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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

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

MEDICAL EVENTS DURING DIFFERENT TIME PERIODS

(From Neuzil KM at al. J Pediatr 2000)

IMPACT OF ILI IN ADOLESCENTS WITH ONCOHEMATOLOGICAL PROBLEMS

(From Esposito S et al. Vaccine 2010)

IMPACT OF ILI OF CHILDREN WITH ONCOHEMATOLOGICAL PROBLEMS ON

HOUSEHOLDS (From Esposito S et al. Vaccine 2010)

INFLUENZA VACCINATION RATES IN ADOLESCENTS WITH HIGH-RISK

CONDITIONS (USA) (From Nakamura MM and Lee GM, Pediatrics 2008)

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

%

PROPORTION OF HIGH-RISK ADOLESCENTS FOR WHOM INFLUENZA VACCINATION IS

RECOMMENDED (From Nakamura MM and Lee,GM Pediatrics 2008)

PREDICTORS OF INFLUENZA VACCINATION IN ADOLESCENTS WITH HIGH-RISK CONDITIONS

(From Nakamura MM and Lee GM, Pediatrics 2008)

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

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

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

INFLUENZA AND ASTHMA: EFFICACY OF THE VACCINATION

(Kramarz P et al., J Pediatr 2000)

•

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%

Am Lung Ass Asthma Clin Res Centers, N Engl J Med 2001

Am Lung Ass Asthma Clin Res Centers, N Engl J Med 2001

CHARACTERISTICS OF ASTHMATIC CHILDREN WITH AND WITHOUT EGG ALLERGY

(Esposito S et al., Vaccine 2008)

No significant between-group difference

(Esposito S et al., Vaccine 2008)

CARDIORESPIRATORY PARAMETERS AND ADVERSE EVENTS IN THE 4 H AFTER INFLUENZA

VACCINATION

(Esposito S et al., Vaccine 2008)

LOCAL ADVERSE EVENTS IN THE WEEK AFTER INFLUENZA VACCINATION

IMMUNOGENICITY OF MF59-ADJUVANTED SEASONAL INFLUENZA VACCINE IN CHILDREN WITH JIA TREATED WITH DIFFERENT

DRUGS (Dell’Era et al., Vaccine 2012)

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

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

METANALYSIS OF STUDIES WHICH EVALUATED TELEPHONE RECALL SYSTEM TO INCREASE

INFLUENZA VACCINATION COVERAGE

Cochrane Database of Systematic Reviews, 2005

INTERVENTIONS TO IMPROVE INFLUENZA VACCINATION COVERAGE AMONG

CHILDREN WITH CHRONIC ASTHMA

%

Esposito et al., ESWI 2008

*p<0.05

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

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

%

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

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

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

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