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Epidemiology

Pre- and Postvaccination Clonal Compositions of Invasive Pneumococcal Serotypes for Isolates Collected in the United States in 1999, 2001, and 2002

Bernard Beall, M. Catherine McEllistrem, Robert E. Gertz Jr., Stephanie Wedel, David J. Boxrud, Antonio L. Gonzalez, Marie-Jo Medina, Rekha Pai, Terry A. Thompson, Lee H. Harrison, Lesley McGee, Cynthia G. Whitney, the Active Bacterial Core Surveillance Team
Bernard Beall
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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  • For correspondence: BBEALL@CDC.GOV
M. Catherine McEllistrem
2University of Pittsburgh Graduate School of Public Health and School of Medicine, Pittsburgh, Pennsylvania
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Robert E. Gertz Jr.
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Stephanie Wedel
3Minnesota Department of Health, Minneapolis, Minnesota
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David J. Boxrud
3Minnesota Department of Health, Minneapolis, Minnesota
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Antonio L. Gonzalez
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Marie-Jo Medina
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Rekha Pai
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Terry A. Thompson
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Lee H. Harrison
2University of Pittsburgh Graduate School of Public Health and School of Medicine, Pittsburgh, Pennsylvania
4Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
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Lesley McGee
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
5Department of International Health, Rollins School of Public Health, Emory University, Atlanta, Georgia
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Cynthia G. Whitney
1Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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DOI: 10.1128/JCM.44.3.999-1017.2006
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  • FIG. 1.
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    FIG. 1.

    Eighty-three clonal sets representing the isolates genotyped and the STs encountered in 1999, 2001, and 2002. Solid lines connect STs within the same clonal group determined by eBURST analysis. STs within the same eBURST group are indicated in boldface. Closely related outliers within the same clonal set are connected to eBURST sets by dotted lines. Numbers in red indicate STs calculated as founders by using eBURST with the STs generated from this study and also calculated as founders by using all known STs (28). Numbers in green indicate STs calculated as founders solely by using all known STs. Numbers in blue indicate STs calculated as founders by using only the STs found in this study for the analysis. Serotypes in parentheses indicate different serotype associations listed at www.mlst.net for the indicated STs. When no parentheses are indicated, no differences in serotype associations for the STs were observed between this study and www.mlst.net .

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    FIG.2.

    Clonal compositions of individual serotypes from invasive surveillance. The left, middle, and right columns represent isolates recovered in 1999, 2001, and 2002, respectively. The NPIs analyzed depict the numbers of isolates from individuals 5 years of age or older that were subjected to PFGE. The PIs analyzed depict the numbers of isolates from individuals less than 5 years of age that were subjected to PFGE. The percentages depict the proportions of invasive pneumococcal isolates within these serotypes that were subjected to genetic analysis. Where the numbers corresponding to these percentages are in parentheses, they refer to the total numbers of ABCs isolates within that age and serotype. The letter P indicates that at least 15% of the indicated clonal set within the indicated serotype were penicillin nonsusceptible. Serotypes in parentheses are shown when the serotype distributions listed in the global database (28) differed in any way from what we observed. Underlines indicate STs directly shared by PMEN clones (27) or clonal complexes containing these STs found among PMEN clones. Up to 30% of the isolates within a given serotype had unique PFGE profiles and were not subjected to MLST (represented by gaps in the columns). Such isolates could possibly belong to any of the clonal sets included or could represent additional clonal sets.

Tables

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  • TABLE 1.

    Invasive pneumococcal disease incidence in 1999 and 2002a

    Serotype(s)Age group (yr)19992002Change in rateP valuec
    No. of casesRatebNo. of casesRate
    All<51,16796.3630824.05−72.31<0.001
    ≥53,14119.082,41813.72−5.36<0.001
    All4,30824.372,72614.42−10.05<0.001
    PCV7 serogroups except 19A<51,06487.8514311.16−76.69<0.001
    ≥52,06712.551,2337.00−5.55<0.001
    All3,13117.711,3767.28−10.43<0.001
    Non-PCV7 serogroups plus 19A<51038.5016512.88+4.38<0.001
    ≥51,0676.481,1856.72+0.240.4
    All1,1706.621,3507.14+0.520.06
    • ↵ a The surveillance areas included California (San Francisco only), Connecticut (state), Georgia (the 20-county Atlanta metro area), Maryland (the 7-county Baltimore II area), Minnesota (the 7-county Twin Cities area), New York (the 15-county Albany and Rochester areas), Oregon (the 3-county Portland area), and Tennessee (4 counties).

