Epidemiology of Pertussis : The Pediatric Infectious Disease Journal (original) (raw)
This review incorporates epidemiologic data on pertussis infection from 17 different countries represented on the Global Pertussis Initiative (GPI), a group of 37 international experts assembled with the primary aims of developing strategies for improving disease control, reducing the morbidity and mortality in unimmunized or incompletely immunized infants and the implementation of effective immunization strategies.1
Globally, 20–40 million cases of pertussis occur each year, 90% of which are in developing countries, and there are up to 400,000 fatalities each year, mostly in young infants. The World Health Organization (WHO) recommended that a pertussis incidence of <1 case/100,000 population be achieved in Europe by 2000. Available data from countries represented in the GPI indicate that this goal has not been achieved in Europe, and only Japan has reached this target. Other countries with low reported national incidences (cases per 100,000 population) include Spain (2.3), the United States (2.7), France (3.4) and the United Kingdom (4). Conversely the highest incidences (cases per 100,000 population) worldwide were reported from Australia (22–58) and Switzerland (180). Understanding the reasons for this wide discrepancy in incidences worldwide may lead to better global control of pertussis. Possible reasons include differences in laboratory confirmation, reporting and surveillance of pertussis, bioevolution of the circulating organism and the various immunization strategies and target groups present in the different countries.
THE CURRENT EPIDEMIOLOGY OF PERTUSSIS
Absolute numbers of cases of pertussis depend on the criteria used to define, diagnose and report the infection, which contribute to the wide variation in incidences reported in different countries. However, as a whole, increases in the peak incidences of pertussis have been reported in many countries over the past 15 years, including Argentina, Australia, Canada, Italy, Japan, the Netherlands, Switzerland and the United States.
INCIDENCE IN INFANTS AND CHILDREN
Despite high immunization rates in infants and children in many countries, pertussis remains endemic, with epidemics superimposed every 2–5 years.2–4 This has remained unchanged from the prevaccine era2,3 and is probably caused by continued transmission of pertussis among adolescents and adults, with passage to susceptible infants, although Beard and Finn5 reported that the epidemic cycle in the United Kingdom may have almost disappeared. However, even though the epidemic cycle in the United Kingdom seems to have become less distinct, pertussis disease continues to remain a problem especially in the young infant population younger than 3 months of age.
From 1970 to 1980 in the United States, the annual incidence of reported pertussis stabilized to an average of 2334 cases/year. However, an analysis of 27,826 cases of pertussis reported to the Centers for Disease Control and Prevention between 1980 and 1989 showed that the incidence has increased in all age groups, compared with the period 1970–1980.6 Importantly infants between 1 and 2 months of age were at the highest risk for pertussis (annual incidence, 62.8/100,000) and had the highest reported rates of complications.6
Pertussis also remains a serious problem in many other countries.4,7–9 In Canada, pertussis remains endemic with cyclic peaks every 25 years. Despite high vaccine coverage rates, in 1998 the incidence of disease in infants younger than 1 year of age was 199 cases/100,000, for children between 1 and 4 years of age it was 119 cases/100,000 and for children between 5 and 9 years of age it was 149 cases/100,000. Since 1990, there has been a resurgence of pertussis among all age groups.
In Finland, the disease cannot be controlled with the current immunization policy a diphtheria-tetanus-pertussis (DTP) booster vaccine is administered at 20–24 months of age and a diphtheria-tetanus-acellular pertussis (DTaP) booster at 6 years of age; see Table 1) despite achieving a 98% coverage rate. There has been an alarming 5-fold increase in the number of pertussis cases in infants younger than 1 year of age, and especially in infants younger than 6 month of age, over the period 1995–1999. About 40% of these infants were younger than 3 months of age, the age at which the first dose of the primary vaccine is administered. Three fatalities were recorded among this patient population between 1998 and 1999, which represents a higher pertussis mortality rate than had been seen in Finland for a number of decades.
