Vaccine Allergy? Skin Testing and Challenge at a Tertiary Pediatric Hospital in Melbourne, Australia.

BACKGROUND: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis. OBJECTIVE: We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. The secondary aim was to identify any significant risk factors for vaccine allergy. METHODS: A retrospective review of all children (<18 years) who underwent vaccine skin testing (skin prick testing or intradermal testing [IDT]) or challenge over a 5-year period (May 1, 2011, to April 30, 2016) at the Royal Children's Hospital Melbourne is presented. RESULTS: There were 95 admissions in 73 children. Eight percent (6 of 73) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to a suspect vaccine but challenge negative to an alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. All children in the positive group either had index reaction within 15 minutes of vaccination or had history consistent with anaphylaxis. CONCLUSIONS: The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to a suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with a suspect vaccine if negative testing or previous nonanaphylactic potential IgE-mediated AEFI.

Atypical aluminium patch tests in children with persistent itching postvaccinal nodules.

Persistent itching nodules related to aluminium-adsorbed vaccines are well known in children with frequent positive patch tests to aluminium when tested. We report two cases of children with persistent postvaccination nodules who presented with atypical eruptions after aluminium patch tests.

Vaccine-induced immune thrombocytopaenia purpura in autologous haematopoietic stem cell transplantation.

Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.

Episodio Hipotonía-Hiporreactividad posterior a la inmunización con vacuna combinada con pertussis de células enteras. Reporte de un caso / Hypotonic-Hyporesponsive Episode after immunization with whole-cell pertussis combination vaccine. Clinical Case Report

Resumen Introducción: El Episodio Hipotonía-Hiporreactividad (EHH) es un efecto adverso tras la vacuna ción, asociado principalmente a vacunas anti-pertussis de células enteras. Se caracteriza por un inicio súbito de flacidez muscular, reducida respuesta a estímulos y palidez cutánea o cianosis. Aunque el EHH es infrecuente, está considerado como un efecto adverso severo. Objetivo: Reportar un caso de EHH posterior a la administración de la vacuna combinada pentavalente con: difteria, tétanos, pertussis celular, hepatitis B y Haemophilus influenzae tipo b (DTwP-HB-Hib), que está incluida en el Programa Nacional de Inmunizaciones (PNI) de Chile, con la finalidad de difundir esta infrecuente complicación de evolución benigna, auto-limitada y de carácter no recurrente. Caso clínico: Lactante de 6 meses de edad, 3 h post-vacunación con la tercera dosis de vacuna DTwP-HB-Hib, presentó compromiso del estado de conciencia interpretado como convulsión atónica y que finalmente se consideró como EHH. El lactante evolucionó favorablemente después de 2 h y fue dado de alta tras 24 h de vigilancia clínica; se cambió el esquema de inmunización del lactante con vacunas anti-per tussis acelulares como medida preventiva. Conclusiones: El desconocimiento sobre el EHH puede desalentar la inmunización infantil. Por lo tanto, es importante que el personal médico informe a los padres de los pacientes sobre este evento benigno, autolimitado y no recurrente. En estos casos, se re comienda continuar con el programa de inmunización del lactante con formulaciones que contengan componentes anti-pertussis acelulares.

Abstract Introduction: Hypotonic-Hyporesponsive Episode (HHE) is an adverse event after vaccination, mainly associated with whole-cell pertussis vaccines. It is characterized by a sudden onset of muscle flaccidity, reduced response to stimuli and pallor or cyanosis. Although the HHE is infrequent, it is considered a severe adverse event. Objective: To report a case of HHE following the administration of the whole-cell pertussis combination vaccine (DTwP-HB-Hib), which is included in National Im munization Program (PNI) of Chile, and to contributing to the knowledge of this adverse event in the country. Case report: A 6-month-old infant, 3 hours post-vaccination with the third dose of DTwP-HB-Hib vaccine, presented a decreased level of consciousness that was interpreted as atonic seizure but finally considered as EHH. The infant progressed favorably after 2 hours of clinical observation and was discharged 24 hours later. Parents were suggested to continue the immunization schedule of the infant with acellular pertussis vaccines as a preventive measure. Conclusions: The lack of knowledge about the EHH may discourage childhood immunization. Therefore, it is important for the medical staff to inform parents of the patients about this benign, self-limited and non-recurrent adverse event. In these cases, it is recommended to continue the immunization schedule of the infant with acellular pertussis vaccines.

