A small comparison between DTaP & DTwP in light of recent articles. Presented in Panchkula in a small group meeting

1. Acellular Vaccines
versus Whole cell
vaccine in
Pertussis Prevention

2. Flow of presentation
 Pertussis – An introduction
 Whole cell Pertussis vaccine
 Advent of Acellular Pertussis vaccine
 Safety and efficacy of Pertussis vaccines
 Recent outbreaks

3. Introduction to Pertussis

4. Introduction
Between 1940-1945, before widespread vaccination, as many as
147,000 cases of pertussis were reported in the United States each year,
with approximately 8,000 deaths caused by the disease.
In 1976, there were 1,010 case of pertussis in the US, the lowest number
of cases ever reported.
Over the past few years the number of reported cases of pertussis has
increased, reaching 25,827 in 2004; worldwide, there are an estimated
300,000 annual deaths due to pertussis.

5. Introduction to Acellular and
Whole pertussis vaccine

6. Pertussis Vaccines: Whole Cell
• EFFICACY VARIABLE : 50 – 98%
• PROTECTION : 36-48% (Italy, Sweden)
• COMMON CHARACTERISTIC: REACTOGENICITY
• LOCAL • SYSTEMIC
– Fever
– Pain – Irritability
– Redness – Others......
– Swelling
• 1970’s Dramatic decrease in vaccination (UK, Japan,
Sweden, Germany)
• US: Legal issues
• LEADING TO DEVELOPMENT OF NEW VACCINES
Gustafsson etal. NEJM 1996; 334(6): 349-55

7. Development of Acellular Pertussis
Vaccines
• After the introduction of pertussis
vaccine in Japan, number of
pertussis cases decreased to 200
cases per year (1970) but vaccine
associated accidents occurred
in 1974-75.
• Vaccine accidents decreased the
vaccine coverage which resulted in
an increase in number of cases.
• In 1981 a new type of acellular
pertussis vaccine combined with
DT toxoids (DTaP) vaccine was
introduced and thereafter the
number of cases decreased.

8. Reactogenicity post-DTwP (whole
cell) vaccine

9. Frequency of Side Effects with
Pertussis Vaccines
Event wP vaccine aP vaccine
Average Average
Fever < 38.3°C 44.5% 20.8%
Fever > 38.3°C 15.9% 3.7%
Erythema 56.3% 31.4%
> 2.0 cm 16.4% 3.3%
Swelling 38.5% 20.1%
Drowsiness 62.0% 42.7%
Significant reduction in adverse reactions with aP Vaccines
Acellular Pertussis Vaccines: Pertinent Issues. Ind Pediatr 2008; 45; 727-729

10. Whole Cell Pertussis Vaccines:
VAERS analyses
• VAERS* analysis demonstrated that the temporal
association between DTwP vaccination and a myriad of
serious AE is not due to coincidence.
• It is believed that the high levels of endotoxin present in
DTwP vaccine may be correlated with a higher incidence
of AEs.
• The recommendation by the AAP to use DTaP beginning
in 1996 seems well justified based upon the results of
the VAERS study.
* Vaccine Adverse Event Reporting System

11. Serious Reactions: Whole cell vs.
Acellular pertussis vaccines
A summary of adverse events reported with an initial onset of symptoms
within 3 days following whole-cell pertussis vaccination in comparison to
acellular pertussis vaccination to VAERS database from 1997 through 1999
Geier DA & Geier MR;- Brain & Dev. 2004, 26(5):296-300

12. Serious Reactions: Whole cell vs.
Acellular pertussis vaccines
• The review of the 1993, Stockholm, Sweden
prospective clinical study found:
– Statistically significant decreases in the incidence
rates of seizures, HHE and high fevers following
DTaP as compared to DTwP.
– True rate developing a serious neurological
condition:
• One case in 725 DTwP immunizations
• One case in 1887 DTaP immunizations
Olin et al. Lancet 1997, 350: 1569-77

13. Serious Reactions: Whole cell vs.
Acellular pertussis vaccines
Decrease in Hospital Admissions for
Febrile Seizures and Reports of
Hypotonic-Hyporesponsive Episodes
Presenting to Hospital Emergency
Departments Since Switching to
Acellular Pertussis Vaccine in Canada: A
Report From IMPACT
Nicole Le Saux, MD*, Nicholas J. Barrowman, PhD,
Dorothy L. Moore, Sharon Whiting, David
Scheifele, and Scott Halperin
PEDIATRICS Vol. 112 No. 5 November 2003, pp. e348-e348

