Whooping cough—a continuing problem

Pertussis has re-emerged in countries with high vaccination coverage and low mortality

News media announced a global resurgence of whooping cough in April this year following a session on pertussis at the 12th European Congress of Clinical Microbiology and Infectious Diseases in Milan, Italy. Subsequently the European Union sent an alert to member states. Pertussis is one of the top causes of vaccine preventable deaths, with nearly 300 000 deaths in children worldwide in 2000.1 However, reports of a global resurgence originated in countries with low mortality and high vaccination coverage. For such countries the issue is how to fine tune effective immunisation programmes. In the rest of the world, priorities are to decrease infant mortality by improving coverage and timeliness of vaccination and implementing pertussis surveillance.2

Pertussis has re-emerged in low mortality countries in the past because of low coverage after a vaccine scare in the 1980s (in the United Kingdom) or the use of vaccines with poor efficacy (Canada, Sweden).3 Sweden and Germany stopped their vaccination programmes completely and only reinstituted vaccination for pertussis after years of recurrent epidemics of whooping cough. More recently some countries with sustained high coverage have experienced increases in pertussis, especially in older children and adults, the reasons for which are complex. 3 4 After an outbreak of pertussis in the Netherlands in 1996, polymorphisms in the genes coding for the Bordetella pertussis virulence factors pertactin and pertussis toxin were reported as evidence for a vaccine driven evolution of circulating strains that has led to a fall in vaccine efficacy.5 Similar studies in other countries have also revealed the emergence of non-vaccine variants of pertactin and pertussis toxin.6 In France, however, an increase in the frequency of non-vaccine variants of both pertussis and pertactin toxin has not been accompanied by a decline in the efficacy of the vaccine.7 The situation in the United Kingdom, where there has not been a re-emergence of pertussis, seems unique in that all of the most recent isolates studied are of the same pertussis toxin type as one of the strains included in the United Kingdom whole cell vaccine.8

In high coverage countries, further development of national policies for the control of pertussis is a challenge because of underdiagnosis and under-reporting, which hinder surveillance, as well as gaps in our knowledge of levels of herd immunity generated by the vaccination programmes. Underdiagnosis occurs because pertussis has mild or atypical forms, because clinicians may not consider pertussis as a cause of cough especially in older children and adults, or because sensitivity of culture, the traditional diagnostic method, is as low as 20-40%. Surveillance is so incomplete that enhanced awareness or improved diagnostic methods can result in apparent epidemics, which may account for some of the observed increase in older individuals in several countries with high vaccination coverage. 4 5 Methods such as enzyme linked immunoassay (ELISA) based serology and polymerase chain reaction have increased diagnostic sensitivity and have only recently become routinely available in some countries, such as from the Public Health Laboratory Service for England and Wales. Improved surveillance will help evaluate the impact of interventions including the preschool booster implemented in the United Kingdom in November 2001.

Infants are at greatest risk of death or severe complications from pertussis.9 We rely on herd immunity to protect the youngest infants before they can be protected directly by vaccination. However, in contrast to diseases such as measles, pertussis vaccination may have an only limited impact on interrupting transmission. The interepidemic period has not increased markedly on implementation of vaccination programmes, so the vaccine may be more effective at preventing disease than infection. Furthermore, vaccine derived immunity wanes over five to 10 years so that pertussis occurs in older vaccinated individuals who may then infect infants. Consequently, unvaccinated infants remain at risk of pertussis despite good vaccination programmes.10 Uncertainty about the level of herd immunity generated by vaccination programmes limits modelling of the potential benefits of booster vaccination.11 Policy makers need more information about the natural history of pertussis in adolescents and adults to determine the potential benefits from booster vaccination in these groups irrespective of any possible benefit to infants through reducing transmission. In view of the limits of surveillance, the answers to specific policy questions may require focused studies in representative populations of the incidence and source of infection in young infants, the incidence and severity of undiagnosed pertussis in adults, and the number of deaths from pertussis particularly in high mortality countries. 2 11 12

For most countries in the world, discussing the possible costs and benefits of adolescent and adult pertussis boosters and molecular diagnostic methods are not a priority. The global priorities remain enabling social, political, and economic stability that are prerequisites for health services capable of delivering high coverage and safe, timely vaccination for all children.2 Pertussis vaccination has the potential to prevent an additional third of a million deaths globally every year. In 2000 the World Health Organization held its first meeting on surveillance of pertussis in 20 years.2 The participants concluded that pertussis had been neglected as a disease, that research on deaths from pertussis should be carried out in high mortality countries, and that basic laboratory surveillance and control measures need strengthening globally.