Re-emergence of Pertussis

What Are the Solutions?

Romina Libster; Kathryn M Edwards

Expert Rev Vaccines. 2012;11(11):1331-1346.

Abstract

Whooping cough, due to Bordetella pertussis and Bordetella parapertussis, is an important cause of childhood morbidity and mortality. Despite widespread pertussis immunization in childhood, there are an estimated 50 million cases and 300,000 deaths due to pertussis globally each year. Infants who are too young to be vaccinated, children who are partially vaccinated and fully-vaccinated persons with waning immunity are especially vulnerable to disease. Since pertussis is one of the vaccine-preventable diseases on the rise, additional vaccine approaches are needed. These approaches include vaccination of newborns, additional booster doses for older adolescents and adults, and immunization of pregnant women with existing vaccines. Innovative new vaccines are also being studied. Each of these options will be discussed and their potential impact on pertussis control assessed.

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Table 1. Pertussis vaccine efficacy trials.
Study (year)	Study design	Vaccine(s)	Absolute vaccine efficacy % (95% CI)	Antigens	Whole-cell vaccine	Case definition	Ref.
Stockholm, Sweden (1986)	Randomized, double-blinded, placebo-controlled study	JNIH-6 JNIH-7	81 (61–90) 75 (53–87)	PT FHA	None	≥21 days cough and ≥9 coughing spasms on at least 1 day and positive culture	[38,39]
Stockholm, Sweden (1992)	Randomized, fully-blinded, placebo- controlled study	SKB-2 Tripacel Connaught DTP	59 (51–66) 85 (81–89) 48 (37–58)	PT, FHA, DT, TTFHA, PRN, FIM2, FIM3	Connaught DTP	≥21 days paroxysmal cough and either: positive culture, confirmed by serologic assay or PCR; twofold PT or FHA IgG rise; or epidemiological link to culture-positive case	[40]
Italy (1992)	Randomized, double-blinded, controlled, comparative study	Infanrix Acelluvax Connaught DTP	84 (76–89) 84 (76–90) 36 (14–52)	PT^†, FHA, PRN, DT, TT PT^‡, FHA, PRN, TT	Connaught DPT	≥21 days paroxysmal cough and either: positive culture, confirmed by serologic assay or PCR	[41]
Goteborg, Sweden (1991)	Randomized, fully blinded, controlled study	Certiva	71 (63–78)	PT, DT, TT	None	≥21 days paroxysmal cough and either: positive culture confirmed by serologic assay or PCR; threefold PT or FHA IgG rise	[31]
Senegal (1990)	Randomized, fully blinded, controlled study	Triavax PMC-Fr DTP	74 (51–86) 92 (81–97)	PT, FHA, DT, TT	PMC-Fr DPT	≥21 days paroxysmal cough and confirmation by culture, serology or epidemiological link	[42]
Erlangen, Germany (1991)	Randomized, double-blinded, controlled study^§	ACEL-IMUNE Lederle DTP	78 (60–88) 93 (83–97)	PT, FHA, PRN, FIM2, DT, TT	Lederle DPT	≥21 days cough with paroxysm, whoop, or vomiting and confirmation	[43]
Mainz, Germany (1992)	Passive monitoring for suspected household cases	Infanrix Behring, SKB DTP	89 (77–95) 98 (83–100)	PT, FHA, PRN, DT, TT	Behring, SKB DPT	≥21 days paroxysmal cough and either: positive culture, or serology in households	[33]
Munich, Germany (1993)	Case–control study	Tripedia Behring, DTP	93 (63–99) 96 (71–100)	PT, FHA, DT, TT	Behring, DPT	≥21 days paroxysmal cough and either: positive culture or household contact with laboratory confirmation	[34]

DTaP: Diphtheria–tetanus toxoid acellular pertussis vaccine.

