PERTUSSIS PROTECTION - CURRENT SCHEDULES IN EUROPE
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Transcript of PERTUSSIS PROTECTION - CURRENT SCHEDULES IN EUROPE
PERTUSSIS PROTECTION -CURRENT SCHEDULES IN
EUROPE – HOW MANY DOSES THROUGHOUT LIFE?
PERTUSSIS PROTECTION -CURRENT SCHEDULES IN
EUROPE – HOW MANY DOSES THROUGHOUT LIFE?
Susanna EspositoPediatric Highly Intensive Care Unit, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale
Maggiore Policlinico, Milan, Italy
AgendaAgenda
� Global burden of pertussis
� Burden of pertussis in infants, adolescents and adults
� Reservoir of Bordetella pertussis and disease transmission
� Pertussis prevention strategies
� Conclusions
Pertussis ‒ The Global ProblemPertussis ‒ The Global Problem
� Remains endemic worldwide� Estimated 20 ‒50 million cases and 300 000 deaths each year 1-3
� Major public health problem, even in countries with sustained high vaccination coverage 4
� Incidences (2/100,000) in Japan to 124/100,000 in S witzerland) 1,5
� Vaccination has reduced the global burden of pertus sis by over 90% compared to the pre-vaccine era 6
� However, major pertussis epidemics have been reporte d over the last decades in many countries, including Europ e, Japan, North and South America, Australia and New Zealand 1‒11
1. Celentano LP, et al. PIDJ 2005;24:761–5. 2. Crowcroft NS, Pebody RG. Lancet 2006;367:1926–36. 3. WHO. WHO-recommended surveillance standard of pertussis. Available at: http://www.who.int/immunization_monitoring/diseases/pertussis_surveillance/en/ (last accessed April 2013). 4. Tan T, et al. PIDJv2005;24:S10–18. 5. Sato Y & Sato H. Biologicals 1999;27:61‒69; 6. Wkly Epidemiol Rec 2010;85:385‒400. 7 Sato H, Sato Y. Clin Infect Dis 1999;28(suppl 2):S124–30. 8. Kamiya H, et al. EID 2012;18:1166‒1169. 9. Hozbor D, et al. J Infect 2009;59:225–31. 10. Hellenbrand W, et al. BMC Infect Dis 2009;9:22. 11. Grant CG & Reid S. NZ Med J 2010;123:46 ‒61
Global incidence of pertussis is decreasing as vaccination
coverage increases
0
10
20
30
40
50
60
70
80
90
0
500000
1000000
1500000
2000000
25000001
98
0
19
90
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
Number of cases WHO/UNICEF estimate
Nu
mb
er
of
case
s
Va
ccin
ati
on
co
ve
rag
e (
%)
(3 p
rim
ary
DT
P d
ose
s)
WHO IVB 2010 http://whqlibdoc.who.int/hq/2010/WHO_IVB_2010_eng.pdf (accessed July 2011)
1980: • almost 2 million reported cases• low (~20%) vaccination coverage
2009: • 106K reported cases• high (~80%) vaccination coverage
Number of reported cases
100
80
60
40
20
01990 1995 2000 2005 2012*
Year
< 1 y
< 1‒6 y
< 7‒10 y
< 11‒19 y20+ y
Inci
denc
e ra
te (
per
100,
000)
Reported Pertussis Incidence by Age Group: 1990 ‒2012*Reported Pertussis Incidence by Age Group: 1990 ‒2012*
*2012 data are provided
CDC data in presentation by J Liang: Tdap Vaccine Recommendations for Pregnant Women. Current Issues in Immunization NetConference. 21 Mar 2013. Available at: http://198.246.98.21/vaccines/ed/ciinc/downloads/2013-03-21/Liang-tdap-2013-03-21.pdf (Accessed April 2013)
21%
18%
26%12% 3%
1%
19%
Reported Pertussis Cases by Age Group – US2010‒2011
Reported Pertussis Cases by Age Group – US2010‒2011
1. CDC. Data on file (2010 Final Pertussis Surveillance Report), Nov 2011. 2. MKT24380 and CDC. Data on file (2011 Final Pertussis Surveillance Report), Oct 2012.MKT26067.
