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Azelluläre Impfstoffe gegen Keuchhusten bei Kindern

Appendices

Appendix 1. Initial search 1997 and 1998

The initial search was carried out in March 1997 and updated in March 1998, covering the period up to and including January 1998. The databases used were MEDLINE (Medline SilverPlatter CD‐ROM) and the Cochrane Central Register of Controlled Trials (CENTRAL). We searched CENTRAL using the term 'pertus* OR whoop*'. We searched MEDLINE using the following strategy:

1. explode PERTUSSIS‐VACCINE / all subheadings
2. explode BORDETELLA‐PERTUSSIS / all subheadings
3. explode WHOOPING‐COUGH / all subheadings
4. PERTUS*
5. WHOOP*
6. #1 or #2 or #3 or #4 or #5

The files downloaded from MEDLINE SilverPlatter were screened for randomised controlled trials using the RCT FILTER.

Appendix 2. April 2009 updated search strategies

In the 2009 updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to April week 2 2009) and EMBASE.com (1974 to April 2009).

We used the following search strategy to search MEDLINE and CENTRAL. The MEDLINE search was combined with the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity‐ and precision‐ maximising version (2008 revision); Ovid format (Lefebvre 2011). We modified the search strategy to search Embase.com (see below).

MEDLINE (Ovid)

1     exp Pertussis Vaccine/
2     pertussis vaccin*.tw.
3     Whooping Cough/
4     whoop*.tw.
5     Bordetella pertussis/
6     pertuss*.tw.
7     1 or 2 or 3 or 4 or 5 or 6
8     exp Vaccines, Acellular/
9     (acellular adj5 vaccin*).tw.
10     8 or 9
11     7 and 10

EMBASE.com

1. 'pertussis vaccine'/de
2. 'diphtheria pertussis tetanus vaccine'/de
3. 'diphtheria pertussis poliomyelitis tetanus vaccine'/de
4. 'diphtheria pertussis tetanus haemophilus influenzae type b hepatitis b vaccine'/de
5. 'diphtheria pertussis tetanus haemophilus influenzae type b vaccine'/de
6. 'bordetella pertussis'/de
7. 'pertussis'/de
8. 'dpt vaccine':ti,ab
9. pertuss*:ti,ab
10. whoop*:ti,ab
11. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10
12. 'acellular vaccine'/de
13. (acellular:ti,ab AND vaccin*:ti,ab)
14. #12 OR #13
15. #11 AND #14
16. 'randomized controlled trial'/de
17. 'controlled clinical trial'/de
18. 'single blind procedure'/de
19. 'double blind procedure'/de
20. 'phase 3 clinical trial'/de
21. random*:ti,ab
22. placebo*:ti,ab
23. 'clinical trial':it
24. 'randomized controlled trial':it
25. (singl*:ti,ab OR doubl*:ti,ab OR trebl*:ti,ab OR tripl*:ti,ab) AND (mask*:ti,ab OR blind*:ti,ab)
26. 'controlled clinical trial':ti,ab
27. 'controlled clinical trials':ti,ab
28. #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27
29. ('nonhuman'/exp OR 'animal'/exp) NOT 'human'/exp
30. #28 NOT #29
31. #15 AND #30

Appendix 3. MEDLINE search strategy

1     exp Pertussis Vaccine/
2     pertussis vaccin*.tw.
3     Whooping Cough/
4     whoop*.tw.
5     Bordetella pertussis/
6     pertuss*.tw.
7     1 or 2 or 3 or 4 or 5 or 6
8     exp Vaccines, Acellular/
9     (acellular adj5 vaccin*).tw.
10     8 or 9
11     7 and 10

