Summary

Despite best efforts by immunization teams and immunologists worldwide, the World Health Organization (WHO) goal that the incidence of pertussis should be reduced to <1 case per 100,000 population in Europe by 2000 has not been achieved.1 Indeed the incidence in some parts of the world is rising. An evaluation of the reasons for these statistics is the first step towards attaining better control of Bordetella pertussis infection on a worldwide basis. The 3 articles in this section of the publication provide an overview of the current epidemiologic situation of pertussis.1–3 EPIDEMIOLOGY OF PERTUSSIS Epidemiologic data from 17 countries, including members of the Global Pertussis Initiative, indicate that the WHO target to reduce the incidence of pertussis has been achieved only in Japan. The incidence of pertussis varies widely between countries.1 The variance in incidence partly reflects the different criteria used to define, diagnose and report and monitor the infection, the bio-evolution of the circulating organism and the various immunization strategies and target groups present in the different countries. However, the fact that increases in the peak incidence of reported cases of pertussis have been documented in a number of countries during the past 15 years gives cause for concern, particularly since the true incidence of pertussis is higher than reported because the disease remains underdiagnosed, in part because clinicians continue to perceive pertussis as a childhood disease. Despite high immunization rates, B. pertussis infection remains endemic in the United States. Until recently in Canada, the highest absolute incidence of pertussis was in infants younger than 1 year of age, with much lower rates seen in adults and adolescents.4,5 However, there was still a 5- to 8-fold increase in peak incidence among these older age groups between 1986 and 19985; and in a pertussis outbreak in British Columbia in 2000, the incidence among older children and adolescents surpassed that of all other age groups.6 Pertussis also remains a serious problem in many other countries. In Finland, the disease remains inadequately controlled despite an immunization policy that achieves a 98% coverage rate (a diphtheria-tetanus toxoids-pertussis booster vaccine is administered at 20–24 months, and a diphtheria-tetanus toxoids-acellular pertussis booster is given at 6 years). Although the number of cases of pertussis in France has remained stable since 1996, a recent retrospective study conducted in French pediatric intensive care units showed that pertussis is the primary infectious cause of mortality in newborns and infants younger than 2 months of age. There were 13 deaths from the infection in 2000.7 Moreover 32% of adults consulting their general practitioner for a persistent cough illness showed evidence of B. pertussis infection.8 In Israel, an outbreak of pertussis in a kibbutz (closed agricultural community) occurred in 78 of the 964 people living in the kibbutz (an incidence of 8000/100,000 population). The incidence was 36.1% (36,000/100,000 of the population) in children 4–11 years old who had all been fully immunized.9 An area of particular concern is Australia, where B. pertussis infection has been endemic since 1993, with the highest reporting rates among children younger than 15 years of age and a small secondary peak among adults between 30 and 49 years of age.10 These statistics highlight the apparent epidemiologic trend in many countries towards infection in older age groups. Data from the Centers for Disease Control and Prevention11 indicate that the greatest increase in the proportion of pertussis cases was seen among persons 10–19 years of age.12 The rate of B. pertussis infection among young adults also appears to be increasing in Israel.13 Similar trends are reported in other areas of the world. In recent years, infant acellular pertussis (aP) vaccines have been incorporated into the immunization schedules of many developed countries, gradually replacing whole cell pertussis (wP) vaccines. This offers the option of booster immunization after 6 years of age, which is not possible with the older wP vaccines. To date, only Australia, Austria, Canada, France and Germany have incorporated an adolescent aP booster dose into their immunization schedules. The necessity of ongoing immunization is highlighted by studies showing that with aP and wP vaccines, immunity lasts for at least 3–5 years after infant immunization14,15 and 7–8 years after booster immunization,16 although the precise duration of immunity is unknown. SOURCES OF INFECTION AND ROUTES OF TRANSMISSION IN THE VACCINATION ERA Humans are the only known hosts for B. pertussis. Direct transmission of the organism is presumed to occur through airborne contact with aerosol droplets from the respiratory tract of an infected, coughing individual.17 Indirect transmission seldom occurs.18,19 Immune-naive individuals are fully susceptible to B. pertussis infection, but infection does not necessarily result in typical disease. The proportion of asymptomatic infection or atypical disease in immune-naive individuals has been estimated to be 25%.20 However, asymptomatic infections with B. pertussis can be considered as “end-point” infections and are thought to contribute little to B. pertussis transmission.3 Individuals with pertussis disease are most infectious during the catarrhal period and the first 2 weeks after the onset of cough,11 often before a diagnosis has been made.21 This may have drastic consequences because pertussis is highly infectious; 90–100% of susceptible contacts develop pertussis when exposed to a symptomatic household member, and the infection rate of household contacts older than 15 years of age has been reported to be as high as 83%.22,23 After infection with B. pertussis, immunity wanes over time. In many countries where vaccination with a pertussis vaccine was restarted or vaccine coverage increased, the incidence of pertussis decreased significantly in both vaccinated and unvaccinated individuals of all ages.24–26 These findings suggest that effective vaccination in childhood strongly induces a certain degree of herd immunity. The increased recognition and apparent shift in the reservoir of B. pertussis toward older children, adolescents and adults is a public health concern, not only because these age groups are playing an increasingly important role in