Key words: superantigen, Staphylococcus aureus, TSST-1, enterotoxin, neonatal exanthematous disease

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1 Key words: superantigen, Staphylococcus aureus, TSST-1, enterotoxin, neonatal exanthematous disease

2 Fig. 1 Clinical course and laboratory findings in a typical case of new neonatal exanthematous disease Supergenic exotoxins, enterotoxin- and TSST-1-producing S. aureus is isolated from the infection foci located in the umbilical region or airway at onset. The systemic exanthema apperes after fever onset and continues for 2 to 3 days. Transient thrombocytopenia returns to normal within 7 days. The course of the disease is short, most infants spontaneously recover within 4 to 5 days. In some preterm infants, the disease maybe follow by TSS or severe staphylococcal infection.

3 Table 1 Exotoxin production and antibiotics susceptibility of S. aureus isolates from patients with neonatal exanthematous disease in Shikoku Island (October 1994 through December 1998)

4 Fig. 2 Comparison of antibody titers to various staphylococcal exotoxins in patients with neonatal exanthematous disease Table 2 Antibody titers to the exotoxins in acute phase paired serum of patient and the mother Serum of mother was obtained within five days after onset Fig. 3 Comparison of antibody titers to various staphylococcal exotoxins in umbilical cord blood from term infants

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6 8) Takahashi N, Nishida H, Kato H, Imanishi K, Sakata Y, Uthiyama T: Exanthemathous disease induced by toxic shock syndrome toxin 1 in the neonatal period. Lancet 1998; 351: ) Todd J, Fishaut M, Kapral F et al.: Toxic-shock syndrome associated with phage-group-1 Staphy- Lancet 1978; 25: lococci. 11) Schievert PM: Staphyloccoal enterotoxin B and toxic-shock syndrome toxin-1 are significantly associated with non-menstral TSS. Lancet ; 25: ) Bass JW, Hadson LB, Peixotto JH: Probable Toxic Shock Syndrome Without Shock andn Multisyutem Involvement. Pediatrics 1982; 70:

7 enterotoxin-like protein in Staphylococcus aureus strains from patients with toxic shock syndrome. 15) Miwa K, Fukuyama M, Kunitomo T, Igarashi H: Rapid assay for detection of Toxic Shock Syndrome Toxin 1 from human sera. J Clin Microbiol Ann Intern Med 1982; 96: ; 32: ) Kunstmann G, Schroder E, Hasbach H, Pulverer G: Immune response to Toxic Shock Syndrome Toxin-1 (TSST-1) and to staphylococcal enter- otoxins A, B and C in Staphylococcus aureus infections. Zbl Bakt Hyg 1989; 271: ) Bergdoll MS, Crass BA, Reiser RF et al.: An

8 A New Exanthematous Disease in Newborn Infants Caused by Exotoxins Producing Staphylococcus aureus; Exotoxins Production of the Isolates and Serum Levels of Antitoxin Antibody in the Patients and Umbilical Cord Blood Takashige OKADA & Seikyou FURUKAWA Division of Pediatrics, National Kagawa Children's Hospital Keishi MIWA & Rumiko SAKAI Medical Devices & Diagnostics Research Laboratories, Toray Industries, Inc Junichi SUGIYAMA Denka Seiken Co., Ltd Recently. in Japan newly neonatal exanthematous disease was elucidated to be caused by staphyloccocal superantigcnic exotoxins, mainly TSST-1. We studied exotoxins producibility of 43 strains of S. aureus isolated from neonates with exanthematous disease and examined antibody titers to staphylococcal enterotoxin A, B, C (SEA, SEB, SEC) and toxic shock syndrome toxin 1 (TSST-1) of the patients and control (umbilical cord blood from term infants). The results were as follows of 43 strains (79%) isolated from the patients were SEC and TSST-1 producing MRSA, 5 strains (12%) were SEB, SEC, and TSST-1 producing MRSA, 1 strain (2%) was SEB and TSST-1 producing MRSA, 2 strains (12%) were SEB producing MSSA and did not produce TSST-1. The 1 strain (2%) was MSSA which produced SEC and TSST neonates with exanthematous disease, who showed typical clinical signs and laboratry findings of thrombocytopenia, with SEC and TSST-1 producing MRSA isolates had significantly low anti-tsst-1 antibody titers at onset (p< 0.05), compared with the control (umbilical cord blood from term infants): TSST-1 appeared to the causative agent for the disease. In two neonates with exanthematous disease, with SEB- and non- TSST-1--producing MSSA isolates, anti-seb antibody titers were low at onset, so SEB appeared to the causative agent for the disease. 3. In Japan, low anti-tsst-1 antibody titers were found in the umbilical blood samples from about 70% of term infants ; and low anti-seb or anti-sec antibody titers were found in samples from only about 10% of them, that is, a number of term infants had anti-seb and anti-sec antibodies. The majority of S. aureus isolated from neonates with exanthematous disease were enterotoxinand TSST-1 producing MRSAs. The results of our study by measuring antitoxin antibody titers suggested that SEB and SEC might not be pathogenically responsible, but TSST-1 was considered to be responsible for the majority of exanthematous disease. Prevalence of TSST-1 producing MRSA in the neonatal and premature baby ward is the main cause for the high incidence of this disease in Japan, whereas the low antibody titer to TSST-1 in the mother, in comparison with the anti- enterotoxin antibody titers, may also be a predisposing factor.

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