Pertussis is shifting to older children and adults: Europe 1998–
2007
Adapted from Zepp et al. Lancet Infect Dis 2011:11;557–70 (Derived from EUVAC NET data: http://www.euvac.net/graphics/euvac/pdf/pertussis1.pdf and
http://www.euvac.net/graphics/euvac/pdf/pertussis2.pdf)
<1 year 1–4 years 5–9 years 10–14 years ≥15 years
42% in ≥15 year olds
1998
1999
2000
2001
2002
2003–2007
0% 20% 40% 60% 80% 100%
~15% in ≥15 year olds
Pertussis Morbidity and Mortality in InfantsPertussis Morbidity and Mortality in Infants
� Highest incidence of morbidity and mortality consis tently in infants< 6 months of age who are too young to have complet ed their primary immunization series� Of the estimated 300 000 deaths yearly worldwide, m ost are in young infants;
90% in developing countries with case-fatality rate s estimated to be as high as 4% of infants < 12 months of age
� Highest complications and hospitalization rate (70% )
� Annually since 1990, 93 ‒100% of pertussis-related deaths in the US have occurred in < 4 months of age
� The number of deaths being reported in the infant p opulation has been steadily rising since the 1980s
Broder et al. MMWR 2006; 55(RR03); 1-34. Celentano LP, et al. Pediatr Infect Dis J 2005;24:761–5. Crowcroft NS, Pebody RG. Lancet 2006;367:1926–36. WHO. WHO-recommended surveillance standard of pertussis. Available at: http://www.who.int/immunization_monitoring/diseases/pertussis_surveillance/en/ (Accessed April 2013).California Department of Public Health, Immunization Branch. Available at: http://www.immunizeca.org/wp-content/uploads/2011/01/CDPH_Pertussis_Pertussis_task_force_1-11-2011.pdf (Accessed May 2013). MMWR 2002;51:73‒76. MMWR 2002;51:616-619. Vitek CR, et al. Pediatr Infect Dis J 2003;22:628‒634
Age (years)
Region 0–4 5–14 15–59 ≥60 Total
African Region 83,586 0 135 27 83,748
Region of the Americas 2,356 0 1 3 2,360
Eastern Mediterranean Region
18,904 0 0 2 18,906
European Region 121 0 2 3 126
South-East Asia Region 89,385 0 0 0 89,385
Western Pacific Region 580 0 1 8 589
World 194,931 0 139 43 195,113
WHO Global Health Observatory Data Repository http://apps.who.int/ghodata/?vid=10015 (accessed July 2011)
The greatest number of pertussis deaths
occur in infants and young children
Estimated pertussis deaths per region and age-group in 2008
The highest pertussis mortality is in infants/young children
Complications of Pertussis in Children ≤ 4 Years of Age in the US, 1997 ‒2000Complications of Pertussis in Children ≤ 4 Years of Age in the US, 1997 ‒2000
Age Hospitalization Pneumonia Seizures Encephalopathy DeathNo. with
Pertussis
< 6 M 4,543 847 103 15 56 7,203
6‒11 M 301 92 7 1 1 1,073
1‒4 Y 324 168 36 3 1 3,137
CDC. MMWR 2002;51(4):73‒76
Age group
Clinical characteristic
Adolescents (%) (10‒19 years)
Adults (%)(≥ 20 years)
Paroxysms 82–100 74–100
Whoop 30–67 8–82
Apnea 19–86 29–92
Cyanosis 6–15 0–12
Vomiting 45–71 10.5–70
Hospitalization 1.4–7.5 3.5–5.7
Clinical Symptoms of Pertussis in Adolescents and Adults
1.Aoyama T, et al. AJDC 1992;146:163‒166; 2. Farizo KM, et al. Clin Infect Dis1992; 14:708‒719; 3. Postels-Multani S, et al. Infection1995;23:139‒142; 4. Schmitt-Grohé, et al. Clin Infect Dis 1995;21:860‒866; 5. Trollfors B & Rabo E. Br Med J Clin Res Ed 1981;283:696‒697.; 6. Yih WK, et al. J Infect Dis 2000;182:1409‒1416; 7. DeSerres G, et al. J Infect Dis 2000;182:174‒179
Pertussis incidence and mortality is underestimated and
underreported�Pertussis burden is likely to be underestimated due to:1