disease transmission to susceptible neonates and infants but also because pertussis disease poses a significant health burden in adults, resulting in considerable morbidity.27 The situation is exacerbated by the fact that the relative role of adolescents and adults in transmitting B. pertussis infection to infants appears to increase with higher immunization coverage and with the duration of the nationwide immunization program, and may reach levels of >50% of all transmission sources.28,29 Parent-to-infant transmission may now play a greater role than child-to-child transmission in maintaining circulation of B. pertussis infection; several studies have suggested that mothers are a significant source of infection for infants.3 Adolescents, grandparents and health care workers have also been suggested as sources.3 By contrast, the main sources of infection for adolescents are schoolmates and friends; for adults, children or work colleagues are the main sources of B. pertussis infection (De Serres et al27). Teachers and health care workers are at increased risk of being exposed to B. pertussis infection. Indeed health care workers may be important vectors of infection to colleagues and patients (Schellekens et al3). Because current immunization strategies do not adequately control the circulation of B. pertussis infection, their expansion to target specific groups should be considered. Identifying the sources of B. pertussis infection and assessing which groups contribute most to the development of pertussis disease in infants will help to determine which groups to immunize, so that the residual burden of pertussis is reduced. DEFINING EPIDEMIOLOGY: CLINICAL, MICROBIOLOGIC AND SEROLOGIC PERSPECTIVES Clinical diagnosis of B. pertussis infection is complicated by the wide heterogeneity in disease expression, modification of disease by immunization, mixed infections, previous infection and a low index of suspicion among many physicians. The classic form of pediatric pertussis disease in the prevaccine era was described as the presence of a paroxysmal cough, posttussive vomiting, inspiratory whoop and duration of cough lasting >28 days and up to 3 months.30,31 However, in the era of immunization, B. pertussis infection has a wide spectrum of clinical expression, affected by patient age, previous exposure to the organism (by vaccination or prior infection), antibiotic administration, the degree of exposure, concomitant infections with other agents and the presence of cross-reacting antibodies (making the interpretation of serologic results problematic).31 Atypical or mild pertussis characterized by the absence of whoop and often a somewhat shorter duration of cough23,32 is more common than typical pertussis among adolescents and adults. The severity of the condition is also variable. It may be asymptomatic in children and adults with strong residual immunity,22,23,32 or present as a more severe and life-threatening disease in unprotected newborns and young infants.33 Misdiagnoses of pertussis13,31,34 contribute to its underreporting. Diagnosis is further complicated by the concurrence of other infections. To compound the problem, there is also low awareness that B. pertussis infection can affect all age groups; and in many developed countries where the disease is relatively well-controlled by immunization programs, there is widespread belief that the infection no longer occurs in the population.35,36 Proper diagnosis of B. pertussis infection should not rely solely on clinical criteria but should also be confirmed by laboratory study. Moreover accurate diagnosis should be made early in the course of the illness to allow prompt intervention and prevent the spread of infection. A sensitive method of diagnosis is required for epidemiologic studies to detect all cases, including milder disease, and atypical forms. Currently there is lack of consistency between case definitions, and standard definitions, such as those by the WHO or Centers for Disease Control and Prevention are not adopted universally, making intercountry comparisons and global evaluations difficult. Presently, culture, direct fluorescent antibody and polymerase chain reaction (PCR) are the most common laboratory methods used to make the diagnosis of pertussis. Although rapid and relatively inexpensive, direct fluorescent antibody is insensitive and might lack specificity. With the proper performance of culture, using PCR, the sensitivity and specificity of the laboratory diagnosis of B. pertussis infection can equal or exceed those for many other bacterial infections. To maximize the rate of organism isolation, the use of correct culture techniques is very important. However, many practical problems affect the sensitivity of the laboratory diagnosis of pertussis. Suboptimal culture results reflect inadequate specimen collection and transport, as well as poor laboratory practice. Appropriate methods for each of these steps have been well described.37–42 Despite this, in both developed and developing countries, there is often a lack of access to diagnostic laboratory methods. Furthermore most routine laboratories are not equipped for the diagnosis of B. pertussis infection and the use of PCR is variable. CONCLUSION Effective vaccines have generally decreased the incidence of pertussis disease globally and major epidemics have been largely avoided. However, the increased reporting rate in recent years, particularly among adolescents and adults, is of concern because infection in these age groups acts as a means of spreading the disease to neonates who are at high risk of pertussis-related morbidity and mortality. More research into the epidemiology of pertussis disease is urgently required to establish the role of specific subgroups (defined by age, occupation and frequency of contact with newborns) in the transmission of pertussis to infants. This will enable immunization strategies to be expanded and optimized. In addition, rapid, easy to use, sensitive and specific laboratory diagnostic techniques must be available, and criteria for laboratory confirmation of B. pertussis infection should be standardized. Particularly important will be the increased use of PCR and single serum serology. Education campaigns targeted at health care professionals and the public should also be implemented to raise awareness of the burden of pertussis.

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