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.

Serum levels of macrophage-colony stimulating factor (M-CSF): a marker of kidney allograft rejection.

BACKGROUND: Macrophage-colony stimulating factor (M-CSF) is the principal factor for survival of monocytes and macrophages that play an important role in allograft rejection. We studied M-CSF serum levels during successful renal transplantation and acute graft rejection. METHODS: A total of 114 kidney allograft recipients were assessed for M-CSF levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: M-CSF serum levels were elevated in pre-transplant haemodialysis patients (611+/-355 IU/ml vs 168+/-61 in normal controls, P<0.01). Following successful renal transplantation, M-CSF decreased in the first month, stabilizing at 257+/-222 IU/ml (not significantly different from normal controls) in 52 post-transplant stable patients. There was no correlation between M-CSF level and creatinine clearance. M-CSF levels increased significantly (2-5 times) during biopsy-proven acute rejection episodes in 20 of 25 patients. All rejection episodes were successfully treated and serum M-CSF decreased rapidly to pre-rejection levels in 17/20 patients. In contrast, in five patients with cyclosporin toxicity and four patients with other causes of allograft dysfunction, M-CSF serum levels did not change. CONCLUSIONS: M-CSF serum level might be a specific marker of acute rejection. The source of increased production during rejection warrants further investigation, with infiltrating T cells and resident kidney cells being likely candidates.