Population Snapshot of Emergent Streptococcus pneumoniae Serotype 19A in the United States, 2005

Matthew R. Moore 0 7 Robert E. Gertz 0 Jr. 0 7 Robyn L. Woodbury 0 7 Genevieve A. Barkocy-Gallagher 0 7 William Schaffner 0 11 Catherine Lexau 0 10 Kenneth Gershman 0 9 Arthur Reingold 0 14 Monica Farley 0 12 Lee H. Harrison 0 13 James L. Hadler 0 8 Nancy M. Bennett 0 4 5 Ann R. Thomas 0 2 Lesley McGee 0 6 Tamara Pilishvili 0 7 Angela B. Brueggemann 0 1 Cynthia G. Whitney 0 7 James H. Jorgensen 0 3 Bernard Beall () 0 7 0 Received 3 September 2007; accepted 26 October 2007; electronically published 5 March 2008. Potential conflicts of interest: none reported. Presented in part: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy , Chicago, IL , 17 September 2007 (abstract S401A-633). Financial support: Emerging Infections Program and Antimicrobial Working Group, Centers for Disease Control and Prevention, and National Vaccine Program Office; and Division of Minority Opportunities in Research, National Institute of General Medical Science, National Institutes of Health (FIRST Institutional Re- search and Academic Career Development Award [K12] to R.L.W.). Atlanta, GA 30333 1 Department of Zoology, University of Oxford , Oxford, United Kingdom 2 Health Division, Oregon Department of Human Services , Portland 3 Department of Pathology, The University of Texas Health Science Center , San Antonio 4 Monroe County Department of Public Health 5 University of Rochester , Rochester, New York 6 Hubert Department of Global Health, Rollins School of Public Health, Emory University 7 Respiratory Diseases Branch, Centers for Disease Control and Prevention 8 Connecticut Department of Public Health , Hartford 9 Colorado Department of Public Health and Environment , Denver 10 Emerging Infections Program, Minnesota Department of Health , Minneapolis 11 Department of Preventive Medicine, Vanderbilt University School of Medicine , Nashville, Tennessee 12 Veterans Affairs Medical Center , Atlanta, Georgia 13 Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland 14 The School of Public Health, University of California , Berkeley Background. Serotype 19A invasive pneumococcal disease (IPD) increased annually in the United States after the introduction of the 7-valent conjugate vaccine (PCV7). To understand this increase, we characterized serotype 19A isolates recovered during 2005. Methods. IPD cases during 1998 -2005 were identified through population-based surveillance. We performed susceptibility testing and multilocus sequence typing on 528 (95%) of 554 serotype 19A isolates reported in 2005. Results. The incidence of IPD due to serotype 19A increased from 0.8 to 2.5 cases per 100,000 population between 1998 and 2005 (P .05), whereas the overall incidence of IPD decreased from 24.4 to 13.8 cases per 100,000 population (P .05). Simultaneously, the incidence of IPD due to penicillin-resistant 19A isolates increased from 6.7% to 35% (P .0001). Of 151 penicillin-resistant 19A isolates, 111 (73.5%) belonged to the rapidly emerging clonal complex 320, which is related to multidrug-resistant Taiwan19F-14. The remaining penicillin-resistant strains were highly related to other clones of PCV7 serotypes or to isolates within major 19A clonal complex 199 (CC199). In 1999, only CC199 and 3 minor clones were apparent among serotype 19A isolates. During 2005, 11 multiple-isolate clonal sets were detected, including capsular switch variants of a serotype 4 clone. Conclusions. PCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States. Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the United States in 2000 led to dramatic reductions in the incidence of invasive pneumococcal dis- - ease (IPD) among children and adults [13]. Because most of the antimicrobial-nonsusceptible pneumococcal strains during the prevaccine period were covered by PCV7, rates of IPD caused by nonsusceptible pneumococci also decreased after vaccine introduction [4]. In the United States, the incidence of IPD caused by serotype 19A increased after the introduction of PCV7 [57]. A recent study showed the important association between serotype 19A and antimicrobial resistance and demonstrated that increased rates of IPD due to serotype 19A and of nonsusceptibility among 19A isolates were caused by new clonal types of serotype 19A [5]. Although serotype 19A is a member of the same serogroup as the PCV7 serotype 19F, PCV7-induced antibodies do not provide cross-protection against serotype 19A [8, 9], nor does PCV7 protect against IPD caused by serotype 19A [10, 11]. Among pneumococcal isolates recovered from the respiratory tract, the proportion that are antibiotic-resistant serotype 19A has also increased significantly [12, 13]. There are at least 3 reasons why serotype 19A has emerged since PCV7 introduction. First, expansion of a single preexisting clone of serotype 19A suggests that this clone has an advantage over other clones of serotype 19A. Second, 1 new clone of serotype 19A might have been introduced into a population [14]. Third, successful clones previously associated with other serotypes might have undergone a recombinational switch to serotype 19A. We explored these possible explanations by obtaining a detailed snapshot of the genetic structure of this rapidly evolving serotype through multilocus sequence typing (MLST) of invasive isolates collected during 2005 from patients of all ages and comparing this information with MLST data obtained before and after PCV7 introduction. PATIENTS, MATERIALS, AND METHODS Surveillance. A case of IPD was defined as detection of pneumococci in a sample from a normally sterile site of an individual in the surveillance population of the Centers for Disease Control and Preventions (CDCs) Active Bacterial Core surveillance (ABCs) system [4, 15]. The trend over time in the incidence of IPD caused by serotype 19A was evaluated by comparing rates in 2005 to rates during 1998 1999 (defined as the prevaccine baseline period) separately for areas under continuous surveillance (i.e., areas under surveillance throughout the study period) and for all areas, including those added to the surveillance system after 1998. Areas under continuous surveillance included all of Connecticut and selected counties in California, Georgia, Maryland, Minnesota, New York, Oregon, and Tennessee. The total population in 2005 for the areas under continuous surveillance was 18,484,400 persons (1,259,400 of whom were children 5 years old) according to 2005 postcensus population estimates. Additional counties were added during 20012003, and the surveillance population ranged from 22.4 million in 2001 to 25.6 million in 2003. ABCs areas for 2004 2005 included the above areas as well as New Mexico, for an estimated total population of 27,000,000. (...truncated)