RESUMO
BACKGROUND: Pertussis (whooping cough) remains a public health problem despite extensive vaccination strategies. Better understanding of the host-pathogen interaction and the detailed B. pertussis (Bp) target recognition pattern will help in guided vaccine design. We characterized the specific epitope antigen recognition profiles of serum antibodies ('the reactome') induced by whooping cough and B. pertussis (Bp) vaccines from a case-control study conducted in 1996 in infants enrolled in a Bp vaccine trial in Sweden (Gustafsson, NEJM, 1996, 334, 349-355). METHODS: Sera from children with whooping cough, vaccinated with Diphtheria Tetanus Pertussis (DTP) whole-cell (wc), acellular 5 (DPTa5), or with the 2 component (a2) vaccines and from infants receiving only DT (n=10 for each group) were tested with high-content peptide microarrays containing 17 Bp proteins displayed as linear (n=3175) peptide stretches. Slides were incubated with serum and peptide-IgG complexes detected with Cy5-labeled goat anti-human IgG and analyzed using a GenePix 4000B microarray scanner, followed by statistical analysis, using PAM (Prediction Analysis for Microarrays) and the identification of uniquely recognized peptide epitopes. RESULTS: 367/3,085 (11.9%) peptides were recognized in 10/10 sera from children with whooping cough, 239 (7.7%) in DTPwc, 259 (8.4%) in DTPa5, 105 (3.4%) DTPa2, 179 (5.8%) in the DT groups. Recognition of strongly recognized peptides was similar between whooping cough and DPTwc, but statistically different between whooping cough vs. DTPa5 (p<0.05), DTPa2 and DT (p<0.001 vs. both) vaccines. 6/3,085 and 2/3,085 peptides were exclusively recognized in (10/10) sera from children with whooping cough and DTPa2 vaccination, respectively. DTPwc resembles more closely the whooping cough reactome as compared to acellular vaccines. CONCLUSION: We could identify a unique recognition signature common for each vaccination group (10/10 children). Peptide microarray technology allows detection of subtle differences in epitope signature responses and may help to guide rational vaccine development by the objective description of a clinically relevant immune response that confers protection against infectious pathogens.
Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Reconhecimento Automatizado de Padrão , Vacina contra Coqueluche/imunologia , Análise Serial de Proteínas/métodos , Coqueluche/sangue , Coqueluche/imunologia , Sequência de Aminoácidos , Criança , Humanos , Imunoglobulina G/sangue , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/imunologia , Proteoma/metabolismo , VacinaçãoRESUMO
Between 1998 and 2009, Bordetella pertussis clinical isolates were collected during three periods, i.e., 1998 to 2001 (n = 102), 2004 to 2005 (n = 154), and 2007 to 2009 (n = 140), from nine countries with distinct vaccination programs, i.e., Denmark, Finland, France, Germany, The Netherlands, Norway, Poland, Sweden, and the United Kingdom. Pulsed-field gel electrophoresis (PFGE) analysis was performed according to standardized recommendations for epidemiological typing of B. pertussis. There were 81 different PFGE profiles, five of which (BpSR3, BpSR5, BpSR10, BpSR11, and BpSR12) were observed in 61% of the 396 isolates and shown to be predominant in almost all countries. The major profile, BpSR11, showed a decreasing trend from 25% to 30% in 1998 to 2005 to 13% in 2007 to 2009, and there were increases in BpSR3 and BpSR10 from 0% and 8% to 21% and 22%, respectively. One difference between these profiles is that BpSR11 contains isolates harboring the fim3-2 allele and BpSR3 and BpSR10 contain isolates harboring the fim3-1 allele. The total proportion of the five predominant profiles increased from 44% in 1998 to 2001 to 63% in 2004 to 2005 to 70% in 2007 to 2009. In conclusion, common PFGE profiles were identified in B. pertussis populations circulating in European countries with different vaccination programs and different vaccine coverages. These prevalent isolates contain the novel pertussis toxin promoter ptxP3 allele. However, there is evidence for diversifying selection between ptxP3 strains characterized by distinct PFGE profiles. This work shows that, even within a relatively short time span of 10 years, successful isolates which spread through Europe and cause large shifts in B. pertussis populations may emerge.
