What Zika Researchers Can Learn From the Rubella Outbreak of 1964

Rubella is mostly a medical curiosity in the developed world today. Vaccines have eradicated the virus in the Western Hemisphere, and many doctors have never seen the disease outside of textbooks.

Now, public-health officials in the United States are looking back to the history of the disease as they try to figure out what to do about a threat unlike anything they’ve seen in decades. The Zika virus, a mosquito-borne illness believed to cause grave outcomes among fetuses infected in utero, has startling—and potentially useful—similarities to rubella.

So far, there have been no local transmissions of Zika in the United States, but officials are preparing for the possibility of an outbreak in several American cities this summer. If such an outbreak occurs, it will be the first of its kind—an epidemic-prone virus believed to cause serious birth defects—since the rubella outbreak of 1964. (Cytomegalovirus is an infection that can cause birth defects, but it isn’t prone to outbreaks.)

“What we learned about rubella and pregnancy, and how we learned it—we are definitely looking to those lessons as we learn more every day about Zika virus,” said Peggy Honein, who is a leading researcher into birth defects on the Centers for Disease Control’s Zika Response Team.

One hundred years ago, rubella—also known as German measles—was believed to be a mild sickness, with a nasty red rash as the most pronounced symptom. But conventional wisdom shifted in the early 1940s, when the scientist Norman Gregg began to ask questions about an unexplained surge of infants with congenital cataracts at the Royal Alexandra Hospital in Sydney, Australia.

There had been an outbreak of rubella in the region the year before, and Gregg found that nearly 90 percent of the mothers of the sick infants recalled having been infected with the virus in the first three months of their pregnancies. Soon, doctors in other countries confirmed similar links between rubella-infected mothers and babies with birth defects. Vision problems were just one complication from the virus—babies also suffered from deafness, congenital heart disease, enlarged spleens, liver problems, abnormalities of the bones and bone marrow, and bleeding disorders.

In the decade that followed, some women tried to build immunity to protect themselves before they got pregnant by holding “rubella parties,” according to a 1962 article in The New York Times. But things got worse before they got better. In 1964 and 1965, a rubella epidemic sickened more than 10 million people in the United States. “We are very fearful,” the director of the National Institute of Neurological Diseases and Blindness told The New York Times in 1965, as public-health officials waited for women infected during the outbreak to give birth. More than 2 million women had been exposed to the virus in the early—and most vulnerable—months of their pregnancies.

“As a consequence,” the Times wrote in April 1965, “thousands of babies bearing the marks of their mothers’ infection during that epidemic will soon be born—some having been delivered already—and there is nothing that can be done about it.”

The outbreak was indeed catastrophic for tens of thousands of babies born in the following months. Some 20,000 infants died from complications associated with rubella, and 30,000 more were born with severe birth defects. Thousands of women infected with rubella in the first trimester terminated their pregnancies.

Health officials raced to develop a rubella vaccine. The first one became available in the United States in 1969; within two years, 23 million children in the U.S. had been vaccinated. Sporadic outbreaks continued through the 1980s, but by the turn of the century, rubella was no longer endemic in the United States.

Now, public-health officials faced with growing evidence that the Zika virus causes birth defects are looking to rubella for clues on how to manage the illness—especially as mosquito season begins in the United States. Like rubella, Zika is usually mild for adults and children, but potentially deadly for fetuses.

“The similarities are great between rubella and Zika. Both are fever-rash illnesses, and both have arthropathy, or arthritis, as manifestations,” said Susan Reef, who leads the rubella team in the CDC’s Global Immunization Division. “Also like rubella, there’s an asymptomatic component to Zika, so not everyone knows when they’re infected with rubella or with Zika.”

One of the keys to treating Zika, Reef told me, will be for doctors to develop a more complete understanding of the clinical manifestations of Zika among pregnant women. With rubella, it took the epidemic of 1964 for that to happen.

Researchers are also trying to compare the mechanisms by which Zika and rubella might affect fetuses. A New England Journal of Medicine study published in March found “many aspects” of the viruses that are similar. Both seem to cross the placenta and restrict organ development. But there are key differences, too—and some of them are alarming.

“A major difference of concern between ZIKV infections in Brazil in 2015–2016 and rubella virus infections in the U.S. pandemic of 1959–1965 is the level of population immunity,” the researchers wrote. “[Today], none of the population has antibodies to ZIKV. In contrast, in the United States during the rubella epidemic, there were 20,000 cases of the congenital rubella syndrome, but in 1959 only 17.5 percent of women of childbearing age lacked rubella antibodies.”

Another crucial difference: Rubella is spread by person-to-person contact; whereas Zika is spread by mosquito bites and sexual transmission. But researchers don’t know how long babies born with Zika remain infected—potentially posing a risk to those around them. “We need more data on the impact of Zika on a neonate,” Reef said. “For rubella, the infants are infectious; they have congenital rubella syndrome for up to a year. But we have no idea about infants born with Zika.”

There are also questions about how congenital Zika might affect babies as they develop. Children with congenital rubella are more prone to thyroid problems and diabetes, but researchers don’t yet know what health problems might be caused by Zika later in childhood. “There is so much we don’t know about Zika,” Reef said.

Another unknown is whether a vaccine for Zika will even be possible—and if it is, how long it will take to create. “There are tremendous challenges in developing vaccines for mosquito borne illnesses,” Honein said.

Beyond that, scientists still don’t know whether there’s any point in a woman’s pregnancy where the risks believed to be associated with a Zika infection are diminished. Early evidence suggests that Zika infections acquired later in pregnancy—including well into the third trimester—can be deadly for fetuses; whereas the risk to the fetus of a mother infected with rubella drops significantly after the first 16 weeks of pregnancy.

Both Honein and Reef, who have each worked in health care for decades, agree Zika represents a rare and serious public-health risk unlike anything the United States has experienced in generations.

“Identifying new causes of birth defects is very challenging,” Honein told me. “It’s a very unusual finding to have a virus that we didn’t previously know was linked to adverse fetal defects. We are learning more every day, but it feels very unusual to me.”