1. Lima et al. The Burden of Pertussis in the Asia-Pacific Region. ESPID 2010;
2. Cherry Pediatr Infect Dis J 2006;25:361–2; 3. Stefanoff et al. ESPID 2011 abstract
Low disease
awareness
Limited facilities
for laboratory
analysis
No common
case-definition
Lack of surveillance
data
Few reliable
reporting systems
� In general the actual incidence of pertussis could be 40–160-fold higher than
official figures2,3
Transmission cycle of pertussis
between adults and infants1,2
Pertussis vaccination in the
first year of life
Pertussis booster vaccination during
childhood
If no pertussis booster vaccination: protection wanes
over time
Non-vaccinated or partly vaccinated infants: susceptible
Adults and adolescents can serve as reservoirs of pertussis infection
cycleThe
of infection
Household members are often the source of pertussis in young infants (in 76–83% of cases)3
New parents are the source of disease transmission in >50% of infant pertussis cases4
1. Wirsing von König CH, et al. Lancet ID 2002;2:744–50. 2. Finger et al. In: Barron S, ed. Barron's Medical Microbiology 1996; 3. Wendelboe et al. Pediatr Infect Dis J 2007; 26:
293–9; 4. Gerbie, Tan. Obstet Gynecol 2009; 113: 399–401
Pertussis Transmission to Young InfantsPertussis Transmission to Young Infants
� Prospective international multicenter study of laboratory confirmed pertussis cases in ≤ 6 M and their household and non-household contacts – France, Germany, US, Canada
� 95 index cases and 404 contacts – source case was identified for 61.5% of index cases�mean age of the infant index case was
2.9 M (35 - < 2 mos; 38 - 2 to 3 mos; 22 - 4 to 6 mos)
Wendelboe AM, et al. Pediatr Infect Dis J 2007;26:293-299
Source cases
Parents
55%
Siblings - 16%
Aunts/Uncles - 10%
Friends/ Cousins - 10%
Grandparents - 6%
Part-time caregivers
2%
Pertussis prevention strategies throughout life
0 3months
Adolescents AdultsChildren
Waning
immunity1
Vaccine induced
protection1
Limited natural
immunity1
Transmission2,3
Elderly
1. Adapted from Wendelboe et al. Pediatr Infect Dis J 2005: 24; S58–S61; 2. Sawyer, Chair ACIP Pertussis Vaccine WG, Oct 24, 2012; 3. CDC. MMWR 2011; 60: 13–15;
4. Tan & Gerbie, Obstetrics Gynecol 2013; 122: 370–3; 5. CDC. MMWR 2011; 60: 1117–23; 6. CDC. MMWR 2012; 61; 66–72; 7. CDC. MMWR 2013; 62: 66–72;
8. Healy et al. Clin Infect Dis 2011; 52: 157–62
Pertussis vaccination
�Pertussis vaccines, available as whole-cell or acellular formulations, are an
important component of vaccination schedules worldwide
WHO. Wkly Epidemiol Rec 2010;85:385-400. CDC. MMWR Morb Mortal Wkly Rep 2011;60:13-5Please refer to local prescribing information for the relevant product or contact GSK in your country for information on GSK products
DTPw /DTPaPrimary vaccination
2, 3, 4 months
3, 4, 5 months
2, 4, 6 months
6, 10, 14 weeks
-------------------------Two-dose schedules in
some countries3 and 5 months
dTpaAdditional booster
Preschool
Adolescent
Adult
DTPw /DTPaBooster
16, 18, 24 months
-------------------------
Booster for children who received the two-dose
primary11–13 months
High vaccine response rates against pertussis antigens
with DTPa-HBV-IPV/Hib (2 + 1 schedule)
GSK, GlaxoSmithKline Biologicals
1. Avdicová et al. Eur J Pediatr 2002; 161: 581–7; 2. Gabutti et al. Scand J Infect Dis 2004; 36: 585–92; 3. Results summary for Study 217744/060. [Accessed 31 Aug 2011]
http://download.gsk-clinicalstudyregister.com/files/2194.pdf;