Assuntos
Bordetella pertussis/classificação , Eletroforese em Gel de Campo Pulsado , Coqueluche/microbiologia , Bordetella pertussis/genética , Bordetella pertussis/isolamento & purificação , Pré-Escolar , Análise por Conglomerados , Europa (Continente)/epidemiologia , História do Século XX , História do Século XXI , Humanos , Lactente , Recém-Nascido , Vacina contra Coqueluche/imunologia , Filogenia , Coqueluche/epidemiologia , Coqueluche/história , Coqueluche/prevenção & controleRESUMO
A real-time PCR method targeting the Bordetella pertussis IS481 gene fragment was evaluated in a vaccine trial setting in which real-time PCR results could be validated against culture and serology results. Two commonly used DNA extraction methods, Amplicor Respiratory Preparation kit and the QIAamp DNA Mini Kit, were compared. An approximately 50-fold higher sensitivity was achieved using the Amplicor kit. 89 of 276 aspirates analysed with the IS481 real-time PCR were positive. Interestingly, six of these were culture negative and came from serology-negative patients. Defining true positive cases either as culture-positive or as PCR-positive cases that had been confirmed with a serology-positive result or verified with a newly constructed recA PCR, the sensitivity and specificity of the IS481 real-time PCR were 89% and 98%, respectively. This study confirms the specificity and high diagnostic sensitivity of IS481-based PCR methods for diagnosis of B. pertussis.
Assuntos
Bordetella pertussis/isolamento & purificação , DNA Bacteriano/análise , Vacina contra Coqueluche , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Coqueluche/diagnóstico , Bordetella pertussis/genética , Ensaios Clínicos como Assunto , Primers do DNA , Humanos , Sensibilidade e Especificidade , Coqueluche/prevenção & controleRESUMO
In a surveillance programme undertaken from 1997 through 2004, Bordetella pertussis isolates and clinical information were collected after introduction of acellular pertussis vaccines (Pa) in 1996. Changes in the B. pertussis population were studied in three incidence peaks: 1999-2000, 2002 and 2004. Available isolates from 158 fully vaccinated children representing all of Sweden, plus 37 from the Gothenburg area 2003-2004, were analysed by pulsed-field gel electrophoresis (PFGE), serotyping and sequencing of the virulence factor genes pertussis toxin subunits 1 and 3 (ptxA, ptxC), pertactin (prn), tracheal colonisation factor (tcfA) and fimbria3 (fim3). Allele ptxA1 was found in all isolates. There was a statistically significant increasing trend in three out of five studied genes, ptxC, prn and tcfA, and for a fourth, Fim3, if Gothenburg strains were included. The PFGE profile BpSR11 appearing in the 1999-2000 peak dominated by >or=23% during the entire period, bringing with it the allele combination 1/2/2/2/B (ptxA1/ptxC2/prn2/tcfA2/fim3B). Other BpSR11-related profiles with the same allele combination and more than 82% similarity--BpSR5 in the 2002 peak and BpSR12 in the 2004 peak--appeared with an increasing trend. Although vaccination with Pa has reduced disease, new variants have emerged representing clones surviving in the immunized population.
Assuntos
Bordetella pertussis/isolamento & purificação , Vacina contra Coqueluche/administração & dosagem , Coqueluche/epidemiologia , Coqueluche/prevenção & controle , Alelos , Bordetella pertussis/genética , Pré-Escolar , DNA Bacteriano/análise , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Incidência , Masculino , População , Sorotipagem , Suécia , Vacinação , Virulência , Fatores de Virulência de Bordetella/genéticaRESUMO
In Sweden, acellular pertussis vaccines were introduced at 3, 5 and 12 months of age in 1996, after a 17-year hiatus without pertussis vaccination. An intensified surveillance of pertussis was initiated in October 1997, including collection of clinical data as well as Bordetella pertussis isolates in culture or PCR-confirmed cases of pertussis among children born from January 1996 to September 2004. We analysed the association of pulsed-field gel electrophoresis (PFGE) profile and serotype with severity of disease for all children followed during the first 7 years of the project. There were in all 927 children for whom both clinical information and strain characterisation data were available. 260 of these children were hospitalised during the pertussis episode. When duration of hospital stay was compared between children with different groups of strains, characterised by PFGE profile or serotype, there was a significantly higher proportion of children with long duration of hospital stay in the most frequent PFGE profile group (BpSR11) compared to the PFGE group of all other profiles (p=0.041). There was no statistically significant association between serotype and hospitalisation rate or duration of hospital stay, neither was there any statistically significant association between serotype or PFGE profile and duration of spasmodic cough or presence of complications.
