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UPDATE ON INFLUENZA VACCINATION IN CHILDREN WITH CHRONIC DISEASES
Susanna Esposito
Pediatric Clinic 1, University of Milan Fondazione IRCCS Ca’ Granda Ospedale
Maggiore Policlinico, Milan, Italy
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CHILDREN AT HIGHER RISK FOR INFLUENZA COMPLICATIONS
• THOSE WHO HAVE CHRONIC PULMONARY (INCLUDING
ASTHMA), CARDIOVASCULAR (EXCEPT HYPERTENSION),
RENAL, HEPATIC, HEMATOLOGICAL OR METABOLIC
DISORDERS (INCLUDING DIABETES MELLITUS)
• THOSE WHO ARE IMMUNOSUPPRESSED (INCLUDING
IMMUNOSUPPRESSION CAUSED BY MEDICATIONS OR HIV)
• THOSE WHO HAVE ANY CONDITION (EG, COGNITIVE
DYSFUNCTION, SPINAL CORD INJURIES, SEIZURE
DISORDERS) THAT CAN COMPROMISE RESPIRATORY
FUNCTION OR THE HANDLING OF RESPIRATORY
SECRETIONS OR THAT CAN INCREASE THE RISK FOR
ASPIRATION
• THOSE WHO ARE RECEIVING LONG-TERM ASPIRIN THERAPY
WHO THEREFORE MIGHT BE AT RISK FOR EXPERIENCING
REYE SYNDROME AFTER INFLUENZA INFECTION
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MEDICAL EVENTS DURING DIFFERENT TIME PERIODS
(From Neuzil KM at al. J Pediatr 2000)
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IMPACT OF ILI IN ADOLESCENTS WITH ONCOHEMATOLOGICAL PROBLEMS
(From Esposito S et al. Vaccine 2010)
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IMPACT OF ILI OF CHILDREN WITH ONCOHEMATOLOGICAL PROBLEMS ON
HOUSEHOLDS (From Esposito S et al. Vaccine 2010)
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INFLUENZA VACCINATION RATES IN ADOLESCENTS WITH HIGH-RISK
CONDITIONS (USA) (From Nakamura MM and Lee GM, Pediatrics 2008)
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INFLUENZA VACCINATION RATES AMONG 5,286 ITALIAN CHILDREN AND
ADOLESCENTS (Esposito S et al., Vaccine 2006)
0
5
10
15
20
25
30
Flu season
2000-2001
Flu season
2001-2002
Flu season
2002-2003
High risk children Healthy children
%
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PROPORTION OF HIGH-RISK ADOLESCENTS FOR WHOM INFLUENZA VACCINATION IS
RECOMMENDED (From Nakamura MM and Lee,GM Pediatrics 2008)
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PREDICTORS OF INFLUENZA VACCINATION IN ADOLESCENTS WITH HIGH-RISK CONDITIONS
(From Nakamura MM and Lee GM, Pediatrics 2008)
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VACCINATED HIGH-RISK CHILDREN (No.=72)
Why is your child vaccinated against influenza?
ANSWER FREQUENCY
Pediatrician’s recommendation
63 (87.5%)
Protection of parents 6 (8.3%)
Protection of an elderly family members
2 (2.8%)
Previous serious influenza-like illness
1 (1.4%)
Esposito S et al., Vaccine 2006
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UNVACCINATED HIGH-RISK CHILDREN (No.=202)
Why is your child not vaccinated against influenza?
ANSWER FREQUENCY
Lack of awareness 173 (85.6%)
Inconvenience 11 (5.5%)
Concern about side effects
18 (8.9%)
Esposito S et al. Vaccine 2006
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PEDIATRICIANS’ OPINIONS CONCERNING INFLUENZA (No.=256)
If you do not recommend influenza vaccination in a child with chronic disease,
what are the reasons?
ANSWER FREQUENCY
Influenza infection not sufficiently severe
68 (26.6%)
Poor efficacy of influenza vaccines
149 (58.2%)
Concern about side effects
39 (15.2%)
Esposito S et al., Vaccine 2006
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INFLUENZA AND ASTHMA: EFFICACY OF THE VACCINATION
(Kramarz P et al., J Pediatr 2000)
•
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ASTHMA AND INFLUENZA VACCINATION (Am Lung Ass Asthma Clin Res Centers, N Engl J Med 2001)
2,032 patients with chronic asthma aged 3-64 years (712 < 14 anni)
Randomized 1:1 to receive TIV or placebo
Asthma exacerbation in the 2 weeks after enrollment:
TIV 28.8%
PLACEBO 27.7%
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Am Lung Ass Asthma Clin Res Centers, N Engl J Med 2001
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Am Lung Ass Asthma Clin Res Centers, N Engl J Med 2001
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CHARACTERISTICS OF ASTHMATIC CHILDREN WITH AND WITHOUT EGG ALLERGY
(Esposito S et al., Vaccine 2008)
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No significant between-group difference
(Esposito S et al., Vaccine 2008)
CARDIORESPIRATORY PARAMETERS AND ADVERSE EVENTS IN THE 4 H AFTER INFLUENZA
VACCINATION
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(Esposito S et al., Vaccine 2008)
LOCAL ADVERSE EVENTS IN THE WEEK AFTER INFLUENZA VACCINATION
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IMMUNOGENICITY OF MF59-ADJUVANTED SEASONAL INFLUENZA VACCINE IN CHILDREN WITH JIA TREATED WITH DIFFERENT
DRUGS (Dell’Era et al., Vaccine 2012)
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INACTIVATED INFLUENZA VACCINE IN CHILDREN WITH CANCER