4. Kilpi et al. Hum Vaccine 2009; 5: 18–25; 5. Van Der Meeren et al. Vaccine 2012; Feb 18. [Epub ahead of print]
• Pooled analysis of four studies (N=626)
• Infants received DTPa-HBV-IPV/Hib (GSK) in a 2 + 1 schedule (3, 5, 11/12 months)1–4
*Vaccine response rate for pertussis antigens defined as the appearance of antibodies in initially seronegative subjects (concentration <5 EL.U/ml), or at
least maintenance of pre-vaccination antibody concentrations in initially seropositive subjects; 1 month post-dose 2 and 1 month post-booster dose
Va
ccin
e r
esp
on
se r
ate
s (%
)*
for
pe
rtu
ssis
an
tig
en
s5
100
80
60
40
20
0
PT FHA PRN
Po
st-d
ose
2
Po
st-b
oo
ste
r
Po
st-d
ose
2
Po
st-d
ose
2
Po
st-b
oo
ste
r
Po
st-b
oo
ste
r
Figure adapted from Van Der Meeren et al. Vaccine 2012; Feb 18. [Epub ahead of print]
A vaccine response against pertussis antigens was observed in >97.7%
of subjects across the four studies5
Booster vaccination with dTpa-IPV was as immunogenic
as DTPa-IPV in children (5–6 years) in Italy
� Open, randomised study:
– N=303 children, primed in a 2+1 schedule of DTPa (GSK)
– One dose of dTpa-IPV (GSK) or DTPa-IPV (Sanofi Pasteur), both co-administered with MMRV (GSK)
Reduced-antigen content dTpa-IPV
GSK
N=139
Primary DTP-IPV
Sanofi Pasteur
N=146
GSK, GlaxoSmithKline Biologicals
Ferrera et al. Hum Vaccin Immunother 2012; 8 [Epub ahead of print]
*Booster response: 4-fold increase in antibody concentration (D, T, polio); ≥20 El.U/mL
in initially seronegative subjects, 4-fold increase in subjects with pre-vaccination
antibody concentrations ≥5 El.U/mL to <20 El.U/mL, ≥2-fold increase in subjects with
pre-vaccination antibody concentrations ≥20 El.U/mL (PT, FHA, PRN); ^There is no PRN
antigen in the DTPa-IPV vaccine
Bo
ost
er
resp
on
se r
ate
re
spo
nse
rate
* (
%)
wit
h 9
5%
CI
Ambro/FreeDigitalPhotos.net
Booster vaccination with dTpa induced a comparable
immune response to other licensed vaccines in
adolescents (13–17 years) in the UK: pertussis antigens
GSK, GlaxoSmithKline Biologicals
Southern et al. Vaccine 2005; 23: 3829−35
An
tib
od
y G
MT
(E
l.U
/mL)
(lo
g)
wit
h 9
5%
CI
dTpaGSKN=68
dTpa Sanofi Pasteur
N=74
dTpa-IPVSanofi Pasteur
N=75
dTSanofi Pasteur
N=71
PT
FHA
PRN
• Randomised single-blind study conducted in the UK (N=323)
• Primed with ≥4 doses of DT-containing vaccine (3+1) with ≥8 years since the last dose
• Head-to-head comparison, subjects received a single dose of one of four vaccines: dTpa (GSK),
dTpa (Sanofi Pasteur), dTpa-IPV (Sanofi Pasteur ), dT (Sanofi Pasteur MSD)
Ambro/FreeDigitalPhotos.net
Reactogenicity of dTpa compared to other licensed
vaccines in adolescents (13–17 years) in the UK
Pain/tenderness SwellingRedness
^‡
†
†dTpa (GSK) vs dT (p=0.265)‡dTpa (Sanofi Pasteur) vs dT (p=0.098)
^dTpa-IPV vs dT (p=0.001)Southern et al. Vaccine 2005; 23: 3829−35
dT (Sanofi Pasteur)
dTpa (Sanofi Pasteur)
Reduced antigen content dTpa (GSK)
dTpa-IPV (Sanofi Pasteur)
Inci
denc
e (%
)
Local symptom
comparable
Adolescent and Adult Groups for whom CDC Strongly Recommends Tdap Vaccine
Adolescent and Adult Groups for whom CDC Strongly Recommends Tdap Vaccine
� ALL Adolescents beginning at 11–12 years of age – No minimal interval between last Td and Tdap vaccine 1,2 – (78.2% immunized) 3
� ALL Adults especially those who are Close Key Conta cts of Infants < 12 months of age 4 – including persons ≥ 65 years of age1,5 – (13% immunized) 6
� Healthcare workers who have direct patient contact i n any hospital or clinic setting 2 – (27% immunized) 6
