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Tag: infectious-disease specialist

  • We Got Lucky With the Mystery Dog Illness

    We Got Lucky With the Mystery Dog Illness

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    In late July 1980, a five-month-old Doberman pinscher puppy in Washington, D.C., started throwing up blood. It died the next day at an animal hospital, one of many pets that suffered that year from a new illness, parvovirus. “This is the worst disease I’ve ever seen in dogs,” a local veterinarian told The Washington Post, in an article describing the regional outbreak. It killed so fast that it left pet owners in disbelief, he said.

    The world was in the middle of a canine pandemic. The parvovirus, which was first recognized in 1978, can live for months outside the body, spreading not just from animal to animal but through feces, sneaking into the yards of dog owners via a bit of excrement stuck to the bottom of a person’s shoe. It quickly traveled across countries and continents, infecting thousands and possibly millions of dogs in the late ’70s and early ’80s. Essentially every dog alive at the time caught it, Colin Parrish, a virology professor at Cornell University’s College of Veterinary Medicine, told me. And untold numbers  died: A single Associated Press report from August 1980 mentions the city of Chicago losing 300 dogs by July of that year, and South Carolina losing more than 700 in just two months.

    A vaccine was quickly developed, but with doses in short supply, the outbreaks dragged on for years. Today, puppies are routinely vaccinated for parvovirus, and the 1978 canine pandemic has faded from public consciousness. Since then, no outbreak has unfolded on that scale, even as dogs have become more integrated into American households. Few people stay up at night worrying about what might happen if a new and devastating disease did appear. Yet, for a moment at the end of last year, it seemed like one might have.

    In late 2023, veterinarians started noticing something odd. They’d seen an uptick in cases of dogs sick with respiratory symptoms responding poorly to antibiotics. Some would develop severe pneumonia quickly and die. Soon, cases of this suspected illness started popping up in states across the country. Around Thanksgiving, media reports began warning dog owners about a “mystery dog illness” spreading nationwide.

    Many experts now suggest that there probably was no “mystery dog illness.” More likely, some mix of previously known illnesses were surging around the same time. Still, the case is not entirely closed, and the prospect of a deadly new disease has left dog owners fearful and jumpy: How much should they worry? Could that seemingly normal cough in the family pet actually be something much more dangerous?

    And if a new disease had started a modern dog pandemic, the world’s first in almost 50 years, what would have happened next is not entirely clear. Unlike humans and livestock, companion animals do not have sophisticated, coordinated infrastructure dedicated to monitoring and managing their diseases. The technology and science might exist to fight a dog pandemic, but any response would depend on what kind of illness we found ourselves dealing with—and whether it could infect humans as well.

    Because dogs don’t interact with one another as much as humans do, dog transmission networks are different from ours. They see one another on walks, in day cares, or in dog parks. Some might travel between states or even between countries, but many just stay in their backyard. Their cloistered networks make it hard for some viruses to move among them. In 2015 and 2016, outbreaks of a nasty canine flu called H3N2, which was traced to a single introduction in the United States from South Korea, never reached full pandemic status. “I just remember seeing so many of these pretty sick dogs, like every day,” Steve Valeika, a veterinarian and infectious-disease specialist in North Carolina, told me. “And then it just stopped.” Most of his cases were from one boarding facility.

    A disease such as parvo, which can spread without direct contact, has a better chance of circulating widely. But even then, authorities could respond quickly, maybe even quicker than in 1978. The same mRNA tools that led to the speedy development of a COVID vaccine for humans could be used in a dog pandemic; the ability to test for dog diseases has improved since parvovirus. Information travels that much faster over the internet.

    Still, as companion animals, dogs and cats fall into an awkward space between systems. “There is no CDC for dogs,” Valeika said. “It’s all very patchwork.” Typically, animal disease is managed by agricultural agencies—in this country, the USDA. But these groups are more focused on outbreaks in livestock, such as swine flu, which threaten the food supply, the economy, or human safety. If an outbreak were to emerge in companion animals, veterinary associations, local health departments, and other dog-health groups may all pitch in to help manage it.

    The dairy and pig industries, for example, are far more coordinated. “If they said, ‘We need to get all the players together to talk about a new emerging disease issue on pigs,’ that’d be easy. They’d know who to call, and they’d be on the phone that afternoon,” Scott Weese, professor in veterinary infectious diseases at the University of Guelph, in Canada, explains. Organizing a conference call like that on the topic of a dog disease would be trickier, especially in a big country like the United States. And the USDA isn’t designed around pets, although “it’s not that they don’t care or don’t try,” he said. (The USDA did not respond to a request for comment.) No one is formally surveilling for dog disease in the way government agencies and other groups monitor for human outbreaks. At base, monitoring requires testing, which is expensive and might not change a vet’s treatment plan. “How many people want to spend $250 to get their swab tested?” Parrish asked.