14. Report from IMPACT
• In 1997–1998, Canada adopted 1 combination acellular pertussis vaccine,
having previously used 1 particular combination whole-cell pertussis
vaccine.
• Active surveillance was performed between 1995 and 2001 by the
Immunization Monitoring Program–Active monitors at 12 hospitals using
standard case definitions.
• The study documented a 79% decrease in febrile seizures associated with
receipt of pertussis vaccine.
• There was a 60% to 67% reduction in HHEs associated with pertussis-
containing vaccines between the same time periods, depending on case
definition.
• Conclusions. The risks of febrile seizures and HHEs after pertussis-
containing vaccine declined significantly with the introduction of acellular
pertussis vaccine in Canada. Active surveillance systems are important for
detecting trends in uncommon adverse events after routine immunizations.
Nicole LS et al. Pediatrics 2003;112;e348

15. What does WHO say?
• Protection against severe pertussis in infancy and early
childhood can be obtained after a primary series of
vaccination with wP or aP vaccine
• The best aP vaccines have shown similar protective
efficacy as the best wP vaccines (≥ 85%)
• All licensed vaccines have proved to be highly effective in
controlling pertussis in infants and young children
WER 28 January 2010, vol. 85, 40 (pp 385-400), WER 28 January 2005, vol. 80, 4 (pp 31-39)

16. Acellular Pertussis Vaccines
available in India
Brand Componenets
Tripacel SP PT, FHA, PRN,
FIM2, FIM3
Pentaxim SP PT, FHA
Infanrix GSK PT, PRN, FHA

17. Efficacy of
DTwP and DTaP vaccines
96 96 98
93 89
85 85 84
71
59
48 36
2
(2-3-4) (3, 4-5,
6 & 15-
18)
The best acellular pertussis vaccines have
[1] Edwards and Decker. In: Vaccines. 4th ed; 2004 [2] Plotkin & Cadoz. PIDJ 1997; 16(5)

18. Long-term clinical effectiveness of an acellular
pertussis component vaccine and a whole cell
pertussis component vaccine.
Lugauer S, Heininger U, Cherry JD, Stehr K.
Source
University Children's Hospital, Erlangen, Germany.
• Calculated efficacy for the 6-year follow-up
period based upon physician diagnosed
pertussis was 89% (95% CI=79 94) for
DTaP and was 92% (95% CI=84-96) for
DT
Eur J Pediatr. 2002 Mar;161(3):142-6.P

19. Recent Outbreak Activity

20. A Pertussis epidemic was declared in
Washington on April 3, 2012. There have been
4,190 cases reported statewide through
September 22, 2012, compared to 427 reported
cases in 2011 during the same time period.
http://www.cdc.gov/Other/disclaimer.html

21. In the USA, 20 469 cases have been reported
compared with 8846 at the same time last year,
with nine infant deaths, according to the US
Centers for Disease Control and Prevention
(CDC).

22. In the UK, the Health Protection Agency (HPA),
reported on July 27, that the number of cases in
England and Wales was continuing to rise with
2466 laboratory confirmed cases reported this
year, more than double the number for 2011.
In 2008, where 421 cases were reported in the
first 6 months.

24. Number and Order of Whole Cell Pertussis Vaccines in
Infancy and Disease Protection
Sarah L. Sheridan, BMed, MAppEpid; Robert S. Ware,
PhD; Keith Grimwood, MB, ChB, MD; Stephen B. Lambert,
MBBS, PhD
Newer Pertussis Vaccines Not As Effective
• Those who received 3-doses of DTaP
showed higher rates of pertussis than those
who received DTwP during the pre-epidemic
period of 1999-2008 (13.2 versus 5.3 per
100,000 per year) and the outbreak period of
2009-2011 (373.1 versus 113.3 per 100,000
per year).
JAMA. 2012;308(5):454-456. doi:10.1001/jama.2012.6364.

25. The challenge for future pertussis vaccine
development is to address the benefit-risk
trade-off, and
To develop vaccines that induce long-
lasting protection from the first dose, without
the adverse events associated with DTwP
use

26. Questions for PPs?
• Is one vaccine more efficacious than the
other?
• Is one vaccine better tolerated than the
other?
• What should we use in our practice?