Invasive group a Streptococcal infection in older adults in long-term care facilities and the community, United States, 1998-2003 (1).

Limited information exists on the incidence and characteristics of invasive group A streptococcal (GAS) infections among residents of long-term care facilities (LTCFs). We reviewed cases of invasive GAS infections occurring among persons [greater than or equal to] 65 years of age identified through active, population-based surveillance from 1998 through 2003. We identified 1,762 invasive GAS cases among persons [greater than or equal to] 65 years, including 1,662 with known residence type (LTCF or community). Incidence of invasive GAS infection among LTCF residents compared to community-based elderly was 41.0 versus 6.9 cases per 100,000 population. LTCF case-patients were 1.5 times as likely to die from the infection as community-based case-patients (33% vs. 21%, p<0.01) but were less often hospitalized (90% vs. 95%, p<0.01). In multivariate logistic regression modeling, LTCF residence remained an independent predictor of death. Additional prevention strategies against GAS infection in this high-risk population are urgently needed.

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Although group A Streptococcus (GAS) most commonly causes pharyngitis and soft tissue infections (1), it also produces severe invasive disease including bacteremia, pneumonia, necrotizing fasciitis (NF), and streptococcal toxic shock syndrome (STSS), especially at the extremes of age (2,3). In the United States, 9,000-11,000 cases and 1,100-1,800 deaths from invasive GAS infection occur each year (3). Those [greater than or equal to] 65 years of age have the highest incidence and case-fatality rate: nearly a third of all cases and half of all deaths occur in this age group (3). In addition to advanced age, cardiac and vascular disease, diabetes, skin breakdown, corticosteroid use, and malignancy are associated with increased risk for invasive GAS infection among adults (4-8). Because underlying conditions are common among long-term care facility (LTCF) residents, this population may be especially vulnerable to invasive GAS infection. Although outbreaks of invasive GAS infections have been well described among LTCF residents (9-16), the extent and characteristics of sporadic invasive GAS infections in this population have not been well defined.

Since 1998, the Active Bacterial Core surveillance (ABCs) of the Emerging Infections Program Network (EIP)--a collaboration between the Centers for Disease Control and Prevention (CDC), state health departments, and academic centers--has collected information on residence (LTCF vs. community) of invasive GAS case-patients. We used ABCs data to compare incidence, characteristics, and factors contributing to death from invasive GAS infections of elderly LTCF residents and similar-aged persons residing in the community.

Methods

Surveillance

ABCs conducts active laboratory- and population based surveillance for invasive infections due to GAS and other bacterial pathogens of public health importance. We reviewed ABCs reports of invasive GAS cases among persons [greater than or equal to] 65 years of age occurring from January 1, 1998, through December 31, 2003, in the following sites: San Francisco, California (3 counties); Baltimore, Maryland (6 counties); Albany and Rochester, New York (15 counties); Portland, Oregon (3 counties); Chattanooga, Knoxville, Memphis, and Nashville, Tennessee (11 counties); and the entire states of Connecticut, Georgia, and Minnesota. Five counties in the Denver, Colorado, metropolitan area were added in 2000. The total surveillance area encompassed a 2000 Census population of 3,446,404 persons [greater than or equal to] 65 years of age (10% of the total US population in this age group).

ABCs methodology has been published previously (2,17). Briefly, ABCs sites maintain active contact with clinical laboratories to identify all cases and perform audits of laboratory records at least every 6 months to ensure complete reporting. Surveillance officers review case-patient medical records to obtain information on demographic characteristics, clinical syndrome, underlying disease, and illness outcome. Case-patients with GAS-positive blood cultures but without an identifiable clinical syndrome are categorized as having bacteremia without focus. Otherwise, multiple clinical syndromes--including cases of pneumonia, cellulitis, osteomyelitis, non-skin abscesses, and other syndromes (18) when accompanied by a sterile site isolate--may be reported for each case. Underlying illness information (18) was not consistently collected in Georgia from 1998-1999, Maryland from 1998-2000, or Tennessee in 1998. Information on smoking status was collected beginning in 2000 and history of cerebrovascular accident (CVA) in 2001.

Case Definitions

ABCs defines a case of invasive GAS infection as isolation of GAS from a normally sterile site (e.g., blood, cerebrospinal fluid) or from a wound when accompanied by STSS or NF in a resident of an ABCs surveillance area. ABCs defines an LTCF as a skilled nursing facility, nursing home, rehabilitation hospital, or other chronic-care facility in which the patient has been living for at least 30 days before GAS infection. The definition did not include facilities in which the patient receives daily outpatient therapy or prisons, group homes, and assisted living facilities.

