Immunogenicity and reactogenicity of combined versus separately administered DTPw-HBV and Hib vaccines given to healthy infants at 2, 4 and 6 months of age, with a booster at 18 months.

OBJECTIVES: To determine the immunogenicity and reactogenicity of a combined DTPw-HBV/Hib vaccine, in comparison with DTPw-HBV and Hib vaccines given as separate concomitant injections. METHODS: In an open, randomized study, healthy infants were injected with either DTPw-HBV/Hib vaccine or separate DTPw-HBV and Hib vaccines at 2, 4 and 6 months of age, with a booster at 18 months. RESULTS: Both vaccination regimens were immunogenic, with seropositivity rates of 100% after the booster vaccination for all vaccine components. Even as early as 2 months after the second dose of the primary vaccination, most patients had seroprotective antibody titers, the proportion of seropositive subjects approaching 100% for tetanus, hepatitis B, and Hib. Post-primary and post-booster geometric mean titers (GMTs) were well above seroprotective thresholds for each vaccine antigen in both groups, with no clinically relevant differences in the groups. The separate and combined administrations showed comparable reactogenicity profiles, and neither showed a significant increase in reactogenicity with successive doses. CONCLUSIONS: The results of this study support the combination of Hib and DTPw-HBV vaccination in routine infant immunization at 2, 4 and 6 months of age with a booster at 18 months. Maximum benefit is obtained from compliance with the full course, but substantial benefit is likely to be achieved even in partially compliant patients, provided they receive at least two doses. Furthermore, these results demonstrate the tolerability of a fourth (booster) administration, where the addition of the Hib vaccine to DTPw-HBV did not lead to an increase in the overall reactogenicity.     

Primary and booster vaccination in Latin American children with a DTPw-HBV/Hib combination: a randomized controlled trial

Background  

Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib).     

Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine.

BACKGROUND: Vaccines are important weapons in the fight against infectious diseases. The World Health Organization (WHO) Expanded Program on Immunization (EPI) has been extended to include recommendations for hepatitis B and Haemophilus influenzae type b (Hib) vaccinations. The WHO has recommended that combined vaccines be used where possible, to reduce the logistic costs of vaccine delivery. This paper reviews the efficacy, safety and cost-effectiveness of Tritanrix-HB/Hib, the only commercially available combined diphtheria, tetanus, whole cell pertussis, hepatitis B and conjugated Hib vaccine. METHODS: The immunogenicity and reactogenicity results of five published clinical trials involving Tritanrix-HB/Hib in a variety of immunization schedules and countries were reviewed. Based on these data and cost-effectiveness studies, an assessment of its suitability for use in national immunization programs was made. RESULTS: Tritanrix-HB/Hib has shown excellent immunogenicity in clinical trials using a variety of schedules, with no reduced immunogenicity observed for any of the components of the combined vaccine. It has similar reactogenicity to DTPw vaccines alone. Pharmacoeconomic analyses have shown combined DTP-HB/Hib vaccines to be cost-effective compared to separate vaccines. CONCLUSIONS: Replacement of DTPw vaccination by Tritanrix-HB/Hib can be done without modifying the existing national immunization programs. This should facilitate widespread coverage of hepatitis B and Hib vaccinations and their rapid incorporation into the EPI.     

Evaluation of the immunogenicity and reactogenicity of a DTPa-HBV-IPV Combination vaccine co-administered with a Hib conjugate vaccine either as a single injection of a hexavalent combination or as two separate injections at 3, 5 and 11 months of age

A combined DTPa-HBV-IPV/Hib vaccine containing diphtheria (D), tetanus (T), acellular pertussis (Pa), hepatitis B (HBV) and types 1, 2 and 3 inactivated polioviruses (IPV) extemporaneously mixed with a conjugated Haemophilus influenzae type b (Hib) vaccine (Group 1) was compared to the DTPa-HBV-IPV and Hib vaccines (Group 2) administered separately at 3, 5 and 11 months of age (n = 440). A microneutralization assay was used to detect antibodies against the 3 polio virus types (cut-off 1:8 dil), RIA for anti-HBs antibodies (cut-off 10 mIU/ml) and ELISA for antibodies against all other vaccine antigens (cut-off: 0.1 IU/ml for anti-tetanus and anti-diphtheria antibodies; 5 El.U/ml for antibodies against each of the 3 acellular pertussis antigens and 0.15 microg/ml for anti-PRP antibodies). Similar immune responses were observed in both groups 1 month after dose 2 as well as after dose 3. Six months after dose 2 however, the proportion of subjects maintaining an anti-tetanus antibody concentration > or = 0.1 IU/ml was lower in Group 2 and a slight group difference in favour of Group 1 was also observed for anti-PRP, anti-diphtheria and anti-polio type 1 antibody persistence prior to the third dose. The overall incidence of local and general solicited symptoms was similar in both groups. One subject discontinued study vaccination following an SAE considered to be related to vaccination. The DTPa-HBV-IPV/Hib combined vaccine is immunogenic and well tolerated when administered according to a 3, 5 and 11 month vaccination schedule and can therefore be considered as a feasible alternative to the separate administration of the pentavalent DTPa-HBV-IPV and the monovalent Hib vaccines.     

