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The flu vaccine is evidence-based – and here’s the evidence

Health Protection Agency consultants Dr Sam Ghebrehewet and Dr Alex Stewart argue there is plenty of evidence to support health professionals being given the flu jab.

In a recent opinion piece for Pulse, Dr Margaret McCartney claimed that 'GPs are not ‘selfish' for refusing flu vaccination. They are just not convinced that it is evidence based … far from being highly evidence-based, for healthcare workers it is actually an intervention that is largely carried out on the basis of faith.'1

To support this assertion she quotes the conclusions of two Cochrane Reviews.2,3

We write to address Dr McCartney's concerns and to show that flu vaccination of healthcare workers (HCW) is evidence based.

Flu vaccination of HCWs reduces illness in vulnerable patients

In the first Cochrane review that Dr McCartney2 referred to, all the trials showed broadly similar protective effects and the pooleddata from the three cluster-Randomized Control Trials (RCTs) showed that vaccination of HCWs reduced influenza-like illness (ILI) and all-cause mortality in residents of care homes. Despite this, the Cochrane review authors concluded that the trials provide insufficiently evidence to support vaccination of HCWs. However, this has been refuted by the authors of the largest trial included in the review,4 who have also succinctly summarised the weaknesses of the Cochrane review.5

Data from other RCTs6-8 has also shown that influenza vaccination of HCWs reduces morbidity and mortality of patients. Furthermore, a systematic review, which included 18 studies, considered the benefits of vaccinating HCWs and whether it is a good use of healthcare resources. This review concluded that vaccinating HCWs was safe, resulting in minimal side effects, and highly effective.9

Flu vaccination prevents flu in healthy adults

The authors of the second Cochrane review referred to by Dr McCartney3 concluded that 'Influenza vaccines have a modest effect in reducing influenza symptoms and lost working days'. Nevertheless, they reported flu vaccine efficacy in healthy adults to be 75% when the vaccine strain matched the circulating flu strain. They reported that efficacy only drops to 50% when there is a mismatch between the vaccine and the circulating flu strains. These findings are not significantly different from the previous Cochrane Review on the same subject which reported flu vaccine efficacy of 68% (95% CI: 49 – 79%) for inactivated parenteral vaccine.10

The comment in the Cochrane review that it is a rare event to have a match between the WHO recommended vaccine strain and the subsequently circulating influenza virus is not borne out by the evidence. Over the 10 years 1987/88 to 1996/97, 23 vaccine strains recommended by the WHO matched with the 30 subsequently circulating virus strains [76%].11

A good match was achieved in all three viral strains (H1N1, H3N2, flu B) in five out of 10 flu seasons, with a further three years matching on two of the three strains (H1N1, flu B), and in the remaining two years matching on the H1N1 strain only. This indicates that over the 10 flu seasons there was 100% match for H1N1. This shows that mismatch is occasional rather than common, as suggested in the Cochrane review.

Trial funding

The Cochrane review stated that industry-funded trials and studies were likely to be published in more prestigious journals and cited more than other studies. This statement describes publication bias and was based on evidence.12 We have no information / evidence to suggest otherwise, nor do we attempt to defend the pharmaceutical industry. However, was there a need to include this statement in the abstract of the Cochrane review3 given that the selection of trials / studies for the Cochrane Review is rigorous and based on quality and robust predetermined criteria? That 15 of 26 studies that were suitable to be included in the review were industry-funded is in our view an indication of the quality of industry-funded trials. Our question of the authors is, was the fact that these studies were industry-funded their only significant limitation that needed to be highlighted in the review? If not, why were the other limitations not included? For example, the authors of the Cochrane Review3 stated that – 'few studies reported influenza circulation in the surrounding community, making interpretation of the results and assessment of their generalisability difficult.' Indeed, it is likely that studies that are conducted when influenza activity is low would underestimate the effectiveness of the vaccine.

Relationship between vaccine efficacy and uptake

Given the complexity of the flu virus and its ability for antigenic drift and shift, along with the evidence we have presented and the continued effort to improve vaccine efficacy, the best way to improve population protection is to increase vaccine uptake.

Vaccine Efficacy (VE %) X Vaccine Uptake (VU %) = Population Protected (PP %)

A 20% improvement in the efficacy of a vaccine would increase the proportion of population protected by 8%: however, a 20% increase in vaccine uptake would increase the proportion of population protected by 14%.

