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New Zika case study fills some research gaps

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Cooperation essential to address Zika threat

We need research to clarify the best way to provide protection and to prevent serious consequences of Zika virus and other flaviviruses that were previously unknown. Until recently, Zika virus was believed to cause only mild disease, which it still does in the majority of cases. The main concern today is the growing body of evidence that Zika virus infection results in severe neurologic complications – Guillain-Barré syndrome in infected patients and microcephaly in unborn babies – combined with the very rapid spread of the virus.

Although vaccines may come too late for countries currently affected by the Zika virus epidemic, the development of a vaccine that can, above all, protect pregnant women and their babies remains an imperative for countries where the epidemic is expected to arrive in the foreseeable future. The goal would be to allow for medium- to long-term control of Zika virus analogous in some ways to the control of rubella. It is critical that we collaborate rather than compete to find answers to the questions that worry millions of women of child-bearing age in areas where Zika virus is spreading rapidly and may become endemic.

Dr. Charlotte J. Haug is an international correspondent for the New England Journal of Medicine; Marie-Paule Kieny, Ph.D., is assistant director-general for health systems and innovation at the World Health Organization; and Dr. Bernadette Murgue is the project manager of the WHO’s R&D Blueprint. They reported having no financial disclosures. These comments are adapted from an editorial (N Engl J Med. 2016 March 30. doi: 10.1056/NEJMp1603734).


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

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A new case study adds yet more evidence to the link between congenital Zika virus infection and fetal brain damage while offering insights into how the virus affects brain development at different stages.

“Our study highlights the possible importance of [Zika virus] RNA testing of serum obtained from pregnant women beyond the first week after symptom onset, as well as a more detailed evaluation of the fetal intracranial anatomy by means of serial fetal ultrasonography or fetal brain MRI,” wrote Dr. Rita W. Driggers of Johns Hopkins University, Baltimore, and her associates (N Engl J Med. 2016 March 30. doi: 10.1056/NEJMoa1601824).

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The study also continues to help fill in the gaps in research highlighted by Dr. Lyle R. Petersen and his associates at the Centers for Disease Control and Prevention, in an overview of the virus published in the same issue (N Engl J Med. 2016 March 30. doi: 10.1056/NEJMra1602113).

“These include a complete understanding of the frequency and full spectrum of clinical outcomes resulting from fetal Zika virus infection and of the environmental factors that influence emergence, as well as the development of discriminating diagnostic tools for flaviruses, animal models for fetal developmental effects due to viral infection, new vector control products and strategies, effective therapeutics, and vaccines to protect humans against the disease,” the CDC authors wrote.

In the case study, a 33-year-old Finnish woman developed an infection from Zika virus in her 11th week of pregnancy while on vacation in Mexico, Guatemala, and Belize. She experienced the common Zika virus symptoms of a mild fever, eye pain, rash, and muscle pain for 5 days and had evidence of Zika virus RNA in her blood between 16 and 21 weeks’ gestation.

Although the fetal head size remained within the normal range during the 16th and 17th weeks of pregnancy, fetal head circumference dropped from the 47th percentile at 16 weeks gestation to the 24th percentile at 20 weeks’ gestation. Ultrasound and MRI imagery found fetal brain abnormalities, including a thin cerebral mantle and potential agenesis of the corpus callosum at 19 and 20 weeks’ gestation, but neither microcephaly nor calcifications in the brain were seen.

“We suspect these reductions in brain growth would have eventually met the criteria for microcephaly,” the researchers wrote. “As this case shows, the latency period between Zika virus infection of the fetal brain and the detection of microcephaly and intracranial calcifications on ultrasonography is likely to be prolonged.”

Negative findings during this time could be “falsely reassuring and might delay critical time-sensitive decision making,” they added.

The woman chose to terminate the pregnancy at 21 weeks, and high viral loads of Zika were found in the fetal brain during a postmortem exam. The fetus also had lower amounts of Zika RNA in the muscle, liver, lung, and spleen, as did the mother’s amniotic fluid.

“Although the evidence of the association between the presence of Zika virus in pregnant women and fetal brain abnormalities continues to grow, the timing of infection during fetal development and other factors that may have an effect on viral pathogenesis and their effects on the appearance of the brain abnormalities are poorly understood,” the case study researchers wrote.

The CDC authors also note the challenges of differentiating Zika virus infections from dengue or other flavivirus infections. “Reliable testing regimens for the diagnosis of prenatal and antenatal Zika virus infection have not been established,” they wrote.

The CDC authors also predict millions more Zika cases in the Americas, given the incidence of dengue and chikungunya cases previously, but the burden of long-term effects is harder to predict. “The long-term outlook with regard to the current Zika outbreak in the Americas is uncertain,” they wrote. “Herd immunity sufficient to slow further transmission will undoubtedly occur, although this will not obviate the need for immediate and long-term prevention and control strategies.”

Researchers from the CDC and those who reported the case study reported having no financial disclosures.

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