Appendix 4. EMBASE search strategy

#14. #10 AND #13 269 17 May 2011
#13. #11 OR #12 861,917 17 May 2011
#12. random*:ab,ti OR placebo*:ab,ti OR factorial*:ab,ti OR crossover*:ab,ti OR 'cross over':ab,ti OR 'cross‐over':ab,ti OR volunteer*:ab,ti OR assign*:ab,ti OR allocat*:ab,ti OR ((singl* OR doubl*) NEAR/1
blind*):ab,ti AND [embase]/lim 822,212 17 May 2011
#11. 'randomized controlled trial'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp AND [embase]/lim 241,991 17 May 2011
#10. #6 AND #9 1,393 17 May 2011
#9. #7 OR #8 1,451 17 May 2011
#8. (acellular NEAR/5 vaccin*):ab,ti AND [embase]/lim 1,321 17 May 2011
#7. 'acellular vaccine'/de AND [embase]/lim 271 17 May 2011
#6. #1 OR #2 OR #3 OR #4 OR #5 25,318 17 May 2011
#5. pertuss*:ab,ti OR whoop*:ab,ti AND [embase]/lim 19,626 17 May 2011
#4. 'bordetella pertussis'/de AND [embase]/lim 4,046 17 May 2011
#3. 'pertussis'/de AND [embase]/lim 5,903 17 May 2011
#2. 'diphtheria pertussis tetanus vaccine'/de OR 'diphtheria pertussis tetanus hepatitis b vaccine'/de OR 'diphtheria pertussis tetanus haemophilus influenzae type b vaccine'/de OR
'diphtheria pertussis tetanus haemophilus influenzae type b hepatitis b vaccine'/de OR 'diphtheria pertussis poliomyelitis tetanus vaccine'/de OR 'diphtheria pertussis poliomyelitis tetanus hepatitis b vaccine'/de OR 'diphtheria pertussis poliomyelitis tetanus haemophilus influenzae type b hepatitis b vaccine'/de AND [embase]/lim 5,402 17 May 2011
#1. 'pertussis vaccine'/de AND [embase]/lim 4,338 17 May 2011

Appendix 5. Biosis Previews (Thomson ISI)

Topic=(pertuss* or whoop* or bordetella*) AND Topic=(acellular vaccin*)

Refined by: Topic=(random* or placebo* or clinical trial* or singl* blind* or doubl* blind*)

Appendix 6. CINAHL (Ebsco)

S18 S7 and S16
S17 S7 and S16
S16 S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15
S15 (MH "Quantitative Studies")
S14 (MH "Placebos")
S13 TI placebo* or AB placebo*
S12 TI random* or AB random*
S11 TI ( singl* blind* or doubl* blind* or tripl* blind* or trebl* blind* or singl* mask* or doubl* mask* or tripl* mask* or trebl* mask* ) or AB (singl* blind* or doubl* blind* or tripl* blind* or trebl* blind* or singl*
mask* or doubl* mask* or tripl* mask* or trebl* mask* )
S10 TI clinic* trial* or AB clinic* trial*
S9 PT clinical trial
S8 (MH "Clinical Trials+")
S7 S5 and S6 Search modes
S6 TI acellular N5 vaccin* or AB acellular N5 vaccin*
S5 S1 or S2 or S3 or S4
S4 TI ( whoop* or pertuss* ) or AB ( whoop* or pertuss* )
S3 (MH "Bordetella Pertussis")
S2 (MH "Whooping Cough")
S1 (MH "Pertussis Vaccine+")

Appendix 7. Comparison of results between the first published (primary) review and the updated reviews

 Minor adverse events: acellular vaccines versus whole‐cell vaccines

Outcomes

Number of  trials

 

Primary    Update

Sample size (n)

 

Primary    Update

Effect size ‐ RR (95% CI)

 

Primary                   Update

Anorexia

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

10               11

7                  8

8                  9

11               14

3                  4

 

13,942      19,632

18,232      18,501

18,385      18,646

1380         1939

8033         8447

 

0.47 (0.35 to 0.64)     0.43 (0.32 to 0.57)

0.50 (0.37 to 0.67)     0.45 (0.33 to 0.60)

0.52 (0.45 to 0.61)     0.50 (0.43 to 0.60)

0.35 (0.24 to 0.51)     0.40 (0.30 to 0.54)

0.41 (0.26 to 0.64)     0.42 (0.31 to 0.58)

Drowsiness

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

11               12

7                  8

8                  9

10               14

2                  3

 

20,200      20,490

19,039      19,308

19,169      19,430

1695         2254

7953         8367

 

0.74 (0.50 to 1.09)     0.72 (0.50 to 1.03)

0.67 (0.43 to 1.03)     0.61 (0.41 to 0.93)

0.56 (0.40 to 0.79)     0.56 (0.40 to 0.77)

0.43 (0.34 to 0.53)     0.48 (0.41 to 0.56)

0.50 (0.45 to 0.55)     0.49 (0.44 to 0.54)

Fever

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

18               19

15               17

15               17

19               25

5                  8

 