To determine whether outbreaks contributed significantly to GAS disease among LTCF residents, we looked for clusters within LTCFs. We defined a GAS LTCF cluster as [greater than or equal to] 2 invasive infections with the same emm type occurring within 12 months (duration of some previously reported GAS outbreaks [10]) among residents [greater than or equal to] 65 years of age living at the same facility. Surveillance staff confirmed the residence of case-patients within each cluster.

Descriptive Epidemiology 

To describe incidence trends for persons [greater than or equal to] 65 years of age (regardless of residence type) from 1998 to 2003, we analyzed GAS cases and deaths reported from 54 ABCs counties that conducted GAS surveillance during the entire 6-year period (1998 population: 1,981,662 persons [greater than or equal to] 65 years of age). For annual rate calculations, we used national census and post-census population estimates for these counties as the annual population denominators.

To calculate incidence of invasive GAS infection among persons [greater than or equal to] 65 years of age stratified by residence type, we included ABCs GAS case-patients during the year 2000 and imputed cases with missing residence information on the basis of distribution of cases with known residence. For the denominator we used residence type specific population estimates from the US Census 2000 Summary File 1 for ABCs counties (19); census data on residence type were only available for the year 2000. To calculate national estimates of disease, we applied age- and race-specific GAS rates from the ABCs surveillance area to the age and racial distribution of the US population in 2000; we redistributed those of unknown race on the basis of the reported distribution for known cases.

For residence-specific analyses, we excluded cases of invasive GAS infection if residence was missing or unknown. To calculate case-fatality ratios (CFRs) we included only case-patients with known outcomes.

Microbiologic Testing

ABCs sites forwarded all available GAS isolates to CDC's Streptococcal Genetics Laboratory. GAS isolates underwent T typing and amplicon restriction profiling of the emm gene as described at www.cdc.gov/ncidod/biotech/strep/protocol_emm-type.htm (20). Using a reference database containing [approximately equal to] 180 group A streptococcal emm sequence types, we categorized an isolate as a given emm type if it had [greater than or equal to] 92% identity over the first 30 codons encoding the processed M protein with one of the reference emm types (21).

Antimicrobial drug susceptibility testing of available GAS isolates in 1999, 2001, and 2003 was performed at CDC by using broth microdilution. To report antimicrobial susceptibility, we used established Clinical and Laboratory Standards Institute breakpoints for MICs and defined isolates with intermediate or high-level resistance as nonsusceptible (22).

Statistical Analysis

We used SAS version 9.1 (SAS Institute Inc., Cary, NC, USA) for all analyses. To analyze incidence trends, we used Cochran-Armitage calculations for linearity and trend. In univariate analysis, we used Cochran-Mantel-Haenszel statistics to compare case-patient and GAS isolate characteristics stratified by case-patient residence; we also analyzed factors associated with death among LTCF residents and community-based case-patients separately.

We used logistic regression to characterize factors associated with death, checking for 2-way interactions and collinearity. We included in our model all variables associated with death on univariate analysis (p<0.15) controlling for age group, race, and sex. We stratified emm type into each of the 10 most common emm types and an 11th category including all remaining emm types ("other"). We classified case-patients with multiple clinical syndromes in the category with the highest CFR. The model was restricted to cases for which information on all variables was available. We considered p values <0.05 statistically significant.

Results

Disease Incidence and Estimated Disease Impact in the Elderly

From 1998 to 2003, a total of 5,889 cases of invasive GAS infection of all ages were reported, including 1,762 (30%) among persons [greater than or equal to] 65 years of age. Incidence of invasive GAS infection in this elderly age group increased from 10.0 cases per 100,000 population in 1998 to 10.9 cases per 100,000 population in 2003 (Table 1). Type of residence was available for 1,662 elderly case-patients (94%). Of these, 383 case-patients resided in LTCFs, accounting for 23% of cases in those [greater than or equal to] 65 years of age. In 2000 (the only year with reliable US Census population estimates for residence type), the incidence of invasive GAS among LTCF residents was almost 6 times higher than among community-based residents (41.0 vs. 6.9 cases per 100,000 persons, p<0.01). Projecting to the US population, we estimate that 650 cases among LTCF-residents and 2,250 cases among community-based residents [greater than or equal to] 65 years of age occurred nationwide in 2000. Among both LTCF- and community-based residents, GAS incidence was highest among black men (78.9 and 13.8 cases per 100,000 persons, respectively) and lowest among white women (35.1 and 4.9 cases per 100,000 persons, respectively).

