One of the criticisms being leveled at the government for the recent adverse flu events is the question of how thoroughly the current 2010 seasonal flu triple antigen has been tested.

This year’s vaccine contains three viral components,
• A/California/7/2009 (NYMC X-181) (A/California/7/2009 (H1N1) – like) 7.5 µg haemagglutinin per dose
• A/Wisconsin/15/2009 (NYMC X-183) (A/Perth/16/2009 (H3N2) – like) 7.5 µg haemagglutinin per dose,
• B/Brisbane/60/2008 (B/Brisbane/60/2008 – like) 7.5 µg haemagglutinin per dose, a combination not used in Australia before.

Ian Barr, the deputy-director of the World Health Organization’s influenza centre in Melbourne, was interviewed for the World Today on ABC radio on Monday April 26th, about the question of whether the current seasonal flu combination has been tested in clinical trials.

IAN BARR: In Australia we don’t require that the influenza vaccine, the seasonal vaccine is tested for combinations but they have done that overseas, so they have tested in fact giving a full seasonal vaccine with the swine flu, so four vaccines at once if you like and there were no untoward effects there.

.

So I think there’s a high expectation that the combination of these three viruses will be no different from any other three viruses which we include every year without doing formal safety testing which takes quite a period of time and it is extremely expensive and time consuming.
.

CHARLOTTE GLENNIE: So in your opinion the fact that it is a combination vaccine would have nothing to do with this situation that we’ve got at the moment as far as you know now?
.

IAN BARR: I think that’s unlikely to be a factor. Certainly all viruses are slightly different but in terms of how they’re produced in the laboratory and tested in laboratory and then made in the commercial scale vaccine production areas, they’re all investigated individually for any particular differences in those viruses which might lead to some of these things we’re seeing currently, such as fever.

.

So I think that it’s unlikely but I guess we have to wait and see on analysis of these particular batches.

.

But subsequent tests by the TGA and other independent agencies have not identified a batch related problem. The Federal Government’s chief medical officer, Professor Jim Bishop, says there is no evidence to suggest that faulty batches of flu vaccine are to blame for adverse reactions in children, although further testing is yet to be completed.

Could old technology be to blame?

But rival vaccine manufacturers are questioning the manufacturing technique used by CSL Limited. Influenza Deeds of Agreement are in place with CSL Limited and Sanofi Pasteur for the supply of seasonal, pre-pandemic and pandemic influenza vaccines, but CSL is the primary supplier of AH1N1 vaccines to the Australian government.

CSL was once a division of  the Federal government. Known as the Commonwealth Serum Laboratories, it was established in Australia in 1916, then incorporated in 1991 and listed on the Australian Stock Exchange in 1994. But CSL continue to maintain a close relationship with the government much to the critique of their rivals.

Flinders University’s Professor Nikolai Petrovsky, the research director of rival vaccine manufacturer Vaxine, says CSL’s relationship with the Federal Government virtually guarantees it funding. So CSL has no interest in developing better vaccines with new technology such as genetically engineered proteins.

“They’re comfortable to really exploit the old technology which is highly profitable to sell each year to the Australian Government.”

CSL’s seasonal flu vaccine, Fluvax, is based on technology which involves growing the influenza virus in eggs – a technology which has been around for about 50 years. Professor Petrovsky says the CSL vaccine varies from batch to batch.

“That’s one of the consequences of using a 50-year-old technology, you get that variability,” he said.

He is calling for an independent inquiry into the Federal Government’s relationship with CSL.

A spike in vaccinations means a spike in reactions?

To date, there have been 57 reports of adverse reactions (including high fevers and convulsions) in WA, six in Victoria, four in NSW and Queensland, two in South Australia and one each in Tasmania and the ACT. One child died in QLD after receiving a flu injection. Initial findings from the coroner did not find the vaccine at fault but tests are ongoing.

Prof Bishop said some three million doses of the seasonal flu vaccine have gone out this year, with up to two-thirds sent to WA.

It could be a “partial explanation” as to why the western state has experienced a much higher rate of complications, normally expected in one out of every 1000 to 10,000 cases, Prof Bishop said.

WA provides the seasonal flu shot for free to children under five, whereas the rest of the country doesn’t.

The WA trials were started after the 2007 flu season, after 8 children across Australia under five years of age, died within 24 hours of developing mild and non-specific symptoms of respiratory infection. Although the cause of death has not been reported in many of these cases, these deaths appeared to be associated with influenza A.

In 2008, almost 65,000 children aged 5 and younger in Western Australia received free flu vaccinations made by CSL and Sanofi- Aventis SA as part of a trial that reduced hospitalizations by 88 percent, the state’s health department said in a statement last year.

Each year, CSL’s Fluvax vaccine contains fragments of three different types of influenza virus as recommended by the TGA and this depends on the strains of infectious flu in the environment. In addition, flu viruses mutate from season to season so vaccines become less effective and need to be modified to keep up with the current mutants.

The components have been tested individually but not in combination.

Although the current Fluvax® combination has not been tested in Australia, the individual components have.

Fluvax® Jnr (2005/2006 batches) showed very good safety and efficacy profile in clinical trial.
.

Safety and efficacy of CSLs Fluvax® Jnr – seasonal flu vax (no thimerosal, no H1N1) This study was undertaken using the 2005-2006 flu vaccines, is designated the Paediatric study CSLCT-FLU-04-05 and was published in 2009.

