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  • The Return of Measles

    The Return of Measles

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    Measles seems poised to make a comeback in America. Two adults and two children staying at a migrant shelter in Chicago have gotten sick with the disease. A sick kid in Sacramento, California, may have exposed hundreds of people to the virus at the hospital. Three other people were diagnosed in Michigan, along with seven from the same elementary school in Florida. As of Thursday, 17 states have reported cases to the CDC since the start of the year. (For comparison, that total was 19, plus the District of Columbia, for all of 2023, and just 6 for 2022.) “We’ve got this pile of firewood,” Matthew Ferrari, the director of the Center for Infectious Disease Dynamics at Penn State, told me, “and the more outbreaks that keep happening, the more matches we’re throwing at it.”

    Who’s holding the matchbook? There’s an easy answer to who’s at fault. One of the nation’s political parties, and not the other, turned against vaccines to some extent during the pandemic, leading to voter disparities in death rates. One party, and not the other, has a presumptive presidential candidate who threatens to punish any school that infringes on parental rights by requiring immunizations. And one party, but not the other, appointed a vaccine-skeptical surgeon general in Florida who recently sidestepped standard public-health advice in the middle of an outbreak. The message from Republicans, as The Washington Post’s Alexandra Petri joked in a recent column, can sound like this: “We want measles in the schools and books out of them!”

    But the politics of vaccination, however grotesque it may be in 2024, obscures what’s really going on. It’s true that vaccine attitudes have become more polarized. Conservative parents in particular may be opting out of school vaccine requirements in higher numbers than they were before. In the blood-red state of Idaho, for example, more than 12 percent of kindergartners received exemptions from the rules for the 2022–23 school year, a staggering rate of refusal that is up by half from where it was just a few years ago. Politicized recalcitrance is unfortunate, to say the least, and it can be deadly. Even so, America’s political divides are simply not the cause of any recent measles outbreak. The virus has returned amid a swirl of global health inequities. Any foothold that it finds in the U.S. will be where hyperlocal social norms, not culture-war debates, are causing gaps in vaccine access and acceptance. The more this fact is overlooked, the more we’re all at risk.

    Consider where the latest measles cases have been sprouting up: By and large, the recent outbreaks have been a blue-state phenomenon. (Idaho has so far been untouched; the same is true for Utah, with the nation’s third-highest school-vaccine-exemption rate.) Zoom into the county level, and you’ll find that the pattern is repeated: Measles isn’t picking on Republican communities; if anything, it seems to be avoiding them. The recent outbreak in Florida unfolded not in a conservative area such as Sarasota, where vaccination coverage has been lagging, but rather in Biden-friendly Broward County, at a school where 97 percent of the students have received at least one MMR shot. Similarly, the recent cases in Michigan turned up not in any of the state’s MAGA-voting, vaccine-forgoing areas but among the diverse and relatively left-wing populations in and around Ann Arbor and Detroit.

    Stepping back to look at the country as a whole, one can’t even find a strong connection—or, really, any consistent link at all—between U.S. measles outbreaks, year to year, and U.S. children’s vaccination rates. Sure, the past three years for which we have student-immunization data might seem to show a pattern: Starting in the fall of 2020, the average rate of MMR coverage for incoming kindergarteners did drop, if only by a little bit, from 93.9 to 93.1 percent; at the same time, the annual number of reported measles cases went up almost tenfold, from 13 to 121. But stretch that window back one more year, and the relationship appears to be reversed. In 2019, America was doing great in terms of measles vaccination—across the country, 95.2 percent of kindergartners were getting immunized, according to the CDC—and yet, in spite of this fantastic progress, measles cases were exploding. More than 1,200 Americans got sick with the disease that year, as measles took its greatest toll in a generation.

    It’s not that our high measles-vaccination coverage didn’t matter then or that our slightly lower coverage doesn’t matter now. Vaccination rates should be higher; this is always true. In the face of such a contagious disease, 95 percent would be good; 99 percent much better. When fewer people are protected, more people can get sick. In Matthew Ferrari’s terms, a dropping immunization rate means the piles of firewood are getting bigger. If and when the flames do ignite, they could end up reaching farther, and burning longer, than they would have just a year or two ago. In the midst of any outbreak large enough, where thousands are affected, children will die.

