Re: Published practice tools article #217 Pneumonia Vaccine for Adults: Is the efficacy as effective as the effort?
To whom it may concern,
I am writing to provide clarifying context and to point out factual errors in the article posted on the Alberta College of Family Physicians’ website under Tools for Practice section (and subsequently shared by the Ontario College of Family Physicians) titled “#224 Pneumonia Vaccine for Adults: Is the efficacy as effective as the effort?,” co-authored by Drs. Jamil Ramji and Michael R. Kolber.
I have a great appreciation for the amount of scientific data the College of Family Physicians has to review and translate into straightforward recommendations. However, due to scientific misinterpretations and inaccuracies found in the article by Ramji and Kolber, I am asking that this publication be withdrawn and reexamined, as it may mislead practicing physicians and cause potential harm to patients.
Infections caused by Streptococcus pneumoniae (the pneumococcs) include pneumonia (which is more common in older adults) and invasive pneumococcal disease (IPD, which is more common in children but does occur in adults). To date no vaccine has been made that covers all of the serotypes of the pneumococcus. Adults become infected with a wider range of serotypes than children so cannot expect that all pneumococcal infections will decease with vaccination, only those that are covered by the vaccines. There is more data on the role of vaccination in preventing Invasive Pneumococcal Disease (IPD) than pneumonia, but the recent CAPiTA trial now provides data on prevention of pneumococcal pneumonia.
The effects of vaccination on Invasive Pneumococcal Disease (IPD)
Rates of IPD caused by serotypes found in vaccines given to children (e.g. PCV7,10,13) have decreased in adults. This is partly due to herd immunity (i.e. children do not transmit them to adults as often) and it is not clear how much is due to direct vaccination of adults. There has not been a reduction in the rates of IPD to serotypes included in the adult vaccine (PPV23) (see Fig 16 & 19 in https://www.canada.ca/en/public-‐health/services/publications/drugs‐health‐products/national‐laboratory‐surveillance‐invasive‐streptococcal‐disease-canada-annual-summary-2014.html#a5a). Until the recent CAPiTA study, the majority of information on the efficacy of pneumococcal vaccination was based on incidence of IPD for a number of reasons including:
- Invasive pneumococcal disease is a reportable disease and PHAC collects data on which of the 90+ serotypes are isolated. This allows examination of which serotypes (i.e. those included in the vaccine or those that are not) have/have not changed at the population level therefore, we can determine whether has there been a reduction of IPD in Canada due to vaccination but not whether an individual’s vaccination history has protected them from infection.
- Assessing risk of pneumonia is challenging as according to NACI, pneumococcal pneumonia amounts to 5-8% of total pneumonia cases in older adults, and as stated above of this percentage, only 13 – 23/80 serotypes would be altered by vaccination.
Since IPD rates are higher in smokers, Indigenous people, those with chronic lung disease (e.g. asthma, COPD), vaccination is recommended for these vulnerable groups.
The effects of pneumococcal vaccination on pneumonia
Studies demonstrating a decrease in community acquired pneumonia due to vaccination are challenging because of the relatively low incidence rate, which would require either a very large number of participants or many years of follow up. Because of these limitations, studies, such as those listed in the original article, that follow for a short period (e.g. < 1 year) likely underestimate efficacy since the protective effects of vaccination is expected to last for years. Proxy measures of efficacy including duration or levels of anti‐pneumococcal antibodies in the serum are more frequently used and multiple studies have found that older adults mount responses that are predicted to be protective against infection1,2.
Because vaccine responses in the very old, frail and immunocompromised are impaired, inferring data from long-term care facilities to community dwelling older adults, as was done in the summary by Ramji and Kolber, is inappropriate. The CAPiTA study 3 was the first large trial to directly test the effects of PCV13 in preventing community acquired pneumonia in healthy older adults. This included over 84,000 participants (roughly half P.3 in the placebo and vaccinated groups respectively) and a follow up time of almost 4 years. This double blinded randomized control trial demonstrated that vaccination with PCV13 reduced the incidence of vaccine‐type community acquired pneumonia and IPD.
Based on this study the National Advisory Council on Immunization has ranked the Level of Evidence as ‘1’ and the Quality of Rating of Evidence as ‘Good’ (their highest recommendations), that vaccination with PCV13 is effective in preventing pneumonia in those greater than 65 years. Specifically NACI states “NACI concludes that there is good evidence, on an individual basis, to recommend in immunocompetent adults aged 65 years and older not previously immunized against pneumococcal disease, the use of PNEU-C‐13 vaccine followed by PNEU-P-23, for the prevention of CAP and IPD caused by the 13 pneumococcal serotypes included in the conjugate vaccine.”
Factual errors in ACFP publication:
The number needed to vaccinate (NNV) of 55 is a vast underestimate and is not supported from the article they cite. In general, NNV is not considered a reliable measure of vaccine efficacy. The risk in COPD exacerbations is also exaggerated4. As mentioned above, the CAPiTAs study is the randomized control trial demonstrating efficacy in older adults without co-morbid conditions.
Considering all of the above, I formally ask you to retract the article in question and allow individuals with specific expertise in vaccine evaluation methodology to review the article in order to provide sound and scientifically–‐based direction to your audience and their patients.
Dr. Dawn Bowdish
Member of the Board of Directors, The Lung Association – Ontario
Associate Professor & University Scholar
Canada Research Chair in Aging & Immunity
MG DeGroote Institute for Infectious Disease Research
McMaster Immunology Research Centre
1. Tinoco JC, Juergens C, Ruiz Palacios GM, et al. Open–‐label trial of immunogenicity and safety of a 13–‐valent pneumococcal conjugate vaccine in adults >/= 50 years of age in Mexico. Clin Vaccine Immunol. 2015;22(2):185–‐192.
2. Jackson LA, Gurtman A, van Cleeff M, et al. Immunogenicity and safety of a 13–‐ valent pneumococcal conjugate vaccine compared to a 23–‐valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–‐naive adults. Vaccine. 2013;31(35):3577–‐3584.
3. Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114–‐1125.
4. Lee TA, Weaver FM, Weiss KB. Impact of pneumococcal vaccination on pneumonia rates in patients with COPD and asthma. J Gen Intern Med. 2007;22(1):62–‐67.