  • VE (70%) X VU (40%) = PP (28%)
  • VE (90%) X VU (40%) = PP (36%)
  • VE (70%) X VU (60%) = PP (42%)

Or, to put it more starkly, even the most efficacious will achieve little if the uptake rate is poor.

England's Chief Medical Officer recent comments

In the UK, the independent advisory body the Joint Committee on Vaccination and Immunisation has recommended that HCWs in direct contact with patients be offered the seasonal 2010/11 trivalent influenza vaccine.13

A nationwide survey (England) found that on the busiest day of the 2010-2011 flu season (4 January 2011) 851 people were in critical care. This compares to 196 cases on the busiest day of the 2009/10 pandemic (5 November 2009). Furthermore, 602 deaths associated with influenza were reported from across the UK in 2010/11, and the majority of these [373 out of the 555 fatal cases with available information (67%)] were under 65 years of age and in one of the at-risk groups who were eligible for vaccination. Influenza A/H1N1 (2009) was the predominant strain.14

The critical care and death rates exceeded those at the peak of the H1N1 pandemic in 2009 indicating that seasonal flu can be just as serious and should be treated no more lightly than an influenza pandemic.

Given that influenza continues to cause significant morbidity and mortality, it is understandable that the CMO strongly desires to improve uptake rates. Frontline HCWs, including GP colleagues, need to think beyond their personal protection and consider the value of being vaccinated as a contribution to improved uptake rates and population protection. Furthermore, the single most important factor influencing the use of influenza vaccine is whether it is recommended by a doctor or not, and all healthcare professionals play a significant role in improving flu vaccine uptake rates.

Yours faithfully

Dr Sam Ghebrehewet, Consultant in Communicable Disease Control & HPA NW Regional Immunisation Lead

Dr Alex G Stewart, Consultant in Communicable Disease Control, Cheshire & Merseyside Health Protection Unit


References

1. McCartney M. Show us the evidence for the flu jab.  Pulse, National GP Magazine, 19th October 2011. http://www.pulsetoday.co.uk/main-content/-/article_display_list/12911759/show-us-the-evidence-for-the-flu-jab

2. Thomas RE, Jefferson T, Lasserson TJ. Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database of Systematic Reviews 2010, Issue 2. Art. No.: CD005187. DOI: 10.1002/14651858.CD005187.pub3. http://www.thecochranelibrary.com/userfiles/ccoch/file/CD005187.pdf

3. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD001269. DOI: 10.1002/14651858.CD001269.pub4 http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001269.pub4/pdf

4. Hayward A, Harling R, Wetten S, et all. Effectiveness of influenza vaccine programme for care home staff to prevent death, morbidity and health service use among residents; cluster randomised control trial. BMJ 2006; 333 (7581): 1241-1247. doi:10.1136/bmj.39010.581354.55   

5. Hayward A, Watson J. Effectiveness of influenza vaccination of staff on morbidity, and mortality of residents of long term care facilities for the elderly. Vaccine 2011; 29: 2357-2358.

6. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997; 175: 1 - 6.

7. Carman WF, Elder AG, Wallace LA, et al. Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: a randomised controlled trial. Lancet 2000; 355: 93-97.

8. Lemaitre M, Meret T, Rothan-Tondeur M, et al. Effect of influenza vaccination of nursing home staff on mortality of residents: a cluster randomised trial. Journal of American Geriatric Society 2009; 57: 1580-1586

9. Burls A, Jordan R, Barton P et al. Vaccinating healthcare workers against influenza to protect the vulnerable--is it a good use of healthcare resources? A systematic review of the evidence and an economic evaluation. Vaccine. 2006 May 8; 24 (19): 4212-4221.

10. Demicheli V, Jefferson T, Rivetti D, Deeks J. Prevention and early treatment of influenza in healthy adults. Vaccine 2000;18:957–1030.

11. Wood JM. Standardization of inactivated influenza vaccines. In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of influenza. London: Blackwell Science, 1998: pp 333-345.

12. Jefferson T, Di Pietrantonj C, Rivetti A, Demicheli V. Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review. BMJ 2009; 338: b354. doi: 10.1136/BMJ.b354

13. Department of Health. (2010). Joint committee on vaccination and immunisationadvice on the H1N1v and 2010/11 seasonal influenza vaccination programmes. http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/dgitalasset/dh_118093.pdf

14. Health Protection Agency. Surveillance of Influenza and other respiratory viruses in the UK, 2010-2011 report.  http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1296687414154