    • ↵ b Number of cases per 100,000 individuals.

    • ↵ c P values are for 1999 versus 2002.

  • TABLE 2.

    Incidence of invasive cases in group less than 5 years of age due to PCV7-nonrelated serotypes and serotype 19A in 2002 relative to incidence in 1999a

    Serotype19992002P valued
    Actual (projectedb) no. of cases% of totalcActual (projected) no. of cases% of total
    16 (7)[0.6]3[1]
    36 (7)[0.6]8 (9)[2.9]0.002
    51[<0.1]0
    7F8 (9)[0.8]11 (13)[4.2]<0.001
    10A1[<0.1]3[1]
    11A1[<0.1]4 (5)[1.6]
    12F12 (14)[1.2]7 (8)[2.6]0.106
    15B/15C/15F6 (7)[0.6]26 (30)[9.7]<0.001
    16F2[<0.1]2[0.6]
    17F01[0.3]
    19A20 (23)[2]41 (47)[15.3]<0.001
    22F7[0.6]9 (10)[3.2]0.002
    24B/24F1[<0.1]0
    33A01[0.3]
    33F8 (9)[0.8]14 (16)[5.2]<0.001
    35B2[<0.1]1[0.3]
    35F01[0.3]
    385 (6)[0.5]11 (13)[4.2]<0.001
    Nontypeable2[<0.1]0
    Total1,167308
    • ↵ a The surveillance areas are the same as those listed in footnote a of Table 1.

    • ↵ b Projected number of cases in the group <5 years of age for the indicated surveillance areas since serotypes were not determined for 171 of the total (n = 1,167) year 1999 isolates and were not determined for 41 of the the total (n = 308) year 2002 isolates.

    • ↵ c Percentage of total isolates recovered from this age group in the indicated year.

    • ↵ d Comparison of proportions for serotypes which have ≥2% of total strains in at least 1 year by using the chi-square or the Fisher exact test.

  • TABLE 3.

    PMEN clones sharing genetic identity or close genetic relatedness to ABCs pneumococcal isolates recovered in 1999, 2001, and 2002

    PMEN clone (ST)Serotype(s) of invasive pneumococcal isolates genetically related to PMEN clonea
    199920012002
    Spain23F-1 (ST81)19F, 23F, 14, 19A19F, 23F19A, 23F
    Spain6B-2 (ST90)6B, 6A6B
    Spain9V-3 (ST156)9V, 6B, 149V, 14, 19F, 9A15B, 9N
    Tennessee23F-4 (ST37)23F23F, 23A23A
    Spain14-5 (ST18)14
    Hungary19A-6 (ST268)23F
    South Africa6B-8 (ST185)6B
    England14-9 (ST9)14, 19F14
    Taiwan19F-14 (ST236)19F19F19A
    Taiwan23F-15 (ST242)23F23F23F
    Maryland6B-17 (ST384)6B6B
    Columbia5-19 (ST289)55
    Portugal19F-21 (ST177)19F19F
    North Carolina6A-23 (ST376)6A6A6A, 19A
    Utah35B-24 (ST377)35B35B35B
    Sweden15A-25 (ST63)15A15A, 14
    Colombia23F-26 (ST338)23A23A
    • ↵ a A total of 1,168 invasive isolates were examined from year 1999, 1,126 invasive isolates were examined from year 2001, and 377 invasive isolates were examined from year 2001.

  • TABLE 4.

    Clonal complex distribution among invasive pneumococcal isolates in 1999, 2001, and 2002

