Skip Navigation

Epidemiology of Invasive Group A Streptococcus Disease in the United States, 1995–1999

  1. Katherine L. O'Brien1,a,
  2. Bernard Beall1,
  3. Nancy L. Barrett6,
  4. Paul R. Cieslak7,
  5. Arthur Reingold8,9,
  6. Monica M. Farley3,4,5,
  7. Richard Danila10,
  8. Elizabeth R. Zell2,
  9. Richard Facklam1,
  10. Benjamin Schwartz1,
  11. Anne Schuchat1, and
  12. Active Bacterial Core Surveillance/Emerging Infections Program Network
  1. 1Respiratory Diseases, Georgia
  2. 2Biostatistics and Information Management Branches, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Georgia
  3. 3Emerging Infections Program, Georgia Department of Human Resources, Georgia
  4. 4Emory University School of Medicine, Georgia
  5. 5Atlanta VA Medical Center, Georgia
  6. 6Emerging Infections Program, Connecticut Department of Public Health, Hartford
  7. 7Emerging Infections Program, Health Division, Oregon Department of Human Resources, Portland
  8. 8California Emerging Infections Program, Berkeley
  9. 9School of Public Health, University of California, Berkeley
  10. 10Emerging Infections Program, Minnesota Department of Health, Minneapolis
  1. Reprints or correspondence: Dr. Katherine L. O'Brien, 621 N. Washington St., Baltimore, MD 21205 (klobrien{at}jhsph.edu).

  1. Presented in part: 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, 28 September—1 October 1997 (abstract K-159), and 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, 24–27 September 1998 (abstract L-098).

  • ↵a Present affiliation: Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

 
Next Section

Abstract

Severe invasive group A streptococcal (GAS) disease is believed to have reemerged during the past 10–20 years. We conducted active, laboratory, population-based surveillance in 5 US states (total population, 13,214,992). From 1 July 1995 through 31 December 1999, we identified 2002 episodes of invasive GAS (3.5 cases per 100,000 persons). Rates varied by age (higher among those <2 or ⩾65 years old), surveillance area, and race (higher among black individuals) but did not increase during the study period. The 5 most common emm types (1, 28, 12, 3, and 11) accounted for 49.2% of isolates; newly characterized emm types accounted for 8.9% of isolates. Older age; presence of streptococcal toxic shock syndrome, meningitis, or pneumonia; and infection with emm1 or emm3 were all independent predictors of death. We estimate that 9600–9700 cases of invasive GAS disease occur in the United States each year, resulting in 1100–1300 deaths.

Group A Streptococcus (GAS) causes invasive, noninvasive, and nonsuppurative diseases. Invasive GAS infections include, among others, bacteremia, pneumonia, puerperal sepsis, necrotizing fasciitis (NF), and streptococcal toxic shock syndrome (STSS) [1, 2]. Nonsuppurative GAS diseases, acute rheumatic fever, and poststreptococcal glomerulonephritis are now uncommon in the United States; however, outbreaks do occur, and such diseases remain important causes of morbidity and mortality globally [3–16].

Beginning in the 1980s, reports suggested a shift in the epidemiology of GAS disease toward the occurrence of more-severe clinical illness [17–22]. The first modern era report of GAS causing a toxic shock—like syndrome was published in the Czechoslovakian literature in 1984 [19, 23], followed by numerous reports from the United States and Europe [18, 21, 24, 25]. The only population-based study from the United States at that time also concluded that a toxic shock—like syndrome caused by GAS had emerged [26]. Subsequently, a case definition for this condition was established [27]. Contemporaneously, laboratory studies revealed an increase in isolates that expressed M protein types 1 and 3 [28, 29]. Hospital-based reports suggested that the occurrence of more-severe GAS disease was accompanied by increases in GAS disease incidence [15, 25, 30, 31], but such an increase was not found in the only available population-based surveillance study [26]. Indeed, the annual rate of invasive GAS disease among defined populations in the United States has been documented to range from 2.6 to 6.8 cases per 100,000 persons, and fluctuations in the annual incidence are certain to exist [17]. The absence of longitudinal population-based surveillance covering large populations in the United States has limited generalizations about real trends in the incidence of invasive GAS infection and in the characteristics of the organism itself.

Methods to prevent or control GAS disease have been limited and currently center on accurate diagnosis and timely, appropriate use of antimicrobial therapy. New efforts at disease prevention are focused on vaccine development, an important component of which involves the accurate assessment of the disease burden and characterization of disease-causing isolates.

In the present article, we describe the burden and emm type distribution of invasive GAS infections in the United States between 1995 and 1999 that were found using population-based active surveillance. Our goals were to determine whether invasive GAS infections have increased in incidence and to provide strain information that can be used in vaccine development.

