Boostrix: An Update on Tdap Vaccine in Pregnancy

1Copyright © 2014 Well Woman Clinic. All rights reserved. 1
An Update on Maternal
Immunisation with Tdap Vaccine
Dr Nupur Gupta

2Copyright © 2014 Well Woman Clinic. All rights reserved.
Maternal Immunization
To protect the
newborn in 6-8
weeks after birth
To protect both
mother and foetus
during pregnancy
Vaccination to boost maternal antibodies, aiming to

Maternal immunization: benefits
to mother, foetus & young infants
Inactivated influenza,
Tetanus toxoid,
Tdap (acellular pertussis vaccines)
Chu HY & Englund JA. Clin Infect Dis 2014;59:560–568

 Tetanus, Diphtheria & pertussis are very serious diseases
 Tdap vaccine can protect against all of these
 Before vaccines, almost 2 lac cases of diphtheria & tetanus
were reported in US each year
 Post vaccination, cases reduced by about 99% for diphtheria &
80% for pertussis
Why Get Vaccinated?

Pertussis (Whooping Cough)
• Highly contagious respiratory infection
• Gram-negative bacterium Bordetella pertussis
• It affects people of all ages (adults – mild, baby not
vaccinated – life threatening)
• Transmission: airborne droplets or direct contact
with nasopharyngeal discharges from an infected
person
• Humans are the only reservoirs

 Severe bouts of coughing
 “Whooping” sound is heard when they try to breathe & gasp
for air
Whooping Cough

• Pertussis has been seen highest in
the period between birth and 6–8
weeks of age2,4
• > 90% of infants under 2months with
pertussis infection are hospitalized3
• 76% of pertussis related deaths occur
in infants aged under 2 months4
1.Berti E, et al. Acta Paediatr 2014;103:846–9.)
2. Meulen et al,CID,2016
3. Hong JY. Update on pertussis and pertussis immunization. Korean J Pediatr 2010;53(5):629–633.
4. Healy CM et al Hum Vac Imm 2016
Prevalence of the Disease

Pertussis Trends
8
January 2016

Pertussis incidence is increasing in
adolescents across the world
Since 2005, there has
been an increase in
pertussis incidence in
the 10–14 year age
group
2010: 80% in ≥10 year
olds
1998: 29% in ≥10 year
olds
Pertussis is not just a childhood disease1. Adolescents account for an
increasing proportion of pertussis cases
Pertussis
cases
increased
by around
50%
England
and
Wales31
USA5
Europe1,4

 is caused by a bacterium often found in soil.
 Once it enters the body it releases a toxin that attacks
the nervous system, causing muscle spasms & death if left
untreated.
Tetanus or Lockjaw

Diphtheria
 a respiratory disease that can cause breathing
problems, paralysis, heart failure, & death.
 It is highly contagious & is spread by coughing &
sneezing

 Without vaccination – 50 infants born in a hospital will
become sick every yr (40 will need hospitalisation)
 With vaccination - Only 4 babies will get whooping
cough
How effective is vaccination in pregnancy
(pertussis)?

 Adolescents 11 – 12 years (if missed, asap)
 Td booster every 10 years
 In every pregnancy
 Contraindications – H/o life threatening allergic reaction or
coma or long repeated seizures to any component of DTP
 Caution – if seizures or GBS
Tdap Vaccine

 Pain, redness, swelling at injection site
 Fever, headache or tiredness
 Nausea, vomiting, diarrhoea or stomach ache
 Chills, bodyache, swelling of the arm
 Allergic reaction – hives, swelling of face, difficulty in
breathing, palpitation, dizziness or weakness
Risks

Childhood
vaccination helps
prevent
complications and
deaths in infants1
Pertussis in
adolescents is
characterized by
Long-lasting,
non-specific,
mostly
misdiagnosed
cough1
However, vaccination does
not confer lifelong
immunity. It wanes off 4-12
years after vaccination2
Immunity against pertussis
wanes over time
Adolescent and pre
school booster
vaccination helps
protect them against
pertussis1
4-6 years
Zepp et al. Lancet Infect Dis 2011;11(7):557–570
Wendelboe et al. Pediatr Infect Dis J 2005:24;S58–61

