Increasing Severity of Invasive Group A Streptococcal Disease in Australia: Clinical and Molecular Epidemiological Features and Identification of a New Virulent M-Nontypeable Clone

Abstract

We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993. Forty-two cases were identified. There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period; more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs. 20%, respectively, with an 88% complication rate over the last 12 months). Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed. An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates. Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable. Invasive GAS disease in Melbourne has become increasingly aggressive. Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains.

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

“…It is now clear from our analysis that a complex multistep (9). Moreover, it has been well documented (2,3,5,7,8,11,12,14,19) that epidemic M1 infections occurred in Norway, Sweden, Finland, Denmark, Australia, and Canada in the ensuing years. The result of the genetic events we describe here was an explosive intercontinental epidemic of serotype M1 human infections including pharyngitis and severe invasive diseases such as necrotizing fasciitis, the "flesh-eating" infection.…”

“…The result of the genetic events we describe here was an explosive intercontinental epidemic of serotype M1 human infections including pharyngitis and severe invasive diseases such as necrotizing fasciitis, the "flesh-eating" infection. GAS causes >600 million cases of human infections yearly, and extensive epidemiologic studies have shown that serotype M1 organisms are frequently the most abundant M protein serotype (3,4,7,9,14,(74)(75)(76). In conclusion, the molecular evolutionary events transpiring in just one bacterial cell ultimately produced many millions of human infections worldwide.…”

“…Group A Streptococcus (GAS, also known as Streptococcus pyogenes), a Gram-positive bacterial pathogen, causes human infections worldwide (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). For example, GAS is responsible for more than 600 million infections globally each year, including a conservative estimate of 10,000-15,000 severe invasive infections annually in the United States (4).…”

“…This organism has a longrecognized proclivity to cause epidemic waves, the reasons for which are largely unknown. After several decades of declining incidence, a striking resurgence of severe invasive infections caused by serotype Emm protein 1 (M1) GAS was reported in many countries in the late 1980s and early 1990s (1)(2)(3)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The resurgence received widespread public interest in part because of the untimely death of Jim Henson, the Muppeteer, of invasive GAS, and because of severe infections occurring in other notable public figures in Canada and elsewhere (21).…”

Site-Specific Manifestations of Invasive Group A Streptococcal Disease: Type Distribution and Corresponding Patterns of Virulence Determinants

“…Since the mid-1980s, a conspicuous increase in the incidence of invasive infections caused by group A streptococci (GAS) has been observed worldwide (3,9,10,18,27,37,38,53,70). Invasive GAS diseases include various clinical syndromes such as bacteremia, arthritis, pneumonia, puerperal sepsis, meningitis, and necrotizing fasciitis.…”