Previous SectionNext Section

Materials and Methods

Surveillance. We conducted population-based, active laboratory surveillance for invasive Streptococcus pyogenes (GAS) from 1 July 1995 through 31 December 1999 in the following regions: Atlanta, Georgia (Cobb, Clayton, Dekalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale counties); Minneapolis/St. Paul, Minnesota (Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, and Washington counties); Portland, Oregon (Clackamas, Multnomah, and Washington counties); the San Francisco Bay area, California (Alameda, Contra Costa, and San Francisco counties); and all of Connecticut. The estimated 1999 aggregate population was 13,214,992 (4.8% of the US population). All clinical microbiology laboratories that processed cultures of samples from normally sterile sites were contacted at least monthly, laboratory records were searched for cases, and audits were conducted every 6 months to identify missed cases. A case was defined by the isolation of GAS from a normally sterile site in a resident of the surveillance area or isolation of GAS from a nonsterile site (e.g., wound culture) in conjunction with NF. This study was reviewed by the Institutional Review Boards of the Centers for Disease Control and Prevention and participating institutions. US Department of Health and Human Services guidelines for conduct of studies were followed.

Clinical syndromes and underlying disease information were determined by chart review or reports from infection-control practitioners. Case patients who had positive results of blood culture for GAS but for whom no clinical syndrome was identified were categorized as having only bacteremia without a source; for all other case patients, data could be categorized under multiple clinical syndromes. Surveillance sites identified case patients as having STSS by reviewing the charts and assessing whether the published case definition was met [27] or by noting that a diagnosis of STSS had been made by the treating physician, with or without fulfillment of the case definition. Case patients were categorized as having NF if this diagnosis was documented in the chart (with or without confirmation by pathologic examination) or if necrosis of tissue was noted on a pathologic or surgical report. Skin and soft-tissue infections included cellulitis, infected ulcers, erisypelas, wound infections, lymphangitis, lymphadenitis, phlebitis, bursitis without a positive culture of joint fluid for GAS, and tenosynovitis but excluded NF. Nosocomial acquisition was presumed to have occurred if the culture was done ⩾3 days after admission.

GAS typing. GAS isolates were sent to the Centers for Disease Control and Prevention (CDC) for identity confirmation and typing. Isolates were typed on the basis of opacity factor reaction, T typing, and sequencing of the variable M protein type—specific region of emm gene amplicons [32–35]. A near-absolute concordance has been established between the 5′ emm variable region sequence type and M serotype [33, 34, 36, 37]; a listing of types can be found at http://www.cdc.gov/ncidod/biotech/infotech_hp.html. We considered any type other than emm types 1–93 to be a newly characterized type—these likely represented some of those types that were listed elsewhere as nontypeable when rabbit antisera were used.

Descriptive epidemiology. Descriptive analyses were conducted that included all cases with onset from 1 July 1995 through 31 December 1999. Incidence calculations included only those cases with onset from 1 January 1996 through 31 December 1999. We used regional and national postcensus population estimates for each year as the denominator values. National estimates of the incidence of cases and the number of deaths due to GAS were calculated by multiplication of the aggregate age- and race-specific incidence in the surveillance areas by the population figures for the United States. Individuals of unknown race (44 in 1996, 53 in 1997, 54 in 1998, and 88 in 1999) were assigned to racial groups on the basis of the proportion observed among those with known race. Case-fatality ratios (CFRs) were calculated on the basis of the number of cases for which the outcome was known (99.3%).

Multivariable models. Risk factors for death were evaluated by use of univariate and multivariable analyses. All variables associated with death in a univariate analysis, as well as age group and race data, were included in a Poisson regression model in which death was the outcome variable. Mutually exclusive clinical syndromes, in descending order of CFR (i.e., STSS, meningitis, pneumonia, NF, bacteremia without a source, abdominal/peritoneal infection, cellulitis, osteomyelitis, and septic arthritis), and emm type (i.e., type 1, type 3, or other emm types) were covariates. Case patients with multiple clinical syndromes were classified in the category of highest severity. The model was restricted to cases for which information on all variables was available; thus, cases caused by GAS with unknown emm types (n = 411) and for which the outcome was unknown (n = 14) were excluded. All 2-way interactions were evaluated. Variables were considered to be associated with death at α < .05. All univariate and multivariable analyses were conducted by use of SAS software (version 8 for Windows).

Previous SectionNext Section

Results

Disease rates. From 1 July 1995 through 31 December 1999, 2002 cases of invasive GAS disease were identified in 2002 patients in the 5 surveillance areas. The average annual incidence of invasive GAS disease for these years was 3.5 cases per 100,000 persons. The incidence of disease varied by area, from 2.2 to 4.8 cases per 100,000 persons (in Georgia and California, respectively), but did not vary significantly from year to year in any individual area (table 1). The overall incidence varied by season, with the preponderance of disease occurring in the winter and early spring (figure 1).

Figure 1
Figure 1

Monthly distribution of invasive group A Streptococcus disease in 5 regions in the United States, 1 January 1996 through 31 December 1999.

