As production slows, the lack of antivenom will put up to 10,000 people in developing African countries at risk for fatal snake bites by June 2016—an Ebola-scale epidemic.
About a decade ago, Thea Litschka-Koen developed a keen interest in snakes. Litschka-Koen, an owner of a management company in her native Swaziland, embraced her newfound fascination with all that slithers, and she immersed herself in studying them. By the late 2000s, she'd completed a set of handling courses, opened a snake-rescue park, and became a (largely self-taught) black mamba expert. Providing snake-removal services, she made her name known locally—and internationally, via a 2009 BBC2 documentary on her work. Given her reputation, it was only a matter of time before someone arrived at her door with a festering snakebite.
Zamokuhle, an 18-month-old girl, had been playing in her house when a Mozambique spitting cobra found its way inside. Averaging three and a half feet in length, these tawny gray serpents with flaring hoods are particularly deadly. Usually, they hock blinding venom at anything they consider a threat. Their poisonous spit can reach a distance of six and a half feet. But Zamo got too close too quickly, so it bit her leg. After visiting four clinics, and receiving only painkillers because there was no antivenom, Zamo and her mother reached Litschka-Koen. The cobra's venom, a necrotizing fluid, had destroyed most of the flesh between her calf and her ankle—so completely, you could see her bones.
Litschka-Koen took the girl to a nearby clinic, where doctors tried to arrest the child's mother for abusive neglect, but she informed officials of the mother's efforts and the other clinics' failures to help. This clinic, despite its judgments, couldn't do anything either. No one in the country could. Litschka-Koen had to call Dr. Sean Bush, an American snakebite expert, who evacuated Zamo to the US for seven months of treatment.
That's when Litschka-Koen realized how major the problem with snakebite treatments in her nation was. Later, she realized it wasn't just Swaziland. All of sub-Saharan Africa is in the middle of a decades-old snakebite crisis. Largely ignored by the media and health officials, the epidemic is vast and growing.
Last September, Doctors Without Borders put out a press release about Fav-Afrique, the most effective polyvalent antivenom in Africa. Production of the serum, used to combat the venom from ten deadly species, including spitting cobras, lapsed at the end of 2014, with no pharmaceutical company set to take over its manufacturing from France's Sanofi Pasteur. According to Doctors Without Borders, the last stocks will expire in June 2016, putting up to 10,000 people in developing countries at risk—an Ebola-scale epidemic.
Sanofi Pasteur announced it was winding down Fav-Afrique in 2010, giving ample reaction time. According to Professors Leslie Boyer and David Warrell, antivenom experts at the Universities of Arizona and Oxford, respectively, other antivenoms already provide similar coverage, and producers are also developing economically and medically viable Fav-Afrique replacements. Yet experts like Dr. Jean-Philippe Chippaux, a snakebite epidemiologist at the French Institute of Research for Development, think the press release was intended to raise awareness about a wider crisis brewing since the 1990s. Over the past quarter-century, sub-Saharan Africa's antivenom stocks dropped from 200,000 reliable doses to about 20,000 less reliable doses today. Chippaux believes the 500,000 doses per year are needed to treat its snakebite load.
A fifth of the world's 5 million annual bites, and more than a quarter of its at least 100,000 bite-related fatalities (not to mention a similar number of permanent disabilities and amputations), occur in sub-Saharan Africa. And those figures are likely conservative. Few snakebite victims make it to statistic-reporting hospitals. Recent epidemiological studies around the world lead Chippaux to suspect that Africa's burden is three to five times higher than these oft-cited figures.
Snakebites kill more annually than all 17 of the neglected tropical diseases combined—a list that includes dengue fever, leprosy, and rabies, for which the World Health Organization (WHO) has special programs. Some regions have more bites than malaria. "In some of the villages where I've worked in northern Nigeria, there's scarcely a family who hasn't lost someone to a snakebite in living memory," said Warrell.
Snakes are the second-deadliest animals in the world, behind mosquitoes. Yet producers are leaving the antivenom market in Africa, stocks are dwindling, and few authorities seem to care.
Antivenom production is difficult and expensive. It's also surprisingly similar to its 1896 origins. Technicians milk snakes for their venom, inject it into horses, wait about two months for antibodies to develop, draw buckets of blood, and separate out the serum. The biggest advance made in the past 119 years is the removal of substances that used to trigger anaphylactic shock, or another condition called "serum sickness," in many patients. But that refinement increases already high baseline costs, before regulatory cuts and shipping.
Each snake requires its own antivenom. Because most regional doctors only get cursory bite-treatment training, and because it requires great expertise to figure out what type of (usually unseen) snake bit someone based on a wound, clinics need to stock antivenoms for all local species. But the distribution of snakes is erratic, and epidemiological data is anemic, mooting targeted single-snake antivenom dissemination. So the production and procurement of polyvalent antivenoms is vital, but even more expensive than already-pricey single-serum antivenoms.
The result is a treatment that, in Africa, costs between $55 and $640, depending on local subsidies, species, healthcare systems, and the number of doses required for a particular bite.
Since meeting Zamo, Litschka-Koen has become a snakebite activist. She founded the Antivenom Swazi Trust Foundation, which raises money to buy serum and leads symposiums on treatment for local doctors low on relevant skill sets. "To treat a single Mozambique spitting cobra bite can cost an annual salary for a worker," she told me. "Our country can't afford to treat all the snakebite victims—there are too many."
