Zika virus and the fetus

FlavivirusAn epidemic of Zika virus infection began in Brazil in April 2015, and six months later there was a surge in the number of infants born with microcephaly. Confirming that Zika virus causes microcephaly will require much more information than is currently available. So far there have been few isolations of Zika virus RNA from microcephalic fetuses or amniotic fluid.

A single case report revealed the entire Zika virus genome in fetal brain tissue from a 25 year old who developed fever, muscle and eye pain, and rash during the 13th week of gestation in Natal, Brazil. The fetus was aborted at 28 weeks of gestation when fetal abnormalities, including microcephaly, were detected. Virus particles 42 to 54 nm in diameter were detected in the brain by electron microscopy.

It is probably not normal to have Zika virus in the fetal brain. However, its presence there might be a consequence of microcephaly, not a cause. As Dr. Steven Seligman writes at ProMedMail, “It is possible that brain tissue in cases of microcephaly become susceptible to Zika virus infection by a mechanism such as diminution of he blood-brain barrier.”

The entire Zika virus genome has also been detected in amniotic fluid, which surrounds the developing fetus. Two pregnant women from the state of Paraíba in Brazil reported clinical symptoms early in pregnancy consistent with Zika virus infection (fever, myalgia, rash). Microcephaly was diagnosed at 21 weeks gestation by ultrasound, and 7 weeks later samples of amniotic fluid were obtained by amniocentesis.

Amniotic fluid was centrifuged to purify virus particles, and RNA was extracted, copied into DNA by reverse transcriptase, amplified by polymerase chain reaction and subjected to deep sequencing.

The complete Zika virus genome sequence was obtained from one sample, and two smaller genome fragments from the second. Sequence analyses revealed 97-100% similarity with Zika viruses isolated from French Polynesia in 2013.

IgM antibodies to Zika virus were detected in both amniotic fluid samples, indicating that the fetus was likely infected and mounting an immune response against the virus (this antibody does not cross the placenta). In contrast, serum and urine from both mothers was negative for Zika virus IgM. This antibody appears first during infection, then subsides as levels of IgG antibody rise. It is possible that the mothers were infected with Zika virus early in pregnancy and cleared the infection, but the virus entered the fetus where it persisted.

Even if Zika virus does cause birth defects, a vaccine will likely not be available for another two years. In the meantime it would be highly advisable to practice mosquito avoidance and control.

Update 2/24/16: I asked Carolyn Coyne how a virus might reach the amniotic fluid. Her reply:

Amniotic fluid is mainly urine from the baby (after month 4ish) so if the virus is being shed in the urine, that is one way. Cells from the baby are also shed into the fluid (these are usually skin cells, but I imagine could also be from the mouth as the baby is usually drinking amniotic fluid at later stages of gestation). I will note that this is usually in a normal pregnancy and I imagine is the fetus were dying/dead (a fetus can die in utero and not be miscarried for a shockingly long time sometimes), the virus might easily enter the amniotic fluid as the fetus begins to decompose (which also happens in utero).

The two routes of entry are hematogenous or ascending. In hematogenous infections, virus present in the maternal blood would have to cross the placenta across the villous trees. In an ascending infection, the virus would be introduced into the vagina, then would have to bypass the cervix and still have to cross the placenta to access the fetus. Usually ascending infections are associated with bacteria (from UTIs mainly, but can be other). In either case, the placenta is there and would have to be crossed.

Update 2/25/16: A report in PLoS Neglected Tropical Diseases describes finding Zika virus RNA by RT-PCR in neuronal tissues but not in heart, lung, liver or placenta, in a stillborn infant with microcephaly and hydrops fetalis. The 20 year old woman from Salvador, Brazil denied having any symptoms consistent with Zika virus infection, but only one in five infections are symptomatic. As in the case described above, we do not know if Zika virus caused the fetal defects, or if virus was able to invade the fetus as a consequence of severe developmental damage.

Comments on this entry are closed.

  • Jorge Alexandre

    Very interesting quote from Stephen Seligman. Do you have anything else on that possibility, that microcephaly from other causes would expose the fetus to zika infection, and not the other way around? thanks, Jorge Pontual

  • I am not aware of reports of viruses invading the fetus secondary to developmental damage. I’ve added to this article the PLoSNTD paper you sent which describes Zika virus RNA in a case of fetal demise. Thank you for sending this.

  • Rashima

    Sir, why does the zika virus , instead of going through all the work of crossing barriers, simply not targeting or affecting the mother’s brain. Also, why are there very few reports on viremia in the Zika case? Shoudn’t it be the first step to detect the presence of virus.

  • angela coral eisenhauer

    Few dates wrong in the above. Women were vaccinated from May, 2015, with T dap vaccine. G SK brand made under licence in Brazil, they got it as early as 20 weeks gestation, the babies were born disabled 20 weeks later in OCTOBER 2015. They are the facts, trying to twist them any other way, is just manipulation, trying to blame a mossie. 5,000 of 5,000 babies damaged were ALL D tap vaccinted, 4 (FOUR) had zika virus. Bit weird how the worlds scientists think the link is blindingly obiously vaccine damage, EXCEPT FOR CDC? Usa has had a corresponding rise, after vaccinting babies in utero with D tap from 400, to 25,000 (2014). Again CDC seem to miss this horrific rise, corresponding exactly to vaccinating babies in utero. USA has more microcephalic births than Brazil, and not a zika mossie in sight.

  • ang

    Well they started vaccinating in May 2015, as early as 20 weeks gest ation, and the deformed babies were born 20 weeks later in October 2015. They are facts. The dates given in the above article are purposely misleading angela offer @ hotmal com can send you all the information. Seems everyone sees the blindingly obvious, except C for Disease and Corruption. USA has more microc births than Brazil, has been like that since they started jabbing preg women in 2013. Again, C for Disease and Corruption, somehow havent noticed?