The incidence varied substantially by race and age (figure 2). The incidence was highest among those ⩾65 years old (9.3 cases per 100,000 persons), followed by those <2 years old (6.3 cases per 100,000 persons). Infection was 1.6 times more likely to occur among black persons than among those of other race (95% CI, 1.4–1.7). Age- and race-adjustment of the surveillance data to the US population yielded an annual incidence of 3.6 cases per 100,000 people, or an estimated 9600–9700 annual cases. The incidence of GAS-associated NF and STSS varied by year, surveillance area, and age group; however, no consistent increase or decrease in disease incidence was evident across any of these strata.

Figure 2
Figure 2

Incidence of invasive group A Streptococcus disease, by age and race. Age-specific case-fatality ratio (CFR) for all races combined is shown by the black line. Dark columns, black race; light columns, other race.

Underlying diseases. The proportion of patients who had cases of invasive GAS disease 1998 and 1999 and had various underlying diseases is shown in table 2. Underlying disease information was collected for 577 (74.1%) of the 779 cases that had onset during these 2 years; underlying disease information for Georgia was not reported for this period of surveillance. HIV infection was more commonly reported among case patients in California than among case patients in the other 3 states for which this information was available (RR, 4.8; P < .001). Injection drug use was more commonly reported among case patients from Oregon and California than among case patients from Connecticut and Minnesota (RR, 5.0; P < .001). After exclusion of those patients with HIV infection or a history of injection drug use, there were no substantial differences in the proportion of case patients with an underlying disease by surveillance area (Connecticut, 84.4%; Oregon, 83.0%; California, 76.6%; and Minnesota, 76.2%). Overall, 82.7% (range, by geographic region, 77.3%–86.8%) of case patients with invasive GAS disease had at least 1 underlying condition. Varicella was noted in 5 (6.3%) of 79 case patients <10 years old and only 4 (0.6%) of 700 patients ⩾10 years old.

Table 1
Table 1

Incidence of invasive group A Streptococcus (GAS) disease, by region and year, in the United States, 1 January 1996 through 31 December 1999.

Table 2
Table 2

Underlying conditions reported among case patients with invasive group A Streptococcus disease in 1998 and 1999, by surveillance area.

Clinical syndromes. The distribution of clinical syndromes among age groups is shown in table 3. Compared with those age ⩾10 years, those age <10 years were less likely to present with a cutaneous/soft-tissue infection, NF, STSS, or endocarditis/pericarditis and were more likely to present with bacteremia without a source, osteomyelitis, or a CNS infection. Pregnancy-related infections accounted for 36 (1.8%) of all invasive GAS cases.

Table 3
Table 3

Clinical syndromes among case patients with invasive group A Streptococcus disease, by age group, and all-age case-fatality ratios (CFRs), 1 July 1995 through 31 December 1999.

The overall CFR for invasive GAS disease was 12.5%. CFRs varied substantially by age and clinical syndrome (table 3; figure 2). Case patients <30 years old were at extremely low risk of death; risk of death increased with each age category (P < .001; χ2 test for trend). The highest CFR was observed among case patients with STSS (44.5%). Among those with NF, the CFR varied substantially, depending on whether the patient also had STSS (41.4% for case patients with STSS and 22.1% for those without STSS). Among patients with neither STSS nor NF, the CFR was 10.1%.

Of the 2002 cases included in our study, GAS was isolated from blood samples in 1485 (74.2%). Among the 517 (25.8%) case patients without documented bacteremia, GAS was isolated from surgical specimens (234 case patients [11.7%]), joint fluid (167 case patients [8.3%]), peritoneal fluid (37 case patients [1.8%]), pleural fluid (36 case patients [1.8%]), bone (17 case patients [0.8%]), CSF (14 case patients [0.7%]), wound specimens (6 case patients [0.3%]), abscess specimens (4 case patients [0.2%]), pericardial fluid (1 case patient [0.05%]), and fluid from the uterus (1 case patient [0.05%]). One hundred nine (5.4%) of the 2002 cases were categorized as having been nosocomially acquired. Of the cases that were related to pregnancy, 5 (13.9%) were categorized as having been nosocomially acquired.

emm sequence types. Of the 2002 cases included in our study, isolates from 1586 (79.2%) were available for evaluation. In the remaining cases, isolates were not obtained, did not survive, or (in a small number of cases) did not produce PCR product. Among those 1586 isolates, the 10 most common emm types were types 1 (20.8%), 28 (9.2%), 12 (7.6%), 3 (7.1%), 11 (4.5%), 4 (4.1%), 114 (3.9%), 89 (3.2%), 77 (3.1%), and 33 (2.5%). The 5 most common types accounted for 49.5% of isolates, and the 10 most common types accounted for 66.0% of isolates identified; 80% of isolates were accounted for by 17 different emm types. The proportion of disease caused by each type varied over the course of time and by surveillance area (data not shown). Only emm types 1, 28, 12, 3, and 11 ranked among the 10 most common in all surveillance areas for the 1995–1999 time period.