Demographic and Clinical Characteristics

In comparison to community-based case-patients, LTCF case-patients were older (median 83 years vs. 75 years for community case-patients, p<0.01) and more frequently female (Table 2). Underlying illness information was available for 1,538 (93%) case-patients. Congestive heart failure (CHF), diabetes mellitus, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease were common in both groups. However, LTCF case-patients more frequently had CHF and a history of cerebrovascular accident but less commonly had diabetes mellitus or were current smokers than community-based case-patients. In addition, LTCF residents were less likely to have penetrating trauma preceding the infection (0.8% vs. 2.7%, p<0.05). Compared to community-based case-patients, LTCF case-patients more commonly had bacteremia without focus and pneumonia but less frequently had cutaneous or soft tissue infections as the possible source of the invasive GAS isolate identified (Table 3).

Isolate Characteristics

GAS was identified from blood cultures in 1,491 (90%) of the 1,662 elderly case-patients with known residence. Of the remaining 171 nonbacteremic patients, GAS was most commonly isolated from joint fluid (n = 57) and surgical specimens (n = 51). GAS was identified from multiple body sites in 125 (8%) case-patients.

GAS isolates were available in 1,414 (85%) of the 1,662 case-patients. From a total of 63 emm types identified, 5 (emm1, emm3, emm12, emm28, and emm89) accounted for most infections (57% among LTCF residents; 62% among community-based residents) (Table 4). Antimicrobial susceptibility testing was performed on 781 GAS isolates including 187 isolates from LTCF case-patients. Fourteen (7%) isolates from LTCF case-patients and 34 (6%) from community-based case-patients were not susceptible to erythromycin (p = 0.38). Three isolates from LTCF case-patients and 5 from community case-patients were not susceptible to levofloxacin; 2 from community case-patients were not susceptible to clindamycin. No isolates were resistant to penicillin, ampicillin, cefazolin, vancomycin, or cefotaxime.

Predictors of Death

The CFR among case-patients [greater than or equal to] 65 years of age was 24%. CFR increased with age among both LTCF- and community-based case-patients. However, when compared to the CFR for the 65- to 74-year-old group, the CFR among 75- to 84-year-old persons and those [greater than or equal to] 85 years of age was significantly greater only among community-based case-patients (Figure). LTCF case-patients were 1.5 times as likely to die from the infection as community-based GAS case-patients (33% vs. 21%, p<0.01); however, this group was less often hospitalized (90% vs. 95%, p<0.01). CFRs among hospitalized and nonhospitalized case-patients were comparable in both LTCF (33% vs. 33%, p = 0.92) and community case-patients (21% vs. 25%, p = 0.44).

Univariate analysis of LTCF case-patients showed that those with CHF had significantly higher CFR (42% with CHF died vs. 27% without CHF, p<0.01) as did those with infections caused by emml (51% vs. 28%, p<0.01) or emm3 (45% vs. 30%, p<0.05) when compared to other emm types. We also observed higher CFR among LTCF case-patients with STSS (73% vs. 31%, p<0.01), NF (64% vs. 31%, p<0.05), or pneumonia (42% vs. 30%, p<0.05) than those with other syndromes. Sex, race, and hospitalization of LTCF case-patients were not significantly associated with death. These same variables were associated with significantly higher case-fatality rates among community-based case-patients.

In the final multivariate logistic regression model, independent predictors of death included LTCF residence; lack of hospitalization; infection due to emm1, emm3, or emm12; disease manifesting as STSS, NF, pneumonia, or bacteremia without focus; and interaction between female sex and presence of congestive heart failure (Table 5). Age was not a significant risk factor associated with death.

Clustering of Cases

We identified 18 GAS clusters comprising a total of 40 cases (10% of LTCF cases). Fourteen clusters consisted of only 2 cases; the other 4 clusters had 3 cases each. The median interval between the first and second cases was 2.5 months (range 0.2-9.2 months). The most common emm types identified were emm28 and emm89, which caused 4 and 3 clusters, respectively. Case-patients in clusters were of similar age (median 85.5 years), sex (68% female), and race (75% white) to overall LTCF GAS case-patients [greater than or equal to] 65 years of age. The most common syndromes of clustered patients were cellulitis (40%) and bacteremia without focus (38%). Fifteen case-patients died (CFR 38%).

Discussion

Although the elderly have the highest rates of disease and death due to invasive GAS infection (2-4), we demonstrated that a subset of persons [greater than or equal to] 65 years of age has an even greater risk. Invasive GAS infection was almost 6 times as likely to develop in elderly LTCF residents. Moreover, such case-patients were 1.5 times more likely to die from this infection than elderly persons living in the community. LTCF case-patients with invasive GAS infection were more likely to be older, female, have a history of CHF or CVA, and have pneumonia or bacteremia without focus compared to community-based case-patients. We found no significant differences in emm type distributions and antimicrobial resistance patterns among GAS isolates that caused infections in LTCF- or community-based case-patients.

