Zika virus in French Polynesia 2013-14: anatomy of a completed outbreak.

The Zika virus crisis exemplified the risk associated with emerging pathogens and was a reminder that preparedness for the worst-case scenario, although challenging, is needed. Herein, we review all data reported during the unexpected emergence of Zika virus in French Polynesia in late 2013. We focus on the new findings reported during this outbreak, especially the first description of severe neurological complications in adults and the retrospective description of CNS malformations in neonates, the isolation of Zika virus in semen, the potential for blood-transfusion transmission, mother-to-child transmission, and the development of new diagnostic assays. We describe the effect of this outbreak on health systems, the implementation of vector-borne control strategies, and the line of communication used to alert the international community of the new risk associated with Zika virus. This outbreak highlighted the need for careful monitoring of all unexpected events that occur during an emergence, to implement surveillance and research programmes in parallel to management of cases, and to be prepared to the worst-case scenario.

Real-Time Assessment of Health-Care Requirements During the Zika Virus Epidemic in Martinique.

The spread of Zika virus in the Americas has been associated with a surge in Guillain-Barré syndrome (GBS) cases. Given the severity of GBS, territories affected by Zika virus need to plan health-care resources to manage GBS patients. To inform such planning in Martinique, we analyzed Zika virus surveillance and GBS data from Martinique in real time with a modeling framework that captured dynamics of the Zika virus epidemic, the risk of GBS in Zika virus-infected persons, and the clinical management of GBS cases. We compared our estimates with those from the 2013-2014 Zika virus epidemic in French Polynesia. We were able to predict just a few weeks into the epidemic that, due to lower transmission potential and lower probability of developing GBS following infection in Martinique, the total number of GBS cases in Martinique would be substantially lower than suggested by simple extrapolations from French Polynesia. We correctly predicted that 8 intensive-care beds and 7 ventilators would be sufficient to treat GBS cases. This study showcased the contribution of modeling to inform local health-care planning during an outbreak. Timely studies that estimate the proportion of infected persons that seek care are needed to improve the predictive power of such approaches.

Guillain-Barré Syndrome (42 Cases) Occurring During a Zika Virus Outbreak in French Polynesia.

Zika virus (transmitted by mosquitoes) reached French Polynesia for the first time in 2013, leading to an epidemic affecting 10% of the total population. So far, it has not been known to induce any neurological complications, but, a few weeks after the outbreak, an unexpectedly high number of 42 patients presented with Guillain-Barré syndrome.We report the clinical and electrophysiological characteristics of this series. Males predominated with a sex ratio of 2.82 (mean age: 46). All patients (except 2) were native Polynesian. At admission, 55% were able to walk unaided against 38% at nadir, 24% had swallowing troubles (nadir: 45%), 74% had motor weakness of the limbs (nadir: 86%) and deep tendon reflexes were diminished or not found in the vast majority of patients. Mean duration of the progressive phase and of the plateau phase was respectively 7 and 9 days. Thirty-eight percent of the patients were admitted in intensive care unit and 10 patients underwent tracheotomy. Nerve electrophysiological studies at admission showed marked distal motor conduction alterations, which had almost completely disappeared at the 4th month; this pattern was more suggestive of acute motor axonal neuropathy (AMAN) than of acute inflammatory demyelinating polyneuropathy (AIDP). Lumbar puncture showed elevated proteins in 90% of the cases, with cell count always inferior to 50/µL.This epidemic raises several questions, such as the potential existence of interactions between Zika virus and Polynesian HLA system and/or the consequences of several recombination events of this virus. This situation should call for increased vigilance, especially in countries where Aedes mosquitoes are present.

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

BACKGROUND: Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome. METHODS: In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays. FINDINGS: 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively). INTERPRETATION: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome. FUNDING: Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.

Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015.

