From the Journals

Current pneumococcal vaccines knock out many serotypes, but others take their place

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Playing pneumococcal serotype elimination ‘whack-a-mole’

“The hope that IPD and antibiotic resistance would disappear after widespread use of PCV vaccines has yet to be realized,” Douglas S. Swanson, MD, and Christopher J. Harrison, MD, wrote in an accompanying editorial (Pediatrics. 2017;140[5]:e20172034).

While some invasive pneumococcal diseases, such as occult bacteremia and meningitis, have been significantly reduced due to PCV7 and PCV13, “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,” the authors noted. Newly dominant strains, such as post-PCV13 serotype 35B, could cause increased IPD in vulnerable populations, becoming the equivalent of a post-PCV7 serotype 19A.

While addressing emerging serotypes in additional PCVs is possible, reformulating the vaccine and obtaining Food and Drug Administration approval would take time and resources, with no clear guarantee of ultimate success, making “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 Streptococcus pneumoniae, regardless of serotype,” Dr. Swanson and Dr. Harrison said.

“Shifts back to less penicillin resistance may soon preclude the need for high dose amoxicillin for acute otitis media, and the near absence of occult Streptococcus pneumoniae 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 work-ups’ performed,” they said.

On-time PCV13 vaccination would help address the risk factor of young age, and judicious antibiotic use could further reduce antibiotic resistance. Social engineering approaches, although difficult, also might help. These approaches include continued parent education to restrict secondhand smoke exposure and the risk of S. pneumoniae nasopharyngeal colonization, as well as having young children spend fewer hours in day care in order to reduce two other risk factors – pathogen exposure and frequency of viral upper respiratory tract infections.

Dr. Christopher J. Harrison

Dr. Christopher J. Harrison

Dr. Swanson and Dr. Harrison are with the division of infectious diseases at Children’s Mercy Kansas City, University of Missouri-Kansas City. Both reported conducting pneumococcal research supported by funding from Pfizer.


 

FROM PEDIATRICS

The introduction of pneumococcal conjugate vaccines 7 (PCV7) and 13 (PCV13) has significantly reduced pneumococcal colonization of the serotypes targeted by the vaccines, but serotypes not covered by these vaccines have picked up the slack, according to an analysis of more than 6,000 young Massachusetts children tested at well child or acute care visits over 15 years.

In the past 15 years, use of pneumococcal vaccines in the United States has led to dramatic declines in invasive pneumococcal disease (IPD) in young children, reductions in pneumonia hospitalizations, and herd protection in older adults against disease that otherwise would be caused by the vaccinated serotypes, studies have found.‍ But not all serotypes of Streptococcus pneumoniae are covered by the vaccines.

Streptococcus pneumoniae CDC/Dr. Mike Miller

The data used in the Massachusetts study included results from nasopharyngeal swabs taken from 6,537 children younger than 7 years of age in various Massachusetts communities during six respiratory illness seasons during 2000-2001, 2003-2004, 2006-2007, 2008-2009, 2010-2011, and 2013-2014. The highest rate of pneumococcal colonization was in 2011 at 32%, and the lowest was in 2004 at 23%, Grace M. Lee, MD, MPH, of the Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston, and her associates reported (Pediatrics. 2017;140[3]:e20170001).

In 2001, PCV7 serotypes were the most common, but after the rapid introduction of the vaccine, infection rates for those serotypes quickly declined, nearly disappearing by 2007. Serotype 19A became the most common serotype in 2004, but after the introduction of PCV13 in 2010, it and other serotypes targeted by PCV13 also began to decline. In 2014, the most common serotypes were 15B/C, 35B, 23B, 11A, and 23A.

Non-PCV13 serotypes accounted for about a third of observed Streptococcus pneumoniae colonizations in 2001, but by 2014 they accounted for nearly all colonizations. In addition, the overall rate of infection did not decrease over the study period. While a reduction was seen from 2011 to 2014, it remains to be seen whether this drop is transient.

“Replacement with nonincluded serotypes remains a risk with vaccines that do not cover the full range of serotype diversity. As new selective pressures are applied, such as the introduction of a vaccine into a community, the void may be filled by nontargeted serotypes,” as was observed after PCV7, Dr. Lee and her fellow researchers noted.

Nonsusceptibility to erythromycin was most common in 2014, with 35% of pneumococcal isolates displaying either moderate susceptibility or resistance. Nonsusceptibility to ceftriaxone (12%), clindamycin (9%), and penicillin (6%) was significantly less common, and no isolates were found to have vancomycin resistance.

“First-line penicillins continue to be the most frequently prescribed antibiotic across all age groups among young children in Massachusetts, which may result in the continued success of 19A associated with penicillin resistance,” the researchers said.

Risk factors associated with colonization by either PCV13 serotypes or non-PCV13 serotypes include younger age, more hours of child care exposure, and having a respiratory tract infection on the day of sampling. The presence of a smoker in the house and recent usage of antibiotics was associated with colonization by PCV13 serotypes but not by non-PCV13 serotypes.

“As newer pneumococcal vaccines are developed, there will continue to be a need for monitoring both the intended and unintended consequences of altering the nasopharyngeal niche through immunization,” Dr. Lee and her associates concluded.

This work was funded by a National Institute of Allergy and Infectious Diseases grant and the National Institutes of Health. Marc Lipsitch, PhD; William P. Hanage, PhD; Ken Kleinman; Stephen Pelton, MD; and Susan S. Huang, MD, MPH, reported various conflicts of interest. Dr. Lee and the remaining investigators indicated that they had no potential conflicts of interest.

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