title: Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database.
abstract: BACKGROUND
  Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination.
  
  
  METHODS
  A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011.
  
  
  RESULTS
  Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010.
  
  
  CONCLUSIONS
  Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely.
authors.affiliation: National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Alcalde-Cabero
authors.affiliation: National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Almazán-Isla
authors.affiliation: National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: García López
authors.affiliation: Neurology Department, Miguel Servet University Hospital, Zaragoza, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Ara-Callizo
authors.affiliation: National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain.
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Avellanal
authors.affiliation: Neuromuscular Unit, Neurology Department, Bellvitge University Hospital, Bellvitge, Biomedical Research Institute (Institut d'Investigació Biomèdica de Bellvitge/IDIBELL), L'Hospitalet de Llobregat, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Casasnovas
authors.affiliation: Neurology Department, Severo Ochoa University Hospital, Leganés, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cemillán
authors.affiliation: Epidemiology Department, Regional Ministry of Health, Madrid Autonomous Region, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Cuadrado
authors.affiliation: Neurology Department, General Hospital, Segovia, Spain.
authors.forename: Jacinto
authors.initials: J
authors.lastname: Duarte
authors.affiliation: Neurology Department, Virgen de las Nieves University Hospital, Granada, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Fernández-Pérez
authors.affiliation: Neurology Department, Carlos Haya University Hospital, Málaga, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Fernández
authors.affiliation: Neurology Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
authors.forename: Juan Antonio García
authors.initials: JA
authors.lastname: Merino
authors.affiliation: Neurology Department, Virgen de la Salud Hospital, Toledo, Spain.
authors.forename: Rosa García
authors.initials: RG
authors.lastname: Montero
authors.affiliation: Spanish Medicines & Medical Devices Agency (Agencia Española de Medicamentos y Productos Sanitarios), Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Montero
authors.affiliation: Neurology Department, University Teaching Hospital Clínico, Santiago de Compostela (Corunna), Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Pardo
authors.affiliation: Neurology Department, La Paz University Hospital, Madrid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Rodríguez-Rivera
authors.affiliation: National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Ruiz-Tovar
authors.affiliation: National Centre for Epidemiology, CIBERNED, Carlos III Health Institute, Madrid, Spain. jpedro@isciii.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: de Pedro-Cuesta
mesh_terms: D000328:Adult; D000368:Aged; D016208:Databases, Factual; D062665:Epidemiological Monitoring; D005260:Female; D020275:Guillain-Barre Syndrome / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000072141:Neurologists; D058873:Pandemics; D011446:Prospective Studies; D062486:Public Health Surveillance; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013997:Time Factors
chemical_list: D007252:Influenza Vaccines
keywords: Guillain-Barré syndrome; ICD-9-CM; Influenza A virus H1N1 subtype; Influenza vaccines; Public health surveillance; Safety