The development of a new heptavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C vaccine: a randomized dose-ranging trial of the conjugate vaccine components.

OBJECTIVE: To assess immunogenicity, antibody persistence, immune memory, and reactogenicity of a novel heptavalent DTPw-HBV/Hib-MenAC (diphtheria, tetanus, whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C) vaccine. DESIGN: This was an open, randomized study in the Philippines, with DTPw-HBV/Hib-MenAC administered at 6, 10, and 14 weeks of age. Three different polysaccharide contents of the conjugate vaccine components were assessed with conjugated PRP (polyribosylribitol phosphate), MenA, and MenC polysaccharides at the following doses: 2.5 microg of each, 5 microg of each, or 2.5 microg of PRP and 5 microg each of MenA and MenC. Controls received licensed DTPw-HBV and Hib or DTPw-HBV/Hib and MenC conjugate vaccines separately. Immune memory was evaluated via plain polysaccharide challenge administered to half of the subjects at 10 months of age. RESULTS: After primary vaccination, at least 97.7% of DTPw-HBV/Hib-MenAC recipients had serum bactericidal antibody (SBA)-MenA and SBA-MenC titers > or =1:8, and at least 99% had anti-PRP antibody concentrations > or =0.15 microg/ml. Immune responses to DTPw-HBV components were not impaired by the lowest dose of Hib-MenAC vaccine. Plain polysaccharide challenge induced marked increases in Hib, MenA, and MenC antibodies in primed subjects, indicative of immune memory. All of the experimental vaccines were well tolerated. CONCLUSION: The lowest dose of DTPw-HBV/Hib-MenAC polysaccharide conjugate vaccine was well tolerated, immunogenic, had good persistence of antibodies, and demonstrated immune memory, and consequently was selected for further development.     

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Background  

Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib_2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.     

Immunogenicity and reactogenicity of two regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio and Haemophilus influenzae type b vaccines administered to infants primed at birth with hepatitis B vaccine

An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).     

Prevalence of hepatitis B surface antigen in vaccinated children and controls in rural Nigeria.

OBJECTIVE: To determine the prevalence of hepatitis B surface antigen (HBsAg) amongst vaccinated children and controls aged 1-4 years in a rural community in mid-western Nigeria. METHODS: The vaccinated children had received at least three doses of hepatitis B vaccine. The vaccines included recombinant hepatitis B vaccine at birth and a combined diphtheria, tetanus, pertussis (whole cell) plus hepatitis B (DTPw-HBV) vaccine. HBsAg was determined by a rapid immunoassay method based on the immunochromatographic sandwich principle. Two hundred and twenty-three children and 219 controls were recruited into the study. RESULTS: The prevalence of HBsAg was significantly lower in the vaccinated group (1.3%) than in the control group (4.6%, p=0.04). The prevalence rates were significantly higher in males (p=0.02) and two-year birth cohort (p=0.01). The controls were estimated to be at a six-fold higher risk of being positive for the surface antigen than the vaccinated children. The vaccine effectiveness was estimated to be approximately 80%. CONCLUSION: These results confirm that hepatitis B vaccine protects against hepatitis B surface antigen carriage and confirm immunogenicity of the combined DTPw-HBV vaccine.     

Primary vaccination with a new heptavalent DTPw-HBV/Hib-Neisseria meningitidis serogroups A and C combined vaccine is well tolerated.

