FROM THE LANCET

The largest study so far of congenital Zika virus syndrome suggests that microcephaly and maternal rash are not sufficient to detect affected babies.

Writing in the June 29 online edition of The Lancet, researchers report on a case series of 1,501 liveborn infants with suspected congenital Zika virus syndrome reported in Brazil. The study found that one in five definite or probable cases of congenital Zika virus syndrome had a head circumference within the range of normal, and in one third of definite or probable cases, the mother had no history of a rash during pregnancy.

Of the total series, 899 were discarded because they showed no obvious clinical or neuropsychomotor abnormalities such as craniofacial disproportion or neurological symptoms (Lancet. 2016 Jun 29. doi: 10.1016/S0140-6736[16]30902-3 ).

Of the remaining 602 cases, 76 were described as definite cases of congenital Zika virus syndrome because of laboratory evidence of Zika virus infection during pregnancy.

Fifty-four babies were considered highly probable cases of congenital Zika virus syndrome because imaging reports showed features such as brain calcifications and ventricular enlargement suggestive of Zika virus infection and which could not be attributed to other pathogens such as syphilis, cytomegalovirus, or toxoplasmosis.

A further 181 were “moderately probable” – they had similar imaging results to the highly probable group but without test results for other infections – while the 291 somewhat probable cases had imaging results that suggested Zika virus was likely involved.

Among the 391 definitely or probable cases where full information was available, half had both microcephaly and a history of maternal rash, while 87% had at least one of these symptoms.

“There were only two significant differences between the four categories: diagnostic certainty was positively associated with reported rashes and with smaller head circumferences before taking gestational age into account,” wrote Giovanny V. A. França, PhD, of the Secretariat of Health Surveillance, Ministry of Health, Brazil, and coauthors.

Researchers also noted that the discarded cases had larger head circumferences, lower first week mortality, and the mothers were less likely to have a history of rash during pregnancy (20.7% vs 61.4%, 95% confidence interval, 0.27-0.42).

Meanwhile, a second case series in the same edition of The Lancet reported on the pathology of five cases of congenital Zika syndrome, providing further evidence of the link between the virus and congenital abnormalities.

Tissue samples from three fatal cases of the syndrome and two spontaneous abortions found antigens to the Zika virus in the cytoplasm of degenerating and necrotic neurons and glial cells, but no immunohistochemical staining for Zika virus was found outside the central nervous system (Lancet. 2016 Jun 29. doi: 10.1016/S0140-6736[16]30883-2 ).

The five cases all showed signs of brain abnormalities including microcephaly, lissencephaly, cerebellar hypoplasia, and ventriculomegaly, while histopathological studies in the three fatal cases revealed microcalcifications, scattered microglial nodules, cell degeneration, and necrosis.

“The absence of a substantial inflammatory response in the brain and a specific cytopathic viral effect distinguishes Zika virus infection from other important viral infections that are also associated with microcephaly and microcalcifications, such as cytomegalovirus and herpes simplex virus,” wrote Roosecelis Brasil Martines, MD, of the National Center for Emerging and Zoonotic Infectious Diseases, CDC, and coauthors.

There was also a range of other congenital malformations evident in the three fatal cases, including multiple congenital contractures, craniofacial malformations, craniosynostosis, pulmonary hypoplasia, and a wide range of brain abnormalities.

“The mechanism for these deformities in Zika virus infection are not entirely clear, but most probably result from neurotropism of the virus with subsequent damage of the brain and interference in neuromuscular signaling leading to fetal akinesia,” the authors said.

No conflicts of interest were declared for either study.

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