An analysis of blood samples from the Zika virus outbreak in French Polynesia in 2013 and 2014 strengthens the link with Guillain-Barré syndrome (GBS) and suggests a GBS incidence of 24 per 100,000 patients with Zika, researchers report in an article published online February 29 in the Lancet. The need for intensive care unit (ICU) and respiratory support for patients with Zika virus who develop GBS is likely to add to the public health challenge of combatting the fast-moving viral disease, they say.
"This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome," write Van-Mai Cao-Lormeau, PhD, from the Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France, and colleagues.
In an accompanying editorial, David W. Smith, MBBS, from the School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, and John Mackenzie, PhD, from the Faculty of Health Science, Curtin University, Bentley, Western Australia, call the new data "the first strong evidence that Zika virus can cause Guillain-Barré syndrome."
However, they note that numerous questions remain. "A little caution should be taken because the data are still scarce and we do not know whether the current Zika virus is identical to that in previous outbreaks, whether it will behave exactly the same in a different population with a different genetic and immunity background, or whether a cofactor or co-infection is responsible."
Dr Cao-Lormeau and colleagues in Paris and Tahiti undertook this study to determine whether Zika virus, with or without concurrent or prior dengue infection (also common in French Polynesia), could be a risk factor for GBS.
All patients with suspected GBS had been routinely referred to the Centre Hospitalier de la Polynésie Française for confirmation by standard motor nerve conduction studies of the median nerve, the ulnar nerve, and the peroneal nerve, and for sensory nerve conduction studies of the radial and sural nerves.
Dr Cao-Lormeau and colleagues analyzed blood samples from all 42 patients diagnosed with GBS at the Centre Hospitalier de la Polynésie Française during the October 2013-April 2014 Zika virus outbreak in French Polynesia, which was the largest known outbreak at that time. They compared those data with data from two control groups. The first control group (n = 98, matched for age, sex, and island of residence) had been treated in the same hospital but did not have a fever. The second, non-GBS group (n = 70) tested positive for Zika virus infection but did not have GBS neurological symptoms.
The patients with GBS presented with generalized muscle weakness (74%), inability to walk (44%), and/or facial palsy (64%). Sixteen of these 42 patients (38%) were admitted to ICU, and 12 (29%) required respiratory assistance. Median hospital stays were 11 days for all patients with GBS and 51 days for those admitted to ICU. All were treated with immunoglobulins, and one had plasmapheresis, but by 3 months after discharge only 24 (57%) had regained the ability to walk without assistance.
None of the patients with GBS had Zika viremia at the time of hospital admission, but 88% reported having had a transient illness a median of 6 days before onset of neurological symptoms. Moreover, 41 of 42 patients with GBS (98%) were positive for Zika virus on the basis of reverse transcription polymerase chain reaction compared with 35 (36%) of the 98 patients in the first control group (Odds ratio [OR], 59.7; P < .0001). All of the patients with GBS (100%) had neutralizing antibodies against Zika virus, as did 54 (56%) of the first control group (OR, 34.1; P < .0001).
History of dengue fever was not significantly different among the three groups of patients, and the researchers conclude that dengue did not add to the risk for GBS in Zika-infected patients.
The authors write, "The results of our study support that Zika virus should be added to the list of infectious pathogens susceptible to cause [GBS]. As Zika virus is spreading rapidly across the Americas, at risk countries need to be prepared to have adequate intensive care beds capacity to manage patients with [GBS]."
The editorialists note that the estimated rate of GBS among patients with Zika needs to be confirmed and tracked carefully to ensure that any apparent increase during the ongoing Zika epidemic reflects an actual increase rather than an increase in reporting.
They also point out that because most of the patients with GBS in the current study reported having Zika symptoms prior to GBS onset, and most Zika cases are asymptomatic, the risk for GBS may be clustered among patient with symptomatic Zika infections.
The study was funded by Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS, and the Wellcome Trust. The authors have disclosed no relevant financial relationships.
Lancet. Published online February 29, 2016