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Analysis of 132 group A streptococcal (GAS) isolates from 151 invasive episodes, including streptococcal toxic shock syndrome (STSS), from 1983 to 1995 showed great genetic variation by use of T serotyping in combination with restriction fragment length polymorphism. In contrast, genetically homogenous T1M1 isolates appeared in epidemic patterns with significantly increased risk of STSS. The speA gene, with the allelic variants speA2 and speA3 carried by the T1M1 and T3M3 serotypes, respectively, was strongly associated with STSS. Infection with a GAS isolate carrying speA, alcohol abuse, and malignancy recently treated with cytostatic drugs were factors independently related to STSS. Neutralization of SpeA lymphocyte mitogenicity was totally absent in sera from patients with STSS and low in sera from persons with uncomplicated bacteremia compared with levels in sera from uncomplicated erysipelas. Neutralization of SpeB was significantly lower in sera of patients with STSS than in sera from persons with bacteremia or erysipelas.

Hyaluronidase has been postulated to be a virulence factor in group B streptococci (GBS). No hyaluronidase activity was found in 15 of 50 GBS isolates from adults studied. Most of these hyaluronidase-negative strains belonged to serotype III. In strains lacking hyaluronidase activity, an insertion of 1317 nucleotides was found in the hyaluronidase gene. The fragment was cloned and sequenced and found to have characteristics of a novel insertion sequence, designated IS1548. As well as in GBS serotype III, this sequence was found in 3 of 6 serotype II isolates and in all 10 group A streptococcal strains (GAS) tested. Homologies were found with repeated sequences in Streptococcus pneumoniae and with H repeats in Escherichia coli. All GBS strains harboring IS1548 and some GAS strains had one copy of IS1548 located downstream of the C5a peptidase gene. IS1548 was present in 9 of 13 GBS isolates from blood in endocarditis patients and in 3 of 22 vaginally colonizing strains.

The proliferative response of lymphocytes induced by a new streptococcal mitogenic factor (MF) and the streptococcal pyrogenic exotoxins (Spe) A and B was determined in sera from 6 healthy persons. Responses were compared to those obtained from reference serum that lacked mitogen-specific ELISA antibodies. The sera showed individual variations in the levels of MF- and Spe-specific antibodies, as determined by ELISA. The experiments showed that most human sera, which contained mitogen-specific antibodies, could neutralize the mitogenicity of the proteins. However, there were sera that contained mitogen-specific antibodies but that did not inhibit the toxin-induced proliferation. Thus, the ELISA antibody titer did not always equal the neutralizing capacity. Sera from 27 patients with group A streptococcal bacteremia had significantly lower neutralizing ability against MF and SpeB than did sera from 25 uncomplicated tonsillitis cases.

Genetic diversity was found at high frequency downstream of the emm1 gene among T1M1 group A streptococci (GAS) isolated in Scandinavia during a recent epidemic. Clonal variation was also seen in the speA and speB genes but at much lower frequency; no variation was detected in the speC gene. Erythrogenic toxin A was found to be expressed at low levels in all strains; erythrogenic toxins B and C were produced in high amounts. All strains were found to harbor the speA, speB, and speC genes, regardless of the amount of toxin produced. No correlation was found between one specific T1M1 clone and the more serious infections when isolates from bacteremic patients (fatalities or survivors), those with uncomplicated infections, and healthy carriers were compared. Similar results were obtained in a family study in which 3 family members were found to be asymptomatic carriers of the same GAS T1M1 clone as in the bacteremic patient, defined by genotypic and phenotypic experiments.

Serotypes of serious, sometimes fatal, streptococcal infections in Sweden during 1988-1989 were analyzed. The T1M1 type totally dominated, representing almost 70% of all group A streptococci from serious and uncomplicated infections at the peak of the outbreak. Immunoblots of isolates from various patient groups showed that all isolates produced high amounts of erythrogenic toxin (ET) B and high amounts of ET-C, whereas ET-A was released only in small amounts and from few isolates. ELISAs showed high antibody levels to these toxins and to the M1 antigen in patients with uncomplicated infections. Low antibody levels against M1 were seen in patients with bacteremia and in fatal cases; the latter also had low antibody levels against ET-B. It seems likely that a combination of production of large amounts of toxin and low antibody titers to it and to the M antigen of the infecting isolate are determining factors for the outcome of the infection. No signs of primary immune deficiency were noted.