IntroductionBetween 1940-1945, before widespread vaccination, as many as147,000 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 numberof cases ever reported.Over the past few years the number of reported cases of pertussis hasincreased, reaching 25,827 in 2004; worldwide, there are an estimated300,000 annual deaths due to pertussis.
Introduction to Acellular and Whole pertussis vaccine
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
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.
Frequency of Side Effects with Pertussis Vaccines Event wP vaccine aP vaccine Average AverageFever < 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 VaccinesAcellular Pertussis Vaccines: Pertinent Issues. Ind Pediatr 2008; 45; 727-729
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
Serious Reactions: Whole cell vs. Acellular pertussis vaccinesA summary of adverse events reported with an initial onset of symptomswithin 3 days following whole-cell pertussis vaccination in comparison toacellular pertussis vaccination to VAERS database from 1997 through 1999 Geier DA & Geier MR;- Brain & Dev. 2004, 26(5):296-300
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
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 toAcellular 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
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)
Efficacy of DTwP and DTaP vaccines 96 96 98 93 89 85 85 8471 59 48 36 2 (2-3-4) (3, 4-5, 6 & 15- 18) The best acellular pertussis vaccines have  Edwards and Decker. In: Vaccines. 4th ed; 2004  Plotkin & Cadoz. PIDJ 1997; 16(5)
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 Childrens 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 DTEur J Pediatr. 2002 Mar;161(3):142-6.P
A Pertussis epidemic was declared inWashington on April 3, 2012. There have been4,190 cases reported statewide throughSeptember 22, 2012, compared to 427 reportedcases in 2011 during the same time period. http://www.cdc.gov/Other/disclaimer.html
In the USA, 20 469 cases have been reportedcompared with 8846 at the same time last year,with nine infant deaths, according to the USCenters for Disease Control and Prevention(CDC).
In the UK, the Health Protection Agency (HPA),reported on July 27, that the number of cases inEngland and Wales was continuing to rise with2466 laboratory confirmed cases reported thisyear, more than double the number for 2011.In 2008, where 421 cases were reported in thefirst 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, PhDNewer 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 vaccinedevelopment is to address the benefit-risktrade-off, andTo develop vaccines that induce long-lasting protection from the first dose, withoutthe adverse events associated with DTwPuse
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?