� Wound Care – Any adolescent or adult who gets a sever e cut or burn and needs protection against tetanus infection 5
� Tdap should be used in place of Td if person has not had a previous dose of Tdap 4
1. MMWR 2011;60(1):13‒15. 2. AAP & CDC. Pediatrics 2011;128:809-812. 3. MMWR 2012;61(34):671‒677. 4. Kretsinger K, et al. MMWR 2006;55(RR17):1–33; 5. MMWR 2012;61(25):468‒470. 6. CDC. Press Briefing Transcript. Telebriefing on US Adult Vaccination rates. Tues Jan 29, 2013. www.cdc.gov/media/releases/2013/t0129_adult_vacc_rates.html (Accessed May 2013)
Adolescent and Adult Groups for Whom CDC Strongly Recommends Tdap Vaccine
Adolescent and Adult Groups for Whom CDC Strongly Recommends Tdap Vaccine
� Pregnant women (after 20 weeks gestation) who have n ot previously received a dose of Tdap should receive a dose1 –(2.8% immunized) 1
� Newest recommendation: dose of Tdap should be given d uring each pregnancy between 27 weeks and 36 weeks regard less of the interval since the last pregnancy 1
� Postpartum administration of Tdap as soon as possible after delivery and before hospital discharge remains a vi able optionfor those women who did not receive the vaccine dur ing pregnancy and have never received a dose of Tdap vac cine in the past 1,2
� Postpartum administration of Tdap is ONLY a one time dose 1,2
1. MMWR 2013;62;7:131‒135; 2. Kretsinger K, et al. MMWR 2006;55(RR17):1–3
Pertussis Incidence, British ColumbiaPertussis Incidence, British Columbia
0
20
40
60
80
100
120
140
160
2003 2006
15–19 year olds10–14 year olds
84% reduction in 10 ‒14 year olds
Tdap 5 begun in 14–16 year olds, 2004
Greenberg DP, et al. Pediatr Infect Dis J 2009;28(6):521–8
Reduction in 10 ‒14 year olds shows evidence of herd immunity
Per
tuss
isin
cide
nce
(cas
es p
er 1
00,0
00)
dTpa elicited a robust increase in pertussis
antibodies when administered as a decennial booster
Australia1 Finland2
1. Booy et al. Vaccine 2011; 29: 45–50
2. Mertsola et al. Clin Infect Dis 2010; 51: 656−62 *Data are presented for group originally vaccinated with dTpa
Seropositivity
threshold
(5 El.U/mL)
� In both studies, the decennial booster was generally well tolerated
An
tib
od
y G
MC
s (E
l.U
/mL)
(lo
g)
wit
h 9
5%
CIs
*
Ambro/FreeDigitalPhotos.net
Adolescent and Adult Pertussis Vaccine Recommendations in Europe
Adolescent and Adult Pertussis Vaccine Recommendations in Europe
EUVAC.NET. Pertussis vaccination overview in European countries. Available at: http://www.euvac.net/graphics/euvac/vaccination/pertussis.html (Last accessed April 2013)
Country Pertussis containing vaccineAustria Tdap 13 years, Tdap 18-20 years, Tdap every 10 years u ntil 60 years, then
every 5 years
Belgium Tdap 14-16 years, cocoon
Finland Tdap 14-15 years
France DTaP-IPV 11-13 years or if missed catch up Tdap-IPV 16-18 years, Tdap-IPV once in adulthood, HCW, CCW, cocoon
Germany Tdap or Tdap-IPV 9-17 years, Tdap once in adulthood, HCW, CCW, cocoon
Greece Tdap 11-12 years, if missed Tdap once in adulthood
Ireland Tdap 11-14 years
Italy Tdap 11-12 years
Luxembourg Tdap-IPV 15-16 years, then every 10 years
Norway Tdap in adults every 10 years until 60 years
Sweden Tdap 14-16 years
Switzerland Tdap 11-15 years, Tdap 25-29 years, cocoon
� Adults are an important source of infection for infants,
particularly family members1
� dTpa vaccination in adults can boost immunogenicity, even in
adults with no previous vaccination for many years2