OBJECTIVE: Safety and reactogenicity of a new heptavalent DTPw-HBV/Hib-MenAC (diphtheria, tetanus, whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C) vaccine was compared with a widely used pentavalent DTPw-HBV/Hib vaccine. METHODS: Three phase III randomized studies comparable in design and methodology, in which healthy infants received DTPw-HBV/Hib-MenAC (N=1334) or DTPw-HBV/Hib (N=446) at 2, 4, and 6 months, were pooled for analysis. Solicited symptoms were recorded for 4 days, and unsolicited adverse events for 31 days after each dose. Serious adverse events (SAEs) were recorded throughout the studies. RESULTS: There were no significant differences between the two groups in the proportion of subjects with fever >39.5 degrees C or >40.0 degrees C (p<0.005). Compared to group DTPw-HBV/Hib, a significantly higher percentage of subjects in group DTPw-HBV/Hib-MenAC reported fever >39 degrees C (21.2% vs. 14.8%, p=0.004). Fever subsided quickly, did not lead to differences in attendance to medical services and did not increase from dose to dose. Sixty-seven SAEs were reported, 56/1334 (4.2%) in group DTPw-HBV/Hib-MenAC and 11/446 (2.5%) in the DTPw-HBV/Hib group. CONCLUSION: Overall, the heptavalent and pentavalent vaccines had similar safety profiles. The difference observed in percentage of subjects with fever >39 degrees C did not lead to differences in medically attended visits for fever.     

A fully liquid diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis--Haemophilus influenzae type b conjugate vaccine: immunogenicity and safety of primary vaccination in Taiwanese infants.

OBJECTIVE: To assess the immunogenicity of a fully liquid diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae type b (DTaP-IPV-Hib) conjugate vaccine compared to DTaP-IPV and lyophilized Hib conjugate vaccines given simultaneously at separate sites as a three-dose primary vaccination in Taiwanese infants. METHODS: Two hundred infants were randomized to receive either DTaP-IPV-Hib or DTaP-IPV plus Hib vaccine at 2, 4, and 6 months of age. Both combined vaccines contained the same five pertussis antigens: pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), fimbriae 2 and 3 (FIM 2&3). Antibody concentrations were measured before the first and after the third dose. Reactogenicity was evaluated from parental reports. All subjects received hepatitis B vaccine at 0, 1, and 6 months of age following the national vaccination schedule of Taiwan. RESULTS: The immunogenicity after the third dose was high for each vaccine antigen in both groups, and the vaccines had low reactogenicity. Statistical analysis showed no differences in the immune responses to the fully liquid DTaP-IPV-Hib vaccine compared with those to the DTaP-IPV plus Hib control vaccines, notably the anti-PRP (polyribose ribitol phosphate capsular polysaccharide) response, with 97-99% of infants having concentrations >or=1.0 microg/mL. Approximately 95% of all infants developed seroprotective levels of anti-hepatitis B surface antigen (HBs) antibodies (>or=10 mIU/mL). CONCLUSIONS: Both combination vaccines had similar high immunogenicity for each antigen, and both were well tolerated. Thus, inclusion of a Haemophilus influenzae type b conjugate vaccine in the combination did not result in clinically significant decrease in the PRP response or increase reactogenicity. The fully liquid pentavalent vaccine has the advantages of not requiring reconstitution and of administration as a single injection.     

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age

OBJECTIVE: The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS: Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 mug/mL or greater and 1.0 mug/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS: The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine.     

Safety and immunogenicity of a primary course and booster dose of a combined diphtheria, tetanus, acellular pertussis, hepatitis B and inactivated poliovirus vaccine

Primary immunization at 3, 4.5, and 6 months and boosting between 15 and 27 months of age with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) vaccine was compared with separate administration of DTPa-HBV and IPV to healthy children (trials DTPa-HBV-IPV-019/033). Antibody titres were measured before and 1 month after primary and booster courses. Solicited local and general symptoms were recorded using diary cards. One month after primary vaccination, all children in both groups developed antibody titres above the assay cut-off for all vaccine components. Significantly higher anti-diphtheria, anti-pertactin (PRN) and anti-polio GMTs were measured following DTPa-HBV-IPV than DTPa-HBV plus IPV. Prior to boosting similar seroprotection/seropositivity rates were recorded in both groups. After boosting all children had seroprotective levels of diphtheria, tetanus, polio and HBV. Criteria for pertussis vaccine response were fulfilled in most children. Significantly higher anti-PRN GMTs were measured following DTPa-HBV-IPV than DTPa-HBV plus IPV. There was no difference between groups in the incidence or intensity of local and general symptoms after primary or booster vaccination, except for fever which was more frequent after the booster dose in the combined vaccine group. Both vaccine regimens were well tolerated and immunogenic, however the combined administration has the advantage of being administered as a single injection.     

