Saturday, October 04, 2014

Does pneumococcal vaccine help? It's complicated.

I love vaccinations. But I have to be honest about the pneumococcal polysaccharide vaccine (PPV) that's been the focus of a publicly reported core measure for years. The evidence is weak. And why? Because so is the vaccine itself, compared to the newer conjugate vaccine as noted in a recent review post at Clinical Correlations:

In the late 1990s, Prevnar 7 was introduced to the US market; it covalently attached the capsular polysaccharide to the highly immunogenic modified diphtheria toxin protein [1]. The result was a more robust immune response that proved effective in children [7]. Coverage was later expanded by 6 serotypes for the development of Prevnar 13, a 13-valent pneumococcal conjugate vaccine (PCV13) [8]. The vaccination was approved for universal use in children to protect against the 13 most common disease-causing S. pneumoniae serotypes in this population [7]. Twelve of the serotypes in PCV13 are also included in the PPSV23 vaccination, serotype 8 is covered by PPSV23 but not PCV13, serotype 6A is covered by PCV13 but not PPSV 23 [5,3].
In 2012, the ACIP recommended the use of PCV13 for specific adult patients, given the vaccination’s vigorous and long-lasting immune response [9]. PPSV23 provides T-cell independent antigens that produce IgG antibodies but have limited immune memory. The stronger immune activation by PCV13 provides T-cell stimulation resulting in higher titers of IgG, memory cell activation, and IgA antibodies that protect mucosal surfaces [9,10]. Studies comparing IgG levels after PCV and PPSV administration have shown much higher titer levels after PCV injection [9,10,11].

The weakness of the evidence in favor of PPV was illustrated in a Cochrane review linked at the Clinical Correlations post:

Main results
Twenty-five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I2 statistic = 0%). There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I2 statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I2 statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I2 statistic = 10%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I2 statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I2 statistic = 31%). This review did not consider adverse events as it was outside the scope of the review.

Authors' conclusions
This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

Weak. Modest at best. It doesn't really prevent pneumonia, at least in the patients we see, nor does it lower mortality. For invasive disease the relative risk reduction looks robust but the absolute risk reduction is low. The NNT must be very very high.

Patients I admit with pneumonia seem to exhibit more skepticism than many of today's policy makers. “I got the shot. How could I now have pneumonia?” they ask.

I believe pneumococcal vaccination is the right thing to do but there's no bang for the buck with PPV. Making PPV a core measure was poorly informed. If vaccination is to remain a core measure I believe PCV should be the singular focus but there remains some debate around that question.

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