Case-control study points to Zika virus as cause of microcephaly




A new study from Brazil demonstrates that microcephaly is strongly associated with congenital Zika virus infections, offering case-control evidence of a causal relationship.

“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” Thalia Velho Barreto de Araújo, PhD, of the Federal University of Pernambuco, Recife, Brazil, said in a statement. “Our findings suggest that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”

In April, officials at the Centers for Disease Control and Prevention determined that Zika virus infection is a cause of microcephaly, following a systematic review of the available Zika virus research.

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In the current study, the investigators looked for cases of infants born with microcephaly at eight public hospitals in Pernambuco, a state in northeastern Brazil. Thirty-two such cases were included for analysis, along with 62 controls. All infants in the study were born between Jan. 15, 2016 and May 2, 2016 (Lancet Infect Dis. 2016 Sep 15. doi: 10.1016/S1473-3099[16]30318-8).

Zika-specific immunoglobulin M (IgM) and reverse transcription–polymerase chain reaction (RT-PCR) tests were conducted on serum from both microcephaly and control infants, and cerebrospinal fluid samples only from infants with microcephaly. Mothers underwent serum testing for Zika virus and dengue virus via plaque reduction neutralization assay testing. Odds ratios and 95% confidence intervals were then calculated to determine the association between congenital Zika virus and microcephaly.

Of the 30 women who gave birth to infants with microcephaly, 24 (80%) had Zika virus infections, compared with 39 of the 61 women (64%) in the control group (P = .12). Additionally, while 13 of the 32 infants born with microcephaly had Zika virus infections confirmed by laboratory testing, none of the infants in the control group had laboratory-confirmed Zika virus infection.

A total of 7 out 27 infants with microcephaly who underwent CT scans showed signs of brain abnormalities, suggesting that “congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities,” according to the investigators.

While the study is still ongoing, the investigators called for more research to assess other potential risk factors and to confirm the strength of association in a larger sample size, as well as to gauge the significance and role of previous dengue infections in the mothers.

The study was funded by the Brazilian Ministry of Health, the Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. The investigators reported having no relevant financial disclosures.

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