Newly characterized emm types accounted for 8.9% of isolates evaluated. One of these, emm114 [38, 39], ranked as the second most common type identified in California, the third most common in Oregon, and seventh most common overall.

Predictors of clinical syndromes. We evaluated the association between emm type and the presence of various clinical syndromes. In a univariate analysis, emm1 strains were associated with STSS (RR, 2.0; P < .001) and pneumonia (RR, 1.7; P < .001); emm3 strains, with STSS (RR, 2.7; P < .001) and NF (RR, 2.9; P < .001); and emm28 strains, with pregnancy-related infections (RR, 4.3; P < .001). We also evaluated whether the presence of underlying conditions was a predictor of clinical syndrome and found that individuals with STSS were more likely than those without STSS to have at least 1 underlying medical condition (94.9% vs. 81.8%, respectively; RR, 1.2; P = .04).

In a multivariable Poisson regression analysis, we assessed predictors of death (table 4). When the analysis was controlled for race, we found that increasing age, disease syndrome (pneumonia, meningitis, or STSS), and emm type (types 1 and 3) were all independent predictors of death.

Table 4
Table 4

Results of multivariable analysis of factors associated with death due to invasive group A Streptococcus disease for cases reported from 1 July 1995 through 31 December 1999.

Previous SectionNext Section

Discussion

The results of our population-based, active surveillance of 5 regions in the United States demonstrate that the incidence of invasive GAS infections was stable between 1996 and 1999. Compared with incidence rates of GAS infection reported by hospital-based or small regional studies done during the 1980s and 1990s, there has been no apparent increase in the incidence since the 1980s. It has been suggested that a transient increase in incidence occurred in the mid- to late 1980s [40]. However, by combining our results for the incidence of invasive GAS disease in Georgia (2.2 cases per 100,000 persons) with those of a 1994–1995 report from the same area (5.2 cases per 100,000 persons) [41], it is evident that variations in the incidence of invasive GAS disease within a region over the course of short periods of time do occur. This likely reflects a combination of the population's susceptibility to particular emm types and variation in the predominant emm types circulating within a community. The relative importance of any individual emm type in the proportion of invasive disease it causes is likely a combination of the relative frequency of strain circulation within a community, the invasiveness of that strain, and the degree of individual and population-level immunity to that strain. Without contemporaneous data on the prevalence of emm strains that circulate in the community but do not cause disease, no conclusions can be drawn about the relative invasiveness of a strain.

In all geographic areas and for all time periods, the incidence of invasive GAS disease among black individuals was higher than the incidence among those of other race. The source of this disparity in incidence is not clear, but the disparity may be due to differences in the prevalence of underlying diseases, socioeconomic conditions, or other, as-yet-uncharacterized risk factors.

Invasive GAS disease results in significant morbidity and mortality. We estimate that, each year in the United States, there are 9600–9700 cases of invasive GAS disease and 1100–1300 resulting deaths, or ∼3–4 times the number of cases of meningococcal disease and resulting deaths. The burden of invasive GAS disease is concentrated at the extremes of age, with the highest incidence of both disease and death in the elderly population, whereas the incidence of meningococcal disease and associated death is concentrated among younger people.

We found that the distribution of GAS emm types varied by geographic region and by year. GAS strains with newly characterized emm types are a significant cause of disease. These strains are more likely to be those that previously were characterized as nontypeable when available rabbit antisera were used than to be strains that had newly emerged [39]. Isolates with newly characterized emm sequence types were most common at the West Coast surveillance sites. The reason for this is not known, but it may reflect introduction from other countries. emm typing of strains from countries in Asia and Latin America indicates that the proportion of strains of newly characterized emm types is significantly greater than that among isolates collected in the United States [42–44]. The present study also shows that emm types are important predictors of clinical syndrome and mortality.

Current strategies for preventing morbidity and mortality resulting from invasive GAS infection are limited. The treatment of STSS with intravenous immunoglobulin and of NF with clindamycin and surgical intervention has been associated with lower mortality in observational studies [1, 45, 46]. Some cases of invasive GAS disease may be prevented through the increased use of varicella vaccine in children [1, 47], chemoprophylaxis of selected contacts of patients with invasive infection [1], improved infection control [1], and prompt investigation of outbreaks in hospitals and nursing homes [48, 49]. Prevention through vaccination against GAS could have a much greater impact than these interventions. Currently, several candidate GAS vaccines are being developed, and some are entering clinical trials. These include targets such as C5a peptidase [50], M type—specific protein [36], M-conserved protein [51, 52], and GAS toxins (streptococcal pyrogenic exotoxins A, B, and C) [53–56].

