7 小児感染免疫 Vol. 9 No. SE staphylococcal enterotoxintsst- toxic shock syndrome toxin-et exfoliative toxin 9 6 6.% SE 6.% TSST- 6.% ET.% SEA staphylococcal enterotoxin type A.%, ETA exfoliative toxin type A.8%, ETB exfoliative toxin type B 9.8% ET 黄色ブドウ球菌は病原性が高く, 皮膚軟部組織感染症, 感染性心内膜炎, 骨髄炎, 関節炎, 肺炎などの侵襲性感染症の原因となる ). 病原因子として種々の毒素を産生し, これらが単独または協調して作用することで多彩な臨床症状を引き起こすことが知られている,).SE(staphylococcal enterotoxin) は食中毒の原因毒素であり, 加えてスーパー抗原としての性質も持つ ).TSST-(toxic shock syndrome toxin-) もまたスーパー抗原として知られている外毒素で,98 年発見された.T 細胞の Vβ 受容体に直接結合し, 強力に T 細胞を活 性化させ, 発熱や臓器障害を惹起する ). 過剰な免疫反応や炎症反応の誘導によって, トキシックショック症候群 (toxic shock syndrome: TSS), 新生児 TSS 様発疹症 (neonatal TSS-like exanthematous disease: NTED) の原因となることが知られている 6). さらに ET(exfoliative toxin) は表皮角質層のデスモグレインを阻害し, 水疱形成を引き起こす外毒素で, ブドウ球菌性熱傷様皮膚症候群 (staphylococcal scalded skin syndrome: SSSS) や伝染性膿痂疹の原因毒素である 7,8). このように, 外毒素は一部の疾患との関連が既に明らかになっているが, その他の疾患に対して担う役割は依然不明な部分が多い. 最近の研究で Key wordstsst- 8-86 -8-9
7 / / / /, は, 菌血症の原因となった黄色ブドウ球菌において SEA (staphylococcal enterotoxin type A) や TSST- 産生遺伝子保有率が高いことや 9), 膿瘍や筋炎などの皮膚軟部組織感染症と骨髄炎の患者から検出された黄色ブドウ球菌のうち,% で SEB(staphylococcal enterotoxin type B) 産生遺伝子を有したことが報告されている ). これらを踏まえて, 本邦の小児における黄色ブドウ球菌感染症の臨床診断名と, 外毒素との関連を調査した. 9 6 SE TSST- ET Clinical and Laboratory Standards Institute: CLSI g/ml 8 g/ml SPSS Statistics IBM p<. H7b-6 96 7 9. :. 86.8.9%
7 小児感染免疫 Vol. 9 No. N= MSSA N= MRSA N=6 6.8.6 7 6.8 SSSS NTED 7 8 6 7.7. 7.8 7. 6....7..... 6. 9.6.....8 8 9....6 6.9.6..6.7.6 9. 6.8 9.8 8 8 6... 8.. 7.7..7.9 6.8 6. 6 6..6 8... 8 7.8 9 7.9 9 7.8 9.9......6.6 6..7..6..7 SSSS staphylococcal scalded skin syndrome: NTED neonatal TSS-like exanthematous disease: TSS methicillin-susceptible Staphylococcus aureus : MSSA 9.6% methicillin-resistant Staphylococcus aureus : MRSA 6.% 6 9 8 6.7% SE 6
7 N= MSSA N= MRSA N=6 p SE 6 6.% 6.8% 6.%. SEA 9 7.% 9.% 7.7%.8 SEB.7% 6.% 7 6.% SEC 9.7%.% 7.9%. SED.%.9%.7% TSST- 6 6.% 6.% 8.8%. ET.% 8 7.% 9.8%. ETA 6.6% 6.% %. ETB.9%.8% 9.8%. 88 8.% 6.% 6.%.. 6 SE TSST- 8 SE SE 6 SE 6.% 8 SEA 7% SEB.7% SEC staphylococcal enterotoxin type C.7% SED staphylococcal enterotoxin type D.% TSST- 6 6.%ET.% ETA exfoliative toxin type A.6% ETB exfoliative toxin type B.9% SE 6.% TSST- 6.% MSSA MRSA MSSA ETA p=. MRSA SEC p<. TSST- p<. ETB p<. SEA.% SEA.6% p=. ET.6% ET % p<. ET SSSS 6 96.% ET MRSA 6 8.6% SE SEA SEB SEC SED SEE staphylococcal enterotoxin type E SEA SED SEE SEB SEC SEA SEB SEC SED ET ETA ETB,ETA ETB ET SE TSST- SSSS ET ET
7 小児感染免疫 Vol. 9 No. N= N=6 N=9 N= N=8 N= N= SE 6 6. % 8 8.% 7.% 7. % 9. %.% 6.% SEA 9 7. %.%.%. % 6.7 %.% % SEB.7 %.% 6.% 6. %.% %.% SEC 9.7 %.% 8.6%.6 %. % 66.7%.% SED. %.8%.% % % % % TSST- 6 6. %.% 6.% 8. % 7.8% 66.7%.% ET. %.6% % % % % % ETA 6.6 % 6.8% % % % % % ETB.9 % 9.8% % % % % % 88 8. % 6 6.%.9%.8% 7 8.9 % % %, 6 SE TSST- 8 SE SE SE 6 SE 6 SSSS 96.% ET ET SEA ET Sina 6 SEA % SEB TSST- % Verkaik 6 88% SEA TSST- 9 MSSA MRSA MSSA ETA MRSA SEC TSST- ETB Verkaik MSSA SEA SEB TSST- 9 Sina Verkaik 88.8% TSST- PVL Panton-Valentine Leukocidin
