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.Pertussis, or whooping cough, was historically considered a serious disease of childhood. Because of the high burden of morbidity and mortality associated with pertussis (1), routine vaccination programs were implemented in many developed countries during the 1940s and 1950s that led, in some instances, to a 99% reduction in reported incidence (2, 3). The success of these vaccination programs in reducing pertussis notifications led to optimism over its potential eradication, a sentiment that has since been replaced by widespread concern following high-profile outbreaks in populations with long-standing immunization, with the United States and Australia arguably experiencing the largest impacts of these resurgences (4–7).Recent attempts to explain contemporary pertussis epidemiology have largely attributed the resurgence to the immunological consequences of vaccination and natural infection. In turn, uncertainty surrounding the role of a number of potentially key players has been highlighted, including the duration of naturally acquired and vaccine-induced immunity (8–11), limited natural immune boosting following the introduction of vaccine programs (10, 12), loss of vaccine efficacy resulting from antigenic divergence (13, 14), and, crucially, whether vaccines prevent pertussis transmission or simply reduce the incidence of disease (15–17). To assess the population-level consequences of immunity, we confront high-resolution incidence reports in Thailand with modern techniques for statistical inference to provide a mechanistic interpretation of the transmission impact of vaccination on pertussis immunity in Thailand. Using a series of competing transmission models, we demonstrate that declines in pertussis incidence coinciding with increases in vaccine uptake between 1984 and 1989 arose following reduction in pertussis circulation. Indeed, the maximum-likelihood estimate associated with each model points to a small or negligible transmission contribution of repeat infections, with vaccination effectively generating herd immunity.To verify our conclusions, we use several empirical metrics to demonstrate that there is a true increase in herd immunity. We document dramatic changes in patterns of pertussis epidemiology, and quantify shifts in population measures of herd immunity. We report that over the time span of this study, there was a drastic decline in reported pertussis cases from Thailand, an effect that is especially pronounced among infants. Coincident with reduced incidence, we also found a rise in the critical community size. Overall, these observations are consistent with reduced pertussis circulation in Thailand.Our findings shed light on key hotly debated aspects of pertussis epidemiology. First, these results indicate that current pediatric immunization programs in Thailand have successfully reduced pertussis transmission. Second, there is no empirical evidence for a resurgence in Thailand, with circulation of Bordetella pertussis effectively controlled by current vaccines. Finally, repeat infections appear to play an insignificant role in pertussis epidemiology in Thailand.     

Rationale for pertussis booster vaccination throughout life in Europe

Although the introduction of universal pertussis immunisation in infants has greatly reduced the number of reported cases in infants and young children, disease incidence has been increasing in adolescents and adults in recent years. This changing epidemiological pattern is probably largely attributable to waning immunity after natural infection or vaccination. Furthermore, improved diagnostic testing, active surveillance, changes in disease susceptibility, vaccine characteristics, and increased awareness of the disease might also be contributing factors. Susceptibility to pertussis in adolescents and adults results not only in direct morbidity in these age groups, but also poses a transmission risk to susceptible non-immune infants who are often too young to be vaccinated. Because vaccination schedules vary across Europe, we review the pertussis situation in this region and propose considerations for use of pertussis booster vaccinations at different ages to reduce individual morbidity and transmission from present rates and increase herd protection.     

