new CDC adult pneumococcal vaccine recommendations

 The CDC just published new and quite different recommendations on pneumococcal vaccinations in adults: see https://www.cdc.gov/mmwr/volumes/72/rr/rr7203a1.htm?s_cid=rr7203a1_w  for the full report (or see pneumococcal vaccine recs 2023 in dropbox). The major change leading to these recommendation changes is the development of the PCV15 and PCV20 vaccines.  Here is a summary of the vaccination recommendations.

 

-- Recommendations in brief (will attach their relevant tables at the end of the blog):

    --no vaccination for healthy adults <65yo

    --for those ≥65yo or 19-64yo with certain underlying medical conditions (see below) but have never gotten any pneumococcal vaccines:

        -- if PCV20 is available, that can be provided as a single dose alone (the preferred approach)

        -- or the PCV15 can be administered with a single dose of the PPSV23 at least one year later (ie, no need for PPSV23 if gets PCV20)F

    --for adults 19-64 with underlying medical conditions who received one dose of PPSV23, they should get either PCV15 or PCV20 at least 1 year after their PPSV23

        -- those at age ≥65 who had both PCV13 and PPSV23 and another PPSV at age ≥65 should  consider a single dose of PCV20 at least 5 years after their last dose of either PCV13 of PPSV23

    --for adults who started their pneumococcal vaccine series with the old PCV13, they should get either PCV20 or PPSV23 at least one year later

    --for those ≥65yo who completed their full pneumococcal vaccination based on prior recommendation, consider a supplemental PCV20 dose, through shared decision-making (see box at end of blog)

 

-- groups at risk for pneumococcal disease with recommendation to vaccinate in the 19-64yo group: 

    -- chronic heart disease (heart failure, cardiovascular, and valvular disease): 3.3 times the odds for community-acquired pneumonia (CAP) and 9.9 times for invasive pneumococcal disease (IPD: infection of normally sterile sites, ie pneumonia with bacteremia, meningitis, osteomyelitis, septic arthritis, bacteremia), and even higher in those with severe heart failure. Vaccination is associated with a 22% decreased all-cause mortality, even in those with very high cardiovascular risk

    -- smoking: increased risk for pneumococcal carriage in a dose-dependent fashion, 2.8-4.2 times increased IPD risk in those who smoked in past year

    -- chronic lung disease: in those >40yo who were hospitalized with CAP, people with COPD have 18 times the risk. Reasons are multifold: inhaled steroids used, reduced airway defense mechanisms (local lung immune function, loss of cilia, etc), smoking…  Asthma was added to the list in 2010 based on a case-control study finding an odds ratio of 2.4 in those with asthma (https://www.nejm.org/doi/full/10.1056/NEJMoa044113 )

    -- diabetes: 1.4 times the risk of CAP and 1.4-5.9 times the risk of IPD; a Danish study found that the pneumonia-related hospitalizations in patients with diabetes had a risk ratio of 3.2 in those <40yo, which decreased with age (1.1 in adults  >80yo)

    -- excess alcohol use: increased CAP risk in dose-dependent fashion; 8.2 times higher in those with clinically-defined alcohol use disorder; 2.3-7.7 times the risk of IPD

    -- chronic liver disease: all-cause pneumonia 4.1-5.6 times higher, pneumococcal pneumonia 4.1 to 6.4 times higher, IPD 6.4-10.2 times higher

    -- cochlear implants: adults ≥65yo have 1.5 times the risk for IPD as well as increased all-cause and pneumococcal pneumonias

    -- CSF leaks (including congenital and post-traumatic/post-surgical): 59% of adults with CSF leak had previous episode of meningitis; another study found 14.0-32.6 times the risk for IPD

    -- asplenia (functional and anatomic): 8.5-18.2 times increased risk for all-cause pneumonia and 14.0-32.6 times increased risk of IPD

    -- chronic kidney disease: esp in those with nephrotic syndrome and end-stage renal disease. Stage 3-4 CKD associated with 1.2 times the risk of IPD; ESRD associated with 3.7 times the risk of IPD, PPSV23 has significantly lower immune response in those with CKD and in those on dialysis

    -- congenital and acquired immunodeficiencies: higher rates of infections or severe manifestations from vaccine-preventable diseases including pneumococcal ones, likely related to immunologic responses (esp to PPSV-23) that are diminished and short-lived. No numbers were presented for this.

 

-- immunogenicity of the vaccine:

    -- as opposed to PPSV23, the conjugate vaccine (eg PCV13, PCV15, PCV20) stimulates mucosal immunity (decreasing nasal colonization by the bacteria), leading to more herd immunity. But there is the emergence of replacement pneumococcal strains

        -- the conjugate vaccines have pretty much eliminated from the population the serotypes covered in these vaccines

    -- in basically healthy adults ≥65yo, the PCV20 vaccine elicited antibody responses that were non-inferior to those in people getting the PCV-13 then PCPSV23 one month later, for all 13 of the PCV-13 serotypes

    -- compared to PPSV23 recipients, those getting PCV20 had a higher percentage of seroresponders to 6 of 7 non-PCV13 serotypes

    -- observational studies on PPSV23 suggested significant decreases in vaccine effectiveness over time: after PPSV23, IPD declined 48% among those vaccinated <2 years previously to 15% by >5 years previously. the studies on CAP were hard to evaluate fully, given differing criteria in the studies in defining CAP, but generally found a significant decline of effectiveness over time; there was also a decline in vaccine effectiveness for IPD cases over time. These declines were regardless of the patient's age at the time of vaccination

 

-- coadministration with other vaccines:

    -- no problems with flu vaccines, some suggestion that the BNT162b Covid vaccine (the Pfizer one) may be associated with lower antibody response to PCV20 if given within 6 months, but not statistically significant. no problem with RSV vaccine

    -- no data on the other vaccines 

 

-- safety:

    --of 6,343 participants getting PCV20, the most frequent adverse reactions in those ≥65yo were injection site pain (55%), muscle pain (39%), fatigue (30%), headache (22%), and joint pain (13%); a bit higher in the younger group

    -- adverse effects within 6 months after vaccination were reported in 1.5% of PCV20 recipients and 1.8% of controls.