Current Immunization Schedules in Selected Countries
In France, the number of cases of pertussis has remained stable since the establishment of a hospital-based surveillance group, RENACOQ, in 1996.10 Although transmission is mainly from parent to infant, nosocomial infections in pediatric wards have also been observed and involve pertussis transmission from infants to nurses or physicians or from nurses to infants.11,12 A recent, retrospective study conducted in 1999–2000 showed that pertussis is the primary infectious cause of mortality in newborns and infants younger than 2 months of age in French pediatric intensive care units. There were 13 deaths from the infection in 2000.13
In Israel, several studies have examined the incidence of pertussis. 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 36,000/100,000 in children 4–11 years of age who had all been fully immunized.14 In a study conducted in a day-care center in Northern Israel,15 46 fully immunized children exposed to a fatal case of pertussis infection were tested for pertussis disease. Of those, 5 (11%) were positive by polymerase chain reaction (PCR): 4 of 16 (25%) 5–6 years of age versus 1 of 30 (3%) 2–3 years of age. Only 2 of the children studied were symptomatic, indicating that even fully immunized very young children can be asymptomatic reservoirs of infection.15 However, in general, asymptomatic infections with Bordetella pertussis can be considered as “end-point” infections and are thought to contribute little, if anything, to B. pertussis transmission.16
In Argentina, national reporting data show that the incidence of whooping cough syndrome (suspicious cases based on the clinical characteristics of the illness) is highest among children younger than 1 year of age and also that there is an important peak among school children 5–9 years of age. National Argentinean reporting data show that the incidence of whooping cough is highest among children younger than 1 year of age with an attack rate of 27/1000, however, there is also an important peak among school children 5–9 years of age with an attack rate of 11.4/1000.
INCIDENCE IN ADOLESCENTS AND ADULTS
The incidence of pertussis in older age groups has been increasing in a number of countries in recent years. During the 1990s, the annual number of reported pertussis cases in the United States varied between 5000 and 8000, with large outbreaks occurring every 3–4 years. Figure 1. illustrates the number of pertussis cases reported to the Centers for Disease Control and Prevention (CDC) in 1990–2000.17,18 When comparing the number of cases in the various groups during the period from 1990–1993 with the period from 1996 to 2000, the incidence of pertussis in the 10- to 19-year group was noted to increase by >100%; whereas the incidence in the ≥20-year group increased by almost 95%. These data indicate that the most significant increase in pertussis disease has been seen among the adolescent and adult populations.
Pertussis cases in the United States, 1990–2000.
In Canada, there has been a resurgence of pertussis from an overall incidence below 10/100,000 during outbreaks in the 1980s to >30/100,000 during outbreak periods in the 1990s.9 The most rapid increase in cases has occurred in preteens and teens.8,9 In 1986 (a cyclic peak), 11% of cases occurred in persons between 10 and 14 years of age, and 10% occurred in those ≥15 years of age. By 1998 (cyclic peak), these proportions had increased to 19 and 17%, respectively, whereas the proportion of cases in persons younger than 4 years of age dropped in 1998 (29%) to nearly one-half that of 1986 (52%).9 In Canada, the greatest relative increase in pertussis incidence nationally has been among adolescents and adults.
In Australia, pertussis has been epidemic since 1993. National notification data, collected since the establishment of the National Notifiable Diseases Surveillance System in 1990,19 show that the incidence is highest among children younger than 15 years of age, with a small secondary peak among adults 30–49 years of age. Between 4000 and 10,000 cases are reported annually, with an incidence of between 22 and 58 per 100,000 population.
In 1999, a French study determined the frequency of B. pertussis infections in adults consulting their general practitioners for a persistent cough lasting from 7 days to 1 month for which no evident diagnosis could be given. The study showed that the evidence of B. pertussis infections in these adults was ∼32%.20
COUNTRIES NOT REPRESENTED ON THE GPI
There has been very little documented about the epidemiology of pertussis in Africa, Asia or Latin America. In theory, all identified cases are reported to the WHO vaccine-preventable diseases program. For the countries represented in the GPI, the data should be interpreted with caution because of the variable rates of underreporting, possible misdiagnoses and different case definitions. However, even though the WHO data represent the largest source of available information on pertussis epidemiology,21 the reported cases may not all be uniform as the criteria used for reporting differs from country to country.
