Acellular Vaccines versus

Whole cell vaccine in

Pertussis Prevention

Flow of presentation

Pertussis – An introduction

Whole cell Pertussis vaccine

Advent of Acellular Pertussis vaccine

Safety and efficacy of Pertussis vaccines

Recent outbreaks

Introduction to Pertussis

IntroductionBetween 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.

Introduction to Acellular and Whole pertussis vaccine

• EFFICACY VARIABLE : 50 – 98%• PROTECTION : 36-48% (Italy, Sweden) • COMMON CHARACTERISTIC: REACTOGENICITY

• LOCAL – Pain– Redness– Swelling

• SYSTEMIC– Fever– Irritability– Others......

• 1970’s Dramatic decrease in vaccination (UK, Japan, Sweden, Germany)

• US: Legal issues

• LEADING TO DEVELOPMENT OF NEW VACCINES

Pertussis Vaccines: Whole Cell

Gustafsson etal. NEJM 1996; 334(6): 349-55

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.

Reactogenicity post-DTwP (whole cell) vaccine

Frequency of Side Effects with Pertussis Vaccines

Acellular Pertussis Vaccines: Pertinent Issues. Ind Pediatr 2008; 45; 727-729

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

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

Geier DA & Geier MR;- Brain & Dev. 2004, 26(5):296-300

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

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: 1569-77Olin et al. Lancet 1997, 350: 1569-77

Serious Reactions: Whole cell vs.

Acellular pertussis vaccines

Decrease in Hospital Admissions for Decrease in Hospital Admissions for Febrile Seizures and Reports of Febrile Seizures and Reports of

Hypotonic-Hyporesponsive Episodes Hypotonic-Hyporesponsive Episodes Presenting to Hospital Emergency Presenting to Hospital Emergency Departments Since Switching to Departments Since Switching to

Acellular Pertussis Vaccine in Canada: A Acellular Pertussis Vaccine in Canada: A Report From IMPACTReport 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

Serious Reactions: Whole cell vs.

Acellular pertussis vaccines

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

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)

Acellular Pertussis Vaccines available in India

Brand Componenets

Tripacel SP PT, FHA, PRN, FIM2, FIM3

Pentaxim SP PT, FHA

Infanrix GSK PT, PRN, FHA

Efficacy of DTwP and DTaP vaccines

71

96 93 9685

48

59

85

9889

84

36

2

(2-3-4) (3, 4-5, 6 & 15-18)

[1] Edwards and Decker. In: Vaccines. 4th ed; 2004 [2] Plotkin & Cadoz. PIDJ 1997; 16(5)

The best acellular pertussis vaccines have

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.

SourceUniversity 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

Recent Outbreak Activity

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

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).

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.

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.

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

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?