    Serotype (clonal complex)aNo. of isolates within complex/no. of isolates analyzed (%) in the following years for the indicated age groups
    199920012002b
    <5 yr≥5 yr<5 yr≥5 yr<5 yr≥5 yr
    1 (ST227)5/6 (83.3)15/15 (100)4/4 (100)28/34 (82.4)4/4 (100)None analyzed
    1 (ST217)1/6 (16.7)0/150/41/34 (2.9)0/4None analyzed
    1 (ST1174) 0/60/60/62/34 (5.9)0/4None analyzed
    3 (ST180)6/6 (100)48/50 (96.0)6/6 (100)68/70 (97.0)8/8 (100)11/11 (100)
    4 (CC899)53/71 (74.6)None analyzed29/35 (82.9)18/34 (52.9)None analyzed1/1 (100)
    4 (ST205)8/71 (11.3)None analyzed6/35 (17.1)11/34 (32.4)None analyzed0/1 (0)
    5 (ST653)100 (1)None analyzed1/1 (100)1/1 (100)No type 5sNone analyzed
    6A (CC1296)19/57 (33.3)0/110/38 (26.3)0/94/13 (30.7)14/41 (34.1)
    6A (CC460)13/57 (22.4)0/111/38 (29.4)3/9 (33.3)3/13 (23.1)0/41
    6A (CC473)5/57 (8.8)0/17/38 (18.4)1/9 (11.1)1/13 (7.7)15/41 (36.6)
    6A (ST395)1/57 (1.8)1/1 (100)3/38 (7.9)0/93/13 (23.1)2/41 (4.9)
    6A (CC490)None detectedb0/12/38 (5.3)0/9None detectedNone detected
    6A (CC138)None detected0/12/38 (5.3)0/9None detectedNone detected
    6A (ST1091)None detected0/11/38 (2.6)0/9None detectedNone detected
    6A (ST1175)None detected0/11/38 (2.6)0/9None detectedNone detected
    6A (ST90)1/57 (1.8)0None detected0/9None detectedNone detected
    6A (ST660)1/57 (1.8)0None detected0/9None detectedNone detected
    6A (ST690) None detected0None detected2/9 (22.2)None detectedNone detected
    6A (CC1292) None detected0/1None detected3/9 (33.3)None detected6/41
    6B (CC138)13/103 (12.6)0/113/45 (28.9)2/15 (9.1)None analyzed1/4 (25.0)
    6B (CC146)22/103 (21.4)0/111/45 (24.4)4/15 (28.6)None analyzed0/4
    6B (ST90)13/103 (12.6)0/113/45 (28.9)5/15 (28.6)None analyzed0/4
    6B (CC384)6/103 (5.8)0/15/45 (11.1)3/15 (20.0)None analyzed0/4
    6B (CC1269)3/103 (2.9)0/1None detected0/15None analyzed0/4
    6B (CC490)None detected0/12/45 (4.4)0/15None analyzed3/4 (75.0)
    6B (ST185)1/103 (1.0)0/1None detected0/15None analyzed0/4
    6B (ST690) None detected1/1None detected1/15 (6.7)None analyzed0/4
    7B (ST664)1/1 (100)No type 7BsNo type 7BsNo type 7BsNo type 7BNo type 7Bs
    7C (ST1207)No type 7CNo type 7CsNo type 7Cs1/1 (100)1/1 (100)1/1 (100)
    7F (ST191)7/7 (100)22/24 (91.7)13/15 (86.7)29/30 (96.7)5/6 (83.3)3/3 (100)
    7F (CC218) 0/71/24 (4.2)None detectedNone detectedNone detected0/3
    8 (ST53)No type 8None analyzed2/2 (100)1/10 (10.0)No type 8100 (1)
    8 (ST1268) No type 8None analyzed0/29/10 (90.0)No type 80/1
    9A (CC156)No type 9ANo type 9As3/3 (100)No type 9AsNo type 9ANo type 9As
    9N (CC66)2/2 (100)9/11 (81.8)3/3 (100)34/37 (91.9)None analyzed3/5 (60.0)
    9N (CC156) 0/2None detected0/3None detectedNone analyzed1/5 (20.0)
    9N (CC1257) 0/2None detected0/3None detectedNone analyzed1/5 (20.0)
    9V (CC156)60/72 (83.3)21/26 (80.1)26/38 (68.4)28/42 (66.7)2/2 (100)7/7 (100)
    9V (CC1269)9/72 (12.5)3/26 (11.5)11/38 (28.9)14/42 (33.3)0/20/2
    10A (CC460)1/1 (100)None analyzed3/3 (100)2/5 (40)3/3 (100)2/2 (100)
    10A (ST1263)0/1None analyzed0/32/5 (40)0/30/2
    11A (CC62)1/1 (100)22/24 (87.5)5/5 (100)41/41 (100)2/2 (100)9/9 (100)
    12F (CC218)11/11 (100)48/49 (97.8)17/17 (100)65/65 (100)4/6 (66.7)1/1 (100)
    12F (ST989)0/11None detected0/170/651/6 (16.7)0/1
    12F (CC1292)0/11None detected0/170/651/6 (16.7)0/1
    13 (CC392) No type 13None analyzedNo type 13s2/2 (100)No type 130/1
    13 (ST1260) No type 13None analyzedNo type 13s0/2No type 131/1 (100)
    14 (CC13)96/208 (46.2)None analyzed48/91 (52.7)19/36 (52.7)None analyzed3/3 (100)
    14 (CC124)78/208 (37.5)None analyzed33/91 (30.0)9/36 (25.0)None analyzed0/3
    14 (CC63)None detectedNone detected6/91 (6.6)0/36None analyzed0/3
    14 (CC1269)5/208 (2.4)None analyzed2/91 (2.2)2/36 (5.9)None analyzed0/3
    14 (CC156)None detectedNone analyzed3/91 (3.3)1/36 (2.8)None analyzed0/3
    14 (CC66)4/208 (1.9)None analyzed1/91 (1.1)1/36 (2.8)None analyzed0/3
    15A (CC63) No type 15AsNone analyzedNo type 15As3/3 (100)No type 15As12/13 (92.3)
    15A (ST817) No type 15AsNone analyzedNo type 15As0/3No type 15As1/13 (7.7)
    15BC (CC199)6/6 (100)None analyzed20/22 (90.9)3/3 (100)27/33 (81.8)5/5 (100)
    15BC (ST1262)0/6None analyzedNone detected0/32/33 (6.1)0/5
    15BC (ST1267)0/6None analyzedNone detected0/32/33 (6.1)0/5
    15BC (ST1259)0/6None analyzedNone detected0/31/33 (3.0)0/5
