Clinical Toxinology and Snake Anti-Venoms in India: Julian White

Research on epidemiology of toxin-based diseases (TBDs) (other than microbial toxin diseases) has long been an area of patchy development, with a few areas undertaking extensive quality research, while many others have fragmentary, unsatisfactory, or virtually non-existent research in this field. This may reflect the reality that TBDs are not a focus for the historic professional groups within medicine, which originated mainly in western communities in Europe, where TBDs are mostly uncommon to rare.

From available research over the last 100 or so years we now know that TBDs are, in fact, an important disease group globally, most notably in the rural tropics and poor communities from the Americas, through Africa, the middle-east and across Asia to the Pacific. Problem TBDs include those caused by both venoms (such as snakebite and scorpion sting) and poisons (such as fugu, ciguatera, and shellfish poisoning).

With climate change, specifically general warming, particularly of oceans, marine poisoning TBDs appear of increasing global importance, especially varieties of shellfish poisoning. These are now affecting developed-world countries such as European nations bordering the Mediterranean Sea. Consequently this group of TBDs is receiving more research attention and so progressively moving out of the “neglected” category.

The rise in development of clinical toxinology as an area of specific medical expertise, over the last 15 years, coincident with the establishment of the international short course in clinical toxinology in 1997 (and still running today), has seen a burgeoning of interest in TBDs and, more particularly, venom-based diseases (VBDs). VBDs such as snakebite have benefitted from the attention of noted researchers and an increasing number of useful epidemiologic and other studies are emerging. For snakebite this has allowed better delineation of the global extent of the problem, resulting in convincing the World Health Organisation (WHO) to devote some resources to this area and declare snakebite a “neglected tropical disease”. WHO has also sponsored development of universal guidelines for antivenom production that should now be used by all antivenom producers to guide their production processes and the expected quality of their products.

It is tragic that India, arguably the nation with the highest toll from VBDs such as snakebite, has historically devoted so little effort to managing these VBDs. The most recent quality epidemiologic research from India indicates in excess of 45,000 Indians die from snakebite every year. The likely number with significant morbidity following snakebite will be far higher. This is an enormous human, social and economic toll on India.

Indian antivenoms (locally and, in my view, inappropriately named “anti snake venom” (ASV)) are available, but of variable quality. More importantly, it appears the Indian health workers are, in general, inadequately trained in the diagnosis and treatment of snakebite and related VBDs. Providing antivenom is not a sufficient response to improving outcomes for snakebite patients. Unless health workers both understand and are prepared to treat snakebite, and are resourced to do so, significant improvements in outcome are unlikely. This requires an ongoing training program. This has been proposed and, on occasion in some locales, actually implemented in recent times, but really requires a whole-of-government commitment and effort and utilisation of actual experts in clinical toxinology to assist in development and deployment of a training system. It is notable that so far, despite invitations, no Indian doctor has attended the Clinical Toxinology Short Course, while a number of doctors from adjacent nations have done so.

It is my understanding, after both reading papers on snakebite from India, and discussing issues with Indian doctors, that antivenom is underused in India because health workers are afraid of treating snakebite and especially afraid of adverse reactions to antivenom. The prime reason for this is inadequate training on the diagnosis and management of snakebite. This needs to be addressed by a national and ongoing training scheme. The secondary reason for reluctance to use antivenom is the quality of the antivenom. Antivenoms made with older standard methods can be associated with high rates of major adverse reactions. Historically Indian antivenoms have been considered as likely to cause major adverse reactions. Modern methods for making antivenoms decrease the likelihood of major adverse reactions to a low rate. It appears that Indian antivenom producers have not accepted these procedures universally.

Snakes are just one type of venomous animal and amongst venomous snakes there are many species and many different venoms and clinical effects. Research into snakebite and antivenom use in another part of the world may not apply to snakebite in India. It is very important that Indian health workers and officials do not take information published by these foreign researchers and assume it applies to India. That is where the expertise of a specialist trained clinical toxinologist is vital, to interpret research and advise on applicability (or not) to India.

Globally there is a wealth of experience with use of antivenom to treat VBDs, particularly snakebite, and most of that experience indicates the positive roll antivenom has in improving patient outcomes. A few, often controversial studies, outside of India, have shown data that antivenom in those particular, non-Indian, circumstances, may not be effective for certain forms of envenoming. Only by undertaking careful research in India, with Indian snakes and antivenoms, in large prospective clinical studies, can we develop knowledge of antivenom effectiveness in the specific Indian setting.

We do already know that Indian antivenoms do not cover all the important venomous snakes and that even for the snakes covered, the methods of production will likely cause deficiencies in coverage. It is essentially to use a venom from geographically diverse sources to make the snake anti-venom effective throughout the nation. Current regulations in India about who can supply snake venom and from where make it difficult or impossible to provide such geographically diverse venom for antivenom production.

