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Discoloration of the leg following vaccination is a relatively unknown entity. We carried out a study of discolored leg syndrome (DLS) during a 10-year consecutive period with the objective of characterizing DLS in infants following vaccination received in the Dutch National Vaccination Program as well as its occurrence and association with different vaccines. Discolored leg syndrome was defined as an even or patchy red, blue or purple discoloration of the leg(s) and/or leg petechiae with or without swelling. All reports of adverse events following immunization that were made to the passive surveillance system between 1994 and 2003 were included-a total of 1162 identified cases. Red, blue, purple discoloration and isolated petechiae were reported in 39, 19, 27 and 14% of these cases, respectively. Of these 1162 cases, 1105 were considered to be related to the vaccination, based on a predefined risk window with symptom onset after vaccination (48 h for discolorations and 2 weeks for petechiae). Of the 1105 cases, about 50% occurred after DTP-IPV+Hib1 vaccinations, and 30% occurred after DTP-IPV+Hib2 vaccinations. Discolored leg syndrome was frequently accompanied by fierce crying (78%). The median time interval between vaccination and the occurrence of DLS was 3.8 +/- 46.7 h, and the median duration was short (2 +/- 61.7 h). Advancing the vaccination schedule from 3 to 2 months of age caused a small increase in DLS. Discolored leg syndrome manifested mainly after the first and/or second vaccination. In addition to dose, the occurrence of DLS may be slightly age-dependent and self-limiting. The pathophysiology is unknown but may be the result of a vasomotor reaction. Future studies should elucidate the recurrence rate, identify risk factors and assess late outcomes.

Reported cases of pertussis (also known as whooping cough) are increasing among infants and adolescents. This rise parallels the number of reported infant deaths associated with pertussis infection, which is caused by the gram-positive bacterium Bordetella pertussis. Adults are a significant vector for transmission of pertussis to children, and people 65 years of age and older make up a substantial portion of this potential transmission pool. Evidence exists of waning immunity in the adult population after either infection or vaccination. A recommendation for the use of a pertussis-containing vaccine (Tdap) in persons 64 years of age and older would be of considerable benefit to the public in preventing some transmission of pertussis to children. Neither of the two Tdap vaccines (pediatric or adult) is licensed for persons older than 65 years of age, and the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention gives no off-label recommendation for use of Tdap in patients 65 years of age or older.

Background: In addition to the routine enhanced passive safety surveillance of the Dutch National Vaccination Programme, RIVM (National Institute for Public Health and the Environment) started a large questionnaire study enrolling approximately 53,000 children from December 2003 until September 2007., Aim: We intended to establish accurate frequency estimates for several more severe adverse events and to compare the incidence rates of three different infant vaccines that were used consecutively., Methods: Whole cell pertussis (wP) DTP-IPV-Hib vaccine (NVI) was replaced by acellulair pertussis (aP) in 2005, first Infanrix-IPV-Hib (GSK) followed by Pediacel (Sanofi) in 2006. Pneumococcal vaccine, Prevenar (Wyeth), was added for children born from April 2006., Results: Parents returned 28,796 questionnaires (response 54%), 15,069 for whole cell pertussis and 13,727 for acellular pertussis vaccine, including 4485 with pneumococcal vaccine. The OR for reported events was 3-6 for whole cell pertussis vaccine compared with acellular vaccine. This was true for prolonged crying for 3h and more after the first dose (1.5% versus 0.4%; 95 CI 1.1-1.9 and 95% CI 0.2-0.7, respectively), and very high fever of 40.5 degrees C and over following the fourth dose (0.8% versus 0.2%; 95% CI 0.5-1.1 and 0.06-0.3, respectively), while possible febrile convulsions were diagnosed only twice after the fourth dose in the whole cell vaccine group and one after acellular pertussis vaccine. Pallor was significantly more frequent after the first dose of whole cell pertussis than after acellulair pertussis vaccination (18.3% versus 3.4%; 95% CI 17.2-19.5 and 95% CI 2.8-4.0 respectively) Collapse after the first dose was rare in both vaccine groups (5 after whole cell vaccine and 1 after acellular vaccine). The addition of conjugated pneumococcal vaccine did not result in statistically significant increased rates of adverse events in the acellular vaccine group., Conclusion: Whole cell pertussis vaccine showed a significantly higher reactogenicity regarding the adverse events analysed, while addition of conjugated pneumococcal vaccine administered simultaneously with acellular pertussis showed no statistically different adverse event profile.

Although vaccines are routinely used to prevent infectious diseases, little is known about the comprehensive influences caused by vaccines. In this study, we showed, using comprehensive gene expression analysis, that pertussis vaccine affected many genes in multiple organs of vaccine-treated animals. In particular, lung was revealed to be the most suitable target to evaluate pertussis vaccine toxicity. The 13 genes identified from the analysis of vaccine-treated lung at day 1 showed a clear dendrogram corresponding to pertussis vaccine toxicity. Furthermore, quantitative analysis of these genes revealed a positive correlation between their respective expression levels and the degree of toxic effects observed in samples that had been treated with various doses of reference pertussis vaccines. The quantification of this 13 gene-set is an indicator of the vaccine toxicity-related reaction.