The increased risk for death among elderly case-patients living in LTCFs compared to case-patients in the community remained significant on multivariate analysis and is likely attributable, in part, to the fact that LTCF residence is a proxy measure of individual frailty. While this surveillance system collects information such as age and underlying conditions, measurements of functional status such as the Karnofsky score or activities of daily living are not obtained. The common use of advanced directives among LTCF residents may also contribute to the higher CFR. Because some directives preclude aggressive clinical management, this may also explain the lower frequency of hospitalization among LTCF case-patients.

Other factors associated with higher CFR included specific emm types and several clinical syndromes. These findings are consistent with past studies in which disease due to emm types 1 and 3 as well as the clinical syndromes pneumonia or STSS were independent predictors of death among all age groups (2). Although advancing age has been found previously to contribute to overall case-fatality rates (2,23), our analysis showed advancing age (e.g., age 75-84 years or [greater than or equal to] 85 years) was no longer significant once presence of CHF, residence type, and emm type were included in the statistical model.

[FIGURE OMITTED]

The true extent of severe GAS infections in the LTCF population is likely greater than our study estimates. First, ABCs identifies only culture-confirmed invasive GAS infections, limiting recognition of GAS syndromes such as cellulitis, for which cultures are not commonly obtained. Furthermore, current guidelines developed through expert opinion do not recommend obtaining blood cultures in residents of LTCFs, largely because of the low yield of blood cultures in this setting (24). Consequently, many LTCF practitioners do not routinely obtain blood cultures in residents with fever; residents are either treated empirically or transferred to an acute-care facility (25,26). In our

analysis of hospitalized LTCF case-patients, only 8% of positive GAS cultures were obtained before the day of hospitalization. Second, ABCs surveillance personnel have noted that residence-type is not always recorded in medical records, potentially leading to misclassification of LTCF residents as community residents. However, this misclassification would also underestimate the extent of severe GAS illness in the LTCF population.

We used available data to estimate the frequency of clusters of invasive GAS infection occurring in LTCFs. Although other studies suggest that many cases of invasive GAS may represent secondary transmission (4,23,27), we found that only 10% of cases among LTCF residents occurred within documented clusters. This finding likely represents underreporting for several reasons: use of empiric antimicrobial agents in LTCFs for mild and moderate infections; presence of disease manifestations for which cultures are not routinely obtained (e.g., cellulitis); and absence of GAS isolates (15%) for emm typing, a criterion we used to define a cluster.

Nonetheless, this study augments findings from other studies that note greater frequency of invasive bacterial infections among the elderly (27-29). Prior analyses of invasive group B streptococcal (GBS) and S. pneumoniae infections found that these infections were [approximately equal to] 4 times more common in LTCF residents than in community-dwelling elderly (28,29), likely due to the advanced age, multiple underlying conditions, and immobility in this population (30). Crowded living quarters may also play a role, as clusters of invasive GAS among healthy persons living in close proximity have been reported previously (31,32). Although less prevalent within nursing homes than illnesses such as urinary tract infection, invasive GAS, GBS, and pneumococcal diseases remain substantial causes for concern given the associated illness and higher deaths with these infections, the risk for outbreaks, and emerging antimicrobial resistance.

In addition to improved LTCF infection control practices, invasive GAS infections could be prevented with the use of an effective GAS vaccine. In the past, development of a GAS vaccine targeting the M protein, a major virulence determinant, has been halted over concerns of possible induction of antibodies that cross-react with brain, joint, and cardiac tissues (33,34). However, current vaccine candidates avoid the risks for cross-reactivity (35,36). Our analysis shows that 82% and 85% of strains causing invasive disease in both LTCF and community elderly, respectively, would be covered by the 26-valent M protein-based vaccine recently tested in phase II trials. If this vaccine also induces a protective response among older adults, it could substantially benefit LTCF residents.

In conclusion, our analysis noted that all older adults, but particularly those living in LTCFs, have significantly higher rates of disease and death from invasive GAS infection. This institutionalized population represents a unique opportunity for prevention through enhanced surveillance to improve case detection and secondary disease prevention, stringent infection control measures, and annual immunization against influenza, a disease for which GAS is a known secondary infection (14,16,23). Finally, vaccination of this population with an effective GAS vaccine may be highly beneficial.

Acknowledgments

We thank Elizabeth Zell, Carolyn Wright, and Ben Kupronis for their substantial contributions to the statistical analysis for this article; Delois Jackson, Varja Sakota, and other members of CDC's Streptococcus Laboratory for streptococcal typing; and the participating clinical laboratories and ABCs staff within each EIP site who made this study possible.

Funding for this study came from the Emerging Infections Program, CDC, Atlanta, Georgia.

