Pertussis
Resurgence
Epidemic Pertussis in 2012 — The Resurgence of a Vaccine-Preventable Disease
- increased awareness of disease
- use of better diagnostic tools
- improved surveillance methods
- waning vaccine-induced immunity
- recently, antigenic divergence under selection pressure
Bordetella pertussis Strains with Increased Toxin Production Associated with Pertussis Resurgence
Abstract
Before childhood vaccination was introduced in the 1940s, pertussis was a major cause of infant death worldwide. Widespread vaccination of children succeeded in reducing illness and death. In the 1990s, a resurgence of pertussis was observed in a number of countries with highly vaccinated populations, and pertussis has become the most prevalent vaccine-preventable disease in industrialized countries. We present evidence that in the Netherlands the dramatic increase in pertussis is temporally associated with the emergence of Bordetella pertussis strains carrying a novel allele for the pertussis toxin promoter, which confers increased ertussis toxin (Ptx) production. Epidemiologic data suggest that these strains are more virulent in humans. We discuss changes in the ecology of B. pertussis that may have driven this adaptation. Our results underline the importance of Ptx in transmission, suggest that vaccination may select for increased virulence, and indicate ways to control pertussis more effectively.
Transmission Models
Whole-cell vaccine effective at blocking transmission
[http://www.pnas.org/content/110/23/9595.full.pdf+html Deciphering the impacts of vaccination and immunity on pertussis epidemiology in Thailand]
Pertussis is a highly infectious respiratory disease that is currently responsible for nearly 300,000 annual deaths worldwide, primarily in infants in developing countries. Despite sustained high vaccine uptake, a resurgence in pertussis incidence has been reported in a number of countries. This resurgence has led to critical questions regarding the transmission impacts of vaccination and pertussis immunology. We analyzed pertussis incidence in Thailand—both age-stratified and longitudinal aggregate reports—over the past 30 y. To dissect the contributions of waning pertussis immunity and repeat infections to pertussis epidemiology in Thailand following a pronounced increase in vaccine uptake, we used likelihood-based statistical inference methods to evaluate the support for multiple competing transmission models. We found that, in contrast to other settings, there is no evidence for pertussis resurgence in Thailand, with each model examined pointing to a substantial rise in herd immunity over the past 30 y. Using a variety of empirical metrics, we verified our findings by documenting signatures of changing herd immunity over the study period. Importantly, this work leads to the conclusion that repeat infections have played little role in shaping pertussis epidemiology in Thailand. Our results are surprisingly emphatic in support of measurable impact of herd immunity given the uncertainty associated with pertussis epidemiology.
Overview
Historical Review of Pertussis and the Classical Vaccine
Abstract
Pertussis is an epidemic disease caused by Bordetella pertussis and also to a lesser extent by Bordetella parapertussis. Classical illness lasts 4-8 weeks and is characterized by paroxysms of coughing with posttussive vomiting and whooping; however, 47.4% of primary infections last 4 weeks or less. Whole cell pertussis vaccines are generally highly efficacious. All whole cell vaccines are reactogenic, causing fever and local reactions in many vaccinees. In the past, these vaccines were thought to cause infant deaths and brain damage. However, several large epidemiologic studies indicate that whole cell vaccines do not cause infant deaths or neurologic disease. Recent studies indicate that neither immunization nor infection give long-term immunity. As a result, B. pertussis infections are endemic in adult populations. The future control of B. pertussis will require immunization schedules with new acellular vaccines that include booster doses in older children and adults.
Epidemiology
In the prevaccine era and in populations where immunization is not done, pertussis is an epidemic disease with cycles every 2-5 years [1-3]. Fine and Clarkson [34] noted that this cycle did not change, despite a reduction in total cases by immunization. This indicates that immunization controls disease but does not control the prevalence of the organism in the population.
From September 1986 to February 1989, my group studied cough illnesses in UCLA students [11]. We found that 26% of those with an illness of 6 days had B. pertussis infections, but none were recognized by their physicians. Since we demonstrated B. pertussis throughout the 2.5-year period, we suggested that B. pertussis infections are endemic in adults and cause the epidemic cycles that predominantly involve unvaccinated children. Since there has been effective routine immunization in the US for > 30 years, these cases in UCLA students occurred in previously vaccinated persons.
The prevailing opinion is that vaccine immunity is relatively short-lived, whereas immunity following infection is lifelong. Studies by UCLA researchers suggest this opinion is wrong. Knowing that IgA antibodies to pertussis antigens (PT, FHA, and pertactin) usually result from infection and not vaccination, their prevalence in young German and American men of similar ages was studied [35]. In Germany, routine childhood immunization was not done during the 1970s and 1980s and pertussis was epidemic. To our surprise, the rate and mean values of IgA antibodies in the two populations were similar, suggesting similar adult infection rates. In another study in Germany, B. pertussis infections were common in adults (133/100,000 population) and often occurred in those with a history of childhood pertussis [16].
These data indicate that in populations in which pertussis is controlled by immunization and in populations in which pertussis is epidemic, endemic disease occurs in adults. This endemic disease is responsible for the cyclic disease observed in unvaccinated children
Summary and Conclusions
Whole cell pertussis vaccines have been highly successful in controlling epidemic pertussis. Their use, however, has not curtailed the circulation of B. pertussis in the population. In addition, whole cell pertussis vaccines are safe but cause considerable short-term discomfort.
In the near future, if the circulation of B. pertussis and pertussis disease is to be controlled, programs involving booster immunizations of older children and adults will be needed. Adult booster immunizations with present whole cell vaccines are not a practical consideration because of reactogenicity. However, endotoxin-free acellular pertussis vaccines should be acceptable for adult use. Immunization programs that include older children and adults may enable the control of B. pertussis circulation as well as pertussis disease.