What Rubella Can Teach Us About Zika
Originally published in the U.S. News & World Report
Doctors say the rampant spread of Zika virus in the Americas evokes parallels to the rubella epidemic in the 1960s that disabled thousands of children in the U.S. and worldwide, prompting many women to seek illegal abortions.
The same trends soon may be unfolding throughout Latin American and the Caribbean where, in the absence of a vaccine or treatment, public health officials in at least 25 countries and territories are working to slow the spread of the mosquito-borne Zika virus, which is believed to be linked to a steep rise in microcephaly, a potentially catastrophic birth defect in which babies are born with small craniums and brains. Suspicion also has risen that the virus is linked to a neurological condition called Guillain-Barre syndrome, which can cause paralysis.
"The fear that people have in these countries is similar to the fear we experienced in the early 1960s when rubella was king," says Dr. Paul Offit, director of the Vaccine Education Center at The Children's Hospital of Philadelphia. "Mothers were scared to death about contracting rubella in the first trimester of pregnancy, because their child would have an 85 percent chance of developing severe permanent defects of the ears, eyes and heart."
In Brazil, around 4,000 babies are estimated to have been born with microcephaly, and cases are expected to begin to mount in other Zika-affected countries as women infected early in pregnancy give birth. In some Latin American countries with local Zika transmission, public health officials have advised women to delay pregnancy. Some pregnant women are traveling abroad to have their babies.
Zika's similarities to rubella are striking, and the lessons learned during the rubella outbreak – especially the importance of a vaccine that can prevent devastating birth defects – are just as timely now as they were then, Offit says.
"Viruses can infect a pregnant woman and cause serious permanent defects in their babies," he says. "We can develop a vaccine to eliminate all that."
The push to develop a rubella vaccine began after an epidemic that took hold in Europe in 1963 spread to the U.S. The rubella virus spreads from person to person with harrowing speed through a cough or a sneeze. Every infected person infected from three to eight others, research showed.
Like Zika, which causes mild symptoms in about 20 percent of people infected by the virus, rubella was once thought to be a minor illness, causing malaise and a fleeting rash. But research soon showed that the virus affected virtually every part of the body, including the brain, lungs, liver, kidney, bone marrow and bones. An Australian doctor linked rubella to cataracts; it also was the leading cause of acquired deafness in infants in the U.S.
The U.S. Centers for Disease Control and Prevention reports that, from 1962 to 1965, 12.5 million people were infected with rubella nationwide. Approximately 85 percent of women of childbearing age were infected with the virus. And the earlier in pregnancy infection took hold, the higher the risk of giving birth to a child with complications. An estimated 20,000 babies were born with rubella complications, including microcephaly, and 2,100 newborns died.
In Philadelphia, 1 of every 100 pregnancies was complicated by rubella infections, says Dr. Stanley Plotkin, emeritus professor of pediatrics at the University of Pennsylvania Perelman School of Medicine and a developer of the widely used rubella vaccine.
As a result, a decade before Roe v. Wade legalized the practice in the U.S. – and before a vaccine was introduced in 1969 – infected mothers-to-be wrestled with decisions about "therapeutic" abortion. "They were properly worried," Plotkin says. "Many chose to terminate their pregnancies because the risk of abnormalities was so high. Naturally, at that time, abortion was illegal, in theory anyway. But it was done. And, in some respects, the rubella outbreak helped make therapeutic abortion acceptable."
It isn't clear how many women chose this option, as the best available estimates combine miscarriages and "therapeutic" abortions. Taken together, 11,250 pregnancies that were complicated by rubella ended in a miscarriage or an abortion, according to CDC statistics.
Plotkin, a pediatrician, practiced at the crossroads of science and patient care, studying the virus in an attempt to develop a rubella vaccine and counseling pregnant women who were fearful they might have contracted rubella, putting their newborns at risk.
"The women who came to see me wanted to complete their pregnancies," Plotkin says. "My role was primarily to determine … whether they had actually been infected."
Some women chose to have their babies, says Plotkin, who then took care of the infants and tracked their progress. For months after their birth, the newborns remained contagious, capable of spreading the virus to others.
"It was, to say the least, a very bad situation," Plotkin says.
