Surveillance of invasive pneumococcal infection in Belgium
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1 Surveillance of invasive pneumococcal infection in Belgium National Reference Laboratory Start in 198 Laboratory Microbiology UH Leuven (prof. J. Vandepitte) Capsular type determination Antibiotic susceptibility Limited clinical data 1
2 Pneumococcus capsular typing Danish nomenclature (Kauffman und Lund, 1954) Nine pooled sera = A-I 93 serovars 26 sera of a single serotype 2 group sera = 2 to 4 cross-reacting serovars (e.g. serogroup 7 = 7F, 7A, 7B, 7C) Since 26 all IPD isolates from subjects aged <18 years belonging to serogroups were further serotyped with factor sera (Statens Seruminstitut Copenhagen) 2
3 3
4 Clinical source of pneumococci (Belgium ) blood and pleural fluid 3439 (82.6) middle ear aspirates 3765 (1.2) cerebrospinal fluid 1781 (4.8) various body fluids 888 (2.4) 4
5 Age distribution of patients with pneumococcal bacteraemia (Belgium ) ,2% 26.6% 16.1% 2.9% 2.2% -4 y 5-9y 1-19y 2-59y >6y 5
6 Pneumococcal polysaccharide vaccine 23-valent vaccine (Pneumo 23),5 ml single dose vial containing purified capsular polysaccharide from each of the 23 types of S. pneumoniae (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 1A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 2 22F, 23F) This vaccine induces B-cell type-specific protective antibody without a contribution of helper T-cells Low antibody titers, particularly in children less than 18 months of age 6
7 number of pneumococci number of PPV 23 vaccine doses Evolution of number of pneumococci isolated from blood and pleural fluid cultures in elderly (>6 years) and number of 23-valent-vaccines ( ) (89) (9) (95) (13) (15) (12) (99) (18) (113) (14) (13) (116)(18) (17) (17) (16) (14) (14) (98) 15 () number of participating laboratories 7
8 Evolution of number of pneumococci isolated from blood and pleural fluid cultures in adults (>2-<6 years) ( ) (89) (9) (95) (13) (15) (12) (99) (18) (113) (14) (13) (116) (18) (17) (17) (16) (14) (14) (98) () number of participating laboratories 8
9 Epidemiology and outcome of invasive pneumococcal disease (29-211) collaboration of 5 hospitals, 1332 patients age group n(%) Type of IPD Total (n=1332) 18-49y (n=22) 5-64y (n=37) 65y (n=742) bacteraemic pneumonia (77,3) 276 (74,6) 63 (81,3) empyema (9,5) 32 (8,6) 41 (5,5) meningits 73 8 (3,6) 32 (8,6) 33 (4,4) bacteraemia without focus 73 8 (3,6) 17 (4,6) 48 (6,5) other (5,9) 13 (3,5) 17 (2,3) J. Verhaegen et al. Eurosurveillance, 214, 19, 7 August 9
10 Epidemiology and outcome of invasive pneumococcal disease (29-211) age group n P-value Comorbidities 18-49y (n=22) 5-64y (n=37) 65y (n=742) any 118 (53%) (84%) <,1 COPD <,1 cancer <,1 heart failure <,1 diabetes <,1 renal insufficiency <,1 immunosuppression ,32 2 comorbidities 5 (45%) (54%),1 J. Verhaegen et al. Eurosurveillance, 214, 19, 7 August 1
11 Disease outcome at discharge by age and type of IPD category n admission ICU n(%) total (32,7) cured n(%) 884 (66,5) Outcome at discharge with symptoms n (%) 237 (17,8) death n (%) 28 (15,7) P-value overall age 18-49y 5-64y 65y (24,5) 154 (41,6) 226 (3,6) 157 (71,7) 24 (64,9) 487 (65,8) 49 (22,4) 83 (22,4) 15 (14,2) 13 (5,9) 47 (12,7) 148 (2,),44 type of IPD bacteraemia pneumonia empyema meningitis bacteraemia without focus other (28,9) 49 (52,1) 59 (8,8) 12 (16,4) 11 (25,6) 722 (69,) 49 (52,1) 38 (52,1) 51 (69,9) 24 (55,8) 169 (16,2) 35 (37,2) 16 (21,9) 4 (5,5) 13 (3,2) 155 (14,8) 1 (1,6) 19 (26) 18 (24,7) 6 (14,),49 J. Verhaegen et al. Eurosurveillance, 214, 19, 7 August 11
12 Pneumococcal conjugate vaccines 7-valent vaccine (PREVENAR) 2 µg of 6 capsular polysaccharides: 4, 9V, 14, 18C, 19F, 23F 4 µg of polysaccharide 6B conjugated to 2 µg mutant non-toxic C. diphtheriae CRM 197 protein no longer available and replaced in 211 by 13-valent vaccine 1-valent vaccine (SYNFLORIX) 1 µg of 7 capsular polysaccharides: 1, 5, 6B, 7F, 9V, 14, 23F 3 µg of 3 capsular polysaccharides: 4, 18C, 19F conjugated to 9-16 µg protein D Haemophilus influenzae or 1 µg (Tetanus anatoxine (18C) or 6 µg C. diphtheriae anatoxine (19F) 13-valent vaccine (PREVENAR 13) 13 capsular polysaccharides: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F conjugated to 2 µg mutant non-toxic C. diphtheriae CRM 197 protein 12