(Esposito S et al., Vaccine 2011)
• Susceptibility to influenza is greater during the first six months of discontinuation of chemoterapy than in normal children or those who have been off-therapy for more than six months
• Children with cancer seem to be able to generate a sufficient immune response to the influenza antigens contained in the vaccines when receiving chemotherapy
• Immune response is weaker than that of healthy children or children with cancer who have discontinued chemotherapy for more than one month
• The safety and tolerability of inactivated influenza vaccine
have always seemed to be very good
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GAPS RELATED TO INLUENZA VACCINATION IN HIGH-RISK CHILDREN
• Few epidemiologic studies on the impact of influenza in each of the high-risk groups
• Few data on the immunogenicity, safety and efficacy of influenza vaccination in each of the high-risk groups
• Absence of clear correlates of protection especially with new vaccines
• Few influenza vaccines are approved for high risk children
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METANALYSIS OF STUDIES WHICH EVALUATED TELEPHONE RECALL SYSTEM TO INCREASE
INFLUENZA VACCINATION COVERAGE
Cochrane Database of Systematic Reviews, 2005
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INTERVENTIONS TO IMPROVE INFLUENZA VACCINATION COVERAGE AMONG
CHILDREN WITH CHRONIC ASTHMA
%
Esposito et al., ESWI 2008
*p<0.05
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Randomisation group Influenza vaccination in
previous season (2005-
2006),
No. (%)
Influenza vaccination with
intervention strategy
(2006-2007),
No. (%)
P value
Group A (n=71) 11 (15.5) 31 (43.7) <0.0001
Chemotherapy completion
<6 mos (n=27)
4 (14.8) 20 (74.1) <0.0001
Chemotherapy completion
6 mos-2 yrs (n=44)
7 (15.9) 11 (25.0) 0.422
Group B (n=64) 12 (18.8) 27 (42.2) 0.007
Chemotherapy completion
<6 mos (n=22)
4 (18.2) 17 (77.2) 0.0002
Chemotherapy completion
6 mos-2 yrs (n=42)
8 (19.0) 10 (23.8) 0.790
Group C (n=70) 19 (27.1) 34 (48.6) 0.014
Chemotherapy completion
<6 mos (n=25)
8 (32.0) 20 (80.0) 0.001
Chemotherapy completion
6 mos-2 yrs (n=45)
11 (24.4) 14 (31.1) 0.637
Cecinati V, Esposito S et al. Human Vacc 2010
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OCCURRENCE OF ACUTE OTITIS MEDIA ACCORDING TO THE USE OF VIROSOMAL
ADJUVANTED INFLUENZA VACCINATION IN CHILDREN WITH RECURRENT AOM
35,80
63,6
0
10
20
30
40
50
60
70
VACCINE GROUP CONTROL GROUP
p =0.01
Marchisio P et al., Clin Infect Dis 2002
%
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EFFECTIVENESS FOR INFLUENZA VACCINATED AND UNVACCINATED CHILDREN WITH
RECURRENT RESPIRATORY TRACT INFECTIONS
STUDY CHILDREN VACCINATED
(N=64)
CONTROLS
(N=63)
P VALUE
NO. OF URTI 1.68 + 1.62 4.52 + 2.43 <0.0001
NO. OF LRTI 0.68 + 0.88 1.24 + 1.32 0.0042
NO. OF FEBRILE RESPIRATORY ILLNESSES
1.59 + 1.49 3.87 + 2.74 <0.0001
NO. OF HOSPITALIZATIONS
0.05 + 0.23 0.10 + 0.25 0.417
NO. OF ANTIBIOTIC PRESCRIPTIONS
1.32 + 1.28 2.35 + 1.59 <0.0001
NO. OF ANTIPYRETIC PRESCRIPTIONS
2.21 + 2.03 3.98 + 2.37 <0.0001
MISSED SCHOOL DAYS
3.10 + 6.23 13.83 + 12.50 <0.0001
Esposito S et al., Vaccine 2003
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EFFECTIVENESS AMONG HOUSEHOLD CONTACTS OF INFLUENZA VACCINATED AND UNVACCINATED CHILDREN WITH RECURRENT
RESPIRATORY TRACT INFECTIONS
HOUSEHOLD CONTACTS VACCINATED CONTROLS P VALUE
LOSS OF MATERNAL WORK
DUE TO CARE FOR THE ILL
CHILD
0.64 + 1.86 4.05 + 5.34 <0.0001
LOSS OF PATERNAL WORK
DUE TO CARE FOR THE ILL
CHILD
0.11 + 0.46 0.97 + 2.24 0.001
NEED FOR HELP DUE TO
CARE FOR THE ILL CHILD
53.5% 74.7% 0.012
NO. WITH RESPIRATORY
ILLNESS
1.88 + 1.68 2.90 + 1.68 0.0005
NO. OF MEDICAL VISITS 1.22 + 1.37 2.06 + 1.77 0.002
NO. OF HOSPITALIZATIONS 0.01 + 0.12 0 0.354
Esposito S et al., Vaccine 2003
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DISCUSSION
• Influenza vaccination has to be strongly recommended in high risk children and active recall systems appear useful to increase the coverage rate
• Children with persistent asthma have significant benefits with the use of influenza vaccines, with no risk of asthma exacerbation
• Studies on immunogenicity and safety of influenza vaccines are available also for other high-risk groups, but further research is needed in this area
• Children with recurrent AOM and those with RRTIs should be included in the high-risk groups for which influenza vaccination is recommended
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CONCLUSIONS
Universal influenza vaccination in pediatric age can also permit to increase vaccination coverage in high-risk children and to reduce the circulation of influenza viruses with their associated complications in high-risk patients