Monkeypox Cases in the US Are Falling. No One Knows Why

Are the vaccines working, are people changing their social behavior, is the virus burning itself out—and how will we know?

The explosive US monkeypox epidemic, now four months old, appears to be slowing down—although new cases, and serious complications, are still arising. The Centers for Disease Control and Prevention announced this week that two men in Colorado and Washington, DC, developed grave neurological problems that left them using walkers. Health authorities in California say a man there died as a result of monkeypox infection, and Texas experts are evaluating the death of a man in that state as well.

With 22,774 cases, the US has racked up almost two-fifths of the world’s total. Nevertheless, a recent CDC assessment says the epidemic’s “rate of growth is slowing.” In July, it took only eight days for the US case count to double; it takes approximately 25 days for the same to happen now. That the epidemic may be slowing is unquestionably good news. But there’s a catch: No one is quite sure why.

The drop in cases is almost certainly due in part to people changing their behavior. In a recent survey of gay and bisexual men, who are at most risk of infection, half said they had reduced their number of partners or types of sexual encounters. It may also be due to protection from the monkeypox vaccine, though that effort has rolled out slowly and a recent preprint (which is not yet peer-reviewed) questions the vaccine’s effectiveness. Or the decline could simply be due to the virus burning itself out as it exhausts the number of people likely to be exposed to it—a remote possibility, but one that researchers have to consider.

Discovering which scenario is correct is important because that knowledge could help predict what happens next. Behavior change regarding sex—using barrier methods, abstaining—is difficult to sustain long-term, because pleasure is a powerful motivator. For evidence, look at how we’ve never stopped syphilis from circulating despite centuries of trying. (Or, for that matter, never stopped unwanted pregnancies from occurring.) Because behavior change can lapse, protection via vaccines would likely be more durable—but only if they are successfully administered to the people who most need them, and only if they create lasting immunity. Not understanding the reasons for the decline makes it difficult to determine where the most effort, and the most money, should be spent: in campaigns for vaccination, for behavior change, or both.

Researchers say it’s far too early to know. “We’re always trying to make these calls very, very early in the game,” says Anne Rimoin, an epidemiologist and professor at the UCLA Fielding School of Public Health. “But the truth is, there’s still a lot that has to play out before we can make that kind of assessment. We’re in the to-be-determined phase.”

Part of the problem is that, despite these months of global emergency response, monkeypox remains an under-researched disease. Though it was endemic in several African countries for years before it broke worldwide in May, few researchers in rich countries considered it a priority. Until now, most epidemiological knowledge was gathered in rural communities where the main route of infection was from animals to humans, not from person to person. “The big problem with monkeypox is that all the data we have are from central and western Africa,” says Andrew Lover, an epidemiologist and assistant professor at the University of Massachusetts Amherst School of Public Health and Health Sciences. “We just really have no idea of what monkeypox looks like in a dense urban environment.”

Add to that: There’s little past experience with the vaccine, known as Jynneos in the US, being used against this disease. It was only approved by the US Food and Drug Administration in 2019, primarily for the prevention of smallpox in case that virus—eradicated from circulation by an earlier vaccine, but retained in two labs—was ever used as a biological weapon. Jynneos underwent human safety studies but was never tested for efficacy against monkeypox in people; those estimates are based on animal work. It has never been available commercially in the US, but was instead held in the National Strategic Stockpile as a safer alternative to that older smallpox vaccine, which can cause dangerous reactions in people with damaged immune systems. It was released to health departments only on the rare occasions when an infected traveler accidentally carried the virus into the US.

As a result, “we have no estimate of vaccine efficacy, given the modes of transmission that we are dealing with, which are very different than the modes of transmission that we traditionally see,” Rimoin says.

Now, of course, Jynneos is being administered everywhere, but it’s too early to draw conclusions about how much immunity those shots are creating. The vaccination campaign has been uneven: At first, there was so much demand in big coastal cities that men lined up for hours, online appointment dashboards filled up in minutes, and to stretch supplies, clinics held back on the second doses that lock in immunity. In response, the White House proposed a dose-splitting strategy that increased availability, though at the cost of requiring a different injection technique that some health care workers were unfamiliar with. Now, clinics in cities that were swamped by the first wave, such as New York, are posting thousands of new appointments regularly and are able to give second doses.

In some areas, in fact, there may be an oversupply. “Our demand has gone down significantly,” says Philip Huang, a physician and director of the Dallas County, Texas Health and Human Services Department. “We have empty appointments every day. We’re giving second doses.”

Health departments based their appointment offerings and vaccine allocation requests on their sense of how many men who have sex with men live in their communities, so those open appointments suggest that everyone who is eligible for protection may not be receiving it. They may not know they are at risk, they may fear the stigma of stepping forward, or they may not be aware the vaccine is available because overworked health departments do not have the time or personnel to craft precise messages to hard-to-reach groups. “We are still in an active public health emergency, a pandemic response, and our health department staffs are tired,” says Lori Tremmel Freeman, CEO of the National Association of County and City Health Officials.

And in a White House briefing this morning, federal health officials acknowledged those departments are strapped for cash to create their campaigns, in some cases moving money from HIV and STD programs to pay for vaccination workers and push out education. “Our local jurisdictions have received no resources specific for monkeypox,” CDC director Rochelle Walensky said. “It speaks to the need for supplemental funds.”

From here, a few different things could happen. People could accept the vaccine and either abstain from sex and skin-to-skin contact or practice safe sex rigorously, cases continue to decline, and the virus runs out of hosts. In another, vaccination doesn’t reach everyone who needs it or isn’t efficacious enough to protect them, and people miss sex and skin contact enough to let their protective behaviors slip. Then case numbers rise again as monkeypox settles in to being a sex-adjacent infection, as common—and potentially as dangerous—as gonorrhea or syphilis can be.

There’s a third scenario, though, and some researchers eyeing the downward trend in cases worry that it might already be happening. In this one, monkeypox appears to vanish but actually sticks around. It moves into groups in which it is less detectable—women, for instance, in whom lesions might be internal and thus harder to see—or it finds a new host in animals. Overall, it percolates at low enough levels to sustain itself. And then it bursts out again.

Andrew Noymer, an epidemiologist, demographer, and associate professor at the University of California, Irvine, describes this as “hyper-low endemicity.” This happened with smallpox, he points out. Accounts from before eradication describe what looks like a seasonal pattern, but even in the low months, transmission did not actually stop. It happens with influenza, which appears to vanish during warm weather as the case burden swaps from one hemisphere to the other. But work over decades has shown that some infections do occur in summer months.

It’s possible, Noymer argues, that this could happen for monkeypox as well. “Instead of hundreds of cases a day, nationwide, there could be a handful of cases a day,” he says. “Very low levels of disease can just go unnoticed. Monkeypox could just percolate through the same networks, causing mild cases until it starts becoming less mild again.”

The problem, as almost all researchers agree right now, is that it’s too soon to tell. There is not enough history to predict monkeypox’s trajectory, and not enough data to model its behavior with precision. The immediate future becomes a gamble, in which we bet that we can improve our knowledge and containment before the virus reveals what it’s capable of.

Monkeypox Cases in the US Are Falling. No One Knows Why

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