    Despite America’s fevered national conversation about vaccines, however, rates of uptake simply haven’t changed that much. Even with the recent divot in our national vaccine rates, the country remains in broad agreement on the value of immunity: 93 percent of America’s kindergartners are getting measles shots, a rate that has barely budged for decades. The sheer resilience of this norm should not be downplayed or ignored or, even worse, reimagined as a state of grace from which we’ve fallen. Our protection remains strong. In Florida, the surgeon general’s lackadaisical response to the crisis at the Broward County elementary school did not produce a single extra case of the disease, in spite of grim predictions to the contrary, almost certainly thanks to how many kids are already vaccinated.

    At the same time, however, measles has been thriving overseas. Its reemergence in America is not a function of the nation’s political divides, but of the disease’s global prevalence. Europe had almost 60,000 cases last year, up from about 900 in 2022. The World Health Organization reports that the number of reported cases around the world surged to 306,000, after having dropped to a record low of 123,000 in 2021. As the pandemic has made apparent, our world is connected via pathogens: Large outbreaks in other countries, where vaccination coverage may be low, have a tendency to seed tiny outbreaks in the U.S., where coverage has been pretty high, but narrow and persistent cracks in our defenses still remain. (In 2022, more than half of the world’s unvaccinated infants were concentrated in just 10 countries; some of these are measles hotspots at this moment.) This also helps explain why so many Americans got measles in 2019. That was a catastrophic year for measles around the world, with 873,000 reported cases in total, the most since 1994. We had pretty good protection then, but the virus was everywhere—and so, the virus was here.

    In high-income countries such as the U.S., Ferrari told me, “clustering of risk” tends to be the source of measles outbreaks more than minor changes in vaccine coverage overall. Even in 2019, when more than 95 percent of American kindergarteners were getting immunized, we still had pockets of exposure where protection happened to be weakest. By far the biggest outbreak from that year occurred among Hasidic Jewish populations in New York State. Measles was imported via Israel from the hot spot of Ukraine, and took off within a group whose vaccination rates were much, much lower than their neighbors’. In the end, more than 1,100 people were infected during that outbreak, which began in October 2018 and lasted for nearly a year. “A national vaccination rate has one kind of meaning, but all outbreaks are local outbreaks,” Noel Brewer, a professor at the University of North Carolina at Chapel Hill and a member of the federal Advisory Committee on Immunization Practices, told me. “They happen on a specific street in a specific group of houses, where a group of people live and interact with each other. And those rates of vaccination in that specific place can drop well below the rate of coverage that will forestall an outbreak.”

    We’ve seen this time and time again over the past decade. When bigger outbreaks do occur in the U.S., they tend to happen in tight-knit communities, where immunization norms are radically out of sync with those of the rest of American society, politics aside. In 2014, when an outbreak of nearly 400 cases took hold in Ohio, almost entirely within the Amish community, the local vaccination rate was estimated to be about 14 percent. (The statewide number for young children at that time was more than 95 percent.) In 2011 and 2017, measles broke out among the large Somali American community in Minnesota, where anti-vaccine messaging has been intense, and where immunization rates for 2-year-olds dropped from 92 percent 20 years ago to 35 percent in 2021. An outbreak from the end of 2022, affecting 85 people in and around Columbus, Ohio, may well be linked to the nation’s second-biggest community of Somalis.

    Care must be taken in how these outbreaks are discussed. In Minnesota, for example, state health officials have avoided calling out the Somali community, for fear of stigmatizing. But another sort of trouble may arise when Americans overlook exactly who’s at risk, and exactly why. Experts broadly agree that the most effective way to deal with local outbreaks is with local interventions. Brewer pointed out that during the 2019 outbreak in New York, for example, nurses who belonged to local Jewish congregations took on the role of vaccine advocates. In Minnesota, the Department of Health has brought on more Somali staff, who coordinate with local Somali radio and TV stations to share its message. Yet these efforts can be obscured by news coverage of the crisis that points to a growing anti-science movement and parents giving up on vaccination all across the land. When measles spread among New York’s orthodox Jews, The New York Times reported on “an anti-vaccine fervor on the left that is increasingly worrying health authorities.” When the virus hit Columbus, NBC News noted that it was “happening as resistance to school vaccination requirements is spreading across the country.”

    Two different public-health responses can be undertaken in concert, the experts told me: You treat the problem at its source, and you also take the chance to highlight broader trends. A spate of measles cases in one community becomes an opportunity for pushing vaccination everywhere. “That’s always an important thing for us to do,” Ferrari said. Even so, the impulse to nationalize the problem will have its own, infelicitous effects. First, it’s meaningfully misleading. By catastrophizing subtle shifts in vaccination rates, we frighten many parents for no reason. By insisting that every tiny outbreak is a product of our national politics, we distract attention from the smaller measures that can and should be taken—well ahead of any upsurge of disease—to address hyperlocal vaccination crises. And by exaggerating the scale of our divisions—by asserting that we’ve seen a dangerous shift on a massive scale, or an anti-vaccine takeover of the Republican Party—we may end up worsening the very problem that worries us the most.

