By Dr. Geoffrey Modest
A brief update on a few developments with Zika virus:
The CDC came out with new recommendations on reducing sexual transmission of Zika (see http://www.cdc.gov/mmwr/volumes/65/wr/mm6505e1er.htm ).
- There are a few cases of very-likely sexual transmission of Zika: one mentioned in prior blog: http://blogs.bmj.com/ebm/2016/01/29/primary-care-corner-with-geoffrey-modest-md-zika-virus/ ), and a recent one in Texas.
- There was a report of a replication-competent Zika virus isolated from a Tahitian man at least 2 weeks and up to 10 weeks after Zika illness onset (the virus might persist in semen after it is no longer detectable in blood). He reported no sexual contacts
- There are not a lot more data: i.e., we do not know the actual length of time that replication-competent Zika virus is present in semen; we do not know if men with asymptomatic disease (which seems to happen in 80% of infections) have the virus in their semen, and if so then for how long; or if the virus is of sufficient quantity to be transmissable; if condoms are in fact completely protective (not the case in all viruses, e.g. HSV); if men can develop Zika (symptomatic or asymptomatic) from infected women; how robust and longstanding is immunity after an initial infection?
- So the recommendations regarding sexual transmission and ways to prevent it are largely guess-work, erring to being overly cautious, and are likely to be modified as our understanding increases. The current recommendations:
- Men with pregnant partners: if the man resided in or traveled to an area with Zika, either abstain from sexual activity or consistently and correctly use condoms. This includes vaginal, oral or anal sex. Pregnant women should mention this to their obstetric providers and should consider Zika virus testing even if they are asymptomatic (see http://www.cdc.gov/mmwr/volumes/65/wr/mm6505e2.htm for updated guidelines).Since we do not know how long viable virus is present in semen, the CDC does not say when it is okay to resume unprotected sex.
- Men with nonpregnant sex partners: if the man resided in or traveled to an area with Zika, he ”might consider abstaining from sexual activity or using condoms consistently and correctly during sex” (again, not sure for how long). At this point testing men for the purpose of assessing risk is not recommended (we need to know a lot more about the incidence, consistency, and duration of viral shedding in semen).
Also, there are news reports of Zika transmission by blood donation, and virus detection in saliva and urine. Again, unclear if these are important means of viral spread. We need lots more information. But it is interesting that this virus has been around since first identified in 1947. This is not new (though it would be good to know for sure if the virus has mutated): why is there so little information? Because of inadequate surveillance in rural Africa? Because perhaps the virus has been around for a lot longer than that and there was a lot of immunity already there? Or it infects little kids who are then immune and not able to acquire a new infection when pregnant later? And the new outbreaks in Brazil and elsewhere reflect the rapid spread in a nonimmune community replete with lots of mosquito vectors and enough infected people coming from Africa or other more endemic areas?
A couple of other points. My guess (assuming this is the same virus as in 1947) is that Zika was prevalent then, infected kids, was not such a serious infection, and created long-term immunity. Again, this is highly speculative, but on my searching around, there were no reported cases of microcephaly in Africa (suggesting that pregnant women were not susceptible to the virus, which suggests that they were infected as kids and that they had longish term immunity). And I am concerned that there may well be nonhuman reservoirs which help the virus spread (both given the rapidity and extent of the current outbreaks, and a finding in the rain forest in Nicaragua that 40 howler monkeys were found dead with no evidence of trauma or other clear cause). The sort-of-good-news is that Zika is similar enough to other flaviviruses that it is likely that we can develop a vaccine pretty rapidly (i.e., 1.5 years vs 3-4 years).
As of 2/11/16: Western Hemisphere countries with confirmed local transmission: Chile, Brazil, Colombia, Suriname, El Salvador, Mexico, Panama, Venezuela, Honduras, French Guiana, Martinique, Puerto Rico, Bolivia, Saint Martin, Haiti, Barbados, U.S. Virgin Islands, Dominican Republic, Nicaragua, Jamaica, Costa Rica, United States
Dr. Paul Sax, a prolific ID specialist from the Brigham and Women’s Hospital in Boston, has a blog with 12 questions about Zika and his answers. The direct URL to his blog does not seem to be working, so I will take the liberty of pasting his questions/responses:
- I’m pregnant or know someone who’s pregnant. Can I/she travel to — [insert country close to one of the countries that has Zika transmission,but is not currently listed]? Yes … but … with a caveat. It’s a highly dynamic situation, and just like dengue and chikungunya, Zika is likely to be reported in many of these adjacent countries soon (especially in the Caribbean). Not only that, incidence frequently rises quickly in countries after they first report the disease. So why not change those travel plans if possible?
- I’m pregnant or know someone who’s pregnant. Can I/she travel to Florida (or Alabama or Mississippi or Louisiana or Texas or Hawaii)? There has been no mosquito-borne Zika transmission in the USA yet, though likely there will be sporadic cases soon. But just like dengue and chikungunya, it seems that a widespread outbreak is unlikely — we have more resources for mosquito control, and way more air conditioning.
- How long after returning from [insert Zika country here] can someone safely get pregnant? After all, since 80% of people who get it are asymptomatic, how does one know if Zika infection even occurred? We don’t know the precise duration of viremia for Zika, or whether the duration of viremia correlates with symptoms. (My gut feeling is that it will, but who knows.) Estimates are that viremia clears on average in about a week. So right now it seems prudent to wait at least a couple of weeks after returning before trying to get pregnant, maybe a month to be on the safe side.
