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Intervention Review

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Vaccines for preventing influenza in people with cystic fibrosis

  1. Poonam Dharmaraj1,*,
  2. Rosalind L Smyth2

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 7 OCT 2009

Assessed as up-to-date: 27 JUN 2011

DOI: 10.1002/14651858.CD001753.pub2


How to Cite

Dharmaraj P, Smyth RL. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD001753. DOI: 10.1002/14651858.CD001753.pub2.

Author Information

  1. 1

    Alder Hey Children's NHS Foundation Trust, Diabetes & Endocrinology, Liverpool, UK

  2. 2

    Alder Hey Children's NHS Foundation Trust, Institute of Child Health, University of Liverpool, Liverpool, Merseyside, UK

*Poonam Dharmaraj, Diabetes & Endocrinology, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP, UK. poonamd@doctors.org.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 7 OCT 2009

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This is not the most recent version of the article. View current version (06 MAR 2014)

 
Characteristics of included studies [ordered by study ID]
Adlard 1987

MethodsA randomised single-blind cohort study over two months.


ParticipantsChildren (n = 19) aged 5 - 13 years with CF attending the CF clinic of the Royal Manchester Children's Hospital, UK.


InterventionsA split virion influenza vaccine (MFV Ject. Institut Merieux) versus A subunit vaccine (Fluvirin, Evans). Both vaccines were 2 IM injections given 1 month apart and contained: A/Philippines/2/82 (H3N2), A/Chile/1/83 (H1N1), B/USSR/100/83.


Outcomes1. Adverse effects
2. Antibody levels


NotesAntibody levels taken before and one month after vaccination.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table used.

Allocation concealment (selection bias)Unclear riskVaccines supplied in individual syringes with pre-attached needles, but not clear if allocation concealed.

Blinding (performance bias and detection bias)
All outcomes
Low riskParents, participants and virology laboratory not aware of which vaccine given.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNumber of withdrawals from each group stated and reasons given. 7 out of 19 dropped out (37%).

Gruber 1994

MethodsA randomised double-blind placebo controlled study over 3 years.


ParticipantsPeople with CF (n = 41) and family members (n = 89) attending the Vanderbilt CF clinic, Nashville, USA.


InterventionsAn intranasal live attenuated cold adapted influenza A vaccine (A/Kawasaki/9/86 (H1N1), A/Los Angeles/2/87 (H3N2) plus IM standard monovalent influenza B vaccine versus egg allantoic fluid nose drops plus IM standard trivalent inactivated influenza A vaccine (A/Taiwan/1/86 (H1N1), A/Shanghai/11/87 (or A/Shanghai/16/89 or A/Beijing/353/89 respectively) (H3N2).


Outcomes1. Number of hospital admissions (as rate per 100 patient years)
2. Adverse effects
3. Antibody levels


NotesAntibody levels taken before and 6 weeks after the vaccination and the following spring for each year.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDescribed as 'randomly assigned' but no details of method given.

Allocation concealment (selection bias)Unclear riskNot discussed.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as double-blind. Since both treatments were given as a combination of nose drops and intramuscular injection, likely that participants and clinicians were the blinded parties.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskStates number of withdrawals in total and reasons for withdrawal, but no details of which treatment group they were from.

King 1987

MethodsA randomised double-blind placebo controlled study over 1 year.


ParticipantsPeople with CF (n = 55) attending the CF Clinic of the St Vincent's Hospital in New York, USA.


InterventionsAn intranasal bivalent cold adapted influenza A vaccine (A/Dunedin/83 CR-64 (H1N1), A/Korea/1/82 CR-59 (H3N2)) plus monovalent inactivated influenza B 1 week later versus intranasal placebo plus parenteral trivalent inactivated influenza vaccine (A/Chile/83 (H1N1), A/Philippines/82 (H3N2) & B/USSR/100/83).


Outcomes1. Adverse effects
2. Antibody level


NotesAntibody levels taken before, 3 weeks and 7 months after vaccination.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDescribed as 'randomly assigned' but no details given as to the method.

Allocation concealment (selection bias)Unclear riskNot discussed.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as double-blind, similar treatments i.e. intranasal followed by parenteral dose of active vaccine or placebo.

