The perils of snakebite affect not just South Africa – with its critical scarcity of anti-venom – but the entire sub-Saharan Africa region, where patients face a “wild west” of ineffective anti-venoms that are badly made, badly marketed and badly regulated. Some are about “as useful as injecting water”, experts have said.
In the Mail & Guardian, the Bureau of Investigative Journalism (TBIJ) reports that it tested samples of anti-venoms bought in three countries, and found some could require more than 70 vials to effectively treat some bites.
One anti-venom company has been accused of fraudulent research. Another business exported an anti-venom for Indian snakes to West Africa, where they knew it would not work – an act experts called unethical and criminal.
Anti-venoms are “antique” medicines that have been made the same way for more than a century: by injecting horses and sheep with snake venom and extracting antibodies from their blood.
This antique origin is one of the reasons anti-venoms have avoided the regulations that now apply to many other drugs. Despite being a life-or-death medicine, they are not held to the same standards as, for example, paracetamol.
There are no requirements for them to go through clinical trials to prove they are safe and effective in humans.
“It’s a cowboy show out there,” said Thea Litschka-Koen, a leading snakebite expert in eSwatini. “Some are selling stuff that honestly, you may as well just pour down the drain.”
A hidden crisis
The damage from a snakebite depends on the snake. If it’s a venomous snake, it can cause life-changing injuries or even death.
“You get horrific wounds,” said Litschka-Koen, who founded the eSwatini Anti-venom Foundation, a charity that raises funds to treat snakebite victims. “So horrific, that pictures will make your eyes water.”
Just how many people are affected by snakebites is a bit of a mystery and often goes unrecorded. The World Health Organisation (WHO) says 5.4m people are bitten each year. Estimates on deaths worldwide range from 80 000 to 140 000. But who is most affected is clear.
“It’s a poor man’s disease,” Litschka-Koen said. Those who are bitten typically live in remote, often rural, areas, mostly concentrated in Africa and South Asia. Farmers and children are most commonly bitten.
While the best treatment is a prompt and effective dose of anti-venom, meaning the chances of survival can be six times higher, for many rural victims, local herbalists are often much easier to reach than conventional medical care.
Even those in major urban centres may face difficulties – snakebite has little to no place on the curriculum at many African medical schools.
In places like Australia, where anti-venom is high quality and free to patients, snakebite causes just one to two deaths a year.
But in many African countries, effective treatment has been plagued by issues for years; in 2023, 20 000 people died from snakebites in sub-Saharan Africa.
Like injecting water
In a building in Valencia, Spain, Professor Juan Calvete examined a small vial with a blue lid. Calvete is respected worldwide as an expert in snake anti-venom.
He peered at the label. It listed the venom of Indian snakes it could be used to treat: some of the label was written in Bengali. It was, unmistakeably, an anti-venom made for India – but purchased by a TBIJ reporter in East Africa.
Snake venom and its effects vary from species to species. An anti-venom formulated to work in one region can be virtually useless against snakebites somewhere else.
Calvete said if you were bitten by a highly venomous African snake like a black mamba and then given the Indian anti-venom he was holding, the consequences would be certain fatality.
His lab at the Instituto de Biomedicina de Valencia is trusted as the sole source of the WHO’s official assessments on anti-venom quality.
Scientific research has long proven that Indian snake anti-venoms won’t work against African snakes.
Calvete tested two Indian anti-venoms bought in Uganda and Nigeria by the TBIJ. Made by Bharat Serums and Vaccines (BSV) and Premium Serums and Vaccines – which also make different African anti-venoms – they showed desperately low capacity to work against sub-Saharan African snake venom.
“Giving a patient this will be almost as if you inject distilled water into the body,” he said.
Both companies denied exporting their products to Uganda and Nigeria respectively.
Dr David Williams, one of the WHO’s leading experts on snake bites, said people who buy anti-venoms for national Health Ministries don’t always understand how they work.
“Nobody tells them what species of snake they’re meant to be looking for,” he said. “They buy the cheapest product they can find. And it’s not until it ends up in the doctor’s hands that somebody discovers it is not for the snakes that come from our country.”
But a manufacturer such as BSV should know where its product will work.
The company, which declares its mission is “to preserve, protect, and enhance quality of life”, has been making anti-venoms for years. It doesn’t make an anti-venom for Africa; when the TBIJ called the company, an employee confirmed that the one anti-venom BSV makes is for use against Indian snakes.
BSV’s actions have caused deaths before. One of its older anti-venoms was made using a mix of venoms from African and Indian snakes. Crucially, it used an Indian species of viper instead of the common African species.
When it was used in Ghana in 2004, research showed it led to a nearly seven-fold rise in mortality compared with patients treated with a different anti-venom.