It was clear from the beginning, he says, that only a vaccine could turn back the tide of babies born with rubella complications – and the growing number of women seeking to terminate pregnancies. The race to develop a vaccine was on, and the technology used to do so is still widely used today. Researchers take a live virus and grow it repeatedly in cell cultures, weakening it to reduce its virulence.
The first rubella vaccines were licensed in 1969 and 1970. By 1971, rubella vaccine was combined with vaccines for mumps and measles in what became known as the MMR vaccine.
By 2005, rubella was declared eliminated from the U.S. – but the jubilation was tempered by growing concerns over vaccine safety. That debate was fueled in 1998 by publication of a now-discredited studyin a medical journal that theorized a link between the MMR vaccine and autism. Since then, scientists have produced overwhelming evidence that the benefits of vaccines far outweigh the risks, and numerous studies have failed to demonstrate a link between autism and the vaccine. Still, some critics fret about vaccine safety, and many object to mandatory vaccination requirements, especially for preschoolers.
"You have to give people information that is easily understood, explaining the benefits and risks of a vaccine, and allow them to make a voluntary decision about whether to use those products," says Barbara Loe Fisher, co-founder and president of the National Vaccine Information Center, a Virginia-based nonprofit that advocates for informed consent protections surrounding vaccines.
Vaccine advocates say many vaccine critics have lost sight of the risks posed by failing to vaccinate children.
"The anti-vaccine movement has been fueled because we don't see diseases like rubella around anymore," says Anna Dragsbaek, president and CEO of The Immunization Partnership, a Texas nonprofit. "They don't understand the gravity of these diseases."
Zika may change that, especially if the virus continues to spread and evidence confirms that infection early in pregnancy leads to microcephaly and other developmental disorders. "Everywhere and anywhere there's vulnerability there's pressure for a vaccine," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
The U.S. government and at least three companies – the goliaths GlaxoSmithKline and Sanofi, as well as a small biotech firm named Inovio Pharmaceuticals, which may be furthest along – are in discussions about or have begun research into possible Zika vaccines. On Wednesday, Bharat Biotech in India announced that it had already developed two candidate vaccines.
Dr. William Schaffner, chairman of the Department of Preventive Medicine at the Vanderbilt University School of Medicine, says he is optimistic that a Zika vaccine is on the horizon. "The technology and the science are much advanced," he says.
But it will inevitably take a long time to develop a Zika vaccine. Even if one is made in much the same way as earlier successes – by taking live virus and weakening it in the laboratory – far stricter regulatory and safety requirements now in place will add years to the research effort, Offit says.
"In the 1960s, you could test a vaccine in 2,000 to 3,000 children," he says. "The consent form was a 3-by-5 inch card."
A trial of that size, he says, serves as a "reasonable" test of a vaccine's efficacy, but not its safety. "You're going to rule out common adverse events," he says, "but you're not going to rule out uncommon adverse events and certainly not rare ones." Those studies were typically done once a vaccine was on the market.
A vaccine must surmount far higher hurdles today. Consider the rotavirus vaccine called Rotarix, introduced by GlaxoSmithKline in 2008 and made using essentially the same technology as employed for rubella vaccine decades earlier. Researchers isolated virus from a boy in Cincinnati in 1989 and weakened it by growing successive generations in cell cultures. "The difference is that [Rotarix] was tested in 60,000 children-plus, and the consent form was 15 pages, double-spaced," Offit says. "Rotarix was a 25-year effort."
The goal: to rule out even rare complications before a vaccine reaches the doctor's office. And the additional effort comes at a steep cost. "In the 1960s, those efforts cost tens of millions," Offit says. "Today, it's a billion."
History suggests that, once a vaccine is developed, public health officials will move to vaccinate as many people as possible to protect them from Zika infection, though they may first target women of reproductive age because they are the most vulnerable, Schaffner says. Meanwhile, researchers have now confirmed a case of Zika spread through sexual intercourse.
"The adverse effects are sufficiently serious and tragic that we would want to vaccinate everybody," Schaffner says.
Clarified on Feb. 3, 2016: This story has been updated to clarify the state of Zika vaccine development efforts.