    15BC (CC156)0/6None analyzedNone detected0/31/33 (3.0)0/5
    16F (CC659)1/1 (100)0/2No type 16Fs7/7 (100)2/2 (100)1/3 (33.3)
    16F (CC30) 0/12/2 (100)No type 16s0/70/22/3 (66.7)
    17F (CC392)No type 17FNone analyzed1/1 (100)None analyzed1/1 (100)None analyzed
    18BCF (CC113)74/93 (79.6)None analyzed28/40 (68.3)9/11 (81.8)2/3 (66.7)2/2 (100)
    18BCF (ST496)8/93 (8.6)None analyzed5/40 (12.5)1/11 (9.0)0/30/2
    18BCF (ST666)1/93 (1.1)None analyzed1/40 (2.4)1/11 (9.0)1/3 (33.3)0/2
    18BCF (CC66)1/93 (1.1)None analyzedNone detected0/110/20/2
    19A (ST199)13/18 (72.2)46/64 (71.9)18/29 (62.1)10/10 (100)27/40 (67.5)32/45 (71.1)
    19A (CC172)None detected2/64 (3.1)2/29 (6.9)0/100/401/45 (2.2)
    19A (ST665)1/18 (5.5)None detected1/29 (3.4)None detected0/400/45
    19A (CC236)None detectedNone detected1/29 (3.4)None detected3/40 (7.5)1/45 (2.2)
    19A (CC1296)None detectedNone detectedNone detectedNone detected4/40 (10.0)5/45 (11.1)
    19A (CC81)1/18 (5.5)None detectedNone detectedNone detected1/40 (2.5)2/45 (4.4)
    19A (ST230)None detectedNone detected2/29 (6.9)None detected0/400/45
    19A (ST1297)None detectedNone detected1/29 (3.4)None detected3/40 (7.5)2/45 (4.4)
    19A (CC62)None detectedNone detectedNone detectedNone detected2/40 (5.0)0/45
    19A (ST1374) None detectedNone detectedNone detected0/100/401/45 (2.2)
    19A (ST847) None detectedNone detectedNone detected0/100/401/45 (2.2)
    19F (CC236)23/110 (20.9)None examined10/47 (21.3)3/12 (25.0)1/2 (50)8/9 (88.9)
    19F (CC251)22/110 (20.0)None examined19/47 (40.4)3/12 (25.0)0/20/9
    19F (CC81)13/110 (11.8)None examined3/47 (6.4)3/12 (25.0)0/20/9
    19F (CC199)10/110 (9.1)None examined1/47 (2.1)1/12 (9.1)0/20/9
    19F (ST655)2/110 (1.8)None examined0/470/120/20/9
    19F (CC177)2/110 (1.8)None examined4/47 (8.5)0/120/20/9
    19F (CC1269)1/110 (0.9)None examined2/47 (4.3)1/12 (9.1)0/20/9
    19F (ST1340)None detectedNone examined0/470/121/2 (50)0/9
    19F (CC13)1/110 (0.9)None examined0/470/120/20/9
    19F (ST43)1/110 (0.9)None examined4/47 (8.5)0/120/20/9
    19F (CC172)None detectedNone examined1/47 (2.1)0/120/20/9
    19F (CC425) 4/110 (3.6)None examined3/47 (6.4)0/120/20/9
    19F (CC63) None detectedNone examined0/471/12 (9.1)0/20/9
    19F (ST1203) None detectedNone examined0/470/120/21/9 (11.1)
    20 (CC899)No type 20None examined1/1 (100)4/6 (66.7)No type 20None examined
    20 (CC1257)No type 20None examined0/133.3 (2)No type 20None examined
    22F (CC433)6/6 (100)30/31 (96.8)19/19 (100)90.2 (46)92.9 (13)100 (2)
    22F (ST1294)0/2None detected0/1None detected7.1 (1)0/2
    23A (CC172)2/2 (100)None examined0/10/1No type 23A5/6 (83.3)
    23A (ST1336)0/2None examined1/1 (100)0/1No type 23A0/6
    23A (ST1338) 0/2None examined02/4 (50.0)No type 23A0/6
    23A (CC37) 0/2None examined02/4 (50.0)No type 23A1/6 (16.7)
    23F (CC37)46/64 (71.9)None examined26/37 (70.3)6/13 (46.2)None examined0/5
    23F (CC81)11/64 (17.2)None examined5/37 (13.5)4/13 (30.7)None examined4/5 (80.0)
    23F (ST242)4/64 (6.2)None examined1/37 (2.7)2/13 (15.4)None examined1/5 (20.0)
    23F (CC662)1/64 (1.6)None examinedNone detected0/13None examined0/5
    23F (CC268)None detectedNone examined1/37 (2.7)1/13 (7.7)None examined0/5
    23F (CC460)None detectedNone examined2/37 (5.4)0/13None examined0/5
    24BF (CC72)No type 24BFNone examined1/1 (100)None examinedNone examined1/1 (100)
    28F (ST546) No type 28FNo type 28FNo type 28FNo 28F isolatesNo 28F isolates100 (1)
    31 (ST568) No type 311/1 (100)No type 312/2 (100)1/1 (100)No type 31
    33F (CC662)7/7 (100)1/1 (100)10/11 (90.9)7/8 (87.5)18/18 (100)1/1 (100)
    33F (ST1012)0/70/11/11 (9.1)1/8 (12.5)0/180/1
    35B (CC377)2/2 (100)10/14 (71.4)2/2 (100)27/35 (77.1)100 (1)18/19 (94.7)
    35B (ST452) 0/24/14 (28.6)0/28/35 (22.9)0/11/19 (5.3)
    35F (ST498)No type 35FNone examined2/2 (100)2/2 (100)None examinedNone examined
    37 (ST447) No type 37None examinedNo type 37None examinedNo type 371/2 (50.0)
    38 (ST393)5/5 (100)None examined7/7 (100)1/1 (100)15/15 (100)None examined
    • ↵ a Clonal complexes in boldface were found only among isolates from individuals ≥5 years of age. Up to 30% of the isolates within a given serotype had unique PFGE profiles and were not subjected to MLST (represented by gaps in the columns in Fig. 2). Such isolates could possibly belong to any of the clonal sets included or could represent additional clonal sets.