These antivenoms almost certainly could be improved further, using new technologies, that may not increase the cost of production. Equally importantly, the coverage of the antivenoms is not ideal and misses some important species such as hump nosed vipers. A better venom immunising mix would allow better coverage for antivenoms, but to obtain this better immunising mix may require changes in government policy about who and how venoms are supplied.

Antivenom can be a very important part of treating snakebite, but it is not the only treatment. A patient with snakebite-induced paralysis may not respond to antivenom, because of the way the venom works. This is not a failure of the antivenom product, but just a reality of venom action. To survive the patient needs external respiratory support and if this is provided effectively, full recovery is likely. Similarly, if venom damages kidneys, temporary support of kidney function is needed and with this most patients should make a full recovery.

It is difficult for a non-Indian doctor to assess how snakebite is rated within the Indian health system. Evidence suggests that, at least in the past, it was an underrated and largely forgotten problem. This may still be the case, but I cannot be sure if changes are already occurring in government policy and action that might change this situation in the future.

The clinicians in this toxinology community, such as myself, remain most interested in assisting India and Indians to develop an effective response to reduce this snakebite toll, but we need to be asked to help by India and Indians, starting at the national government level, but also involving ordinary Indian health workers. It is these health workers who hold the key to improving outcomes for Indian snakebite patients. It is they who ultimately and into the future must deliver care to these patients. We need to empower them to do so effectively and with confidence born from proper training and adequate resourcing. At the same time as improving treatment of bitten patients, every effort should be made to improve prevention, to reduce the number of patients with snakebite.

Prof. Julian White MB, BS, MD, FACTM
Consultant Clinical Toxinologist
Director, Clinical Toxinology Short Course
Head of Toxinology
Women’s & Children’s Hospital
North Adelaide, Australia

Related Links : Clinical Toxinology Resources (http://www.toxinology.com )

Note : This is the full text of an e-mailed interview of Prof White conducted in 2013 .

Snakebite should be a notifiable disease In India : VV Pillay

Dr. V.V.Pillay MD, DCL
Chief, Poison Control Centre
Head, Dept of Analytical Toxicology
Professor, Forensic Medicine & Medical Toxicology
Amrita Institute of Medical Sciences & Research
Cochin, Kerala 682041
India

The Registrar General of India’s ‘Million Death Study’ has, for the first time, provided a direct estimate of mortality due to snake bite, nationally and in each state. Verbal autopsy was used to identify the causes of all deaths in 6671 randomly chosen sample areas, each covering about 1000 people. In 2005, 46000 people died of snake bite, approximately 1 for every 2 HIV/AIDS deaths. It must be noted that the total number of deaths due to snake bite may be even higher since some victims of nocturnal krait envenoming do not realize that they have been bitten and present with mysterious ‘early morning paralysis’ or seizures. Snake bite accounts for 3% of all deaths in children of the age of 5–14 years. Uttar Pradesh had the highest number of deaths (8700/year) and Andhra Pradesh the highest incidence of mortality due to snake bite (6.2/100 000 population/year).( Natl Med J India 2011; 24(6): 321-324. )

Snake_charmer_in_Sri_LankaNinety seven per cent of the victims of snake bite die in rural areas, 77% of them outside health facilities, presumably because they choose traditional healers. The reason is probably because most bitten people hail from uneducated strata and have more faith in traditional systems of medicine than allopathy. The problem can be addressed by increasing awareness about the dangers of such alternative therapies and the uitility of allopathic remedies, especially anti-snake venom. There are a few Govt-aided programs to tackle this issue, as well as some initiatives by a few NGOs. But they are not enough.
It is important to get snakebite included as a “notifiable disease”, which will make it mandatory for all snakebites to be reported to the public health authorities by doctors and hospitals across India involved in admitting snakebite cases. This will help us get exact figures of incidence of bites and mortality.

Use of snake anti-venom (SAV) in the healthcare system
The Indian Society of Toxicology had come out with a National Snakebite Management Protocol in 2006, based on the proceedings of a national conference in Cochin, Kerala. But the protocol has not received wide publicity or acceptance. As there are no nationally accepted guidelines for the management of snakebite in India, individual doctors and hospitals follow their own regimens. Some doctors claim that they have achieved very good results without employing SAVs, but these claims have not been subjected to peer scrutiny. SAVs are available erratically in the primary healthcare scenario. Sometimes there is adequate supply, and at other times there are no stocks.
SAVs are generally effective in the management of many snakebite cases, but contain antivenoms effective against only the 4 major venomous snakes: Common cobra, Common krait, Russells viper and Saw-scaled viper. Dialysis is often needed in viper envenomations where the patient was taken late to a hospital, or SAV therapy was inadequate or ineffective.
The focus of research in India is on diseases such as hypertension, diabetes, AIDS, etc. As a result, research in the field of snakebite has suffered. A lot needs to be done.