One possible limitation of strategies that use M type—specific targets is the need for a multivalent vaccine similar to that used against pneumococcal infection. Population-based studies outside North America that could be used to estimate the coverage of an emm type—specific GAS vaccine against invasive disease are limited [57]. Reports in the United States have shown that the most common types among patients with uncomplicated pharyngitis were 1, 2, 3, 4, 12, and 28, whereas types 3 and 18 have been associated with rheumatic fever [28, 58]. Studies from developing countries have found a greater diversity of emm types than is found in the United States, with many isolates being M-nontypeable when available antisera are used [42, 59]. emm typing has now been performed on a substantial number of these strains from developing countries, and this has confirmed that a large number of types are being newly recognized (CDC, unpublished data). Country- or region-specific surveillance data would be required to determine which types are appropriate for inclusion in a serotype-specific vaccine. Multivalent type-specific GAS vaccines based on emm sequence types might need to be adapted to changes in prevalence if the relative importance of various emm types proves to be highly dynamic.

The findings of the present study are limited in some respects. The incidence rates of STSS and NF disease are minimum estimates. The results of the CDC Active Bacterial Core Surveillance routine procedures for syndrome determination were compared with those of more detailed data-collection procedures used on the same cases in selected surveillance areas. When the more detailed form is used as the standard, the routine case-report form procedures categorized only 50% of STSS cases and 40% of NF cases correctly (CDC, unpublished data). The information collected on varicella infection preceding the onset of GAS disease was not uniformly collected and likely represents an underestimation of the proportion of subjects with this underlying condition. Finally, the characterization of the strains collected during the course of this surveillance does not include data on toxin production or other potential vaccine targets. These strains, however, could be evaluated for such properties.

Ongoing studies of trends in invasive and noninvasive GAS disease incidence, clinical manifestations, and emm type distribution are warranted to monitor trends in disease incidence, guide public health prevention activities, and inform new strategies for disease control. Data on invasive GAS disease epidemiology are not paralleled by data of equivalent quality on strains that cause pharyngitis or noninvasive cutaneous infections, even though those disease entities result in a significant disease burden. The collection of such data should be considered a priority, along with ongoing surveillance for invasive GAS disease, to address the broad range of public health issues of GAS disease [58].

Although the reemergence of severe invasive GAS disease in the mid-1980s attracted substantial concern, we found no evidence for an increase in the absolute incidence of disease since that time. However, GAS causes a substantial burden of endemic disease, which is manifested in large part by syndromes associated with severe morbidity and high mortality. The reporting of invasive GAS disease through population-based surveillance provides a basis for tracking trends in disease incidence rates, evaluating strains that cause disease, targeting vaccine development efforts, and addressing other means of controlling disease. The control of invasive GAS disease requires a long-term commitment to prevention strategies, including the evaluation of vaccines.

Previous SectionNext Section

Acknowledgments

We acknowledge Theresa Hoenes, Raji Viswanathan, Zhongya Li, and Holly Starling, for excellent laboratory assistance; Karen R. Stefonek, Margaret Dragoon, Jane Donegan, Wendy Baughman, and Molly Bardsley, for surveillance activities; and Carolyn Wright, Katherine Robinson, Ariane Kraus, and Chris Van Beneden, for expertise in data management, analysis, and manuscript preparation.

Previous SectionNext Section

Footnotes

  • Financial support: Emerging Infections Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention.

