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Vaccine Timeliness
Amy Mckay
Senior Lecturer (London South Bank University)
Family Nurse (SEPT)
Co-Writer
Edward Purssell
Kings College London University
Aims
• To identify the importance of vaccine
timeliness
• To discuss research in relation to vaccine
timeliness
• To consider recommendations for practice
Vaccination
• Challenging an individual with antigens to
stimulate an adaptive immune response
• Provides immunological memory
• Aim is to prime the immune system in an
effort to protect against natural infection at a
later date thus preventing the disease (DoH 2010)
Immulogical memory
(Hofmeyr
1997)
UK vaccination schedule
Age
Vaccine
2 months
DTaP/IPV/Hib
(diptheria, tetanus, pertussis, polio,
Hib)
Pneumoccocal
3 months
DTaP/IPV/Hib
Meningitis C
4 months
DTaP/IPV/Hib
Pneumoccocal
Meningitis C
Between 12 and 13 months
MMR (measles, mumps and rubella)
DtaP/IPV (diptheria, tetanus, pertussis
and polio)
DoH
2010
12 -13 years
HPV (cervical cancer)
13-18 years
Td/IPV (diptheria, tetanus and polio)
Importance of vaccine timeliness
• Cost-effective
• Global appropriately timed vaccinations have
saved over 20 million lives in the last two
decades via preventing disease outbreak
(Unicef 2010)
Early vaccination
• Suboptimal immune response due to
immaturity of the immune system
• Transient protection against a disease (European
Centres for Disease Prevention and Control 2009).
Delayed vaccination
• Early protection is particularly important for
Hib and Pertussis where morbidity is high in
infancy (Crowstoft et al 2003, Pertola 2000)
• Increased individual susceptibility
• Reduced herd immunity
Vaccine intervals
• Vaccines administered at intervals less than
the recommended schedule can produce
increased rates of local or systemic reactions
• Robust immune response requires adequate
spacing
British guidance
• No UK policies or guidelines stipulating what
constitutes vaccine timeliness
– Age
– Spacing
• Unspecific in relation to how many days
constitutes a month
Space between the ending of the 2nd month
and beginning of the 3rd month
Birth to 2 months
Birth
2 months
3 months
Start of
appropriately
timed first dose
End of
appropriately
timed first dose
62 days: maximum
possible amount of
days (two months
with 31 days;
December and
January
OR
59 days: least
possible amount of
days (February (28
days), March (31
days)
OR
56 Days (8 weeksweek constituting 7
days)
86 days: least
possible amount of
days (February (28
days), March (31
days) April (30
days))
OR
91 days (12 weeksweek constituting 7
days)
OR
92 days: maximum
possible amount of
days (November (30
days), December
(31 days) January
(31 days))
4 months
onwards
Start of the
timing of the
second dose
of the
primary
vaccination
course
Classification of vaccine timeliness
Timeliness Classification
Dayan et al (2006)
Akmatov et al (2008)
Months constitute 30.5 days
Hull et al (2006)
Months constitute 30 days (delay
counting from 31 days)
Luman et al (2005a, 2005b)
Months constitute maximum/minimum
amount of calendar days.
Luman et al (2008)
Months constitute maximum/minimum
calendar amount of days using ACIP
guidelines (CDCP 2006).
Delay= maximum amount of days + 4 days
Early= minimum amount of days- 4 days
Coverage vs Timeliness
• COVER collects coverage data at one, two and five years
(HPA 2010b)
• Data for every child with whom the PCT have
responsibility is collected
• Benefits are that it is quick, comprehensive and easily
understood
• COVER is unable to identify the length of time infants
are delayed or early in receiving their vaccines.
• COVER provides no information regarding the
proportions of infants vaccinated at specific time points
(vaccine uptake rates)
Vaccine timeliness study
• Aims: to assess the timeliness of the primary
vaccination course for a cohort of infants born
between 1st April 2008 and 31st March 2009,
and to assess this as a method of vaccine
surveillance that can be used to complement
the 1, 2 and 5 year coverage levels monitored
through the COVER programme.