From the Cover: Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.Pertussis is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis (1, 2). Infection results in a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to a severe cough illness accompanied by marked leukocytosis and the hallmark inspiratory whoop and posttussive emesis (3). Because acellular pertussis vaccines replaced whole-cell vaccines in the 1990s, pertussis has reemerged at a startling rate in the United States despite nationwide vaccine coverage in excess of 95% (4). With a 50-y high of 42,000 reported cases in the United States in 2012, pertussis is the most common of the vaccine-preventable diseases (5). This resurgence is mirrored throughout the industrial world despite similar high rates of vaccination (6–9). Two common hypotheses for the resurgence have been proposed: i) current acellular pertussis vaccines (aP) vaccines are less effective than the whole-cell pertussis (wP) vaccines they replaced and ii) aP-induced immunity wanes more quickly than anticipated (10–13). However, pertussis resurgence is not completely understood (14, 15).Hampering our ability to counteract this resurgence is the fact that pertussis pathogenesis and immunity to natural infection have not been well studied in humans because typical pertussis is sporadic given high rates of vaccination in developed countries. Human challenge studies have been proposed but never conducted due to a variety of logistical and ethical problems including the potential for severe disease, the lack of an effective therapeutic for established disease, and the highly contagious nature of pertussis. Although a variety of small-animal models have been used to study pertussis, none of them adequately reproduce the human disease (16). To address this gap, we recently developed a nonhuman primate model of pertussis using baboons (Papio anubis) and found the disease is very similar to severe clinical pertussis. Upon challenge, baboons experience 2 wk of heavy respiratory colonization and leukocytosis peaking between 30,000–80,000 cells/mL, similar to the range in pertussis-infected infants (1, 17). In addition, baboons experience a paroxysmal cough illness characterized by repeated fits of 5–10 coughs. The coughing fits last on average >2 wk in the baboon, although this is less than some severely infected children, where the cough can last up to 12 wk (1, 17). We also characterized airborne transmission of B. pertussis from infected to naïve animals, which is the route of transmission postulated to occur between humans (18). Because this is the only model of pertussis to reproduce the cough illness and transmission of the human disease, we believe it provides the unique opportunity to test our hypothesis that aP vaccines fail to prevent B. pertussis colonization, thus enabling transmission among vaccinated individuals.Using this model we have confirmed that, as in humans, aP vaccines provide excellent protection against severe disease in baboons. However, aP vaccines do not prevent colonization following direct challenge or infection by transmission. In addition, aP-vaccinated animals are capable of transmitting disease to naïve contacts. By comparison, wP-vaccinated animals cleared infection significantly more quickly than aP-vaccinated or naïve animals. We also found that aP vaccination induces T helper 2 (Th2) and T helper 1 (Th1) immune memory responses, whereas infection and—to a lesser extent—wP vaccination induce Th17 and Th1 memory. Our results suggest that in addition to the potential contribution of reduced efficacy and waning immunity of aP, the inability of aP to prevent colonization and transmission provides a plausible explanation for pertussis resurgence.     

Combating pertussis resurgence: One booster vaccination schedule does not fit all

Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine “leakiness.” For scenarios I–IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.Reconciling the historical successes of routine infant pertussis vaccination programs in reducing incidence (1–3) with the recent resurgence in a number of highly vaccinated countries (4, 5) has proved challenging, especially in the context of the global heterogeneity in contemporary pertussis epidemiology (6). A variety of explanations for pertussis resurgence have been proposed, ranging from improvements in surveillance and diagnostics (7) to reduced protection afforded by vaccination, whether due to the waning of vaccine-derived immunity (8), the evolution of the etiological agent (the bacterium Bordetella pertussis) (9), the switch from whole-cell to acellular vaccines (10), or the invasion and spread of Bordetella congeners (11). It has also been demonstrated that even in the absence of changes in the nature of transmission, vaccine, or reporting, pertussis resurgence might be expected in some countries as an inevitable consequence of insufficient historical vaccination (12).Disentangling the many pathways to pertussis resurgence is particularly difficult because pertussis immunity and, in particular, vaccine-derived immunity are not well understood (13). With no known reliable serological marker of protection (14), the properties of infection- and vaccine-derived immunity against pertussis must be inferred indirectly (15). However, the models of pertussis immunity that best reconcile individual-level clinical data (16) and population-level incidence data (17), respectively, are strikingly different. Data from serological studies (16, 18) and animal models (19) paint a picture of a vaccine that protects against disease for a limited duration and may afford little protection against transmission. In contrast, large-scale pertussis incidence data from countries such as Denmark (20), England and Wales (21), Thailand (17), and Sweden (22, 23) are consistent with long-lasting vaccine-derived immunity and sufficiently little transmission among vaccinated and previously infected individuals as to generate herd immunity.Despite the discussion surrounding the efficacy and epidemiological effectiveness of pertussis vaccines, several countries experiencing increased pertussis incidence have supplemented their existing routine infant immunization schedule with additional booster doses (24). Importantly, the timing and number of recommended booster doses vary considerably among countries. To examine the conundrum of how best to mitigate pertussis, we used a validated age-stratified transmission model integrated within a genetic algorithm (GA) framework. Our aim is to identify, assuming different causes of pertussis circulation, booster schedules that afford the greatest reduction in disease burden for the least economic cost.     

