- AOM —
- acute otitis media
- IPD —
- invasive pneumococcal disease
- PCV —
- pneumococcal conjugate vaccine
- PCV7 —
- 7-valent pneumococcal conjugate vaccine
- PCV13 —
- 13-valent pneumococcal conjugate vaccine
- NP —
- SPN —
- Streptococcus pneumoniae
In this issue of Pediatrics, Lee et al1 report surveillance data from Massachusetts communities regarding Streptococcus pneumoniae (SPN) colonization during the pneumococcal conjugate vaccine (PCV) era. Nasopharyngeal (NP) colonization is thought to precede SPN disease, so it is a reasonable measure of circulating (and potentially disease-producing) pneumococcal strains. Three aspects are notable: (1) shifting serotypes of known invasive pneumococcal disease (IPD) producers; (2) risk factors for colonization; and (3) evolving antibiotic resistance.
Excluding HIV-associated pneumococcal deaths, global estimates attribute ∼11% of all deaths in children 1 to 59 months of age to SPN disease.2 SPN remains a concern for US practitioners, causing both IPD (eg, meningitis, pneumonia, and bacteremia) and noninvasive disease (eg, acute otitis media [AOM] and sinusitis). Practitioners likely see at least 1 child per week for whom SPN bacteremia, pneumonia, or meningitis is a concern. A preventive vaccine targeting the most common IPD strains seemed a reasonable strategy to reduce disease burden and ease providers’ fears of missing an impending severe IPD case.
Introduced in 2000, 7-valent PCV (PCV7) markedly decreased IPD among PCV7 recipients,3–6 and also among non-PCV7 recipients through herd immunity.4,5,7 Pneumonia,8 AOM,9,10 tympanostomy tube procedures,11 and NP colonization12 also declined. However, non-PCV7 serotypes emerged to colonize and cause disease (serotype replacement).13–15 Serotype 19A was a major culprit sustaining both IPD and difficult-to-treat noninvasive infections, adding to the problem of high-level multidrug resistance.16,17 In 2010, 13-valent PCV (PCV13) included the main post-PCV7 replacement serotypes and was successful in reducing IPD from the 6 added PCV13 serotypes, including 19A18–20 and multidrug-resistant strains.20,21
Lee et al’s1 data confirm that PCV7 and PCV13 caused a rapid but transient decrease in NP colonization, followed by increasing colonization due to newly emerged replacement serotypes. One concern is whether some replacement serotypes could have invasive disease potential. For example, post-PCV7, there was increased severity of IPD from non-PCV7 serogroup organisms among children in the Intermountain West of the United States.22 Although Stockmann et al23 identified an initial increase in diversity of IPD serotypes after PCV7 and PCV13, the diversity soon reversed, presumably because of selective competition and the emergence of new dominant strains. They hypothesize that these new strains could cause increased IPD, especially in vulnerable populations. Thus, post-PCV13 serotype 35B may become the equivalent of post-PCV7 serotype 19A.
But occult bacteremia has nearly disappeared and meningitis is less frequent. Despite this, the authors report ongoing risk factors for colonization with potential IPD strains. These risks, described previously in smaller short-term studies, offer targets for action. The risk factor of young age can be addressed by on-time PCV13 administration to provide protection as soon as possible. Advising fewer hours at daycare can reduce pathogen exposure and frequency of upper respiratory tract infections (2 other risk factors). Educational efforts to restrict second hand smoke exposure and minimize antibiotic use can also decrease the risk for SPN NP colonization. Of these, judicious antibiotic use and on-time PCV13 are actions providers can impact the most.
The authors’ data1 confirm the rise and fall of antibiotic resistance, particularly in the multidrug-resistant 19A strain, which peaked from 2008 to 2010. By 2014, only ∼5% of SPN were penicillin nonsusceptible, but new replacement strains increased ceftriaxone and macrolide nonsusceptibility. Indeed, serotype 35B accounted for >80% of ceftriaxone nonsusceptibility. Interestingly, the nonsusceptible 35B strains appear to have originally had 9V capsules. They switched to a 35B capsule post-PCV13,24 confirming the concerns of some experts that SPN could change its capsule under antibody pressure like people change their clothes for different weather. The considerable macrolide nonsusceptibility, likely due to past azithromycin exposure, is important given azithromycin’s overuse for outpatient pneumonia25 and AOM.26
Is there a better strategy? From the pool of >90 SPN serotypes, new types emerged after each PCV was implemented. More serotypes in a multivalent PCV will not likely solve this problem because of limits on the number of new serotypes that can be added. Auxiliary PCVs that address only emerging non-PCV13 serotypes may be possible. However, the time and/or resources to reformulate and obtain Food and Drug Administration approval make this strategy seem like playing a game of whack-a-mole.
To overcome the phenomenon of serotype replacement, vaccine strategies need to expand beyond serotype specificity by identifying antigens common to all SPN, regardless of serotype. Meanwhile, studies like this one by Lee et al,1 that monitor pneumococcal seroepidemiology will inform treatment and vaccine strategies. The hope that IPD and antibiotic resistance would disappear after widespread use of PCV vaccines has yet to be realized.
Yet there is progress. Shifts back to less penicillin resistance may soon preclude the need for high dose amoxicillin for AOM, and the near absence of occult SPN bacteremia may drastically reduce empirical ceftriaxone for fever without a focus. To assist providers in ongoing vigilance for the now less frequent IPD, algorithms based on new epidemiologic data are in development and should decrease the number of “sepsis workups” performed.
- Accepted August 9, 2017.
- Address correspondence to Douglas S. Swanson, MD, Infectious Diseases, Children’s Mercy Kansas City, 2401 Gillham Rd, Kanas City, MO 64108. E-mail:
Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.
FINANCIAL DISCLOSURE: Children’s Mercy Kansas City has received research support from Pfizer Inc for which Drs Swanson and Harrison are investigators.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: Drs Swanson and Harrison conducted pneumococcal research that was supported by funding from Pfizer Inc, New York, a manufacturer of pneumococcal conjugate vaccine.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2017-0001.
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- Copyright © 2017 by the American Academy of Pediatrics