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1.
Neural Comput ; 31(7): 1419-1429, 2019 07.
Article in English | MEDLINE | ID: mdl-31113302

ABSTRACT

This letter shows by digital simulation that a simple rule applied to one-dimensional self-organized maps for integrating sensory perceptions from two identical sources yielding position information as integers, corrupted by independent noise sources, yields almost statistically optimal results for position estimation as determined by maximum likelihood estimation. There is no learning of the corrupting noise sources nor is any information about the statistics of the noise sources available to the integrating process. The simple rule employed yields a measure of the quality of the estimated position of the source. The letter also shows that if the Bayesian estimates, which are rational numbers, are rounded in order to comply with the stipulation that integers be identified, the Bayesian estimation will have a larger variance than the proposed integration.


Subject(s)
Learning , Perception/physiology , Psychomotor Performance/physiology , Sensation/physiology , Algorithms , Bayes Theorem , Computer Simulation
2.
Clin Vaccine Immunol ; 21(2): 165-73, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24307240

ABSTRACT

Bordetella pertussis fimbriae (Fim2 and Fim3) are components of a five-component acellular pertussis vaccine (diphtheria-tetanus-acellular pertussis vaccine [DTaP5]), and antibody responses to fimbriae have been associated with protection. We analyzed the IgG responses to individual Fim2 and Fim3 in sera remaining from a Swedish placebo-controlled efficacy trial that compared a whole-cell vaccine (diphtheria-tetanus-whole-cell pertussis vaccine [DTwP]), a two-component acellular pertussis vaccine (DTaP2), and DTaP5. One month following three doses of the Fim-containing vaccines (DTwP or DTaP5), anti-Fim2 geometric mean IgG concentrations were higher than those for anti-Fim3, with a greater anti-Fim2/anti-Fim3 IgG ratio elicited by DTaP5. We also determined the responses in vaccinated children following an episode of pertussis. Those who received DTaP5 showed a large rise in anti-Fim2 IgG, reflecting the predominant Fim2 serotype at the time. In contrast, those who received DTwP showed an equal rise in anti-Fim2 and anti-Fim3 IgG concentrations, indicating that DTwP may provide a more efficient priming effect for a Fim3 response following contact with B. pertussis. Anti-Fim2 and anti-Fim3 IgG concentrations were also determined in samples from two seroprevalence studies conducted in Sweden in 1997, when no pertussis vaccine was used and Fim2 isolates predominated, and in 2007, when either DTaP2 or DTaP3 without fimbriae was used and Fim3 isolates predominated. Very similar distributions of anti-Fim2 and anti-Fim3 IgG concentrations were obtained in 1997 and 2007, except that anti-Fim3 concentrations in 1997 were lower. This observation, together with the numbers of individuals with both anti-Fim2 and anti-Fim3 IgG concentrations, strongly suggests that B. pertussis expresses both Fim2 and Fim3 during infection.


Subject(s)
Antibodies, Bacterial/blood , Antibody Formation , Antigens, Bacterial/immunology , Fimbriae Proteins/immunology , Pertussis Vaccine/immunology , Virulence Factors, Bordetella/immunology , Whooping Cough/immunology , Adolescent , Child , Child, Preschool , Female , Humans , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Pertussis Vaccine/administration & dosage , Sweden , Vaccines, Acellular/administration & dosage , Vaccines, Acellular/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology
3.
Vaccine ; 30(21): 3239-47, 2012 May 02.
Article in English | MEDLINE | ID: mdl-22094282

ABSTRACT

OBJECTIVES: Shortly after pertussis vaccination was reintroduced in Sweden in 1996, an intensified pertussis disease surveillance programme was set up. In this study, we report on in-depth analyses of age-dose-number-specific incidences and the rate of pertussis hospitalisation for children with no, 1 or 2 doses of an acellular pertussis vaccine before pertussis disease. Vaccine coverage, the timeliness of childhood vaccination and the effect of later than scheduled pertussis vaccination(s) are also examined. STUDY DESIGN: Children with notified laboratory-confirmed (culture or PCR) pertussis disease were evaluated among the surveillance population of about 1 million infants, born between 1996 and 2007 and followed for pertussis disease from October 1997 to December 2007, for nearly 6 million person-years. Birth and vaccination dates of the diseased children are known from the surveillance programme. To estimate denominators of the age-dose-number-specific pertussis incidences, we used birth and vaccination dates from a vaccine trial with more than 72,000 infants combined with national pertussis vaccine coverage data for children in the surveillance population. RESULTS: For infants from 3 to <5 months of age, the incidence of pertussis disease with at least 14 days of cough decreased from 264/100,000 for unvaccinated infants to 155/100,000 for infants with one dose of a pertussis vaccine prior to onset of the disease. In the age range 5 to <12 months, the age-dose specific incidences were 526, 95, and 24/100,000 for infants with no, 1 and 2 doses, respectively. The rate of hospitalisation for infants with 1 dose of a pertussis vaccine prior to onset of the disease was significantly lower than for unvaccinated infants of the same age. For many infants, there is a delay in administration of the vaccine doses according to the regular 3-5-12 month schedule (which has been the case for many years). Hypothetically, if all infants had been vaccinated exactly on schedule, we would expect about 28% fewer pertussis cases with at least 14 days of cough and 38% fewer hospitalisations due to pertussis, of cases possible to influence by vaccinations on schedule. CONCLUSION: Pertussis vaccination had a significant effect among infants already after the first dose. This is particularly important for premature infants and infants with severe respiratory and cardiac diseases. A moderate decrease in the incidence of pertussis disease in infants and rate of hospitalisation could be expected if primary vaccinations were carried out closer to the scheduled time than is currently the practice in Sweden.