Assuntos
Bordetella pertussis/química , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Coqueluche/imunologia , Criança , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Eletroforese em Gel de Campo Pulsado , Humanos , Vigilância da População , Sorotipagem , Suécia/epidemiologia , Vacinação , Coqueluche/classificação , Coqueluche/epidemiologia , Coqueluche/prevenção & controleRESUMO
The present study reports the diversity of rotavirus strains circulating in León, Nicaragua during three years. There was a shift of G and P genotypes with increment of one specific genotype during the second most important peak of diarrhea occurring in the beginning of every year.
Assuntos
Infecções por Rotavirus/epidemiologia , Rotavirus/classificação , Rotavirus/genética , Pré-Escolar , Genótipo , Humanos , Nicarágua/epidemiologia , Análise de Sequência com Séries de Oligonucleotídeos , Prevalência , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/metabolismo , Infecções por Rotavirus/virologia , Análise de Sequência de DNARESUMO
We describe two newly developed methods for rapid typing of the pertussis toxin subunit 1 gene (ptxS1). A real-time PCR assay based on hybridization probes and a Pyrosequencing assay were developed and the specificity, sensitivity, cost, hands-on time and post-assay data processing were compared to Sanger sequencing. Both methods enabled discrimination of all four allelic variants, correctly identified all ptxS1 alleles of 143 strains tested and proved suitable for large-scale screening of B. pertussis strains.
Assuntos
Bordetella pertussis/genética , Toxina Pertussis/genética , Alelos , Bordetella pertussis/classificação , DNA Bacteriano/química , DNA Bacteriano/genética , Humanos , Toxina Pertussis/química , Vacina contra Coqueluche/genética , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Coqueluche/microbiologiaRESUMO
The increasing incidence of pertussis in a number of countries, despite good vaccination coverage, is a cause for concern. We used pulsed-field gel electrophoresis (PFGE) typing to examine the genetic diversity of 101 clinical isolates of Bordetella pertussis, recovered during 1999-2001, and circulating in five different European countries to evaluate temporal and geographical distribution. This DNA fingerprinting approach seems to be a more discriminative epidemiological tool than sequencing of individual genes. Despite differences in vaccination policies in the five countries, these European isolates were found to be very similar and fell into the same major PFGE profile groups, with a predominance of one profile group. There was no evidence of geographic clustering, except that one new profile subgroup was predominantly found in one country. This study provides a baseline for continued surveillance of the B. pertussis population in Europe.
Assuntos
Bordetella pertussis/genética , Vacina contra Coqueluche/administração & dosagem , Bordetella pertussis/isolamento & purificação , Cromossomos Bacterianos , Análise por Conglomerados , DNA Bacteriano/análise , Eletroforese em Gel de Campo Pulsado , Europa (Continente)/epidemiologia , Variação Genética , Humanos , FilogeniaRESUMO
Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.
Assuntos
Bordetella pertussis/classificação , Bordetella pertussis/genética , Vacina contra Coqueluche/imunologia , Vacinação/métodos , Coqueluche/epidemiologia , Coqueluche/microbiologia , Adaptação Biológica , Bordetella pertussis/imunologia , Bordetella pertussis/isolamento & purificação , Análise por Conglomerados , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Evolução Molecular , Genoma Bacteriano , Saúde Global , Humanos , Lactente , Vacina contra Coqueluche/administração & dosagem , FilogeniaRESUMO
Pertussis is still poorly controlled in both adolescents and adults. As a result, an adolescent pertussis booster vaccine dose has already been implemented or decided on in many countries. The reasons for this have been twofold: a worrying increase of infections in the target group of adolescents and a wish to prevent serious pertussis disease among young yet unvaccinated, and partly vaccinated, infants. Currently, it is still too early to evaluate the effect of the late booster on the circulation of Bordetella pertussis owing to the lack of relevant follow-up data. A universal adolescent booster vaccination will reduce the incidence of pertussis in the target group but the duration of immunity is uncertain. It is an open question as to what extent boosters should be offered to older age groups or if natural infections would be preferable. On the one hand, circulating B. pertussis may be hazardous to the youngest unvaccinated infants. On the other hand, subclinical natural boosters might be beneficial to population immunity. As the duration of immunity is shorter after vaccination than after natural infections, an unwanted consequence of adolescent boosters might shift the infection peak to older child-bearing adults. It is therefore recommended that recurrent serosurveys are used to follow the influence of vaccination on the antigenic pressure, as well as the duration of protective immunity. For this purpose, standardization of symptoms and laboratory criteria used for notification, as well as the methodology for seroepidemiology, must be established. Adverse reactions after adolescent vaccination and outbreaks owing to new B. pertussis variants must also be carefully monitored. In this article, we have used Swedish surveillance data and the results from Swedish seroepidemiology to illustrate these problem areas.