Susceptibility to Resurgent COVID-19 Outbreaks Following Vaccine Rollouts: A Modeling Study

Using the recently proposed Susceptible–Asymptomatic–Infected–Vaccinated–Removed (SAIVR) model, we study the impact of key factors affecting COVID-19 vaccine rollout effectiveness and the susceptibility to resurgent epidemics. The SAIVR model expands the widely used Susceptible–Infectious–Removed (SIR) model for describing epidemics by adding compartments to include the asymptomatic infected (A) and the vaccinated (V) populations. We solve the model numerically to make predictions on the susceptibility to resurgent COVID-19 epidemics depending on initial vaccination coverage, importation loads, continuing vaccination, and more contagious SARS-CoV-2 variants, under persistent immunity and immunity waning conditions. The parameters of the model represent reported epidemiological characteristics of the SARS-CoV-2 virus such as the disease spread in countries with high levels of vaccination coverage. Our findings help explain how the combined effects of different vaccination coverage levels and waning immunity lead to distinct patterns of resurgent COVID-19 epidemics (either surges or endemic), which are observed in countries that implemented different COVID-19 health policies and achieved different vaccinated population plateaus after the vaccine rollouts in the first half of 2021.     

Recent developments in pertussis

Pertussis causes nearly 300,000 deaths in children every year. Most deaths take place in developing countries, but the infection remains a priority everywhere. Pertussis vaccination protects infants and children against death and admission to hospital, but breakthrough disease in vaccinated people can happen. In high-mortality countries, the challenge is to improve timeliness and coverage of childhood vaccination and surveillance. In regions with low mortality and highest coverage, pertussis is frequently the least well-controlled disease in childhood vaccination programmes. Some countries have reported a rise in pertussis in adolescents, adults, and pre-vaccination infants, but how much these changes are real or a result of improved recognition and surveillance remains uncertain. In response, several countries have introduced adolescent and adult acellular pertussis vaccine boosters. The effect so far is unknown; assessment is impeded by poor data. Uncertainties still persist about key variables needed to model and design vaccination programmes, such as risk of transmission from adults and adolescents to infants. New vaccination strategies under investigation include vaccination of neonates, family members, and pregnant women.     

La coqueluche en pratique en 2006

Universal vaccination of infants against pertussis has transformed the epidemiology of the disease. Pertussis has however become frequent, although not often diagnosed, in adolescents and adults and thus contributes to permanent transmission of Bordetella pertussis in France and contamination of young infants at risk of severe disease. Control of transmission of pertussis in France necessitates reinforcement of vaccination with late boosters in adolescents and adults and, in addition, education of physicians to recognize and treat early cases of pertussis, especially in adolescents and adults with a persistant or chronic cough, and to take appropriate prophylactic measures (antibiotics and recall vaccination) of those in contact with confirmed cases. Effective treatment does little to reduce symptoms but it does reduce transmission. Macrolides are the recommended treatment for pertussis.     