Manufacturers are not always involved in the distribution of anti-venoms. But BSV is: records show it made several shipments of its Indian anti-venom to Mali, where it couldn’t work
BSV denied exporting its product to Somalia, Tanzania and Uganda, but said its exports to Mali had been approved by the country’s health ministry. The Malian health ministry denied this.
Claims by Inosan
Even anti-venoms created specifically for Africa vary wildly in quality. Inoserp Pan-Africa, made by the Mexican and Spanish company Inosan Biopharma, claims to combat bites from 18 different snake species.
But the TBIJ’s testing showed that per vial, Inoserp was the worst of all the African anti-venoms tested. In fact, in tests against sub-Saharan African snake venom, it performed worse than one of the products made for Indian snakes.
The problem is not that it contains the wrong anti-venom but that there’s not enough of it in the bottle. In the lab, Inoserp’s binding capacity against mamba venom was shown to be 10 times less per vial than a rival’s product (PANAF Premium).
The implications for patients are severe. For instance, the test results suggest that medics could need more than 70 of these vials to treat the bites of some of the most dangerous snakes. That many doses would introduce two problems: delay, and high costs.
In reality a medic is unlikely to administer that many vials.
First, a doctor will wait hours between each dose of anti-venom to see how a patient responds. So it would probably take too long for the medicine to work. Second, the costs would be prohibitive.
The problem, as testing reveals, is that compared with competitors, Inosan puts a fraction of the active ingredient needed into a vial of Inoserp.
Inosan has sold $3.2m worth of Inoserp to at least 13 sub-Saharan African countries over the past five years.
The company told the TBIJ that Inoserp has undergone several clinical trials, and “almost all” testing has shown “acceptable neutralisation and meets specifications with respect to similar products”.
Red flags in regulation, research
The WHO has its own approval process as a safety net for countries without the means to check anti-venoms. It threw out Inosan’s last application. It was unable to guarantee that the benefits of using Inoserp would outweigh the risks, based on the evidence presented.
Dr Abdul-Subulr Yakubu leads the cardiology unit at Tamale teaching hospital, Ghana, but he ends up regularly treating snake bites; this is snake country.
He often has to give a patient several times the recommended dose of anti-venoms, including one made by Indian company Vins.
The WHO threw out Vins’ assessment of its sub-Saharan African products, as it did Inosan’s, in 2017. “We’re not sure if we have to give large volumes because it’s not very effective,” Yakubu said.
After all, there are many other factors that can complicate treating a snakebite.
Many patients who go to hospital have been to local healers first, delaying their treatment and sometimes introducing infections. Some come in too late for anti-venom to work. Others don’t know what kind of snake has bitten them, making it harder to give the best treatment.
Vins applied to get a WHO recommendation for its anti-venom in 2016. The process was cancelled when, among other issues, Vins submitted a paper on its medicine supposedly by two respected researchers, both of whom denied having any involvement in the study.
Professor Kate Jackson, one of the listed authors on the paper, confirmed: “I didn’t collect those snakes and they don’t exist in (the Republic of the) Congo.” She doesn’t recall Vins contacting her about the paper.
Vins claimed “a senior employee” presented the research under Jackson’s name and their contract was “immediately terminated” when the company found out.
It’s another example of questionable practices and the scarcity of reliable research. Without it, health workers told the TBIJ they try the available anti-venom and hope for the best, without ever being sure if it was the medicine, or the patient’s luck, that had the most effect.
The TBIJ tested a vial of Vins purchased in Uganda. It contained far more of the active ingredient than Inosan’s product.
Having performed poorly in tests in the past, Vins was overall the best-performing anti-venom in the TBIJ’s testing and against three out of four snakes it outperformed one of the only anti-venoms approved by the WHO for use against some snakes in sub-Saharan Africa — PANAF, the anti-venom made by Premium Serums.
Neglected by the world
Very little anti-venom is manufactured in sub-Saharan Africa: the region receives as little as 2.5% of the anti-venom it needs, and depends on imports.
Snakebite is known as the most neglected of the neglected tropical diseases, only cementing its place on the WHO’s list of priority neglected tropical diseases in 2017, years after other diseases.
Most countries have agreed to a goal of halving global mortality and disability from snake bites by 2030.
However, in the five years since that goal was set, snakebites have received just $83m in funding for research and development. By comparison, Ebola got $1.65bn in similar funding. Ebola killed 2 485 people in those five years; snakebites may have killed more than 150 times as many.
Mail & Guardian article – The new snake oil: Anti0venoms that are as useless as water (Open access)
See more from MedicalBrief archives:
SA stocks of snake, scorpion and spider anti-venom dry up
Anti-venom failure leads to novel toxin immunology discovery
eSwatini’s snakebite success on shaky ground as US funding ends