Subject(s)
Hospitalization/statistics & numerical data , Pertussis Vaccine/immunology , Whooping Cough/epidemiology , Whooping Cough/prevention & control , Child , Child, Preschool , Humans , Incidence , Infant , Infant, Newborn , Pertussis Vaccine/administration & dosage , Sweden/epidemiology , Vaccination/methods , Whooping Cough/pathology
4.
Expert Rev Clin Pharmacol ; 4(6): 705-11, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22111856

ABSTRACT

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.


Subject(s)
Bordetella pertussis/immunology , Immunization Schedule , Immunization, Secondary/methods , Pertussis Vaccine/administration & dosage , Vaccination/methods , Adolescent , Age Factors , Animals , Humans , Pertussis Vaccine/immunology
5.
Neural Comput ; 23(8): 2101-39, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21521039

ABSTRACT

The multimodal self-organizing network (MMSON), an artificial neural network architecture carrying out sensory integration, is presented here. The architecture is designed using neurophysiological findings and imaging studies that pertain to sensory integration and consists of interconnected lattices of artificial neurons. In this artificial neural architecture, the degree of recognition of stimuli, that is, the perceived reliability of stimuli in the various subnetworks, is included in the computation. The MMSON's behavior is compared to aspects of brain function that deal with sensory integration. According to human behavioral studies, integration of signals from sensory receptors of different modalities enhances perception of objects and events and also reduces time to detection. In neocortex, integration takes place in bimodal and multimodal association areas and result, not only in feedback-mediated enhanced unimodal perception and shortened reaction time, but also in robust bimodal or multimodal percepts. Simulation data from the presented artificial neural network architecture show that it replicates these important psychological and neuroscientific characteristics of sensory integration.


Subject(s)
Algorithms , Neural Networks, Computer , Perception/physiology , Speech/physiology , Brain/physiology , Humans , Neurons/physiology
6.
Vaccine ; 29(18): 3438-42, 2011 Apr 18.
Article in English | MEDLINE | ID: mdl-21396900

ABSTRACT

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.


Subject(s)
Bordetella Infections/microbiology , Bordetella pertussis/genetics , Immunization Programs , Pertussis Vaccine/administration & dosage , Antigens, Bacterial/genetics , Bacterial Typing Techniques , Bordetella Infections/epidemiology , Bordetella pertussis/classification , Child , Fimbriae Proteins/genetics , Gene Frequency , Genotype , Humans , Pertussis Toxin/genetics , Pertussis Vaccine/genetics , Sweden/epidemiology , Virulence Factors, Bordetella/genetics
7.
Clin Vaccine Immunol ; 17(5): 741-7, 2010 May.
Article in English | MEDLINE | ID: mdl-20335431

ABSTRACT

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.


Subject(s)
Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Bordetella pertussis/immunology , Pertussis Vaccine/immunology , Whooping Cough/immunology , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay/methods , Germany , Humans , Infant , Sweden , Time Factors
8.
APMIS ; 117(11): 797-807, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19845530

ABSTRACT

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.


Subject(s)
Bordetella pertussis/immunology , Pertussis Vaccine/immunology , Vaccination/standards , Whooping Cough/immunology , Antibodies, Bacterial/blood , Child, Preschool , Enzyme-Linked Immunosorbent Assay/methods , Humans , Infant , Kinetics , Multivariate Analysis , Pertussis Vaccine/standards , Retrospective Studies , Sensitivity and Specificity , Vaccines, Acellular/immunology , Vaccines, Acellular/standards , Whooping Cough/prevention & control
10.
APMIS ; 117(9): 660-71, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19703126

ABSTRACT

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.


