As of this month, there have been more than 750 cases of measles in the U.S. this year across 23 states—the most since 1994, according to the Centers for Disease Control and Prevention. Measles was considered “eliminated” in the U.S. in 2000, although there have been small, sporadic outbreaks since then. A new study looks at how countries have pulled themselves out of past outbreaks of the disease—strategies that may need to be adapted in light of current vaccine hesitancy.

According to the study, published Thursday in Science, a country’s control of measles passes along a continuum with three different categories: a large number of cases every year, fewer cases overall but lots of year-to-year variability, and finally, consistently few or no cases. Knowing where a country lies in this continuum–referred to as a “canonical path”—could help it plan its response to the next outbreak, says senior author Justin Lessler, an epidemiologist and associate professor at the Johns Hopkins Bloomberg School of Public Health.

“This was really driven by the laws that govern measles transmission and measles epidemic dynamics,” Lessler says. In the past, “as you had increases in vaccination rates and decreases in birth rates it would really drive countries along this expected path.”

How different countries have progressed along the consistent and predictable path for measles outbreaks, 1990-2017. Credit: Matthew Graham, Amy K. Winter, Matthew Ferrari, Bryan Grenfell, William J. Moss, Andrew S. Azman, C. Jessica E. Metcalf, Justin Lessler

Lessler and his colleagues conducted a statistical analysis of measles outbreaks in countries worldwide between 1980 and 2017. By looking at weighted averages of measles cases and year-to-year variability, the researchers placed countries and regions at different points on the continuum. For example, Africa in 2008 was at almost exactly the same stage the Americas were in 1995, according to the research.

The study should also help a country direct its vaccination efforts, rather than fighting an outbreak based on the patterns of previous ones, Lessler says. If a prior outbreak was particularly severe among small children, many countries will be inclined to focus vaccination efforts on this age bracket, he says. But that is probably not the right approach. If childhood vaccination rates are high and birth rates low, the new analysis suggests that older children and teens may now be the most vulnerable, he says. “The path [the outbreak takes is] dictated by the size of the population you have that’s susceptible to measles,” Lessler says. “You could use the position along the path to understand the age distribution of susceptibility, which could help target vaccination efforts.”

Shweta Bansal, an associate professor of biology at Georgetown University in Washington, D.C., says the study allows countries to use a minimal amount of data to identify where they might be on that path. “As a public health communication tool, I think it’s quite powerful,” says Bansal, who was not involved in the research.

But as the current U.S. outbreaks demonstrate, even countries that had been almost completely measles-free for years are suddenly vulnerable again because people are declining to get vaccinated.

John Brownstein, an epidemiologist at Harvard Medical School who was not involved in the new study, says social media has changed the dynamics around measles and other vaccine-preventable diseases—and it is unclear what the repercussions will be. Brownstein says that when he was featured in a recent Facebook video encouraging measles vaccination, the post was flooded with comments opposing vaccines and spreading inaccurate information about both the disease and the vaccine. “It was pretty unbelievable,” says Brownstein, who is also Chief Innovation Officer at Boston Children’s Hospital. “I started trying to comment back to clarify, and the wave [of responses] just was too big for me to be able to handle.”

It is not clear, Brownstein says, whether historic trends of controlling diseases with vaccines can continue when so many people are passionately opposed to them. Vaccine hesitancy is not new or U.S. specific, he says: “Every location on earth has vaccine confidence issues.” But the internet makes it easier for people who oppose vaccines to find each other and share their opinions.

“There’s a combination of mistrust around government and pharmaceutical companies that is probably different” than with other public concerns, Brownstein says. “There’s also a component of the invasiveness of the needle that’s also at play in our psychology.”

Before vaccination, measles infected more than 95 percent of all children and was responsible for more than four million deaths worldwide each year. After the introduction of the measles vaccine in the 1960s, childhood deaths from not just measles but a wide range of infectious diseases dropped substantially. Measles seems to erase immune protections that the child has from other infectious diseases. According to a 2015 study in Science that examined historical data, measles outbreaks predict deaths from other childhood diseases two to three years later, suggesting that a measles infection made these children more vulnerable to diseases such as pneumonia and diarrhea.

Many people see measles infections as benign, particularly in young children, but teens and young adults suffer terribly, says Jeffrey Griffiths, a professor in the Department of Public Health and Community Medicine at Tufts University School of Medicine. “It’s a vicious, bad disease and it’s not like getting a cold,” he says. Malnourished children and those with vitamin A deficiencies are particularly vulnerable, with a death rate as high as 50 percent in parts of Africa, Griffiths adds.

The World Health Organization had hoped to eliminate measles worldwide by 2020. Lessler says that date is not realistic, but he and Bansal say they still believe it will someday be possible to eradicate measles. “Doing this kind of work requires strong optimism,” Bansal says. She adds that measles “represents an ideal case for eradication” because the pathogen is well understood, an effective vaccine exists—the recommended two doses seem to provide long-lasting immunity—and past U.S. experience shows it is possible to limit transmission of the disease for an extended period. “We have a much better chance of [eradicating measles] than other infections, but the challenge of vaccine hesitancy is certainly giving us all cause for concern,” she says.