Booster vaccination with a reduced-antigen-content dTpa, pediatric DTPa or adult Td vaccine in DTPa-primed children aged 4-6 years was evaluated. Immunogenicity and CMI was assessed one month and 3.5 years after vaccination. Symptoms were solicited for 15 days post-vaccination. There were no differences between groups in diphtheria or tetanus seroprotection or pertussis vaccine-response rates. Anti-diphtheria and anti-PRN concentrations were higher after DTPa, but groups differences reduced over time. Non-significant trends toward reduced reactogenicity of dTpa were observed. Many factors influence vaccine choice at preschool age. The dTpa vaccine was as immunogenic and possibly better tolerated than DTPa at this age.

The Netherlands vaccination schedule has been advanced by 1 month. The reporting rate of collapse or hypotonic-hyporesponsive episode increased from 5.2 [95% confidence interval (CI): 4.8-5.7] to 8.5 (95% CI: 8.0-9.1) and from 1.2 (95% CI: 1.0-1.4) to 2.5 (95% CI: 2.2-2.8) per 10,000 first and second doses, respectively. At 3 months of age it fell from 5.2 to 2.5. This suggests some protection by the first dose. Different mediators in primary and secondary immune response may play a role.

For over 50 years, concerns have been raised about the risk of pertussis vaccine-induced childhood encephalopathy and epilepsy. This article reviews the scientific literature, and the social and historical context in which the scientific, public health and societal views have not always been aligned. Large-scale studies of this issue have produced conflicting results, although the recent consensus is that the risk of vaccine-induced encephalopathy and/or epilepsy, if it exists at all, is extremely low. Risk estimates in the literature have included: risk of a febrile seizure 1 per 19,496 vaccinations; risk of an afebrile seizure 1 per 76,133 vaccinations; risk of encephalopathy after pertussis infection nil-3 cases per million vaccinations. A recent study showed that encephalopathy in 11 out of the 14 children studied, although previously attributed to vaccination, was in fact due an inherited genetic defect of the SCNIA gene that codes for the voltage gated neuronal sodium channel. This study is important because it provides a solid alternative explanation for the perceived pertussis vaccine-encephalopathy association. The interesting possibility is raised that the encephalopathy apparently due to pertussis itself may, in some cases, be due to an SCNIA mutation. It may also, by analogy, shed some light on the continuing debate about other serious long-term adverse effects of vaccination in general.

Protective, immunogenic, toxic, and sensitizing properties of acellular pertussis vaccine (aPV) developed according to original technology were studied, aPV had marked protective activity which lasted more than 2 years. Sera of mice immunized by aPV also possess protective properties, and they were more prominent than in sera of mice immunized by pertussis bacteria suspension (PS). Immune sera to aPV neutralized cytopathogenic effect of pertussis toxin (PT) on ovarian Chinese hamster cells in 1:250 dilution, whereas neutralizing activity of sera to PS was very low. Level of antibodies to PT was higher in rabbits immunized, according to schedules and dosage recommended for children, by aPV than by PS. High immunogenicity of aPV was proved also by levels of IgG to PT in sera of mice immunized three times by aPV in human dosage. During experiments on mice and guinea pigs aPV had mild toxicity, did not induce autoimmune process, did not have anaphylactogenic properties compared with bacterial suspension characterized by high anaphylactogenic activity. Histamine-sensitizing abilityof aPVwas 40 times lower than that of PS. Assessment of pyrogenic properties of aPV and PS performed on rabbits showed that aPV was 1,000 times less pyrogenic than PS. Obtained results demonstrate high protective and immunogenic properties of domestic acellular pertussis vaccine and its low toxic and sensitizing characteristics.

The article presents comparative study of the incidence of adverse effects following vaccinations with whole cell and acellular pertussis vaccines, based on data collected in obligatory routine surveillance of AEFI in the period of 2001-2005 in Poland. Comparisons done in children less then 2-years-old show in general about twice as high incidence of adverse effects following the whole-cell than the acellular vaccine. The biggest rate of proportions (RR = 4,75) was observed for high pitch cry. There was no significant difference in incidence of the most severe reactions, including encephalopathy and nonfebrile seizures, and there was no significant difference in allergic reactions.