    Dogs aren’t human. But they are close to humans, and it is easy to imagine that, in a dog pandemic, owners would go to great lengths to keep their pets safe. Their closeness to us, in this way, could help protect them. It also poses its own risk: If a quickly spreading dog disease jumped to humans, a different machinery would grind into gear.

    If humans could be vulnerable and certainly if they were getting sick, then the CDC would get involved. “Public health usually takes the lead on anything where we’ve got that human and animal side,” Weese told me. These groups are better funded, are better staffed, and have more expertise—but their priority is us, not our pets. The uncomfortable truth about zoonotic disease is that culling, or killing, animals helps limit spread. In 2014, after a health-care worker in Spain contracted Ebola, authorities killed her dog Excalibur as a precaution, despite a petition and protests. When the woman recovered, she was devastated. (“I’ve forgotten about everything except the death of Excalibur,” she later told CNN.) Countries routinely cull thousands of livestock animals when dealing with the spread of deadly diseases. If a new dog-borne pathogen threatened the lives of people, the U.S. would be faced with the choice of killing infected animals or dedicating resources to quarantining them.

    A scenario in which pet owners stand by while their dogs are killed en masse is hard to imagine. People love their pets fiercely, and consider them family; many would push to save their dogs. But even in a scenario where humans were safe, the systems we’ve set up might not be able to keep pets from dying on a disturbing scale. Already, there’s a nationwide shortage of vets; in a dog-health emergency, people would want access to emergency care, and equipment such as ventilators. “I am concerned that we don’t have enough of that to deal with a big pandemic as it relates to pets,” Jane Sykes, a medicine and epidemiology professor at the UC Davis School of Veterinary Medicine and the founder of the International Society for Companion Animal Infectious Diseases, told me.

    Congress has mandated that the CDC, USDA, and Department of the Interior, which oversees wildlife, work on strengthening “federal coordination and collaboration on threats related to diseases that can spread between animals and people,” Colin Basler, the deputy director of CDC’s One Health Office, wrote in an email statement. A new, deadly canine disease would almost certainly leave experts scrambling to respond, in some way. And in that scramble, pet owners could be left in a temporary information vacuum, worrying about the health of their little cold-nosed, four-legged creatures. The specifics of any pandemic story depend on the disease—how fast it moves, how it sickens and kills, and how quickly—but in almost any scenario it’s easy to imagine the moment when someone fears for their pet and doesn’t know what help will come, and how soon.

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    Caroline Mimbs Nyce

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  • America May Be Missing Out on a Better COVID Treatment

    America May Be Missing Out on a Better COVID Treatment

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    Japan is home to an untold number of conveniences and delights that American consumers regularly go without: Faster public transit! Better sunscreen! Lychee KitKats! But as we head into sick season, one Japanese invention would be especially welcome on the U.S. market: an antiviral pill that appears to shorten COVID symptoms, might protect against chronic disease, and doesn’t taste like soapy grapefruit.

    Ensitrelvir, a drug made by the Osaka-based pharmaceutical company Shionogi, was conditionally approved in Japan last November. Like Paxlovid, ensitrelvir works by blocking an enzyme that the SARS-CoV-2 virus uses to clone itself inside the human body. But for the millions of Americans who will likely get COVID in the coming months, the new drug is almost certain to be out of reach. In 2021, Pfizer waited just five weeks for Paxlovid to receive its emergency use authorization. But ensitrelvir is still sitting in the approval pipeline, stuck in another round of clinical trials that may run well into 2024.

    Existing data (not all of which have been peer-reviewed) show that people with COVID who promptly take ensitrelvir, marketed as Xocova in Japan, test negative about 36 hours faster than people who take a placebo. Fever, congestion, sore throat, cough, and fatigue disappear about a day earlier too. Even smell and taste loss appear to resolve more quickly. The company also has some tentative evidence suggesting that the drug can help protect patients from developing long COVID.

    These findings were not enough for the FDA, but they are extremely encouraging, says Michael Lin, a bioengineering professor at Stanford University who works on drugs for treating coronavirus infections. Xocova “looked as good or a little bit better than Paxlovid,” he says. For instance, Pfizer’s clinical trials failed to show that Paxlovid clears symptoms any faster than a placebo in people who aren’t at high risk of developing severe COVID. Shionogi’s did just that.

    Reshma Ramachandran, a family physician at Yale, told me that if the early Xocova results hold up in additional trials, she’d be inclined to prescribe it to her vaccinated patients in place of Paxlovid, simply because the evidence supporting its use is more direct. She said she’d be especially keen to give Xocova if the long-COVID finding can be reproduced.