Prevention of pertussis

Pertussis (whooping cough) is an acute respiratory disease caused by Bordetella pertussis. It occurs worldwide and is an important cause of morbidity and mortality in areas where immunization rates are low, particularly among children less than 1 year of age. The characteristic presentation of pertussis is paroxysmal coughing followed by a long inspiratory effort that produces the classic whoop. Lymphocytosis is frequently present. Complications include pneumonia and seizures secondary to hypoxia. The paroxysmal and convalescent stages of the illness can each last several weeks. Transmission occurs readily by respiratory droplets, and atypical or mild cases in older children and adults can be important in spread of the infection. Isolation, early erythromycin therapy, and erythromycin prophylaxis can reduce transmission, but vaccination is the primary means of control. An inactivated whole cell suspension of the bacterium has been an effective vaccine for protecting against pertussis since the 1950s, but whole cell vaccine may allow mild infections to occur and has been associated with local and systemic reactions that have eroded public acceptance. Component or acellular pertussis vaccines that are less reactogenic have been in use in Japan since 1981 and appear to be effective there. Development of an acellular preparation that is equally or more efficacious than whole cell vaccine may be possible, but clinical trials for measurement of protection against pertussis are difficult and trials with new pertussis vaccines will have to be carefully performed to avoid the controversies generated by earlier trials.     

Immune response to postprimary tuberculosis in mice: Mycobacterium tuberculosis and Miycobacterium bovis bacille Calmette-Guérin induce equal protection

We addressed the question of whether protective immunity induced by natural infection with Mycobacterium tuberculosis and that induced by vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) differ in the murine model. We infected mice with M. tuberculosis Erdman, cured them by chemotherapy, and subsequently reinfected them with a low dose of M. tuberculosis H37Rv. The course of tuberculosis was compared with that in mice previously vaccinated with BCG Danish 1331. Protection against postprimary M. tuberculosis infection did not differ significantly between the 2 groups. After challenge infection, numbers of interferon- gamma -positive splenocytes did not differ between mice with primary infection and vaccinated mice. Splenocytes from primary M. tuberculosis-infected mice conferred marginally higher protection than did those from BCG-vaccinated mice. Serum transfer did not protect against reinfection in either group. Our data emphasize that natural infection with M. tuberculosis and vaccination with BCG do not differ in their capacity to induce protective immunity against tuberculosis and support the notions that reinfection contributes to the development of active disease and that any novel vaccine against tuberculosis has to perform better than both vaccination with BCG and immunity evoked by natural infection.     

Pertussis – eine impfpräventable Erkrankung

Pertussis (whooping cough) is caused by Bordetella pertussis and B. parapertussis. It is a purely respiratory infection, which can be highly contagious. In countries with vaccination programs, the main targets are young infants, older non-vaccinated children, adolescents and adults. The disease remains endemic and cyclical worldwide, even in countries with a sustained high vaccination coverage. Pertussis is a notifiable disease in Germany but epidemiological data might not reflect the true burden of the disease. The main symptom is coughing for prolonged periods, which can be paroxysmal. The disease can take a severe course in infants with a possible fatal outcome but adults can also have a high rate of complications. Pertussis can be diagnosed by detecting Bordetella DNA by PCR or by detection of IgG antibodies to pertussis toxin. Antibiotics, such as macrolides can stop transmission but might not relieve the symptoms. Infant vaccination, which in Germany is carried out with four doses of combination vaccines with acellular pertussis components, can prevent the majority of cases. As immunity after infection and vaccination is not permanent, additional strategies comprising school entry boosters and the vaccination of adolescents and adults, as well as vaccinating special risk groups, such as pregnant women are recommended.     

