Around 300 species of snakes are prevalent in India. Why are anti-venoms available only for ‘Big 4’?
Around 300 species of snakes are prevalent in India. Why are anti-venoms available only for ‘Big 4’?
While many antivenoms are relatively effective, the complex nature of snake venom can make treatment difficult. Access to antivenom can be patchy and treatments with it can be expensive.
Snake bites are a growing health crisis, especially in India. According to a report by elife in 2020, India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. The study also revealed that Russell’s vipers, kraits, and cobras were responsible for most deaths. The remaining deaths were caused by at least 12 other species of snakes. The study also found that between 2001 and 2014, some 70% of the snake bite deaths occurred in eight states – Bihar, Jharkhand, Madhya Pradesh, Odisha, Uttar Pradesh, Andhra Pradesh, Telangana, Rajasthan, and Gujarat.
According to experts, snakebite takes a huge toll on India partly because the subcontinent is home to so many different types of snakes: 60 of the country’s nearly 300 species are highly venomous.
In 2017, the World Health Organization (WHO) designated poisoning by snakebite a neglected tropical disease in 2017. In 2020, WHO launched a global initiative to halve the number of deaths and disabilities it causes by 2030. According to experts, many of the bites are treatable with existing anti-venoms however, they are not accessible all the time.
Despite the alarming figures, snakebites are not treated as a major public health concern. Most of the time victims don’t get proper treatment on time. Due to this many of the patients suffer from life-changing injuries such as amputation and permanent disability.
“The snake bite disease is underestimated as most patients in rural India go to traditional healers and the cases go unreported as it is not a Nationwide Notifiable disease. Additionally, the Primary Health Centres are not fully equipped in terms of knowledge, training and management of snakebites. Hence the urgent need to include Snakebites in the medical curriculum that will help in building awareness and knowledge of treatments,” Dr. Aldon Fernandes, Vice President-Equine, Bharat Serum & Vaccines Ltd (BSV) told Financial Express.com.
Menace of Snakebites–A neglected public health issue in India
Snakebite disease takes a huge toll on India partly because the subcontinent is home to so many different types of snakes: 60 of the country’s nearly 300 species are highly venomous. A study published in The Nature journal reveals that snakebites annually cost India’s citizens the equivalent of 3 million years of health and productivity.
“Snake bites mainly affect the rural areas where people mainly in home remedies and spiritual therapies leading to a lot of under-reporting. Lack of knowledge on the types of snakes and the bites and the causes of the syndrome are widespread all over India. The inability of the anti-snake venom across the nation is also a significant contributing factor. All of these lead to a lot of neglect and thus makes India the snakebite death capital across the world,” Dr. Khusrav B Bajan, Consultant Physician & Intensivist, Department of Medicine and Critical Care at P. D. Hinduja Hospital, Mumbai told Financial Express.com.
Dr. Fernandes also informed that over 58,000 deaths occur in India due to snakebites annually. In addition, four times this number suffer from permanent loss-of-function injuries, such as amputations leading to the loss of livelihood of India’s hundred thousand annual snakebite victims.
“People who get bitten by snakes never enter hospitals or healthcare centres, they are not formally recorded, and researchers frequently underestimate the impact of the bites across the globe. Snakebite also doesn’t receive a lot of attention because it “is a poor man’s disease”, affecting mainly impoverished farmers and their families in rural areas. Snakebite is a neglected tropical disease worldwide and it was only in 2017 that the WHO reinstated snakebite envenoming to its list of category A neglected tropical diseases (NTDs), which is an important milestone in disease control,” Dr. Fernandes told Financial Express.com.
“This poses a serious public health hazard as well as an economic challenge. However, with snakebites being recognised as an NTD, it allows for an impetus to antivenom development and next generation snake bite therapy as well as prevention and treatment access initiatives,” he said.
Snakes of India
The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. Most importantly, it can also be impossible for those bitten in remote parts of the country to get treatment because the nearest health clinic might be several hours away. Even then, clinics don’t always have anti-venom on hand, and if they do, it might not have been stored properly or be of good quality.
Russell’s viper (Daboia russelii), kraits (Bungarus species), and cobras are among the most important biting snake species in India, yet other often unidentified species also represent a threat.
The Indian cobra typically attacks after dark and causes internal bleeding, which requires immediate medical attention. Russell’s viper, a generally aggressive snake, is widespread across India and South Asia. It feeds on rodents and so is often found near human settlements, both in urban and rural areas. The Indian krait is normally docile during the day but becomes belligerent at night. It can grow up to 1.75m (5ft 9in) in length.
While many antivenoms are relatively effective, the complex nature of snake venom can make treatment difficult. Access to antivenom can be patchy and treatments with it can be expensive. A majority of the victims are males the 15-45 years residing in rural India who are farmers, labourers, shepherds, and migrant population. These are mostly breadwinners and thus the economic implication, Dr. Fernandes said.