Objective: To determine the adverse reactions to the combined vaccine against diptheria, acellular pertussis, tetanus, poliomyelitis and Haemophilus Infuenzae type B (DTP-IPV-Hib) before and after the introduction of an acellular pertussis component., Design: Descriptive., Method: Safety surveillance of the Dutch National Vaccination Programme is performed by the National Institute for Public Health and Environment (RIVM). It is based on an enhanced passive reporting system and complemented by targeted survey-based studies. The data obtained were analysed., Results: The passive surveillance system showed a large increase in reports in 2004, probably linked to increased media attention on the efficacy and safety of the whole-cell DTP-IPV-Hib vaccine. The Health Council recommended transitioning to the use of a DTP-IPV-Hib vaccine with an acellular pertussis component, which was implemented in January 2005. The number of reports dropped sharply in 2005 to a level below that of 2002-2003. Results of a survey study on adverse events following DTP-IPV-Hib vaccination that began in late 2003 and continued in 2005 confirmed the wide coverage ofthe enhanced passive surveillance system and revealed low rates of underreporting of rare adverse events, such as collapse and convulsions., Conclusion: This study confirms the data from the passive surveillance system, which show that the newly introduced acellular DTP-IPV-Hib vaccine is associated with fewer adverse events than the whole-cell vaccine that was used previously.

Objective: Our goal was to evaluate the immunogenicity and safety of pertussis booster vaccination in children infected with HIV on highly active antiretroviral therapy (HAART)., Patients and Methods: HIV-infected children on stable HAART for > or = 3 months with plasma HIV-RNA concentrations of < 30,000 to 60,000 copies per mL who previously received > or = 4 doses of diphtheria-tetanus-pertussis (DTP)-containing vaccine were eligible. Diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered to subjects 2 to < 7 years old who had 4 previous DTP-containing vaccines, subjects 2 to < 7 years old who had > or = 5 previous DTP-containing vaccines and negative tetanus antibody, and subjects > or = 7 to < or = 13 years old who had negative tetanus antibody. Pertussis toxin and filamentous hemagglutinin antibodies were measured before and 8, 24, and 72 weeks after DTaP vaccine., Results: Ninety-two subjects received DTaP vaccine and met criteria for analysis. Antibody concentrations were low at entry: pertussis toxin geometric mean concentration at 4.8 enzyme-linked immunosorbent assay units (EU) per mL and filamentous hemagglutinin geometric mean concentration at 4.1 EU/mL. Pertussis toxin and filamentous hemagglutinin geometric mean concentrations rose to 22.3 and 77.0 EU/mL, respectively, 8 weeks after the study DTaP vaccine. Antibody concentrations fell by 24 weeks after vaccination but remained higher than before vaccination. Predictors of response 8 weeks after DTaP vaccine included the concentration of homologous antibody, lower HIV-RNA level, and higher CD4 percentage at entry. One vaccinated subject experienced erythema and induration of > or = 25 mm., Conclusions: A DTaP vaccine booster was well tolerated by children on HAART and induced increases in antibodies. Antibody concentrations after vaccination were lower than those reported in populations uninfected by HIV. Although comparison among studies must be made with caution, these data suggest that children infected with HIV may be deficient in immunologic memory from previous DTP-containing vaccination and/or that immune reconstitution with HAART may be incomplete for pertussis antigens.

The aim of the study was to assess the incidence and severity of local reactions and systemic events among 4-year-old children receiving a fifth dose of diphtheria-tetanus-inactivated poliovirus (dT-IPV) and acellular pertussis (aP) vaccines. Of 810 children, 483 had no adverse events following immunization. Of the reported local reactions of 281 children, pain was the most frequent (n=246). Eighty-one children developed redness, and 54, swelling. Pain, reduced use of the arm, redness, and swelling occurred significantly more often at the dT-IPV injection site than at the aP injection site (p<0.05). Local reactions were mainly mild and transient. Among the 104 reported systemic events, fever was the most frequent (n=42). In general, the vaccinations for the 4-year-olds are well tolerated.

The boy (case 1) at the age of 12 weeks started having attacks and jercked after the first injection of triple vaccine (diphtheria, retanus and whole cell pertussis) The electro-encephalogram (EEG) confirmed the typical features of hypsarrhythmia. Intramuscular ACTH was commenced for 2 weeks. No problem was reported until the age of 9 years when he started having attacks of jercking. He was treated with sodium valproate. The boy of the second case was a first cousin of case 1. At the age of 11 years the boy had momentary black outs. The EEG showed findings of idiopathic epilepsy. Treatment with sodium valproate was commenced. The children of both cases belong to a family in which there is a trendency to seizures. It seems unlikely the triple vaccine produced the infantile spasms in case 1.