Table 2 provides a summary of the number of pertussis cases reported to WHO, per region. It shows a general global improvement in pertussis incidence during the past 3 decades. However, the levels of improvement are variable. Although Europe is a developed region, it still has one-third of the incidence 25 years ago.
Number of Pertussis Cases Reported to World Health Organization, Per Region
Pertussis is an important pathogen in developing countries and is considered to be a reemerging problem in developed countries. Whereas only 5–25% of all cases in developed countries are estimated to be reported because of difficulties associated with laboratory confirmation or atypical cases, there are no such estimates for developing countries.
The higher incidences observed among the poorest countries, the higher case-fatality rates (1–3% in developing versus 0.04% in developed countries) and the widespread migration phenomenon are all major factors contributing to this complex issue and underscore the urgent need for coordinated efforts to study pertussis and develop strategies for its control.
EPIDEMIOLOGIC TRENDS
In some countries, data describing the age distribution of cases have only recently become available; therefore it is not possible to identify any changes in the age distribution of pertussis. However, many countries are now observing a shift in the incidence of pertussis disease toward older age groups.
Figure 1 shows the number of pertussis cases reported to the CDC in the United States, stratified by age, collected from 1990 to 2000. These data demonstrate that the greatest increase in the proportion of pertussis cases was observed among persons 10–19 years of age.
In Canada also, there is growing recognition that pertussis may be an important cause of prolonged cough illness in older age groups.8,22,23 A recent large outbreak of pertussis in British Columbia, Canada during 2000 highlights the growing importance of pertussis in older age groups. Although infant rates were still higher than those of preschool children, during this outbreak the highest incidence occurred in preteens and teens (10–14 years of age). This is the first time that incidence in preteens and teens has been documented to surpass all other age groups in Canada.24 Growing awareness and the recent introduction of PCR methods of confirming pertussis in persons with mild illness or prolonged cough may have enabled this trend to be detected.
A recent study in Israel has also demonstrated a shift in the age distribution of pertussis.25 Of 95 previously immunized individuals 5–30 years of age with serologically confirmed pertussis, the mean age was 8.9 years. The symptoms manifested were commonly atypical, with only 6% having the classic inspiratory whoop of pertussis.
A number of hypotheses have been put forward to explain the observed disease resurgence, including waning natural and vaccine-induced immunity and a lack of natural boosting, a reduction in vaccine coverage or poor vaccine immunogenicity and efficacy and the emergence of new bacterial variants.
EFFECT OF IMMUNIZATION COVERAGE RATES ON EPIDEMIOLOGY
After widespread immunization, major pertussis epidemics have been reduced in many countries.10,26 For example, in Finland the introduction of the DTP vaccine in 1952 eradicated major epidemics, and in the late 1960s and 1970s pertussis was seldom reported. Although vaccine-induced protection decreased after a few years, it was not possible to give booster immunizations with whole cell pertussis (wP) vaccine after 6 years of age. However, as it was considered that mild, atypical pertussis disease in school age children was the preferred alternative to pertussis disease in young adults, a preschool booster dose was not included in the immunization program, because this might have shifted the epidemiology toward young adults who could put their own children at risk. However, the current immunization program administers a DTP booster vaccine at 20–24 months of age and a DTaP booster at 6 years of age with vaccine coverage rates of ∼98% for 4 doses of DTP.
Vaccine coverage has remained very high in France since its introduction; coverage was 89% in 1997 with 4 doses of wP vaccine,10 and vaccine efficacy was ∼94%.27 However, a comparative study focusing on determining the reservoirs of pertussis disease was undertaken in 2 large cities (Paris and Marseille), with a 30% difference in rate of immunization coverage in infants 16 to 18 months of age. The study demonstrated that children were the main contributors to pertussis transmission in Marseille, the city with low immunization coverage, whereas adults were the main reservoirs of disease in Paris, the city with high immunization coverage.28
In recent years, acellular pertussis (aP) vaccines have been incorporated into the immunization schedules of many developed countries represented on the GPI, gradually replacing wP vaccines. Finland, the Netherlands and the United Kingdom all recommend a wP vaccine for primary immunization and an aP vaccine as a booster dose. In contrast, Australia, Belgium, France, Germany, Israel, Italy, Japan, Spain, Switzerland, Canada and the United States all currently use aP vaccines for both the primary series and booster dose(s). Of the GPI participating countries, only Argentina and Brazil continue to use a wP vaccine for both primary and booster immunization.
