Preventing pertussisBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4518 (Published 17 July 2014) Cite this as: BMJ 2014;349:g4518
- Eugene D Shapiro, professor1
- 1Departments of Pediatrics, Epidemiology of Infectious Diseases, and Investigative Medicine, Yale University School of Medicine and Graduate School of Arts and Sciences, New Haven, CT 06520-8064, US
Pertussis (whooping cough) continues to be a major cause of morbidity and mortality throughout the world and is one of the leading causes of deaths from vaccine preventable diseases. In recent years, large outbreaks of pertussis have been reported in many developed countries, despite widespread use of vaccines.1 2
The United Kingdom is no exception.3 Two linked papers examine issues surrounding pertussis vaccination in the UK.4 5 Wang and colleagues (doi:10.1136/bmj.g3668) looked at children aged 5-15 with persistent cough identified in 22 general practices in the Thames Valley from November 2010 to December 2012. At least 20% had evidence of recent infection with Bordetella pertussis, based on raised concentrations of specific IgG antibodies in saliva.4 Moreover, among these children with persistent cough (which in many cases was severe), the risk of pertussis was more than four times higher in children who had received the preschool pertussis vaccine booster dose seven years or more earlier compared with those who had received the booster more recently. Donegan and colleagues (doi:10.1136/bmj.g4219) report results from 20 074 pregnant women who had received the combined low dose diphtheria, acellular pertussis, and inactivated poliovirus vaccine during the first six months after the campaign to immunize pregnant women against pertussis was introduced in October 2012.5 They found no discernible increase in the risk of serious adverse events such as stillbirth, eclampsia, low birth weight, or death of the mother or the baby.
There is uncertainty about the causes of the apparent resurgence of pertussis. Possible contributors include more sensitive and more readily available methods for diagnosis; enhanced awareness and more complete reporting; decreased duration of adaptive immunity after immunization with acellular vaccines (compared with whole cell vaccines), perhaps related to a decreased T helper type 1 immune response; and mismatch between the antigens in the acellular vaccines and those of circulating strains of B pertussis. Although the largest increase in reported incidence seems to be in adolescents, children aged <3 months are at highest risk of serious morbidity and mortality from pertussis.
Immunity to pertussis, whether vaccine induced or from natural infection, is not life long. So there is a large pool of susceptible adults and adolescents to serve as a reservoir for pertussis in the community. There is now substantial evidence, however, that immunity induced by acellular pertussis vaccines, which in many countries have replaced the more reactogenic whole cell vaccines, wanes most rapidly.6
The findings of Wang and colleagues of a time dependent increased risk of pertussis in adolescents after their preschool booster dose is consistent with similar findings in reports from other countries.7 8 Some studies have suggested that children who had received one or more doses of the whole cell pertussis vaccine in their primary series have a more durable immune response to subsequent booster doses of acellular vaccines.9 Unfortunately, Wang and colleagues did not compare the risk of pertussis between children exposed to whole cell vaccines during their primary series and those who received only acellular vaccines.
The question now is what should we do about resurgent pertussis? A multi-pronged approach seems prudent. In the short term, a key priority is to protect young infants, who are particularly vulnerable to the effects of pertussis. Young children are most likely to acquire pertussis from household contacts, mostly from adults and adolescents. Immunization of pregnant women, which protects the mother and provides protection for the infant through transplacental transfer of antibodies to the fetus and by reducing the likelihood that the mother will acquire and subsequently transmit B pertussis to the infant postpartum, is a strategy that has been adopted by some countries. The study by Donegan and colleagues provides additional assurance about the safety of this approach.
Another strategy by which susceptible infants can be protected—cocooning—involves immunizing all close contacts of the infant, particularly household members, thereby reducing the likelihood that the infant will be exposed to B pertussis. Both immunization of pregnant women late in pregnancy and cocooning have been shown to be cost effective.10 11 The United States has adopted both approaches, with an official recommendation to immunize pregnant women during every pregnancy so that high concentrations of antibodies are induced to pass to the fetus. In addition, a booster dose of the vaccine is recommended for all adolescents and for adults who have not received a dose since their preschool booster. The findings of Wang and colleagues are likely to bolster calls for the National Health Service (NHS) to incorporate a booster dose of pertussis vaccine in early adolescence into the vaccine schedule of the UK.
Modifications of current vaccines might also help in the near term. If formulations of acellular pertussis vaccines were available without other components, such as diphtheria toxoid or inactivated polio vaccine, it might encourage recommendations for more frequent booster doses of pertussis vaccine to reduce the pool of susceptible persons. Improving the immune response by adding extra antigens of B pertussis to existing vaccines, changing adjuvants, or adding new ones could be another short term solution.
However, there is general agreement that new and more durable vaccines are needed.12 Unfortunately, development and licensure of such new products require a substantial investment of money and time. Examples of such longer term solutions include new live attenuated vaccines that could be administered intranasally or perhaps a genetically engineered vaccine that uses bacteria, viruses, or other vehicles to deliver bacterial antigens. It is clear that we need redoubled efforts to combat the real, persistent, and potentially lethal threat of pertussis.
Cite this as: BMJ 2014;349:g4518
Funding: This publication was made possible, in part, by support from CTSA grants UL1TR000142 and KL2 TR000140 from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Science (NCATS), components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.
Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: None.
Provenance and peer review: Commissioned, not externally peer reviewed.