Assuntos
Bordetella pertussis/imunologia , Esquemas de Imunização , Imunização Secundária/métodos , Vacina contra Coqueluche/administração & dosagem , Vacinação/métodos , Adolescente , Fatores Etários , Animais , Humanos , Vacina contra Coqueluche/imunologiaRESUMO
After introduction of a mono-component vaccine, containing only pertussis toxoid (PT), the incidence of pertussis was significantly higher in the Gothenburg area among children during the period October 1, 1997 until end of 2006 compared to the Rest of Sweden where a vaccine containing PT and two other pertussis antigens was used. To investigate a possible cause of this difference, the Bordetella pertussis populations in both regions were compared by determining the fimbrial serotype (Fim), the PFGE-type and the pertussis toxin promoter allele type (ptxP). Strains with the ptxP1 allele were successively replaced by ptxP3 strains producing more pertussis toxin. In Gothenburg compared to the Rest of Sweden, Fim3 and ptxP3 strains were observed earlier and reached higher frequencies in the studied period. Since ptxP3 strains have been shown to be more virulent, their higher prevalence may have contributed to the higher incidence of pertussis in the Gothenburg area. In addition we found a high degree of linkage between PFGE-profile and ptxP3. Our results highlight the importance of strain typing to gain insight into the mechanisms of immunity-associated selection of microbial subtypes and the causes of changes in incidences of infectious diseases.
Assuntos
Infecções por Bordetella/microbiologia , Bordetella pertussis/genética , Programas de Imunização , Vacina contra Coqueluche/administração & dosagem , Antígenos de Bactérias/genética , Técnicas de Tipagem Bacteriana , Infecções por Bordetella/epidemiologia , Bordetella pertussis/classificação , Criança , Proteínas de Fímbrias/genética , Frequência do Gene , Genótipo , Humanos , Toxina Pertussis/genética , Vacina contra Coqueluche/genética , Suécia/epidemiologia , Fatores de Virulência de Bordetella/genéticaRESUMO
To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA). In this study, a single nucleotide polymorphism (SNP) typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in The Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis.
Assuntos
Bordetella pertussis/classificação , Bordetella pertussis/genética , Polimorfismo de Nucleotídeo Único/genética , Eletroforese em Gel de Campo Pulsado , Evolução Molecular , Filogenia , Sequências de Repetição em Tandem/genéticaRESUMO
The prevalence of IgG ELISA antibodies against Haemophilus influenzae polyribosyl ribitol phosphate (anti-Hib) was studied in two Swedish seroepidemiologic materials. One study was performed in 1997 5 years after the introduction of universal Hib vaccination (N=3320). Ten years later, a similar study was carried out to analyze the effect of vaccination on anti-Hib prevalence (N=2383). The median values of anti-Hib concentrations (EU/mL) were almost identical in the two materials. The antigenic pressure including vaccination, natural infections and possible cross-immunizations was thus assumed to be constant. The joint median was 0.50 EU/mL (95% confidence interval: 0.46, 0.56). However, there were also indications of reduced exposure to 'Hib-antigens' over a 10-year period. The proportion above the cut-off point for protection, 0.15 EU/mL, decreased significantly for children aged 2-19 years from 78% in 1997 to 74% in 2007 (p=0.034), and there was a significant increase in values below the minimal level of detection for adults from 17% in 1997 to 20% in 2007 (p=0.009). In the 2007 material no specific age group could be identified with a lower immune profile than other age groups older than 3 years and there was a significant downward trend of invasive infections caused by Hib according to notification data for the period 1997-2008. Therefore, the conclusion is that presently there is no need for a booster dose of Hib vaccine in Sweden after primary vaccination but the situation should be carefully monitored.
