A crisis in the production of antivenoms is killing tens of thousands of people a year. Can scientists harness HIV technology to create a universal defence against the serpents? Colin Freeman and Paul Nuki report

This article has an estimated read time of 10 minutes

Three-year-old Shaibu Musa lies on a hospital trolley, his terrified eyes staring at his swollen right arm. The burning pain seems out of all proportion to the pinpricks left on his hand by the intruder in his bed last night. 

All he knows is that when he woke screaming, a small, brown creature no longer than his forearm slithered away into the dark. His parents, though, realised it was probably a carpet viper – a common killer here in north east Nigeria, and one of the deadliest snakes worldwide.

"It happened about 2 o'clock this morning, while he was asleep in bed with his mother," says his father Musa Abdullahi, 37, a cattle farmer from Bauchi State. "I was terrified that he might die, so I got him to the hospital straight away."

In north-east Nigeria, that did not mean a quick dash by ambulance. Instead, Mr Abdullahi had to drive his son four hours through the night to the Snakebite Treatment and Research Hospital at Kaltungo, in neighbouring Gombe State. 

The spartan 200-bed facility does not look state-of-the-art, but its doctors are true specialists. Here in the “Snake Belt” – as this arid, reptile-friendly region of north east Nigeria is known – more people are said to suffer snakebites than in any other corner of the world.

All too often, they die: some cannot reach hospital quickly enough, others waste time by seeking out remedies from traditional healers instead. But Musa’s father, Mr Abdullahi, has learned the hard way.

“I’ve had three other family members bitten by snakes over the years, so I knew to bring my son here straight away,” he says.

Also lying on the hospital trolley is the serpent from last night, severed in two pieces. Aware that doctors would want to know which snake had bitten his son, Mr Abdullahi hunted it down, killed it with a machete, and stuffed it into an old mineral water bottle.

Its coils bear the brown, diamond-hued pattern – reminiscent of a 1970s floor covering – that gives the carpet or saw-scaled viper its name. In the local Tangale language, it is called: “Small and dangerous”. In Hausa, its name translates as: “You will not see tomorrow.”

Its notoriety is deserved. It accounts for nearly 90 per cent of the clinic’s admissions and, although small, it is highly irritable and fast to strike. Locals say they have seen them become so angry and agitated they bite their own tails.

Most people who are bitten are subsistence farmers or herders, often women and children who work barefoot and without gloves in the fields. At planting and harvest times the clinic’s wards become jammed. It’s the same story worldwide.

“It’s a very aggressive snake, and it will often bite even if not provoked,” said Dr Sulaiman Muhammad, one of the clinic’s senior medics. “The venom is hemotoxic, which means it stops the blood from clotting. That can lead to patients bleeding from the mouth, nose, and internally, including in the brain. If it isn’t treated, they can die within a few hours.”

Snakebite is arguably the world’s biggest hidden health crisis.

Every year 5.4 million people are struck by snakes and between 81,000 and 138,000 die from those bites. Of those who survive, 400,000 suffer life changing injuries including amputations, nerve damage, sight loss and terrible open ulcers that never heal.

The burden of death and disability is greater than any other neglected tropical disease and equal to that of prostate or cervical cancer worldwide.

Despite these numbers – and the terror snakes strike in most of us – snakebite has received little sustained attention from the international health community. A condition of the rural poor in far-flung parts of Africa, Asia and South America, it has been easy to dismiss as just another unfortunate fact of life.

But now that is set to change, and change dramatically.

Two years ago the World Health Organization (WHO) formally classified snakebite as a neglected tropical disease and will later this month launch a global strategy which aims to halve the numbers of deaths and cases of disability by 2030.

Then on Wednesday came two funding announcements which experts describe as “game changing”.

The Wellcome Trust, one of the world’s largest biomedical charities, announced a new £80 million programme to transform the way snakebite is managed globally. And the UK Department for International Development (Dfid) released £9 million to fund the development of the Holy Grail of snakebite treatments – a universal snake antivenom.

“These investments are profound, they are game changing,” said Professor Robert Harrison, head of the Centre for Snakebite Research and Interventions at the Liverpool School of Tropical Medicine and a global authority on snakebite. “For the first time in my lifetime there is coordinated global strategy and the money to back it. It’s a watershed moment.”

The reason so many people die of snakebite is because of a “global crisis” in the manufacture and supply of antivenoms, say Professor Harrison and Wellcome. Most of us imagine a simple injection carried in a rucksack can reverse the effects of any snakebite but the truth is very different.

Antivenoms are still made by injecting horses or sheep with tiny amounts of snake venom and then bleeding them to collect the antibodies they produce. It is a laborious and inefficient process that has not changed much since the early 1900s and has no common production, safety or efficacy standards. In Africa up to 90 per cent of antivenom is thought to be ineffective.

Even the best antivenoms protect against only a handful of the 250 different venomous snakes and often need to be administered in huge doses. Severe reactions, some life threatening, are so common they can only be used in hospitals or clinics with resuscitation facilities. Even then treatment is not always effective and the patient can take weeks to recover.

The new funding, it is hoped, will allow scientists to take a twin track approach: one group will focus on improving the manufacture, regulation and distribution of traditional animal derived antivenoms for particular snakes, while another will seek to develop a new “humanised” product offering “near universal protection” against all snakebites.

“The ultimate aim is to have a product that can be easily carried and administered in a field or on a roadside without the risk of provoking an adverse reaction,” said Professor Harrison. “At the moment the problem is not just that many antivenoms are poor but that so few people can get to where they are stored and administered.”