  • Received July 8, 2002.
  • Revision received March 15, 2002.
Previous Section
 

References

  1. ↵
    1. Davies HD,
    2. McGeer A,
    3. Schwartz B,
    4. et al
    . Invasive group A streptococcal infections in Ontario, Canada. N Engl J Med 1996;335:547-54.
    CrossRefMedlineWeb of Science
  2. ↵
    1. Stevens DL
    . Invasive group A Streptococcus infections. Clin Infect Dis 1992;14:2-13.
    Abstract/FREE Full Text
  3. ↵
    1. O'Brien KL,
    2. Fischer M,
    3. Bixler D,
    4. Ewert D,
    5. Ballinger S,
    6. Schwart B
    . Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy (New Orleans). Washington, DC: American Society for Microbiology; 1996. Acute rheumatic fever in Indiana: where did prevention fail [abstract K69]?; p. 262.
    1. Veasy LG,
    2. Wiedmeier SE,
    3. Orsmond GS,
    4. et al
    . Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 1987;316:421-7.
    MedlineWeb of Science
    1. Hosier DM,
    2. Craenen JM,
    3. Teske DW,
    4. Wheller JJ
    . Resurgence of acute rheumatic fever. Am J Dis Child 1987;141:730-3.
    Abstract/FREE Full Text
    1. Congeni B,
    2. Rizzo C,
    3. Congeni J,
    4. Sreenivasan VV
    . Outbreak of acute rheumatic fever in northeast Ohio. J Pediatr 1987;111:176-9.
    MedlineWeb of Science
    1. Wald ER,
    2. Dashefsky B,
    3. Feidt C,
    4. Chiponis D,
    5. Byers C
    . Acute rheumatic fever in western Pennsylvania and the tristate area. Pediatrics 1987;80:371-4.
    Abstract/FREE Full Text
    1. Wallace MR,
    2. Garst PD,
    3. Papadimos TJ,
    4. Oldfield EC
    . The return of acute rheumatic fever in young adults. JAMA 1989;262:2557-61.
    Abstract/FREE Full Text
    1. Centers for Disease Control and Prevention
    . Acute rheumatic fever among army trainees—Fort Leonard Wood, Missouri, 1987–1988. MMWR Morb Mortal Wkly Rep 1988;37:519-22.
    Medline
    1. Westlake RM,
    2. Graham TP,
    3. Edwards KM
    . An outbreak of acute rheumatic fever in Tennessee. Pediatr Infect Dis J 1990;9:97-100.
    MedlineWeb of Science
    1. Griffiths SP,
    2. Gersony WM
    . Acute rheumatic fever in New York City (1969 to 1988): a comparative study of two decades. J Pediatr 1990;116:882-7.
    CrossRefMedlineWeb of Science
    1. Leggiadro RJ,
    2. Birnbaum SE,
    3. Chase NA,
    4. Myers LK
    . A resurgence of acute rheumatic fever in a mid-south children's hospital. South Med J 1990;83:1418-20.
    MedlineWeb of Science
    1. Zangwill KM,
    2. Wald ER,
    3. Londino AV
    . Acute rheumatic fever in western Pennsylvania: a persistent problem into the 1990s. J Pediatr 1991;118:561-3.
    CrossRefMedlineWeb of Science
    1. Veasy LG,
    2. Tani LY,
    3. Hill HR
    . Persistence of acute rheumatic fever in the intermountain area of the United States. J Pediatr 1994;124:9-16.
    CrossRefMedlineWeb of Science
  15. ↵
    1. Rotta J,
    2. Tikhomirov E
    . Streptococcal diseases worldwide: present status and future prospects. Bull World Health Organ 1987;65:769-82.
    MedlineWeb of Science
  16. ↵
    1. Jamison D,
    2. Mosley WH,
    3. Measham AR,
    4. Bobadilla JL
    1. Michaud C,
    2. Treijo-Gutierrez J,
    3. Cruz C,
    4. Pearson TA
    . Rheumatic heart disease. In: Jamison D, Mosley WH, Measham AR, Bobadilla JL, editors. Disease control priorities in developing countries. New York: Oxford University Press; 1993. p. 221-32.
  17. ↵
    1. O'Brien KL,
    2. Levine OS,
    3. Schwartz B
    . The changing epidemiology of group A Streptococcus infections. Semin Pediatr Infect Dis 1997;8:10-6.
    CrossRef
  18. ↵
    1. Cone LA,
    2. Woodard DR,
    3. Schlievert PM,
    4. Tomory GS
    . Clinical and bacteriologic observations of a toxic shock-like syndrome due to Streptococcus pyogenes. N Engl J Med 1987;317:146-9.
    MedlineWeb of Science
  19. ↵
    1. Hribalova V
    . Streptococcus pyogenes and the toxic shock syndrome. Ann Intern Med 1988;108:772.
    Abstract/FREE Full Text
    1. Chiobotaru P,
    2. Yagupsky P,
    3. Fraser D,
    4. Dagan R
    . Changing epidemiology of invasive Streptococcus pyogenes infections in southern Israel: differences between two ethnic population groups. Pediatr Infect Dis J 1997;16:195-9.
    CrossRefMedlineWeb of Science
  21. ↵
    1. Martin PR,
    2. Hoiby EA
    . Streptococcal serogroup A epidemic in Norway 1987–1988. Scand J Infect Dis 1990;22:421-9.
    MedlineWeb of Science
  22. ↵
    1. Stromberg A,
    2. Romanus V,
    3. Burman LG
    . Outbreak of group A streptococcal bacteremia in Sweden: an epidemiologic and clinical study. J Infect Dis 1991;164:595-8.
    Abstract/FREE Full Text
  23. ↵
    1. Fanta J Jr,
    2. Drabkova J,