Tdap in Pregnancy & Adolescents
Inactivated non infectious
bacterial products
Boostrix (GSK)

Adacel (Sanofi Pasteur)
Tdap in Adolescents

Optimal Timing
 27 to 36 weeks (To take advantage of naturally occurring
process of antibody transfer) (Also to achieve higher antibody
concentration in the fetus)
 Or at least 2 weeks prior to delivery
 Protection of infant is up to 6 months of delivery till their
routine course is completed

Postpartum Tdap is not protective
 It takes 2 weeks after administration that protective
antibodies are formed
 So does not provide immunity to infant
 Women who have received a Tdap as adolescents or adults
but not in pregnancy, should not receive the vaccine
postpartum.

Cocooning may not be effective
 It means vaccinating anyone who comes in
close contact with the infant
 It is hard to implement
 It is costly too

Tdap should not be offered as part of
preconception care
 Because protection does not last long
 Even if given, has to be repeated in pregnancy (rapid waning
of antibody levels)

Tdap can be given in early pregnancy also
 For wound care or during a community outbreak
 Should not be repeated between 27 to 36 weeks
pregnancy (only one dose is recommended)
 Considered safe at any gestation if indicated

Despite high DTP coverage, pertussis cases
reported
Global distribution - 1,39,535 pertussis cases WHO in 2016

Pertussis cases in India (2000-2016)
0
10000
20000
30000
40000
50000
60000
70000
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Pertussiscases
2
> 30,000 reported cases each year
India is the top country by pertussis
cases in the world1

Pertussis is under estimated
The true incidence of pertussis is likely
to be higher in both developed &
developing countries due to
under-diagnosing & under-reporting

Who is at risk of Pertussis?
Infants Adolescents Adults
Recommendation to vaccinate is since 2006

Pertussis: Complications in young infants
Hong. Korean J Pediatr 2010;53(5):629–633
<2 months of age
Complication Rate, %
Hospitalisation >90
Pneumonia 15–25
Seizures 2–4
Encephalopathy 0.5–1
Death 0.5–1

0
5
10
15
20
25
30
35
40
Mother Father Sibling Grandparent Other
Mothers: MC source of pertussis for
newborns
Percentageoftotalsourcecontactswithpertussis
37.3
17.6
26.8
4.2
14.9
Main source of infection
Sources of infant pertussis cases by contact category (%)
Wiley KE, et al. Vaccine 2013; 31:618–625.

Adolescents AdultsChildren
Waning
immunity1,4
Vaccine-induced
protection1,4 Limited
immunity1,4
Transmissio
n
Elderly
Complications
& death5
Older individuals represent a reservoir of infection, potentially transmitting disease
to unvaccinated or partially vaccinated infants
Young infants
As per current practice, only children are
vaccinated with DTP, starting at 6 weeks
What happens when only children are vaccinated

Highly
effective in
protecting
infants from
pertussis4
Vaccination strategies that may help protect
young infants from pertussis
Adolescent &
Adult booster
vaccination
Cocooning
Maternal
immunisation

What is Tdap vaccine ?

Boostrix Prescribing Inform.Version BTX/PI/IN/2017/01 dated 04 Apr 2017
Posology and method of administration
 A single 0.5 ml dose recommended IM preferably in the
deltoid region
 Boostrix has shown no vaccine related adverse effect on
pregnancy or on the health of the foetus in the 3rd &
2nd trimester/newborn child
 It also doesn’t harm the foetus at any trimester of
pregnancy

Argentina (safety data > 1.2 Million Doses)
51%
67%
57%
0% 20% 40% 60% 80%
2012
2013
2014
Maternal Vaccination coverage (%)
National Immunization program
2012 to 2014
Objective: Maternal & infant outcomes
20 adverse events (rate:1.59/100,000 )
7 were mild (2 episodes of rash & 5 had local pain,
redness & swelling)
There were no serious or fatal events reported1

