Guillain-Barré syndrome – France - French Polynesia
On 24 November 2015, health authorities in French Polynesia reported unknown and unspecified causes of morbidity and mortality in the context of concomitant outbreaks of Zika and dengue (serotypes 1 and 3) viruses. This update provides additional information on the clinical findings as well as the epidemiological and laboratory investigations of these cases.
Between October 2013 and April 2014, French Polynesia experienced the largest Zika virus outbreak ever recorded in the country. During this period of time, 32,000 patients (11.5% of the population) were assessed for the infection and 8,750 suspected cases were reported by the national surveillance system. Of the suspected cases, 383 were later laboratory-confirmed by reverse transcription polymerase chain reaction (RT-PCR).
During the Zika virus outbreak, 42 patients were admitted to hospital with Guillain-Barré syndrome (GBS). This represents a 20-fold increase in incidence of GBS in French Polynesia compared with the previous four years. Of the 42 patients, 16 (38%) required admission to an intensive care unit (ICU) and 12 (29%) received mechanical ventilation. The duration of hospital stay for patients that were not admitted to ICU ranged between 7 to 20 days (median=11). The duration of hospital stay for patients that were admitted to intensive care went from 16 to 70 days (median=51). No deaths were reported. The majority of these cases (88%) reported symptomatic Zika virus infection in the days (median=6) that preceded the onset of neurological symptoms.
Further investigations were carried out to identify the potential role of previous infections known to be associated, or potentially associated, with GBS. The investigations carried out by the Bureau de Veille Sanitaire-Direction de la Santé de Polynésie Française showed that 41 of the 42 cases of GBS (98%) had IgM or IgG antibodies against Zika virus; furthermore, all GBS cases (100%) had positive seroneutralisation against Zika virus. Results for the matched non-febrile illness control group were significantly different: elevated IgM or IgG antibodies were detected in 35 of the 98 control patients (36%); additionally, neutralising antibodies against Zika virus were detected in 54 control patients (56%).
Analysis of dengue serology (immunofluorescent assay, microsphere immunoassay, and seroneutralisation) did not support recent dengue infection, even though most cases (95%) had pre-existing dengue immunity. Other known causes of GBS were investigated and excluded, including Campylobacter jejuni, Cytomegalovirus, HIV, Epstein–Barr and Herpes simplex viruses.
WHO risk assessment
This is the first report of a large number of patients who developed GBS after contracting Zika virus. The study provides strong evidence of a possible causal relationship between Zika virus infection and GBS. Since all 42 cases had serological tests suggesting successive dengue and Zika virus infections, this association might be a predisposing factor for developing GBS. Further investigations are needed to understand the implications of pre-existing dengue infections, together with recent Zika infections, in the pathogenesis of GBS.
Similarly to French Polynesia, it is likely that countries that are currently reporting autochthonous Zika virus transmission will face a rise in the number of GBS cases in the coming months. A number of countries in Latin America have already started to report an increase in the incidence of GBS while experiencing a rise in the cases of Zika virus infection. Nevertheless, it is critical to ensure that in all these countries, the reported increases in the incidence of GBS are the result of a real change rather than enhanced surveillance. WHO continues to monitor the epidemiological situation and conduct risk assessment based on the latest available information.
WHO recommends Member States affected or susceptible to Zika virus outbreaks to:
- monitor the incidence and trends of neurological disorders, especially GBS, to identify variations against their expected baseline values;
- develop and implement sufficient patient management protocols to manage the additional burden on health care facilities generated by a sudden increase in patients with Guillain-Barre Syndrome;
- raise awareness among health care workers and establish and/or strengthen links between public health services and clinicians in the public and private sectors.
The proximity of mosquito vector breeding sites to human habitation is a significant risk factor for Zika virus infection. Prevention and control relies on reducing the breeding of mosquitoes through source reduction (removal and modification of breeding sites) and reducing contact between mosquitoes and people. This can be achieved by reducing the number of natural and artificial water-filled habitats that support mosquito larvae, reducing the adult mosquito populations around at-risk communities and by using barriers such as insect screens, closed doors and windows, long clothing and repellents. Since the Aedes mosquitoes (the primary vector for transmission) are day-biting mosquitoes, it is recommended that those who sleep during the daytime, particularly young children, the sick or elderly, should rest under mosquito nets (bed nets), treated with or without insecticide to provide protection.
During outbreaks, space spraying of insecticides may be carried out following the technical orientation provided by WHO to kill flying mosquitoes. Suitable insecticides (recommended by the WHO Pesticide Evaluation Scheme) may also be used as larvicides to treat relatively large water containers, when this is technically indicated.
Basic precautions for protection from mosquito bites should be taken by people traveling to high risk areas, especially pregnant women. These include use of repellents, wearing light colored, long sleeved shirts and pants and ensuring rooms are fitted with screens to prevent mosquitoes from entering.
WHO does not recommend any travel or trade restriction to France and its overseas departments based on the current information available.