Assuntos
Cápsulas Bacterianas/imunologia , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/imunologia , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/imunologia , Imunização/métodos , Vacinas Conjugadas/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Cápsulas Bacterianas/administração & dosagem , Criança , Pré-Escolar , Estudos Transversais , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/normas , Humanos , Imunização Secundária/métodos , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Suécia/epidemiologia , Vacinas Conjugadas/administração & dosagem , Adulto JovemRESUMO
In a previous study, it was found that the antibody response to a nonvaccine pertussis antigen in children who were vaccine failures was reduced compared with the response in nonvaccinated children who had pertussis. In two acellular pertussis vaccine efficacy trials in Sweden, we studied the convalescent-phase enzyme-linked immunosorbent assay (ELISA) geometric mean values (GMVs) in response to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM 2/3) in vaccine failures and controls with pertussis. In Germany, the antibody responses to Bordetella pertussis antigens PT, FHA, PRN, and FIM-2 were analyzed by ELISA according to time of serum collection after onset of illness in children with pertussis who were vaccine failures or who were previously unvaccinated. Antibody values were also compared by severity of clinical illness. In Sweden, infants who had received a PT toxoid vaccine and who were vaccine failures had a blunted response to the nonvaccine antigen FHA compared with the response in children who had received a PT/FHA vaccine. Similarly, infants who had pertussis and who had received a PT/FHA vaccine had a blunted response to the nonvaccine antigens PRN and FIM 2/3 compared with the response in children who were vaccine failures and who had received a PT, FHA, PRN, and FIM 2/3 vaccine. In Germany, in sera collected from 0 to 15 days after pertussis illness onset, the GMVs for all 4 antigens (PT, FHA, PRN, and FIM-2) were significantly lower in an unvaccinated group than in children who were diphtheria-tetanus-acellular pertussis (DTaP) vaccine failures. In the unvaccinated group, the GMV of the PT antibody rose rapidly over time so that it was similar to that of the DTaP vaccine recipients at the 16- to 30-day period. In contrast, the antibody responses to FHA, PRN, and FIM-2 at all time periods were lower in the diphtheria-tetanus vaccine (DT) recipients than in the DTaP vaccine failures. In both Sweden and Germany, children with less severe illness had lower antibody responses than children with typical pertussis. Our findings indicate that upon exposure and infection, previous vaccinees have more-robust antibody responses to the antigens contained in the vaccine they had received than to Bordetella antigens that were not in the vaccine they had received. In addition, over time the antibody responses to FHA, PRN, and FIM-2 were greater in children with vaccine failure (primed subjects) than in unvaccinated children (unprimed subjects) whereas the responses to PT were similar in the primed and unprimed children, as determined from sera collected after 15 days of illness. Our findings lend support to the idea that DTaP vaccines should contain multiple antigens.
Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Bordetella pertussis/imunologia , Vacina contra Coqueluche/imunologia , Coqueluche/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Alemanha , Humanos , Lactente , Suécia , Fatores de TempoRESUMO
The prevalence of IgG ELISA antibodies against pertussis toxin (anti-PT) was studied in two Swedish seroepidemiological studies. One was performed in 1997 when the new pertussis vaccination program was 1 year old (n = 3420). In 2007, when Pa vaccines had been used countrywide for 10 years in the universal child vaccination program, this study was repeated to analyze the effect of vaccination on anti-PT prevalence (n = 2379). Before the statistical analysis of seroprevalence, children vaccinated within the last 2 years before the serosurveys were excluded. The results indicate a reduced exposure to Bordetella pertussis in the population. The proportion of sera without measurable anti-PT antibodies increased significantly, aggregated over all comparable age groups, from 3.8% in people sampled in 1997 to 16.3% in people sampled in 2007. For cord blood, 1% was without measurable anti-PT antibodies in 1997 compared to a significantly higher level, 12%, in 2007. With anti-PT concentrations of > or =50 and > or =100 EU/ml as cutoff points for 'recent infection' the proportion above the cutoff points for younger children was significantly higher in 1997 than in 2007 at both cutoff points. For all adults, 20 years of age and older, the difference in proportions above the lower cutoff point was close to statistically significant, comparing 1997 with 2007. This was not the case at 100 EU/ml. In the 1997 samples of children, there was a significant downward trend of 'recent infections' at both cutoff points for three sampled age groups between 5 and 15 years of age from 21% at 5.0-5.5 years of age to 7% at 14.7-15.7 years for the lowest cutoff. In the 2007 samples of children, on the contrary, there was a significant continuous upward trend of 'recent infections', at both cutoff points, for four sampled age groups between 4 and 18 years of age - from 4% at 4-5 years of age to 16% at 17-18 years at the lowest cutoff. The continuous increase, with age of children with high anti-PT concentrations, supports the recent change in the general Swedish childhood vaccination program to include a pre-school booster at 5-6 years and a school-leaving booster at 14-16 years of age.
Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Toxina Pertussis/imunologia , Vacina contra Coqueluche/imunologia , Coqueluche/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacina contra Coqueluche/administração & dosagem , Estudos Soroepidemiológicos , Suécia/epidemiologia , Vacinação , Coqueluche/imunologia , Coqueluche/microbiologia , Adulto JovemRESUMO
Sera from 96 young children in a vaccine trial were analysed for kinetics of ELISA IgG anti-pertussis toxin (anti-PT) after a laboratory-verified pertussis infection. The antibody decay curves after infection were biphasic and similar in shape to those after vaccination. The change from a rapid to a slower decay after the peak occurred about 4-5 months from the first day of cough. In a group of children given a two- or a five-component acellular pertussis vaccine the proportion of sera above the tentative cut-off values for anti-PT of 20, 50 or 100 EU/ml 12 months after onset of the infection were 19%, 0% and 0% respectively. Corresponding figures for a whole-cell or placebo vaccine group of infected children were significantly higher, 73%, 39% and 30%, i.e. the antibody decay after infection in young children depends on vaccination status as well as on the pertussis vaccine given. In a large group of non-infected children vaccinated with the same five-component acellular vaccine 13%, 0% and 0% had sera above 20, 50 and 100 EU/ml at 12 months after the third vaccine dose and all were below the minimum level of detection 2 years after vaccination. In conclusion, knowledge about anti-PT kinetics is essential for the interpretation of seroepidemiological data but hardly offers the possibility to establish valid cut-off values for anti-PT in single sample serology. An option would be to identify a grey zone between the positive and negative ends of the distribution for follow-up testing by a second serum.
Assuntos
Bordetella pertussis/imunologia , Vacina contra Coqueluche/imunologia , Vacinação/normas , Coqueluche/imunologia , Anticorpos Antibacterianos/sangue , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Lactente , Cinética , Análise Multivariada , Vacina contra Coqueluche/normas , Estudos Retrospectivos , Sensibilidade e Especificidade , Vacinas Acelulares/imunologia , Vacinas Acelulares/normas , Coqueluche/prevenção & controleRESUMO
The anti-Fim response and long-term persistence after vaccination and infection may be of importance in understanding population immunity. Longitudinal serum samples (n = 1330) from 542 non-infected children related to a Swedish vaccine trial showed that the post vaccination (DTPa5) antibody decay curve for pertussis ELISA IgG anti-fimbriae2/3 (anti-Fim2/3) was bi-phasic. A slower one followed an initial rapid decay approximately 5-6 months after the third dose at 12 months of age. After 71 months, however, 60% still had concentrations above > or =5 EU/ml, a level that had been shown to correlate with decreased risk of disease. Booster responses after re-vaccination with DTPa5 at 4, 5 and 6 years of age were strong and appeared within 1 week after vaccination, indicating immune memory. Ninety-six young children with verified pertussis infection, for whom we had serum samples both before, during and after the infection, showed a high response if they had been primed with fimbriae (either DTPa5 or DTPwc). In contrast, 76% of infected children not primed with fimbriae (a DTPa2 or DT group) only had concentrations below the minimum level of detection in all samples taken during and after the infection. In two Swedish seroepidemiological surveys, one from 1997 just after reintroduction of universal childhood vaccination against pertussis and one from 2007, the proportion of children 2-3 years with anti-Fim2/3 concentrations <5 EU/ml was similar and above 90%. This reflects that the two- or three-component pertussis vaccines (DTPa2 and DTPa3) that were introduced in Sweden in 1996 do not induce anti-Fim2/3 antibodies. In previous studies it was shown in multivariate analyses that levels of IgG anti-Fim2/3 > or =5 EU/ml reduced short-term risk of pertussis in small children. As the antibody response to Fim2/3 after infection is poor in children who have not been primed earlier in life, inclusion of immunogenic Fim2/3 in future pertussis vaccines should be considered.