    3. Rehak F,
    4. Smat V,
    5. Votocek K,
    6. Frankova V
    . Primary peritonitis imitating the toxic shock syndrome (TSS). Prakt Lek (Prague) 1984;64:674-6.
  24. ↵
    1. Stevens DL,
    2. Tanner MH,
    3. Winship J,
    4. et al
    . Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. N Engl J Med 1989;321:1-7.
    MedlineWeb of Science
  25. ↵
    1. Wheeler MC,
    2. Roe MH,
    3. Kaplan EL,
    4. Schlievert PM,
    5. Todd JK
    . Outbreak of group A Streptococcus septicemia in children: clinical, epidemiologic, and microbiological correlates. JAMA 1991;266:533-7.
    Abstract/FREE Full Text
  26. ↵
    1. Hoge CS,
    2. Schwartz B,
    3. Talkington DF,
    4. Breiman RF,
    5. MacNeill EM,
    6. Englender SJ
    . The changing epidemiology of invasive group A streptococcal infections and the emergence of the streptococcal toxic shock-like syndrome: a retrospective population-based study. JAMA 1993;269:384-9.
    Abstract/FREE Full Text
  27. ↵
    1. Defining the group A streptococcal toxic shock syndrome: rationale and consensus definition
    . Working Group on Severe Streptococcal Infections. JAMA 1993;269:390-1.
    Abstract/FREE Full Text
  28. ↵
    1. Johnson DR,
    2. Stevens DL,
    3. Kaplan EL
    . Epidemiologic analysis of group A streptococcal serotypes associated with severe systemic infections, rheumatic fever, or uncomplicated pharyngitis. J Infect Dis 1992;166:374-82.
    Abstract/FREE Full Text
  29. ↵
    1. Schwartz B,
    2. Facklam AR,
    3. Breiman RF
    . Changing epidemiology of group A streptococcal infection in the USA. Lancet 1990;336:1167-71.
    CrossRefMedlineWeb of Science
  30. ↵
    1. Givner LB,
    2. Abramson JS,
    3. Wasilauskas B
    . Apparent increase in the incidence of invasive group A beta-hemolytic streptococcal disease in children. J Pediatr 1991;118:341-6.
    CrossRefMedlineWeb of Science
  31. ↵
    1. Rathore MH,
    2. Barton LL,
    3. Kaplan EL
    . Suppurative group A beta-hemolytic streptococcal infections in children. Pediatrics 1992;89:743-6.
    Abstract/FREE Full Text
  32. ↵
    1. Whatmore AM,
    2. Kapur V,
    3. Sullivan DJ,
    4. Musser JM,
    5. Kehoe MA
    . Noncongruent relationships between the variation in emm sequences and the population genetic structure of group A streptococci. Mol Microbiol 1994;14:619-31.
    MedlineWeb of Science
  33. ↵
    1. Beall B,
    2. Facklam RR,
    3. Thompson T
    . Sequencing emm-specific PCR products for routine and accurate typing of group A streptococci. J Clin Microbiol 1996;34:953-8.
    Abstract/FREE Full Text
  34. ↵
    1. Facklam R,
    2. Beall B,
    3. Efstratiou A,
    4. et al
    . emm typing and validation of provisional M types for group A streptococci. Emerg Infect Dis 1999;5:1-7.
    MedlineWeb of Science
  35. ↵
    1. Beall B,
    2. Facklam R,
    3. Elliott JA,
    4. et al
    . Streptococcal emm types associated with T-agglutination types and the use of conserved emm gene restriction fragment patterns for subtyping group A streptococci. J Med Microbiol 1998;47:893-8.
    Abstract/FREE Full Text
  36. ↵
    1. Dale JB
    . Multivalent group A streptococcal vaccine designed to optimize the immunogenicity of six tandem M protein fragments. Vaccine 1999;17:193-200.
    CrossRefMedlineWeb of Science
  37. ↵
    1. Beall B,
    2. Gherardi G,
    3. Lovgren M,
    4. Facklam RR,
    5. Forwick BA,
    6. Tyrrell GJ
    . emm and sof gene sequence variation in relation to serological typing of opacity factor positive group A streptococci. Microbiology 2000;146:1195-209.
    Abstract/FREE Full Text
  38. ↵
    1. Beall B,
    2. Facklam RR,
    3. Hoenes T,
    4. Schwartz B
    . Survey of emm gene sequences and T-antigen types from systemic Streptococcus pyogenes infection isolates collected in San Francisco, California; Atlanta, Georgia; and Connecticut in 1994 and 1995. J Clin Microbiol 1997;35:1231-5.
    Abstract/FREE Full Text
  39. ↵
    1. Facklam R,
    2. Martin D,
    3. Lovgren M,
    4. et al
    . Extension of the Lancefield classification for group A streptococci by addition of 22 new M protein gene sequence types from clinical isolates: emm103 to emm124. Clin Infect Dis 2002;34:28-38.
    Abstract/FREE Full Text
  40. ↵
    1. Kaplan EL,
    2. Johnson DR,
    3. Rehder CD
    . Recent changes in group A streptococcal serotypes from uncomplicated pharyngitis: a reflection of the changing epidemiology of severe group A infections? J Infect Dis 1994;170:1346-7.
    FREE Full Text
  41. ↵
    1. Zurawski C,
    2. Bardsley MS,
    3. Beall B,
    4. et al
