After emerging dramatically in Brazil in 2015, Zika, a virus that can cause devastating birth defects, spread fear across the United States as the weather warmed and mosquitoes took flight. However, 2017 saw a dramatic decline, and at the end of September the CDC shut down its emergency response to Zika. Is the threat over?

Unfortunately, no. While the virus is in retreat, the CDC still warns pregnant women against traveling to Brazil and other areas in South America and the Caribbean. (See CDC map at: http://bit.ly/2m50Lf7.) Also, men who travel to such areas are advised to either abstain from sex or use condoms for at least six months upon return. The Zika virus is primarily spread by female Aedes aegypti seeking blood meals necessary to successfully reproduce. In the summer months, this mosquito has a broad range over much of the country and is known as an aggressive daytime feeder.

An A. aegypti mosquito carrying Zika can inject the virus into the bloodstream during a quick feeding. A mosquito bite, typically a mere nuisance, becomes something else entirely when the mosquito carries Zika. It sets off a series of risks and variables that reach their most dire consequence if the virus reaches a human fetus, particularly during the first trimester of pregnancy.

While emerging epidemics all have their particular aspects of anguish and dread, Zika threatens the quintessence of vulnerability — the unborn. It is hard to shake the first images of live infants with microcephaly, a congenital defect in which brain formation is limited by partial collapse of the skull. Other physical and neurological blights appeared thereafter, undermining a broad spectrum of child development. From 2015 through Dec. 19, 2017, the CDC reported 2,364 pregnant women with any laboratory evidence of Zika virus in the U.S. There were 101 liveborn infants with Zika-associated birth defects in the U.S., and nine pregnancy losses.¹

“Microcephaly is kind of the most phenotypical, obvious manifestation of congenital Zika syndrome,” says Tyler Sharp, MD, a CDC epidemiologist and Zika outbreak investigator in Puerto Rico. “It is not something that babies will grow out of. Those babies will be affected for life. There are a variety of other conditions across the spectrum as well, many of which are going to be lifelong conditions. So, at least for those babies that have been born with congenital Zika syndrome, the expectations are that they will need additional healthcare the rest of their lives.”

About 6% of infants born to Zika-infected mothers had defects in 2016, with the CDC estimating that the risk of fetal harm increases twenty-fold compared to a non-Zika pregnancy. Another report² on infectious threats and natural disasters said, “[T]here is currently no vaccine or medicine approved for Zika. The cost of care for an infant with severe microcephaly to adulthood is up to $10 million, and in just one year, the total costs for hospital care of people with birth defects exceeds $23 billion.”

Indeed, though several lines of research are underway, the lack of an approved vaccine gives Zika an opening to resurge in a susceptible population. Zika, first detected in Africa in the 1940s, was afterward detected in other regions, but never the Americas. Now, Zika has been detected in 49 states, three U.S. territories, most of South and Central America, Africa, South Asia, and the Pacific Islands, the aforementioned report states.

This is the first time Zika or any other mosquito-borne virus has been associated with birth defects, so there is some suggestion a mutation has occurred. Still, the general consensus remains that most Zika infections are largely asymptomatic and inconsequential unless the infected person is pregnant or has had unprotected sex while the virus is circulating in the blood or persisting in a human reservoir like semen. The question now is whether it can simmer quietly and strike again when enough susceptible people — those not previously infected — accumulate in an area where A. aegypti has a habitat, which unfortunately includes much of the planet.

“It is still on our radar, but we do not expect to see additional large outbreaks in the next couple of years — somewhere in that time frame,” Sharp says. “That becomes relevant to the U.S. because a very large majority of infections that occur in the continental U.S. are imported. [An individual was] on vacation somewhere in the tropics, got infected, and then came to the U.S. and got sick or presented for care in the U.S. In some cases, not very common but it does happen, those infected individuals are bitten locally, [and] then you get local transmission. With infections abroad decreasing dramatically, then the risk of local transmission to occur in the U.S. is lower as well.”

The Epidemic Curve

There were 261 Zika virus infections in returning travelers in 2015 in the U.S., but the outbreak exploded to more than 5,000 cases the following year. Overall, 2016 saw 5,102 symptomatic Zika cases in the U.S., with 4,830 cases in travelers returning from affected areas. There were 218 cases of mosquito-borne transmission in Florida and six cases in Texas in 2016. There were 46 cases of sexual transmission, including one from a female to a male, and one case of a healthcare worker infected by a needlestick. In addition, 2016 saw the strange case of a 73-year-old patient in the U.S. who apparently transmitted Zika to a visiting acquaintance — possibly through tears — before dying with an incredibly high level of circulating virus in the blood.³ The secondary case developed symptomatic Zika infection, but subsequently recovered. It is possible that hormonal treatment for prostate cancer somehow accelerated viral replication in the index case, investigators concluded.

From Jan. 1 to Dec. 20, 2017, the CDC reported 385 symptomatic Zika virus disease cases in the U.S. Of those, 378 were in travelers returning from affected areas. There were three cases of local transmission by mosquitoes in the U.S. in 2017, with two in Texas and one in Florida. In addition, there were four cases of Zika acquired via sexual transmission last year in the U.S.

