A systematic review of the burden of pertussis disease in infants and the effectiveness of maternal immunization against pertussis

ABSTRACT

Introduction

Infants too young to be fully immunized are the most vulnerable to severe pertussis disease. To close this susceptibility gap, passive infant immunization through vaccination of pregnant women against pertussis was first introduced in 2011 in the United States and has been extended since then to more than 40 countries.

Areas covered

We conducted two systematic literature searches to describe the worldwide burden of pertussis disease in infants <6 months of age since 2005, and the effectiveness and impact of maternal pertussis vaccination in preventing infant pertussis since 2011.

Expert opinion

Pertussis disease incidence rates in infants aged <2-3 months were substantial in all countries with available data, exceeding 1000 cases per 100,000 population during outbreaks. Virtually all pertussis deaths occurred in this age group. Data from Africa, Eastern Mediterranean, and Asia were limited, but suggest a similar or higher disease burden than in Europe or the Americas. Estimates of effectiveness of second/third trimester pertussis vaccination in preventing pertussis disease in <2-3 months old infants were consistently high (69%–93%) across the observational studies reviewed, conducted in various settings with different designs. Maternal vaccination programs appear to be achieving their goal of reducing the burden of disease in very young infants.

Plain language summary

What is the context?

• Pertussis, also known as whooping cough, is a highly contagious disease of the respiratory tract.

• Infants too young to be fully vaccinated are at the highest risk of severe pertussis disease, hospitalization, and death.

• Vaccinating pregnant women against pertussis with a Tdap vaccine is recommended in more than 40 countries as a safe and effective strategy to protect infants for the first months of life.

What is new?

• This review summarizes recent literature describing the burden of pertussis disease in infants worldwide prior to the introduction of maternal vaccination programs; pertussis disease incidence rates in infants aged <2-3 months were substantial in all countries with available data, exceeding 1000 cases per 100,000 population during outbreaks.

• Immunization of pregnant women with a Tdap vaccine can prevent about 70–90% of pertussis disease and up to 90.5% of pertussis hospitalizations in infants under 3 months of age.

What is the impact?

• Limited available data suggest that incidence rates of pertussis disease after the introduction of Tdap maternal immunization have declined in infants.

• Current knowledge supports the implementation of Tdap maternal immunization programs.

KEYWORDS:

• Acellular pertussis vaccine
• burden of disease
• epidemiology
• incidence
• maternal immunization
• Bordetella pertussis
• vaccine effectiveness
• vaccine impact
• whooping cough
• infant

Article highlights

• Worldwide, the highest incidence rates of pertussis disease are in infants aged <6 months, with the majority of pertussis-related deaths, hospitalizations, and ICU admissions in this age group.

• Infants aged <2-3 months are most at risk. Annual pertussis disease incidence rates in this age group ranged from 132 per 100,000 population to as high as 1390 per 100,000 during outbreaks.

• The point estimates of maternal Tdap effectiveness in preventing pertussis in infants below 3 months of age ranged between 69% and 93%.

• Maternal Tdap vaccination has been shown to prevent between 58.3% and 94% of pertussis-associated hospitalizations up until the age of 6 months.

Maternal Tdap vaccination is proving an effective means by which to reduce pertussis disease, hospitalization, and death in young infants who are too young to be fully vaccinated.

Acknowledgments

The authors would like to thank Joanna Fraczek-Goffin, Amanda McGillivray, and Judith van den Bosch for their contribution to the source documents (Pallas reports).

Writing support was provided by Sara Rubio and Joanne Wolter (Modis on behalf of GlaxoSmithKline); editorial support and publication management was provided by Fabienne Danhier (Modis on behalf of GlaxoSmithKline).

Author contributions

All authors participated in the design or implementation or analysis, and interpretation of the study. CvdE and EB performed the search strategy, article selection, and data extraction. All authors had full access to the data and participated in the development of the manuscript, revised it critically for important intellectual content, approved the final version before submission, and agreed to be accountable for all aspects of the work.

VJ: contributed to the design of the study, interpretation of the data, and writing the manuscript.

Declaration of interest

V. A. Jenkins, M. A. Ceregido, and A. Guignard are employed by the GlaxoSmithKline group of companies and V. A. Jenkins and A. Guignard hold shares in the GSK group of companies. W. Kandeil was an employee of GlaxoSmithKline at the time of the study. C. van den Ende and E. Bunge are employed by the Pallas company grants from GlaxoSmithKline Vaccines during the conduct of the study; as well as grants from GlaxoSmithKline Vaccines and from Sanofi Pasteur outside the submitted work. The Pallas company received consultancy fees from GlaxoSmithKline for the performed source reports. Writing assistance was utilized in the production of this manuscript: J Fraczek-Goffin and A McGillivray both of GlaxoSmithKline, and J van den Bosch (Pallas, Health Research and Consulting, Rotterdam, The Netherlands), contributed to the source documents (Pallas reports); J Wolter (independent medical writer c/o GlaxoSmithKline) and S Rubio (Modis c/o GlaxoSmithKline) provided writing support services; F Danhier (Modis c/o GlaxoSmithKline) provided publication coordinating services; all services were funded by GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Trademark statement

Boostrix and Boostrix-IPV are registered trademarks of the GlaxoSmithKline group of companies. Adacel and Repevax are registered trademarks of Sanofi Pasteur.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

GlaxoSmithKline Biologicals SA funded all costs associated with the development and the publishing of the present manuscript.