Major outbreak of toxic shock-like syndrome caused by Streptococcus mitis

Abstract

Severe illness caused by viridans streptococci rarely occurs in immunocompetent hosts. Between December 1990 and May 1991, thousands of patients in the YangZi River Delta area of Jiangsu Province, China, suffered from scarlet fever-like pharyngitis. Fewer cases occurred in subsequent years with the same seasonality. Approximately half of the cases developed complications characteristic of streptococcal toxic shock-like syndrome (TSLS). Throat cultures yielded predominant growth of alpha-hemolytic streptococci. All cases admitted to Haian People's Hospital were investigated. Clinical specimens were collected, medical records were reviewed, and bacterial isolates were identified phenotypically and analyzed by 16S rRNA gene sequencing and pulsed-field gel electrophoresis (PFGE). Proteins were purified from culture supernatants by extraction, ammonium sulfate precipitation, and fast-protein liquid chromatography. Biological activities of protein components were determined by subcutaneous inoculation into rabbits. A total of 178 cases of non-beta-hemolytic streptococcal scarlet fever-like pharyngitis were studied. In 88 (79.3%) of 111 patients, oropharyngeal swab cultures grew morphologically identical alpha-hemolytic streptococci. A protein in culture supernatants was pyrogenic in rabbits, was mitogenic for splenocytes, and enhanced rabbit susceptibility to endotoxin challenge. The N-terminal amino acid sequence of this 34-kDa protein showed no homology with known Streptococcus pyrogenic exotoxins. The organism was identified as Streptococcus mitis based on biochemical and 16S rRNA sequence analyses. Representative outbreak isolates from 1990 to 1995 displayed identical PFGE patterns. This TSLS outbreak in southeastern China was caused by a toxigenic clone of S. mitis. An apparently novel toxin may explain the unusual virulence of this organism.

FIG. 1.

Neighbor-joining analysis of DNA sequences from specimens found to have homology with the human isolates. Phylogenetic analysis was based on whole 16S rRNA gene sequences. Five clinical isolates arbitrarily selected from each year from 1991 to 1995 show identical 16S rRNA gene sequence information. The scale shows relative phylogenetic distance.

FIG. 2.

Fever in rabbits after injection of a secreted 34-kDa S. mitis protein. Mean rectal temperature change (in degrees centigrade ± the standard deviation) from four rabbits in each group is shown.

FIG. 3.

PFGE patterns of SmaI-digested genomic DNA of clinical S. mitis isolates. Lanes 1 to 5 are S. mitis isolates recovered from 1991 to 1995, respectively. Lanes 6 to 10 were S. mitis isolates recovered from the throats of local healthy volunteer during the same period. Molecular sizes are in kilobases.