Background: Between July 1997 and April 1998, universal childhood immunization programs in Canada changed from using a whole-cell pertussis to a 5-component acellular pertussis-containing vaccine. To assess effects on pertussis epidemiology of this nationwide change, we analyzed hospitalizations during 1991-2004 using the Canadian Immunization Monitoring Program, Active (IMPACT) pertussis database., Methods: IMPACT is an active surveillance network based in 12 pediatric tertiary-care hospitals across Canada. Characteristics of hospitalized cases of pertussis were compared by type of vaccine received or by birth date (if immunization records were unavailable or the child was unvaccinated). Age-stratified incidence rates were calculated by year and vaccine type., Results: Two thousand ninety-six cases of pertussis were admitted to IMPACT centers, 1174 during the whole-cell vaccine program (WCV-P) and 842 during the acellular vaccine program (ACV-P). Pertussis incidence among children <5 years old decreased significantly during the ACV-P, causing an increase in the residual proportion of cases either too young to be immunized (<2 months old: ACV-P 39% versus WCV-P 26.1%; P < 0.0001) or too young for a second dose (2-3 months old: 42.9% versus 34.2%, respectively; P < 0.0001). A significantly smaller proportion of cases (ACV-P 15.1% versus WCV-P 27.3%) occurred in infants who were old enough (4-11 months of age) to have received 2 or 3 doses of vaccine., Conclusions: With ACV-P, pertussis hospitalizations in children 4-59 months old decreased in frequency, consistent with improved vaccine effectiveness, but remained prominent among very young infants. Improved control strategies are needed to reduce infections among infants too young for pertussis vaccination.

We describe 3 children with neurological disorders that developed in association with their receipt of the whole-cell pertussis vaccine. Newer studies supported the ability of the wP vaccine to adversely affect the CNS. The possibility that it worsened their clinical course in infancy by causing additional damage should not be disregarded.

The increasing number of pertussis cases reported on the last twenty years and the existence of new acellular vaccines reinforce the need of research for experimental models to assure the quality of available pertussis vaccines. In this study, allotments of whole-cell and acellular pertussis vaccines were tested through the Intranasal Challenge Model (INM) using conventional NIH mice. The results have been compared to those achieved by the "Gold standard" Intracerebral Challenge Model (ICM). In contrast to ICM, INM results did not show intralaboratorial variations. Statistical analysis by Anova and Ancova tests revealed that the INM presented reproducibility and allowed identification and separation of different products, including three-component and four-component accellular pertussis vaccines. INM revealed differences between pertussis vaccines. INM provides lower distress to the mice allowing the reduction of mice number including the possibility of using conventional mice (less expensive) under non-aseptic environment. Thus, INM may be used as an alternative method of verifying the consistence of allotment production, including acellular pertussis vaccines.

The efficacy, the ability to confer protection against a target disease and the safety of a vaccine are assessed in great detail before licensure. However, inherent limitations in the prelicensure assessment necessitate continued epidemiological evaluations of efficacy and safety issues after the introduction of vaccines into use. In Denmark, the opportunities available for epidemiological research are unique. In 2001, an initiative was undertaken to take advantage of these opportunities to study the postlicensure epidemiology of childhood vaccination with respect to effectiveness and safety. First, we describe the unique opportunities for postlicensure research in Denmark with respect to the data sources available and the epidemiological and statistical methods used. We then describe a number of recent postlicensure studies of effectiveness and safety that took advantage of these opportunities. Specifically, studies on the effectiveness of Haemophilus influenzae type b vaccination, the effectiveness of pertussis vaccination, the impact of a preschool pertussis booster on infant pertussis, measles-mumps-rubella vaccine and autism, thimerosal-containing vaccine and autism, measles-mumps-rubella vaccine and febrile seizures, childhood vaccination and Type 1 diabetes, and childhood vaccination and nontargeted infectious disease are discussed.

New vaccines are being recommended for adolescents at a brisk pace. Immunization is an effective preventive measure, and by bringing adolescents in for a medical intervention, the new vaccines promise not only to protect adolescents from the specific diseases they address, but also to enhance other health care services, including screening for other health risk behaviors. This article discusses the newest vaccination recommendations for adolescents pertaining to the meningococcal and tetanus, diphtheria, and acellular pertussis vaccines and reviews the human papillomavirus vaccines developed for use in the United States. With the advent of these new vaccines, the potential exists to improve adolescent health significantly through prevention, adding new incentive to increase adolescent immunization rates for all indicated vaccines.

Epidemiological studies suggest the hypothesis that the increase in asthma and allergies in the industrialized world can be explained by a decline in the number of infectious diseases occurring during childhood. In the context of this 'hygiene hypothesis', is immunization in early life a risk factor for promoting allergic diseases? The majority of studies, especially those conducted with more extensive populations, have not found an increased risk, and although 'not finding an increased risk' is not the same as 'the non-existence of any risk at all', it seems that the evidence is tipped in favor of the absence of risk. Conversely, although some surveys have described a protective effect of vaccination, the majority refuted this result. If there is any effect, it is probably a weak one.

After the introduction of the pertussis vaccine the number of cases decreased substantially, albeit, the disease remains present affecting mostly young infants in whom it causes severe complications, adolescents and adults. Adults are the main reservoir of Bordetella pertussis and serve as vehicle of transmission reservoir to infants. The new pertussis vaccines, manufactured for adolescents and adults, have good immunogenicity, safety and efficacy (92%) profile. The introduction of this vaccine into a universal vaccination program for adolescents and adults, would decrease the incidence of the disease in this population and more importantly, transmission of the microorganism to infants.

