The seroepidemiology of measles in Western Europe

The European Regional Office of WHO has targeted measles for elimination from the region in 2007. Large national, age and sex stratified serological surveys of measles antibody were conducted in seven Western European countries from 1994-8 as part of the European Seroepidemiology Network. Three patterns were observed in the country-specific measles seroprofiles, ranging from (very) low susceptibility (four countries) to high susceptibility (one country). Susceptibility levels amongst 2-4-year-olds ranged from 2.9 to 29.8%, in 5-9-year-olds from 2.5 to 25% and 10-19-year-olds from 2.1% to 13.9%. A country's susceptibility profile was highly associated with vaccine coverage for the first dose. First dose coverage ranged from 91 to 97.5% for low susceptibility countries, 75 to 85% for intermediate susceptibility countries and 55% for the high susceptibility country. Only the high susceptibility country still reports epidemic measles. In low susceptibility countries, which have achieved or are very close to measles elimination, the priority will be to maintain high MMR vaccine coverage in all geopolitical units for both vaccine doses. In moderate susceptibility countries there is still some endemic transmission, but also risk of outbreaks as pools of susceptibles accumulate. In the high susceptibility country the priority will be to increase infant vaccine coverage and reduce regional variation in coverage levels.     

The seroepidemiology of B. pertussis infection in Catalonia, Spain

A survey of the seroprevalence of pertussis antibodies in a representative sample of the population from Catalonia was carried out. Ninety-seven municipalities and 30 schools were randomly selected to recruit the 2126 subjects who participated in the study. A serum sample was obtained from all individuals participating in the study in order to determine levels of pertussis toxin (PT) and filamentous hemagglutinin (FHA) antibodies by ELISA test. Sociodemographic data were collected for all subjects. The prevalence of PT antibodies was 75% and that of FHA antibodies 89%. Significant increments were observed with age, both in the prevalence of PT (P < 0.0001) and of FHA (P = 0.018). Of the sociodemographic variables studied, only urban habitat was significantly associated to PT antibodies. The agreement observed among the two types of antibodies studied was weak (K = 0.264). Routine revaccination with the acellular vaccine in children over 7 years of age, in adolescents and adults seems a reasonable strategy to prevent the appearance of cases of pertussis in the community.     

The seroepidemiology of rubella in western Europe

Most of the countries in western Europe have now implemented mass infant rubella immunization programmes, instead of or in addition to selective vaccination in order to achieve the elimination of congenital rubella syndrome. The European countries Denmark, England and Wales, Finland, France, Germany, Italy and the Netherlands undertook large, national serological surveys collecting several thousand serum specimens during 1994-8. Antibodies against rubella virus were detected by a variety of enzyme immuno-assays. Comparability of the assay results was achieved by a standardized methodology. The age- and sex-stratified serological results were related to the schedules, coverage of rubella vaccination and the incidence in these countries. The results show widely differing levels of immunity to rubella both in the general population and in the specific age groups of males and females. A low rate (< 5%) of susceptibles in childhood and adolescents of both sexes was obtained only in Finland and the Netherlands. Countries such as Italy with only moderate coverage for the infant immunization programme currently have both high susceptibility levels in the general population and in the at-risk population. The likelihood is of continued epidemics of rubella with cases of congenital rubella syndrome. The continued implementation of selective vaccination will help to offset the impact of this ongoing transmission and to protect women on reaching childbearing age.     

Macrolide-resistant Bordetella pertussis infection in newborn girl, France

A macrolide antimicrobial drug was administered to a newborn with cough. On day 23 of hospitalization, macrolide-resistant Bordetella pertussis was isolated from nasopharyngeal aspirates. DNA sequencing and PCR-restriction fragment length polymorphism showed a 2047 A-to-G mutation in the 3 copies of the 23S rRNA gene. Monitoring for macrolide resistance is essential in infants <6 months of age.     