Dr Thigpen works for the Division of HIV/AIDS Prevention at CDC. He developed this project to analyze national data from CDC's ABCs system to determine the incidence and case-characteristics of invasive GAS among the elderly.

References

(1.) Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005;5:685-94.

(2.) O'Brien KL, Beall B, Barrett NL, Cieslak PR, Reingold A, Farley MM, et al.; Active Bacterial Core Surveillance/Emerging Infections Program Network. Epidemiology of invasive group A streptococcus disease in the United States, 1995-1999. Clin Infect Dis. 2002;35:268-76.

(3.) Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs) reports, Emerging Infections Program Network: group A Streptococcus 1998-2003 [cited 2007 Aug 7]. Available from http://www.cdc.gov/ncidod/dbmd/abcs/survreports.htm

(4.) Davies HD, McGeer A, Schwartz B, Green K, Cann D, Simor AE, et al. Invasive group A streptococcal infections in Ontario, Canada. N Engl J Med. 1996;335:547-54.

(5.) Hoge CW, Schwartz B, Talkington DF, Breiman RF, MacNeill EM, Englender SJ. The changing epidemiology of invasive group A streptococcal infections and the emergence of streptococcal toxic shock-like syndrome. A retrospective population-based study. JAMA. 1993;269:384-9.

(6.) Stevens DL. Invasive group A Streptococcus infections. Clin Infect Dis. 1992;14:2-11.

(7.) Factor SH, Levine OS, Schwartz B, Harrison LH, Farley MM, McGeer A, et al. Invasive group A streptococcal disease: risk factors for adults. Emerg Infect Dis. 2003;9:970-7.

(8.) Arnold KE, Schweitzer JL, Wallace B, Salter M, Neeman R, Hlady WG, et al. Tightly clustered group A streptococcal outbreak in a long-term care facility. Infect Control Hosp Epidemiol. 2006;27:1377-84.

(9.) Barnham M, Kerby J. Streptococcus pyogenes pneumonia in residential homes: probable spread of infection from the staff. J Hosp Infect. 1981;2:255-7.

(10.) Ruben FL, Norden CW, Heisler B, Korica Y. An outbreak of Streptococcus pyogenes infections in a nursing home. Ann Intern Med. 1984; 101:494-6.

(11.) Centers for Disease Control and Prevention. Epidemiologic notes and reports nursing home outbreaks of invasive group A streptococcal infections--Illinois, Kansas, North Carolina, and Texas. MMWR Morb Mortal Wkly Rep. 1990;39:577-9.

(12.) Auerbach SB, Schwartz B, Williams D, Fiorilli MG, Adimora AA, Breiman RF, et al. Outbreak of invasive group A streptococcal infections in a nursing home: lessons on prevention and control. Arch Intern Med. 1992;152:1017-22.

(13.) Harkness GA, Bentley DW, Mottley M, Lee J. Streptococcus pyogenes outbreak in a long-term care facility. Am J Infect Control. 1992;20:142-8.

(14.) Schwartz B, Ussery XT. Group A streptococcal outbreaks in nursing homes. Infect Control Hosp Epidemiol. 1992;13:742-7.

(15.) Greene CM, Van Beneden CA, Javadi M, Skoff TH, Beall B, Facklam R, et al. Cluster of deaths from group A Streptococcus in a long-term care facility--Georgia, 2001. Am J Infect Control. 2005;33:108-13.

(16.) Thigpen MC, Thomas DM, Gloss D, Park SY, Khan AJ, Fogelman VL, et al. Nursing home outbreak of invasive group A streptococcal infections caused by two distinct strains. Infect Control Hosp Epidemiol. 2007;28:68-74.

(17.) Centers for Disease Control and Prevention. Active Bacterial Core Surveillance: methodology [cited 2007 Aug 7]. Available from http://www.cdc.gov/ncidod/dbmd/abcs/methodology.htm

(18.) Centers for Disease Control and Prevention. Active Bacterial Core Surveillance: case report form [cited 2007 Aug 7]. Available from http://www.cdc.gov/ncidod/dbmd/abcs/

(19.) US Census Bureau. Census 2000 Summary File 1 [cited 2007 Aug 7]. Available from http://www.census.gov/press-release/www/2001/ sumfile1.html

(20.) Espinosa LE, Li Z, Gomez Barreto D, Calderon Jaimes E, Rodriguez RS, Sakota V, et al. M protein gene type distribution among group A streptococcal clinical isolates recovered in Mexico City, Mexico, from 1991 to 2000, and Durango, Mexico, from 1998 to 1999: overlap with type distribution within the United States. J Clin Microbiol. 2003;41:373-8.

