Zika: The Expanding and Deepening Threat

Marc Gozlan, MD


November 14, 2016

The case/control study[32] described the clinical and electrophysiologic characteristics of 42 patients who were diagnosed with GBS during the French Polynesia Zika outbreak. The researchers compared the clinical and laboratory profiles of those patients with patients matched for age, sex, race, and residence who presented at the hospital with a nonfebrile illness (control group 1) and with a second control group of patients with acute Zika virus infection but without neurologic symptoms.

This study was the first to provide evidence for Zika virus infection causing GBS.

Serology tests showed that 98% of patients with GBS had anti-Zika virus IgM or IgG, and 100% had neutralizing antibodies against Zika virus compared with 56% of patients in control group 1. Thirty-nine patients (93%) with GBS had Zika virus IgM, and 37 patients (88%) had experienced a transient illness in a median of 6 days before the onset of neurologic symptoms. Electrophysiologic testing revealed that patients with GBS had findings compatible with acute motor axonal neuropathy and showed a rapid progression of disease, shorter than that described in other series of GBS. Sixteen people required intensive care unit treatment, with 12 of them needing respiratory assistance. No patients died. Full recovery occurred after 3 months in 57% of patients.

This study was the first to provide evidence for Zika virus infection causing GBS.[32] The estimated incidence of GBS in this outbreak has been 0.24 per 1000 Zika virus-infected individuals.

Early March 2016. The ECDC reported that GBS had been observed in five countries since October 2015.[34] Among them, Brazil, Suriname, and Venezuela reported GBS cases with laboratory confirmation of Zika virus infection.

The links between Zika virus infection and devastating cases of microcephaly and GBS prompted new laboratory research into what appeared more and more clearly to be a neurotropic and neuropathic virus. A study showed that Zika virus directly infected human cortical neural progenitors cells with high efficacy.[35] The virus increased cell death and dysregulated cell-cycle progression, resulting in stunted growth of this cell population. This study also provided an in vitro model that could be used to investigate the impact and mechanism of Zika virus on human brain development, and serve as a platform to screen therapeutic compounds.[35]

At that time, Zika virus was also detected in the cerebrospinal fluid of patients with other serious neuropathologic manifestations. Acute myelitis was thus described 7 days after Zika virus infection in a 15-year-old girl from the French Caribbean island of Guadeloupe.[36] Meningoencephalitis was observed in the course of Zika virus infection in a 81-year-old man returning to France after a cruise in the area of New Caledonia.[37] Two cases of encephalopathy (one with seizures, one with EEG changes) were also reported in patients with Zika virus infection detected in Martinique.[38]

March 8, 2016. Only 5 weeks after WHO said that the association between Zika and the cluster of microcephaly cases and other neurologic disorders reported in Brazil constituted a Public Health Emergency of International Concern, the United Nations agency advised pregnant women not to travel to areas with ongoing outbreaks of Zika virus owing to the potential risk for birth defects.[39]

Previously, on January 15, January 22, and February 3, 2016, the CDC had issued alerts for people traveling to regions and certain countries where Zika virus transmission was ongoing. The US agency had advised that pregnant women should consider postponing travel to these areas (Figure 3).

Figure 3. Pregnancy and traveling infographic. Courtesy of the World Health Organization.

The deleterious effects of congenital Zika virus infection were also reinforced by a cohort study of infected pregnant Brazilian women whose infants had been followed prospectively.[40] Fetal growth restriction and abnormalities in CNS development were observed on ultrasound in 29% of these women.[40]


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