A seasonal flu vaccine that contains the pandemic H1N1 strain has been suspended from use in Australia after one hundred children suffered febrile convulsions linked to the jab.
Febrile convulsions were seen in children under five years of age an average of seven hours after inoculation. The results of an investigation into the incident, published this month by the Australian Therapeutic Goods Administration (TGA), give few insights into what caused the adverse reactions. The incident raises questions about whether similar events could be seen in other countries when immunisation against seasonal flu begins in coming months.
The vaccine in question, Fluvax, is made by the Australian pharmaceutical company CSL Limited and is available in two different dose formulations. This year’s seasonal flu immunisation programmes began in Australia in March, and Fluvax was one of three vaccines available until it was suspended from use in Western Australia in April. All three available seasonal vaccines contain the seasonal influenza H3N2 and B strains, as well as the 2009 pandemic H1N1 strain.
Adverse events reported
In the report, the TGA says that by early June it received more than 1700 reports of suspected adverse events following immunisation with seasonal flu vaccines, and 1379 of these were linked to the Fluvax vaccine. In a further 257 cases showing adverse reactions, the brand of flu vaccine used was not specified.
By analysing the information contained in reports of these incidents, the TGA identified 100 cases of confirmed febrile convulsions in children under five years of age. Of these, 99 are thought to be “causally related” to the seasonal flu jab, and 58 were reported in Western Australia.
“Fluvax or Fluvax Junior was used in all 66 cases where the brand of the seasonal influenza vaccine was reported,” writes the TGA.
Based on the number of suspected cases reported, the rate of febrile convulsions linked to Fluvax was nine for every 1000 doses given in Western Australia, and five per 1000 doses given in other parts of the country, according to the TGA. By comparison, a recent US estimate of febrile convulsions linked to seasonal vaccines used over the past five years puts the rate at 0.16 per 1000 doses.
“It was a big surprise for a very reputable [vaccine] manufacturer,” Terry Nolan, head of the Melbourne School of Population Health at the University of Melbourne tells EHTF News. “It has come out of the blue.”
Nolan notes that febrile convulsions in childhood do not lead to long-lasting health complications. He emphasises that the risk of convulsions needs to be balanced against the benefit of vaccination. The risk of febrile convulsions from the flu illness itself is vastly higher than that from the vaccine, he adds.
Causes remain a mystery
Scientists do not know what caused the adverse reactions seen in Australia. Ongoing tests on samples of the vaccine have not yet found any impurities or contamination, says the TGA. TGA officials visited the CSL vaccine manufacturing facilities in Melbourne in May and June but found nothing in the manufacturing process that could be linked to a risk of febrile convulsions.
Raina MacIntyre, Head of the School of Infectious Diseases Epidemiology at The University of New South Wales in Sydney, says that the reactions were most likely down to the use of a vaccine that is more reactogenic (capable of causing an immunological reaction) than others used previously. So it caused more cases of fever than usual, “and therefore [it caused] more febrile convulsions, which may occur in young children during fever of any cause”, she explains.
The reason for this reactogencity is still unknown, says MacIntyre. It could be linked to the particular combination of antigens in the vaccine, she adds.
But Patrick Zuber, leader of the Global Vaccine Safety group at the World Health Organization (WHO), says that no interactions between the three components of the seasonal flu vaccine have been identified.
A review of clinical trial data collected during testing of the vaccine also ruled out the possibility of an immunological reaction caused by earlier exposure to the 2009 pandemic H1N1 flu, either through vaccination or natural infection, says the TGA. In fact, the TGA report found that children who had immunological signs of exposure to the pandemic virus were significantly less likely to experience a febrile seizure after receiving the 2010 seasonal flu jab.
Implications for other 2010 seasonal vaccines
In Australia, there are no signs of a higher-than-average rate of febrile convulsions after vaccination with the other two seasonal jabs available in the country — Influvac made by the Solvay/Abbott pharmaceutical company, and Sanofi-Pasteur’s Vaxigrip.
“It is possible that it could occur with any other [seasonal flu] vaccine as we don’t know why it happened,” adds Nolan.
As the Fluvax vaccine has been used most widely in Australia so far, there are limited data on the incidence of febrile convulsions seen with either of the other two vaccines, explains Nolan. The Influvac jab has been given to more than 4000 children in the country, according to the TGA report. “We have modest data on this, and we can speculate that it is unlikely to happen with this vaccine,” Nolan tells EHTF News.
For now, scientists do not have enough data about Vaxigrip to rule out an increased risk of febrile convulsions, he adds. There is a possibility it could, he speculates, so data about the vaccine are being collected from other countries where the formulation is used. Vaxigrip is being used in South American countries, but many of these only have passive surveillance systems in place to detect adverse vaccine-related events, says Nolan.
MacIntyre agrees that the other seasonal flu vaccines have not been used widely enough in Australia to determine whether they are less problematic than Fluvax. “We will only know whether there is an increased rate of fevers and febrile convulsions once large numbers of children are vaccinated,” she says.
CSL Limited uses embryonated hen eggs to produce its seasonal flu jab. Similar methods are used in the manufacture of the other seasonal vaccines available in Australia, and those due to become available elsewhere in the world for the 2010–11 flu season. The CSL paediatric vaccine has not been distributed outside Australia this year, according to a Bloomberg News report.
Each flu vaccine is unique, notes Zuber, even if all are manufactured using similar processes. “Therefore it is not justified, from a scientific viewpoint, to extrapolate from the product of one manufacturer to another,” he tells EHTF News in an email.
Resource
Australian Government Department of Heath and Ageing, Therapeutic Goods Administration (TGA). Investigation into febrile reactions in young children following 2010 seasonal trivalent influenza vaccination (status report as at 2 July 2010).
Report World Health Organization information about influenza
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