Zika from sex, the byway but not the highway

FlavivirusCan Zika virus be sexually transmitted? Perhaps in very rare cases, but the main mode of transmission is certainly via mosquitoes. That’s why I’ve shamelessly stolen a quote on this topic from Dr. William Schaffner of Vanderbilt University:

Mosquito transmission is the highway, whereas sexual transmission is the byway. Sexual transmission cannot account for this sudden and widespread transmission of this virus.

If you just read the news headlines, which many people do, you will think that Zika virus spreads like HIV. But it does not.

Let’s make a clear distinction between sexually transmitted viruses (like HIV – sex is the main mode of transmission, along with contaminated blood), versus sexually transmissible viruses. The latter includes viruses that now and then might be sexually transmitted under certain circumstances, but which normally are transmitted by another route. Zika virus is transmitted among humans by mosquitoes. If sexual transmission occurs, it is very, very rare, given the large number of Zika virus infections that have been documented.

Is Zika virus sexually transmissible?

The first hint of sexual transmission of Zika virus came from the story of two American scientists working in Senegal in 2008, where they were sampling mosquitoes. Between 6-9 days after returning to their homes in Colorado, they developed a variety of symptoms of infection including fatigue, headache, chills, arthralgia, and a maculopapular rash. The wife of one patient had not traveled to Africa, yet she developed similar symptoms three days after her husband. Analysis of paired acute and convalescent sera from all three patients revealed antibodies against Zika virus. The authors of the study do not conclude that transmission from husband to wife was via sexual activity – they suggest it as a possiblity. Their data could not prove sexual transmission.

More recently infectious Zika virus was detected in semen of a French Polynesian male who had recovered from infection. The presence of virus in semen is compatible with sexual transmission, but the patient was not known to have transmitted infection to anyone.

The CDC has concluded that Zika virus was transmitted to an individual in Texas who had sex with a traveler returning from Venezuela. As of this writing I do not know exactly how the CDC came to this conclusion.

What would be needed to prove that Zika virus is sexually transmissible?

Polymerase chain reaction (PCR) is used to diagnose many viral diseases. This assay detects small fragments of viral nucleic acid and can be very specific. However as we are trying to establish for the first time that Zika virus can be transmitted sexually, more than PCR must be done – infectious virus should be recovered from the donor and recipient. A positive PCR result does not mean that infectious virus is present in the sample, only fragments of the genome, which of course would not be infectious. It is important to correlate the presence of infectious virus with sexual transmission.

Not only should infectious virus be recovered from both donor and recipient, but the viral genome sequences should be nearly identical, providing strong evidence for sexual transmission. If the viral genome sequences were substantially different, this result could imply that the infection was acquired from someone else.

Looking for anti-viral antibodies in serum is a good way to confirm virus infection when virus is no longer present. However it is not as specific as PCR or virus isolation, and does not provide information about the genome of the donor and recipient virus.

Sexual transmission of Ebolavirus still remains speculative. There are several suspected cases, and many examples of PCR positive semen samples from men who have recovered from the disease. It’s not easy to prove that a virus can be transmitted sexually, especially when it is a rare event.

Just as we are not sure that Zika virus causes microencephaly, we are not sure if it can be sexually transmitted.

TWiV 368: Infected, you will be

On episode #368 of the science show This Week in Virology, a plaque of virologists explores the biology of Zika virus and recent outbreaks, and the contribution of a filamentous bacteriophage to the development of biofilms.

You can find TWiV #368 at www.microbe.tv/twiv.

TWiV 361: Zombie viruses on the loose

On episode #361 of the science show This Week in Virology, the TWiVsters discuss Frederick Novy’s return from retirement to recover a lost rat virus, and evidence for persistence of Ebolavirus in semen.

You can find TWiV #361 at www.microbe.tv/twiv.

TWiV 334: In vino virus

On episode #334 of the science show This Week in Virology, the TWiVles talk about endogenous viruses in plants, sex and Ebolavirus transmission, an outbreak of canine influenza in the US, Dr. Oz, and doubling the NIH budget.

You can find TWiV #334 at www.microbe.tv/twiv.

TWiV 322: Postcards from the edge of the membrane

On episode #322 of the science show This Week in Virology, the TWiVodes answer listener email about hantaviruses, antivirals, H1N1 vaccine and narcolepsy, credibility of peer review, Bourbon virus, influenza vaccine, careers in virology, and much more.

You can find TWiV #322 at www.microbe.tv/twiv.

TWiV 312: She sells B cells

On episode #312 of the science show This Week in Virology, the TWiVbolans discuss the finding that human noroviruses, major causes of gastroenteritis, can for the first time be propagated in B cell cultures, with the help of enteric bacteria.

