Pneumococcal disease rates drop, new strains appear

Although vaccine type diseases are fading, new non-vaccine type replacement diseases have surfaced.

Issue: July 2007

Cynthia G. Whitney

TORONTO — A large decrease in invasive and noninvasive pneumococcal disease rates in young children are accredited to the pneumococcal conjugate vaccine; however, replacement disease is a problem physicians are now closely following, according to Cynthia G. Whitney, MD.

“The pneumococcal conjugate vaccine [PCV7; Prevnar, Wyeth] has had a substantial impact on all forms of pneumococcal disease since its introduction in the United States, with the effect being larger than anticipated,” Whitney, of the CDC, told Infectious Diseases in Children.

These findings were presented at the Pediatric Academic Societies’ Annual Meeting, held in Toronto.

PCV7 effects

“Although the pneumococcal conjugate vaccine has been available since 2000, shortages in the early years slowed its use. Physicians are now more fully seeing effects surfacing from the use of the vaccine,” Whitney said.

Following the introduction of the conjugate vaccine, invasive disease rates caused by vaccine serotypes dropped dramatically in young children.

Whitney and colleagues found that PCV7 prevented invasive disease in both healthy and chronically ill children aged 3 months to 59 months.

The study included 782 cases and 2,512 controls who were identified through the CDC’s Active Bacterial Core Surveillance program, which is an active population-based system that tracks invasive pneumococcal infection in certain parts of eight states.

“The total population under surveillance is about 20 million and includes 1 million children younger than the age of 5 years,” Whitney said.

Study results showed 96% effectiveness (95% CI, 93%-98%) of one or more doses of the PCV7 vaccine against vaccine serotypes in healthy children and 81% effectiveness (95% CI, 57%-92%) in children with coexisting disorders.

“You can get some protection with one dose [of this vaccine], but it really does help to get more doses with each child,” Whitney said. “Most of the schedules were highly effective, and we really had a hard time distinguishing between them, although we did find that if you give three doses plus a booster, you get more protection than without a booster.”

Other noninvasive syndromes, such as otitis media and pneumonia, have also been reduced with the conjugate vaccine, according to studies by Grijalva et al and Poehling et al.

“All-cause pneumonia hospitalizations dropped 39% by 2004 in children aged younger than 2 years, and to me, this is just huge. Overall, this represents 41,000 fewer pneumonia hospitalizations in 2004 alone,” Whitney said.

In Poehling et al, after introduction of PCV7, there was an 8% to 33% reduction in the diagnosis of frequent otitis media by the age 2 years and a 3% to 23% reduction in pressure-equalizing tube insertions.

In another study by Poehling et al, the researchers found a 50% reduction in invasive disease in infants younger than 2 months, too young to have received vaccine, and a reduction of similar size has been seen in the Active Bacterial Core Surveillance program data for children aged 5 to 17 years who were too old to have received the vaccine.

“This observed reduction in vaccine type diseases in children is larger than what may have been expected,” Whitney said. “There is clear evidence that herd immunity appears to be protecting unvaccinated children, but there is now a small increase in replacement disease.”

Replacement disease occurs when the vaccine type diseases fade out and new, non-vaccine types surface.

“The one strain in particular that we are worried about is the 19A type, which is causing more invasive disease than it used to,” Whitney said. “In the general population, there has not been a lot of the replacement disease, but in a study by Singleton et al, Alaska Natives who are highly susceptible to pneumococcal infections in general were found to have significant rates of replacement disease. The replacement disease in this population is eroding the benefit of the effectiveness of the vaccine overall.”

Adults benefit

Vaccination of children with pneumococcal conjugate vaccines has also benefited adults, including the elderly and other adults at high risk for pneumococcal disease. In Flannery et al, researchers found that the indirect effects of herd immunity have also affected people aged 18 to 64 years with HIV or AIDS.

“Although replacement disease has occurred in adults, it has only been significant in adults with HIV or AIDS,” Whitney said. “It is clear that giving PCV7 to children may be our most effective means for preventing disease in adults. In a nutshell, the impact in adults has been huge … it is not something we had counted on ahead of time. The indirect benefits of this vaccine have really been important,” Whitney said.

Looking ahead, pneumococcal vaccines are in development and are expected to cover more disease serotypes than the existing vaccine.

“The currently licensed pneumococcal conjugate vaccine only covers seven of 90 known serotypes, and some serotypes that are not in the vaccine are important causes of disease. Next-generation conjugate vaccines and common protein vaccines in development will be designed to provide protection against more strains,” Whitney said. – by Jennifer Southall

For more information:

Grijalva CG, Nuorti JP, Arbogast PG, et al. Decline in pneumonia admissions after routine childhood immunization with pneumococcal conjugate vaccine in the USA: A time-series analysis. Lancet. 2007;369:1179-1186.

Peters TR, Poehling KA. Invasive pneumococcal disease: The target is moving. JAMA. 2007;297:1825-1826.

Poehling KA, Szilagyi PG, Grijalva CG, et al. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. 2007;119:707-715.

Singleton RJ, Hennessey TW, Bulkow LR, et al. Invasive pneumococcal disease caused by nonvaccine serotypes among Alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA. 2007;297:1784-1792.

Whitney CG. Direct and indirect effects of pneumococcal conjugate vaccine. Presented at: the Pediatric Academic Societies’ Annual Meeting; May 5-8, 2007; Toronto.

Whitney CG, Pilishvili T, Farley MM, et al. Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: A matched case-control study. Lancet. 2006;368:1495-1502.