Cost-effectiveness of hepatitis C virus antiviral treatment for injection drug user populations

Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in most developed countries. HCV antiviral treatment (peginterferon-α + ribavirin) has been shown to be cost-effective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injecting drug users (IDUs) as compared with treating ex/non-IDUs or no treatment. A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after treatment failure, potential reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes measured in quality adjusted life years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic prevalence settings, with ICERs compared with no treatment of ￡ 521 and ￡ 2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared with no treatment of ￡ 6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared with ex/non-IDUs are halved. CONCLUSION: Despite the possibility of reinfection, the model suggests providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up and its impact on prevalence is warranted.     

Pertussis of adults and infants

Bordetella pertussis continues to circulate even in populations where a high vaccine coverage of infants and children is achieved. Cases in adolescents and adults are reported with increasing frequency in many countries. Adults are a reservoir for infections in very young infants, in whom pertussis may be severe and life-threatening. The salient clinical feature of pertussis in adolescents and adults is prolonged coughing, and recognising that pertussis does occur in these age groups is the most important step in its diagnosis. A laboratory diagnosis can be made by bordetella-PCR from nasopharyngeal swabs or secretions and by detection of antibodies, mainly to pertussis toxin; laboratory diagnosis is, however, not well standardised. Vaccination of adolescents and adults is now possible with acellular pertussis vaccines, which are well tolerated, immunogenic, and effective. Adolescent boosters and the vaccination of health-care workers are already included in vaccination calendars in some countries. Vaccine-recommending bodies and national health-care organisations must have locally relevant information on the transmission of pertussis from adults to infants to be able to make decisions on the advisability, feasibility, and priority for booster immunisation against pertussis.     

Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine

Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity.     

Patterns of susceptibility in an outbreak of Bordetella pertussis: Evidence from a community-based study

OBJECTIVE:

To describe an outbreak of Bordetella pertussis and to assess which factors were associated with the development of clinical pertussis in children and adults during the outbreak.

DESIGN:

A case series was described to define the epidemiology of the pertussis outbreak. A school-based survey of children was used to measure the incidence of clinical pertussis over the previous six months. Vaccination records from the local public health facility were used to look at the relationship between age and vaccination parameters, and susceptibility to clinically diagnosed pertussis. A cross-sectional survey of teachers, parents and some hospital workers was used to assess these associations in adults.

SETTING:

An outbreak of pertussis in an isolated northern community in British Columbia.

POPULATION STUDIED:

All children in the community who attend daycare, kindergarten or school, and their parents were surveyed. In addition, some health care workers and mothers of preschool children were surveyed.

MAIN RESULTS:

A total of 31 suspected cases of pertussis were identified over a three-month period. Ninety per cent of the affected children who had available vaccination records had received four or five doses of pertussis vaccine. Sixty per cent of the town''s 209 children returned completed surveys. Of these, 69% had available vaccination records. Thirty-six children (28%) reported symptoms that fit the case definition for pertussis over the previous three months. Attack rates were highest for the group of children aged 10 to 14 years. In a multivariate logistic regression analysis, receiving prophylactic medication and an increased number of years from the last vaccine dose were found to be significant predictors for developing pertussis. Thirty-four per cent of the estimated 291 adults in the community returned completed surveys. The attack rate of pertussis in the adults was only 9%. Being a member of the school staff and/or having a household contact with pertussis were significant predictors of developing pertussis.

CONCLUSIONS:

Immunity to pertussis appears to wane during childhood. Peak susceptibility appears to be during early adolescence. Adults do not seem to be at greater risk than adolescents for developing the disease, but it seems unlikely that this is due to better immunity. Rather, it is probably related to a lower risk of exposure to pertussis and a lower rate of progression to symptomatic disease when adults are infected.Key Words: Immunity, Pertussis, VaccinationVaccination against Bordetella pertussis has resulted in a dramatic reduction in the incidence of this disease in Canada. Outbreaks of pertussis, however, still occur. While many outbreaks reported elsewhere occur in populations where vaccination rates have declined, many others occur in populations with high vaccination coverage (1,2). This has not changed with the introduction of the acellular pertussis vaccine. The reasons for this are not clear, but waning immunity and the transmission of disease from adolescents and adults to younger children have been proposed as possible mechanisms (3,4). An additional constraint in studying this problem is that there is no known level of antibody that can be shown to be protective against developing pertussis (5).The idea of waning immunity has been challenged recently. De Serres and colleagues (6) found that the attack rates were the same in adolescent (12%) and adult (11%) household contacts of pertussis index cases. The authors (6) felt that this similar attack rate was more consistent with a decreasing proportion of susceptible subjects with age and with longlasting immunity. They did not suggest that this immunity comes solely from vaccination, but more likely from subclinical boosting from endemic disease. Clearly, this has implications as to the utility of introducing an adolescent booster dose to reduce further the incidence of disease in the population.In May 2000, an outbreak of pertussis was reported in an isolated northern community in British Columbia. Pertussis outbreaks have been known to occur in three- to five-year cycles in British Columbia. The last such outbreak occurred in 1996 and 1997, and resulted in more than 1100 reported cases. Increased rates of pertussis transmission had already been reported throughout the province since January 2000 (British Columbia Centre for Disease Control, internal report). By mid-May 2000, nearly 400 cases had been reported to the British Columbia Centre for Disease Control. Rates of infection were highest among young adolescents (aged 10 to 14 years), followed by older children (aged seven to nine years). The Northwest Coastal Health Services Society (the region that includes the town of Stewart) was not among those health regions that had previously reported increased numbers of cases.The town of Stewart, which has a population of approximately 500 people, has one health centre for both curative and preventive care, and is more than 150 km from the nearest settlement (excluding the hamlet of Hyder, Alaska, which is only 1.6 km away). There are three schools - a public primary school, a public secondary school and a small, private Christian school. The local health region and the Department of Health Care and Epidemiology at the University of British Columbia initiated an investigation of the pertussis outbreak in Stewart. It was thought that the relative isolation of the community and its small size would allow investigators to see whether immunization status, age and the length of time from the last vaccine dose would significantly affect disease attack rates. It was hoped that vaccination records for most of the town''s children could be verified and then compared with the results of a school-based survey for pertussis-like symptoms. As well, a survey of adults was undertaken to determine whether symptoms also occurred in this susceptible group, and whether this was related to recalled vaccination history. Disease control measures (7), including erythromycin prophylaxis of close contacts of index cases and enhanced surveillance among symptomatic individuals, had already been implemented before the present study was undertaken and were not interrupted during the course of the study.     

Tos ferina en España. Situación epidemiológica y estrategias de prevención y control. Recomendaciones del Grupo de Trabajo de Tos ferina

A large increase of pertussis incidence has been observed in recent years in countries with high vaccination coverage. Outbreaks of pertussis are increasingly being reported. The age presentation has a bipolar distribution: infants younger 6 months that have not initiated or completed a vaccination schedule, and adolescents and adults, due to the lost of natural or vaccine immunity over time. These epidemiological changes justify the need to adopt new vaccination strategies in order to protect young infants and to reduce pertussis incidence in all age groups.     

Modeling rotavirus strain dynamics in developed countries to understand the potential impact of vaccination on genotype distributions

Understanding how immunity shapes the dynamics of multistrain pathogens is essential in determining the selective pressures imposed by vaccines. There is currently much interest in elucidating the strain dynamics of rotavirus to determine whether vaccination may lead to the replacement of vaccine-type strains. In developed countries, G1P[8] strains constitute the majority of rotavirus infections most years, but occasionally other genotypes dominate for reasons that are not well understood. We developed a mathematical model to examine the interaction of five common rotavirus genotypes. We explored a range of estimates for the relative strength of homotypic vs. heterotypic immunity and compared model predictions against observed genotype patterns from six countries. We then incorporated vaccination in the model to examine its impact on rotavirus incidence and the distribution of strains. Our model can explain the coexistence and cyclical pattern in the distribution of genotypes observed in most developed countries. The predicted frequency of cycling depends on the relative strength of homotypic vs. heterotypic immunity. Vaccination that provides strong protection against G1 and weaker protection against other strains will likely lead to an increase in the relative prevalence of non-G1 strains, whereas a vaccine that provides equally strong immunity against all strains may promote the continued predominance of G1. Overall, however, disease incidence is expected to be substantially reduced under both scenarios and remain below prevaccination levels despite the possible emergence of new strains. Better understanding of homotypic vs. heterotypic immunity, both natural and vaccine-induced, will be critical in predicting the impact of vaccination.     