Dosing schedules also vary between countries on the GPI (see Table 1). Primary immunization with 3 doses of the pertussis vaccine administered within the first 6 months of life is used in most countries. At least 1 booster dose is recommended in all countries. Some countries provide a second booster dose, for which the timing varies. Only Australia, Canada, France and Germany have incorporated an adolescent booster dose into their current immunization schedules nationally, in recognition of the rising incidence of pertussis in adolescents and adults. Thus far, uptake of the adolescent booster dose in Germany has been estimated at <10%, but the recommendation to immunize adolescents has been in place only since 2000.
OTHER FACTORS INFLUENCING EPIDEMIOLOGY
Adverse Events.
The occurrence of specific adverse reactions, which may be associated with immunization against pertussis disease or perceived “concerns” surrounding vaccine safety, may play a contributory role in disease epidemiology. Because of an increase in the number of adverse reactions in the 1970s in Japan, the mass immunization program was temporarily suspended, and the incidence of pertussis increased significantly. A similar effect was seen in the United Kingdom in the 1970s, where vaccine uptake rates decreased from 75% to 25% (approximate values) after media reports criticizing vaccine safety; 2 major epidemics occurred in 1977–1979 and 1982–1983.29
Vaccine Efficacy.
Humoral and cellular immunity induced by different vaccines in children between 2.5 and 5 years of age who had been immunized (primary vaccination at 2, 3 and 4 months and a booster dose at 16–18 months) with either the aP or wP vaccine have been studied. These studies suggest that immunity lasts for at least 3–5 years.30,31 Anti-PT titers decrease rapidly after immunization (PT detection rate was 50% at 3 months postvaccination) and are very low around 4–5 years (PT detection rate was 11.5% at 57 months postvaccination) after the booster immunization at 16–18 months old. However, even though anti-PT titers were found to be low, it was observed that in the absence of any vaccine booster dose, titers measured 7–8 years later were increased over previous levels (PT detection rate was 20.5% at 86 months postvaccination) reflecting natural boosting from contact with B. pertussis.32 This study also suggests that immunity induced by wP vaccines does not last >7–8 years after the booster vaccine is given. These observations led to the hypothesis favored in France that immunity wanes as a result of a reduction in natural boosters caused by the substantially reduced circulation of pertussis after the introduction of immunization and also lack of a vaccine booster dose for adolescents and adults. Immunity after natural infection does not seem to persist longer than after immunization with wP vaccine according to a recent study to determine the evidence of B. pertussis infections in adults.20 Therefore both natural and vaccine-induced immunity wane considerably 5–8 years after the last booster dose, making these individuals more susceptible to pertussis disease.
Genetic Variants.
One hypothesis for the observed resurgence is that it is caused by the emergence of new pertussis variants. B. pertussis isolates circulating within European populations differ from those strains that form the basis of either wP or aP vaccines (vaccine strains). In France, the isolates collected during the 1990s were analyzed and compared with vaccine strains and isolates collected before the introduction of generalized wP and aP immunization.4 This analysis confirmed that the circulating isolates differ from both the vaccine strains and the isolates circulating before generalized immunization. However, a continuous evolution of B. pertussis occurring during the late 1990s was also observed. At the present time, there is no conclusive evidence of a causal relationship between genetic variations in circulating isolates, effectiveness of immunization practices or vaccine types and the resurgence of pertussis disease being observed. Also there is no laboratory or epidemiologic evidence to suggest the phenomenon is clinically important. However, surveillance must be performed carefully to analyze the evolution of B. pertussis isolates because it will be valuable to compare regions with and without an extensive immunization program and to explore the impact of vaccine types and immunization practices on the emergence of genetic variants.
