The Parallels Between Congenital Rubella Syndrome & Congenital Zika Infection

The similarities between the early discovery of congenital rubella syndrome (CRS) and congenital Zika infection (CZI) provide some hope that “successes against rubella will be replicated against Zika virus, including the rapid development of an effective vaccine,” reported a team of researchers at the 2017 Annual Pediatric Academic Societies (PAS) meeting in San Francisco, California, on May 6-9.

The group, led by J.B. Cantey, MD, a physician in the department of pediatrics at Texas A&M Health Science Center in Temple, Texas, reviewed the history of CRS starting with the literature describing a 1940-1941 rubella epidemic in Australia, which ultimately led to the first description of the infection as a congenital issue. “An ophthalmologist named N. McAllister Gregg described 78 infants with congenital cataracts whose mothers had rubella during pregnancy,” Dr. Cantey explained during a “historic” poster session at PAS. He added that subsequent studies revealed that other symptoms of CRS, such as sensorineural hearing loss and patent ductus arteriosus, decreased in severity when the mothers became infected closer to their due dates. By 1969, a vaccine for rubella had been developed, and, a decade later, “CRS incidence had declined by more than 75%.” He concluded saying that CRS was considered “eradicated” in the United States in 2009.

“The history of CRS is similar to the early timeline of the CZI epidemic, including abrupt onset, rapidly accumulating literature, and efforts to fast-track a vaccine,” said Dr. Cantey. He said that, although it “remains to be seen” whether a successful Zika vaccine will eventually eradicate CZI, the parallels between the two epidemics give cause for hope. In addition, the group also cited the “long lag between initial discovery and identification as a congenital pathogen” to be another parallel between the two congenital syndromes. CRS was initially discovered in 1814, but it was not identified as a congenital disease until more than a century later, in 1941. Zika’s lag time is shorter, at about 63 years; the infection was discovered in 1952 and the congenital disease was identified in 2015 and confirmed in 2016 due, in large part, to a major outbreak in South America between 2014 and 2015. With CRS, once the congenital infection was confirmed, doctors began identifying mild and asymptomatic infants less than a year later and developed a vaccine within 5 years.

Should that pattern hold for Zika, an effective vaccine could be on the horizon. Given that Zika now has an animal model —on a similar timeline, again, to CRS – hopefully that vaccine is already underway. According to the National Institutes of Health (NIH)’s NIAID, multiple vaccines are currently in testing, with vaccines in trials between phases 1 and 2. One vaccine recently made headlines for a March phase 2 launch aiming to enroll around 2500 adults and adolescents in North and South America.

Another similarity between CZI and CRS is the “gradual recognition of other symptoms beyond the initial primary association,” Dr. Cantey said. With CZI, that “primary association” is microcephaly in infants, while with CRS it was congenital cataracts. Secondary associations for Zika account for a number of abnormalities, according to the Centers for Disease Control and Prevention (CDC), including “decreased brain tissue with a specific pattern of brain damage, damage to the back of the eye, congenital contractures, and hypertonia restricting body movement soon after birth.” The CDC also reports a link between CZI and several neurologic abnormalities, issues with neurologic function, and “excessive and redundant scalp skin.”

As the list of symptoms becomes more well-known, hopefully the next benchmark, the identification of “mild and asymptomatic infants,” will be in close reach, Dr. Cantey and his team hope. Soon thereafter, “the development of an effective vaccine that confers lifelong immunity to women of childbearing age and subsequent reduction in (and hopefully elimination of) CZI” will be developed, according to the presentation.