    . Invasive group A streptococcal disease in metropolitan Atlanta: a population-based assessment. Clin Infect Dis 1998;27:150-7.
    Abstract/FREE Full Text
  42. ↵
    1. Jamal F,
    2. Pit S,
    3. Facklam R,
    4. Beall B
    . New emm (M protein gene) sequences of group A streptococci isolated from Malaysian patients. Emerg Infect Dis 1999;5:182-3.
    MedlineWeb of Science
    1. Tran P,
    2. Johnson D,
    3. Kaplan E
    . The presence of M protein in nontypeable group A streptococcal upper respiratory tract isolates from Southeast Asia. J Infect Dis 1994;169:658-61.
    Abstract/FREE Full Text
  44. ↵
    1. Jamal F,
    2. Pit S,
    3. Johnson D,
    4. Kaplan E
    . Characterization of group A streptococci isolated in Kuala Lumpur, Malaysia. J Trop Med Hyg 1995;98:343-6.
    MedlineWeb of Science
  45. ↵
    1. Kaul R,
    2. McGeer A,
    3. Norrby-Teglund A,
    4. et al
    . Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome—a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis 1999;28:800-7.
    Abstract/FREE Full Text
  46. ↵
    1. Kaul R,
    2. McGeer A,
    3. Low D,
    4. et al
    . Population-based surveillance for group A streptococcal necrotizing fasciitis: clinical features, prognostic indicators, and microbiologic analysis of seventy-seven cases. Am J Med 1997;103:18-24.
    CrossRefMedlineWeb of Science
  47. ↵
    1. Barker J,
    2. Gratten M,
    3. Riley I,
    4. et al
    . Pneumonia in children in the Eastern Highlands of Papua New Guinea: a bacteriologic study of patients selected by standard clinical criteria. J Infect Dis 1989;159:348-52.
    FREE Full Text
  48. ↵
    1. Auerbach S,
    2. Schwartz B,
    3. Williams D,
    4. et al
    . Outbreak of invasive group A streptococcal infections in a nursing home. Arch Intern Med 1992;152:1017-22.
    Abstract/FREE Full Text
  49. ↵
    1. Schwartz B,
    2. Elliott JBJ,
    3. Simon P,
    4. Jameson B,
    5. Welch G,
    6. Facklam R
    . Clusters of invasive group A streptococcal infections in family, hospital, and nursing home settings. Clin Infect Dis 1992;15:277-84.
    Abstract/FREE Full Text
  50. ↵
    1. Cheng Q,
    2. Carlson B,
    3. Pillai S,
    4. et al
    . Antibody against surface-bound C5a peptidase is opsonic and initiates macrophage killing of group B streptococci. Infect Immun 2001;69:2302-8.
    Abstract/FREE Full Text
  51. ↵
    1. Fischetti VA
    . Streptococcal M protein: molecular design and biological behavior. Clin Microbiol Rev 1989;2:285-314.
    Abstract/FREE Full Text
  52. ↵
    1. Brandt EK,
    2. Hobb R,
    3. Hayman W,
    4. et al
    . New multi-determinant strategy for a group A streptococcal vaccine designed for the Australian Aboriginal population. Nat Med 2000;6:455-9.
    CrossRefMedlineWeb of Science
  53. ↵
    1. Matsuka Y,
    2. Pillai S,
    3. Gubba S,
    4. Musser J,
    5. Olmsted S
    . Fibrinogen cleavage by the Streptococcus pyogenes extracellular cysteine protease and generation of antibodies that inhibit enzyme proteolytic activity. Infect Immun 1999;67:4326-33.
    Abstract/FREE Full Text
    1. Lukomski S,
    2. Burns E,
    3. Wyde P,
    4. et al
    . Genetic inactivation of an extracellular cysteine protease (SpeB) expressed by Streptococcus pyogenes decreases resistance to phagocytosis and dissemination to organs. Infect Immun 1998;66:771-6.
    Abstract/FREE Full Text
    1. Roggiani M,
    2. Stoehr J,
    3. Olmsted S,
    4. et al
    . Toxoids of streptococcal pyrogenic exotoxin A are protective in rabbit models of streptococcal toxic shock syndrome. Infect Immun 2000;68:5011-17.
    Abstract/FREE Full Text
  56. ↵
    1. McCormick J,
    2. Tripp T,
    3. Olmsted S,
    4. et al
    . Development of streptococcal pyrogenic exotoxin C vaccine toxoids that are protective in the rabbit model of toxic shock syndrome. J Immunol 2000;165:2306-12.
    Abstract/FREE Full Text
  57. ↵
    1. Gaworewska E,
    2. Colman G
    . Changes in the pattern of infection caused by Streptococcus pyogenes. Epidemiol Infect 1988;100:257-69.
    Medline
  58. ↵
    1. Shulman ST,
    2. Tanz RR,
    3. Kabat W,
    4. Kabat K
    . US nationwide streptococcal pharyngitis serotype surveillance [abstract 277]. Clin Infect Dis 2001;33:1136.
  59. ↵
    1. Pruksakorn S,
    2. Sittisombut N,
    3. Phornphutkul C,
    4. Pruksachatkunakorn C,
    5. Good MF,
    6. Brandt E
    . Epidemiological analysis of non-M-typeable group A streptococcus isolates from a Thai population in Northern Thailand. J Clin Microbiol 2000;38:1250-4.
    Abstract/FREE Full Text
| Table of Contents

This Article

  1. Clin Infect Dis. (2002) 35 (3): 268-276. doi: 10.1086/341409
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most