6 7 limitation ETA 6 MSSA ETA USA ST8 SEA.% ETA.8% ETB 9.8% ET limitation 7 Lowy FD : Staphylococcus aureus infections. N Engl J Med 9 : -, 998 Tristan A, et al : Virulence determinants in community and hospital meticillin-resistant Staphylococcus aureus. J Hosp Infect 6 : -9, 7 Nhan TX, et al : Prevalence of toxin genes in consecutive clinical isolates of Staphylococcus aureus and clinical impact. Eur J Clin Microbiol Infect Dis : 79-7,,,, multiplex PCR. 9 : -, Stach CS, et al Staphylococcal superantigens interact with multiple host receptors to cause serious diseases. Immunol Res 9 : 77-8, 6, 7 : 89-9, 999 7 Lamand V, et al : Epidemiological data of staphylococcal scalded skin syndrome in France from 997 to 7 and microbiological characteristics of Staphylococcus aureus associated strains. Clin Microbiol Infect 8 : E-, 8, : 9-, 8 9 Verkaik NJ, et al : Immunogenicity of toxins during Staphylococcus aureus infection. Clin Infect Dis : 6-68, Sina H, et al : Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections. BMC Microb : 88, Clinical and Laboratory Standards Institute : Performance standards for antimicrobial susceptibility testing. Twenty-sixth informational supplement, 6, M-S6
7 小児感染免疫 Vol. 9 No. 7 Exotoxin production profile of Staphylococcus aureus and types of infections Yoshiaki CHO, Kahoru, FUKUOKA,Takayuki YAMANAKA, Takemi MURAI, Mihoko FURUICHI,Yuta AIZAWA, Kenta ITO, Takayo SHOJI, Yuho HORIKOSHI Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children s Medical Center Division of General Pediatrics, Department of General Pediatrics, Aichi Children s Health and Medical Center Division of Pediatric Infectious Diseases, Shizuoka Children s Hospital Staphylococcus aureus, a common pathogenic bacterium, produces various exotoxins related to virulence. Toxic shock syndrome toxin- (TSST-) and staphylococcal enterotoxin (SE), which act on T-lymphocytes as super antigens, cause toxin-mediated diseases and extreme allergic reactions, while exfoliative toxin (ET) is responsible for staphylococcal scalded skin syndrome (SSSS), a condition effecting the epidermis. Although staphylococcal toxins are known for their pathogenicity, studies on the relationship of these toxins to clinical diseases among children are limited in Japan. The aim of this study was to examine the relationship of clinical diseases to exotoxin-producing S. aureus in children at Tokyo Metropolitan Children s Medical Center seen between September and March 6. Methicillin-resistant S. aureus comprised half of the cases reviewed. Infections of the skin and soft tissue, blood stream, and bone-joints occurred in 6, 9 and cases, respectively. Among these, 6.% of isolates were positive for at least one staphylococcal exotoxin. SE, TSST-, and ET were detected in 6.%, 6.% and.% of the cases, respectively. The SE type A-producing strain was found.% of bone-joint infections. ET type A and B-producing strains occurred in.8% and 9.8% of skin and soft tissue infections, respectively. Notably, all ET-producing strains caused skin and soft tissue infections. Our finding indicated that staphylococcal exotoxins were associated with specific diseases in children. 6 7 6