A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations.

OBJECTIVE: Prophylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. METHODS: Subjects received prophylactic paracetamol or ibuprofen at 0, 6-8, and 12-16 h after vaccination, or 6-8 and 12-16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. RESULTS: After the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. CONCLUSIONS: Prophylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration. ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1.

Internações sensíveis à atenção primária específicas de mulheres / Sensitive female-specific hospitalization in primary care

Objetivou-se analisar as internações por condições sensíveis à atenção primária (ICSAP) específicas em mulheres e os fatores que determinam ou influenciam a ocorrência dessas internações (fatores socioeconômicos, sociodemográficos e controle de saúde) por meio de um inquérito de morbidade hospitalar realizado com amostra de 429 mulheres internadas em hospitais conveniados ao Sistema Único de Saúde. O percentual de ICSAP foi 49,42% (n = 212), com destaque para as internações específicas do sexo feminino 19,35% (n = 83). Associaram ao risco de internar por CSAP: idade superior a 60 anos, baixa escolaridade, internação prévia, realização de controle regular de saúde, falta de vínculo com a Estratégia Saúde da Família (ESF) e ser gestante. As causas evidentes foram as condições relacionadas à gravidez, ao parto e ao puerpério e às inflamações nos órgãos pélvicos femininos. Os resultados sugerem falhas no atendimento ambulatorial que deveria ser oportuno e resolutivo no contexto da saúde da mulher.

The scope of this paper was to analyze female-specific sensitive hospitalization occurring in primary care conditions and factors that determine or affect the occurrence of such hospitalizations (social, economic and demographic factors; health control). Analysis was performed by surveys on hospital morbidity with a sample of 429 females attended in Unified Health System (SUS) contracted hospitals. The sensitive hospitalizations percentage in primary care reached 49.42% (n = 212), highlighting female-specific hospitalization at 19.35% (n = 83). Hospitalization risks comprised elderly people over sixty, low schooling, previous hospitalizations, normal health control, lack of association with the Family Health Strategy and pregnancy. Evident causes were related to conditions of pregnancy, childbirth, post-partum and inflammations of the female pelvic organs. Results suggested flaws in outpatient attendance that should be adequate and provide solutions in women’s health.

How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study.

UNLABELLED: The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. CONCLUSION: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines.

A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.

Safety and immunogenicity of 2 mixed primary infant immunization schedules of pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, and Haemophilus influenzae Type B vaccines at 2, 4, and 6 months of age: a randomized controlled trial.

