16 mo 3. A 97% 16 mo A / / 100

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1 A Margaret H. Danchin, PhD a,b,c, Susan Rogers, MSc b, Loraine Kelpie, BHlthSc(Nurs) b, Gowri Selvaraj, BSc b, Nigel Curtis, PhD a,b,c, John B. Carlin, PhD a,b, Terence M. Nolan, PhD b,d and Jonathan R. Carapetis, PhD a,b,c,e a Department of Paediatrics; b Murdoch Children s Research Institute, Parkville, Australia; c Department of General Medicine, Royal Children s Hospital, Melbourne, Australia; d School of Population Health, University of Melbourne, Melbourne, Australia; e Menzies School of Health Research, Charles Darwin University, Darwin, Australia A mo (853)13 12 A 97% 16 mo (5 12 ) A A / / 100 A 43% 1 13%1 A 13% 8% 16% 2% A (acute pharyngitis); A (group A Streptococci); (incidence); (transmission); (carriage); (serology); (school-aged children) GAS = group A Streptococcus SES = socioeconomic status ASO = antistreptolysin O ADB = anti-dnase B ULN = upper limit of normal CI = confidence interval RR = relative risk Address correspondence to Margaret H. Danchin, PhD, Murdoch Children s Research Institute, Department of Paediatrics, Flemington Road, Parkville 3052, Australia. margie. danchin@rch.org.au PEDIATRICS

2 [1] A (GAS) [2] [37] 2060 GAS GAS (GAS ) GAS ( ) [8, 9] GAS GAS GAS 16 mo (Royal Childrens Hospital Ethics in Human Research Committee) 3 Deer Park Essendon North Nepean Deer Park (SES) Deer Park ( ) Essendon NorthNepean ( ) [10] GAS 5 10 y GAS [11] 1 ( ) ( ) GAS1 2wk () 2 wk(3 4wk) 98 DANCHIN et al

3 1 / n (%) Nepean Essendon North Deer Park P b a (3) 196 (97) 66 (34) 67 (34) 63 (32) a (6) 828 (94) 286 (35) 300 (36) 242 (29) (71) 358 (43) 122 (43) 127 (42) 109 (45) (83) 159 (44) 56 (46) 60 (47) 43 (39) (17) 199 (56) 66 (54) 67 (53) 66 (61) (28) 470 (57) 164 (57) 173 (58) 133 (55) /y (29) 84 (18) 22 (13) 39 (23) 23 (17) (57) 331 (70) 118 (72) 114 (66) 99 (74) (14) 55 (12) 24 (15) 20 (12) 11 (8) (50) 230 (49) 85 (52) 83 (48) 62 (47) (50) 240 (51) 79 (48) 90 (52) 71 (53) (14) 35 (8) 13 (8) 9 (6) 13 (11) / 80 2 (14) 78 (18) 25 (16) 34 (22) 19 (16) (72) 317 (74) 117 (75) 113 (72) 87 (73) (100) 430 (92) 155 (91) 156 (90) 119 (89) a () b 3 χ 2 P 3 4mo GAS GAS ( ) GAS GAS 2 wk 2 wk GAS ( ) 5 d GAS30 d GAS emm () 3 GASGAS GAS GAS GAS O (ASO) DNase B (ADB) 0.2 log-10 ASOADB ASOADBGAS PEDIATRICS

4 GAS 7d ( [12, 13] )ASO () ADB (ULN) ASOADBULN ULN [14] GAS GASGAS [15] GAS M (Lancefield ) emm (M ) GAS10% 160 ( 240 ) % (CI) (10 4) % (20 5.3) % 20% χ 2 Fishers Poisson logistic GASStata 7 (Stata) Amies 24 h37 5% CO 2 24 h [16, 17] (Stretex Oxoid Basingstoke United Kingdom) β- (A C G) Wayne Devenish ASOADB [18] 202 (853)196 (828 ) 97% (1)3Deer Park SES Nepean 1 /3 16% 41% ( 2) 2 GAS A / / / / / / y 100 y 95% CI 95% CI y 100 y y 100 y 95% CI /y a a DANCHIN et al

5 3 GAS (%) (n = 828) (n = 84) (n = 331) (n = 55) (n =358) a (15) 129 (52) 26 (10) 57 (23) GAS 54 (22) 4 (11) 32 (25) 3 (12) 15 (26) 35 (65) 2 (50) 20 (63) 1 (33) 12 (80) 12 (22) 1 (25) 8 (25) 1 (33) 2 (13) 7 (13) 1 (25) 4 (13) 1 (33) 1 (1) b 19 (35) 2 (50) 11 (34) 1 (33) 5 (33) GAS 32 6 (19) 18 (56) 3 (9) 5 (16) 21 (66) 5 (83) 12 (67) 2 (67) 2 (40) 3 (10) 0 (0) 2 (11) 0 (0) 1 (20) 8 (25) 1 (17) 4 (22) 1 (33) 2 (40) b 9 (28) 3 (75) 4 (22) 0 (0) 2 (40) a GAS GAS b GAS GAS GAS 5432GAS ( 3) 26%GAS 20% 5 12 GAS (25%) 48% (RR) 0.52 (95% CI ) P GAS RR 1.2 (95% CI )P= (3) 41% 2/ GAS 1.8 RR 1.8 (95% CI ) P =0.003 GAS 19GAS16 GAS (35 3) (32%) ASO 10 (21%) ADB ( ) ASO350 U () 733 U (21) d GAS GAS GAS GAS %13% 8% 14% 5%3% 1 GASGAS PEDIATRICS

