Analysis of blood samples from 42 patients diagnosed with Guillain-Barré syndrome (GBS) during the Zika virus outbreak in French Polynesia provides the first evidence that Zika virus might cause GBS, a severe neurological disorder, according to new research published in The Lancet today. Based on the analysis of data from French Polynesia, if 100000 people were infected with Zika virus, 24 would develop GBS.
"This is the first study to look at a large number of patients who developed Guillain-Barré syndrome following Zika virus infection and provide evidence that Zika virus can cause GBS," says lead author Professor Arnaud Fontanet from the Institut Pasteur, Paris, France. "Most of the patients with GBS reported they had experienced symptoms of Zika virus infection on average 6 days before any neurological symptoms, and all carried Zika virus antibodies." 
In between October 2013 to April 2014, French Polynesia experienced the largest Zika outbreak to be reported at the time. An estimated 32000 patients consulted a doctor about a suspected Zika virus infection, and 42 patients were diagnosed with GBS between November 2013 and February 2014. Zika virus infection is associated with symptoms such as fever, rash, joint and muscle pain and conjunctivitis. The current Zika outbreak in Central and South America was followed by increased reports of cases of microcephaly and GBS, leading the World Health Organisation to declare it a global emergency.
Guillain-Barré syndrome (GBS) is a disorder which affects the immune and nervous systems, and is the leading cause of non-trauma related paralysis. Symptoms develop rapidly and include weakness in the legs and arms, muscle weakness and pain. In about 20-30% of cases, severe GBS can lead to respiratory failure, and about 5% of patients die. GBS is usually triggered by an infection and can sometimes develop following infections of herpes, influenza or dengue virus. Across Europe and North America, GBS affects approximately 1-2 people out of 100000 per year. 
The aim of the study was to determine the link between Zika virus infection and GBS. Since French Polynesia is also prone to outbreaks of dengue virus, the researchers also wanted to see whether dengue virus was an additional risk factor for GBS.
All 42 patients with GBS diagnosed at the Centre Hospitalier de Polynésie Française in Papeete, Tahiti were included in the study. Researchers recruited two control groups. The first control group (CTR 1), matched for age, gender and island of residence, consisted of 98 patients who attended the same hospital but did not have a fever. The second control group (CTR 2) consisted of 70 patients who tested positive for Zika virus infection, but did not develop any of the neurological symptoms associated with GBS. Blood samples were collected from all patients.
Most (88%) of the patients with GBS reported symptoms of Zika virus infection approximately 6 days before the onset of neurological symptoms. While none tested positive for a Zika virus infection once in hospital, blood tests showed that 41 (98%) were carrying Zika virus antibodies, and all (100%) had neutralizing antibodies against Zika virus.
By comparison, only 54 (56%) of the patients without a fever (CTR 1 group) were carrying Zika virus neutralizing antibodies. Most patients with GBS (95.2%) had signs of past dengue virus infection, as did most patients in the two control groups (88.8% in CTL 1; 82.9% in CTL 2). The authors therefore concluded that, in this case, past infection with dengue virus did not increase the risk of GBS among patients infected with Zika virus.
All 42 patients were diagnosed with a type of GBS called 'acute-motor axonal neuropathy' (AMAN), but few carried the biological markers typically associated with AMAN, suggesting a previously unknown disease mechanism. The patients in the study generally recovered faster than is usually expected with GBS.
Of the 42 patients with GBS, 16 (38%) were admitted to the hospital's intensive care unit and 12 (29%) required breathing assistance. On average, patients were hospitalised for 11 days, but those in intensive care remained for longer (51 days). Three months after discharge, 24 (57%) patients were able to walk without assistance. No patients with GBS died.
Based on an attack rate for Zika virus of 66% in French Polynesia, the authors estimate that the risk of Guillain-Barré syndrome in the general population during the outbreak in French Polynesia is 0·24 per 1000 Zika virus infections (or 24 people per 100000 infections).
Professor Fontanet adds: "Although it is unknown whether attack rates of Zika virus epidemics will be as high in affected regions in Latin America than in the Pacific Islands, high numbers of cases of Guillain-Barré syndrome might be expected in the coming months as the result of this association. The results of our study support that Zika virus should be added to the list of infectious pathogens susceptible to cause Guillain-Barré syndrome." 
Writing in a linked Comment, Professor David W Smith, University of Western Australia, Australia says: "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. Suffice to say Zika virus can be added to our list of viruses that can cause Guillain-Barré syndrome, and investigation of these cases should include tests for Zika when there is a possibility of infection by that virus. Whether Zika will be proven to pose a greater threat in causing Guillain-Barré syndrome than its various flavivirus cousins remains to be determined."
NOTES TO EDITORS:
The Study was funded by Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS, and Wellcome Trust.
 Quotes direct from author and cannot be found in the text of the Article.
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 Proportion of new cases in the at-risk population.