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The hidden health crisis of snakebites


People in rural parts of Sub-Saharan Africa, Asia and Latin America fear getting bitten by a snake more than natural disasters or diseases like malaria or tuberculosis.  

The WHO estimates that about 5.4 million people are bitten by snakes every year, resulting in an estimated 1.8-2.7 million cases of envenoming and 130,000 deaths. Some 400,000 people end up with long-term disabilities such as blindness, disfigurement or amputation.

India alone accounts for around a third of all snakebite deaths. Other snakebite hotspots are Sub-Saharan Africa, tropical Asia, New Guinea as well as Central and South America.

Most victims are farmers who cross paths with venomous snakes as they tend to their crops and livestock. Many never make it to a medical facility to be counted, because they live too far away or cannot afford the crippling cost of medical treatment — which means that the real death toll from snakebite could be much higher than estimated.

Snakebite envenoming is regarded as an affliction of the poor. WHO statistics from Australasia say that on average just two people die every year from snakebites in Australia, home to more than 170 snake species, including 100 venomous snakes. Yet, in nearby New Guinea, which has similar snake populations, there are more than 1,000 snakebite deaths every year.

More people are killed by snakebite than other neglected tropical diseases (NTDs) such as dengue fever or leishmaniasis, but the problem has largely been ignored by governments.

“The aim is to reduce the scale of the problem by achieving a 50 per cent reduction in deaths and disabilities by 2030.”

David Williams, WHO

There are signs of change. In 2017, the WHO restored snakebite envenoming to its list of NTDs, after removing it in 2013. This year (2018), the World Health Assembly mandated the WHO to come up with an action plan to tackle snakebites.

“The aim is to reduce the scale of the problem by achieving a 50 per cent reduction in deaths and disabilities by 2030,” says David Williams, a member of the WHO’s core working group on this issue and head of the Australian Venom Research Unit at the University of Melbourne.

Scientists agree that achieving this will require greater access to safe, effective, low-cost antivenoms. But there are hurdles such as lack of skill among health workers, under-equipped health facilities and the preference of many snakebite victims to go to a traditional healer rather than a hospital for treatment.

On the positive side, relatively simple preventive measures such as wearing shoes when outside and using bed nets could make a big difference.  


What happens when a snake injects you with venom?


Snake venom is a white or yellow-coloured liquid containing a cocktail of chemicals produced by glands behind the snake’s eyes and pumped down a duct to the snake’s hollow fangs. The fangs act like a hypodermic needle, injecting venom into its prey.

There are three main types of venom which attack the body in different ways. Haemotoxic venom causes bleeding by interfering with blood clotting. This can lead to fatal haemorrhaging, shock and convulsions.

Neurotoxic venom attacks the central nervous system. Victims may experience lockjaw and difficulty in breathing. Paralysis, which typically starts at the head and moves down the body, can cause respiratory failure as the muscles responsible for breathing stop working.

Cytotoxic venom attacks the area around the bite, destroying cells and tissue. Entire limbs can be affected and wither away, necessitating amputation.

Venoms can also cause low blood pressure, increased heart rate, vomiting, diarrhoea and kidney failure. Women and children suffer more severe effects of snake envenoming because of their smaller body size.


Long-term suffering for victims and communities


Snakes thrive in tropical, rural areas and their victims are some of the poorest people in the world —  subsistence farmers, labourers and cattle herders working barefoot in the fields.

Besides physical injuries, snakebite victims are shunned by neighbours, relatives and friends who believe it is a bad omen. Women who have been bitten are less likely to get married and disfigured survivors are reduced to poverty.  

In many cases, families have no option but to sell what little they own to pay for treatment. Children may be taken out of school to care for a parent or sibling, or because their families can no longer afford school fees.


Which snakes are the most venomous?


There are more than 3,000 kinds of snakes in the world. About 600 snake species are venomous, and between 200 and 250 are responsible for most of the global deaths, injuries and disabilities.

