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Zika virus found in amniotic fluid

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Case-control studies needed to establish microcephaly risk

The temporal association between Zika virus outbreaks and microcephaly in Brazil strongly suggests that Zika virus infection during pregnancy might cause severe neurological damage in neonates. The challenge now is to provide empirical evidence for the link between Zika virus and microcephaly, and the demonstration that Zika virus can cross the placental barrier and infect the neonate strongly favors this association.

Even if all these data strongly suggest that Zika virus can cause microcephaly, the number of microcephaly cases related to Zika virus is still unknown. The next step will be to do case-control studies to estimate the potential risk of microcephaly after Zika virus infection during pregnancy, other fetal or neonatal complications, and long-term outcomes for infected symptomatic and asymptomatic neonates.

These comments were adapted from commentary by Dr. Didier Musso, Institut Louis Malardé, Tahiti, French Polynesia, and Dr. David Baud, University of Lausanne and University Hospital, Lausanne, Switzerland (Lancet Infect Dis. 2016 Feb 17. doi: 10.1016/S1473-3099[16]0096-7). Dr. Musso and Dr. Baud reported no conflicts of interest.


 

FROM THE LANCET INFECTIOUS DISEASES

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A case study conducted in Brazil revealed the presence of Zika virus in the amniotic fluid of two pregnant women, suggesting that the virus can cross the placental barrier and potentially infect the developing fetus.

Both women in the study had their amniotic fluid samples taken at 28 weeks, and later gave birth to babies with microcephaly.

The finding, published online Feb 17 in The Lancet Infectious Diseases (Lancet Infect Dis. 2016 Feb 17. doi: 10.1016/S1473-3099[16]00095-5), does not prove that Zika virus infection causes microcephaly but does suggest the biological plausibility of such a link.

In the same study, the researchers, led by Dr. Ana de Filippis of Oswaldo Cruz Institute in Rio de Janeiro, applied reverse transcription polymerase chain reaction and viral metagenomic sequencing to the viral samples, allowing them to establish that the virus was very closely related to the Zika virus that caused an outbreak in French Polynesia in 2013, and was not a recombinant strain.

Amniotic fluid samples were analyzed in Dr. Ana de Filippis' lab. ©Oswaldo Cruz Institute

Amniotic fluid samples were analyzed in Dr. Ana de Filippis' lab.

The women in the study, age 27 and 35, were from the Brazilian state of Paraíba. Neither woman reported smoking, using recreational drugs or alcohol, or taking medications known to affect fetal development.

Zika virus was not found in the blood or urine of either woman when the amniotic samples were taken, though both had reported earlier symptoms consistent with Zika infection. Other infections, including HIV, dengue, chikungunya, rubella, and herpes viruses, were ruled out.

The results provide important insight into the origin of the Zika virus circulating in Brazil, the researchers wrote in their analysis. Moreover, “our group is the first, to our knowledge, to isolate the whole genome of Zika virus directly from the amniotic fluid of a pregnant woman before delivery, supporting the hypothesis that Zika virus infection could occur through transplacental transmission,” wrote Dr. de Filippis and her colleagues.

Still, little is known about the effects of Zika on the developing central nervous system, the researchers wrote. A connection between Zika virus infections and poor CNS outcomes “remains presumptive, and is based on a temporal association. New studies should be done to investigate whether the Zika virus can infect either neurological precursor cells or final differentiated cells.”

The researchers cautioned that congenital microcephaly has been associated with genetic disorders, chemical exposures, brain injury and uterine infections. Other possible contributors to the current high rate of microcephaly in Brazil, which last year was 20 times higher than in previous years, need to be investigated, they wrote.

Agencies within Brazil’s national government and the city of Rio de Janeiro funded the study, and investigators disclosed no conflicts of interest.

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