An outbreak of the Zika virus in the continental United States could begin any day now. But while there is plenty of discussion about mosquito bites, some researchers are beginning to worry more about the other known transmission route: sex.
Intimate contact may account for more Zika infections than previously suspected, these experts say.
The evidence is still emerging, and recent findings are hotly disputed. All experts agree that mosquitoes are the epidemic’s main driver.
But two reports now suggest that women in Latin America are much more likely to be infected than men, although both are presumed to be equally exposed to mosquitoes.
The gender difference appears at the age at which sexual activity begins, and then fades among older adults.
Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, called the evidence ‘striking’. Like other scientists, he had doubts about aspects of the data, but thought the results justified a more rigorous study, probably in Puerto Rico, of the role of sex in transmitting the Zika virus.
‘I can’t say it’s not true that women are more at risk,’ he said.
The Zika virus can persist for months in semen, even in men who have had very mild infections. That’s why women who are pregnant or trying to conceive are routinely warned not to have unprotected sex with men who have been in areas where the virus is spreading.
Ten countries — Argentina, Canada, Chile, France, Germany, Italy, New Zealand, Peru, Portugal, and the continental United States — have reported infections that were almost undoubtedly passed via sex. No case of female-to-male transmission has been documented.
If sexual transmission is more common than believed, efforts to protect women may draw health officials in many of these countries into conflict with those who oppose greater access to birth control or more explicit discussion of sexual practices.
In most parts of the United States, including New York City, health officials have presumed that the risk of Zika infection is low, except possibly at the peak of summer, the height of the mosquito season.
But wider sexual transmission may alter that calculus. Prevention campaigns, for instance, would have to be retooled with a greater emphasis on protected sex.
Thousands of men return to the United States every week from countries in which the virus circulates. New York State alone has a quarter of the country’s travel-related cases.
The most disputed piece in this medical puzzle is a relatively obscure study released in May by Brazilian and European biostatisticians. In Rio de Janeiro, a city of 6.4 million, they found ‘a massive increase of Zika in women compared to men.’
The authors, from the Getulio Vargas Foundation and other Brazilian, French and Scottish research organisations, adjusted their figures for two confounding factors: Pregnant women are tested for Zika more frequently than anyone else, and women generally visit doctors more often than men do.
Even after removing pregnant women from the data, the researchers found women were 90% more likely than men their age to be infected. To adjust for doctor-visit differences, the team compared the current Zika outbreak to two outbreaks of dengue, which is not sexually transmitted.
Even after that adjustment, said Flavio C. Coelho, a Vargas Foundation biostatistician and the lead author, women were still 60% more likely than men to be infected with the Zika virus. Sexual transmission, he said, ‘was the most probable cause.’
The paper’s ‘very intriguing’ conclusions ‘merit further study,’ said Dr. John T. Brooks, an expert on the sexual transmission of disease at the Centres for Disease Control and Prevention (CDC).
But other experts, including Donald A. Berry, a leading biostatistician at the University of Texas M.D. Anderson Cancer Centre, dismissed the study. Women’s fear of Zika is so great, and confusion over dengue, which has similar symptoms, so common that these variables alone could have accounted for the difference in observed infections between men and women, Dr. Berry said.
‘Women seek to find out whether they have Zika, while men blow it off,’ he said. ‘This bias is so large that it could easily explain differences much greater than 60%.’
The biostatistics experts at the National Institute of Allergy and Infectious Diseases were also skeptical of the conclusions, Dr. Fauci said. But another study, published on June 15 in The New England Journal of Medicine, produced similar data.
That study, by researchers at the Colombian Health Ministry and the C.D.C., was set up to look at birth defects linked to the virus. But the authors also found age and gender disparities among those infected.
Young boys and girls in Colombia were infected with the Zika virus at roughly the same rates. Then, after age 15, once sexual activity began, the rates in females shot up.
By age 25 to 29, women in Colombia were three times as likely as men of the same age to be diagnosed with Zika. As they aged, the margin tapered off; after age 65, the infection rates were close to the same again.
The ‘most intriguing difference,’ said Margaret A. Honein, chief of the C.D.C.’s birth defects branch and one of the study’s authors, was that in Colombia women 45 to 64 years old were still almost twice as likely as men of that age group to be infected.
If large numbers of those women were still sexually active, but very few were worried about pregnancy or fetal damage, then male-to-female sexual transmission ‘might be one explanation’ for the higher infection rates, she said.
On the other hand, she said, ‘men may just be more stubborn about seeing a doctor, while women are more sensible.’
The C.D.C. knows of just 13 sexually transmitted cases of Zika in the continental United States thus far. It does not try to count them in Puerto Rico because it cannot distinguish them from mosquito-borne cases. Because 80% of all infections are asymptomatic, the real number is probably higher.
To find out for sure how often sex spreads the virus, researchers would need to choose hundreds of men and women at random and quiz them about how often they were bitten by mosquitoes, how often and with whom they had sex, and how readily they sought medical care, among other factors. Then their blood would have to be tested for the infection.
It might not be possible to do that survey, Dr. Fauci said.
Not only has Congress been reluctant to authorise more spending on Zika prevention, but the most practical tests for such surveys — antibody tests — are the least accurate for Zika infections, because earlier infections with dengue or yellow fever create false positives.
Scientists have documented similar age disparities in HIV infections in Africa, where the gap clearly indicates sexual transmission. In some African cities, teenage girls are five times as likely as boys their age to be infected with HIV, according to UNICEF.
In that epidemic, the difference is driven by infected older men having sex with younger women through rape, incest or ‘sugar daddy’ relationships.
C.D.C. tests on Yap blood samples found infections slightly higher over all in males. But they were not broken down by age.
In Polynesia, ‘we did not find any evidence of a sex difference in our first seroprevalence surveys,’ said Dr. Henri-Pierre Mallet, an epidemiologist in that French territory’s health department.
However, both those outbreaks spread extremely rapidly and died out within months, so swarms of mosquitoes may have simply overwhelmed signs that sex also served as a driver of those epidemics.