“The government of India guidelines has laid down protocols for snakebite management, and it has come in the year 2015 December. These are reasonably up to date. The protocols depend upon the snake, the bite that it causes, and the syndromes. For example, snake bites are divided into occult bites where the history of bites is unknown and overt bites. They are also divided into symptomatic and asymptomatic. Forex – If it’s an occult bite, mainly it’s caused by a krait, which leads to Neuroparalytic symptoms. It also causes severe vomiting and abdominal problems, and this needs anti-snake venom and ventilator strategies. If it’s a viper and an asymptomatic overt bite, that can lead to progressive painful symptoms at the site. If it’s a cobra or a krait, it can lead to neuorparalytic changes, and in this, the patient’s breathing ability is sacrificed. Suppose it is a Russel viper or a saw-scaled viper. In that case, it can lead to vascular toxicity,” Dr. Bajan told Financial Express.com.
He also said that the patients can have Disseminated intravascular coagulation (DIC) and bleed, leading to a hemorrhagic shock and kidney failure. If it is a snake that is flat-tailed or a sea snake, it can lead to myotoxicity, rhabdomyolysis, compartment syndrome, and again kidney failure. All these big fours would need anti-snake venom, he added.
“There are established protocols for the management of venomous snakebites including the one published by the Ministry of Health and Family Welfare, Government of India, and Guidelines for the Management of Snake Bites by the World Health Organisation. The critical aspect of adherence to treatment protocols is important in the overall management of snake bites. It must be pointed out that the management of snakebite and its treatment is included in the Ayushman Bharat coverage allowing for wider access to the treatments that in saving more lives in India. Further, It’s important that the quality of anti-snake snake venom should be the most important criteria while selecting brands. Further, it’s important from a patient safety perspective that high-quality anti-snake venom be made available to them,” Dr. Fernandes told Financial Express.com.
Over 60 species of snakes in India but anti-venoms only for “big four”
India has some of the cheapest antivenoms in the world, costing around $6.5-11 (£4.7-8) per vial, but problems with quality and availability often mean patients do not get the treatment they require.
Hospitals in India also primarily use a polyvalent (or multipurpose) antivenom as an antidote against the “big four” snakes that cause the majority of bites – the spectacled cobra, the common krait, saw-scaled viper, and Russell’s viper. It is produced using venom from these four snakes. However, India has more than 60 venomous species of snake and there is no specific antivenom against most of them.
Instead, the “big four” antivenom is often used as a general snake bite treatment. Antivenoms are manufactured against the Big four species as these are the only venoms authorised to be milked from Wild snakes in India for the manufacturing of commercial antivenoms. However, recent research has found that it is largely ineffective against the venom of other important snakes in the country.
“India is home for over 300 snake species, 60 of which are venomous. Out of those 60, the majority of the Snake bites occur due to the Big 4 species Daboia russelii (Russell’s viper), Naja naja (common Indian Cobra), Bungarus caeruleus (common krait), and Echis carinatus (saw-scaled viper), hence the development and availability of the polyvalent antivenoms solely against Big 4 Snake Venoms. Nevertheless, the Big 4 are not uniformly spread across the country due to various factors but not limited to rainfall, altitude, habitat and availability of prey,” Dr. Fernandes told Financial Express.com.
He also said that there are certain species that are specific to certain geographical areas and whose venom is not neutralised by the available polyvalent anti-snake venom. These include the Naja kaouthia, Bungarus fasciatus, Bungarus niger, Bungarus sindanus, Trimeresurus species, Hypnale hypnale, Echis carinatus sochureki, Ovophis monticola and Ophiophagus hannah.
“In certain parts of our country, bites from the above-mentioned species are more common than that of the Big 4 species. It was assumed that the available polyvalent would cross-react and neutralize the venom. But unfortunately, there is no literature to support the hypothesis and neutralization studies done in vitro using venom from the non-Big 4 snakes suggest poor degree of neutralization with the available polyvalent hence making it a pressing need to develop region-specific anti-venoms,” he added.
‘Need for regionally-specific anti-venoms’
Researchers suggest that for anti-venom treatment to be effective, it has to be developed based on the region, especially in snakebite hotspots in India. Last year, a team of scientists from the Indian Institute of Science (IISc) conducted a study to understand why common anti-venom did not work in most snakebite cases. The researchers also suggested for anti-venom treatment to be effective, it has to be developed based on the region, especially in snakebite hotspots in India. They had also said that a long-term strategy, developing an anti-venom that would work pan-India, after gathering adequate information about all kinds of venom.
Earlier this year, the research institute collaborated with Bharat Serums and Vaccines (BSV) to evaluate the effectiveness of regional anti-venoms in neutralising toxins in region-specific snake bite cases compared to the existing ones. As a part of this collaboration the research institute will produce test batches of non-commercial anti-snake venoms (ASVs).
“BSV has entered into a meaningful collaboration with the ‘Evolutionary Venomics Lab’, at the Indian Institute of Science (IISc) Bangalore, to develop region-specific antivenoms to pioneer next-generation snakebite therapy in India. Further to this, IISc has started collecting venoms and is in the process characterising them. Once this process is completed, BSV will initiate development studies of immunisation followed by antibody characterisation,” Dr Aldon Fernandes, Vice President-Equine, Bharath Serum & Vaccines Ltd (BSV) told Financial Express.com.
