Adverse health events—such as sudden deaths, spontaneous abortions, and Guillain-Barré syndrome—will occur in the general population whether or not they have been vaccinated against H1N1 influenza. These background rates must be taken account of when such events occur during a vaccination campaign, so that the public does not panic and believe they are caused by vaccination. Careful consideration of data in this manner will allow authorities to identify when adverse events truly connected to or caused by vaccination have occurred. These issues are considered in a Public Health paper published Online First and in an upcoming edition of The Lancet, written by Dr Steven Black, Cincinnati Children's Hospital, OH, USA, and colleagues.
A team of investigators from 13 global medical institutions and health agencies reviewed medical data from prior studies and from hospital databases to identify background rates of health events that occurred without any vaccine. Their review showed the rates of adverse events varied by year, country, and age and sex of the population.
The authors use several examples to highlight their case. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, around 22 cases of Guillain-Barré syndrome and six cases of sudden death would be expected to occur within six weeks of vaccination as coincident background cases. Guillian-Barré Syndrome is a disorder in which the body's immune system mistakenly attacks part of the nervous system. There were increased cases of this syndrome during the 1976-77 flu pandemic in the USA. It normally affects about one out of every 100,000 people in a year. Based on this background rate, if 100 million people in the USA are vaccinated against H1N1 flu, 215 co-incident background cases of Guillian-Barré could be expected to occur within six weeks of vaccine—but they would occur whether or not the vaccine had been given.
The data show that 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. However, this rate would be expected to occur on any day, whether during a vaccination campaign or not. Despite this, it is easy to see how, should clusters of abortions occur during a vaccination campaign, public alarm could be raised despite rates being no higher than these expected background rates.
The authors say: "Background rates can provide the media, the public, public-health officials, and politicians with important information about the expected number of events that can occur in the absence of any vaccination programme. Additionally, they can be used to estimate the number of such events that will occur after immunisation of any number of individuals."
Not taking account of background rates can delay or endanger vaccination campaigns. The authors refer to the 2006 seasonal flu vaccination campaign in Israel, where four deaths occurred within 24 hours of vaccination. This was entirely normal, and in fact mortality was lower than expected based on background rates. However, despite these patients being at high risk of death due to underlying medical conditions, their deaths caused widespread panic and global news coverage.
The authors conclude: "Misinterpretation of adverse health outcomes that are only temporally related to vaccination will not only threaten the success of the pandemic H1N1 influenza vaccine programme, but also potentially hinder the development of newer vaccines. Therefore, careful interpretation of vaccine safety signals is crucial to detect real reactions to vaccine and to ensure that temporally related events not caused by vaccination do not unjustly affect public opinion of the vaccine. Development and availability of data banks that can provide locally relevant background rates of disease incidence are important to aid assessment of vaccine safety concerns."
In an accompanying Comment, Dr Frank DeStefano and Dr Jerome Tokars, Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA, discuss international collaborations and a number of surveillance initiatives in the US that will monitor vaccine safety in the USA. These include a new web-based active surveillance system that is being implemented to prospectively follow tens of thousands of vaccinees for medically attended adverse events. The Comment authors conclude: "These extensive international safety-monitoring activities and collaborations represent an unprecedented commitment to assuring the safety of H1N1 2009 vaccines, as well as a model for how we might improve tracking of safety for all vaccines going forward."
For Dr Steven Black, Cincinnati Children's Hospital, OH, USA, please contact Nick Miller, CCH Communications Office, T) +1 513-803-6035 E) stevblack@gmail.com / Steven.Black1@cchmc.org / Nicholas.Miller@cchmc.org
For Dr Frank DeStefano, Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA, please contact CDC media relations. T) +1 404-639-3286 E) media@cdc.gov
For full Public Health paper and Comment, see: http://press.thelancet.com/bradverse.pdf
Note to editors: Extra contact information
USA
Dr. Steven Black,Professor of Pediatrics, Division of Infectious Diseases and The Center for Global Health, Cincinnati Children's Hospital T) +1 513-803-0747/+1 510 219-7372 E) Steven.Black1@cchmc.org (NOTE: on Friday, cell phone is best as he will be at the IDSA meeting in Philadelphia.)
Dr. Neal Halsey,Johns Hopkins Bloomberg School of Public Health T) 410-955-6964 E) nhalsey@jhsph.edu
Finland
Dr. Juhani Eskola,National Institute for Health and Welfare, Helsinki, Finland T)+358206106006 (office) or +358407710597 (cell) E) juhani.eskola@thl.fi
UK
Drs. Elizabeth Miller and Nicolas Andrews, Press officeHealth Protection Agency Centre for Infections Communicable Disease Surveillance Centre, London. T) +44 (0)20 8327 6690 E) CFI-Pressoffice@hpa.org.uk
Switzerland
Dr. Claire-Anne Siegrist, Department of Pediatrics, University of Geneva, Switzerland, Center for Vaccinology and Neonatal Immunology, Department of Pediatric, University of Geneva; Geneva, Switzerland.T) +41 22 379 57 78 E) claire-anne.siegrist@unige.ch
Canada
Dr. Barbara Law,Vaccine Safety Section, Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada, Ottawa, Ontario. T) +1 613-941-8189
Dr. Noni MacDonald,Division of Infectious Diseases, Department of Pediatrics, Dalhousie. University, Halifax Nova Scotia, Canada T) +1 902 470 8498 E) noni.macdonald@dal.ca
Brazil
Dr. Gabriel Oselka, Department of Pediatrics, Faculty of Medicine University of São Paulo, São Paulo, Brazil T) +55-11-3887-6111 E) gabriel@edipi.com.br
Australia
Dr. Michael Gold. Discipline of Paediatrics, School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia / Women's and Children's Hospital Adelaide T) +61 413855993 / +61 8 8161 7266
WHO
Dr. Patrick Zuber , Group leader global vaccine safety. Quality, Safety and Standards (QSS), Department of Immunizations, Vaccines and Biologicals (IVB) Family and Child Health (FCH) , WHO, Swtizerland. T) +41 22 791 1521
Journal
The Lancet