Table 2. Current pertussis immunization schedules and vaccine coverage according to regions.
Country	Primary vaccination schedule	Pediatric boosters	Adolescent–adult boosters	2010 first dose of diphtheria toxoid, tetanus toxoid and pertussis vaccine coverage level (%)	2010 third dose of diphtheria toxoid, tetanus toxoid and pertussis vaccine coverage level (%)
Canada	2, 4 and 6 months: DTaP–IPV–Hib	18 months: DTaP–IPV–Hib; 4–6 years: DTaP–IPV	14–16 years: Tdap (or Td)	92	80
USA	2, 4 and 6 months: DTaP or DTaP–IPV–HBV	15–18 months: DTaP or DTaP–Hib; 4–6 years: DTaP	11–12 years: Tdap	99	95
Mexico	2, 4 and 6 months: DTP–Hib–IPV	18 months: DTP–Hib–IPV and 4 years: DTP		96	95
Austria	3 and 5 months: DTaP–IPV–Hib–HBV	12–24 months: DTaP–IPV–Hib–HBV; 7–9 years DTaP–IPV	13–15 years: Tdap	93	83
Belgium	2, 3 and 4 months: DTaP–Hib–IPV–HBV	15 months: DTaP–Hib–IPV–HBV; 5–7 years DTaP–IPV	14–16 years: Tdap	99	99
Czech Republic	13 weeks, 4 and 5 months: DTaP–Hib–HBV–IPV	18 months and 5 years: DTaP–Hib–HBV–IPV		99	99
Denmark	3, 5 and 12 months: DTaP–IPV–Hib	5 years: Tdap–IPV		93	90
Finland	3, 5 and 12 months: DTaP–HBV–IPV	4 years: DTaP–IPV	14–15 years: Tdap	99	99
France	2, 3 and 4 months: DTaP–IPV–Hib or DTaP–IPV–Hib–HBV	16–18 months: DTaP–IPV–Hib or DTaP–IPV–Hib–HBV	11–13 years: DTaP–IPV	99	99
Germany	2, 3 and 4 months: DTaP–IPV–Hib–HBV	11–14 months: DTaP–IPV–Hib–HBV; 5–6 years: Tdap	9–17 years: Tdap	97	93
Greece	2, 4 and 6 months: DTaP–IPV–Hib–HBV	15–18 months and 4–6 years: DTaP		99	99
Hungary	2, 3 and 4 months: DTaP–IPV–Hib	18 months and 6 years: DTaP–IPV–Hib	11 years: Tdap	99	99
Iceland	3 and 5 months: DTaP–IPV–Hib	12 months: DTaP–IPV–Hib; 4–5 years: DTaP–IPV	14 years: Tdap–IPV	98	96
Ireland	2, 4 and 6 months: DTaP–IPV–Hib–HBV	4–5 years: DTaP–IPV		98	94
Israel	2, 4 and 6 months: DTaP–IPV–Hib	12 months: DTaP–IPV–Hib; 7 years: DTaP–IPV	13 years: Tdap	96	96
Italy	2, 4 and 10 months: DTaP–IPV–Hib–HBV	5–6 years: DTaP	11–15 years: Tdap	98	96
Luxembourg	2 and 3 months: DTaP–IPV–Hib–HBV; 4 months: DTaP–IPV–Hib	11–12 months: DTaP–IPV–Hib–HBV; 5 years: Tdap	15–16 years, then every 10 years: Tdap	99	99
Portugal	2, 4 and 6 months: DTaP–IPV–Hib	18 months: DTaP–Hib; 5–6 years: DTaP–IPV		99	98
The Netherlands	2, 3 and 4 months: DTaP–IPV–Hib–HBV	11 months: DTaP–IPV–Hib–HBV; 4 years: DTaP–IPV		99	97
Norway	3, 5 and 11–12 months: DTaP–IPV–Hib	7 years: DTaP–IPV		99	93
Poland	2, 3–4 and 5 months: DTP	16–18 months: DTP; 6 years: DTaP		99	99
Spain	2, 4 and 6 months: DTaP–IPV–Hib–HBV	15–18 months: DTaP–IPV–Hib; 4–6 years: DTaP	13 years, then every 10 years: Tdap	99	97
Sweden	3, 5 and 12 months: DTaP–IPV–Hib	5–6 years: DTaP	10 years: Tdap	99	98
Switzerland	2, 4 and 6 months: DTaP–IPV–Hib–HBV	15–24 months: DTaP–IPV–Hib–HBV; 4–7 years: DTaP–IPV	11–15 years: Tdap	98	96
UK	2, 3 and 4 months: DTaP–IPV–Hib	3–5 years: DTaP–IPV		98	96
Argentina	2, 4 and 6 months: DTP–Hib–HBV	18 months: DTP–Hib; 6 years: DTP	11 years: Tdap	98	94
Brazil	2, 4 and 6 months: DTP–Hib	15 months and 4–6 years: DTP		99	98
Chile	2, 4 and 6 months: DTP	18 months and 4 years: DTP		93	92
El Salvador	2, 4 and 6 months: DTP–Hib–HBV	18 months and 4 years: DTP		97	92
Nicaragua	2, 4 and 6 months: DTP–Hib–HBV	18 months: DTP		99	98
Peru	2 and 4 months: DTP–Hib–HBV; 3 months: DTP	18 months and 4 years: DTP		97	93
Uruguay	2, 4 and 6 months: DTP–Hib–HBV	12 months: DTP–Hib–HBV; 5 years: DTP		98	95
Australia	2, 4 and 6 months: DTaP–IPV–HBV or DTaP–IPV–Hib–HBV	4 years: DTaP–IPV	15–17 years: Tdap	97	92
China	3, 4 and 5 months: DTP	18–24 months: DTP		99	99
Indonesia	2, 3 and 4 months: DTP or DTP–HBV			94	83
Japan	3–12 months: 3 doses DTaP	18 months: DTaP		99	98
Republic of Malaysia	2, 3 and 5 months: DTaP–Hib–IPV	18 months: DTaP–Hib–IPV	15 years: Tdap	98	94
New Zealand	6 weeks, 3 months and 5 months: DTaP–IPV	15 months: DTaP–Hib; 4 years: DTaP–IPV	11 years: Tdap–IPV	95	93
Thailand	2, 4 and 6 months: DTP or DTP–HBV	18–24 months and 4–5 years: DTP		99	99
Ethiopia	6, 10 and 14 weeks: DTP–Hib–HBV			90	86
Burkina Faso	2, 3 and 4 months: DTP–Hib–HBV			98	95
Burundi	6, 10 and 14 weeks: DTP–Hib–HBV			99	96
Central Africa	6, 10 and 14 weeks: DTP–Hib–HBV			64	54
South Africa	6, 10, 14 weeks: DTaP–Hib–IPV	18 months: DTaP–Hib–IPV		63	53