    No lab or pharmaceutical company has yet published a study that pits Xocova against Paxlovid head-to-head in treating COVID, so it’s impossible to say with certainty which one is better. You can’t draw conclusions just by comparing Pfizer’s clinical-trial results with Shionogi’s: Their drugs were tested in different populations with different levels of immunity at different points in the pandemic when different variants were circulating. Shionogi also required clinical-trial participants to start taking Xocova within three days of feeling sick, whereas patients in the Paxlovid trials began their treatment up to five days after symptoms started. Daniel Griffin, an infectious-disease specialist at Columbia University, told me that timing is everything when it comes to antivirals: In general, the sooner a patient starts taking a drug, the better it works.

    A Pfizer spokesperson told me that the efficacy and adverse-event rates of Paxlovid and Xocova cannot directly be compared, and emphasized Paxlovid’s power to stave off hospitalization and death. (Xocova’s clinical trials were not able to provide meaningful data on those outcomes, which are now much rarer than they were in 2021.) “Since the beginning of the pandemic, we’ve known it will take multiple treatment options and preventative measures for the world to overcome the challenges of COVID-19,” he said in an email.

    Even if Xocova turns out to be no more effective than Paxlovid, it still has several practical advantages. For one thing, it is literally easier to swallow. Paxlovid must be taken twice a day for five days, and each time you have to gulp down three pills: two containing nirmatrelvir (which actively combats the virus), plus one containing ritonavir (which slows the metabolism of nirmatrelvir, keeping it in your system longer). Xocova is taken just once a day for five days, and after the first three-pill dose, it’s one pill at a time. Paxlovid can also cause dysgeusia, a.k.a. Paxlovid mouth—a sour, metallic, taste that may last for hours after swallowing. Xocova seems to taste just fine.

    Experts hope that Xocova will be more widely accessible than Paxlovid, too. Pfizer announced last week that the price of Paxlovid will soon rise from $529 to $1,390 when the drug enters the commercial market. Shionogi hasn’t decided on Xocova’s price in the U.S. market, but there’s reason to think it will be cheaper. In Japan, the only market where both drugs are currently available, a course of Xocova costs 51,851 yen (about $346), and Paxlovid is nearly double the price, at 99,027 yen (about $661). And whereas Japanese health authorities—like those in the U.S.—have recommended Paxlovid for use by patients at high risk of severe COVID, Xocova has been shown to benefit people with infections regardless of their risk status. Finally, whereas Paxlovid’s reach is limited by its many harmful interactions with other drugs, Xocova might pose fewer problems because it doesn’t contain ritonavir, Lin told me. The newer drug’s interaction profile is still being ironed out, but a company spokesperson pointed me to a running list from the University of Liverpool. (According to that source, you should avoid taking Paxlovid and Adderall at the same time—but going on Xocova is fine.)

    Xocova may also sidestep one of patients’ most commonly voiced concerns about Paxlovid: that it will make their COVID go away and then return. One recent observational study of COVID patients found that symptoms rebounded among 19 percent of Paxlovid takers, versus 7 percent of nontakers. By contrast, Shionogi has reported that symptom rebound was vanishingly rare in its clinical trials of Xocova.

    Neither Shionogi nor the FDA would give me an estimate of Xocova’s approval timeline in the U.S., but earlier this year, the company’s CEO estimated that it might get the nod in late 2024. This past spring, the FDA gave the drug “fast track” status, which means Xocova will be eligible for an expedited review process once the company submits its application. (The FDA declined to comment on Xocova’s prospects for approval, citing federal disclosure laws.) Until then, it’s running more clinical trials in the U.S. and abroad. One of them, conducted in partnership with the National Institutes of Health, will evaluate the drug’s performance in hospitalized patients. Another will evaluate its efficacy against long COVID, among other things.

    To some experts, Xocova’s track is not nearly fast enough. David Boulware, an infectious-disease specialist at the University of Minnesota, told me that the FDA appears to be “slow walking” the approval process. Lin, too, would like to see more action. But it’s not clear how, exactly, that would happen. “I think the FDA is doing all that they can,” Ramachandran said; an emergency use authorization for Xocova isn’t a realistic option, given that the COVID public-health emergency has expired. Plus, Griffin said, caution is prudent when dealing with new drugs. “We want to make sure it’s safe. We want to make sure it’s effective,” he told me. “We also don’t want to fall into the trap we fell in with molnupiravir,” an earlier antiviral that looked promising at first, but ultimately offered disappointing benefits to COVID patients (though a surprising utility for cats).

    If the FDA were to approve Xocova tomorrow, demand for Paxlovid likely wouldn’t disappear, experts told me. Lin said the two drugs might compete for users, like Motrin and Aleve. People who are in danger of being hospitalized or dying from COVID could still opt for Paxlovid. “But there’s a much larger group of people who just feel crummy, and they just want to feel better,” Griffin told me. For them, Xocova could make more sense. They just won’t have a choice until the FDA approves it.

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    Rachel Gutman-Wei

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