During the recent chikungunya fever outbreak in French Polynesia in October 2014 to March 2015, we observed an abnormally high number of patients with neurological deficit. Clinical presentation and complementary exams were suggestive of Guillain-Barré syndrome (GBS) for nine patients. All nine had a recent dengue-like syndrome and tested positive for chikungunya virus (CHIKV) in serology or RT-PCR. GBS incidence was increased four- to nine-fold during this period, suggesting a link to CHIKV infection.

Angiostrongylus cantonensis eosinophilic meningitis: a clinical study of 42 consecutive cases in French Polynesia.

INTRODUCTION: In endemic areas, eosinophilic meningitis is mainly caused by Angiostrongylus cantonensis. We describe a series of this poorly-known condition. METHODS: Retrospective cohort study (2000-2012) including all patients diagnosed with eosinophilic meningitis in French Polynesia. RESULTS: Forty-two patients (males: 61.9%, age: 22 (IQR 17-32)) were diagnosed with a serologically proven (n=13) or probable A. cantonensis meningitis, mostly during the dry season (66.6%) and following the consumption of or prolonged contact with an intermediate/paratenic host (64.3%). No differential diagnosis was found in probable cases, in whom serological tests were performed earlier (7.5 days (6.5-10)) compared to positive patients (7.5 (6.5-10) versus 11 (7-30) days, p=0.02). The most commonly reported symptom was headache (92.8%). Fever (7.1%) and biological inflammatory syndrome (14.3%) were rare. Blood eosinophil count was 1200/mm(3) (900-2548). Cerebrospinal fluid (CSF) analysis disclosed a protein level of 0.9 g/L (0.7-1.1), a CSF/plasma glucose ratio of 0.50 (0.40-0.55), and 500 leucocytes/mm(3) (292-725; eosinophils: 42.0% (29.5-60); lymphocytes: 46.5% (32.5-59.0)). Thirteen cases (31.0%) were severe, with 11 focal neurological deficits. A delayed hospital referral (OR 1.13, p=0.05) was associated with severity. CONCLUSIONS: A. cantonensis meningitis must be evocated in young patients with meningitic syndrome, severe headache, and CSF inflammation with predominance of eosinophils.

Good's syndrome and IgA monoclonal gammopathy of undetermined significance.

Characterised by the association of a thymoma, hypogammaglobulinaemia, and B-cell and T-cell dysfunction, Good's syndrome (GS) is a rare cause of adult immunodeficiency leading to recurrent infections, and autoimmune manifestations related to the thymoma. We describe a 70-year-old woman in whom the diagnosis of GS was made after 7 years follow-up of a monoclonal gammopathy of undetermined significance (MGUS). After thymectomy, she received monthly intravenous immunoglobulin perfusions in order to maintain a normal plasmatic IgG level. To our knowledge, this is the fifth described case of GS associated with an MGUS. This rare condition should not be misdiagnosed, as the prognosis is determined by infectious and autoimmune complications, which could be prevented.

[Neurological manifestations of dengue]. / Manifestations neurologiques de la dengue.

BACKGROUND: An epidemic of type 4 dengue was raging in the Pacific from 2008 to 2010. During this period, several patients were hospitalized at the Hospital Centre of Tahiti for neurological disorders occurring during a dengue fever. These events are not the typical picture, which is represented by a flu-like syndrome and sometimes, in severe cases, a haemorrhagic syndrome or shock. METHOD: We have established a review of the literature reporting the cases of dengue fever associated with neurological disorders with the terms "dengue" and "neurology". Despite the retrospective nature and incomplete data, we attempted to establish the epidemiological characteristics of these events, to give an order of frequency of these symptoms and the pathophysiological mechanisms involved. RESULTS: Among patients with neurological disorders occurring during a dengue fever, disorders of central nervous system are the most common. Among disorders of central nervous system, encephalopathy is by far the most encountered. CONCLUSION: None of observed neurologic disorders presenting with specific manifestation, discussion of dengue as etiology in endemic areas or in return from endemic area is well-founded.