By: Dr. Geoffrey Modest
NEJM had an article from South Africa looking at the efficacy of the pneumococcal conjugate vaccine from 2005-2012 (initially PCV-7, then PCV-13 as of 2011) in kids and adults (see DOI: 10.1056/NEJMoa1401914). They identified 35,192 cases of invasive pneumococcal disease (IPD) and assessed incidence before the vaccine (baseline), with after. Results:
–In children <2 yo, rate of IPD declined from 54.8 to 17.0 cases/100,000 person-years overall, and from 32.1 to 3.4 of the PCV-7 covered serotypes, translating to a 69% decrease in all serotypes, 89% decrease in PCV-7 covered serotypes, but a nonsignificant increase of 6% in nonvaccine serotypes (from 186 to 205/100,000 person-years)
–In children not infected with HIV, IPD decreased in the specific PCV-7 serotypes by 85%, though disease caused by noncovered strains increased 33% (though the absolute numbers were very low: 1/5 of the IPD cases). In those infected with HIV, the incidence of IPD is 25x higher, the efficacy of vaccine pretty similar, and there was no increase in noncovered strains
–By 2012, the incidence of IPD from the PCV-13 serotypes not included in the PCV-7 vaccine declined 57% in children
–In those younger than 10 weeks old, IPD decreased 36%, nonsignificant increase of 2% in nonvaccine serotypes
— In older kids, vaccine still effective: age 2-4 yo — 60% decrease in all serotypes; age 5-9yo, 44% decrease; age 10-14yo, nonsignificant decrease of 6%, though the incidence was very low; 15-24 yo: 30% decrease
–In adults aged 25-44, rate of IPD declined from 11.9 to 7.9 cases/100,000 person-years overall, and from 3.7 to 1.6 of the PCV-7 covered serotypes, translating to a 34% decrease in all serotypes, 57% decrease in PCV-7 covered serotypes, but a nonsignificant decrease of 11% in nonvaccine serotypes (from 559 to 555/100,000 person-years). Small difference in 45-64 yo at 14% decrease; no difference in those >64yo
–Also, of note, the rate of IPD in children <2yo caused by penicillin-nonsusceptible strains declined by 82% and by penicillin-susceptible strains by 47%. and multi-drug resistant strains by 84% and non-multi-drug resistant strains by 38%
So, a few issues.
–As background, South Africa has a remarkably high incidence and mortality from IPD in kids (and adults). And, they have an exceptionally high rate of antibiotic resistance to IPD (and most of the resistant strains are included in PCV-7). This antibiotic resistance was highlighted in MMWR a couple of decades ago, also noting increased incidence of pneumonia overall there (which, as I remember, was attributed to men working in coal mines, breathing dust which could affect local lung immunity mechanisms, as well as crowded conditions). There was significant concern for the spread of multi-drug resistant strep pneumonia, both within and outside of South Africa.
–In this study above, they gave kids PCV-7 at ages 6 and 14 weeks of age with a booster at 9 months (different from US recommendations: primary series age 2, mo, 4 mo, 6 mo, followed by booster 12-15 months old). Not sure how much this would affect results.
–They confirmed a remarkable reduction in vaccine-associated serotypes and in general major decreases in IPD in South Africa, as noted above.
–PCV-13 vaccination is one of most important vaccines we give. It is highly immunogenic and has dramatically decreased IPD in kids in the US, as is evident even in our health center (i cannot recall any admissions for pneumococcal meningitis since the introduction of PCV-7, with several cases — some fatal — previously).
–One issue with vaccines in general and IPD in particular, is that we conceivably could be selecting for much more lethal non-covered strains (new strains of strep pneumo colonize the nasopharynx on a regular basis, and at an increased rate in South Africa). And the good news so far is that this does not seem to be the case (ie, no significant increase in noncovered serotype infections, and most pointedly — no increase in highly virulent strains), and, to boot, it is reassuring that PCV-13 seems to confer increased protection against antibiotic-resistant strains.
–And this study confirms that immunizing kids helps adults (especially young adults who likely have the most exposure to those precious, but disease-ridden kids…)