Adult immunization--a neglected issue in Southeast Asia

Adult immunization is a neglected and underpublicised issue in Southeast Asia. Vaccine-preventable diseases cause unnecessary morbidity and mortality among adults in the region, while inadequate immunization results in unnecessary costs, including those associated with hospitalization, treatment, and loss of income. Childhood vaccination coverage is high for the EPI diseases of diphtheria, tetanus and pertussis; however, unvaccinated, undervaccinated, and aging adults with waning immunity remain at risk from infection and may benefit from vaccination. Catch-up immunization is advisable for adults seronegative for hepatitis B virus, while immunization against the hepatitis A and varicella viruses may benefit those who remain susceptible. Among older adults, immunization against influenza and pneumococcal infections is likely to be beneficial in reducing morbidity and mortality. Certain vaccinations are also recommended for specific groups, such as rubella for women of child-bearing age, typhoid for those travelling to high-endemicity areas, and several vaccines for high-risk occupational groups such as health care workers. This paper presents an overview of a number of vaccine-preventable diseases which occur in adults, and highlights the importance of immunization to protect those at risk of infection.     

Impfungen im Alter

Respiratory tract infections occur more frequently in the elderly and more often show a severe course, in particular community-acquired pneumonia and influenza. Within the last decade an increase in pertussis infections in the elderly has been reported from many industrialized countries. There are licensed vaccinations against influenza, pertussis and some of the 91 known pneumococcal serotypes. Despite the fact that clinical studies have clearly demonstrated the benefit of vaccination in the elderly, vaccine efficacy is limited because of the aging immune system. Immunosenescence can at least in part be compensated by special vaccination strategies (e.g. adjuvants, intradermal injection, repeated vaccinations and conjugated vaccines). This review discusses the recommendations for vaccination against respiratory pathogens (e.g. pneumococci, influenza and pertussis) in the elderly.     

Neutralizing antibodies to pertussis toxin in whooping cough

The development and duration of neutralizing antibodies (antitoxin) to pertussis toxin were studied in 38 patients with culture-verified infections due to Bordetella pertussis and one patient with infection due to Bordetella parapertussis. An in vitro neutralization test in microplate culture of Chinese hamster ovary cells was used. An antitoxin response was recorded in 36 patients, the exceptions being two patients treated early with erythromycin (one of whom developed clinical pertussis two years later) and the patient with infection due to B. parapertussis. A long-term follow-up for several months to several years after disease showed maintenance of high antitoxin levels. These results are in accordance with the hypothesis that antibodies to pertussis toxin mediate long-term immunity to whooping cough.     

Consensus on the clinical and microbiologic diagnosis of Bordetella pertussis, and infection prevention. Expert Group on Pertussis Vaccination

Pertussis continues to be responsible for a significant disease burden worldwide. Although immunization practices have reduced the occurrence of the disease among children, waning vaccine- and infection-induced immunity still allows the disease to affect adolescents and adults who, in turn, can transmit the disease to non-immunized or partially immunized infants. This document is the result of a meeting in Mexico City of international experts who analyzed recent medical information in order to establish the current status of the epidemiology, diagnosis and surveillance of pertussis and, especially, the value of the dTpa booster dose in adolescents and adults as a pertussis prevention strategy in Mexico.