The seroepidemiology of pertussis in Australia during an epidemic period

Studying the epidemiology of pertussis and impact of differing vaccine schedules is difficult because of differing methods of case ascertainment. The advent of internationally standardized serological diagnosis for recent infection has allowed comparison of age-specific pertussis infection among European countries and was applied in Australia at the time of a major national epidemic. In 1997 and 1998, a nationally representative serum bank using residual sera from diagnostic laboratories was established. Measurement of pertussis toxin (PT) IgG level was conducted by a reference laboratory using an enzyme-linked immunosorbent assay standardized for a number of European countries. A titre of 125 EU/ml was interpreted as indicative of recent pertussis infection. The serological data were correlated with age, gender, region and disease epidemiology in Australia. The highest prevalence of recent pertussis infection was in the 5-9 years age group, and the lowest in 1-4 and 25-64 years age groups. In the 5-14 years age group, 29.7% (5-9 years) and 14.6% (10-14 years) of the sample had serological evidence of recent infection, correlating with the pattern of epidemic notifications. The 15- to 24-year-olds had similar high titres but the same notification rate as 25- to 44-year-olds, suggesting ascertainment bias may result in under-notification in the former age group. The prevalence of high titres observed was up to 20-fold higher than some European countries during a similar time period. Although vaccination has reduced the transmission of pertussis in the youngest and most vulnerable age group, pertussis is still endemic in Australia, particularly in older children and the elderly. The Australian vaccination schedule has been changed in an attempt to address this problem, by spacing doses more widely, with the fifth dose at 15-17 years of age. Seroepidemiology for pertussis offers the potential to compare patterns of pertussis between countries and examine the impact of vaccine schedule changes independent of notification and diagnostic bias.     

The outbreak that had to happen: Bordetella pertussis in north-west Western Australia in 1999

In late 1999, an outbreak of Bordetella pertussis occurred in a small town in North-West Western Australia. We undertook an investigation to describe the outbreak and to identify strategies to minimise the impact of future pertussis outbreaks in Australia. In November, people with respiratory symptoms were reviewed in an emergency pertussis clinic, which provided antibiotic treatment or prophylaxis. We conducted a school survey to enhance case ascertainment and followed up those attending the clinic by telephone. Fifty-nine cases of confirmed or probable B. pertussis infection were identified from 124 households (482 persons). Ages ranged from 5 months to 67 years, with children aged 9 to 11 years comprising 24 cases (41%). Early missed diagnoses and a school camp in September attended by 2 symptomatic children appeared to facilitate spread of infection, with the outbreak peak occurring in November. From immunisation records, childhood vaccine coverage in this sample was estimated at 96 per cent. All 21 cases of pertussis among the group under 10 years of age were at least partially vaccinated. There was only one laboratory confirmed case in the high-risk, under one-year of age category. Even in highly immunised populations periodic pertussis outbreaks are inevitable reflecting a vaccine efficacy of about 80 per cent and waning immunity with increasing age. Prevention of pertussis outbreaks depends not only on high vaccination coverage among young children but also early diagnosis and management of cases and their contacts. Clinicians should consider pertussis in the differential diagnosis of persistent cough illness in people of all ages--even those previously immunised.     

Serospecific protection of mice against intranasal infection with Bordetella pertussis

The ability of purified serospecific agglutinogens from Bordetella pertussis to protect mice against intranasal infection has been examined. Immunization with agglutinogen 2 protected mice against infection with 1.2.0 or 1.2.3 serotypes of B. pertussis, whereas immunization with agglutinogen 3 protected mice against infection with all serotypes. More importantly immunization with serospecific agglutinogen resulted in immune selection so that organisms recovered following infection did not express the immunizing antigen. The results are consistent with the suggestions that protection of children with whole cell pertussis vaccine is to some extent serospecific and that agglutinogens should be considered as constituents of acellular pertussis vaccines.     

