition and identification of the species of snake responsible, inadequate power and lack of blinding and controls, objective end-points, standardised dosage regimens etc.).