22,977      23,267

21,652      22,001

21,390      21,731

2513         3381

9012         9879

 

0.17 (0.13 to 0.21)     0.17 (0.13 to 0.20)

0.31(0.25 to 0.37)     0.31 (0.26 to 0.37)

0.34 (0.29 to 0.38)     0.34 (0.30 to 0.38)

0.33 (0.24 to 0.45)     0.33 (0.26 to 0.43)

0.38 (0.21 to 0.68)     0.35 (0.22 to 0.55)

Irritability/fretfulness    

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

13               15

10               12

11               13

13               16

4                  6

 

20,337      20,707

19,080      19,429

19,170      19,511

1978         2596

9165         9856

 

0.50 (0.43 to 0.58)     0.48 (0.42 to 0.56)

0.51 (0.43 to 0.60)     0.48 (0.41 to 0.56)

0.55 (0.49 to 0.62)     0.53 (0.47 to 0.59)

0.32 (0.23 to 0.45)     0.36 (0.28 to 0.47)

0.48 (0.44 to 0.51)     0.48 (0.44 to 0.51)

Prolonged crying

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

7                 8

5                 6

6                 7

4                 7

2                 2

 

16,849      17,184

16,078      16,347

16,248      16,545

955           996

7943         7943

 

0.14 (0.12 to 0.18)     0.15 (0.11 to 0.19)

0.29 (0.24 to 0.35)     0.29 (0.24 to 0.35)

0.32 (0.24 to 0.44)     0.33 (0.24 to 0.46)

0.23 (0.10 to 0.55)     0.21 (0.10 to 0.48)

0.48 (0.22 to 1.02)     0.27 (0.02 to 3.12)

Vomiting

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

7                 8

6                 7

5                 6

5                 6

1                 1

 

11,160      11,450

10,716      10,985

10,552      10,813

703           744

86             86

 

0.78 (0.67 to 0.90)     0.77 (0.66 to 0.88)

0.71 (0.60 to 0.85)     0.62 (0.45 to 0.86)

0.80 (0.66 to 0.97)     0.69 (0.46 to 1.04)

0.35 (0.15 to 0.82)     0.50 (0.22 to 1.11)

1.07 (0.10 to 11.34)   1.07 (0.10 to 11.34)

Pain/tenderness  

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

10               13

8                 11

9                 12

16               21

3                 5

 

11,683      14,180

10,710      13,186

10,938      13,333

2433         3051

1572         2263

 

0.21 (0.16 to 0.28)     0.20 (0.16 to 0.25)

0.19 (0.16 to 0.22)     0.18 (0.15 to 0.22)

0.21 (0.19 to 0.25)     0.20 (0.17 to 0.24)

0.40 (0.31 to 0.51)     0.43 (0.36 to 0.53)

0.36 (0.26 to 0.49)     0.43 (0.32 to 0.58) 

Redness

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

  

11               13

10               12

11               13

16               22

3                  5

  

6783          7253

6078          6427

6291          6632

2187          3055

1572          2263

  

0.30 (0.22 to 0.40)     0.30 (0.23 to 0.39)

0.42 (0.32 to 0.55)     0.39 (0.29 to 0.51)

0.48 (0.41 to 0.56)     0.47 (0.41 to 0.54)

0.52 (0.43 to 0.63)     0.51 (0.44 to 0.59)

0.67 (0.51 to 0.89)     0.65 (0.52 to 0.80)

Swelling/induration

Primary dose 1

Primary dose 2

Primary dose 3

aP booster (pre wP)

aP booster (pre aP)

 

13               15

12               14

13               15

17               22

4                  6

 

14,242      14,612

13,430      13,779

13,575      13,916

2433         3301

1730         2421

 

0.24 (0.19 to 0.31)     0.24 (0.19 to 0.31)

0.38 (0.30 to 0.47)     0.35 (0.28 to 0.45)

0.41 (0.30 to 0.57)     0.40 (0.29 to 0.54)

0.51 (0.44 to 0.59)     0.51 (0.46 to 0.57)

0.61 (0.47 to 0.80)     0.68 (0.58 to 0.80)

CI: confidence interval
RR: risk ratio

Appendix 8. Incidence of severe adverse events: acellular vaccines versus whole‐cell vaccines

