Childhood acellular pertussis vaccines were licensed and implemented in the US in the 1990s following an effort to improve on the safety profile of whole-cell vaccines. However, waning of immunity from acellular vaccines may be driving the recent resurgence of pertussis, raising the need to consider new prevention strategies.
"This is consistent with earlier Canadian data where rates of 10 to <15 year olds from 2002–2004 were elevated compared to other children , and this may be attributed to the lower efficacy of the combined adsorbed diphtheria-tetanus-pertussis whole-cell vaccine used in children in Canada between 1980 and 1997 . Recent resurgence of pertussis with a shift towards higher rate in adolescents and young adults has also been reported in United States and Australia [30,31]. About half of the pertussis cases in our study had completed their immunization series with a median age of 12.9 years. "
[Show abstract][Hide abstract] ABSTRACT: ProvLab Alberta provides all laboratory testing for Bordetella pertussis including sporadic cases and outbreak investigations through collaborations with provincial public health partners. We describe B. pertussis activity in Alberta from July 2004 to December 2012.
Laboratory testing for pertussis were analyzed using interpreted laboratory data that was generated by DIAL, a secure web-based platform. Duplicate specimens from the same individual <=90 days were excluded to generate a case-based dataset. Immunization status of confirmed pertussis cases from the provincial immunization repository was reviewed.
Overall, 7.1% of suspected pertussis cases tested positive with a higher positivity rate in outbreak as compared to sporadic setting. Annual variations in sporadic pertussis cases were observed across the province with higher positivity rates in 2005, 2008, 2009 and 2012. A significantly higher positivity rate was observed in a northern region of Alberta. While the positivity rate in sporadic setting was highest in adolescents aged 10 to <15 years old (14.8%), population-based disease burden was highest in young children <5 years old. Of the 81.6% (n = 1,348) pertussis cases with immunization records, 48.3% were up-to-date with immunization. The pertussis cases that were up-to-date with their immunization were older (median age 12.9 years) as compared to those with incomplete (median age 9.7 years) or no pertussis immunization (median age 3.8 years).
Cyclic pattern of annual pertussis activity with geographic variation was observed in Alberta with no obvious case finding effect from outbreak investigations. The high positivity rates in adolescents suggested an underestimation of disease burden in this age group.
"The disease is most severe and fatal in infants too young to be protected by the current vaccination programs . Several strategies are being explored to protect this most vulnerable age group , including maternal immunization, universal lifespan vaccination to limit Bordetella pertussis circulation, and a cocooning strategy of vaccinating people in close contact with infants to prevent transmission to this group. However, they all suffer from their inherent limitations . "
[Show abstract][Hide abstract] ABSTRACT: Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins.
We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 10(3), 10(5) or 10(7) colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination.
Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups.
BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups.
PLoS ONE 01/2014; 9(1):e83449. DOI:10.1371/journal.pone.0083449 · 3.23 Impact Factor
"Pertussis continues to be the most poorly controlled bacterial vaccine-preventable disease despite high levels of vaccine coverage . Since the 1980s, different pertussis epidemics have arisen with a high burden of disease among teenagers, a group that previously had a low risk of pertussis    . Increased awareness and improved diagnostics coincide with increased notification of pertussis , but do not completely account for it. "
[Show abstract][Hide abstract] ABSTRACT: To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n=11) or an acellular pertussis vaccine (aP; n=13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4(+) and CD8(+) T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon-γ or tumor necrosis factor-α producing CD4(+) T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA(-)CCR7(-) effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP-compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines.
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