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Emerging evidence strengthens association between Zika, microcephaly
According to multiple, independently published case reports, the presence of Zika virus in fetal tissue indicated a strong association between Zika and microcephaly, while other testing confirmed Zika virus in the brain tissue of a microcephallic fetus.
“We present a case of vertical transmission of Zika virus in a woman who was probably infected with Zika virus in northeastern Brazil at the end of the first trimester of pregnancy,” Jernej Mlakar, MD, of the Institute of Pathology at the University of Ljubljana’s Faculty of Medicine, Slovenia, and colleagues wrote in the New England Journal of Medicine. “This case shows severe fetal brain injury associated with Zika virus infection with vertical transmission.”
The researchers tested fetal tissue from a terminated pregnancy, after ultrasonography revealed severe microcephaly in the brain and placenta. The mother, a European woman, lived and became pregnant while in Brazil. At week 13 of pregnancy, the patient experienced onset of Zika-like symptoms, including high fever, musculoskeletal pain, retro-ocular pain and itching. A confirmed Zika virus diagnosis, however, was never made, and fetal growth was normal at 14 and 20 weeks’ gestational age. After returning to Europe, ultrasonography revealed fetal anomalies at 29 weeks.
Reverse transcriptase (RT)-PCR assay testing revealed the presence of Zika virus in the fetal brain tissue. The researchers wrote that the number of viral copies found in the tissue were significantly higher than those normally found in adult Zika patients. Study results also showed that no indications of Zika virus or pathological changes were found in any other part of the fetus, suggesting neurotropism of the virus.
The researchers noted that it remains unclear why Zika virus infected the nervous tissue of the growing fetus.
“Further research is needed to better understand the potential implications of these observations,” Mlakar and colleagues wrote. “It is likely that the rapid spread of Zika virus around the globe will be a strong impetus for collaborative research on the biologic properties of the virus, particularly since the risk of neurotropic and teratogenic virus infections places a high emotional and economic burden on society.”
Further positive cases
In research published recently in MMWR, investigators wrote that tissue from four pregnancies, complicated by microcephaly, tested positive for Zika virus infection.
“This report describes evidence of a link between Zika virus infection and microcephaly and fetal demise through detection of viral RNA and antigens in brain tissues from infants with microcephaly and placental tissues from early miscarriages,” Roosecelis Brasil Martines, MD, PhD, of the infectious diseases pathology branch at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, and colleagues wrote. “Histopathologic findings indicate the presence of Zika virus in fetal tissues.”
Figure 1. This is a digitally-colorized transmission electron micrograph (TEM) of Zika virus, which is a member of the family Flaviviridae. Virus particles, here colored red, are 40 nm in diameter, with an outer envelope, and an inner dense core.
Source: Cynthia Goldsmith, Centers for Disease Control and Prevention
The report detailed RT-PCR assay findings from two newborns with microcephaly who died within 20 hours of birth and two miscarriages in Brazil. All four mothers had clinical signs of Zika virus during pregnancy; however, symptoms had resolved at delivery in all four cases. Zika virus was not serologically confirmed in any of the mothers.
RT-PCR assay results showed that all four cases tested positive for Zika virus. Again, RT-PCR-evidence of Zika was only detected in brain tissue. The researchers ruled out other possible infections, such as dengue fever.
The researchers said their findings suggest brain and placenta tissue may be the optimal source of tissue for postmortem viral testing.
“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,” Martines and colleagues wrote. – by David Costill
Disclosure: The researchers report no relevant financial disclosures.