    We are a highly vaccinated nation, our politics notwithstanding. Telling people otherwise only fosters more division; it feeds the feeling that taking or refusing measles shots is an important mode of self-expression. It further polarizes health behavior, which can only widen the cracks in our defenses. “We have become quite militant and moralistic about vaccination,” Brewer told me, “and we probably would do well to be less absolute.” Measles outbreaks overseas are growing; measles outbreaks here will follow. Their specific causes ought not be ignored.

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    Daniel Engber

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  • A Gaping Hole in Cancer-Therapy Trials

    A Gaping Hole in Cancer-Therapy Trials

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    This article was originally published by Undark Magazine.

    In October 2021, 84-year-old Jim Yeldell was diagnosed with Stage 3 lung cancer. The first drug he tried disrupted his balance and coordination, so his doctor halved the dose to minimize these side effects, Yeldell recalls. In addition, his physician recommended a course of treatment that included chemotherapy, radiation, and a drug targeting a specific genetic mutation. This combination can be extremely effective—at least in younger people—but it can also be “incredibly toxic” in older, frail people, says Elizabeth Kvale, a palliative-care specialist at Baylor College of Medicine, and also Yeldell’s daughter-in-law.

    Older patients are often underrepresented in clinical trials of new cancer treatments, including the one offered to Yeldell. As a result, he only learned of the potential for toxicity because his daughter-in-law had witnessed the treatment’s severe side effects in the older adults at her clinic.

    This dearth of age-specific data has profound implications for clinical care, because older adults are more likely than younger people to be diagnosed with cancer. In the U.S., approximately 42 percent of people with cancer are over the age of 70—a number that could grow in the years to come—yet they comprise less than a quarter of the people in clinical trials to test new cancer treatments. Many of those who do participate are the healthiest of the aged, who may not have common age-related conditions like diabetes or poor kidney or heart function, says Mina Sedrak, a medical oncologist and the deputy director of the Center for Cancer and Aging at City of Hope National Medical Center.

    For decades, clinical trials have tended to exclude older participants for reasons that include concerns about preexisting conditions and other medications and participants’ ability to travel to trial locations. As a result, clinicians cannot be as certain that approved cancer drugs will work as predicted in clinical trials for the people most likely to have cancer. This dearth of data means that older cancer patients must decide if they want to pursue a treatment that might yield fewer benefits—and cause more side effects—than it did for younger people in the clinical trial.

    This evidence gap extends across the spectrum of cancer treatments—from chemotherapy and radiation to immune-checkpoint inhibitors—with sometimes-dire results. Many forms of chemotherapy, for example, have proved to be more toxic in older adults, a discovery that came only after the drugs were approved for use in this population. “This is a huge problem,” Sedrak says. In an effort to minimize side effects, doctors will often tweak the dose or duration of medications that are given to older adults, but these physicians are doing this without any real guidance.

    Despite recommendations from funders and regulators, as well as extensive media coverage, not much has changed in the past three decades. “We’re in this space where everyone agrees this is a problem, but there’s very little guidance on how to do better for older adults,” Kvale says. “The consequences in the real world are stark.”


    Post-approval studies of cancer drugs have helped shed light on the disconnect between how these drugs are used in clinical trials and how they are used in clinics around the country.

    For example, when Cary Gross, a physician and cancer researcher at Yale, set out to study the use of a new kind of cancer drug known as an immune-checkpoint inhibitor, he knew that most clinicians were well aware that clinical trials overlooked older patients. Gross’s research team suspected that some doctors might be wary of offering older adults the treatments, which work by preventing immune cells from switching off, thus allowing them to kill cancer cells. “Maybe they’re going to be more careful,” he says, and offer the intervention to younger patients first.

    But in a 2018 analysis of more than 3,000 patients, Gross and his colleagues found that within four months of approval by the FDA, most patients eligible to receive a class of immune-checkpoint inhibitors were being prescribed the drugs. And the patients receiving this treatment in clinics were significantly older than those in the clinical trials. “Oncologists were very ready to give these drugs to the older patients, even though they’re not as well represented,” Gross says.