    • ↵ b Year 2002 isolates were primarily selected from non-PCV7 serotypes.

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Pre- and Postvaccination Clonal Compositions of Invasive Pneumococcal Serotypes for Isolates Collected in the United States in 1999, 2001, and 2002
Bernard Beall, M. Catherine McEllistrem, Robert E. Gertz Jr., Stephanie Wedel, David J. Boxrud, Antonio L. Gonzalez, Marie-Jo Medina, Rekha Pai, Terry A. Thompson, Lee H. Harrison, Lesley McGee, Cynthia G. Whitney, the Active Bacterial Core Surveillance Team
Journal of Clinical Microbiology Mar 2006, 44 (3) 999-1017; DOI: 10.1128/JCM.44.3.999-1017.2006

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Pre- and Postvaccination Clonal Compositions of Invasive Pneumococcal Serotypes for Isolates Collected in the United States in 1999, 2001, and 2002
Bernard Beall, M. Catherine McEllistrem, Robert E. Gertz Jr., Stephanie Wedel, David J. Boxrud, Antonio L. Gonzalez, Marie-Jo Medina, Rekha Pai, Terry A. Thompson, Lee H. Harrison, Lesley McGee, Cynthia G. Whitney, the Active Bacterial Core Surveillance Team
Journal of Clinical Microbiology Mar 2006, 44 (3) 999-1017; DOI: 10.1128/JCM.44.3.999-1017.2006
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KEYWORDS

Pneumococcal Vaccines
Streptococcus pneumoniae

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