Even when healthcare providers can afford antivenoms, they can't always store them. Many serums are liquid or freeze-dried, requiring refrigeration. In rural areas, where 95 percent of regional venom poisonings and 97 percent of deaths can occur, that's either unavailable or inaccessible.
And where serums are available and storable, according to Boyer, "the physicians in some places have completely lost faith in antivenom because they've been buying fraudulent products."
Warrell singled out two Indian manufacturers as key culprits in Africa: "Bharat Serums and Vaccines and the Serum Institute of India have produced antivenoms that purported to be for Africa, but were misleading and inappropriate." He said the companies used the Asian rather than the African species of particular snakes, leading to relative impotence and increased side effects. In response to studies about the relative ineffectiveness of the antivenom in question when used on bites from African species of the snake, BSaV said that the inclusion of Asian venom is listed in the product inserts or liner notes. However, this information may not always be readily visible to purchasers. "It has been a really, I think, criminal deception of slightly naïve purchasing authorities," Warrell said.
About a decade ago, when clinicians in Chad and northern Ghana switched from Fav-Afrique to budget antivenoms (sold at up to a tenth of Western product prices), they saw mortality rise from 2 to 15 percent. Litschka-Koen used to drive from clinic to clinic, reporting Indian antivenoms to the minister of health. For fear of similar results, she crusaded to get the clinics to finally stop ordering the inferior products.
Inaccessibility and bad experiences, combined with preexisting mistrust of healthcare systems, mean that only ten to 20 percent of snakebite victims seek and use antivenom treatments. Instead, many lean on suspect traditional healers. These cases largely go unreported, decreasing the perceived gravity of snakebites for outsiders. They also signal to manufacturers that there's no market for serious antivenoms, triggering production declines and pullouts.
"Why does Latin America not have the problem that Africa does?" Boyer asked. It's a fair question. Latin America has its share of venomous snakes, remote and ill-provisioned locales, and traditional healers. Yet the region has done well in terms of antivenom.
"Latin America has a long-standing tradition of providing its own antivenom," said Boyer, adding that its governments subsidize the treatment, evading supply and demand traps. "And lyophilized products [which survive on open shelves in the tropics] have been used [there] for years and years. Even though there are, periodically, small shortages, Latin American countries typically have pretty low prices because their ministries of health make massive purchases from these companies" and distribute the antivenom effectively via relatively adequate, reliable healthcare systems.
Not every African nation can have its own antivenom industry—only South Africa does—but many believe that outreach programs would restore faith in serums (which most will still use if they're cheap and proven effective). The creation of nationwide buying programs and better regulations on antivenom quality, combined with advances in epidemiological knowledge and production techniques, could produce viable, affordable antivenoms, even for remote usage.
A number of companies from Costa Rica to Spain to India are developing new techniques to produce economically and medically promising African polyvalent antivenoms. Spurred on by evolving crises involving counterfeit antimalarial drugs, nations are tackling fraudulent medications in general, which could help to rebuild confidence in antivenoms. There's currently research being conducted on the potential to make E. coli excrete protective proteins that can work as a prophylactic for numerous snake toxins.
Getting institutional support to fund research is the issue. There's so little money available that the aforementioned E. coli research is being crowdfunded. Even major antivenom producers often have to (or embrace the excuse to) forego proper clinical tests before rollout.
"It's very rarely that people will take snakebites seriously unless it's a day-to-day problem" for them, Warrell told me. "A snakebite is regarded as funny, scary, sort of biblical in its connotations, and something that can be laughed off and denied."
"A snakebite is a poor man's disease," said Litschka-Koen. "If snakebites affected the middle and upper class, we would have had a solution a long time ago. These people have no voice."
Plus, you can't eradicate snakes. They're environmental risks, and bites are difficult to mitigate. Perhaps that's why, in 2013, the WHO downgraded snakebites from a neglected tropical disease to a neglected condition with no major program to address them. From one vantage, that's a fair prioritization of scarce resources. From another, it leaves tens of thousands of the world's most vulnerable people at risk.
In 2012, Chippaux and some African colleagues formed the African Society of Toxinology. Over three years, the collective of activists and experts has crafted best practices and raised the visibility of snakebites. Through ambitious guidelines for willing states, they hope to reduce African bite mortality by 90 percent by 2020. It sounds utopic. But today, officials in at least seven nations have started working with the African Society of Toxinology on subsidy, training, and education programs, foreshadowing a possible sea change in countries' reticence to acknowledge or seriously, openly tackle snakebites.
The publicity Doctors Without Borders provided has given antivenom activists a shot in the arm by demonstrating the power and vectors of an effective snakebite PR campaign.
While awaiting breakthroughs, activists look to education as an immediate preventative tool. Getting people to wear shoes, use flashlights, and sleep with mosquito nets can drastically reduce bites. Kids, common victims, might not absorb these messages, and habitat encroachment is making it harder to avoid snakes. But education can help local and national leaders to see snakebites as something you can systematically address rather than an inevitable ailment. Community education could serve as a catalyst for the already promising changes the African Society of Toxinology and its allies are pushing forward across the continent. So there is hope.