While scientists can’t say with certainty that congenital Zika virus is causing the massive spike in cases of microcephaly seen in Brazil, evidence of a strong association continues to mount.
Two reports, published Feb. 10 in the Morbidity and Mortality Weekly Report and in the New England Journal of Medicine, confirm through laboratory testing that fetuses and infants with microcephaly also were positive for Zika virus infection.
In the MMWR report, researchers from the United States and Brazil present evidence of a link between Zika virus infection and microcephaly and fetal demise through detection of viral RNA and antigens in brain tissues with infants with microcephaly, as well as placental tissues from early miscarriages.
The findings are based on laboratory testing of tissue samples from two newborns with microcephaly who died within 20 hours of birth and two miscarriages (at 11 and 13 weeks’ gestation). The samples were submitted to the Centers for Disease Control and Prevention from the state of Rio Grande do Norte, Brazil, in December 2015. All four mothers had clinical signs of Zika virus infection during the first trimester but did not have signs of active infection at the time of delivery or miscarriage.
Specimens from all four cases were positive by reverse transcription-polymerase chain reaction (RT-PCR) testing, and sequence analysis provided additional evidence of Zika virus infection (Morb Mortal Wkly Rep. 2016 Feb;65:1-2. doi: 10.15585/mmwr.mm6506e1er).
“To better understand the pathogenesis of Zika virus infection and associated congenital anomalies and fetal death, it is necessary to evaluate autopsy and placental tissues from additional cases, and to determine the effect of gestational age during maternal illness on fetal outcomes,” the researchers wrote.
In the New England Journal of Medicine report, Dr. Jernej Mlakar of the University of Ljubljana, Slovenia, and colleagues, presented the case of a previously healthy 25-year-old pregnant woman who had become ill while living in Brazil. During the 13th week of gestation, she had a high fever, followed by severe musculoskeletal and retro-ocular pain, as well as an itchy generalized maculopapular rash. Zika virus was suspected at the time but virologic diagnostic testing was not performed.
Ultrasound at 14 weeks and 20 weeks showed normal fetal growth and anatomy, but ultrasound at 29 weeks showed signs of fetal abnormalities. At 32 weeks, physicians confirmed intrauterine growth retardation and microcephaly with calcifications in the fetal brain and placenta.
The woman requested termination of the pregnancy and an autopsy was performed on the fetus. Positive results for Zika virus were obtained on RT-PCR assay in the fetal brain sample. All autopsy samples were tested on PCR assay and found to be negative for other flaviviruses, including dengue, yellow fever, West Nile, and tick-borne encephalitis (N Engl J Med. 2016 Feb 10. doi: 10.1056/NEJMoa1600651).
In an editorial accompanying the report, physicians from the Harvard School of Public Health and Massachusetts General Hospital, both in Boston, wrote that there are still many unanswered questions about Zika virus in pregnancy. Assuming the association between Zika virus and microcephaly exists, researchers do not know whether the timing of the infection during pregnancy has an effect on the risk of fetal abnormalities. Additionally, it’s unknown whether asymptomatic or minimally symptomatic disease poses a risk to the fetus (N Engl J Med. 2016 Feb 10. doi: 10.1056/NEJMe1601862).
The researchers for both case reports had no financial disclosures.
mschneider@frontlinemedcom.com
On Twitter @maryellenny