 

Commentary:

-- pneumococci colonize the upper respiratory tract, with the highest prevalence in the first 2 years of life (ie children are a common reservoir and vector to higher risk individuals)

-- pneumococcal carriage rates are higher in older adults, those living in nursing homes, those who smoke cigarettes, or those who have regular contact with children <6yo

-- pneumococcal carriage is a precursor to disease, both in the lungs and otitis through direct spread and elsewhere (ie, invasive pneumococcal disease, IPD) including pneumonia with bacteremia, meningitis, osteomyelitis, septic arthritis, bacteremia

    -- 10% of patients hospitalized with community-acquired pneumonia (CAP) have pneumococcal pneumonia

-- there were more than 100 pneumococcal serotypes documented as of 2020, though 60-75% of all IPD cases in adults are caused by 24 serotypes

    -- the old PCV-13 vaccine covered 4.6% of the cases of all-cause pneumonia, the new PCV20 covers an additional 3.3%

    -- it should be noted that the actual serotypes of pneumococcus do change: the introduction of pneumococcal vaccines, for example, leads to serologic replacement (ie, non vaccine-covered serotypes do tend to flourish in the void left by the covered ones): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380097/

    -- the standard pneumococcal vaccination in kids has led to really dramatic decreases in invasive and highly aggressive pneumococcal disease. But the wide-spread use of this vaccine has also led to a decrease in the vaccine-associated pneumococcal serotypes (of course, the strikingly huge benefit for kids has undeniably been a positive thing…)

-- vaccine coverage for pneumococcal disease in the US is pretty low, on the order of 23% of adults 19-64yo who are at increased risk for IPD, and about 32% of adults ≥65yo. Those with HIV have the highest immunization rate, but still only at 48%; those with alcohol dependence have the lowest, at 6%

    -- and, as per usual in the US, ethnic minorities have lower rates, reflecting glaring inequities in both health care and public health initiatives in the US

 

-- there are still several unanswered questions:

    -- this information predates any assessment of real clinical outcomes for PCV20 (too early to get outcome data), but all of the prior PCV vaccines and PCV20 rely on conjugation with the same CRM197, though with more pneumococcal serotypes in the new one

    -- one cannot always assume that the more, the better. However,

        -- a Canadian study found that on comparing the very old PCV7 with the then newcomer PCV13, the vaccine effectiveness was lower with the latter, especially around 2 serotypes (3 and 19A, neither of which were in the PCV7 vaccine), though the number of administered vaccinations for these 2 vaccines differed: 4 for PCV7 vs 3 for PCV13;  overall there was more benefit of protection with PCV13: https://pubmed.ncbi.nlm.nih.gov/35351324/

        -- a study comparing PCV15 to PCV13 found the PCV15 to be more immunogenic overall and equally as good for the 13 covered serotypes in PCV13

 

Limitations

-- unfortunately, this CDC report has no clear flowcharts to help elucidate who should get what. The best they had is the array of tables below.  

    -- However, there is a great smartphone app that allows entering minimal information on the patient and displays the current recommendations: PneumoRecs VaxAdvisor

-- there is a lot of information in the article itself. I did not include the different charts specifically for patients with cochlear implants, CSF leaks, hematopoietic stem cell transplants.  Please see the article for information on this

-- there have not been studies yet on the actual major clinical outcomes of PCV20 vaccination (both benefits and risks), though one may assume that higher coverage will lead to fewer pneumococcal diseases (they all have just about the same quantity of each serotype in them), and the adverse effects are likely to be similar. But maybe including these 20 serotypes will lead to increased selection of other, perhaps more toxic serotypes (ie replacement strains filling in for the vacuum of displaced prior strains)????

-- the concept of a single adult dose of PCV20 being effective in both young adults with higher-risk conditions and all over ≥65yo is great. but how long will clinical protection actually last??

-- the actual data presented above on many of the high-risk conditions are often not so clear in terms of the specific hazard ratios attributed to them. some were pretty small studies. or eclectic populations. some had insufficient analysis to compensate for other potential confounders. But, it is still probably safer to immunize than not.

 

so, though presented in a rather complex and not so provider- or patient-friendly way, these new guidelines are much simpler than the older ones. 

-- basically, if one has the PCV20 available, it is a simple one shot affair, either as a new person to the vaccine, as a complement to an incomplete set of the prior vaccines, or as a reinforcement for those ≥65 who had had the full set of vaccines (after shared decision-making, though this does seem to be reasonable, especially given the documented decreased long-term immunogenicity/effectiveness of the PPSV23 vaccine as part of the PCV15 and older PCVs)

    -- though, will one shot be sufficient (only time will tell)? if so, maybe we should be vaccinating all adults with one shot, independent of health status, since pneumococcal disease hits all adult age groups??

-- as with recommendations on any new vaccine or medication, we clinicians (and patients) need to balance the likely benefits from the studies done to date with the potential of subsequent findings of either decreased vaccine effectiveness or increased adverse effects. it is reassuring that this new PCV vaccine is just another extension of the previous conjugate vaccines.

 

Here are the tables

 

 

 

 

 

geoff

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