BACKGROUND: Two pentavalent infant vaccines that contain either 5 or 3 component acellular pertussis antigens are authorized in Canada. Because of changes in vaccine use by provinces over time and movement of families across jurisdictions, it is possible that children are exposed to different combination vaccines during the primary infant immunization schedule. The safety and immunogenicity of mixed primary infant schedules is unknown. METHODS: In a double-blind multicenter trial, 2-month-old healthy infants were randomized to 1 of 2 schedules at 2, 4, and 6 months of age (either Pediacel, Pediacel, Infanrix [PPI] or Infanrix, Pediacel, Pediacel [IPP]). Solicited local and systemic adverse events (AEs) were collected by parent diary on days 0 through 7; unsolicited AEs were collected for 31 days after each dose. Immune responses to polypolyribosylribitol phosphate capsular polysaccharide (PRP) (Haemophilus influenzae type b) and pertussis antigens were assessed before the first dose and 28 days after the 6 month (third) dose. RESULTS: In all, 127 infants were randomized to IPP and 126 to PPI. The percentage of children with anti-PRP responses ≥0.15 µg/mL after dose 3 was higher in the IPP than in the PPI group (98.3, 95% CI: 94.1, 99.8 vs. 86.1%, 95% CI: 78.6, 91.7, P < 0.001). Antipertussis toxin and anti-fimbriae 2 and 3 responses were statistically significantly higher in the IPP than in the PPI group. Higher filamentous hemagglutinin responses occurred in PPI than in IPP. No difference between groups was observed in pertactin responses.Systemic AEs were similar between the 2 vaccine schedules. Irritability (67.2 vs. 51.6, P = 0.014) and mild crying (35.2% vs. 23.0%, P = 0.037) were more common after the 6-month dose in the PPI compared with the IPP group, as were overall systemic reactions (any intensity) for the PPI group after this dose (80.0 vs. 68.0, P = 0.042). CONCLUSION: Mixed 2-, 4-, 6-month pentavalent infant vaccine schedules had different immunogenicity and reactogenicity, with a PPI schedule being more reactogenic, and less immunogenic for PRP and fimbriae 2 and 3 antigens at 7 months. It is preferable to complete the primary infant 3-dose vaccine series with the same vaccine, rather than considering infant vaccines as interchangeable.

Vaccination as a probable cause of incontinentia pigmenti reactivation.

We report a female infant with recurrent biopsy-proven vesicobullous incontinentia pigmenti occurring after her 12-month and 18-month immunizations. To our knowledge, incontinentia pigmenti vesicobullous recurrence following immunizations has not been reported. We propose that vaccinations may serve as triggers for incontinentia pigmenti reactivation.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6 percent and 98.4 percent of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100 percent seroprotection (>0.15 µg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7 percent, 100 percent and 99.9 percent, respectively, for DTP/Hib-BM, three lots altogether and 99.2 percent, 100 percent and 100 percent for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

Safety and immunogenicity of a DTaP-IPV(Vero) (serum-free) combination vaccine in comparison to DTaP-IPV(Mkc) when administered simultaneously with Haemophilus influenzae type B conjugate vaccine (PRP-T) in children at 2, 3.5, 5 and 16 months of age.

In a phase III, double blind, randomized, noninferiority, multi-centre clinical trial, 817 infants were included and randomly assigned to vaccination with DTaP-IPV(Vero) (N=410) or DTaP-IPV(Mkc) (N=407) vaccines (Statens Serum Institut (SSI), Denmark) in the right thigh. All infants were vaccinated with Act-HIB (Sanofi Pasteur, France) in the left thigh at the same time. The vaccination schedule was 2, 3.5, 5 and 16 months and serum samples were obtained at 6, 16 and 17 months. The primary objective was to demonstrate noninferiority of DTaP-IPV(Vero) to DTaP-IPV(Mkc) as regards immunological protection against polio virus types 1, 2 and 3. Furthermore, the immunogenicity of all vaccine antigens and the safety profile of the vaccines were assessed. The study demonstrated that DTaP-IPV(Vero) was noninferior to DTaP-IPV(Mkc). All antibody concentrations/titres remained at an acceptable level from the end of the primary vaccination series (i.e. 2, 3.5 and 5 months) until the time of the booster vaccination at 16 months. A good booster response was, furthermore, demonstrated for all antigens. No vaccine-related serious adverse events and no injection site granulomas or swelling of the entire thigh occurred. The frequencies of local injection site erythema and swelling as well as systemic adverse events such as fever, irritability, somnolence and decreased appetite were low and acceptable in both treatment groups. In conclusion, DTaP-IPV(Vero) is immunogenic and safe for primary vaccination and for booster vaccination of healthy children.

Macrophagic myofasciitis in children is a localized reaction to vaccination.