Outcomes

Number of trials

Acellular vaccines

n/N*                 Incidence #

Whole‐cell vaccines

n/N                  Incidence

RR 95% CI

Primary series non‐completion due to adverse events

11

248/80,060         3.09

338/28,849      11.72

0.23 (0.12 to 0.43)

Death (infection)

Primary series

 

13

 

5/22,154             0.23

 

3/12,344           0.24

 

0.97 (0.23 to 4.16)

Death (all causes)

Primary series

 

16

 

81/86,863           0.93

 

61/35,588         1.71

 

0.87 (0.62 to 1.22)

Encephalopathy

Primary series

 

9

 

0/81,601            0.0

 

0/32,161           0.0

 

Convulsions

Primary series

Booster

 

15

11

 

43/88,513          0.49

1/2250              0.44

 

41/35,874         1.14

0/397                0.0

 

0.47 (0.31 to 0.73)

0.46 (0.02 to 11.2)

Hypotonic hyporesponsive episodes

Primary series

Booster

 

11

7

 

70/86,347         0.81

0/2171              0.0

 

51/35,226         1.45

0/316                0.0

 

0.26 (0.08 to 0.81)

*n/N: number of events/number of recipients
# Incidence: number of events per 1000 recipients
CI: confidence interval
RR: risk ratio

Appendix 9. Incidence of minor adverse events over the primary series: acellular vaccines versus whole‐cell vaccines

 

Outcomes

Dose 1

Acellular            Whole‐cell

n/N*                     n/N   

Incidence#        Incidence

Number of trials

Dose 2

Acellular            Whole‐cell

n/N                      n/N   

Incidence           Incidence

Number of trials

Dose 3

Acellular            Whole‐cell

n/N                      n/N   

Incidence           Incidence

Number of trials

Anorexia

1275/12,310        1896/7322

103.57                 258.95

11

1047/11,653        1208/6848

89.85                   176.40

8

941/11,840         966/6806

79.48                  141.93

9

Drowsiness

3427/12,813        2435/7677

267.46                 317.18

11

2087/12,134        1500/7174

171.99                 209.09

9

1548/12,301          1231/7129

125.84                   172.67

10

Fever

898/14,910          3900/8357

60.23                   466.67

19

1809/14,167         3427/7834

127.69                  437.45

17

2270/14,024           3439/7707

161.87                   446.22

17

Irritability/fretfulness

3645/12,875         4488/7832

283.11                  573.03

15

3763/12,144         3695/7285

309.86                  507.21

12

3482/12,268           3228/7243

283.83                    445.67

13

Prolonged crying

116/10,364           395/6820

11.19                    57.92

8

161/9867              248/6480

16.32                    38.27

6

68/10,096               94/6449

6.74                        14.58

7

Vomiting

530/8126              269/3324

65.22                    80.93

8

356/7885              189/3100

45.15                    60.97

7

322/7788                148/3025

41.35                      48.93

7

Pain/tenderness

733/10,279           1840/3901

71.31                    471.67

13

710/9642              1606/3544

73.64                    453.16

11

712/9769               1358/3564

72.88                      381.03

12

Redness

512/5348               620/1805

95.74                     343.49

13

599/4821              551/1606

124.25                  343.09

12

807/4972                583/1660

162.31                    351.20

13

Swelling/induration

1238/10,606          1670/4006

116.73                   416.87

15

1842/10,034         1576/3745

183.58                   420.83

14

2791/10,157           1658/3759

274.79                    441.07

15

*n/N: number of events/number of recipients
# Incidence: number of events per 1000 recipients

Appendix 10. Incidence of minor adverse events in boosters: acellular vaccines versus whole‐cell vaccines

 

Outcomes

aP booster (previous wP) versus wP booster (previous wP)

Acellular                    Whole‐cell

n/N*                             n/N   

Incidence#                 Incidence

Number of trials

aP booster (previous aP) versus wP booster (previous wP)

