Does Zika virus (ZIKV) cause fetal microcephaly?
In February the WHO declared that the spread of ZIKV infection, which is sweeping through South and Central America resulting in more than a million cases so far, was a global health emergency. Infection with this flavivirus, endemic for decades in areas of Africa and Asia where the vector Aedes species mosquitoes breed, is usually sporadic and either asymptomatic or results in benign disease similar to dengue and chikungunya virus infections. Although ZIKV can, in common with many other viral infections, trigger the rare neurological Guillain-Barré syndrome, it is the recently observed correlation between cases of infection with the virus and infants born with microcephaly that has prompted the WHO’s declaration. So what evidence is there to support the hypothesis that intrauterine infection with ZIKV can result in fetal brain abnormalities?
ZIKV spread to the Pacific Islands nine years ago, and it was during the outbreak in French Polynesia from December 2013 (affecting 11% of the population) that robust laboratory tests including RT-PCR confirmed transmission of ZIKV from two mothers to their neonates. Also, a retrospective investigation of this outbreak documented an increase in infants born with severe cerebral malformations. Brazil notified the WHO of a disease that proved to be ZIKV spreading through the north-eastern states a year ago, and the reporting of a possible link between the virus and microcephaly in neonates resulted in an alert being issued by the Pan American Health Organization and WHO that stressed the need for reliable laboratory detection of the virus. But the strongest evidence for a link so far, published very recently in the NEJM, concerns a pregnant European woman who became ill at the end of her first trimester whilst working as a volunteer in Brazil. On her return to Slovenia an ultrasound at 32 weeks confirmed severe fetal brain disease and microcephaly, the pregnancy was terminated and an autopsy of the fetus, involving electron microscopy as well as RT-PCR, revealed ZIKV RNA confined to the brain. No other pathogens were found.
Since there will be few terminations so late in pregnancy, particularly in the Americas, this is likely to be the most robust evidence obtainable. So what is the immediate need? Surely rapid diagnostic tests, and the provision of reliable contraception and pregnancy termination services – at least until there is widespread immunity in the population at risk.