Public Health England (PHE), 2014
A national pertussis outbreak was declared in April 2012 by
the Health Protection Agency in the UK
Vaccination was recommended for pregnant women from 28
to 32 weeks of pregnancy, to ensure that high levels of
antibodies against pertussis cross the placenta from the
mother to passively protect the baby when it is born
There are no safety concerns at any stage of pregnancy

Immunogenicity of Tdap vaccine in
Maternal Immunisation
Showed efficient transplacental transfer
of pertussis specific antibodies
Results in high infant antibody concentrations
Was associated with the highest umbilical cord
antibody when Tdap was administered
between 27~31 weeks of gestation

Lakshmi Sukumaran et al, JAMA. 2015;314(15):1581-1587
Morgan JL, et al, Obstet Gynecol. 2015 Jun;125(6):1433-8
United States (What if freq vaccination?)
Among women who received Tdap during pregnancy,
• No increased risk of acute adverse events or adverse
birth outcomes for those who had been previously
vaccinated < 2 yrs before or 2 to 5 yrs before
compared with those who had been vaccinated > 5
yrs before.
• These findings suggest that relatively recent receipt
of a prior tetanus-containing vaccination does not
increase risk after Tdap in pregnancy.

3
Thailand: reactogenicity in Tdap vaccinated pregnant
women with prior TT vaccine
A prospective randomized controlled study involved healthy Thai pregnant
women (631 screened, 370 were enrolled) aged 18–45 year who were
offered Boostrix between 26-36 weeks of gestation
It did not increase the incidence and severity of any solicited
Adverse Events nor resulted in prolonged duration of the
symptoms. There was no premature delivery
98 women received in addition to Boostrix at least one extra dose of TT
containing vaccine during the same pregnancy
(1 dose in 37 women, 2 doses in 60 women,3 doses in 1 woman).
N. Wanlapakorn et al. / Vaccine 36 (2018) 1453–1459

Safety of Boostrix + FLU vaccinations
in pregnancy
Sukumaran L,et al. Obstet Gynecol 2015 Vol. 126, NO. 5, Nov 2015
• Concomitant group - No statistically significant increased risk of fever
or any other Adverse Effect
• Both groups - No difference in preterm delivery, LBW, or small for
gestational age neonates
36,844 pregnancies - Tdap & Flu vaccines
- concomitantly in 8,464 (23%) pregnancies
- sequentially in 28,380 (77%) pregnancies
Retrospective, cohort study of pregnant women using the Vaccine
Safety Datalink from 2007 to 2015

No increased risks for any pre-specified maternal
safety outcomes within 42 days of vaccination
More evidence: generally well tolerated profile
Kharbanda EO Vaccine. 2016;34(7):968-73;
Morgan et al. Obstet Gynecol 2015;125:1433–8)
Vizzotti C et al. Vaccine 2015;33:6413-19
Tdap vaccines safety cohort included 53,885
vaccinated pregnant women

FOGSI Recommendation
Tetanus diphtheria acellular pertussis (Tdap) vaccination
can be considered instead of the second dose of tetanus
toxoid(TT) to offer protection against diphtheria and
pertussis in addition to tetanus
FOGSI Good Clinical Practice Recommendations on PRECONCEPTION CARE - 2016
"Tdap should be administered during pregnancy in order
to provide optimal protection to the baby during its first
months of life

ACOG Recommendations(Sep 2017)
ACOG UPDATE ON Immunization & Pregnancy Sep 2017(718)
Administer Tdap vaccine to all pregnant woman as early as 27–36
weeks
Pregnant women should be counseled that Tdap during each
pregnancy is safe and important to make sure that newborn protected
against pertussis at birth
If not administered during pregnancy, the Tdap vaccine be given
immediately postpartum if the woman has never received a prior dose
of Tdap as an adolescent, adult, or during a previous pregnancy

IAP recommendation
“One dose of Tdap vaccine between 27 to 36 wks gestation
regardless of number of years from
prior Td or Tdap vaccination”
ACVIP (Advisory Committee on Vaccines and Immunization Practices)

Australia
A 1:1 matched case-control study
16.8.15 to 17.8.16 at New South Wales
Vaccine effectiveness (VE) against hospitalization
was 94% (95% CI 59–99%)

United States
California, Connecticut, Minnesota, New Mexico & New York
The Vaccine Effectiveness was 90.5%
(95% CI: 65.2- 97.4) against preventing
infant pertussis hospitalization
A case–control study
1 January 2011 and December 2014.