Acellular                   Whole‐cell

n/N                            n/N  

Incidence                 Incidence

Number of trials

Anorexia

129/1149                   244/790

112.27                        308.86

14

457/4474                   735/3973

102.15                       184.99                  

4

Drowsiness

203/1453                    292/801

139.71                         364.54

13

532/4419                  913/3948

120.39                       231.26

3

Fever

191/2184                    305/1197

87.45                           254.80

24

1320/5838                 2058/4041

226.10                       509.28

8

Irritability/fretfulness

314/1728                    445/868

181.71                         512.67

17

1256/5837                 1379/4019

215.18                       343.12

6

Prolonged crying

7/666                          20/330

10.51                           60.61

6

9/4105                       15/3838

2.19                           3.91

2

Vomiting

18/551                        13/193

32.67                           67.36

6

2/56                           1/30

35.71                         33.33

1

Pain/tenderness

620/2018                     661/1033

307.23                         639.88

21

691/2015                   203/248

342.93                       818.55

5

Redness

503/1980                     523/1075

254.04                         486.51

21

692/2015                   135/248

343.42                       544.35

5

Swelling/induration

446/2144                     493/1157

208.02                         426.10

22

575/2139                   112/282

268.82                       397.16

6

 *n/N: number of events/number of recipients
# Incidence: number of events per 1000 recipients 

Appendix 11. Incidence of severe adverse events: acellular vaccines versus placebo/DT

 

Outcomes

Number of trials

Acellular vaccine

n/N*                 Incidence#

Placebo/DT

n/N                  Incidence

RR 95% CI

Primary series non‐completion due to adverse events

4

65/19,092         3.40

28/6809           4.11

0.70 (0.38 to 1.29)

Death (infection)

Primary series

 

4

 

5/19,093           0.26

 

1/6809             0.15

 

1.21 (0.19 to 7.80)

Death (all causes)

Primary series

 

4

 

10/19,092         0.52

 

2/6809             0.29

 

1.08 (0.26 to 4.42)

Encephalopathy

Primary series

 

2

 

0/14,521           0.0

 

0/4129             0.0

 

Convulsions

Primary series

 

4

 

27/19,092         1.41

 

28/6809           4.11

 

0.44 (0.12 to 1.69)

Hypotonic hyporesponsive episodes

Primary series  

  

4

 

 2/19,092          0.10

 

 2/6809            0.29

  

0.29 (0.02 to 5.13)

*n/N: number of events/number of recipients
# Incidence: number of events per 1000 recipients
CI: confidence interval
RR: risk ratio

Appendix 12. Incidence of minor adverse events over the primary series: acellular vaccines versus placebo/DT

 

Outcomes

Dose 1

Acellular           Placebo/DT

n/N*                    n/N   

Incidence#        Incidence

Number of trials

Dose 2

Acellular            Placebo/DT

n/N                     n/N   

Incidence          Incidence

Number of trials

Dose 3

Acellular           Placebo/DT

n/N                     n/N  

Incidence          Incidence

Number of trials

Anorexia

750/8000            325/3526

93.75                  92.17 

2

656/7903            276/3483

83.00                  79.24 

2

418/5085             195/2538

82.20                   76.83

1

Drowsiness

1696/7557          792/3397

224.43                 233.15

2

1145/7334           549/3286

156.12                 167.07

2

718/5085             350/2538

141.20                  137.90

1

Fever

557/7762             230/3493

71.76                   65.85

3

1053/7476            502/3377

140.85                  148.65

3

1135/5070            552/2584

223.87                  213.63

2

Irritability/fretfulness

2373/8000           1084/3526

296.63                 307.43

2

2716/7903            1267/3483

343.67                  368.53

2

1848/5085            958/2538

363.42                  377.46

1

Prolonged crying

132/7999              50/3526

16.50                     14.18

2

181/7903               78/3483

22.90                     22.39

2

55/5085                26/2538

10.82                    10.24

1

Vomiting

513/8000              209/3526

64.13                    59.27

2

370/7903               185/3483

46.82                     53.12

2

241/5085              131/2538

47.39                    51.62

1

Pain/tenderness

458/7940               226/3511

57.68                     64.37

2

630/7772               289/3430

81.06                     84.26

2

511/5085              253/2538

100.49                  99.68

1

Redness

9/2787                   1/937

3.23                       1.07

1

160/2661               6/874

60.13                     6.86

1

‐                              ‐

Swelling/induration

933/8042               391/3610

116.02                   108.31

3

1549/7874             663/3527

196.72                   187.98

3

2340/5184            1030/2632

451.39                  391.34

2

*n/N: number of events/number of recipients
# Incidence: number of events per 1000 recipients

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 1

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 1 Primary series non‐completion due to adverse events.
Figuras y tablas -
Analysis 1.1

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 1 Primary series non‐completion due to adverse events.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 2 Death (all causes).
Figuras y tablas -
Analysis 1.2

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 2 Death (all causes).

