Rabies is a terrifying disease. Once the virus enters a human host — typically by way of a bite from an infected animal — it creeps along from nerve cell to nerve cell until it reaches the brain. It usually takes a month or more for symptoms to show. But when they do, the ensuing illness is usually marked by chilling neurological signs: delirium, hallucinations, aggressiveness, and a combination of hydrophobia (often including an intolerance for swallowing water) and increased saliva production, which leads to the hallmark foaming at the mouth. The luckier patients slip into a coma. Death is virtually inevitable. There have been only 29 documented survivors of rabies worldwide, and most suffered long-term neurological damage.
Luckily, the disease is also almost completely preventable — as long as the wound is thoroughly cleaned and a preemptive treatment, known as post-exposure prophylaxis, or PEP, is administered as quickly as possible before symptoms set in. Yet, as a physician assistant at an urgent care center, I find that some patients forego PEP after suffering animal bites that potentially expose them to rabies. Others pursue PEP when it's unlikely to be needed. Why?
As with many public health issues, the question is best understood in terms of costs and benefits. In the United States, the costs of rabies treatments are unnecessarily high, which may prevent lifesaving help from getting to the people who need it most. At the same time, the benefits of an individual treatment are difficult to estimate, so hasty decisions driven by fear of a deadly disease often result in PEP being recommended to the wrong patients.
It's worth noting that rabies is extremely rare in the U.S. Thanks mostly to strides in pet vaccination, there were just 18 cases of rabies acquired within U.S. borders between 2009 and 2018. Since the canine-specific variant was eradicated in 2004, the remaining virus survives mainly in the wild, carried predominantly by bats, raccoons, and skunks. The disease is uncommon enough to have become a safe target for comedy: It was a punchline in a 2007 episode of "The Office."
PEP treatments are expensive and time intensive. The Centers for Disease Control and Prevention estimates an average cost of $3,800 for the entire two-week course, not including fees for wound care and administration. Often the only place to get PEP is at a hospital emergency room, further adding to the tally. Some patients have reported medical bills exceeding $10,000. Even when insurance will cover the treatment, some bite victims decide it's not worth the time and effort, given the vanishingly small chances that a bite will lead to rabies.
But many patients do opt for PEP — some 55,000 Americans per year, according to the CDC. Collectively, the U.S. spends more than $200 million a year on PEP, or at least $500,000 for each prevented case of rabies, according to one estimate. Are all of these treatments necessary?
Several studies suggest the answer is no. A study of more than 2,000 animal exposure cases at 11 urban emergency departments throughout the country in the late 1990s found that, of the 136 patients who were given PEP, 40 percent did not meet the CDC's criteria for receiving the treatment. Some patients, for instance, were treated even though they were bitten by a dog or cat that could have been observed or a wild animal that could have been tested. (The study also identified 119 patients who were undertreated — not given PEP despite meeting the criteria for it. But all but one of those cases involved domestic animal bites, none of the patients developed rabies, and most were in low-risk regions where the study's authors posited that guidelines could be safely relaxed.)
Likewise, a recent study in suburban Cook County, Illinois found that more than half of patients who received PEP were given the treatment unnecessarily. Another recent study in King County, Washington found a similar rate of overtreatment. If even one third of rabies PEP treatments are given unnecessarily, that would mean about $70 million is wasted each year.
What is the ethical approach to rabies prevention when the risk from any individual bite is vanishingly small, but the cost of a mistake is almost certain death? Real tradeoffs are involved, but public health guidelines often adopt a level of conservatism akin to buying hurricane insurance in Nebraska. In France, for instance, where rabies is even rarer than in the U.S., researchers estimated that the existing approach to rabies prevention costs more lives — due to fatal traffic accidents involving patients driving to treatment centers — than it saves.
Rabies treatment guidelines vary from state to state. Ostensibly, they reflect the differences in rabies strains and animal populations between regions in the U.S., but it can be hard to tell why two states' recommendations differ. Compare Arkansas and Colorado: In Arkansas, if you are bitten by a pet dog and the attack wasn't provoked and the animal can't be found, the state recommends immediate rabies treatment. In Colorado, public health officials would instead recommend a thorough risk assessment based on the circumstances of the bite and where in the state it occurred. In each state, skunk and bat rabies predominate, and in each state a total of six dogs tested positive for rabies from 2013 to 2018.
While states make their own risk assessment decisions, all conform to the same PEP regimen: four doses of vaccine injected into the muscle at separate visits, plus several injections of antibodies around the wound at the first visit. This regimen is unnecessarily long and wastes precious vaccine. Techniques that inject vaccine into the skin rather than the underlying muscle, called intradermal shots, offer the same protection using less than half the amount of vaccine. Far from a fringe approach, a three-dose intradermal regimen for rabies PEP has been approved by the World Health Organization.
Despite this technological progress, public health authorities in the U.S. have been slow to adapt. The CDC's Advisory Committee on Immunization Practices (ACIP), which endorsed the current regimen in 2010, will update its recommendations this year or next. Agam Rao, a CDC medical officer who co-leads the ACIP Rabies Work Group, said that members of the committee are considering a shorter regimen, but skepticism remains. And whereas the WHO had to weigh the costs and benefits in countries where resources are limited in making its decision, Rao says that the U.S. can move more deliberately. "There really need to be robust data to support changing those recommendations," she said. "We can prioritize the data much more than maybe they could."
To be sure, given the horrifying consequences of rabies, preventive measures must err on the side of overtreatment. "You must have overkill in rabies vaccine," said Mary Warrell, a veteran rabies researcher from the University of Oxford. But Warrell, who has overseen some of the trials that point to the efficacy of shorter, cheaper PEP regimens, also criticized the U.S. approach: "It's ridiculously expensive, and it's an outdated regimen."
A shorter and less wasteful protocol in the U.S. would not only save money, it might free up resources to be used in countries with more rabies cases. Though rabies is rare in most of the rich world, it is an everyday threat in parts of Africa and Asia, where it kills an estimated 56,000 people a year. Many of those victims die because they cannot afford or cannot access vaccine and antibodies.
For the sake of the greater good, states should reexamine rabies guidelines with an eye toward relaxing them where it is safe to do so. In most cases, medical providers should consult with public health officials before recommending PEP. And when post-exposure prophylaxis is warranted, the treatment should be simplified by adopting a two or three-visit intradermal regimen, administered, when possible, in public health departments, primary care offices, or urgent care centers rather than emergency rooms. These simple changes based on sound science would enable the U.S. to keep overdoing it — but with less waste and lower costs.
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Gustav Cappaert is a physician assistant based in Black Mountain, North Carolina.