13 13
14 number of pneumococci number of conjugate vaccines Evolution of number of pneumococci isolated from blood and pleural fluid cultures in young children ( 4 years) ( ) (89) (9) (95) (13) (15) (12) (99) (18) (113) (14) (13) (116) (18) (17) (17) (16) (14)(14) (98) 15 () number of participating laboratories PCV7 PCV13 14
15 Percentage (%) Evolution of number of invasive infections and percentage of capsular types included in the three different conjugate vaccines in children <2 years in Belgium (26-213) ,53 45,89 4,58 33,77 52,59 13,64 28,81 66,1 32,5 64,8 41,7 55,4 31,8 63,6 54,7 42,3 5,8 2,7 2,8 4, ,7 15,3 not included in vaccine 1-valent vaccin + 13 valent vaccin (= 7-valent vaccin + 1, 5, 7F) (=1- valent vaccin +3, 6A, 19A) 7-valent vaccin (= 4, 6B, 9V, 14, 18C, 19F, 23F) Year N of isolates PCV7 PCV13 15
16 Evolution of some capsular types in invasive pneumococcal infections not included in the 13 valent-conjugate vaccine in children 2y (Belgium ) 16
17 Percentage (%) Evolution of number of invasive infections and percentage of capsular types included in the three different conjugate vaccines in children 2 - <4 years in Belgium (26-213) ,12 1,43 59,59 62,61 28,28 26,96 16,8 72,8 1,4 1,8 1,6 1,4 1,2 1,5 Year N of isolates PCV7 PCV13 24,4 73,8 18,4 8 22,2 76,4 25,8 73 4,9 57,6 not included in vaccine 13-valent vaccin (= 7-valent vaccin + 1, 3, 5, 6A, 7F, 19A) 7-valent vaccin (= 4, 6B, 9V, 14, 18C, 19F, 23F) 17
18 number of pneumococci Evolution of number of pneumococci isolated from cerebrospinal fluid in different age groups (Belgium ) y 2<6y 5-<2y 2-<5y 3 -<2y
19 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % Evolution of relative percentage of vaccine serogroups among invasive pneumococcal infections ( 5 years, ) 7,9 1,4 1,8 26,2 55,1 32,1 36,2 47,3 43,8 1,8 1,2 9,2 211 (N=186) 212 (N=1161) 213 (N=115) remaining PCV23 PCV13 PCV7 19
20 2
21 Evolution of antibiotic resistance in invasive S. pneumoniae isolates (Belgium ) ,6 25,7 27,6 28,9 23,8 25,5 26,9 25,8 24, ,4 11,8 9,7 1,1 1,8 2,4 1,7,5,1 Peni tetra ofl ery cefotax MIC >,6 mg/l MIC > 1 mg/l Oflox = levofloxacin since August
22 22
23 Percentage Evolution of penicillin-resistance in S. pneumoniae (Belgium ) , Pen intermediate resistance (,12-1 mg/l) Pen resistance ( 2 mg/l) 23
24 Evolution of antibiotic resistance in some capsular types of S. pneumoniae (Belgium, ) penicilline erythromycine tetracycline All isolates type type type type type type
25 Evolution of prevalence of some SGT s in blood isolates of S. pneumoniae (>95% 19A) '8- '83 '84- '85 '86- '87 '88- '89 '9- '91 '92- '93 '94- '95 '96- '97 '98- '99 '- '1 '2 '3 '4 '5 '6 '7 '8 ' PCV7 available 25 JV-214 PCV7 reimbursed PCV13 reimbursed 36
26 Evolution of prevalence of some SGT s in blood isolates of S. pneumoniae (>95% 19A) '8- '83 '84- '85 '86- '87 '88- '89 '9- '91 '92- '93 '94- '95 '96- '97 '98- '99 '- '1 '2 '3 '4 '5 '6 '7 '8 ' JV-214 PCV7 available PCV7 reimbursed
27 Fluctuation of antibiotic-resistance in S. pneumoniae total number of IPD isolates, referred to the reference laboratory increased from 122 in 2 to 251 in 29, followed by a progressive decrease to 1735 in 213 in children: between 27 and 211, PCV 7 SGTs disappeared (<2% in 211) but the evolution was countered by the rise of non-vaccine types overall number of IPD remain stable since 211, PCV13 SGTs decreased significantly without replacement JV
28 Fluctuation of antibiotic-resistance in Result of: S. pneumoniae different campaigns for rational use of antibiotics? decrease of capsular type 14 (PCV7) with replacement by capsular types 1 and 19 followed by decrease of both capsular types after introduction of PCV13 28
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