L’allergie aux vaccins associés chez l’enfant. Une étude de 30 cas fondée sur les tests cutanés à lecture immédiate,semi-retardée et retardée,sur les dosages des anticorps spécifiques et sur les injections de rappel

Skin tests (prick and intradermal) were performed with vaccines containing diphtheria, pertussis, tetanus, polio and Haemophilus influenzae type b antigens (D.P.T.Pol.Hib), and with selected components of the vaccines in 30 children reporting reactions suggestive of allergy to these vaccines. Serum-specific IgE and IgG against components of the vaccines were also studied. Immediate responses in skin tests and specific IgE determinations strongly suggested the diagnosis of immediate-type hypersensitivity to tetanus or diphtheria toxoids in ten children (33.3%), including four of the six children with anaphylaxis, and six of the 16 children with urticaria and angioedema. In the other 20 children, immediate, semi-late and late responses in skin tests and specific IgE determinations were negative. Booster immunizations were given with monovalent or bivalent vaccines in 14 of these children, and were well tolerated. Our results suggest that most large local reactions and mild to moderately severe generalized skin reactions to multivalent vaccines are not allergic, but instead result from a nonspecific inflammatory reaction. However, our results show that toxoids may induce immediate-type hypersensitivity reactions in children, and suggest that skin tests with vaccines and vaccine components, and the determination of specific IgE against vaccine components, are of diagnostic value in children with anaphylaxis, and immediate and accelerated urticaria and angioedema induced by booster injections of multivalent vaccines.     

Pediatric disease burden and vaccination recommendations: understanding local differences

BackgroundDiphtheria (D), tetanus (T), pertussis (P), hepatitis B (HepB), invasive Haemophilus influenzae type b (Hib) disease, and measles cause substantial global morbidity and mortality.MethodsThis unique review highlights geographic differences in disease burden across certain countries in the African, Americas, Mediterranean, South-East Asian, and Western Pacific World Health Organization (WHO) regions, and relates this to vaccination coverage and local vaccine recommendations using the authors’ countries as illustrations.ResultsSubstantial differences were observed in the incidence of these diseases and in vaccination coverage between the countries studied. Disease incidence often reflected inadequate surveillance, but also variable or poor vaccination coverage. Vaccination coverage against HepB was particularly low in the African and South-East Asian WHO regions; vaccination coverage against invasive Hib disease was low in these regions and in the Eastern Mediterranean and Western Pacific WHO regions. Vaccination schedules within some countries in these regions do not include, or have only recently included, vaccinations against HepB and Hib disease. The use of DTwP–HepB–Hib (diphtheria, tetanus, whole-cell pertussis, HepB, Hib) combination vaccines has now been adopted by some countries to help increase vaccination coverage.ConclusionsVaccination coverage and vaccination schedules vary markedly between the countries studied, often according to the resources available. DTwP–HepB–Hib combination vaccines represent a cost-effective option, with the potential to substantially reduce the burden associated with these diseases by increasing coverage and compliance.     

Erythema multiforme minor following vaccination with paediatric vaccines

We present 2 cases of erythema multiforme following a combined tetanus and diphtheria revaccination and a combined diphtheria, tetanus, acellular pertussis inactivated polio and Haemophillus influenzae type B vaccine respectively, suggesting vaccines containing diphtheria and tetanus toxoids as a potential precipitating factor to erythema multiforme.     

The new DTPw-HBV-Hib combination vaccine can be used at the who schedule with a monovalent dose of hepatitis B vaccine at birth

An open, randomized, clinical trial was conducted in order to assess the reactogenicity and immunogenicity of DTPw-HBV and Haemophilus influenzae type b (Hib) vaccines when given either as a mixed administration or as separate concomitant injections using the WHO schedule at 6, 10 and 14 weeks of age, following a dose of HBV at birth. There were no clinically relevant differences in the immune response to any component between the mixed and separate administrations. In fact the anti-tetanus GMTs were significantly higher (p=0.002) in mixed administration (3.9 IU/ml) compared with the separate administration (1.9 IU/ml). However although all subjects achieved anti-PRP titers > or = 0.15 microg/ml, higher anti-PRP GMTs were seen in the group receiving the separate administration. Importantly, the addition of Hib did not adversely alter the reactogenicity profile of DTPw-HBV. This report which demonstrates that this novel combination can be used in WHO recommended schedule.     

