Chris A. Van Beneden

Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America a

Abstract The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000–2004

BACKGROUND Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. METHODS From January 2000 through December 2004, we collected data from Centers for Disease Control and Preventions Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. RESULTS We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950-11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050-1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. CONCLUSIONS GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.

Executive Summary: Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America

The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Population-Based Study of Invasive Disease Due to β-Hemolytic Streptococci of Groups Other than A and B

BACKGROUND Beta-hemolytic streptococci of groups other than A and B (NABS) are increasingly recognized as causes of clinically significant disease, but precise information about this heterogeneous group is lacking. We report the incidence of NABS infection and describe the epidemiologic and clinical characteristics. METHODS Active, population-based surveillance for invasive NABS was performed over a 2-year period in the 8-county metropolitan Atlanta, Georgia, area and the 3-county San Francisco Bay, California, area. Clinical records were reviewed, and available isolates were sent to the Centers for Disease Control and Prevention (Atlanta) for additional microbiologic characterization. Incidences were calculated using year-appropriate US Census Bureau data. RESULTS A total of 489 cases of invasive NABS infection were identified (3.2 cases per 100,000 population). The median age of patients was 55 years; 64% of patients were males, and 87% had underlying diseases. The incidence was higher among black persons than white persons (4.0 vs. 2.5 cases per 100,000 population; P < .01) and increased with age among all races. Infections were community acquired in 416 cases (85%). Among the 450 patients (94%) with NABS infection who were hospitalized, 55 (12%) died. Of 266 isolates (54%) speciated at the Centers for Disease Control and Prevention, 212 (80%) were Streptococcus dysgalactiae subspecies equisimilis; 46 (17%) were members of the Streptococcus anginosus group. S. dysgalactiae subspecies equisimilis primarily presented as skin and soft-tissue infection in older patients, whereas individuals with invasive S. anginosus group infections were more likely to be younger patients with intra-abdominal infections. CONCLUSIONS NABS comprise multiple distinct species that cause a significant number of community-acquired invasive infections. Clinical manifestations differ by species. Thus, speciation of invasive NABS may be warranted in clinical settings.

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences

Significance Epidemics of microbial infections are a considerable threat to human and animal health. Analysis of 3,615 genome sequences, coupled with virulence studies in animals, permitted us to delineate the nature and timing of molecular events that contributed to an ongoing global human epidemic of infections caused by group A Streptococcus, the “flesh-eating” pathogen. We clarified decades-long uncertainty about the timing and sequence of genomic alterations that underpinned the global epidemic. Analyses of this type are crucial for developing better strategies to predict and monitor strain emergence and epidemics, formulate effective protective public health maneuvers, and develop or modify vaccines. We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD+-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.

Incidence and Severity of Invasive Streptococcus pneumoniae, Group A Streptococcus, and Group B Streptococcus Infections Among Pregnant and Postpartum Women

BACKGROUND The epidemiology of streptococcal infection in pregnant and postpartum women is poorly described in recent literature. We used data from multistate surveillance for invasive Streptococcus pneumoniae, group A Streptococcus (GAS), and group B Streptococcus (GBS) infections to estimate disease incidence and severity in these populations. METHODS Cases were reported through the Centers for Disease Control and Prevention Active Bacterial Core surveillance, an active population- and laboratory-based system. A case was defined as illness in a woman aged 15-44 years with streptococcus isolated from a normally sterile body site during 2007-2009. Pregnant or postpartum status was recorded at the time of culture. Incidence was calculated as cases per 1000 woman-years with use of national Census data; 95% confidence intervals were calculated on the basis of λ distribution. We used multivariable logistic regression to explore associations between pregnant or postpartum status and hospital length of stay, a marker of disease severity. RESULTS We identified 1848 cases in women; 6.0% of women were pregnant, and 7.5% were postpartum. Pregnant women had a higher mean incidence of GBS disease, compared with nonpregnant women (0.04 cases per 1000 woman-years [range, 0.03-0.05 cases per 1000 woman-years] vs 0.02 cases per 1000 woman-years [range, 0.02-0.02 cases per 1000 woman-years]). Postpartum women had elevated mean incidence of all 3 pathogens, compared with nonpregnant women (S. pneumoniae: 0.15 cases per 1000 woman-years [range, 0.09-0.25 cases per 1000 woman-years] vs 0.052 cases per 1000 woman-years [range, 0.049-0.056 cases per 1000 woman-years]; GAS: 0.56 cases per 1000 woman-years [range, 0.42-0.70 cases per 1000 woman-years] vs 0.019 cases per 1000 woman-years [range, 0.017-0.021 cases per 1000 woman-years]; GBS: 0.49 cases per 1000 woman-years [range, 0.36-0.64 cases per 1000 woman-years] vs 0.018 [range, 0.016-0.020 cases per 1000 woman-years]). Neither pregnancy nor postpartum status was associated with longer length of stay among women infected with any of the 3 pathogens. CONCLUSIONS Although invasive streptococcal infections do not appear to be more severe in pregnant or postpartum women, postpartum women have a 20-fold increased incidence of GAS and GBS, compared with nonpregnant women.