Adolescents, who comprise 14% of the US population, are historically resistant to receiving health care. As a result, adolescents have low immunization rates and are becoming more susceptible to diseases that are preventable by vaccine, such as pertussis. The incidence of pertussis has increased during the past 25 years, with a notable shift in incidence from young children to adolescents and young adults. New vaccines that provide protection against pertussis for use in adolescents have been proven to be safe, effective, and cost-beneficial. Regional epidemics among infants and other vulnerable populations can be reduced or eliminated with improved immunity in adolescents.

The effect of injection site on reactogenicity and specific immunogenicity was assessed in participants in a pertussis vaccine efficacy trial. The percent of DTwP and DTaP recipients with any reaction was slightly lower in subjects injected in the buttock compared with those injected in the thigh. This finding was most common in DTwP recipients. Geometric mean antibody values to pertactin, filamentous hemagglutinin and fimbriae (Bordetella pertussis antigens) were lower in DTaP vaccinees when buttock was utilized as the injection site. Our findings present evidence against the use of the buttock as the site of immunization for DTaP vaccines since the benefit with regards to reactogenicity is minimal and the immunologic response to an important antigen of B. pertussis, pertactin, is decreased.

Background: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy., Methods: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens., Results: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years., Conclusions: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children., (Copyright 2005 Massachusetts Medical Society.)

Background: Previous studies on vaccination and childhood leukaemia generated inconsistent results., Methods: In the Northern California Childhood Leukaemia Study, a case-control study with incident cases and matched birth certificate controls, detailed written vaccination records were collected. A total of 323 cases aged 0-14 years at diagnosis and 409 controls were included in this analysis. All vaccinations were censored on the reference date (date of diagnosis for cases and the corresponding date for matched controls). Conditional logistic regression analysis was conducted, adjusting for potential confounding factors. A primary variable of interest is the number of administrations (doses) of various types of vaccines., Results: Vaccinations against diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, and rubella were not associated with the risk of leukaemia. The odds ratio for each dose of Haemophilus influenzae type b (Hib) vaccine was 0.81 (95% CI 0.68-0.96). Compared with children who received two or fewer doses of Hib vaccine, those who received three or more doses had a significantly reduced risk of childhood leukaemia (odds ratio = 0.55, 95% confidence interval 0.32-0.94). The number of doses of hepatitis B vaccine received was not associated with leukaemia risk., Conclusions: Hib vaccination is associated with a reduced risk of childhood leukaemia. Future studies with detailed exposure assessment and large sample sizes are needed to further address the role of vaccinations in the etiology of childhood leukaemia.

A new Bordetella pertussis strain isolated from a whooping cough Brazilian patient was characterized under molecular and immunological aspects and compared with strains used in the production of whole-cell pertussis vaccine. The isolate, named 21A1, exhibited the bacteriological characteristics classically described for B. pertussis. RAPD and SDS-PAGE analysis showed similar DNA and proteic profiles between classical vaccinal strains and the new isolate. Comparative analysis about the efficacy of vaccines in protecting mice against the intracerebral challenge showed that the 21A1 vaccine was able to induce the highest mouse protection when compared with other B. pertussis vaccines. The results presented here indicate that the inclusion of selected new strain isolates in the composition of the B. pertussis vaccines can be an alternative to maintain or increase vaccine potency.

The toxicity and immunogenicity of the anthrax and pertussis vaccine combinations used in the 1991 Gulf War was assessed in NIH, A/J and Balb/c mice. Inoculation of pertussis vaccines, vaccine combinations, or aluminium salt caused illness, splenomegaly and significant weight loss. Although some animals recovered eventually, a lethal form of ascites developed in some NIH mice and body weights of A/J and Balb/c mice remained below normal levels. Inoculation of anthrax vaccine produced little effect. Exposure to diluted vaccine combinations produced less serious side effects of shorter duration. Single vaccinations induced specific IgG1 antibodies whereas a mixture of IgG1 and IgG2a was produced after multiple injections. Antigen stimulation of spleen cells from mice exposed to pertussis vaccines induced high levels of NO and IL-6, whereas stimulated spleen cells from mice exposed to anthrax vaccine produced only low levels of IL-6. In mice, pertussis vaccines act as an adjuvant for anthrax vaccine, but these vaccines are also the major cause of toxicity of the vaccine combination. The relatively high vaccine dose used, together with the low sensitivity of mice to anthrax toxin, emphasises that caution should be exercised in applying these results to human recipients of these vaccines.