The CDC appropriately called for full vigilance in the U.S. last spring as the summer months neared, warning that Zika virus could dramatically return. It came back, albeit in much reduced numbers. Moreover, the case count has dropped dramatically in the epicenter in South America, making imported cases via travelers less likely.

“Vigilance is important. We continue to monitor activities throughout our state, but in particular South Florida where we have seen active transmission from mosquitoes,” says Celeste Philip, MD, Florida Surgeon General and secretary of the state department of health.

Philip fielded a Zika question from Hospital Infection Control & Prevention at a recent press conference assessing national readiness for emerging diseases and natural disasters.

“We use the numbers from other countries to predict what kind of activity we will see in our state,” Philip says. “When we look at [2017’s] number of travel-related cases, we are in the two-hundreds compared to [2016] when we had over 1,000 cases. A decrease in Zika internationally means a decrease in travel-related cases in Florida, so fortunately we have not seen any ongoing local transmission in our state.”

Given the propensity of infectious diseases to re-emerge when healthcare responses become complacent, public health must remain alert for a reintroduction of Zika.

“We continue our testing to identify travel-related cases,” Philip says. “Our mosquito control districts go out to where that individual lives and works and conduct mosquito control activities. We are hopeful, at least for now, that we will continue to see lower numbers and that meanwhile there is progress toward a potential vaccine.”

Will Zika Resurge?

Though the threat has waned, Zika did not mysteriously vanish like the global outbreak of SARS coronavirus in 2003. Zika still exists in nature along with the thousands of other endemic infectious threats for which public health officials must remain vigilant. Zika virus is in remission, having passed through susceptible populations in Brazil and other temperate climes in an immense epidemic wave that has left those infected now immune.

“If you go three to four years back, Zika had not circulated in the Americas as far as we can tell,” Sharp says. “Basically, everybody was susceptible and that creates a very ripe territory. If you introduce Zika, chances are very good you are going to get a lot of people infected. That is what occurred. It was introduced into Brazil as far as we can tell and it was spread from there to basically everywhere [in the Americas] that has Aedes aegypti mosquitoes.”

It remains somewhat unresolved, as research continues on the virus, how long someone asymptomatically infected can transfer the virus from their blood via a mosquito bite. Nor is there any exact science on what percentage of herd immunity must be lost for Zika to again begin spreading widely and causing outbreak.

“In most regions, for a variety of reasons, where Zika has been introduced, basically all of them have had large outbreaks,” Sharp says. “Those outbreaks are probably sufficient now to prevent additional large outbreaks from occurring in the near future. That does not mean Zika is gone, however. In most regions where Zika has been introduced it now probably is still circulating, but at relatively low levels. We don’t know how long that will last. It may become like Dengue or other mosquito-borne viruses that favor warmer climes and are occasionally imported to other lands by returning travelers.”

“The most common reservoir that we know of, by far, is humans,” Sharp says. “Just like we see with Dengue virus, Zika will probably circulate between mosquitoes and humans in relatively low rates for months, potentially years. As long as you have a large enough population that still has immunologic susceptibility to infection — we’re talking about infection rates in the [Caribbean and South American] population[s] to date being anywhere from 20% to 70% — that still leaves a good chunk that is susceptible. In most cases, that probably is going to be sufficient for the human-mosquito transmission cycle to continue, but not at levels that would manifest an outbreak.”

The key difference is that Zika, in addition to being the first mosquito-borne virus to cause birth defects, is the first of these types of viruses to be sexually transmitted.

“We do anticipate that there is going to be continued risk to travelers and other people in the area who are still susceptible to Zika,” Sharp says.

The CDC still recommends that pregnant women not travel to areas with an endemic level of Zika (e.g., Brazil). In addition, women who travel to such areas should abstain or have only protected sex for two months. Men should abstain or have only protected sex with condoms for six months after travel to a Zika area. There have been some reports of carriage of Zika in semen for longer periods, but the CDC is confident these are outliers, some of which deal with viral fragments, and should not be a basis for public health policy.

“The CDC recommendations for men cover the very large majority of individuals that have been identified with Zika virus infection and how long they have viral nucleic acid detectable in their semen,” he says.

Reseachers have found some outliers that have had nucleic acid detectable in their semen for longer than six months, Sharp says, “but it is very, very few.”

Sharp says the CDC’s timeframe is appropriate to “capture the overwhelming majority with Zika virus infections. If you have nucleic acid detectable in your semen, that means you are infectious to your partner if you are not following those guidelines. Having infectious virus in semen versus having some small component of the virus being detectable are not necessarily the same thing, so we are still trying to work out what that correlation is.”

REFERENCES

1. CDC. Zika Virus. Available at: http://bit.ly/2kvWeQD.
2. Trust for America’s Health. Ready or Not? Protecting the Public’s Health From Diseases, Disasters, and Bioterrorism. 2017. Available at: http://bit.ly/2FpqZif.
3. Swaminathan S, Schlaberg R, Lewis J, et al. Correspondence: Fatal Zika Virus Infection with Secondary Nonsexual Transmission. New Engl Jrl Med 2016;375(19):1907-1909.