CDC Director Tom Frieden, M.D., M.P.H., observed during a Feb. 5 press briefing(www.cdc.gov) that because the current Zika virus outbreak is new and continually evolving, the CDC is discovering more about it every day.
"With each passing day, the linkage between Zika and microcephaly becomes stronger," he said. "In addition, the linkage between Zika and Guillain-Barré syndrome becomes stronger the more we learn."
Indeed, a study published online Feb. 10(www.nejm.org) in the New England Journal of Medicine clearly demonstrates a tie between maternal infection with the virus and fetal microcephaly.
The study report's authors describe a 25-year-old, previously healthy European woman's presentation to a Slovenian academic medical center in mid-October with reduced fetal movement and suspected fetal anomalies. She became pregnant in late February 2015 while working as a volunteer in Natal, Brazil. At 13 weeks' gestation, she became ill with a high fever, severe diffuse myalgias and arthralgias, and rash. Zika virus was circulating in the community at the time, so infection with that pathogen was suspected but no virologic diagnostic testing was performed. Ultrasonography at 14 and 20 weeks' gestation showed normal fetal growth and anatomy.
- The CDC has issued new interim guidance on Zika virus testing in asymptomatic pregnant women and prevention of sexual transmission of the virus.
- A recent study clearly documented the presence of Zika virus in fetal brain tissue.
- In other research, ocular abnormalities were seen in a significant proportion of infants with microcephaly born to mothers who contracted the virus during pregnancy.
Shortly after her return to Europe, ultrasonography performed at 29 weeks' gestation showed the first signs of fetal abnormality and she was referred to the medical center. At 32 weeks' gestation, ultrasound confirmed extreme intrauterine growth retardation, including microcephaly, as well as placental calcifications and other anomalies. Based on the poor fetal prognosis, she requested that the pregnancy be terminated at that time. Prominent microcephaly was noted at delivery.
Neuropathological findings on autopsy included micrencephaly and numerous calcifications in the cortex and subcortical white matter in the frontal, parietal and occipital lobes. Reverse transcription-polymerase chain reaction assay of fetal brain tissue was positive for Zika virus, and genomic sequencing of the virus showed high alignment with strains isolated in French Polynesia in 2013 and Sao Paulo, Brazil, in 2015. No virus or pathological changes were detected in other body tissue samples, which, said the researchers "suggests a strong neurotropism of the virus."
Updated CDC Guidance for Clinicians
Also during the CDC briefing, Frieden discussed an update to the agency's interim guidelines for health care professionals(www.cdc.gov) caring for pregnant women and women of reproductive age with possible Zika virus exposure that was released in a Feb. 5 Morbidity and Mortality Weekly Report (MMWR). The update includes a recommendation that physicians offer serologic testing to asymptomatic pregnant women who have traveled to areas with ongoing Zika virus transmission.
"I can say that over the past two weeks, we've learned several things," he said. "First, the serological test, which is an (immunoglobulin M) test, which tests for an acute infection, is performing better than we had hoped. So we have more confidence in this test than we did even two weeks ago."
Frieden said because the test has been shown to be so accurate, the guidance for testing has been expanded from testing pregnant women with symptoms of Zika virus to also testing those without symptoms who had traveled to areas with active Zika virus transmission. This testing is to occur between two and 12 weeks after these patients have returned from a country with active Zika virus infection cases.
In addition, for pregnant women with clinical illness consistent with Zika virus disease, testing is recommended during the first week of illness.
Frieden also pointed to interim guidance on preventing sexual transmission of the Zika virus, as was recently reported in Texas. That guidance also was published as an early-release MMWR article(www.cdc.gov) on Feb. 5.
The CDC's guidance on sexual transmission prevention reflects the fact that although the three cases reported to date that appear to involve sexual transmission have each involved men who showed symptoms of infection, it cannot be assumed that asymptomatic infected men won't transmit the infection.
The agency's advice is basically twofold:
- Men who reside in or have traveled to an area with active Zika virus transmission who have a pregnant partner should either abstain from sexual activity or consistently and correctly use condoms during sex (i.e., vaginal intercourse, anal intercourse, or fellatio) for the duration of the pregnancy.
- Men who reside in or have traveled to an area with active Zika virus transmission who are concerned about transmitting the virus sexually might consider abstaining from sexual activity or using condoms consistently and correctly during sex.
In addition, pregnant women should discuss their male partner's history of travel and possible exposure to mosquitoes with their physician.
At this time, Zika virus testing to assess the risk of sexual transmission is of uncertain value and is not recommended.
Possible Zika-related Ocular Abnormalities
In other Zika virus-related news, a JAMA Ophthalmology study(archopht.jamanetwork.com) published online Feb. 9 explored the connection between ocular abnormalities in infants with microcephaly and suspected congenital infection with the Zika virus.
Researchers found that congenital Zika virus infection did, in fact, correspond with vision-threatening eye issues, which included bilateral macular and perimacular lesions, as well as optic nerve abnormalities.
The study was conducted from Dec. 1 to Dec. 21 and involved 29 women and their infants with microcephaly who were evaluated with ophthalmic examinations at Roberto Santos General Hospital in Salvador, Brazil.
Anterior segment and retinal, choroidal and optic nerve abnormalities were documented using a wide-field digital imaging system. Differential diagnoses of toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis and HIV infection were ruled out through clinical examination and serologic testing.
Of the 29 mothers, almost 80 percent reported Zika virus infection signs and symptoms during pregnancy: 18 women in the first trimester, four in the second trimester and one in the third trimester.
Among these women's infants, ocular abnormalities were present in almost 30 percent of their eyes. Bilateral findings in seven of the 10 patients who presented with ocular lesions included focal pigment mottling of the retina and chorioretinal atrophy (about 65 percent of eyes), followed by optic nerve abnormalities (about 47 percent), bilateral iris coloboma (about 12 percent) and lens subluxation (about 6 percent).
"This study can help guide clinical management and practice," said the authors. "Infants with microcephaly should undergo routine ophthalmologic evaluations to identify such lesions."
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