(21.) Centers for Disease Control and Prevention. Streptococcus pyogenes emm sequence database [cited 2007 Aug 7]. Available from http:// www.cdc.gov/ncidod/biotech/strep/strepindex.htm

(22.) Performance standards for antimicrobial susceptibility testing: sixteenth informational supplement. CLSI document M100-S16. Vol 26. Wayne (PA): Clinical and Laboratory Standards Institute; 2006.

(23.) Muller MP, Low DE, Green KA, Simor AE, Loeb M, Gregson D, et al. Clinical and epidemiologic features of group A streptococcal pneumonia in Ontario, Canada. Arch Intern Med. 2003;163:467-72.

(24.) Bentley DW, Bradley S, High K, Schoenbaum S, Taler G, Yoshikawa TT. Practice guidelines for evaluation of fever and infection in long-term care facilities. Clin Infect Dis. 2000;31:640-53.

(25.) Nicolle LE, Bentley D, Garibaldi R, Neuhaus E, Smith P. Antimicrobial use in long-term care facilities. Infect Control Hosp Epidemiol. 2000;21:537-45.

(26.) Richards CL Jr, Steele L. Antimicrobial-resistant bacteria in long-term care facilities: infection control considerations. J Am Med Dir Assoc. 2003;4:S110-4.

(27.) Zurawski CA, Bardsley M, Beall B, Elliott JA, Facklam R, Schwartz B, et al. Invasive group A streptococcal disease in metropolitan Atlanta: a population-based assessment. Clin Infect Dis. 1998;27:150-7.

(28.) Henning KJ, Hall EL, Dwyer DM, Billmann L, Schuchat A, Johnson JA, et al. Invasive group B streptococcal disease in Maryland nursing home residents. J Infect Dis. 2001; 183:1138-42.

(29.) Kupronis BA, Richards CL Jr, Whitney CG. Invasive pneumococcal disease in older adults residing in long-term care facilities and in the community. J Am Geriatr Soc. 2003;5l: 1520-5.

(30.) Loeb M, McGeer A, McArthur M, Walter S, Simor AE. Risk factors for pneumonia and other lower respiratory tract infections in elderly residents of long-term care facilities. Arch Intern Med. 1999;159:2058-64.

(31.) Centers for Disease Control and Prevention. Outbreak of group A streptococcal pneumonia among Marine Corps recruits--California, November 1-December 20, 2002. MMWR Morb Mortal Wkly Rep. 2003;52:106-9.

(32.) Roy S, Kaplan EL, Rodriguez B, Schreiber JR, Salata RA, Palavecino E, et al. A family cluster of five cases of group A streptococcal pneumonia. Pediatrics. 2003;112:e61-5.

(33.) Cunningham MW. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev. 2000;13:470-511.

(34.) Kotloff KL, Dale JB. Progress in group A streptococcal vaccine development. Pediatr Infect Dis J. 2004;23:765-6.

(35.) Hu MC, Walls MA, Stroop SD, Reddish MA, Beall B, Dale JB. immunogenicity of a 26-valent group A streptococcal vaccine. Infect Immun. 2002;70:2171-7.

(36.) McNeil SA, Halperin SA, Langley JM, Smith B, Warren A, Sharratt GP, et al. Safety and immunogenicity of 26-valent group A Streptococcus vaccine in healthy adult volunteers. Clin Infect Dis. 2005;41:1114-22.

Address for correspondence: Michael C. Thigpen, Centers for Disease Control, 1600 Clifton Rd, Mailstop E45, Atlanta, GA 30333, USA; email: [e-mail]

(1) Presented at the 42nd Annual Meeting of the Infectious Diseases Society of America, September 30-October 3, 2004, Boston, Massachusetts, USA.

Michael C. Thigpen, * Chesley L. Richards Jr., * Ruth Lynfield, ([dagger]) Nancy L. Barrett, ([double dagger]) Lee H. Harrison, ([section]) Kathryn E. Arnold, ([paragraph]) Arthur Reingold, # Nancy M. Bennett, ** Allen S. Craig, ([dagger])([dagger[) Ken Gershman, ([double dagger])([double dagger]) Paul R. Cieslak, ([section])([section]) Paige Lewis, * Carolyn M. Greene, * Bernard Beall, * and Chris A. Van Beneden, * for the Active Bacterial Core surveillance/Emerging Infections Program Network

* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) Minnesota Department of Health, Minneapolis, Minnesota, USA; ([double dagger]) Connecticut Department of Public Health, Hartford, Connecticut, USA; ([section]) Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; ([paragraph]) Georgia Department of Human Resources, Atlanta, Georgia, USA; # University of California at Berkeley School of Public Health, Berkeley, California, USA; ** University of Rochester School of Medicine and Dentistry, Rochester, New York, USA; ([dagger])([dagger]) Tennessee Department of Health, Nashville, Tennessee, USA; ([double dagger])([double dagger]) Colorado Department of Public Health and Environment, Denver, Colorado, USA; and ([section])[(section]) Oregon State Public Health, Portland, Oregon, USA