Many countries recommend diphtheria, tetanus and/or poliomyelitis boosters in adolescents or adults and the need for pertussis booster vaccination beyond childhood is increasingly recognized. A new combined reduced-antigen-content dTpa-IPV vaccine provides booster vaccination against all four diseases in one single injection. The immunogenicity and safety of the dTpa-IPV vaccine was compared to that of licensed dTpa+IPV or Td-IPV vaccines in 806 adolescents >14 years of age and adults with a heterogeneous vaccination history. The dTpa-IPV vaccine was immunogenic and well tolerated. No clinically significant differences were observed between groups. Anti-tetanus antibody kinetics indicated that each of the vaccines could be used for tetanus prophylaxis in acute wound management. For all vaccines, the lowest post-vaccination antibody concentrations were observed in subjects >40 years of age, those seronegative prior to vaccination and those subjects whose last vaccination was > or =20 years ago. In conclusion, dTpa-IPV vaccination of subjects over 14 years of age was as immunogenic and well tolerated as the licensed dTpa+IPV or Td-IPV vaccines. Vaccination coverage of adults is poor and the use of combined vaccines such as dTpa-IPV during vaccination visits, or for wound management, maximizes opportunities for boosting in these difficult to reach age groups.

Bullous pemphigoid (BP) is a disease that characteristically affects the elderly, although cases have been described in children. We present a case of BP in a two-month-old infant with bullous lesions on the palms and soles, which appeared one week after receiving the first dose of the hepatitis B, polio, DTP and HiB vaccine. She was treated with sulphated water, dexamethasone and fusidic acid, and the lesions disappeared. One month later, she presented with a new, more generalized outbreak, three days after the second dose of the same vaccine. The skin eruption completely subsided 3 months after treatment with deflazacort was initiated (1 mg/kg/day). After five years of follow up, the patient has not presented with lesions again, despite having received the rest of the vaccines on the official schedule.

An antivaccine movement developed in Japan as a consequence of increasing numbers of adverse reactions to whole-cell pertussis vaccines in the mid-1970s. After two infants died within 24 h of the vaccination from 1974 to 1975, the Japanese government temporarily suspended vaccinations. Subsequently, the public and the government witnessed the re-emergence of whooping cough, with 41 deaths in 1979. This series of unfortunate events revealed to the public that the vaccine had, in fact, been beneficial. Furthermore, researchers and the Japanese government proceeded to develop safer pertussis vaccines. Japan now has the most experience worldwide with acellular pertussis vaccines, being the first country to have approved their use. This review describes the major events associated with the Japanese vaccination program. The Japanese experience should be valuable to other countries that are considering the development and use of such vaccines.

Routine vaccines include those listed on the Recommended Childhood and Adolescent Immunization Schedule and the Recommended Adult Immunization Schedule. The disease burden, rationale for vaccination, efficacy, adverse reactions, and recommendations are discussed in relation to each vaccine. Pictures of vaccine-preventable diseases are included.

No child should be denied immunisation without serious consideration given to the consequences. In the past, many contraindications to vaccination were based on theoretical concerns. These concerns often assumed an immunoallergic mechanism for adverse reactions, whereas many such events are often due to other causes. Other contraindications were based on evidence of excess risk, but this risk was not always balanced against the higher risk of disease. Therefore, contraindications often varied between countries and over time. In recent years, the widespread availability of less reactogenic vaccines and the common use of combined preparations have prompted a review of contraindications in many countries. Accumulated experience worldwide has allowed the list of conditions that contraindicate vaccination to be reduced. The international consensus now is that there are very few situations in which a child should not be immunised and the only true contraindication applicable to all vaccines is a history of anaphylaxis to a vaccine component or following a previous dose of the vaccine. Health professionals should feel confident in accepting national recommendations and, if in doubt, should refer children for an expert opinion, rather than deny a child protection against a serious infection.

Background: Real evaluation of any vaccine can only be done after the vaccine has been in routine use for a substantially long period of time. In Japan, acellular pertussis vaccine was introduced and totally replaced whole cell pertussis vaccine in 1981. From 1982 to 1988 40.3 million doses of acellular pertussis vaccine were given to 2-year-olds and from 1989 to 2001 59.3 million doses of acellular pertussis vaccine were given to 3-month-olds. It is now time to evaluate the efficacy and safety of acellular pertussis vaccine by the use of national data officially supplied by the Government., Methods: Government national surveillance of pertussis, which began in 1981, was used to analyze epidemiology of pertussis. Official Government reports on acceptance rates of pertussis were analyzed. A peer review has been made on all severe neurological illnesses/death occurring after pertussis immunization which have been applied for through the Vaccine Injury Compensation System, Ministry of Health Labor and Welfare, Japan., Results: High acceptance rates of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) has been maintained and a dramatic decrease in pertussis was noted over the past 23 years. Neurological illnesses temporally associated both with whole cell and with acellular pertussis vaccination has been a rare phenomenon. However, incidences of encephalopathy/encephalitis and status epileptics/frequent convulsions, febrile seizures/provocation of convulsions, and sudden deaths were significantly lower with acellular pertussis vaccination than with whole cell pertussis vaccination., Conclusion: With the use of acellular pertussis vaccine which has been accepted by the public, pertussis has been well controlled in Japan.