Subject(s)
Antigens, Bacterial/administration & dosage , Antigens, Bacterial/immunology , Bordetella pertussis/immunology , Fimbriae Proteins/administration & dosage , Fimbriae Proteins/immunology , Pertussis Vaccine/administration & dosage , Pertussis Vaccine/immunology , Virulence Factors, Bordetella/administration & dosage , Virulence Factors, Bordetella/immunology , Adolescent , Antibodies, Bacterial/blood , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, Secondary , Immunoglobulin G/blood , Immunologic Memory , Infant , Longitudinal Studies , Seroepidemiologic Studies , Sweden/epidemiology , Whooping Cough/epidemiology , Whooping Cough/immunology , Whooping Cough/prevention & control
11.
APMIS ; 117(12): 912-22, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20078557

ABSTRACT

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.


Subject(s)
Antibodies, Bacterial/blood , Bordetella pertussis/immunology , Pertussis Toxin/immunology , Pertussis Vaccine/immunology , Whooping Cough/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Pertussis Vaccine/administration & dosage , Seroepidemiologic Studies , Sweden/epidemiology , Vaccination , Whooping Cough/immunology , Whooping Cough/microbiology , Young Adult
12.
APMIS ; 115(6): 736-42, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17550382

ABSTRACT

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.


Subject(s)
Bordetella pertussis/chemistry , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Whooping Cough/immunology , Child , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Electrophoresis, Gel, Pulsed-Field , Humans , Population Surveillance , Serotyping , Sweden/epidemiology , Vaccination , Whooping Cough/classification , Whooping Cough/epidemiology , Whooping Cough/prevention & control
13.
APMIS ; 115(4): 299-310, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17504296

ABSTRACT

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.


Subject(s)
Bordetella pertussis/isolation & purification , Pertussis Vaccine/administration & dosage , Whooping Cough/epidemiology , Whooping Cough/prevention & control , Alleles , Bordetella pertussis/genetics , Child, Preschool , DNA, Bacterial/analysis , Electrophoresis, Gel, Pulsed-Field , Female , Humans , Incidence , Male , Population , Serotyping , Sweden , Vaccination , Virulence , Virulence Factors, Bordetella/genetics
14.
Pediatrics ; 118(3): 978-84, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16950988

ABSTRACT

OBJECTIVES: The purpose of this work was to evaluate the long-term effectiveness of vaccination with acellular pertussis vaccines at 3, 5, and 12 months of age. METHODS: Clinical follow-up of reported culture- and polymerase chain reaction-confirmed cases of pertussis was initiated during October 1997 in most of Sweden (except Gothenburg and environs). The study population included 90% of Swedish children born during 1996 or later (ie, who received diphtheria-tetanus-acellular pertussis vaccines at 3, 5, and 12 months of age) and children who had participated in a large pertussis vaccine trial in 1993-1996. Age-specific incidences were estimated using reported culture- or polymerase chain reaction-confirmed pertussis from October 1997 to September 2004 in areas covered by enhanced surveillance. In addition, annual overall and age-specific incidences of pertussis throughout Sweden before and after introduction of acellular pertussis vaccines were estimated. RESULTS: The overall incidence of notified culture- and polymerase chain reaction-confirmed pertussis dropped from 113 to 150 per 100,000 during 1992-1995 to 11 to 16 per 100,000 during 2001-2004. In areas of enhanced surveillance, the incidence of pertussis was 31 per 100,000 person-years after 2 doses and 19 per 100,000 person-years after the third dose at 12 months of age. The age-specific incidence remained low for approximately 5 years after the third dose but increased in children aged 6 to 8 years, becoming 32 and 48 per 100,000 person-years, respectively. The highest incidence occurred among infants who were unvaccinated or had received only 1 dose of diphtheria-tetanus-acellular pertussis vaccine. CONCLUSIONS: The increased incidence among 7- to 8-year-olds (ie, mainly acellular pertussis vaccine-vaccinated children) suggests waning of vaccine-induced protection from pertussis. Along with a concomitant increase in incidence among infants, most likely infected by older siblings, these data suggest a booster dose of acellular pertussis vaccine is warranted from 5 to 7 years of age.