Research Site
• The PCT encompasses areas of affluence and
deprivation
• Approximately 3.8% of the population are
under the age of one year
• 93% uptake of the primary vaccinations as
measured by COVER in 2008 (HPA 2008)
Sample
• Total population sample: 4,418 infants
• Sampling frame
– System One
– All infants born between 1st April 2008 until 31st
March 2009 who had completed their primary
vaccination course
Data
• Provided anonymously
• Data included
– Child’s date of birth
– Vaccination date
– Ethnicity
– Gender
– Ward of residence
Vaccine Timeliness Classification
 ACIP advice:
Valid vaccine is one given on the day due +/- 4
days
e.g. Child born on 10/04/08
2 month: 10/06/08
3 months: 10/07/08
Therefore: early vaccination would be classified as
prior to 06/04/08 and late vaccination after
14/07/08
Pilot Study
• 320 children
• Born prior to the study cohort (March 2008)
• Identified the need to collapse ward of living
and ethnicity categories into smaller groups
Findings: Bar graph displaying proportions
vaccinated early, timely and late
90
80
70
p e r c e n ta g e
60
50
40
30
20
10
0
Early T imely Lat e
Vaccine1
Early T imely
Vaccine2
Lat e
Early T imely Lat e
Vaccine3
Findings: Kaplan-Meier survival curve,
1st dose
1.00
88 days
0.95
In s t an t an eo u s rat e o f v acci n at i o n u p t ak e
0.80
0.60
0.40
0.20
0.00
50
100
150
Days of Age
183
Findings: Kaplan-Meier survival curve, 1st dose
1.00
I n st a n t a n e o us r a t e o f v a c c in a t io n up t a k e
0.96
Delayed
vaccination
0.80
0.60
0.40
0.20
Early
vaccination
0.03
0.00
55
96
160
Days of Age
Findings: Kaplan-Meier Survival Curve 3rd dose
221days
In s t a n t a n e o u s ra t e o f v a c c in a t io n u p t a ke
1.00
0.80
0.60
0.40
0.20
0.06
0.00
100 116
157
200
250
Days of Age
300
350 365
Findings: Kaplan-Meier Survival Curve 3rd dose
In s t a n t a n e o u s ra t e o f v a c c in a t io n u p t a ke
1.00
0.80
Delayed
vaccination
0.60
0.40
Early
vaccination
0.20
0.06
0.00
100 116
157
200
250
Days of Age
300
350 365
Findings: demographic analysis
• Gender: No clinically significant findings were
obtained
• Ethnicity:
Vaccine 1
(n= 4101)
Vaccine 2
(n= 3948)
Vaccine 3
(n=4050)
Median days of
vaccination:
White
Other
63
62
98
97
135
132
p value
0.027
<0.0005
<0.0005
Locality of living
• 1st Vaccine dose: those living in areas of high
IMD (Index of Multiple Deprivation) had the
highest percentages of infants receiving their
vaccines early and delayed
• 3rd Vaccine dose: no association of vaccination
early or late according to IMD.
Recommendations
• Vaccine timeliness using survival analysis is a
useful tool to support COVER data
• Consideration of policy and guidance
regarding vaccine timeliness would be
beneficial.
Future research
• The effect of suboptimal vaccination
• Trialling of Kaplan-Meier Survival analysis
utilisation within the UK
• Consideration of the reason for suboptimal
vaccination (parental and professional
viewpoint)
Recommendations
• Need for professionals to be informing
parents/guardians of not only the need to
vaccinate but also the importance of this
being timely
• Flexibility of vaccination (drop-in clinics and
opportunistic vaccination)
Summary
• Vaccine timeliness reporting is cost-effective
and has health implications for infants.
• Kaplan-Meier Survival analysis is a useful tool
to complement current surveillance
techniques adopted by COVER.
• It is suggested that clarification in respect of
policy/guidance is required in relation to
vaccine timeliness
References
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Akmatov M, Kretzschmar M, Kramer A, Mikolajczyk R (2008) Timeliness of
vaccination and its effects on fractions of vaccinated populations. Vaccine. 26:
3805-3811
Crowstoft N, Stein N, Duclos P, Birmingham M (2003) How best to estimate the
global burden of pertussis? The Lancet: Infectious Diseases. 3: 413-418
Dayan G, Shaw K, Baughman A, Orellana L, Forlenza R, Ellis A, Chaui J, Kaplan S,
Strebel P (2006) Assessment of delay in age-appropriate vaccination using survival
analysis. American Journal of Epidemiology. 163 (6): 561-570
Department of Health (2010) Immunisations against infection diseases-‘The Green
Book’. [Online] Available:
http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicy
AndGuidance/DH_079917 (accessed 09/10/10)
European Centres for Disease Prevention and Control (2009) Scientific panel on
childhood immunisation schedule: Diphtheria-tetanus-pertussis (DTP) vaccination.
[Online] Available:
http://ecdc.europa.eu/en/publications/Publications/0911_GUI_Scientific_Panel_o
n_Childhood_Immunisation_DTP.pdf (accessed 11/11/10)
References
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Health Protection Agency (2008) Health protection report; weekly report. [Online] Available:
http://www.hpa.org.uk/hpr/archives/2008/hpr1908.pdf (accessed 06/06/10)
Hofmeyr S (1997) Immune Memory. [Online] Available:
http://www.cs.unm.edu/~immsec/html-imm/memory.html (accessed 07/11/10)
Hull B, McIntyre P (2006) Timeliness of childhood immunisations in Australia. Vaccine. 24:
4403-4408
Luman E, Barker L, McCauley M, Drews-Botsch C (2005a) Timeliness of childhood
immunizations: A state-specific Analysis. American Journal of Public Health. 95(8): 1367-1373
Luman E, Baker L, Shaw K (2005b) Timeliness of childhood Vaccination in the United States:
Days Under vaccinated and number of vaccines delayed. Journal of the American Medical
Association. 293(10): 1204-1211
Luman E, Shaw K, Stockley S (2008) Compliance with vaccination recommendations of U.S
children. American Journal of Preventive Medicine. 34(6): 463-470
Pertola H (2000) Worldwide Haemophilius Influenza type b disease at the beginning of the
21st century: global analysis of the disease burden 25 years after the use of polysaccharide
vaccine and a decade after the advent of conjugates. Clinical Microbiology Reviews. 13:302317
Unicef (2010) Expanding immunisation coverage. [Online] Available:
http://www.unicef.org/immunization/index_coverage.html (accessed 20/10/10)