6 60% 20% 15% ( 2) GAS ( ) % 4% ( 4) 3 GAS 13% 8% 16% 2% GAS Poisson GAS / SESGAS GAS ( ) ( 5) GAS GAS 43% 1 (18 / 42) 1 (11 / 18) 2 ( )13% (95% CI 9 18)GAS81% (26 / 32) emm96% (25 / 26) emm emm 22emm emm emm emm GAS 50 y GAS5 12 GAS (13%) [19, 20] 15%18% SES GAS GAS 23% [21] 26% [22] GAS 4 GAS GAS GAS / / 100 / /100 y y 95%CI y y 95%CI /y DANCHIN et al

7 5 GAS Poisson /IRR(95% CI) A / / IRR (95% CI) IRR (95% CI) a 1.00 a 1.00 a ( ) 0.81 ( ) 0.68 ( ) a 1.00 a 1.00 a ( ) 0.23 ( ) 0.18 ( ) ( ) 0.40 ( ) 0.38 ( ) a 1.00 a 1.00 a ( ) 1.61 ( ) 1.87 ( ) ( ) 1.59 ( ) 1.77 ( ) 1.00 a 1.00 a 1.00 a 1.76 ( ) 2.50 ( ) 1.62 ( ) 1.74 ( ) 1.56 ( ) 0.96 ( ) a 1.00 a 1.00 a ( ) 1.12 ( ) 0.50 ( ) ( ) 0.67 ( ) 0.57 ( ) IRR a 50% 95% 30% [3, 4, 23] GAS GAS GAS [23] GAS 1 /4 (1 / 3) 1 /3 GAS ( ) 2/3GAS GAS GAS GAS 24% 36% [2427] GAS GAS GAS GAS 1 1 8d GAS PEDIATRICS

8 [13] GAS [2830] ( 1 7d ) ULN () 1 GAS GAS 20% 5 GAS GAS (26%) GAS [31] (27%) GAS [32] GASSES [19, 25, 33, 34] [4] GAS [4] [3] GAS SES GAS () [4, 35, 36] GAS [37] GAS GAS 50 y GAS 1 GAS 1 Charles J, et al. Med J Aust 2004;180: Bisno AL, et al. Clin Infect Dis 2002;35: Lennon D. Rheumatic fever: a preventable disease? The New Zealand experience. In: Martin DR, et al, eds. Streptococci and Streptococcal Diseases: Entering the New Millennium Proceedings of the XIVth Lancefield International Symposium on Streptococci and Streptococcal Diseases. Auckland, New Zealand: ESR; Nandi S, et al. Bull World Health Organ 2001;79: Kaplan EL, et al. Lancet 2001;358: Zwart S, et al. BMJ 2003;327: Martin JM, et al. Pediatrics 2004;114: Kotloff KL, et al. Pediatr Infect Dis J 2004;23: McNeil SA, et al. A double-blinded, randomized, controlled phase II trial of the safety and immunogenicity of a 26 valent 104 DANCHIN et al

9 group A Streptococcus vaccine in healthy adults. Presented at: XVIth Lancefield International Symposium on Streptococci and Streptococcal Diseases; September 25 29, 2005; Palm Cove, Australia 10 Australian Bureau of Statistics census data. Available at: Accessed September 11, Centor RM, et al. Med Decis Making 1981;1: Lancefield RC. J Exper Med 1959;103: McCarty M. The antibody response to streptococcal infections. In: Streptococcal Infections. NY: Columbia University Press; 1954: Danchin MH, et al. J Paediatr Child Health 2005;41: Gerber MA, et al. Am J Dis Child 1988;142: Russell FM, et al. J Clin Microbiol 2006;44: Johnson DR, et al. Laboratory Diagnosis of Group A Streptococcal Infections. Geneva, Switzerland: World Health Organization; Johnson DR, et al. Determination of anti-streptolysin O. In: Johnson DR, et al, eds. Laboratory Diagnosis of Group A Streptococcal Infections. Geneva, Switzerland: World Health Organization; Cornfeld D, et al. Am J Public Health Nations Health 1961;51: Schneider WF, et al. N Engl J Med 1964;265: Holmes MC, et al. J Hyg 1958;56: Moffett HL, et al. Pediatrics 1964;33: El Kholy A, et al. J Med Microbiol 1973;6: Steinhoff M, et al. Lancet 1997;350: Breese B. Pediatrics 1966;38: Stillerman M, et al. Am J Dis Child 1961(101): Kaplan E, et al. J Infect Dis 1971;123: Rantz LA. Science 1946;103: Weinstein L, et al. Proc Soc Exp Biol Med 1946;63: Kilbourne ED, et al. J Clin Invest 1948;27: Berkovitch M, et al. Clin Pediatr (Phila) 1999;38: Smith TD, et al. Pediatrics 1989;83: Dingle J. Streptococcal infections. In: Illness in the Home: A Study of 25,000 Illnesses in a Group of Cleveland Families. Cleveland, OH: Press of Western Reserve University; 1964: James WE, B et al. N Engl J Med 1960;262: Levine J, et al. J Lab Clin Med 1966;67: Ransome OJ, et al. S Afr Med J 1983;64: Breese B, et al. War Med 1945;7:143 PEDIATRICS 2007;120(5): PEDIATRICS

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