Epidemiology of Invasive Group A Streptococcal Infections in the United States, 2005–2012

BACKGROUND Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. METHODS From January 2005 through December 2012, we collected data from the Centers for Disease Control and Preventions Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data. RESULTS We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The case-fatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649-13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136-1607 deaths. In a 30-valent M-protein vaccine, emm types accounted for 91% of isolates. CONCLUSIONS The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact.

Invasive Pneumococcal Infections among Vaccinated Children in the United States

OBJECTIVE Because 7-valent pneumococcal conjugate vaccine (PCV7) is highly efficacious, pneumococcal infections in vaccinated children raise concerns about immunologic disorders. We characterized a case series of US children in whom invasive pneumococcal infections developed despite vaccination. STUDY DESIGN We reviewed invasive (sterile site) pneumococcal infections in children aged <5 years who had received > or =1 PCV7 dose as identified from October 2001 to February 2004 through national passive surveillance and the Centers for Disease Control and Preventions Active Bacterial Core surveillance. Vaccine serotype infections were considered breakthrough cases; the subset of breakthrough cases occurring in children who completed an age-appropriate vaccination series were considered PCV7 failures. RESULTS We identified 753 invasive infections; 155 infections (21%) were breakthrough cases, predominantly caused by serotypes 6B (n = 50, 32%) and 19F (n = 45, 29%). The proportion of breakthrough cases decreased with the increasing number of PCV7 doses received (P < .001, Chi(2) for linear trend). Children with co-morbid conditions accounted for 31% of breakthrough infections. Twenty-seven cases (4%) were classified as vaccine failures. Most failures (71%) occurred in children who were vaccinated according to catch-up schedules; 37% had co-morbid conditions. CONCLUSION Invasive pneumococcal infections identified in vaccinated U.S. children were primarily caused by disease resulting from serotypes not covered with PCV7, rather than failure of the vaccine. Incomplete vaccination and co-morbid conditions likely contribute to breakthrough vaccine-type pneumococcal infections.

Group A Streptococcal Disease in Long-Term Care Facilities: Descriptive Epidemiology and Potential Control Measures

Group A streptococci (GAS) are an important cause of severe, life-threatening illness among the elderly population, particularly those individuals residing in long-term care facilities (LTCFs). Outbreaks of GAS infection are potentially devastating in this vulnerable population and often require large-scale control efforts involving LTCF staff, public health officials, and infectious diseases practitioners. Although multiple outbreaks of GAS infection in LTCFs have been described in the medical literature, this topic has not been reviewed for 15 years, and there is a need for updated guidance on how to approach GAS infection outbreak control. We reviewed published documents on GAS infection in LTCFs to describe the current understanding of the diseases epidemiology in this setting, identify techniques for outbreak investigation and prevention, and expose areas where additional research is needed. We highlight well-accepted prevention and control strategies that can be employed during investigation and control of GAS infection outbreaks in LTCFs.

Investigation of a Group A Streptococcal Outbreak Among Residents of a Long-term Acute Care Hospital

BACKGROUND In January 2008, a long-term acute care hospital (LTACH) in New Mexico reported a cluster of severe group A Streptococcus (GAS) infections. METHODS We defined a case as illness in a patient in the LTACH from 1 October 2007 through 3 February 2008 from whom GAS was isolated from a usually sterile site or with illness consistent with GAS infection and GAS isolated from a nonsterile site. To identify carriers, we swabbed the oropharynx and skin lesions of patients and staff. We observed facility procedures to assess possible transmission routes and adherence to infection control practices. We also conducted a case-control study to identify risk factors for infection with use of asymptomatic patients who were noncarriers as control subjects. RESULTS We identified 11 case patients and 11 carriers (8 patients and 3 staff). No carriers became case patients. Significant risk factors for infection in univariate analysis included sharing a room with an infected or colonized patient (6 [55%] of 11 case patients vs 3 [8%] of 39 control subjects), undergoing wound debridement (64% vs 13%), and receiving negative pressure wound therapy (73% vs 33%). Having an infected or colonized roommate remained associated with case patients in multivariable analysis (odds ratio, 15.3; 95% confidence interval, 2.5-110.9). Suboptimal infection control practices were widespread. CONCLUSIONS This large outbreak of GAS infection was the first reported in an LTACH, a setting that contains a highly susceptible patient population. Widespread infection control lapses likely allowed continued transmission. Similar to the situation in other care settings, appropriate infection control and case cohorting may help prevent and control outbreaks of GAS infection in LTACHs.