REASONS FOR THE WIDE DISCREPANCIES IN PERTUSSIS INCIDENCES WORLDWIDE
Differences in National Reporting Systems.
In the majority of countries where pertussis is a notifiable disease, a case-based national surveillance system is in place. However, different case definitions, methods of diagnosis, reporting and surveillance systems make direct intercountry comparisons difficult. Moreover pertussis is not a statutory notifiable disease in every developed country. Nevertheless there is general consensus that reported incidences are likely to be considerably lower than the actual incidence of pertussis.33–36 Underreporting, as suggested in Australia, Spain, the United Kingdom and the United States, is common.33–36 The true incidence of pertussis could be >3-fold higher than the official notification rate.33–36 Underreporting is a particular problem in older age groups.25,37,38 Prolonged cough might be the only clinical feature in adolescents or adults, who may present for diagnosis late (precluding laboratory confirmation) or not at all. When they do present, their condition is often misdiagnosed because, in part, clinicians continue to perceive pertussis as a childhood disease.
In countries where detailed case reporting information has not been available, the impact of immunization on pertussis epidemiology can only be estimated. For example, in Spain pertussis has been a national notifiable disease since 1982, although individual notification, on a case-by-case basis, was not available at this time. However, the notification criteria changed in 1997 to individual notification, allowing a clearer picture of pertussis epidemiology to be obtained. A laboratory reporting system is also in place. Cases are now reported by physicians, laboratories, hospital infection control personnel and other health care professionals to the local and national health departments. In other countries, such as Germany, no reporting of cases and deaths is required by federal law, although outbreaks are reported by physicians.
In Japan, a voluntary reporting system was used to monitor trends of pertussis epidemiology in Japan until 1981, when the Ministry of Health and Welfare started a national surveillance system for common pediatric infectious diseases to supplement the existing reporting system. Pertussis is included among the diseases surveyed by this system. Reporting of pertussis in Japan is based primarily on clinical findings (minimum of 2 weeks of paroxysmal cough); however, increasingly, suspected cases also include laboratory confirmation in the diagnosis (culture or serologic demonstration). Doctors in various districts report the number of patients they see each week to their local health center. The surveillance system was designed to observe the trends in epidemics of infectious disease such as pertussis, but it does not attempt to identify all cases of pertussis occurring in Japan.39
In the United States, a case-based national surveillance system for pertussis has been in place since the 1920s. Cases are reported by physicians, laboratories, hospital infection control personnel and other health care professionals to local and state health departments. These health departments subsequently report cases to the CDC through 3 distinct national reporting systems that are currently in place: (1) the National Notifiable Disease Surveillance System, in which core information about pertussis cases is reported electronically through the National Electronic Telecommunications System for Surveillance; (2) the Supplementary Pertussis Surveillance System; a paper-based system introduced in 1979; (3) a new electronic work sheet linked to the National Electronic Telecommunications System for Surveillance, introduced in 1994.17
Differences in Case Definitions.
Insight into pertussis epidemiology based on case reporting is hampered by changes in case definition for notification, availability and interpretation of laboratory diagnostic tests, diagnostic practice and notification rate. The reporting of cases by physicians in some countries, such as the Netherlands is low. Also in countries where the country case definition is highly specific, significant underreporting can occur. Trends in hospital admissions are likely to reflect the incidence of severe pertussis and are therefore a less sensitive marker for pertussis incidence than case reporting and hospital admission data, but may facilitate more meaningful comparisons between countries.
Clinical criteria for case definition vary between countries, and this impacts on the number of cases of pertussis detected and reported. In most countries, the case definition includes cough lasting at least 14 days with one of the following symptoms: paroxysms of coughing; inspiratory whoop; or posttussive vomiting with no other apparent cause. In outbreak settings, the clinical case definition may be varied in some countries. However, reporting of cases may also depend on whether there has been a laboratory diagnosis. In some countries, contact with a confirmed case is sufficient to report a case.
