What’s behind the prediction of 3 to 4 million cases of Zika virus this year?

The announcement Thursday by the World Health Organization that 3 million to 4 million cases of the Zika virus could appear in the Americas this year set off alarms around the world. But public health officials emphasized that the understanding of the virus remains hazy and that their estimates could be subject to significant revisions.

The figures were based on models of how dengue spreads and the number of cases seen in Brazil last year, which public officials have pegged between 500,000 and 1.5 million, Dr. Sylvain Aldighieri, an official with the WHO’s Pan American Health Organization, told reporters. But much of the data in Brazil has not been verified, Aldighieri said.

“We have big gaps in terms of confirmation of the real situation,” Aldighieri said. “These are estimates.”

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Part of the problem is that Zika is so poorly understood — it hasn’t been thought of as a major threat to human health until now — and difficult to identify that public health officials are still facing challenges trying to build disease models that could provide better case estimates.

“I think we just have to be clear on some of the uncertainty because these numbers are going to change over time as we get a better fix on some of the underlying characteristics of the virus and its spread,” said Dr. Bruce Aylward, WHO’s assistant director general for outbreaks and health emergencies.

Scientists are still trying to determine if the virus can definitively cause microcephaly in infants born to infected mothers, as well as Guillain-Barré syndrome, a condition that temporarily paralyzes patients and, in rare cases, can lead to death. And if Zika does cause microcephaly, researchers aren’t sure what percentage of pregnant women who contract the virus will have a child with the condition.

Alex Hogan/STAT Zika virus, which can be transmitted by mosquitos, has exploded onto the world stage.

In the United States, places in the South, particularly Florida and Texas, are seen as most vulnerable to Zika transmission. But public health officials here have said they expect any outbreaks to be small and contained, comparing them to past cases of chikungunya and dengue that were limited by strong housing construction and greater use of air conditioning and windows with screens.

Another reason Zika is so difficult to track is because the majority of people infected with the virus — up to 75 or 80 percent of cases — show no or few symptoms, including rash, aches, and fatigue. Plus, existing antibody tests can’t differentiate between Zika and dengue, which is also present in Brazil.

“It would be really challenging to distinguish Zika from other arboviruses,” said Maia Majumder, a doctoral student at the Massachusetts Institute of Technology’s Engineering Systems Division who has tracked the spread of Ebola and Middle East respiratory syndrome. (An arbovirus is one transmitted by arthropods, including mosquitos and ticks.)

Advanced diagnostic laboratories can identify Zika in blood or tissue samples, but those samples need to be examined within about a week of infection, experts say.

Dr. Trish Perl, senior epidemiologist at Johns Hopkins Health System, said a colleague had a patient who had recently traveled to a country with Zika and was showing symptoms upon returning. Doctors eventually had to send the blood to the Centers for Disease Control and Prevention for testing, but it took time to get the necessary permission.

“If we have 4 million cases, you can’t do that,” Perl said.

To build a better model for predicting cases, researchers typically try to conduct a serological survey, in which they draw blood from people in areas known to have a virus and see how many people test positive for it. They also try to determine what’s called an attack rate — a measure of new cases in a given population of susceptible people.

WHO officials said Thursday uncertainty about the attack rate of Zika persists. A serological survey in this case would be complicated by the fact that Zika is not easily distinguished from other viruses.

Researchers around the world are trying the understand how the virus is unfolding across the Americas, but John Brownstein, the chief innovation officer at Boston Children’s Hospital, said: “The reality is we’re left with a lot of unknowns right now.”

Helen Branswell contributed reporting.

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