Vizzotti C, et al. Vaccine. 2015 Nov 25;33(47):6413-9
- Reduction in mortality: 87%
- Overall fatality rate: 69.9%
0
10
20
30
40
50
60
70
80
2011 2012 2013
0
0.5
1
1.5
2
2.5
3
0.9
1.7
2.6
103276
Years
Numberofdeaths
No. of deaths Fatality rate
Fatalityrate
Infants <2 months of age
Argentina (2011- 2013)

Spain
The adjusted Vaccine effectiveness (VE) was 90.9%
(95%CI- 56.6 to 98.1)
in protecting newborns against laboratory confirmed
pertussis infection
A matched case control study was undertaken in the
period between 1.3.15 to 29.2.16

Countriesthatimplementorrecommendpertussisbooster
vaccineinMaternalImmunisation
Country with maternal immunisation recommendation
Country without maternal immunisation recommendation
> 31 countries have
Recommendation/implementation
 UK
 S Korea
 India
 Australia
 New Zealand
 Italy
 Taiwan
 Greece
 Qatar
 Colombia
 Suriname
 Switzerland
 USA
 Canada
 Spain#
 Belgium
 Israel
 Ireland
 El Salvador
 Panama
 Brazil
 Argentina
 Paraguay
 Costa Rica
1.Ivo Vojtek et al. Annals of Medicine,2018:1-16-MI: where are we now & how to move forward
2.Data on file-1

27−30+6 weeks
31−36 weeks
or >36 weeks
Timing: Which is better?

Efficient transplacental transfer of pertussis
specific antibodies
Antibody responses to pertussis
antigens in umbilical cord sera
1.12
17.13 10.6217.81
190.16 162.09
0
50
100
150
200
250
PT FHA PRN
AntibodyGMC(IU/mL,95%CI)
No Tdap
(n=20)
Tdap b/w 27–30+6 wks was
associated with the highest
umbilical cord IgG GMCs to PT
& FHA compared with
immunisation beyond 31 wks
of gestation
Abu Raya B et al. Vaccine 2014;32(44):5787–5793
GMC, geometric mean concentration; PT, pertussis toxin; FHA, filamentous haemagglutinin; PRN, pertactin

To Summarise
The use of Tdap may be considered
during the third trimester of pregnancy
Tdap in the 3rd trimester have shown no vaccine
related adverse effect on pregnancy or on the
health of the fetus/newborn child

Boost their immunity with
Boostrix
Children due for their
second DTP booster at
4- 6 years of age
Children aged 10 years
+ due for their
adolescent booster
4- 6 years 10 years +

Future Research
• Long-term impact of maternal vaccination in pregnancy on
vaccine effectiveness in children & adults
• Safety & impact of repeated Tdap in subsequent pregnancies;
• Safety of immunization earlier in pregnancy;
• Cost-effectiveness of maternal pertussis immunization in
pregnancy
• Development of more effective infant pertussis vaccines

Boostrix: An Update on Tdap Vaccine in Pregnancy

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Boostrix: An Update on Tdap Vaccine in Pregnancy

Similar to Boostrix: An Update on Tdap Vaccine in Pregnancy (20)

More from Dr Nupur Gupta High Risk Obstetrician

More from Dr Nupur Gupta High Risk Obstetrician (20)

Recently uploaded

Recently uploaded (20)

Boostrix: An Update on Tdap Vaccine in Pregnancy

Editor's Notes