The scientific challenge in creating a universal vaccine is far from insignificant. Snake venom is as multivarious as it is toxic, with each species and subspecies of venomous snake carrying a unique poison refined over millions of years of evolution.

Some bites result in local tissue damage, causing the flesh and muscle around the bite to blister and liquify, often resulting in permanent lesions or, if untreated, gangrene, amputations and death.

Others induce so called “systemic effects” where the poison destroys or shuts down one or more of the victim’s vital organs.

The fangs of cobras and mambas, for example, inject neurotoxins which stop electrical signals being transmitted through the nervous system. Victims remain fully conscious but become paralysed and die through suffocation as the muscles controlling their breathing cuts off.

There are stories of jungle explorers being kept alive for days in this helpless state while their companions take it in turns to pump their chest to keep them ticking over.

Vipers and adders on the other hand typically deliver hemotoxins, poisons which course through the veins causing red blood cells to burst or clump together. Victims die from widespread internal bleeding, organ failure or clots that cause stroke or heart attack.

Professor Harrison and his team know these risks well not only because they have spent years travelling the world studying them but because on the top floor of their Liverpool office they have a herpetarium housing more than 100 of the most venomous snakes on the planet.

Contained (we are assured) in rows of plastic boxes and glass-faced tanks, here are the serpents nightmares are made of: cobras that track the glint of your eyes with the precision of a factory robot and spit a jet of neurotoxin at them if you make the slightest move forward; a puff adder so eager to strike that its window is covered with a curtain; and big fat rattlers that sound their terrifying alarm the moment you step in their direction.

In the herpetarium, the professor defers to lead herpetologist, Paul Rowley, who has looked after the animals since graduating from the reptile house of Chester Zoo in 1993. Rowley handles the creatures with a cool confidence, regularly milking them for their venom. Nevertheless, he has ended up in intensive care three times over his 25-year career after being out-manoeuvred – each time by a rattler.

“Paul has the quickest hands of all of us,” says his assistant Ed Crittenden. Just as well, as he picks up a Gila monster – a slow-moving lizard regarded as having the most painful venom of any vertebrate. “It won’t kill but there are people who have cut off their hands after being bitten because of the pain,” says Rowley.

In the drive to produce a universal vaccine, scientists will leverage the technology and processes that led to the discovery of drugs to combat HIV.

The International AIDS Vaccine Initiative – in partnership with Liverpool School of Tropical Medicine and snakebite specialists from Kenya, Nigeria, USA and India – will work together as a consortium to identify and synthetically produce antibodies capable of neutralising the venoms of all the major snakes in Africa and Asia.

Once the correct antibodies are identified they will be “humanised”, much reducing the risk of toxic shock that almost all animal derived antivenoms cause. The goal is to produce a single universal vaccine that works for all or nearly all snakes and can ultimately be self administered in a field.

The initiative is the brainchild of the American HIV scientist Dr Devin Sok who deduced that the same method of finding antibodies for all the diverse strains of HIV could be applied to the equally complex field of snakebite. He got in touch with Professor Harrison and together they have - inch by inch - nudged it towards fruition.

“It is what the mission of the Liverpool School of Tropical medicine is all about, innovating to reduce the burden of sickness and mortality in the world’s poorest countries,” says Harrison.

The consortium is funded by Dfid and will run until March 2021 when a pre-clinical prototype of the antivenom is expected to be produced. Clinical trials would then need to follow.

The new International Development Secretary Rory Stewart said that, if successful, the project could save many hundreds of thousands of lives across Africa and Asia.

“In parts of Africa and Asia snakebites are a daily threat, causing life-changing disabilities or – in the worst case – death.

“More than 80,000 people die every year from snakebites and because of the huge variety of snake venoms, people often do not get the treatment they need in time, if at all.

“UK aid has invested in [this] research to identify the complex antibodies needed to develop an affordable, accessible, effective treatment.

“This is a fantastic example of how UK aid can make a real difference in the world.” 

In Nigeria’s Snake Belt the new initiative is welcome but will not come anything like soon enough for many.

May and June are peak season for the clinic, when the start of the farming season leads to labourers getting bitten as they clear areas of grassland and bush. Sometimes a dozen patients arrive every day, some even from over the border in neighbouring Cameroon, nearly 200 miles away.

Those who reach the clinic are treated with basic anti-venoms, which are offered free of charge and will usually see recovery within a few days. Yet many victims choose to remain at home, putting their faith in traditional remedies such as rubbing the wound with bark, or slashing it open in a hopeless bid to “bleed out” the poison.

One such case is Emmanuel Samuel, 12, who was bitten on the foot by a carpet viper four nights ago while out playing. The creature clung on his foot with its fangs, meaning it probably delivered a full dose of venom, but for the first 12 hours, his grandmother treated him by feeding him garlic paste.

“Luckily a member of our own staff happens to live in his village, and when they found out they told him to come here straight away,” said Dr Muhammad, as he examines Emmanuel’s leg. Although the swelling has subsided, it is covered in blisters and lesions, while the remaining skin is shiny and fragile like clingfilm.

“By the time he got here, he was hardly able to speak,” Dr Muhammad adds. “If he’d stayed at home, he would have died.”

In 2017, the Kaltungo clinic treated some 4,400 patients, around one per cent of whom died, said Professor Abdulrazaq Habib, another medic at the clinic.

Occasionally, there are also logistical problems with the supply of antivenom. Dr Muhummad said that a shortage over a fortnight last autumn let to several patients being turned away, some of whom he presumes subsequently died.

Locals could also do with more education on the risks of using traditional medicine: “We tell them that the herbal cures are useless, but people do not always listen,” he says.

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