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 3 Death (infection).
Figuras y tablas -
Analysis 1.3

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 3 Death (infection).

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 4 Encephalopathy.
Figuras y tablas -
Analysis 1.4

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 4 Encephalopathy.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 5 Convulsions.
Figuras y tablas -
Analysis 1.5

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 5 Convulsions.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 6 Hypotonic hyporesponsive episodes.
Figuras y tablas -
Analysis 1.6

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 6 Hypotonic hyporesponsive episodes.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 7 Anorexia.
Figuras y tablas -
Analysis 1.7

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 7 Anorexia.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 8 Drowsiness.
Figuras y tablas -
Analysis 1.8

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 8 Drowsiness.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 9 Fever.
Figuras y tablas -
Analysis 1.9

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 9 Fever.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 10 Irritability/fretfulness.
Figuras y tablas -
Analysis 1.10

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 10 Irritability/fretfulness.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 11 Prolonged crying.
Figuras y tablas -
Analysis 1.11

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 11 Prolonged crying.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 12 Vomiting.
Figuras y tablas -
Analysis 1.12

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 12 Vomiting.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 13 Pain/tenderness.
Figuras y tablas -
Analysis 1.13

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 13 Pain/tenderness.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 14 Redness.
Figuras y tablas -
Analysis 1.14

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 14 Redness.

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 15 Swelling/induration.
Figuras y tablas -
Analysis 1.15

Comparison 1 Safety: acellular versus whole‐cell pertussis vaccines, Outcome 15 Swelling/induration.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 1 Primary series non‐completion due to adverse events.
Figuras y tablas -
Analysis 2.1

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 1 Primary series non‐completion due to adverse events.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 2 Death (all causes).
Figuras y tablas -
Analysis 2.2

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 2 Death (all causes).

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 3 Death (infection).
Figuras y tablas -
Analysis 2.3

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 3 Death (infection).

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 4 Encephalopathy.
Figuras y tablas -
Analysis 2.4

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 4 Encephalopathy.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 5 Convulsions.
Figuras y tablas -
Analysis 2.5

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 5 Convulsions.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 6 Hypotonic hyporesponsive episodes.
Figuras y tablas -
Analysis 2.6

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 6 Hypotonic hyporesponsive episodes.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 7 Anorexia.
Figuras y tablas -
Analysis 2.7

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 7 Anorexia.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 8 Drowsiness.
Figuras y tablas -
Analysis 2.8

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 8 Drowsiness.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 9 Fever.
Figuras y tablas -
Analysis 2.9

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 9 Fever.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 10 Irritability/fretfulness.
Figuras y tablas -
Analysis 2.10

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 10 Irritability/fretfulness.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 11 Prolonged crying.
Figuras y tablas -
Analysis 2.11

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 11 Prolonged crying.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 12 Vomiting.
Figuras y tablas -
Analysis 2.12

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 12 Vomiting.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 13 Pain/tenderness.
Figuras y tablas -
Analysis 2.13

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 13 Pain/tenderness.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 14 Swelling/induration.
Figuras y tablas -
Analysis 2.14

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 14 Swelling/induration.

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 15 Redness.
Figuras y tablas -
Analysis 2.15

Comparison 2 Safety: acellular vaccines versus placebo/DT, Outcome 15 Redness.

Comparison 1. Safety: acellular versus whole‐cell pertussis vaccines

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Primary series non‐completion due to adverse events Show forest plot

14

108909

Risk Ratio (M‐H, Random, 95% CI)

0.23 [0.12, 0.43]

2 Death (all causes) Show forest plot

16

122451

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.62, 1.22]

2.1 Primary series

16

122451

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.62, 1.22]

3 Death (infection) Show forest plot

13

34498

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.23, 4.16]

3.1 Primary series

13

34498

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.23, 4.16]

4 Encephalopathy Show forest plot

9

113762

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.1 Primary series

9

113762

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Convulsions Show forest plot

26

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Primary series

15

124387

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.31, 0.73]

5.2 Booster

11

2647

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.02, 11.20]

6 Hypotonic hyporesponsive episodes Show forest plot

18

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Primary series

11

121573

Risk Ratio (M‐H, Random, 95% CI)

0.26 [0.08, 0.81]

6.2 Booster

7

2487

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Anorexia Show forest plot

26

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Primary series: Dose 1

11

19632

Risk Ratio (M‐H, Random, 95% CI)