You can find TWiV #312 at www.microbe.tv/twiv.

TWiV 309: Ebola email

On episode #309 of the science show This Week in Virology, the TWiVocytes answer questions about Ebola virus, including mode of transmission, quarantine, incubation period, immunity, and much more.

You can find TWiV #309 at www.microbe.tv/twiv.

The press concludes that arboviruses can be sexually transmitted

zika virus distributionWhat would you conclude if you read the following headlines: Man sexually transmits insect-borne disease to wife (Fox News); Zika virus: First insect borne STD? (HuffPo); Scientist gives insect-borne disease to wife during sex (New York Magazine), and A scientist contracts a mosquito-borne virus and gives it to his wife as std (Time). What would be your impression if you read the journal article on which these headlines are based, which does not conclude that the infection was transmitted sexually?

Zika virus was isolated in 1947 from a monkey in Uganda, and subsequently shown to be transmitted by mosquitoes. Zika is classified as a flavivirus, along with well-known human pathogens such as yellow fever virus, dengue virus, and West Nile virus. Infection of humans with Zika virus leads to headache, fever, malaise, myalgia, and formation of  a maculopapular rash on the face, neck, trunk, and arms. The virus is found mainly in African and parts of Asia (see map).

The case that has precipitated incorrect reporting began with two American scientists working in Senegal in 2008, where they were sampling mosquitoes. Between 6-9 days after returning to their homes in Colorado, they developed a variety of symptoms of infection including fatigue, headache, chills, arthralgia, and a maculopapular rash. The wife of one patient, who had not traveled to Africa, developed similar symptoms three days after her husband. Analysis of paired acute and convalescent sera from all three patients revealed antibodies against Zika virus. The two individuals who had traveled to Africa also had antibodies to yellow fever virus, a consequence of immunization with the vaccine.

Here is what the authors conclude from these data:

Evidence suggests that patients 1 and 2 were infected with ZIKV, probably in southeastern Senegal, by bites from infected mosquitoes…Circumstantial evidence suggests direct person-to-person, possibly sexual, transmission of the virus (italics are mine).

The authors do not conclude that transmission from husband to wife was via sexual activity – they suggest it as a possiblity. The authors know that one cannot prove sexual transmission from such a small study. They go on to write:

If sexual transmission could be verified in subsequent studies, this would have major implications toward the epidemiology of ZIKV and possibly other arthropod-borne flaviviruses.

What other ways might the infection have been transmitted from husband to wife? Virus is likely present in the skin of infected individuals, as a rash is a prominent feature. It is possible that virus was transmitted via cuts or abrasions in the skin. Another possibility is that virus is present in saliva or other body fluids, and is transmitted to others by close contact. The authors don’t believe this to be the case because they write that ‘illness did not develop in the 4 children of patients 1 and 3‘. However physical contact between husband and wife is substantially different from the contact between parents and children, which could have a major role in determining virus transmission.

Here is another way to put this puzzling state of affairs into context. In 2009 a group of scientists published a paper in Science indicating that they had found a retrovirus, XMRV, in the blood of 68 of 101 patients with chronic fatigue syndrome. To this day whether or not XMRV causes chronic fatigue syndrome is still being debated, despite studies in hundreds of individuals. In light of this situation, why does the press conclude from a study of three individuals that Zika virus can be sexually transmitted? Could it be that the journalists didn’t read the journal article (poor excuse – it’s quite short), or if they did, they decided that the conclusions were not sufficiently interesting? Or maybe the sex angle – always a good way to get the reader’s attention – was too good to resist, never mind that it might not be correct. Either way, the public is being misinformed about science – again.

Update: There has been discussion in the comments section that the news articles I cite don’t do such a bad job in presenting the science, and it’s the headlines that are the main problem. I don’t agree with that conclusion about the articles – in my opinion they don’t accurately portray the content of the paper. My journalist friends tell me that the headline writers often take liberty with conclusions; but I don’t see why we should use that as an excuse to forgive inaccurate headlines. How many people never get past the headlines? Both the headline and the article need to be consistent and they need to accurately represent the science.

Foy, B.D., Kobylinski, K.C., Foy, J.L.C., Blitvich, B.J., da Rosa, A.T., Haddow, A.D., Lanciotti, R.S., & Tesh, R.B. (2011). Probable non–vector-borne transmission of Zika virus, Colorado, USA. Emerging Infectious Diseases : 10.3201/eid1705.101939

Hayes, E. (2009). Zika Virus Outside Africa Emerging Infectious Diseases, 1347-1350 DOI: 10.3201/eid1509.090442