Pneumococcal vaccine reduces the rates of pneumococcal meningitis in children

Article Outline

• Question
• Design
• Setting
• Participants
• Outcomes
• Main Results
• Conclusions
• Commentary
• Copyright

Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, Craig AS, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 2009;360:244-56.

Back to Article Outline

Question 

What has the been the effect of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) on pneumococcal meningitis since its introduction in 2000?

Back to Article Outline

Design 

Population-based surveillance study.

Back to Article Outline

Setting 

Eight active bacterial core surveillance sites in the United States

Back to Article Outline

Participants 

Patients with pneumococcal meningitis, diagnosed between 1998 and 2005.

Back to Article Outline

Outcomes 

Changes in the incidence of pneumococcal meningitis from 1998 through 2005 were assessed against baseline values from 1998–1999. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others).

Back to Article Outline

Main Results 

There were 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100000 persons between 1998–1999 and 2004–2005 (a 30.1% decline, P < .001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P < .001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P < .001) among patients of all ages. Although rates of PCV7-related serotype disease decreased by 32.1% (P = .08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P < .001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P = .01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P = .03).

Back to Article Outline

Conclusions 

Rates of pneumococcal meningitis have decreased among children and adults since PCV7 was introduced. Although the overall effect of the vaccine remains substantial, a recent increase in meningitis caused by non-PCV7 serotypes, including strains nonsusceptible to antibiotics, is a concern.

Back to Article Outline

Commentary 

Hsu et al report significant reductions of 64% in children < 2 years of age and 54.0% in adults ≥65 years old in the overall incidence of pneumococcal meningitis (P < .001 for each comparison). For all ages, the rate of disease for the 7 serotypes in the vaccine decreased by 73.3% (P < .001), the rate of PCV-7 related serotypes decreased by 32.1 (P < .08). However, the rate of non-PCV7 serotypes increased by 60.5% (P < .001). The increase in disease caused by non-PCV7 serotypes was primarily accounted for by serotypes 19A, 22F, and 35B, but significant increases also occurred for serotypes 11A and 16F. Although the overall incidence of non-PCV7 meningitis remained low, increasing from only from 0.32 cases to 0.51 cases per 100000 person-years, the change was most dramatic in children < 2 years of age where the incidence increased from 0.77 to 2.87 cases per 100000 person-years. Although much attention has been focused in past years on the emergence of serotype 19A after PCV7 introduction, these data demonstrate a more diverse variability of pneumococcal serotype dynamics. Although the increasing numbers of 19A cases have been primarily antibiotic-resistant clones, this was not the case for other serotypes such as 35B. This indicates that even though antibiotic selection pressure may have played a role in the emergence of serotype 19A, other factors such as vaccine selection pressure or perhaps normal cyclic variability in the incidence of individual serotypes may be behind changes observed for other serotypes. Regardless, the fact that non-vaccine serotypes are causing an increasing amount of disease and that only some of these serotypes are present in newer pneumococcal conjugate vaccines could mean that our battle against this pathogen will be long and complicated.