Pneumococcal colonization changes after PCV7 introduction

November 2005

Pneumococcal colonization has changed in serotype distribution and in patterns of antibiotic resistance since the introduction of the heptavalent conjugate pneumococcal vaccine (PCV7; Prevnar, Wyeth), according to a study.

“The good news is that high level penicillin resistance did decrease, since this has been concentrated in PCV7 strains, and carriage of these serotypes has gone down,” said researcher Jonathan A. Finkelstein, MD, MPH, associate professor in the department of ambulatory care and prevention and the department of pediatrics at Harvard Medical School in Boston. “The bad news is that intermediate nonsusceptibility is increasing in the expanding population of non-PCV7 isolates.”

Since PCV7’s availability in 2000, public health officials have raised concerns about the replacement with nonvaccine serotypes in invasive disease and asymptomatic carriage and the increasing cases of antibiotic resistance.

“Pneumococcal conjugate vaccine has been a great success in terms of decreasing invasive infection in young children in the United States. However, it has not solved the problem of antibiotic resistance among pneumococci in the community,” he told Infectious Diseases in Children. “Continued efforts to use antibiotics judiciously are certainly warranted.”

Finkelstein and colleagues evaluated colonization changes since the introduction of this vaccine and found an increase in the frequency of non-PCV7 strains. They also found that the proportion of non-PCV7 isolates that are not susceptible to penicillin has tripled, according to the study, which appeared in Pediatrics.

Change determined

In 2001, the researchers randomly surveyed children for pneumococcal carriage as part of the microbiological collection. These children resided in 16 Massachusetts communities.

Then, in 2004, Finkelstein and colleagues resampled the same communities to determine changes in the commonly circulating serotypes – PCV serotypes, PCV7 cross-reactive serotypes and non-PCV7 Streptococcus pneumoniae serotypes — and their antimicrobial resistance patterns.

Thirty-one private practices participated in the 2001 sample, and 23 of those participated in the follow-up trial.

The researchers collected 994 nasopharyngeal swab samples for pneumococcal isolates from children younger than 7 at primary care offices during well-child care or care for minor illnesses. They performed antibiotic susceptibility testing and serotyping on isolated S. pneumoniae strains and reviewed the children’s medical records to obtain their PCV7 vaccination history.

Findings indicated that among colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% in 2001 to 14% in 2004. The fraction of serotypes that were not included in the vaccine increased from 34% to 55%, and the fraction of these non-PCV isolates that were not susceptible to penicillin tripled from 8% to 25%.

Findings indicated that overall carriage of S. pneumoniae remained relatively stable from 2001 (26%) to 2004 (23%). Likewise, carriage of potentially cross-reactive serotypes did not change much (30% to 31%), according to Finkelstein.

The most common non-PCV7 serotypes that researchers detected in 2004 were 15, 29 and 11A followed by 22F, 10A and 35F, according to the study.

Finkelstein and colleagues also found a substantial increase in penicillin nonsusceptibility. In 2001, nonsusceptibility for non-PCV7 serotypes was 8%. However, that percentage increased to 25% in 2004, of which 35% were highly resistant.

Among PCV7 serotypes, penicillin nonsusceptibility slightly increased from 45% in 2001 to 56% in 2004. PCV7 potentially cross-reactive strains remained relatively stable at 51% in 2001 compared with 54% in 2004, according to the study.

“Despite the significant decline in PCV7 serotypes, overall pneumococcal carriage did not change between 2001 and 2004 because of significant increases in the carriage of non-PCV7 serotypes,” the researchers wrote in their study. “This serotype replacement was seen in all pediatric age groups studied and resulted in similar proportions of pneumococcal carriage in age groups between six and 36 months for both sampling periods.”

Prevention of disease

Other recent findings indicate similar trends to that of Finkelstein’s.

According to CDC surveillance data, routine pediatric immunization with PCV7 substantially reduced cases of severe disease, particularly invasive pneumococcal disease (IPD), caused by S. pneumoniae.

CDC researchers assessed the effects of routine vaccination with PCV7 in adults and children across the United States using population-based data from the Active Bacterial Core surveillance (ABCs) of the Emerging Infections Program Network. The CDC and several state health departments worked together to create ABCs.

Participating areas included the state of Connecticut and selected counties in California, Georgia, Maryland, Minnesota, New York, and Oregon, according to the report.

The researchers sought to assess the change in incidence of IPD after PCV7 and the projected number of vaccine-type (VT) IPD cases directly and indirectly prevented by PCV7. They compared IPD rates for 2001 through 2003 with the average rates for 1998 through 1999.

Findings indicated that:

• Pediatric routine vaccination with PCV7 continued to result in statistically significant declines in incidence of IPD through 2003 among children and adults
• The vaccine prevented more than twice as many IPD cases in 2003 through indirect effects on pneumococcal transmission than through its direct effect of protecting vaccinated children.
• Increases in disease caused by pneumococcal serotypes not included in the vaccine occurred in certain populations, but were small compared with overall declines in vaccine-serotype disease.

“Routine use of PCV7 in young children has reduced the incidence of VT [vaccine type] and overall IPD in children and adults, and these reductions have increased since 2001,” they wrote. “The most substantial decline in the rate of VT disease has been in the target population of children aged [less than] 5 years.”

Specifically, immunization prevented more than 29,000 cases of bacterial disease in 2003 alone. Incidence of VT IPD among children younger than 5 years old declined 94% compared to the pre-vaccine rates. Children vaccinated with PCV7 have a reduced prevalence of colonization with vaccine-types in their nasopharynx, according to the study.

“Because the vaccine prevents spread of the bacteria between individuals, we found that serious disease was less common even in people who were not targeted for vaccination,” CDC researchers wrote in the Morbidity and Mortality Weekly Report. “This ‘herd immunity effect’ was twice as large as the direct protective effect of the vaccine on immunized children in 2003 and is what makes a vaccine like this so important for public health.”

CDC officials suggested that ongoing surveillance should monitor the balance of disease reduction (particularly among vulnerable populations), assess whether reductions in vaccine-serotype IPD are sustained and if replacement disease will alter the benefits of routine vaccination.

Finkelstein suggested that further research is needed to more completely define the changes in the population genetics underlying these changes, which may help predict the long-term effect of PCV7 and other pneumococcal conjugate vaccines currently in development.

“Since these non-PCV7 serotypes tend to account for less invasive disease, the clinical impact of these changes requires both more time and further study to understand fully,” he said.

For more information:

• Huang SS, Platt R, Rifas-Shiman SL, et al. Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. Pediatrics. 2005;116:408-413.
• CDC. Reingold A, Hadler J, Farley MM, et al. Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease - United States, 1998-2003. MMWR. 2005;54:893-897.