    In another analysis, published this year, Gross and his colleagues examined how these drugs helped people diagnosed with certain types of lung cancer. The team found that the drugs extended the life of patients under the age of 55 by a median of four and a half months, but only by a month in those over the age of 75.

    The evidence doesn’t suggest that checkpoint inhibitors aren’t helpful for many patients, Gross says. But it’s important to identify which particular populations are helped the most by these drugs. “I thought that we would see a greater survival benefit than we did,” he says. “It really calls into question how we’re doing research, and we really have to double down on doing more research that includes older patients.”

    People over the age of 65 don’t fare well with other types of cancer treatments either. About half of older patients with advanced cancer experience severe and even potentially life-threatening side effects with chemotherapy, which can lead oncologists to lower medication doses, as in Yeldell’s case.

    There’s a strong connection between the lack of evidence from clinical trials and worse outcomes in the clinic, according to Kvale. “There’s a lot of enthusiasm for these medicines that don’t seem so toxic up front,” she says, “but understanding where they do or don’t work well is key—not just because of the efficacy, but because those drugs are almost toxically expensive sometimes.”

    Since the earliest reports of this data gap, regulators and researchers have tried to fix the problem. Changes to clinical trials have, in principle, made it easier for older adults to sign up. For instance, fewer and fewer studies have an upper age limit for participants. Last year, the FDA issued guidance to industry-funded trials recommending the inclusion of older adults and relaxing other criteria, to allow for participants with natural age-related declines. Still, the problem persists.

    When Sedrak and his colleagues set out to understand why the needle had moved so little over the past few decades, their analysis found a number of explanations, beginning with eligibility criteria that may inadvertently disqualify older adults. Physicians may also be concerned about their older patients’ ability to tolerate unknown side effects of new drugs. Patients and caregivers share these concerns. The logistics of participation can also prove problematic.

    “But of all these, the main driving force, the upstream force, is that trials are not designed with older adults in mind,” Sedrak says. Clinical trials tend to focus on survival, and although older adults do care about this, many of them have other motivations—and concerns—when considering treatment.


    Clinical trials are generally geared toward measuring improvements in health: They may track the size of tumors or months of life gained. These issues aren’t always top of mind for older adults, according to Sedrak. He says he’s more likely to hear questions about how side effects may influence the patient’s cognitive function, ability to live independently, and more. “We don’t design trials that capture the end points that older adults want to know,” he says.

    As a group, older adults do experience more side effects, sometimes so severe that the cure rivals the disease. In the absence of evidence from clinical trials, clinicians and patients have tried to find other ways to predict how a patient’s age might influence their response to treatment. In Yeldell’s case, discussions with Kvale and his care team led him to choose a less intensive course of treatment that has kept his cancer stable since October 2022. He continues to live in his own home and exercises with a trainer three times a week.

    For others trying to weigh their choices, researchers are developing tools that can create a more complete picture by accounting for a person’s physiological age. In a 2021 clinical trial, Supriya Mohile, a geriatric oncologist at the University of Rochester, and her colleagues tested the use of one such tool, known as a geriatric assessment, on the side effects and toxicity of cancer treatments. The tool assesses a person’s biological age based on various physiological tests.

    The team recruited more than 700 people with an average age of 77 who were about to embark on a new cancer-treatment regimen with a high risk of toxicity. Roughly half of the participants received guided treatment-management recommendations based on a geriatric assessment, which their oncologists factored into their treatment decisions. Only half of this group of patients experienced serious side effects from chemotherapy, compared with 71 percent of those who didn’t receive specialized treatment recommendations.

    This type of assessment can help avoid both undertreatment of people who might benefit from chemotherapy and overtreatment of those at risk of serious side effects, Mohile says. It doesn’t compensate for the lack of data on older adults. But in the absence of that evidence, tools such as geriatric assessment can help clinicians, patients, and families make better-informed choices. “We’re kind of going backwards around the problem,” Mohile says. Although geriatric oncologists recognize the need for better ways to make decisions, she says, “I think the geriatric assessment needs to be implemented until we have better clinical-trial data.”

    Since 2018, the American Society of Clinical Oncology has recommended the use of geriatric assessment to guide cancer care for older patients. But clinicians have been slow to follow through in their practice, in part because the assessment doesn’t necessarily show any cancer-specific benefits, such as tumors shrinking and people living longer. Instead, the tool’s main purpose is to improve quality of life. “We need more prospective therapeutic trials in older adults, but we also need all of these other mechanisms to be funded,” Mohile says, “So we actually know what to do for older adults who are in the real world.”

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    Jyoti Madhusoodanan

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