Differences in Laboratory Practices.
Accepted laboratory diagnostic methods for pertussis include culture, PCR, serologic testing or Western blot. Most countries use culture methods for definitive laboratory confirmation of pertussis. PCR or serology is used in 13 of the 17 GPI countries and forms part of the case-based notification systems for 11 of these countries. In Argentina and Italy, laboratory confirmation is not required in the reporting of pertussis.
Different laboratory techniques are acceptable for the diagnosis of pertussis in different countries. In the United States, cases are confirmed based on established clinical, laboratory or epidemiologic criteria.40 Initially the laboratory criterion was culture-based, but in June 1996, this was revised to include a PCR assay which if positive for B. pertussis is confirmation of pertussis.41 However, PCR is not universally available.
Although the current epidemiology of pertussis in the Netherlands is based mainly on case reporting,42 a restrictive case definition was introduced in 1988 that included clinical symptoms and criteria for laboratory diagnosis. Laboratory confirmation is defined as either positive culture of B. pertussis or Bordetella parapertussis, or positive 2-point serology (ie, the detection of a significant >4-fold rise of IgG antibodies against PT and/or IgA antibodies against B. pertussis in paired sera). In April 1997, a positive PCR and positive 1-point serology were also accepted as laboratory confirmation.43 The National Health and Medical Research Council of Australia defines pertussis cases as “isolation of Bordetella pertussis from a clinical specimen, or elevated B. pertussis IgA in serum, or B. pertussis antigen in a nasopharyngeal specimen using immunofluorescence, with a history of a clinically compatible illness.”
The biologic diagnostic methods used in France are culture and PCR (direct methods), Western blot (routinely used, direct method) and enzyme-linked immunosorbent assay (ELISA, direct method used uniquely by the National Reference Center). Reimbursement is an issue in France, because it is offered for culture diagnosis and is recommended for infants, nonimmunized children and adolescents and adults during the first 3 weeks after the onset of cough. PCR (for which reimbursement is not available) is recommended for all patients during the first 3–4 weeks of the cough. Pertussis diagnosis by PCR is a more sensitive method than culture. For routine serologic diagnosis, Western blot is chosen rather than ELISA because reimbursement is offered for Western blot and not for ELISA.
In Germany, accepted methods for surveillance are culture, PCR and serologic testing. PCR testing for B. pertussis has been available in Switzerland since 1994, to verify all reported cases notified to the Swiss Sentinel Surveillance Network,44,45 whereas in the United Kingdom laboratory methodology is culture-based (serology and PCR methods are not available46). Likewise isolation of B. pertussis from a clinical specimen, elevated B. pertussis antibodies in serum and detection of B. pertussis antigen in a nasopharyngeal specimen using immunofluorescence are not available for use in the public health sector in Argentina.
Given the large amount of variation that exists among different countries for the diagnosis of pertussis, better standardized techniques for the identification and characterization of circulating pertussis isolates would give us a more accurate assessment of the amount of disease that is in circulation and would greatly improve our understanding of vaccine efficacy in immunization programs against pertussis disease.47
Underdiagnosis and Underreporting of Pertussis.
In many parts of the world, physicians in general, especially those who primarily care for adults, consider pertussis to be a disease that occurs only in infants and young children and is not a disease that is seen in the adolescent and adult populations. Because of this lack of awareness and the atypical clinical characteristics that are often associated with pertussis infection in adolescents and adults, underreporting is common. Many physicians do not suspect pertussis in adolescent and adult patients with prolonged cough, especially given that these patients are unlikely to consult the physician until some weeks after the beginning of the illness, by which time the probability of isolating B. pertussis from nasopharyngeal secretions is greatly reduced.
