Wednesday, September 27, 2017

Australian CMO Statement On Flu Vaccine Effectiveness


Although I am well aware of its limitations, I get the flu vaccine every fall, and I urge others to consider doing so as well.  Whether through blind luck, the protective effects of the flu shot, or my maniacal  use of hand sanitizer outside the home, I've managed to avoid the flu (and any other respiratory infection) for the past 8 years, and have hopes of increasing that streak again this winter. 
But the flu shot doesn't guarantee 100% protection. In fact, depending on the recipient's age, immune health, and the current strain of influenza in circulation, the flu shot's effectiveness can often drop below 50%. 
This is hardly a new revelation, as five years ago Michael Osterholm and his group at CIDRAP released their 160-page Comprehensive Influenza Vaccine Initiative (CCIVI) report that called for the creation of more efficient vaccine technology (see CIDRAP: The Need For `Game Changing’ Flu Vaccines).

And we have seen some small improvements, including the move to a quadrivalent vaccine, and for those over 65, the availability of Fluzone High-Dose Seasonal Influenza Vaccine and starting last year, the introduction of FLUAD™: An Adjuvanted Flu Vaccine Option For Those Over 65.
But seasonal flu is an agile adversary, and with the required 6 months lead time to produce and deploy a vaccine, the virus can sometimes mutate away from the vaccine strain. That doesn't necessarily negate the vaccine's effectiveness, but it can reduce it. 
While we've seen pretty good vaccine effectiveness (VE) numbers against H1N1, and influenza B, as we discussed two months ago in The Enigmatic, Problematic H3N2 Influenza Virus, the track record against seasonal H3N2 has been less successful.

The problem is, H3N2 has split into numerous subclades, which co-circulate and battle constantly for dominance.  New mutations - like N171K and N121K have recently appeared - and their impact on this year's vaccine effectiveness is being examined.

Yesterday, in Seasonal influenza circulation patterns and projections for Sep 2017 to Sep 2018 by Trevor Bedford & Richard Neher, published on BioRxIv, seasonal H3N2's evolution was described as:
H3N2: H3N2 continues to diversify with many coexisting clades, all of which carry several amino acid mutations at previously characterized epitope sites. The majority of viruses fall into the 3c2.a clade which has been dominating globally for >3 years, but 3c3.a viruses continue to persist. The common ancestor of circulating H3N2 viruses is now more than 5 years old, which is rare for H3N2. Despite extensive genetic diversity, serological assays suggest limited, but non-zero, antigenic evolution. We expect multiple competing clades within 3c2.a to persist into the future with no clear immediate winner 
And therein lies the problem; H3N2 a diverse, meandering subtype of seasonal flu, without one distinctly dominant strain to design a vaccine against.  How well this year's vaccine works will depend in large portion, to what `flavor' of H3N2 visits your neighborhood this winter.
By now, everybody knows that Australia has come off their worst flu season in recent memory, and there are concerns that we could see a similarly rough season ahead in the Northern Hemisphere (see UK: NHS Warns Of A Potentially Rough Flu Season Ahead).

Today Australia's Chief Medical Officer has issued a statement which cites a lower than usual VE against H3N2 - particularly among the elderly - as a contributing factor to this year's high mortality rate.

27 September 2017
Statement from the Chief Medical Officer on seasonal influenza vaccines

The Australian Government is committed to immunisation and to ensuring Australia has the best possible vaccination program underpinned by sound evidence and effective vaccines.
The National Immunisation Program (NIP) provides free seasonal influenza vaccines to those most at risk of influenza and its complications. The program is demand driven, which means any eligible individual can access a free vaccine. In 2017, over 4.5 million doses have been distributed to meet the current take up of eligible Australians for the free vaccine.

Currently only around 70% of eligible Australians currently take up the free vaccine. The Australian Government strongly encourages the approximately 2.5 million eligible Australians, who do not currently have the vaccine, to be vaccinated and will make available sufficient vaccine to meet demand each year.

Each year, seasonal influenza causes significant mortality and morbidity in the Australian community. The virus is extremely complex and dynamic which means a new vaccine is required every year but also makes it very difficult to manufacture and distribute influenza vaccines each year.

2017 has been characterised by high levels of influenza A (H3N2) which disproportionately affects the elderly. We have seen reports of high numbers of deaths in nursing homes this year and also amongst healthy adults. These are tragic events which underscore the message that influenza is a serious disease and that vaccination is absolutely critical for protecting individuals and the community.

We do know that the 2017 vaccines have had a relatively good match with circulating strains, which provides the best opportunity for protection. There is, however evidence that the effectiveness of the vaccines has been less than usual this year, particularly in terms of protecting the elderly against influenza A (H3N2).

The quadrivalent seasonal influenza vaccines supplied through the NIP are similar to those supplied in like countries (eg: the United Kingdom) and also on the private market.
To be supplied through the NIP, vaccines must be registered by the Therapeutic Goods Administration and recommended by the Pharmaceutical Benefits Advisory Committee (PBAC). These processes ensure vaccines are safe and effective. In addition, competitive tendering arrangements have meant the Australian Government has been able to achieve value for money when purchasing vaccines – that is good news for the Australian community.

Of the vaccines supplied internationally specifically for the elderly, one (a high dose formulation) is not registered in Australia and the other (an adjuvanted vaccine) does not have an up to date registration in Australia. The PBAC has not yet received a submission for either vaccine.

The Australian Government has been carefully monitoring vaccine effectiveness for seasonal influenza vaccines and is committed to exploring enhanced vaccination program arrangements through the NIP, including the use of advanced vaccines for those aged 65 years and over into the future.

Media contact: email:

Unlike in the United States, the FluZone High Dose and FluAd Adjuvanted  vaccines were not licensed, or available in Australia.  Whether that would have made much of a difference is unknown, although the CDC does say:
Why is a higher dose vaccine available for adults 65 and older?

Human immune defenses become weaker with age, which places older people at greater risk of severe illness from influenza. Also, ageing decreases the body’s ability to have a good immune response after getting influenza vaccine. A higher dose of antigen in the vaccine is supposed to give older people a better immune response, and therefore, better protection against flu.

Does the higher dose vaccine produce a better immune response in adults 65 years and older?

Data from clinical trials comparing Fluzone to Fluzone High-Dose among persons aged 65 years or older indicate that a stronger immune response (i.e., higher antibody levels) occurs after vaccination with Fluzone High-Dose. Whether or not the improved immune response leads to greater protection has been the topic on ongoing research. A study published in the New England Journal of Medicine indicated that the high-dose vaccine was 24.2% more effective in preventing flu in adults 65 years of age and older relative to a standard-dose vaccine. The confidence interval for this result was 9.7% to 36.5%. A separate study published in The Lancet Respiratory Medicine reported that more immunogenic, high-dose vaccines can reduce the number of hospital admission for people aged 65 years or older, especially those living in long-term care facilities. The study compared hospitalization rates among more than 38,000 residents of 823 nursing homes in 38 states during the 2013-14 flu season.

The CDC and its advisory committee do not recommend these enhanced vaccines over the getting the regular flu shot, and their use is linked to a slight increase in (generally mild) adverse effects, so those over 65 will want to consult their doctor.  
While we can't know what kind of flu season lies ahead, the epidemics in Australia, Hong Kong, and Southern China over the past 5 months may give us an advance indicator of what we can expect.
As always, even for those who do get the flu shot, the smart money is on practicing good flu hygiene (washing hands, covering coughs & sneezes, staying home when sick) all throughout the flu and cold season.

And if you do fall ill, early administration of antivirals - particularly for those at high risk of complications - can reduce both the length and severity of infection.  

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