Incomplete outcome data (attrition bias)
All outcomes
High riskDoes not report drop outs, but clear from paper that at least 2 data sets are missing from each group.

Schaad 2000

MethodsAn open randomised multicentre study over 4 weeks.


ParticipantsChildren with CF (n = 64) in 5 paediatric centres in Switzerland.


InterventionsA trivalent virosomal influenza vaccine (ASingapore/6/86 (H1N1); A/Shandong/9/93 (H3N2) B/Panama/45/90) (given as either single or 2 doses 4 weeks apart) versus a trivalent subunit influenza vaccine (A/Singapore/6/86 (H1N1); A/Shandomg/9/93 (H3N2); B/Panama/45/90) (given as 1 or 2 doses 4 weeks apart).


Outcomes1. Adverse effects
2. Antibody level rise


NotesAntibody levels taken before and 4 weeks after the single or the second immunisation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDescribed as randomised, but no details of method given.

Allocation concealment (selection bias)Unclear riskNot discussed.

Blinding (performance bias and detection bias)
All outcomes
High riskNot possible as dose regimens in the treatment groups differ - some participants received a single injection and others received two injections.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskStates number of withdrawals, but does not give details of which treatment group they were from or the reason for withdrawal.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Doudounakis 20001. The study compared two dose regimens (single dose versus 2 half doses) of the same split virus vaccine.
2. Randomisation and blinding was not stated.

Ong 19911. The study was non-randomised and non-blinded.
2. The 2 groups enrolled to this study were not comparable: people with CF versus healthy volunteers.

 
Comparison 1. Intranasal live vaccine versus intramuscular trivalent inactivated vaccine

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Death1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 2 Adverse events2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Redness
141Risk Ratio (M-H, Fixed, 95% CI)1.23 [0.50, 3.02]

    2.2 Swelling
141Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.28, 1.98]

    2.3 Fever
296Risk Ratio (M-H, Fixed, 95% CI)0.42 [0.14, 1.23]

    2.4 Rhinorrhoe
296Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.85, 1.63]

    2.5 Cough
296Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.45, 1.67]

    2.6 Increased Sputum Production
141Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.28, 1.98]

 
Comparison 2. Intramuscular subunit vaccine versus intramuscular split virus vaccine

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Pain
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Swelling
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Fever
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Intramuscular virosome vaccine versus intramuscular subunit vaccine

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events with one vaccine dose1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Pain
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Induration
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Redness
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Swelling
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Headache
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.6 Fatigue
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.7 Nausea
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.8 Cough
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.9 Coryza
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.10 Vertigo
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.11 Irritability
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Adverse events with two vaccine doses1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 Pain
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Induration
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Redness
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 Swelling
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.5 Headache
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.6 Fatigue
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.7 Nausea
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.8 Cough
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.9 Coryza
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.10 Vertigo
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.11 Irritability
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Table 1. Serological response to vaccination (King 1987)

OutcomeIntranasal liveInactivated


NMeanNMean

GMT rise to H1N1 with primary vaccination211.12.528

GMT rise to H3N2 with primary vaccination0.8271.228

 GMT: geometric mean titre
 
Table 2. Serological response to vaccination (Gruber 1994)

OutcomeIntranasal liveIM inactivated


NMeanNMean

GMT rise to H1N1 with primary vaccination202.00213.00

GMT rise to H1N1 with 1st revaccination201.20210.20

GMT rise to H1N1 with 2nd revaccination201.30211.00

GMT rise to H3N2 with primary vaccination202.90212.70

GMT rise to H3N2 with 1st revaccination201.00211.20

GMT rise to H3N2 with 2nd revaccination201.40212.00

 GMT: geometric mean titre
 
Table 3. Serological response to vaccination (Adlard 1987)

OutcomeSplit virion groupSubunit group


NMeanNMean

GMT rise to H1N1 with primary vaccination10228.009279.00

GMT rise to H1N1 with revaccination10115.009283.00

GMT rise to H3N2 with primary vaccination10520.009283.00

GMT rise to H3N2 with revaccination10570.009470.00

 GMT: geometric mean titre