The safety, tolerability and immunogenicity of Fluvax® vaccine was tested in 298 participants from a paediatric population (> 6 months to < 3 years and > 3 years to < 9 years).

.

Group A
Equal to or greater than 6 months to less than 3 years old
Biological: Influenza Virus Vaccine
2 dose vaccine regimen: 2 X 0.25mL vaccinations 30 days apart and a booster vaccination was administered 12 months after the first dose
.

Group B
Equal to or greater than 3 years to less than 9 years old
Biological: Influenza Virus Vaccine
2 dose vaccine regimen: 2 X 0.50mL vaccinations 30 days apart and a booster vaccination was administered 12 months after the first dose
.
The total number of participants was 298 (Group A n=151; Group B n=147). There were no reports of serious adverse events related to Fluvax® vaccine during the vaccination period. Within 7 days after administration of Fluvax® vaccine, all adverse experiences reported with an incidence of 2% or greater. Unsolicited adverse events were collected for 30 days post-vaccination. Very common unsolicited events (< 1/10) reported were rhinitis, cough, teething and influenza-like illness.

.

Panvax® Jnr was tested in a 2009 trial and showed ~30% adverse effects in children under the age of 8.

.

Testing began on CSLs 2009 H1N1 Influenza Vaccine (CSL425) in July 2009, on 370 kids aged between 6 Months to 8 Years.
.
CSL Limited makes two AH1H1 vaccines, Panvax® and Panvax® Jnr (thimerosal free). The clinical trial is registered and published here.
.

Mild adverse effects were defined as adverse events easily tolerated by the participant, causing minimal discomfort and do not interfere with everyday activities (e.g., soreness at injection site)?.
Following the first vaccination:
.

• 16.3% had a mild fever (>37.5 degrees C < 38.5 degrees C) in the 15µg group
.

• 23% had mild fever in the 30 µg group
.

Combined mild adverse reactions, for 15 µg and 30 µg were 31.9% and 33.7%, respectively.

For moderate adverse reactions, 15 µg and 30 µg were 18.9% and 27.2%, respectively. This was defined as significantly discomforting, interferes with daily activity.

.

The clinical trial data was evaluated by the Therapeutic Goods Administration (TGA) and reviewed by the expert Advisory Committee on Prescription Medicines (ACPM). The evaluations found the vaccine, delivered in two doses not less than 28 days a part in children aged 6 months to 9 years, to be both safe and to offer good protection.

Panvax® was approved by the TGA on December 3, 2009 and the national immunisation program began on 30 September 2009.

The TGA has been closely monitoring any side effects from the use of the vaccine. To that date approximately 6 million doses of Panvax® had been distributed in Australia. As at 31 December 2009 a total of 1289 suspected side effects have been reported to the TGA following vaccination with Panvax® in Australia.

This is the current trial of the 2010 vaccine, containing A/California/7/2009 (NYMC X-181), (A/California/7/2009 (H1N1) – like)  A/Wisconsin/15/2009 (NYMC X-183), (A/Perth/16/2009 (H3N2) – like)  & B/Brisbane/60/2008 (B/Brisbane/60/2008 – like)
.

Current Influenza Vaccine Study in 6 month to 17 year olds
.

Australia is considering introducing the Influenza vaccine for all children under 5 years. At the same time, this study aims to improve our knowledge of the safety of Fluvax® in children aged from 6 months to 17 years old. Information from this study will help future decisions on how best to use Fluvax® in children.
.

What does the study involve? Each participant will be in the study for about 6 or 7 months. They will receive 1 or 2 doses of Fluvax®, depending on their age and how many doses of ‘flu vaccine they have had in the past. You will be asked to record certain reactions that might occur for 30 days following each vaccination.

.
This study has been approved by a human research ethics committee. In Perth the study is run by the research staff at the Vaccine Trials Group, Telethon Institute for Child Health Research in conjunction with Princess Margaret Hospital for Children and the University of Western Australia School of Paediatrics.

The latest information on the website says; “recruitment complete” which means they have enough people for the trial. I don’t know what stage they are at with respect to results. There is a brochure available here.

Parents call for calm.

Meanwhile, some parents are calling for calm and warning others not to shun vaccines completely.

Kellie Connolly writing for the Daily Telegraph on April 30th, recounts how her three year old contracted swine flu last year and was extremely ill for 2 months. He couldn’t keep food down for 13 days, lost a third of his body weight and he eventually developed pneumonia.

When she took him for his flu shot this year, around the time of the recent scare, he suffered an adverse reaction of high temperatures, vomiting and headaches.

Kellie says that of course she has concerns and she expects the authorities to thoroughly investigate them, but she was adamant;

“..As a mother of a child who’s had a terrible case of swine flu, and then witnessed an adverse reaction to a vaccine, I still say VACCINATE for everything else recommended by our health officials.”

Similarly,
Kylie Orr on the Essential Baby blog says;

“Why would I question a free service provided by the government, which has been exhaustively researched and documented? I am not a scientist, medical practitioner or spokesperson for a pharmaceutical company.”

Ultimately, I am a mum and if the experts tell me immunising my child is the best bet for keeping them safe from potentially deadly diseases, well that’s enough for me. If someone offers a counter argument, showing me figures and relevant links, backed up by science…..”

The vaccination programme for under fives remains suspended. You can report an adverse effect to vaccination, or other drugs at the TGA website.

Browse Timeline

• « Flu vax programme for kids suspended due to vaccine reactions
• » Software glitch hampering adverse reactions reporting