Table 1. Invasive group A streptococcal infection cases and
deaths among persons age [greater than or equal to] 65 y,
by site, ABCs areas, 1998-2003 *

                    1998   1999   2000   2001   2002   2003
No. cases/100,000
population

  CA                 8.4   10.3   11.1    9.8    7.6    9.5
  CT                 8.7    9.4   11.3    9.8   10.2   11.5
  GA                10.5    7.3    9.7   12.5    6.4    9.5
  MD                13.7    9.0    9.3   15.4   11.4   15.3
  MN                11.4   10.5   10.6   13.1   10.3    9.8
  NY                 7.7   12.6   10.3   10.2   12.9   10.2
  OR                 9.2    6.5    4.0    4.6    6.6    9.0
  All sites         10.0    9.3   10.0   11.1    9.2   10.9

No. deaths/100,000
population

  All sites          2.2   1.9   2.3   2.2   2.2   2.6

*ABCs (Active Bacterial Core surveillance) areas: San Francisco,
California (3 counties), Connecticut (entire state), Atlanta,
Georgia, metropolitan area (20 counties), Baltimore, Maryland
(6 counties), Minneapolis/St. Paul, Minnesota (7 counties),
Rochester, New York (7 counties), and Portland, Oregon
(3 counties).

Table 2. Characteristics of persons age [greater than or
equal to] 65 y with invasive group A streptococcal infection
by known residence, ABCs areas, 1998-2003 *

                                  No. LTCF      No. community-based
                                case-patients    case-patients (%),
Characteristic                  (%), n = 383         n = 1,279

Age, y
  65-74                           72 (18.8)         584 (45.7)
  75-84                          149 (38.9)         465 (63.3)
  [greater than or
    equal to] 85                 162 (42.3)         230 (18.0)

Female sex                       238 (62.1)         626 (48.9)

Race [dagger]
  White                          282 (82.5)         914 (78.9)
  Black                           50 (14.6)         182 (15.7)
  Other                           10 (2.9)           63 (5.4)

Case-fatality ([dagger])         124 (32.6)         268 (21.1)
Hospitalization ([dagger])       346 (90.3)         1211 (94.8)
Presence of underlying
  illnesses ([dagger])
    Congestive heart failure     104 (29.3)         237 (20.5)
    Cerebrovascular accident      39 (16.8)          71 (9.4)
    Diabetes mellitus             86 (24.2)         346 (30.0)
    Current smoker                 6 (2.1)           61 (6.5)
    Chronic obstructive
      pulmonary disease           62 (17.5)         172 (14.9)
    Atherosclerotic
      cardiovascular disease      95 (26.7)         351 (30.4)
    Renal failure/dialysis        30 (8.5)           103 (8.9)
    Alcohol abuse                 19 (5.4)           48 (4.2)
    Immunosuppressive
      therapy ([double dagger])   19 (5.4)           87 (7.5)

Characteristic                  p value

Age, y                           <0.01
  65-74
  75-84
  [greater than or
    equal to] 85

Female sex                       <0.01

Race ([dagger])                   0.16
  White
  Black
  Other


Case-fatality ([dagger])         <0.01
Hospitalization ([dagger])       <0.01
Presence of underlying
  illnesses ([dagger])
    Congestive heart failure     <0.01
    Cerebrovascular accident     <0.01
    Diabetes mellitus            <0.05
    Current smoker               <0.01
    Chronic obstructive
      pulmonary disease          0.24
    Atherosclerotic
      cardiovascular disease     0.19
    Renal failure/dialysis       0.78
    Alcohol abuse                0.34
    Immunosuppressive
      therapy ([double dagger])  0.16

* ABCs, Active Bacterial Core surveillance; LTCF, long-term
care facility. Case-patients with missing responses for
residence type or individual characteristics were excluded
from analysis.

([dagger]) Data were not available for all case-patients.
Denominators by residence varied for the following: race
(LTCF 342, community 1,159), outcome (LTCF 380, community
1,270), hospitalization (LTCF 383, community 1,278),
underlying illnesses (LTCF 355, community 1,154) except
for cerebrovascular accident (LTCF 232, community 758) and
current smoker (LTCF 285, community 936).

([double dagger]) Includes steroids chemothera y and
radiation therapy.

