One year into the Zika outbreak: how an obscure disease became a global health emergency

A dramatic new profile for a “harmless” old disease

In mid-July 2015, Brazil informed WHO of an uptick in the detection of neurological disorders, including Guillain-Barré syndrome, mainly from the northeastern state of Bahia, an early epicentre of Zika virus transmission. That finding was later repeated in other countries with large outbreaks, including Colombia, Dominican Republic, El Salvador, Honduras, Suriname, and Venezuela. In most of these countries, the syndrome was detected about three months after virus circulation was confirmed. A link with Zika was strongly suspected.

The most riveting news emerged at the end of October 2015, when Brazil informed WHO that 54 cases of microcephaly among newborns had been detected since August. The possibility that a mosquito bite during pregnancy could be linked to severe brain abnormalities in newborns alarmed the public and astonished scientists. Though evidence was scant, paediatric neurologists in Brazil were convinced that the brain abnormalities were linked to Zika. Subsequent findings would prove them right.

The detection of microcephaly in Brazil prompted a retrospective investigation of the outbreak in French Polynesia. The results, communicated to WHO in November 2015, identified at least 17 newborns with different severe brain malformations, including microcephaly and neonatal brainstem dysfunction.

In late January 2016, a second report from French Polynesia informed WHO that further research had now convincingly linked Zika to the surge in cases of Guillain-Barré syndrome.

On 1 February 2016, WHO declared that the association between Zika and the cluster of microcephaly cases and other neurologic disorders reported in Brazil, following a similar cluster in French Polynesia, constituted a Public Health Emergency of International Concern.

A flurry of studies followed, as newborns, miscarriages, and stillbirths with brain abnormalities and their mothers were investigated. Zika was detected in amniotic fluid, the placenta, the umbilical cord, fetal blood, and fetal brain tissue. In one case of severe brain malformations, live Zika virus was cultured from fetal brain tissue.

Many of these studies excluded co-infection with dengue and chikungunya and eliminated other known infectious causes of microcephaly, strengthening the evidence of causality. Further evidence came from laboratory studies demonstrating that Zika is neurotropic, meaning that it preferentially affects brain cells.

Some of the foetuses studied were consistent with the so-called “fetal brain disruption sequence”, an extreme form of microcephaly in which the fetal brain stops growing, the skull partially collapses, and excess scalp skin shows distinctive folds. The concept of a “congenital Zika syndrome” emerged as a typical pattern including severe microcephaly, brain calcifications, and other brain anomalies, sometimes accompanied by impaired eyesight and hearing loss.

In children and adults, the full spectrum of effects on the central nervous system is likely yet to be discovered, as hinted by case reports of inflammation of the spinal cord, and cases consistent with a syndrome involving inflammation of the spinal cord and brain that resembles multiple sclerosis. For newborns, many experts believe that a virus capable of causing such severe abnormalities is likely to cause additional neurological problems as children develop.

Based on these and other studies, WHO concluded at the end of March 2016 that there is scientific consensus that Zika virus is a cause of microcephaly and Guillain-Barré syndrome. At that time, cases of microcephaly had been reported in Brazil, Cabo Verde, Colombia, Martinique, and Panama as well as French Polynesia.

A subsequent paper by scientists from the US Centers for Disease Control and Prevention, published in April 2016 in the New England Journal of Medicine, put to rest remaining doubts about the causal association between Zika infection during pregnancy and microcephaly in newborns.