Subject(s)
Immunization Schedule , Immunization, Secondary , Pertussis Vaccine/administration & dosage , Whooping Cough/prevention & control , Child , Child, Preschool , DNA, Bacterial/analysis , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Polymerase Chain Reaction , Population Surveillance , Sweden/epidemiology , Whooping Cough/epidemiology
15.
Vaccine ; 23(46-47): 5359-64, 2005 Nov 16.
Article in English | MEDLINE | ID: mdl-16051400

ABSTRACT

Longitudinal serum samples were collected from 542 children that had participated in a Swedish pertussis vaccine trial 1992-1995 [Gustafsson L, Hallander HO, Olin P, Reizenstein E, Storsaeter J. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 1996;334(6):349-355] and who did not contract pertussis. The sera were analyzed for post vaccination antibody decay and for booster response of anti-PT (IgG antibodies against pertussis toxin), as measured by ELISA. Generally, an initial rapid decay of antitoxin antibody concentration was followed by a slower decay; the change occurring when the geometric mean level of antitoxin concentration reached 8-9 ELISA Units/mL (EU/mL). The time needed to reach this level was 8-9 months after the third dose in a 2, 4, and 6 months schedule. A "best-fit" combined regression model was used to predict when 50% of the children have less than the minimum level of detection of anti-PT (1EU/mL). This occurred about 65 months after dose 3 at an age of 6 years. The anti-PT response to a booster dose was evident but the post-booster geometric mean values decreased with number of years after the third dose and the response appeared later. The results indicate that a pre-school booster might be considered at 6 years of age or earlier.


Subject(s)
Antitoxins/analysis , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Whooping Cough/immunology , Antibodies, Bacterial/analysis , Child , Child, Preschool , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunization Schedule , Immunization, Secondary , Infant , Male , Sweden , Vaccines, Acellular/immunology
16.
J Clin Microbiol ; 43(6): 2856-65, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15956409

ABSTRACT

The Swedish population of Bordetella pertussis strains was characterized from 1,247 isolates covering a whole-cell vaccine program up to 1979, a 17-year period without vaccination (1979 to 1996), and a period after the introduction of general vaccination among newborns with acellular pertussis vaccines (1997 to 2003). Strains were characterized by serotyping and genotyping of pertactin and ptxA and by means of pulsed-field gel electrophoresis (PFGE). With emphasis on vaccine-related markers, the vast majority of circulating strains were of nonvaccine type. There were shifts of serotype connected with shifts of vaccination program. Serotype Fim3 was most frequent during the periods with general vaccination schedules, whereas serotype Fim2 was predominant during the 17-year vaccine-free period. Pertactin 1 was predominant during the pertussis whole-cell (Pw) vaccine period but was thereafter replaced by prn2 and has not reappeared after the introduction of acellular pertussis (Pa) vaccines. ptxA (1) was predominant over all three decades. There was a significant difference in the distribution of serotypes between vaccinated and unvaccinated individuals, but not for pertactin. A few PFGE profiles were predominant over the years: BpSR25 (serotype Fim3 prn1/7) and BpSR18 (serotype Fim3 prn2) during the Pw period, BpSR1 (serotype Fim2 prn2) during the 17 years without general vaccination, and BpSR11 (serotype Fim3 prn2) after the reintroduction of general vaccination in 1996. Despite differences between the pertactin and toxin types of Pa vaccines and circulating strains, there is no evidence that there is a threat, i.e., the vaccination program so far has been effective against whooping cough, and there seems to be no impact on the effectiveness of the vaccination program from the bacterial polymorphism.


Subject(s)
Bordetella pertussis/classification , Bordetella pertussis/genetics , Genetic Variation , Immunization Programs/methods , Pertussis Vaccine/administration & dosage , Vaccines, Acellular/administration & dosage , Whooping Cough/epidemiology , Bacterial Outer Membrane Proteins/genetics , Bordetella pertussis/isolation & purification , Child , Child, Preschool , Electrophoresis, Gel, Pulsed-Field , Genotype , Humans , Infant, Newborn , Pertussis Toxin/genetics , Serotyping , Sweden/epidemiology , Vaccination , Virulence Factors, Bordetella/genetics , Whooping Cough/microbiology
17.
J Autism Dev Disord ; 34(2): 189-98, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15162937