As shown in this work, the synthetic immunomodulator glucosaminylmuramyldipeptide (GMDP) can be included into acellular pertussis vaccine (APV). The optimal doses of GMDP, ranging from 0.001 to 0.0001 microg, have been found. These doses enhance the protective activity of APV, especially its low-active doses. GMDP decrease the manifestations of toxic, anaphylactogenic and pyrogenic properties of APV, which may lead to the decrease of the antigenic load of APV on the body of the vaccines and thus to lessening the side-effects of vaccination. GMDP has been shown to considerably increase, in comparison with common pertussis vaccine and APV, the percentage of phagocytizing leukocytes by day 14. The immunization of mice with APV with and without GMDP in doses of 0.01 and 0.001 microg leads to a change in T-lymphocyte/B-lymphocyte ratio in the population of spleen lymphocytes.

Our goal was to assess the role of early childhood vaccination in the occurrence of respiratory symptoms and allergic sensitization in 7-8-year-old Dutch and German children. A nested case-control study was conducted among children participating in a large longitudinal study on respiratory health, to study the relationship between vaccination (bacille Calmette-Guérin (BCG), pertussis, measles/mumps, rubella, and Haemophilus influenza type b (Hib)) and respiratory symptoms and allergic sensitization. Parents of 510 7-8-year-old children with respiratory complaints and an equal number of randomly selected children without respiratory complaints were asked to complete a questionnaire. Blood samples were collected for specific serum IgE analysis. Vaccination status was assessed through the records of the participating Municipal Health Services. No association between vaccination against pertussis, measles, rubella, or Hib and respiratory symptoms or allergic sensitization was found. For sensitization against house dust mite, BCG vaccination resulted in an increased risk (OR, 2.28; 95% CI, 1.05-4.96). Birth order was inversely associated with allergic sensitization, but was not related to respiratory symptoms. We found an association between BCG vaccination and the subsequent risk for sensitization against house dust mite. No evidence was found for an association between vaccination and respiratory symptoms. Earlier reports of an association of birth order with atopic disease were supported by the results of the present study.

Background: Animal data suggest an association between recent vaccination with a pertussis-containing vaccine and increased severity of respiratory syncytial virus (RSV) infection. We sought to determine whether such an association exists in humans by studying a population-based cohort of young children., Patients and Methods: We performed a nested case-control study of 280 children younger than 24 months of age hospitalized with RSV infection in Olmsted County, MN from January 1990 to December 1999. Controls (2 per case) consisted of nonhospitalized residents of Olmsted County matched to cases by date of birth and sex. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for the odds of hospitalization for RSV infection among subjects with a recent pertussis-containing vaccination in proximity to the cases' date of hospitalization relative to the odds among subjects with no vaccination., Results: The OR for receipt of a pertussis-containing vaccine within 0 to 6 days of a case's hospitalization for RSV disease was 0.8 (95% CI 0.4-1.8). For the time intervals 7-13, 14-20 and > or =21 days, the OR were 1.3 (95% CI 0.5-3.0), 1.3 (95% CI 0.5-3.2) and 0.7 (95% CI 0.3-1.5), respectively. Adjusting for vaccine delay and for risk status did not alter the findings. The median interval between the most recent pertussis-containing vaccine and the case's date of hospitalization was 40 days for cases and 42.5 days for controls (P = 0.69). Among the RSV cases, pertussis vaccination in the month preceding hospitalization was not a risk factor for oxygen requirement (P = 0.82), intensive care unit admission (P = 0.46) or need for mechanical ventilation (P = 0.28)., Conclusion: In our study, recent immunization with a pertussis-containing vaccine was not a risk factor for hospitalization for RSV infection. In addition, among children hospitalized with RSV infection, recent pertussis immunization was not associated with a more severe clinical course.

Purpose: The objective of this study was to assess the local and systemic tolerability of two batches of the Biken acellular pertussis (Pa) vaccine following administration of a single vaccine dose to adults with or without a history of prior pertussis immunization. The results from this study were compared to data from published literature., Patients and Methods: In a controlled, open-labeled double-blind trial, 518 healthy male and female adults with or without primary pertussis immunization were enrolled at three centers. All study participants had received one single dose (0.5 ml) of the Biken two-component (23.4 mg PT; 23.4 mg FHA) Pa vaccine deeply intramuscularly. Local and systemic adverse events were solicited for 4 days using diary cards. On two occasions, between day 4-7 and between day 12-16 postvaccination, vaccinees were reexamined. At the end of the observation period (day 28) vaccinees had to send a preprinted letter to the study center indicating their state of health., Results: One serious adverse event (acute appendicitis) occurred and was considered not to be related to the study vaccine. At the injection site, redness > 20 mm was observed in one subject (0.2%), and swelling > 20 mm was seen in ten subjects (1.98%). Edematous swelling occurred in three subjects (0.59%). In 27 subjects (5.34%) a "late-onset muscle mass swelling" could be palpated, usually occurring on day 6-12 postvaccination. 429 subjects (84.78%) experienced none or only slight tenderness on pressure during the. rst 4 days postvaccination, moderate tenderness on pressure was reported by 60 subjects (11.86%) and severe tenderness by 16 vaccinees (3.16%). Systemic side effects were rare: no fever > 38.5 degrees C was observed, and only seven subjects (1.39%) took antipyretics. Five patients (0.99%) experienced exhaustion or nausea. The vast majority of the participants (97.43%) would opt for the vaccination again., Conclusion: The study vaccine was safe and induced only infrequently and mostly mild, local or general symptoms that all resolved spontaneously. It was well tolerated and accepted in adults.