0.43 [0.32, 0.57]

7.2 Primary series: Dose 2

8

18501

Risk Ratio (M‐H, Random, 95% CI)

0.45 [0.33, 0.60]

7.3 Primary series: Dose 3

9

18646

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.43, 0.60]

7.4 aP booster (previous wP) versus wP booster (previous wP)

14

1939

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.30, 0.54]

7.5 aP booster (previous aP) versus wP booster (previous wP)

4

8447

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.31, 0.58]

8 Drowsiness Show forest plot

25

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Primary series: Dose 1

12

20490

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.45, 0.68]

8.2 Primary series: Dose 2

9

19308

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.35, 0.60]

8.3 Primary series: Dose 3

10

19430

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.40, 0.77]

8.4 aP booster (previous wP) versus wP booster (previous wP)

13

2254

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.41, 0.56]

8.5 aP booster (previous aP) versus wP booster (previous wP)

3

8367

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.44, 0.54]

9 Fever Show forest plot

46

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Primary series: Dose 1

19

23267

Risk Ratio (M‐H, Random, 95% CI)

0.17 [0.13, 0.20]

9.2 Primary series: Dose 2

17

22001

Risk Ratio (M‐H, Random, 95% CI)

0.31 [0.26, 0.37]

9.3 Primary series: Dose 3

17

21731

Risk Ratio (M‐H, Random, 95% CI)

0.34 [0.30, 0.38]

9.4 aP booster (previous wP) versus wP booster (previous wP)

24

3381

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.26, 0.43]

9.5 aP booster (previous aP) versus wP booster (previous wP)

8

9879

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.22, 0.55]

10 Irritability/fretfulness Show forest plot

33

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Primary series: Dose 1

15

20707

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.42, 0.56]

10.2 Primary series: Dose 2

12

19429

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.41, 0.56]

10.3 Primary series: Dose 3

13

19511

Risk Ratio (M‐H, Random, 95% CI)

0.53 [0.47, 0.59]

10.4 aP booster (previous wP) versus wP booster (previous wP)

17

2596

Risk Ratio (M‐H, Random, 95% CI)

0.36 [0.28, 0.47]

10.5 aP booster (previous aP) versus wP booster (previous wP)

6

9856

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.44, 0.51]

11 Prolonged crying Show forest plot

14

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Primary series: Dose 1

8

17184

Risk Ratio (M‐H, Random, 95% CI)

0.15 [0.11, 0.19]

11.2 Primary series: Dose 2

6

16347

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.24, 0.35]

11.3 Primary series: Dose 3

7

16545

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.24, 0.46]

11.4 aP booster (previous wP) versus wP booster (previous wP)

6

996

Risk Ratio (M‐H, Random, 95% CI)

0.21 [0.10, 0.48]

11.5 aP booster (previous aP) versus wP booster (previous wP)

2

7943

Risk Ratio (M‐H, Random, 95% CI)

0.27 [0.02, 3.12]

12 Vomiting Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

12.1 Primary series: Dose 1

8

11450

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.66, 0.88]

12.2 Primary series: Dose 2

7

10985

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.45, 0.86]

12.3 Primary series: Dose 3

7

10813

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.46, 1.04]

12.4 aP booster (previous wP) versus wP booster (previous wP)

6

744

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.22, 1.11]

12.5 aP booster (previous aP) versus wP booster (previous wP)

1

86

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.10, 11.34]

13 Pain/tenderness Show forest plot

35

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

13.1 Primary series: Dose 1

13

14180

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.16, 0.25]

13.2 Primary series: Dose 2

11

13186

Risk Ratio (M‐H, Random, 95% CI)

0.18 [0.15, 0.22]

13.3 Primary series: Dose 3

12

13333

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.17, 0.24]

13.4 aP booster (previous wP) versus wP booster (previous wP)

21

3051

Risk Ratio (M‐H, Random, 95% CI)

0.43 [0.36, 0.53]

13.5 aP booster (previous aP) versus wP booster (previous wP)

5

2263

Risk Ratio (M‐H, Random, 95% CI)

0.43 [0.32, 0.58]

14 Redness Show forest plot

35

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

14.1 Primary series: Dose 1

13

7153

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.23, 0.39]

14.2 Primary series: Dose 2

12

6427

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.29, 0.51]