ABSTRACT

Autism is a developmental disorder with possibly multiple pathophysiologies. It has been theorized that cortical feature maps in individuals with autism are inadequate for forming abstract codes and representations. Cortical feature maps make it possible to classify stimuli, such as phonemes of speech, disregarding incidental detail. Hierarchies of such maps are instrumental in creating abstract codes and representations of objects and events. Self-Organizing Maps (SOMs) are artificial neural networks that offer insights into the development of cortical feature maps. Attentional impairment is prevalent in autism, but whether it is caused by attention-shift impairment or strong familiarity preference or negative response to novelty is a matter of debate. We model attention shift during self-organization by presenting a SOM with stimuli from two sources in four different modes, namely, novelty seeking (regarded as normal learning), attention-shift impairment (shifts are made with a low probability), familiarity preference (shifts made with a lower probability to the source that is the less familiar to the SOM of the two sources), and familiarity preference in conjunction with attention-shift impairment. The resulting feature maps from learning with novelty seeking and with attention-shift impairment are much the same except that learning with attention-shift impairment often yields maps with a somewhat better discrimination capacity than learning with novelty seeking. In contrast, the resulting maps from learning with strong familiarity preference are adapted to one of the sources at the expense of the other, and if one of the sources has a set of stimuli with smaller variability, the resulting maps are adapted to stimuli from that source. When familiarity preference is less pronounced, the resulting maps may become normal or fully restricted to one of the sources, and in that case, always the source with smaller variability if such a source is present. Such learning, in a system with many different maps, will result in very uneven capacities. Learning with familiarity preference in conjunction with attention-shift impairment surprisingly has higher probability for the development of normal maps than learning with familiarity preference alone.


Subject(s)
Attention , Autistic Disorder/physiopathology , Brain Mapping , Neural Networks, Computer , Exploratory Behavior , Humans , Problem Solving , Recognition, Psychology
18.
Neuroscientist ; 10(3): 189-91, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15155057

ABSTRACT

Narrow neural columns have been suggested to be a neuroanatomical abnormality in autism. A previous hypothetical explanation, an unbalance between excitatory and inhibitory lateral feedback in the neocortex, has been found to be difficult to reconcile with the relatively high comorbidity of autism with epilepsy. Two alternative explanations are discussed, an early low capacity for producing serotonin, documented in autism, and insufficient production of nitric oxide. An early low level of serotonin has in animal experiments caused narrow neural columns. Insufficient nitric oxide is known from neural network theory to cause narrow neural columns.


Subject(s)
Autistic Disorder/pathology , Neocortex/pathology , Neurons/pathology , Animals , Autistic Disorder/complications , Autistic Disorder/physiopathology , Epilepsy/complications , Epilepsy/pathology , Epilepsy/physiopathology , Humans , Nitric Oxide/metabolism , Serotonin/metabolism
19.
Vaccine ; 21(25-26): 3542-9, 2003 Sep 08.
Article in English | MEDLINE | ID: mdl-12922081

ABSTRACT

Prospectively collected data in a Swedish vaccine efficacy trial were used to investigate transmission of pertussis from small study infants to other household members. Forty one percent (258/627) of the exposed persons with paired serology had laboratory confirmed pertussis. The majority of those with laboratory confirmed pertussis had less than 14 days of cough and many were asymptomatic. High susceptibility to symptomatic pertussis was found among persons with low initial IgG antibody concentrations against pertussis toxin, especially those without previous history of pertussis vaccination or disease.


Subject(s)
Antibodies, Bacterial/analysis , Bordetella pertussis/immunology , Whooping Cough/immunology , Adolescent , Adult , Child , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Disease Susceptibility/immunology , Female , Humans , Immunoglobulin G/analysis , Male , Whooping Cough/transmission
20.
Vaccine ; 21(17-18): 2015-21, 2003 May 16.
Article in English | MEDLINE | ID: mdl-12706691

ABSTRACT

Acellular pertussis vaccines were introduced nation-wide in Sweden in 1996, 17 years after the withdrawal of whole-cell pertussis vaccine from the childhood immunisation schedule. We report national data on age specific incidence of culture-confirmed Bordetella pertussis for 1986-2000, and clinical follow-up for 3 years (October 1997-September 2000) in children born in 1996-2000 and from children born in 1993-1994 who had participated in a trial of pertussis vaccines. The annual incidence of culture-confirmed B. pertussis was 89-150 per 100,000 before introduction of acellular pertussis vaccines and has dropped to 17-26 per 100,000. The data suggest that unimmunised infants and children who have received only one dose of pertussis vaccine were provided some protection. The decline is most obvious from the second dose onwards and remained stable for 4-5 years after the third dose in the absence of any booster dose. The first signs of waning immunity were observed at 6-7 years of age in the trial cohort. The short-term benefits reflect high vaccination coverage and high initial efficacy. The full impact of the acellular pertussis vaccination programme in infants remains to be established.


Subject(s)
Pertussis Vaccine/therapeutic use , Whooping Cough/epidemiology , Adolescent , Adult , Aged , Bordetella pertussis/genetics , Bordetella pertussis/isolation & purification , Child , Child, Preschool , Follow-Up Studies , Humans , Incidence , Infant , Middle Aged , Polymerase Chain Reaction , Sweden/epidemiology , Time Factors , Vaccination/methods
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