• Double-blind, randomised, controlled trial in 460 adults
≥40 years of age with no diphtheria or tetanus vaccination for
20 years or unknown vaccination history2
• ≥96.4% seropositivity/seroprotection observed for all antigens
after 3 doses of dTpa or dTpa-IPV (GSK) 2
1. Zepp et al. Lancet Infect Dis 2011: 11; 557–70; 2. Theeten et al. Curr Med Res Opin 2007; 23: 2729–39
Immunogenicity in adults can be boosted with dTpa even in
a catch-up setting
Cost-effectiveness of Adult Pertussis VaccinationCost-effectiveness of Adult Pertussis Vaccination
� A German model has suggested that an adult pertussi svaccination program would be cost effective� A one-time adult vaccination strategy would prevent 498,000 cases� A decennial adult vaccination strategy would preven t 1 million
cases
� The programs would cost� €366 million and €687 million, respectively � €160 and €200 per case prevented, respectively
Lee GM, et al. Vaccine 2008;26(29–30):3673–9
Antepartum and Cocooning Programs
Major objective � Protect young infants, who are too young to be immu nized, from getting
pertussis disease 1‒4
Rationale � Targeted Tdap immunization of all potential adolesce nt and adult contacts
of infants 1,2
Vaccination strategies close contacts of the infant� Pregnant women between 27 and 36 weeks gestation wi th each
pregnancy and postpartum mothers 1,3,4
� Family members and relatives 1,2,4
� Babysitters, nannies, daycare providers� Other close contacts 4
1. Forsyth KD, et al. Vaccine 2007;25:2634–42. 2. Coudeville L, et al. PLoS ONE 2009;4(7):e6284. 3. Healy CM, et al. Vaccine 2009;27(41):5599–5602. 4. Gerbie MV and Tan TQ. Obstet Gynecol 2009;113(2pt1):399–401
Countries with cocooning recommendations
1. Australian Immunisation Handbook 9th edition 2008; Part 2.3.2, available from: http://www.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook-
specialgroups (accessed June 2011); 2. Kinkhoest (pertussis) – vaccinatie. Available from: http://www.zorg-en-gezondheid.be/Ziektes/Vaccinaties/Vaccins-A-Z/Kinkhoest-
%28pertussis%29---vaccinatie/ (accessed June 2011; 3. Haut conseil de la santé publique. Bulletin Épidémiologique Hebdomadaire 2009;16–17:46–76; 4.
Impfempfehlungen der Ständigen Impfkommission am Robert Koch-Institut/Stand: Juli 2010. Epidem Bull 2010;30:279–98; 5. New Zealand Ministry of Health
Immunisation Handbook 2011; Ch 6; 6. CDC. MMWR 2011;60:13–5; 7. http://www.cdc.gov/vaccines/recs/provisional/default.htm (accessed August 2011); 8. WHO
vaccination schedule, available from: http://apps.who.int/immunization_monitoring/en/globalsummary /ScheduleSelect.cfm (accessed June 2011)
Country withcocooning recommendation
Country withoutcocooning recommendation
ConclusionsConclusions
� Pertussis remains a major public health problem esp ecially in adolescents and adults where the incidence of disea se is increasing and causing a substantial disease burden
� Most infants are infected by an adolescent or adult contact
� Development of improved surveillance systems and re cognition of adolescent and adult pertussis disease is needed
� In order to control spread of disease, vaccine stra tegies focused on increasing vaccination rates in the adolescent and adult populations are critical
� Cocooning is an increasingly common method to prote ct infants from disease
� Educational interventions are required for HCW and patients to increase awareness of adolescent and adult pertussis disease and importance of Tdap vaccination