Table 3. Proposed changes to improve disease control.
Proposed change	Pros	Cons
Retain the current primary and booster DTaP vaccination schedule, but give more frequent acellular vaccine boosters	Multicomponent DTaP vaccines are safe and effective for the primary series as well as for booster doses; Repeated doses would combat waning immunity	Additional research would be needed to evaluate the long-term efficacy of the acellular pertussis vaccine when administered at more frequent intervals than the recommended schedule; Increased cost; May see increased local reactions with more boosters
Add an adjuvant to the current vaccine	Enhance immune responses with long-lasting effect; Potential use as a single-shot vaccine; Potential use in neonates	Reactogenicity and adverse events may be increased; Would require complete re-evaluation of the adjuvanted vaccines in combination with the other regularly scheduled vaccines; No studies in humans published to date
Resume use of the conventional whole-cell pertussis vaccine	Good efficacy profile and duration of protection	Probably would not be accepted in the developed world given its more severe reactogenicity profile
Live-attenuated vaccines	Potential protection after a single intranasal administration; Potential impact on the incidence of whooping cough caused by other strains of Bordetella; Low production costs, making it especially attractive for developing countries; Needle-free, easy and safe mode of administration; Potential to induce mucosal immunity in addition to systemic immunity	Still in development and no evidence it would be effective; Biosafety issues since it is a live vaccine. May revert and become less attenuated; Potential pathogenicity needs to be carefully considered, especially in immunocompromised individuals; Would require complete evaluation of the vaccine in combination with other recommended vaccines
Include new pertussis antigens or change the strains used to derive the antigens for use in new vaccines	Potential enhanced vaccine efficacy against new and more virulent stains	Continued need for active surveillance for pertussis organisms and culture for characterization; Increased cost that would be an issue for developing countries