14.3 Primary series: Dose 3

13

6632

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.41, 0.54]

14.4 aP booster (previous wP) versus wP booster (previous wP)

21

3055

Risk Ratio (M‐H, Random, 95% CI)

0.51 [0.44, 0.59]

14.5 aP booster (previous aP) versus wP booster (previous wP)

5

2263

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.52, 0.80]

15 Swelling/induration Show forest plot

39

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

15.1 Primary series: Dose 1

15

14612

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.19, 0.31]

15.2 Primary series: Dose 2

14

13779

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.28, 0.45]

15.3 Primary series: Dose 3

15

13916

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.29, 0.54]

15.4 aP booster (previous wP) versus wP booster (previous wP)

22

3301

Risk Ratio (M‐H, Random, 95% CI)

0.51 [0.46, 0.57]

15.5 aP booster (previous aP) versus wP booster (previous wP)

6

2421

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.58, 0.80]

Figuras y tablas -
Comparison 1. Safety: acellular versus whole‐cell pertussis vaccines
Comparison 2. Safety: acellular vaccines versus placebo/DT

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Primary series non‐completion due to adverse events Show forest plot

4

25901

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.38, 1.29]

2 Death (all causes) Show forest plot

4

25901

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.26, 4.42]

2.1 Primary series

4

25901

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.26, 4.42]

3 Death (infection) Show forest plot

4

25902

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.19, 7.80]

3.1 Primary series

4

25902

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.19, 7.80]

4 Encephalopathy Show forest plot

2

18650

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.1 Primary series

2

18650

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Convulsions Show forest plot

4

25901

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.12, 1.69]

5.1 Primary series

4

25901

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.12, 1.69]

6 Hypotonic hyporesponsive episodes Show forest plot

4

25901

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.02, 5.13]

6.1 Primary series

4

25901

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.02, 5.13]

7 Anorexia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Primary series: Dose 1

2

11526

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.93, 1.20]

7.2 Primary series: Dose 2

2

11386

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.66, 1.46]

7.3 Primary series: Dose 3

1

7623

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.91, 1.26]

8 Drowsiness Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Primary series: Dose 1

2

10954

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.96, 1.11]

8.2 Primary series: Dose 2

2

10620

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.91, 1.09]

8.3 Primary series: Dose 3

1

7623

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.91, 1.15]

9 Fever Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Primary series: Dose 1

3

11255

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.73, 1.90]

9.2 Primary series: Dose 2

3

10853

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.91, 1.11]

9.3 Primary series: Dose 3

2

7654

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.94, 1.13]

10 Irritability/fretfulness Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Primary series: Dose 1

2

11526

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.93, 1.05]

10.2 Primary series: Dose 2

2

11386

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.93, 1.03]

10.3 Primary series: Dose 3

1

7623

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.91, 1.02]

11 Prolonged crying Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Primary series: Dose 1

2

11525

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.71, 2.34]

11.2 Primary series: Dose 2

2

11386

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.83, 1.40]

11.3 Primary series: Dose 3

1

7623

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.66, 1.68]

12 Vomiting Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

12.1 Primary series: Dose 1

2

11526

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.94, 1.30]

12.2 Primary series: Dose 2

2

11386

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.76, 1.07]

12.3 Primary series: Dose 3

1

7623

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.75, 1.13]

13 Pain/tenderness Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

13.1 Primary series: Dose 1

2

11451

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.78, 1.32]

13.2 Primary series: Dose 2

2

11202

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.81, 1.51]

13.3 Primary series: Dose 3

1

7623

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.87, 1.16]

14 Swelling/induration Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

14.1 Primary series: Dose 1

3

11652

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.62, 2.68]

14.2 Primary series: Dose 2

3

11401

Risk Ratio (M‐H, Random, 95% CI)

2.08 [0.54, 8.01]

14.3 Primary series: Dose 3

2

7816

Risk Ratio (M‐H, Random, 95% CI)

1.13 [1.07, 1.20]

15 Redness Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

15.1 Primary series: Dose 1

1

3724

Risk Ratio (M‐H, Random, 95% CI)

3.03 [0.38, 23.85]

15.2 Primary series: Dose 2

1

3535

Risk Ratio (M‐H, Random, 95% CI)

8.76 [3.89, 19.72]

15.3 Primary series: Dose 3

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Figuras y tablas -
Comparison 2. Safety: acellular vaccines versus placebo/DT