Age-specific long-term course of IgG antibodies to pertussis toxin after symptomatic infection with Bordetella pertussis

To investigate the possible dependence on age of the rate of decline of IgG antibodies to pertussis toxin (IgG-PT) after natural infection with Bordetella pertussis we measured IgG-PT in follow-up sera of 121 patients (age 0-94 years) obtained after 123 episodes of B. pertussis infection. For analysis we applied a dynamic model for the inactivation of B. pertussis by the immune system. There were no significant differences in rise, peak and decline of IgG-PT between different age groups, although there was a tendency for a more rapid increase, a higher peak and a faster decline with increasing age. The IgG-PT cut-off of 100 U/ml for serodiagnosis of pertussis appeared valid in all age groups. A decline of IgG-PT to < 10 U/ml was associated with increased risk of re-infection with B. pertussis.     

Conversion of Bordetella pertussis to Bordetella parapertussis.

The epidemiological and drug susceptibility data on whooping cough suggested a possibility that Bordetella pertussis converts in some way to Bordetella parapertussis. To prove this, B. pertussis strain 75 was treated with N-methyl-N'-nitro-N-nitrosoguanidine and a mutant resistant to staphcillin v and eight mutants resistant to trimethoprim were isolated. The staphcillin V-resistant mutant of B. pertussis agreed with all of the criteria of B. parapertussis and the trimethoprim-resistant mutants also agreed with many of these criteria. Thus, a hypothesis is presented that B. parapertussis is a mutant of B. pertussis which appeared in nature probably by a selective pressure of antibiotics.     

Serotyping Bordetella pertussis strains

The serotyping scheme for Bordetella pertussis, developed in the 1950s, depends on the presence or absence of various strains of three major agglutinogens, two of which have been shown to be fimbrial proteins, and several minor agglutinogens, the biochemical nature of which is unknown. This article reviews the reasons for the confusion which has recently arisen over the nomenclature of the serotype antigens and proposes a simplified serotyping scheme based on the fimbrial components.     

An aerosol challenge model of Bordetella pertussis infection as a potential bioassay for acellular pertussis vaccines

Whole cell and five different types of acellular pertussis vaccine were assayed using a mouse aerosol challenge model which permitted delivery of a controlled, consistent dose of Bordetella pertussis to the lower respiratory tract. Using this system, the viable counts in the lungs of vaccinated mice were immunisation dose-dependent and allowed the protective capacity of different vaccine preparations to be distinguished. This model may thus provide the basis for a protection assay for pertussis vaccines. Comparison of acellular vaccines with a whole cell pertussis vaccine showed that the latter gave better active protection in mice but with a different dose-response relationship. Thus the two types of vaccine are not directly comparable in the same assay and require different reference standards. A pentavalent type acellular vaccine is suggested as a possible candidate standard for the acellular vaccine potency test. The results suggest that this aerosol challenge model has potential for use as a potency test for acellular pertussis vaccines.     

Comparison of acellular pertussis vaccines-induced immunity against infection due to Bordetella pertussis variant isolates in a mouse model

A significant increase in the incidence of pertussis in adolescents and adults has been observed in vaccinated populations. Concomitantly, emergence of novel pertussis toxin and pertactin types in circulating Bordetella pertussis isolates was noticed. In this study, immunity induced by acellular vaccines against infection due to isolates expressing different pertactin types and fimbriae was monitored in a mouse model. In accordance with previous studies, the effect of a bicomponent DTPa vaccine on bacterial clearance was lower when compared with tri- or pentavalent DTPa vaccines. Whatever the isolates used to infect mice, the tri- or pentavalent DTPa vaccines were both efficacious in inducing immunity that resulted in clearance of infection. These findings suggest that re-emergence of pertussis might not be related to emergence of isolates escaping vaccine protection. The present study reduces potential concerns about acellular vaccine efficacy, but frequent monitoring of protection and surveillance of the evolution of the B. pertussis population remains of particular importance.     

Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence

Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetella pertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation.