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25% of sepsis cases following PCV13 introduction caused by S. pneumoniae
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One-quarter of all community-acquired sepsis cases among Swiss children were attributable to Streptococcus pneumoniae shortly after the introduction of the 13-valent pneumococcal conjugate vaccine, or PCV13, according to research published in Clinical Infectious Diseases.
The researchers wrote that despite the vaccine’s efficacy, infection caused by a vaccine serotype and pneumococcal meningitis were risk factors for more severe disease.
“S. pneumoniae is a leading cause of sepsis, meningitis and community-acquired pneumonia, resulting in significant mortality in children worldwide,” Sandra A. Asner, MD, MSc, head of the pediatric infectious diseases unit and staff physician at Lausanne University Hospital, and colleagues wrote. “There is a lack of recent population-based studies determining the burden and outcomes of pneumococcal sepsis in children.”
Switzerland’s Federal Office of Public Health suggested that all children aged younger than 2 years should be vaccinated with PCV13 in 2011. The researchers examined rates of pneumococcal sepsis following the vaccine’s introduction. Between September 2011 and December 2015, children aged younger than 17 years with blood culture-confirmed pneumococcal sepsis who had systemic inflammatory response syndrome were prospectively recruited to the study.
“Importantly, our study was started in the first year of introduction of PCV13 into the general vaccine schedule in Switzerland,” the researchers wrote.
Asner and colleagues defined vaccine failure as infection caused by a vaccine serotype in a child who was up to date with all PCV doses.
The researchers detected 117 cases of pneumococcal sepsis and a crude incidence of two cases per 100,000 children (95% CI, 1.7-2.4). Pneumococcal sepsis accounted for 25% of all community-acquired sepsis episodes, they said, and the infection had an 8% case-fatality rate. Most children with pneumococcal sepsis (83%) were aged younger than 5 years and did not have known risk factors for invasive pneumococcal disease. Pediatric ICU admission was required for 36% of patients with pneumococcal sepsis.
Nonvaccine pneumococcal serotypes were responsible for most meningitis cases among children following the introduction of PCV13 (69% vs. 31%). Vaccine failure occurred in 26% of children, and 11 of these children were infected with serotype 3.
The researchers also observed an increased risk for pediatric ICU admission for children with pneumococcal meningitis (OR = 6.8; 95% CI, 2.4-19.3) or serotype 3 infection (OR = 2.8; 95% CI, 1.1-7.3). Additionally, children infected with serotype 3 — which is included in the vaccine — were more likely to have longer hospital stays.
Previous research examining the incidence of pneumococcal disease in the United Kingdom following PCV13 introduction was conducted at a time when vaccination rates for three doses was at 93.5%. Asner and colleagues speculated that herd immunity had not yet been achieved in their population because vaccine coverage with three doses of PCV13 was only between 75% and 80%.
“The inclusion of a large number of children who did not qualify for PCV vaccination because of their age (older than 5 years) were not or (younger than 5 months) not yet fully protected, or who did not follow the recommendations may account for this finding,” the researchers wrote. “Recent national surveillance data reported a 50% decrease in invasive pneumococcal disease among children aged younger than 5 years between 2009 and 2017 that may be increasing to 80% to 90% as seen in other countries, thus supporting the efficacy of PCV13 vaccination.”
The researchers noted, however, that the rate of infection with vaccine serotype 3 highlights the need for more effective vaccines and immunization schedules. – by Katherine Bortz
Disclosures: Asner reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Sheldon L. Kaplan, MD
Asner and colleagues presented prospectively collected data on the incidence and outcome of pneumococcal sepsis in Switzerland for the 4 years following the introduction of PCV13 in 2011 as part of the Swiss Pediatric Sepsis Study. This report focused on sepsis defined as a patient with blood cultures positive for S. pneumoniae and meeting the current pediatric criteria for systemic inflammatory response syndrome. This population of patients is different from those of other studies that reported on invasive pneumococcal disease (IPD), which is based on cultures from normally sterile body sites testing positive for S. pneumoniae. The Swiss group found that pneumococcus accounted for 10% of all bacterial sepsis episodes. However, the study could not address how much pneumococcal sepsis has declined since PCV13’s introduction because similar data were not available in the pre-vaccine era.
Almost 60% of episodes were caused by serotypes included in PCV13, with serotype 3 accounting for almost 25% of cases. Overall mortality was 8% and was greater in the group of patients with bacterial meningitis and those with serotype 3 infection. Serotype 3 has been the dominant PCV13 serotype in all other studies describing the impact of PCV13 on IPD in children and presents a unique challenge for developing protective antibody levels following immunization with polysaccharide-based vaccines.
PCV7 and then PCV13 have been remarkably successful in significantly reducing the burden of IPD in children around the world. Next-generation PCVs are being developed by adding up to another seven or more serotypes to those included in PCV13. However, with more than 90 pneumococcal serotypes that could potentially cause IPD, other strategies will be necessary to prevent IPD altogether, assuming this is a wise approach. As always, continued surveillance of IPD, and perhaps infections that may be caused by nonpneumococcal bacteria replacing S. pneumoniae, is critical.
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