Long-term global threat posed by Zika virus remains unknown, review finds

Investigator pictured

The Zika virus could become endemic in parts of Central and South America, but the long-term global threat posed by the virus remains unclear without more research, according to the authors of a paper published online in today’s issue of the journal Science.

“One of the big questions about this outbreak is whether Zika virus will stick around or disappear after causing this sizeable outbreak across many countries in the region,” said Derek Cummings, a professor of biology at the Emerging Pathogens Institute and a co-author of the review. “Two major determinants of the ability of the virus to persist are the role of immunity and the breadth of host species that can contribute to the ongoing transmission of the virus.”

Genetic analysis of the Zika virus suggests that there are already permanent viral reservoirs in other regions.

Discovered in the Zika forest of Uganda in 1947, the virus soon split into African and Asian “clades” or viral strains. The African strain is maintained in an enzootic cycle of transmission, where transmission between non-human primates occurs regularly and the role of transmission among humans is unclear.

“The clear split of Asian and African Zika virus isolates into distinct clades provides some evidence of endemic transmission in these regions,” said Kyra Grantz, a research assistant working with Cummings. Grantz, a contributing author to the paper, conducted the phylogenetic analysis of Zika virus for the review.

Said Cummings: “Humans may be infected regularly in many settings in Africa, supporting long-term transmission, or they may be infected only occasionally, and non-human primates play the central role of maintaining the virus.

“In all places where there is evidence of persistent transmission of Zika, there is a plausible role for non-human primates in contributing to the maintenance of transmission,” he added. “In the Americas, non-human primates could also contribute to Zika persisting after this initial outbreak, as ZIKV has been detected in two species of non-human primates.”

While scientists have shown that the Zika virus is enzootic within Sub-Saharan Africa, they’re still not sure whether primate species, including humans, are the only group of animals that can host the Zika virus, or whether the range of potential hosts includes other animals groups as well.

The role of genetically related pathogens in determining the global pattern of Zika is also unclear.

“Zika is closely related to dengue and several other flaviviruses whose epidemiology, natural history, and public health impact is much better studied,” Grantz said. “Yet it remains to be seen just how similarly Zika virus will behave to its genetic relatives. It is also possible that past exposure to closely related flaviviruses could give rise to protective immunity against Zika virus, or even enhance risk of Zika virus infections and severe clinical outcomes.”

The durability of immune responses mounted in response to a Zika virus infection will also be an important determinant of the persistence of Zika virus. Other flaviviruses induce a protective immune response that is long-lived, suggesting that if Zika virus follows suit, people can only be infected with Zika virus once in their lives, reducing the probability that Zika virus transmission will be maintained after a large outbreak.

The duration that people maintain infection and can transmit to others by either sexual transmission or by mosquito-borne transmission could also impact the probability that Zika is transmitted persistently in any setting. Sexual transmission has been observed in this outbreak and in other settings.

The Zika virus caught the world’s attention last January as reports from Brazil indicated that infection of pregnant women could lead to microcephaly in newborn babies. The report indicates that those infected with the Zika virus have an increased risk of developing Guillain-Barré syndrome.

A rare neurological disorder, Guillain-Barré syndrome occurs when the immune system attacks the peripheral nervous system. Depending on the strength of the disease, symptoms can range from mild discomfort in the legs to severe pain and paralysis.

The article suggests that the risk of attaining Guillain-Barré after contracting the Zika virus is 24 per 100,000 Zika virus infections. Though still extremely rare, that number is more than 10 times the general risk for the disease in the U.S., which is 1.8 per 100,000 people.

Several other birth complications associated with the Zika virus are also discussed in the article. Brazilian researchers found that only 1 in 4 babies born with abnormalities from Zika virus-infected mothers met the standards for microcephaly. Other complications include intracranial calcifications, ocular impairment, intrauterine growth restriction (IUGR) and fetal demise.

The review, “Assessing the Global Threat from Zika Virus,” that appears in Science was a collaboration among researchers at the University of Florida (Kyra Grantz, Derek Cummings), Johns Hopkins University (Justin Lessler, Lelia Chaisson, Lauren Kucirka, Qifang Bi, Andrea Carcelen, Cassandra Ott, Jeanne Sheffield, Isabel Barraquer), Imperial College (Neil Ferguson), Institut Pasteur (Henrik Salje) and Princeton University (Jessica Metcalf).