- A guy travelled to [insert Zika location here]. How long after travel should he wait before having sex with his pregnant partner?We don’t know how long Zika virus remains in semen after infection, nor (again) whether this duration correlates with symptomatic infection (again, my guess is that it does). Since Zika acquisition during pregnancy is what we’re trying to avoid, these guidelinesrecommend abstinence or condom use during the pregnancy, which makes sense to me. Now what about the more common scenario, partner isn’t pregnant? Next question, please.
- A guy travelled to [insert Zika location here]. How long after travel should he wait before having sex with his non-pregnant partner? The guidelines linked in the previous question state that these couples “might consider abstaining from sexual activity or using condoms consistently and correctly during sex,” but no duration for this “safe sex” practice is given. Note the use of the word, “might” — this is CDC parlance for, “Look, we’re not going to tell you that doing nothing is totally safe, but we don’t feel that strongly about this recommendation.” (Check out the rabies guidelines for plenty of “mights” in this mode.) After all, Zika infection is pretty mild, and there have only been 2 documented sexual transmissions. In fact, one could argue that if other forms of contraception are being used, that transmitting the infection would have a benefit — namely, immunity for a future pregnancy. For worried folks, I’ve been saying they “might” as well wait a month. For unworried folks, I’m not saying anything. Importantly, there is no evidence that prior infection with Zika will have a negative impact on future pregnancies, once the infection clears.
- Can’t the woman who wants to get pregnant — or even the guy with the pregnant partner — just get a Zika blood test when they return from a Zika country/region, and find out if they were infected? That would make us all less anxious. Not yet. Zika testing is now done mostly through CDC (someone from Florida told me they had local access to testing), and there isn’t the capacity to test everyone. This is why testing is now recommended only for pregnant women who were in Zika transmission areas. Initially it was recommended only for women with symptoms; this was broadened last week to include allpregnant women, even those without symptoms. And remember, the test isn’t so great — there is extensive cross-reactivity with dengue and prior Yellow fever vaccination. So while it would be ideal to have a widely available, rapid, and accurate Zika test, our current test misses on all these marks. I suspect (hope) this will improve shortly.
- I read a vaccine is in the works. When will it be available?Vaccines take years to develop, and many, many millions of dollars. While some have stated that it should be technically feasible to produce a Zika vaccine, that doesn’t mean it will work in humans, or even that if one does work, that it will be marketed. So put this one on the way back burner (unless you’re a vaccine researcher).
- The virus was discovered decades ago. Why hasn’t the link to microcephaly been reported before? A couple of theories, not mutually exclusive: 1) It is likely that in areas where Zika is already established, initial infections predominantly occur during the pre-childbearing years, which induces immunity. 2) The incidence of an infection is often highest after infections enter a community for the first time, as the pathogen encounters a large pool of susceptible hosts. In areas with established infection, the combination of some regional immunity and lower incidence means that fewer women acquire the infection during pregnancy — making it much harder to identify an association.
- I read that some countries with Zika transmission are recommending that women delay pregnancy — isn’t the virus still going to be around for years to come, maybe indefinitely? They can’t be expected to delay having babies indefinitely. This is a controversial recommendation, and indeed the WHO does not endorse it. However, it makes some sense, largely for the reasons cited in the previous question — the delay could allow immunity-inducing infection to occur in some non-pregnant women of childbearing age. Even if this doesn’t happen, the incidence of infection should be sharply lower once a substantial fraction of the population has been infected.
- How do we know that Zika even causes microcephaly? I’m a skeptic.It’s true that we don’t know definitively that Zika causes microcephaly. And it’s highly likely that reporting bias has to at least some degree increased the number of cases, especially in Brazil. But the number of cases reported in Zika-transmission countries is many fold higher than usual, beyond what public health officials would consider solely the result of reporting bias — read this excellent piece in the New York Times, which conveys vividly what was happening as the epidemic accelerated. Lending further support to the connection, researchers have isolated the virus from babies with microcephaly, and there are now reports that French Polynesia may well have had an increase in CNS abnormalities in babies around the time that their Zika outbreak occurred in 2014. Finally, one needs to consider the source of the travel advice — our CDC is very cautious about issuing such travel warnings (substantial geopolitical and economic consequences), and would not make this recommendation unless the evidence were very strong.
- How about Zika and the Guillain-Barré syndrome syndrome?Though there have been reports of Guillain-Barré syndrome after Zika virus infection, whether Zika causes this neurologic syndrome is not conclusively established — more research is needed here, though again the anecdotal data are suggestive. There are, of course, other infections linked to Guillain-Barré, most notably campylobacter, so the association is plausible.
- I hear the virus can be transmitted not just by Aedes aegypti, but also the much more widespread Aedes albopictus. Isn’t it just a matter of time before this virus is charging through the United States like it is through Central and South America? With the important upfront caveat that prognostications on disease spread are notoriously iffy, experts in vector-borne illnesses do not think that this scenario is likely — related to the lower “efficiency” of viral transmission from Aedes albopictus,and the experiences to date with dengue and chikungunya. But sure, there will always be worst-case scenarios — and noisy champions of these views who get lots of attention