Table 3. Clinical syndromes areas among persons [greater than or
equal to] 65 y with invasive group A streptococcal infection,
by residence and overall GFR, ABCs 1998-2003 *

                              No. LTCF      No. community-based
                            case-patients   case-patients (%),
Clinical syndrome              N = 383           N = 1,279

Bacteremia without focus     145 (37.9)         406 (31.7)
Pneumoniat                    97 (25.3)         225 (17.6)
Cellulitist                  121 (31.6)         498 (38.9)
Septic arthritis ([dagger])   20 (5.2)           90 (7.0)
Osteomyelitis ([dagger])       7 (1.8)           26 (2.0)
STSS                          15 (3.9)           82 (6.4)
Necrotizing fasciitis         15 (3.9)           80 (6.3)
Abscess ([dagger]
  [double dagger])             8 (2.3)           47 (3.9)

                                                  Overall
Clinical syndrome              p value            CFR, %

Bacteremia without focus        <0.05              25.1
Pneumoniat                      <0.01              34.0
Cellulitist                     <0.01              16.3
Septic arthritis ([dagger])      0.21               11.8
Osteomyelitis ([dagger])         0.80                6.1
STSS                             0.07               55.7
Necrotizing fasciitis            0.08               36.6
Abscess ([dagger]
  [double dagger])               0.15               14.5

* CFR, case-fatality ratio; ABCs, Active Bacterial Core
surveillance; LTCF, long-term care facility; STSS,
streptococcal toxic shock syndrome. Case- patients with
missing responses for residence type, outcome, or clinical
syndrome were excluded from analysis. Data for case-patients
could be categorized under [greater than or equal to] 1
syndrome except for case-patients identified as having
bacteremia without a focus.

([dagger]) Occurring in conjunction with isolation of
group A streptococcal infection from a sterile site
(e.g., blood culture).

([double dagger]) Data not available for all years.
Denominators: LTCF 349; community 1,205.

Table 4. Most common emm types identified in persons
[greater than or equal to] 65 y with invasive group A
streptococcal infection, by residence, ABCs areas,
1998-2003 *

           No. LTCF case-patients   No. community-based
                (%), N = 324           case-patients
emm type                                 N = 1,090

1                55 (17.0)              233 (21.4)
3                44 (13.6)              141 (12.9)
28               39 (12.0)              122 (11.2)
12                21 (6.5)              116 (10.6)
89                27 (8.3)               61 (5.6)
77                9 (2.8)                39 (3.6)
6                 12 (3.7)               22 (2.0)
18                6 (1.9)                28 (2.6)
11                10 (3.1)               23 (2.1)
4                 11 (3.4)               21 (1.9)

* ABCs, Active Bacterial Core surveillance, LTCF, long-term
care facility. Case-patients with missing responses for
residence type and emm type were excluded from analysis.
Table stratified by overall frequency.

Table 5. Results of multivariate logistic regression analysis
of factors associated with death from invasive group A
streptococcal infection among case-patients [greater than
or equal to] 65 y of age, ABCs areas, 1998-2003 *

Characteristic                    Adjusted odds ratio (95% CI)

Age group, y
  [greater than or equal to] 85          1.4 (0.9-2.1)
  75-84                                  1.2 (0.8-1.8)
  65-74                                    Reference

Race
  Black                                  0.8 (0.5-1.2)
  Other than black                         Reference

Residence
  Long-term care facility                1.6 (1.1-2.2)
  Community                                Reference

Hospitalized
  Hospitalized                           0.5 (0.3-0.9)
  Not hospitalized                         Reference

Syndrome
  Bacteremia without focus               2.6 (1.7-3.8)
  Pneumonia                              3.7 (2.4-5.8)
  Necrotizing fasciitis                  3.6 (1.7-7.4)
  STSS                                  11.1 (6.4-19.3)
  Other syndrome                           Reference

emm type
  emm1                                   2.3 (1.4-3.6)
  emm3                                   1.9 (1.1-3.1)
  emm4                                   1.7 (0.6-4.5)
  emm6                                   0.6 (0.2-2.1)
  emmll                                  0.4 (0.1-2.0)
  emm12                                  1.9 (1.1-3.4)
  emm18                                  1.3 (0.5-3.9)
  emm28                                  0.9 (0.5-1.7)
  emm77                                  1.3 (0.5-3.4)
  emm89                                  1.5 (0.8-3.0)
  Other emm types                          Reference

Sex and history of CHF ([dagger])
  Females with CHF                       2.4 (1.5-3.8)
  Females without CHF                    0.9 (0.7-1.4)
  Males with CHF                         1.2 (0.7-2.0)
  Males without CHF                        Reference

* ABCs, Active Bacterial Core Surveillance; CI, confidence
interval; STSS, streptococcal toxic shock syndrome; CHF,
congestive heart failure. A total of 1,140 case-patients
with complete data were included in the final model.
Significant results are shown in boldface.

([dagger]) Interaction between sex and history of CHF.