A recent study in the United Kingdom concluded that the true incidence of pertussis is probably 3 times higher than notification rates.33 Another study was conducted in a single U.K. community practice, where enhanced investigations, particularly serology, were undertaken in a group of patients (predominantly adults) presenting with severe or persistent cough. The data showed an incidence of 330 cases per 100,000 per annum, whereas national notification rates at that time were 4 per 100,000.35 Similarly studies from other countries have also shown that the incidence of pertussis in the adolescent and adult populations were much higher than previously recognized.36
APPROACHES TO PERTUSSIS PREVENTION
As it has become apparent that the epidemiology of pertussis is gradually shifting to the adolescent and adult age groups and pertussis cannot be controlled by the current immunization programs, many countries are augmenting their programs by having introduced, or are planning to introduce, an aP booster dose for use in children 6 years of age or in the adolescent age group (Table 1). As we continue to learn more about the epidemiology of pertussis disease, changes with regard to the current immunization programs will continue to occur globally in order for use to gain control of this disease.
In other countries, such as Argentina, whooping cough syndrome seems to be under control, at least in school children, as a consequence of improved coverage of immunization with diphtheria-tetanus toxoids-whole cell pertussis vaccine (coverage with 3 doses at the age of 1 year increased from 44.4% in 1980 to 87.1% in 1990).
In the Netherlands, a pertussis outbreak in 1996 was attributed partially to a possible mismatch between circulating strains and vaccine strains.26,48 In response to the outbreak, the amount of PT in the wP vaccine was enhanced in November 1997. In addition, in 1999, the immunization schedule was changed (to 2, 3, 4 and 11 months instead of 3, 4, 5 and 11 months) and in July 2001, a booster dose at the age of 4 years with an aP vaccine was introduced.49 As yet, the short and long term epidemiologic effects of these measurements are unclear; therefore various surveillance sources will be used to distinguish surveillance artifacts from real epidemiologic effects.
FUTURE RESEARCH
In infants and children, the clinical spectrum and age distribution of pertussis disease in countries with low rates of immunization have yet to be established. There is no consistent definition of mild or atypical pertussis in immunized children 4–9 years of age and no correlation of symptoms with age, immunization status, exposure, host and organism factors or passive antibody exposure. The long term effects of infant pertussis (eg, on central nervous system and pulmonary functions) remain to be established. Further research is also necessary to identify host/organism factors associated with severe disease and death (genetic, immunologic, cytokine response, transmission studies, duration of vaccine-induced immunity, etc), so that individuals at the highest risk of morbidity and mortality can be identified and targeted for prophylaxis and/or immunization and immunization scheduled may be optimized.
For older individuals, a consistent case definition needs to be established and applied across all regions and countries. This will help to establish the incidence of mild disease in each age group, including the clinical spectrum and incidence of complications in the elderly. Sensitive and specific laboratory tests for diagnosis are also needed and will improve the accuracy of diagnosis. As in children, identifying host/organism factors associated with severe disease or prolonged cough in the adult population will enable individuals at greatest risk to be identified. In addition, the immunogenicity and duration of adolescent and adult aP immunization warrants further research.
Specialist surveillance activities and mathematical models are also needed to estimate the burden of pertussis disease and the impact of interventions.
Finally more research is needed into the factors that may affect the impact of childhood pertussis on parents, such as education and socioeconomic status, and the household composition (eg, number of siblings, whether there is extended family to help with support).
SUMMARY
The use of effective vaccines against pertussis has significantly decreased the incidence of pertussis disease globally, and major epidemics have been largely eliminated. However, during recent years, there has been a reported increase in the number of cases in many countries, particularly among adolescents and adults, which is of special concern because adolescents and young adults are a recognized reservoir of infection for neonates and infants, who are at particular risk from pertussis-related morbidity and mortality.
Several factors make it difficult to define the increase in reported incidence of pertussis disease; there are wide disparities in national reporting systems, case definitions, laboratory practices and approaches to disease prevention, all of which make it almost impossible to make direct intercountry comparisons. Despite these international inconsistencies, it is widely agreed that underrecognition and underreporting of pertussis cases are common. It is important to gain a better understanding of the link between the different contributing factors and the observed increase in the incidence of pertussis disease, so that effective and consistent strategies can be developed to control pertussis disease on a global basis.
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Keywords:
pertussis; epidemiology
© 2005 Lippincott Williams & Wilkins, Inc.