February 7th, 2016

Twelve Zika Questions, One ID Doctor’s Answers (Sort Of)

Aedes_aegyptiGot a Zika question? Welcome to the club — once again, as with any “new” or “emerging” infection, this is uncharted territory, and there are plenty of answers to these questions that could be summarized with 3 words: We Don’t Know.

But never mind that — ever-intrepid ID doctors are most assuredly called upon as experts, even though for obvious reasons the overwhelming majority of us have never seen a case. Remember this outbreak from 2014? The time from first description of an infectious outbreak to the widespread demand for information is fast. People (patients, doctors, the vast public) have questions, and we need to try and answer them. For the record, with Zika, the obstetricians are in the same boat.

In that spirit, I thought I’d share some of the more common or challenging questions I’ve received on Zika, along with my best efforts at answering them. These answers may well be out of date soon, so I enthusiastically refer you to the outstanding Zika coverage on the CDC site, which is being updated regularly.

  1. 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?
  2. 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)?  Yes. 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.
  3. 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.
  4. 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 guidelines recommend 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.
  5. 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.
  6. 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 all pregnant 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.
  7. 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).
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.

You ID doctors and obstetricians out there — any other questions you’re getting? And from anyone, feel free to offer corrections, insights, other queries, or whatever general thoughts you have in the comments section below.

Hey, isn’t there a “football” game on later today?

[youtube http://www.youtube.com/watch?v=2sD_8prYOxo]

7 Responses to “Twelve Zika Questions, One ID Doctor’s Answers (Sort Of)”

  1. Loretta S says:

    I also read the NY Times article this morning and I was struck by the passion of the epidemiologists involved. Dr. Turchi’s description of staying up all night talking “shop” with other epidemiologists and infectious disease specialists, and her sense that she was working on something that was literally history unfolding before her eyes reminded me how important people like her are during an outbreak.

  2. Jenny says:

    Hi Paul

    Thanks so much for this clear set of collated guidance. One question I’ve been getting pertains to Zika testing and how pregnant women should judge the accuracy of a positive test (since cross-reactions could lead to false-positives as you mention). If a patient knows she was previously vaccinated against yellow fever ~ten years ago and has a positive test, could you (and would you?) consider testing yellow fever IgG? It would be of no diagnostic value if positive, but if yellow fever IgG negative, wouldn’t that raise suspicion that a positive zika test is a true positive?

    Would be very grateful for your thoughts on this!

  3. Great, thought-provoking blog.

    I’m, one of those people who remains skeptical about the link between Zika virus and microcephaly.

    Until and unless you can find evidence that microcephaly rates have increased in tandem with rising Zika virus prevalence, and other indications of causality, the link seems fairly tenuous – see my blogs: http://peterenglish.blogspot.co.uk/2016/01/how-worried-should-we-be-and-what.html and http://peterenglish.blogspot.co.uk/2016/02/microcephaly-in-brazil-not-as-clear-cut.html

    Best wishes,

    Peter English.


    Given that there seems to be only one serotype, is long-lasting immunity expected after first Zika virus infection? In other words, no more concerns in Zika virus IgG positive women?

  5. Peter English says:

    Pablo’s question has prompted another: given that serology (antibody testing) struggles to distinguish between these closely related arboviruses (Dengue, Zika, Cikungunya, West Nike and Yellow Fever), does previous infection with one provide cross protection against others? (Another link at the evidence re Dengue that accumulated while researching a vaccine might offer clues.)

    And, having mentioned Dengue, is it the case that a second infection can be more serious than the first? Does this apply also with Zika or other Flaviviruses?

  6. Marshall Kubota says:

    Hi Paul,

    What / who is the chronic reservoir if this is not a chronic infection?

  7. Sanjat Kanjilal says:

    Another intriguing question based on Fauci/Moren’s editorial in NEJM (http://www.nejm.org/doi/full/10.1056/NEJMp1600297) pertains to the fact that Zika outbreaks seem to follow Chikungunya outbreaks.

    One (possibly crazy) hypothesis is that there is an increased susceptibility to Zika from a previously generated Chikungunya immune response and this is common enough that it occurs on a population level. An obvious epidemiologic study would be to survey the proportion of those who have / had proven Zika infection who also had Chik in the prior 2 years, but the only valid way to investigate is to have a diagnostic with high enough specificity to distinguish serologies between the two.

    Is there precedent for this type of epidemiologic phenomena with other arboviruses?

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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NEJM Journal Watch
Infectious Diseases

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