Changing Pneumococcal Serotypes Causing Disease

Abstract & Commentary

By Hal B. Jenson, MD, FAAP, Professor of Pediatrics, Tufts University School of Medicine, and Chief Academic Officer, Baystate Medical Center, Springfield, MA, is Associate Editor for Infectious Disease Alert.

Synopsis: An increase in non-vaccine pneumococcal serotypes, especially serotype 19A, accompanied by decreased antibiotic susceptibility, was observed in cases of invasive pneumococcal disease in Massachusetts from 2001 to 2007. The new PCV13 vaccine provides protection against at least 44% of non-PCV7 serotypes causing invasive pneumococcal disease.

Source: Hsu KK, et al. Changing serotypes causing childhood invasive pneumococcal disease; Massachusetts, 2001-2007. Pediatr Infect Dis J. 2010;29:289-293.

Clinical laboratories in Massachusetts are required to submit to the state all isolates of Streptococcus pneumoniae cultured from blood, cerebrospinal fluid, or other normally sterile body fluids from children < 18 years of age. Pneumococcal isolates were serotyped using the Quellung reaction, and antibiotic susceptibility to penicillin, ceftriaxone, and azithromycin were determined by E-test and minimum inhibitory concentration interpretations based on the Clinical and Laboratory Standards Institute (CLSI) 2007 guidelines.

A total of 569 cases of invasive pneumococcal disease were identified from October 2001 through September 2007. There were no significant changes in the distribution of invasive pneumococcal disease, hospitalization rates, or mortality rates during the study period. Among 433 (74%) isolates available for serotyping, 366 (85%) were caused by non-PCV7 serotypes and 67 (15%) were caused by PCV7 serotypes, which occurred primarily from 2001 to 2005. The most common serotypes identified during the six years were 19A (20%), 7F (12%), 6A (7%), 22F (6%), 33F (6%), 15B/C (5%), and 3 (5%).

PCV7 serotypes accounted for 25% of isolates in 2001 and 2002, and none of the isolates in 2006 and 2007. During the six years of the study, there were no significant changes in the incidence of invasive pneumococcal disease, which averaged 6.5 cases/100,000 children < 18 years of age. There was a decline of PCV7 serotype disease from 1.0 cases/100,000 in 2001-2002 to 0 cases in 2006-2007. Non-PCV7 serotype disease progressively increased from 3.0 cases/100,000 in 2001-2002 to 5.3 cases/100,000 in 2005-2006.

The highest age-specific rates of invasive pneumococcal disease were among children < 1 year of age. Black and Hispanic children continued to be a higher risk for invasive pneumococcal disease than white children. This difference was not attributable to unequal vaccination coverage. During this period, an increasing proportion of invasive pneumococcal disease was reported among recipients with at least two doses of PCV7 (39% in 2001-2002 vs. 63% in 2006-2007). Statistically significant shifts were noted only for serotype 19A, with steadily increasing incidence from 0.4 cases/100,000 (95% CI, 0.1-0.7) in 2001-2002, to 1.4 cases/100,000 (95% CI, 0.8-2.0) in 2003-2004, to 1.7 cases/100,000 (95% CI, 1.0-2.3) in 2006-2007.

Using a penicillin breakpoint of > 0.06 mcg/mL to define non-susceptible isolates, penicillin nonsusceptible isolates constituted 39% of isolates in 2001-2002, 28% of isolates in 2002-2003, and approximately half of isolates in 2003-2007 (p = 0.03). Using a ceftriaxone breakpoint of > 0.5 mcg/mL to define non-susceptible (intermediate and resistance) isolates, ceftriaxone non-susceptible isolates constituted < 10% of isolates in 2001-2002, compared to almost 20% of isolates in 2005-2007 (p = 0.01).

Commentary

The heptavalent pneumococcal vaccine (PCV7) was introduced in the United States in February 2000, and included serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F linked to the protein carrier CRM197, a nontoxic mutant of diphtheria toxin. This vaccine was recommended in a three-dose primary series for all infants beginning at two months of age, followed by a booster dose at 12-15 months of age. The study shows a decrease in the rate of invasive disease caused by PCV7 serotypes, accompanied by an increase in the rate of invasive disease caused by non-PCV7 serotypes, resulting in stable incidence of invasive pneumococcal disease over this period.

During the six years of the study, there was an increase in ceftriaxone non-susceptibility to 22% in 2006-2007. The increase in ceftriaxone non-susceptibility was not observed to be associated with significant changes in hospitalization or mortality rates.

On February 24, 2010, a 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13) was licensed by the FDA for use among children six weeks-71 months of age. PCV13 succeeds PCV7, and includes the additional serotypes 1, 3, 5, 6A, 7F, and 19A conjugated to the same carrier protein. These additional six serotypes accounted for at least 44% of the non-PCV7 serotypes causing invasive pneumococcal disease in Massachusetts during 2001-2007. This underscores the significant benefit that is expected with the new 13-valent vaccine. As PCV13 becomes available in providers' offices, unvaccinated children, and children incompletely vaccinated with PCV7, should complete the immunization series with PCV13.

The results of this study demonstrate the continued need for surveillance of pneumococcal disease — incidence, serotypes, and antimicrobial susceptibilities — to guide vaccine development and also clinical management including presumptive antibiotic choices in critically ill children.