In India, the Big Four — the Indian cobra, the Russell’s viper, the Indian saw-scaled viper and the Indian krait — cause the majority of serious bites. In Southern India and Sri Lanka, the hump-nosed pit viper has emerged as a particularly dangerous species.

In Africa, cobras, saw-scaled vipers and puff adders are major culprits, although in some areas mambas are responsible for numerous bites along with other species of viper.

In Central and South America, a range of pit-viper species, particularly lanceheads and rattlesnakes, are responsible for most bites.

In New Guinea, the majority of bites are caused by the taipan and death adders.


Innovations in antivenom


The use of antivenom is the most reliable treatment for snakebite. However, snake venom differs across species and within species, depending on factors like age, environment, diet and season. Therefore, antivenoms must be snake-specific as well as region-specific to be effective.

Since the late 19th century, antivenom has been made by injecting snake venom into horses or other large animals to trigger the immune system to produce antibodies. Blood plasma containing the antibodies is extracted from the animal to make antivenom in an expensive, labour- intensive process.

In recent years, scientists have been trying out innovative approaches to the production of antivenom.

For example, Andreas Hougaard Laustsen, associate professor at the Technical University of Denmark’s department of biotechnology, is developing an antivenom based on human antibodies as a safer and cheaper alternative to horse serum — which can trigger serum sickness or life-threatening anaphylactic shock.  

Scientists at the University of California are looking at nanoparticles to prevent the spread of venom through the body. The hope is that one day injectable nanoparticles could be loaded into a device like an EpiPen, which could be easily and immediately administered to a snakebite site. This could buy the victim more time to get treatment in a hospital. Researchers are excited about the work of Matthew Lewin, who has been looking at drugs that failed their intended therapies but find use against snake venom. One drug, varespladib, initially investigated as an anti-inflammatory agent, has shown good results in neutralising enzymes in snake venom.


Little incentive for antivenom manufacturers


Effective and safe antivenoms are available but the cost is beyond the reach of many patients, who instead turn to traditional healers or cheaper alternatives. But low price means the drugs are usually of poor quality, untested or even fake. Soon enough patients no longer place their faith in medication, and demand for antivenom drops even further.

As a result, manufacturers either raise their prices or stop production altogether, as was the case with the French pharmaceutical company Sanofi, which in 2010 stopped producing Fav-Afrique, a highly effective and affordable pan-African antivenom. The company deemed the African market not lucrative enough.

One factor that contributes to low demand for antivenom is lack of data on snakebite deaths and injuries around the world, which results in national health authorities under-estimating requirements.

As part of its action plan, the WHO will test antivenom quality to ensure that only effective versions are sold. By scaling up production of quality-assured antivenoms, recommended by the WHO, it is hoped that prices will drop but manufacturing will continue.
 
This piece was produced by SciDev.Net’s Global desk.


References

[1] World Health Organization: Snakebite envenoming
[2] 71st World Health Assembly Resolution: Addressing the burden of snakebite envenoming
[3] Global Snakebite Initiative
[4] Health Action International
[5] Medecins Sans Frontieres
[6] Minutes to Die
[7] Andreas H. Laustsen et al, In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies, Nature Communications(2018). DOI: 10.1038/s41467-018-06086-4
[8] O’Brien J, Lee S-H, Gutiérrez JM, Shea KJ (2018) Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis. PLoS Negl Trop Dis 12(10): e0006736. https://doi.org/10.1371/journal.pntd.0006736
[9] Lewin, M.R.; Gutiérrez, J.M.; Samuel, S.P.; Herrera, M.; Bryan-Quirós, W.; Lomonte, B.; Bickler, P.E.; Bulfone, T.C.; Williams, D.J. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal
[10] Doses of Papuan Taipan (
Oxyuranus scutellatus) Venom. Toxins 2018, 10, 380 https://doi.org/10.3390/toxins10100380

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