Randomized trial of the immunogenicity of fractional dose regimens of PRP-T Haemophilus influenzae type b conjugate vaccine

To assess the immunogenicity of more economical regimens of Haemophilus influenzae type b (Hib) conjugate vaccine, a randomized trial of fractional doses of polyribosylribitol phosphate-tetanus toxoid (PRP-T) Hib vaccine was undertaken in the Dominican Republic. Six hundred children were assigned to one of six regimens with PRP-T vaccine: full-dose, half-dose, and one-third-dose of Hib vaccine given separately or combined with diphtheria, tetanus, and pertussis (DTP) vaccine at ages 2, 4, and 6 months. Regimens that elicited antibody levels > 1.0 microg/mL in >70% of children and < or = 0.15 microg/mL in > 90% of children were considered acceptable. At 1 month post Dose 3, all regimens met the criteria for acceptable response. Among those who received Hib as a separate injection, geometric mean concentrations of anti-PRP bodies (GMCs) at age 1 month post Dose 3 were 11.2, 11.9, and 16.3 in the full, half, and one-third dose groups, respectively. Among those who received Hib and DTP combined, the GMCs were 6.4, 5.2, and 5.7 in the full-, half-, and one-third-dose groups respectively.     

A fourth dose of DTPa-IPV vaccine given to 4-6 year old children in Italy and Sweden following primary vaccination at 3, 5 and 11-12 months of age

Healthy 4-6 y old children from Italy and Sweden immunized with DTPa and inactivated or oral polio vaccines at 3, 5 and 11-12 months of age, received 1 dose of combined DTPa-IPV (n = 211) or DTPa + IPV as separate doses (n = 205) in a randomized trial. The pre-booster seroprotection rates were similar in each group and were above 60% against all antigens except diphtheria (31.3% and 37.0%) and PT (21.5% and 25.9%) in the DTPa-IPV and DTPa + IPV groups, respectively. At least 99.5% of subjects had seroprotective antibody levels against diphtheria, tetanus and polioviruses and > or = 96% showed a vaccine response to each pertussis antigen after vaccination. Post-booster antibody levels increased at least 51-fold for anti-diphtheria and anti-tetanus, at least 18-fold for anti-pertussis antibodies and at least 32-fold for antibodies against all 3 poliovirus types, compared to prior levels. DTPa-IPV was comparable to DTPa + IPV in terms of seroprotection rates and mean antibody levels against each vaccine antigen. Similar reactogenicity profiles were observed between groups including swelling > 50 mm [13% (9.1, 18.7) vs 17% (12.4, 23.4)] or involving an adjacent joint [0% (-,-) vs 1.5% (0.3, 4.3)] and were consistent with previous reports. The combined DTPa-IPV vaccine could be used to add DTP valences to the IPV vaccine currently given to children in Scandinavia and Italy at 4-6 y of age and reinforce protection against 4 diseases.     

Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993-2003).

BACKGROUND: Acute bacterial meningitis remains an important cause of morbidity, neurologic sequelae, and mortality in children in Latin America. METHODS: We retrospectively reviewed the hospital-based medical records of children diagnosed with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city referral Hospital in Mexico City, for a 10-year period (1993-2003). To characterize the epidemiology, clinical features, and outcomes of acute bacterial meningitis, we subdivided our study into two time periods: the period prior to the routine use of Haemophilus influenzae type b (Hib) vaccine (1993-1998) and the period after the vaccine became available (1999-2003). RESULTS: A total of 218 cases of acute bacterial meningitis were identified during the study period. The most frequently affected age group was that of children aged between 1 and 6 months. Hib was the most commonly isolated pathogen, found in 50% of cases. However, its incidence declined significantly after the introduction of the combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP-HB/Hib) pentavalent vaccine into the universal vaccination schedule for children in 1998. Streptococcus pneumoniae followed as the second most commonly isolated bacterial pathogen. Neisseria meningitidis was isolated in only a few cases, confirming the historically low incidence of this pathogen in Mexico. Identified risk factors for death were found to include the presence of septic shock and intracranial hypertension, but were not attributable to any particular bacterial pathogen. CONCLUSIONS: In our hospital, acute bacterial meningitis remains a severe disease with important sequelae and mortality. The incidence of Hib meningitis cases has declined since the introduction of the Hib vaccine. However, S. pneumoniae persists as an important cause of bacterial meningitis, highlighting the need for the implementation of vaccination policies against this pathogen.     

Low seroprevalance of diphtheria,tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination

BackgroundTetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital.MethodsBlood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values.ResultsA total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases—Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis.ConclusionsWe demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood—diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of “lifelong vaccination” should be implemented and every encounter with the patient should be regarded as a chance for catch-up.