Improved vaccine coverage and earlier completion of the primary pertussis vaccine schedule reduced pertussis notifications and provided earlier protection against disease in England/Wales from 1990 onward. The preschool booster was introduced when coverage was high and disease incidence relatively low. The main aim was to reduce disease in older age groups, thereby decreasing transmission to unprotected young infants who are at highest risk for severe disease. The effect of the preschool booster was apparent in the continued overall reduction in pertussis incidence among children <10 years of age. This effect was particularly marked in hospitalization data, which are likely to be most consistent through time, with evidence of an indirect protective effect in infants <3 months of age. Calculated 4-dose VE was ≈95.3% with <7 years of follow-up, although numbers were small. Persistence of immunity 6–9 years after an aP3 booster dose in the second year of life (20) and no evidence of waning immunity 4 years after a preschool booster (21,22) have been reported.

Marked increases in pertussis notifications and laboratory confirmations, but not hospitalizations, were observed for adolescents and adults in England/Wales during 1998–2009. Different explanations have been proposed for the rising pertussis incidence in these age groups in countries with high vaccine coverage. The relevance of apparent increased pertussis among persons of these ages, in whom illness tends to be milder, atypical, and underdiagnosed (7,23), relates to whether the increases are real or driven by improved case ascertainment. A concomitant rise in pertussis in unprotected young infants would be consistent with a true increase at older ages. In England/Wales serologic testing, together with publications promoting higher awareness (24), improved case ascertainment. Testing of oral fluid samples from notified case-patients whose infection was not laboratory confirmed was also piloted nationally during June 2007–August 2009. These data are excluded from national datasets, but the pilot may have influenced testing and notification practice for noninfant case-patients.

Despite a reduction in pertussis among younger children and infants, rates of pertussis-related sickness and death remain high compared with rates for other vaccine-preventable diseases. In England, ≈300 hospitalized infants each year receive a diagnosis of pertussis. Relatively high hospitalization rates for patients with laboratory-confirmed cases suggest that national surveillance in England/Wales is proficient at ascertaining serious cases in young children. One US study reported that 67% of infants with pertussis were hospitalized (25), compared with 90% of infants in our study in England/Wales. The US study reported CFRs of 1% for infants 0–1 month of age; in our study, the CFR was 39/1,000 for infants <56 days of age. An earlier HPA study found incomplete pertussis diagnoses even in severely ill, hospitalized infants (26); routine PCR testing for hospitalized infants was therefore introduced. Differences between rates of laboratory-confirmed cases and hospitalization among infants have since been reduced (Table 1). Studies highlighting unrecognized pertussis-related deaths (27,28) may also have increased awareness and improved recording accuracy, but underreporting persists.

The United States, New Zealand, and Australia have reported increased pertussis incidence among infants despite use of an aP vaccine booster (25,29,30). In Australia, hospitalization rates of >400 hospitalizations/100,000 infants were reported during 2008–2009 (30). The Netherlands reported pertussis epidemiology similar to that for England/Wales after a preschool booster was introduced. Infant hospitalization rates were comparable: 134 hospitalizations/100,000 infants <6 months of age in the Netherlands during 2002–2005, compared with 156 hospitalizations/100,000 infants <3 months of age during 2002– 2005 in England/Wales (22). However, direct comparisons between countries are problematic because of differences in case definitions, vaccine schedules, and VE.

Consistent with findings in a previous study (2), we found high short-term effectiveness for the wP and aP5 vaccines used in England/Wales. As in other studies (20,31), there was evidence of waning protection 10–15 years after completing a wP primary vaccine course. Greater waning after aP vaccine has been reported (20), underlining the need for continued surveillance. In a study seeking laboratory evidence of pertussis in all school-aged children who visited their primary care doctor for cough, 86% of children with and 97% without evidence of pertussis infection had been immunized (24), giving an estimated VE of 82%, a result consistent with our findings. However, patients who seek health care might have pertussis that represents the more severe end of the clinical spectrum of disease, for which VE is likely to be higher (24,32,33). An earlier HPA study showed higher VE estimates in nonepidemic (93%) than in epidemic (87%) years, which suggests that when awareness of the disease is high, the threshold for investigation and diagnosis of milder cases may be lower and thus reduce estimates of VE (32).

When coverage is exceptionally high and VE estimates are <90%, small coverage variations can markedly change VE calculated by the screening method. For example, in this study, VE for patients 10–16 years of age who received the DTwP vaccine under the accelerated schedule would increase from 82% to 90% if coverage increased from 97.7% to 98.7%. When VE is high, as with most estimates in this study, there is little effect from coverage inaccuracies; population booster dose coverage of 50% and 79% give 4-dose VE estimates of 93.3% and 95.3%, respectively.

Continued improvements in pertussis control in children <10 years of age, including disease reduction in young infants, have been observed in England/Wales since the preschool booster was introduced. Inclusion of the booster in the preschool vaccination schedule endorses the flexible World Health Organization (WHO) recommendation for a booster at age 1–6 years, with timing guided by local factors (34). Pertussis control is far from optimal, however, and disease continues predominantly in young infants and in teenagers and adults, in whom immunity may have waned. This presents 2 major policy issues: how to better protect vulnerable infants and whether pertussis in teenagers and adults warrants targeted prevention. Potential strategies to protect young babies have recently been reviewed by the WHO Strategic Advisory Group of Experts (SAGE) on Immunization: selective immunization of close family members of neonates (cocooning) and universal adolescent, maternal, and neonatal immunization (34).

Household contacts are often the source of pertussis exposure for young infants (26,35). Consequently, some countries have adopted the cocooning strategy, a resource-intensive approach with little evidence of clinical effectiveness and one not recommended by SAGE (34). Our data suggest that household contacts were a key part of disease transmission, but a high proportion of responses indicated no known exposure; thus, other unrecognized transmission sources may also be relevant.

Studies suggest that pregnant women mount a good immune response to wP vaccines, and this response should provide protection to neonates (34). The duration of protection in infants and the degree of interference with primary vaccine responses remains unknown. Although this strategy is the only potential way to protect children against pertussis from birth, SAGE found insufficient evidence to propose this strategy (34). In the United States, the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recently recommended that pregnant women who have not been vaccinated against pertussis receive the tetanus-diphtheria-pertussis vaccine after their 20th week of pregnancy rather than delaying to the postpartum period (36). No other country currently recommends this vaccine during pregnancy.

Pertussis immunization at birth has been proposed after the demonstration of immune responses in neonates (37,38). However, immune interference to different antigens in the primary course remains a concern (39,40). No monovalent pertussis vaccine is licensed for use in neonates. Our data suggest that pertussis infection among infants can be reduced with an accelerated primary immunization schedule and that protection lasts well into school age. Although 43% of pertussis cases in infants in England/Wales occurred among those <2 months of age, even 1 dose of pertussis vaccine confers some protection in infants 9 weeks to <6 months of age, and high VE is conferred by 3 doses. This finding highlights the need for high coverage and timely administration of each pertussis vaccine dose as advocated by WHO.

Universal adolescent vaccination may be considered in countries in which it has been shown to be cost-effective, primarily to reduce adolescent disease rather than indirectly protect infants (34). In England/Wales it is not clear that the rise in pertussis incidence in adolescents and adults observed during 1998–2009 reflects a true increase. Better understanding of the disease at older ages is needed to assess the potential effect of additional vaccine doses and the role of adolescents in disease transmission to infants. Although vaccine boosting of adolescents may reduce disease within targeted age groups, the potential for this policy to shift disease to the main childbearing population needs to be better understood.