Aim: To observe reactogenicity of a three-component acellular pertussis (aP) vaccine simultaneously given with dT-IPV vaccine at the age of 4 years., Results: Of 813 subjects 36% had no adverse events. At the first day the score for pain was 47-55% (aP versus dT-IPV), for redness 3-4% and for swelling 5-6%. Irritability and loss of appetite had a score of 20%. In 3% of the children fever was present. Most symptoms disappeared within 3 days., Conclusion: Boostervaccination with an aP vaccine simultaneously given with dT-IPV vaccine at the age of 4 years is well tolerated.

Context: The prevalence of allergic diseases has increased considerably over the last decades. The hygiene hypothesis has emerged, linking reduced microbial exposure and infections early in life with the development of allergic diseases. Especially some of currently available non-replicating infant vaccines are unlikely to mimic a natural infection-mediated immune response that protects against the development of allergic diseases. Moreover, several studies suggested infant vaccinations to increase the risk of allergic diseases., Objective: To determine whether infant vaccinations increase the risk of developing allergic disease., Data Sources: We searched MEDLINE from 1966 to March 2003 and bibliography lists from retrieved articles, and consulted experts in the field to identify all articles relating vaccination to allergy., Study Selection and Data Extraction: We selected epidemiological studies with original data on the correlation between vaccination with diphtheria, pertussis, tetanus (DPT), measles, mumps, rubella (MMR) and Bacillus Calmette-Guérin (BCG) vaccine in infancy and the development of allergic diseases, and assessed their quality and validity., Data Synthesis: Methodological design and quality varied considerably between the studies we reviewed. Many studies did not address possible confounders, such as the presence of lifestyle factors, leaving them prone to bias. The studies that offer the stronger evidence, including the only randomized controlled trial at issue published to date, indicate that the infant vaccinations we investigated do not increase the risk of developing allergic disease. Furthermore, BCG does not seem to reduce the risk of allergies., Conclusions: The reviewed epidemiological evidence indicates that, although possibly not contributing to optimal stimulation of the immune system in infancy, current infant vaccines do not cause allergic diseases.

Serious neurological disorders reported following whole-cell pertussis in comparison to acellular pertussis vaccines were evaluated. The Vaccine Adverse Events Reporting System (VAERS) was analyzed for Emergency Department (ED) visits, life-threatening reactions, hospitalizations, disabilities, deaths, seizures, infantile spasms, encephalitis/encephalopathy, autism, Sudden Infant Death Syndrome (SIDS) and speech disorders reported with an initial onset of symptoms within 3 days following whole-cell pertussis and acellular pertussis vaccines among those residing in the US from 1997 to 1999. Controls were employed to evaluate potential biases in VAERS. Evaluations as to whether whole-cell and acellular vaccines were administered to populations of similar age and sex were undertaken because these factors might influence the study's results. Statistical increases were observed for all events examined following whole-cell pertussis vaccination in comparison to acellular pertussis vaccination, excepting cerebellar ataxia. Reporting biases were minimal in VAERS, and whole-cell and acellular pertussis vaccines were administered to populations of similar age and sex. Biologic mechanisms for the increased reactogenicity of whole-cell pertussis vaccines may stem from the fact that whole-cell pertussis vaccines contain 3,000 different proteins, whereas DTaP contains two to five proteins. Whole-cell pertussis vaccine contains known neurotoxins including: endotoxin, pertussis toxin and adenylate cyclase. Our results, and conclusions by the US Institute of Medicine, suggest an association between serious neurological disorders and whole-cell pertussis immunization. In light of the presence of a safer and at least equally efficacious acellular pertussis vaccine alternative, the Japanese and US switch to using acellular pertussis vaccine seems well justified. Other countries using whole-cell pertussis-containing vaccines should consider following suite in the near future.

Safety, reactogenicity and immunogenicity of GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix)hexa) was assessed when used for primary vaccination at 3, 4 and 5 months of age (N = 2163), compared to the separate administration of DTPa-IPV/Hib and HBV vaccines (N = 720). A similar safety and reactogenicity profile was demonstrated for both vaccine regimens, as well as a good immune response for all antigen components. By offering protection against six diseases in a series of single injections, the hexavalent DTPa-HBV-IPV/Hib vaccine was shown to be a safe, well tolerated and immunogenic alternative to primary immunization with licensed separately administered vaccines.