According to Dr. Bajan, the anti-snake venom dose depends on the toxicity like neuroparalytic or the Disseminated intravascular coagulation (DIC), vascular toxicity, or cardiotoxicity that it may cause.
“Depending upon that, the dose of the snake bite venom is usually ten vials which should be given immediately if the patient is brought early as soon as possible and if always look for reactions in which the patient can have severe anaphylactic reactions which may again prompt the need for adrenaline injections to save a life. If the patient does not improve, certain snake bites would deserve a second dose after about half an hour or one hour or repeat doses every 6 hours depending upon the snake bite. Here we would be using 6 vials every 6 hours in the worst-case scenario,” he said.
Dr. Bajan also explained that the big 4 snakes, the cobra, krait, saw-scaled viper, and Russell’s viper account for 90 percent of the snake bites in India. But there are some snakes called the monocled cobra, banded krait, and sand krait mainly found in Arunachal Pradesh, Bangalore, and Mysore that would probably not be treated by the anti-snake venom which is currently available.
“If the patient is brought early irrespective of the type of snake from any region, they would be treated pretty well with the polyvalent anti-snake venom which is available. Having said that again, there is a need to have more and more region-specific tweaking of the anti-snake venoms available. Most vulnerable groups are the extremes of age like the elderly and the children, farmers, forest workers, rural areas, and patients from low socio-economic strata who don’t even have proper footwear and have to go to work or live in those areas which are infested with a lot of snakes. More than 1.2 million snakebite deaths have occurred in the last two decades making India the world capital of snake bites. Prompt identification of the snake and the bite, the syndromes it causes, immobilization of the limb, early recognition of the symptoms and early hospitalization, supportive care, and the full of anti-snake venom given as soon as possible save more and more lives. I would request everyone across India to not indulge in home remedies and other spiritual remedies and waste time because prompt action, and early recognition is the key to the treatment,” Dr. Bajan told Financial Express.com.
On when these anti-venoms will be available for the public, Dr. Fernandes explained that it takes an estimated two to five years for this product to be made available in the country depending on the requirements of Clinical studies.
“People in rural areas are most vulnerable. However, it has been our resolve to expand access to the treatment of snakebites. For this, BSV has partnered with States which facilitate long-term arrangement of antivenoms at reasonable prices,” he added.
How to deal with the menace of snakebites in India?
Dr. Fernandes emphasised that while it is critical to set up breeding centres for harvesting venom and venom collection centres that pool venoms from lesser-known species as well as develop snake venom antiserum, it is equally important to have an enabling, progressive and pragmatic regulatory and legislative landscape.
“…so that it encourages research and provides grants and financial support for end-to-end Venom-Antivenom Projects; creates a registry of snakebite; re-looks at the Wildlife Protection Act for capture and breeding of lesser-known species; includes snakebite treatment in community medicine curriculum as well as in school curriculum that could build an awareness,” he added.
Additionally, partnerships between antivenom manufacturers and States for the procurement of antivenoms and more importantly robust regulatory practices for faster approvals should be put in place to encourage research and development of antivenoms by the industry and antivenom manufacturers, he said.
“From a diagnostics perspective, it is equally critical to have snake venom detection kits that can help identify the type of snake venom and have treatments that are far more effective and concerted. Awareness plays a critical role in the management of snakebites. And setting up 24×7 helplines could be useful. With technology evolving, BSV as a pioneer and market leader has created an application that maps the closest treatment sites where snakebite victims could be taken. This helps in management and treatment of snakebites through wider access and availability of treatments as well as assists in building a registry of patients,” Dr. Fernandes told Financial Express.com.
Dr. Fernandes also said that a collaborative and concerted effort from every stakeholder including Government, healthcare providers, antivenom manufacturers, forest departments, caregivers, organisations and industry bodies, scientists, herpetologists and the public at large, will collectively help in addressing this public health concern.
“The snake bite disease is underestimated as most patients in rural India go to traditional healers and the cases go unreported as it is not a Nationwide Notifiable disease. Additionally, the Primary Health Centres are not fully equipped in terms of knowledge, training, and management of snakebites. Hence the urgent need to include Snakebites in the medical curriculum that will help in building awareness and knowledge of treatments,” he said.
Dr. Fernandes also explained that there are some challenges that persist in the regulations, permissions, and test license requirements that need to be addressed.
“We remain committed to developing region-specific antivenoms to address region-specific species as well as expand access to treatment in order to save lives. However, some challenges remain on the regulations, permissions and test license requirements that need to be addressed. It is necessary to explore a fast-tracked new drug approval system that encourages antivenom manufacturers to bring newer treatments to patents, quicker and sooner. To address these challenges BSV has initiated an awareness drive on the “ Right Treatment at Right Place with Right Dose”. We at BSV are also working on creating awareness through collaboration with SHE, an organization dedicated to addressing snakebite-related issues in India,” he added.
Additionally, BSV through the application “Serpent” supports health practitioners in providing the right education around managing snakebite victims while driving awareness and educating on the importance of reaching the right treatment centres for snake bites.
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