Snakebite neglected, forgotten and victims abandoned: David A Warrell

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?

Photo by Ayyappan Ram on Pexels.com

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?

Continue reading “Snakebite neglected, forgotten and victims abandoned: David A Warrell”

Why do patients fail to take medicines correctly?

HIFA20151

“More than 50% of all medicines are prescribed, dispensed or sold inappropriately, and half of all patients fail to take medicines correctly.”
WHO Fact Sheet 2012

So why do half of all patients fail to take medicines correctly?

Issues of adherence are different depending on whether the condition in acute chronic. For example, it is extremely common for patients to fail to take the complete course of antibiotics for an acute infection, thereby predisposing to antibiotic resistance. For background on adherence in relation to chronic conditions, you can freely download the WHO publication ‘Adherence to Long-term Therapies’ (1.5Mb): (Open Access)

Here are the “Take-home messages” (reproduced from the report):

1. Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude
Adherence to long-term therapy for chronic illnesses in developed countries averages 50%. In developing countries, the rates are even lower. It is undeniable that many patients experience difficulty in following treatment recommendations.

2. The impact of poor adherence grows as the burden of chronic disease grows worldwide
Noncommunicable diseases and mental disorders, human immunodeficiency virus/acquired immunodeficiency syndrome and tuberculosis, together represented 54% of the burden of all diseases worldwide
in 2001 and will exceed 65% worldwide in 2020.The poor are disproportionately affected. The consequences of poor adherence to long-term therapies are poor health outcomes and increased health care costs

3. Poor adherence to long-term therapies severely compromises the effectiveness of treatment making this a critical issue in population health both from the perspective of quality of life and of health economics. Interventions aimed at improving adherence would provide a significant positive return on investment through primary prevention (of risk factors) and secondary prevention of adverse health outcomes.

Continue reading “Why do patients fail to take medicines correctly?”

Dualities : Living with Cancer

Cancer We are often pulled in different, opposing directions, and take time to find the balance between acceptance and anger, surrender and control, individual and group, being and thinking, living and dying. How we find balance and what that balance is influences our attitude. Continue reading “Dualities : Living with Cancer”

Wrong Site Surgery

 

SurgeryWrong Site Surgery WSS (and wrong site procedures: wrong site anaesthetic, implement fitting, etc) might not be as uncommon as you think. Here is an insight into the problem.Continue reading “Wrong Site Surgery”

Why do doctors prescribe expensive branded drugs ?

We all know that there are generic drugs available , which cost a fraction of what the expensive branded drugs do, but are as effective as them. Even though a considerable amount of money would be saved if doctors prescribed only generics, why do doctors continue to prescribe the expensive branded drugs ?Continue reading “Why do doctors prescribe expensive branded drugs ?”

From the Blog to the World

The RTI expose in this Blog on post offices in New Delhi lacking facilties for the disabled higlighted in the post “India Post: “Paper Tigers” in “ease of access for the disabled”  published on the 1st of November 2012 as a Guest Editorial by Dr Satendra Singh , the phenomenal man behind the RTI expose has been today (5th November 2012) featured in the first page of one of the oldest and most respected national dailies The Statesman.(Click on Image )Continue reading “From the Blog to the World”

India Post: “Paper Tigers” in “ease of access for the disabled”

Minister of Communications & IT while unveiling the new logo of India Post said, “The government is taking steps to make India Post a parcel and logistics giant, in the domestic as well as international sector.” The new logo was termed as a synthesis between service proposition and modernity and the launch was heralded as a landmark with the promise that the new corporate identity will unfold higher level of customer services. That was 4 years ago.

Sitting in my office in one of the premier institutes of India, I try to accomplish majority of work via emails. It’s not that I am against snail mail but I dread at the thought of visiting Post Offices (PO). Continue reading “India Post: “Paper Tigers” in “ease of access for the disabled””

Lesson to Learn from The Death of a Celebrity

One fine morning in the autumn of 2012 Indians were informed about the sad demise of the greatest comedian’s of post liberalisation India, Jaspal Bhatti .  ” Bhatti was sitting in the rear seat of the car and received serious head injuries which killed him.”–was the entire summary of the end of the life of a humorist who had an uncanny ability to laugh at himself while exposing serious issues of importance to the common man .  In death too he exposed anomalies in India’s motor safety laws and the lackadaisical attitude of those supposed to maintain it.

For starters, there is a whole lot of confusion about the offence one commits when travelling without seat belts while sitting in the rear seat of the car in India .Continue reading “Lesson to Learn from The Death of a Celebrity”