Macrophagic myofasciitis is a novel, "inflammatory myopathy" described after a variety of vaccinations, almost exclusively in adults. We examined the relevance of histological findings of this myopathy to the clinical presentation in pediatric patients. Muscle biopsies from 8 children (7 months to 6 years old) with histological features of macrophagic myofasciitis were reviewed and correlated with the clinical manifestations. Patients underwent quadriceps muscle biopsy for suspected mitochondrial disease (4 patients), spinal muscular atrophy (2 patients), myoglobinuria (1 patient), and hypotonia with motor delay (1 patient). All biopsies showed identical granulomas composed of periodic acid-Schiff-positive and CD68-positive macrophages. Characteristic aluminum hydroxide crystals were identified by electron microscopy in 2 cases. The biopsy established diagnoses other than macrophagic myofasciitis in 5 patients: spinal muscular atrophy (2), Duchenne muscular dystrophy (1), phospho-glycerate kinase deficiency (1), and cytochrome c oxidase deficiency (1). Three children with manifestations and/or a family history of mitochondrial disease had otherwise morphologically normal muscle. All children had routine vaccinations between 2 months and 1 year before the biopsy, with up to 11 intramuscular injections, including the biopsy sites. There was no correlation between histological findings of macrophagic myofasciitis in biopsies and the clinical symptoms. We believe that macrophagic myofasciitis represents a localized histological hallmark of previous immunization with the aluminum hydroxide adjuvants contained in vaccines, rather than a primary or distinct inflammatory muscle disease.

Incidência de episódios hipotônicos-hiporresponsivos associados à vacina combinada DTP/Hib usada no Programa Nacional de Imunizações / Incidence of hypotonic-hyporesponsive episodes associated to the combined DTP/Hib vaccine used in Brazilian National Immunizations Program

OBJETIVO: Avaliar a segurança da vacina combinada de difteria-tétano-coqueluche de células inteiras e Haemophilus influenzae tipo b usada no Programa Nacional de Imunizações, e em especial a incidência de episódios hipotônicos-hiporresponsivos. MÉTODO: Acompanhamento de uma coorte de 21.064 lactentes (20.925 ou 99,7 por cento aderiram ao protocolo de estudo), nas 48 horas após a aplicação da vacina de difteria, tétano, coqueluche de células inteiras e Haemophilus influenzae tipo b em centros de saúde na cidade do Rio de Janeiro, para determinar e investigar eventos adversos graves, espontâneos e solicitados. Cada criança foi monitorada durante somente uma dose. RESULTADOS: A incidência de episódios hipotônicos-hiporresponsivos foi de 1:1.744 doses (casos confirmados) e de 1:1.495 doses (casos confirmados mais casos suspeitos). A taxa de incidência de convulsões foi de 1:5.231 doses. Não foram detectados casos de apnéia. Esses resultados são comparáveis àqueles relatados na literatura para a vacina contra difteria-tétano-coqueluche de células inteiras. CONCLUSÃO: A vacina contra difteria, tétano, coqueluche de células inteiras e Haemophilus influenzae tipo b em estudo pode ser usada com segurança no Programa Nacional de Imunizações, de acordo com as precauções e contra-indicações correntes.

OBJECTIVE:To evaluate the safety of a combined diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine used on the Brazilian National Immunizations Program, chiefly the incidence of hypotonic-hyporesponsive episodes. METHOD: Follow-up of a cohort of 21,064 infants (20,925 or 99.7 percent adhered to the study protocol), within 48 hours of vaccination with diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine in health care units in the City of Rio de Janeiro, to ascertain and investigate spontaneous and solicited severe adverse events. Each child was followed-up for one dose only. RESULTS: The rate of hypotonic-hyporesponsive episodes was 1/1,744 doses (confirmed cases) and 1/1,495 doses (confirmed plus suspect cases). The rate of convulsions was 1/5,231 doses. No cases of apnea were detected. These results are comparable to those found in the literature with diphtheria-tetanus-whole cell pertussis vaccine. CONCLUSION: The diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine under study can be safely used in the National Immunizations Program, according to the current precautions and contraindications.

Vaccination history and risk of childhood leukaemia.

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.

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).

Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine.

OBJECTIVE: The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4). METHODS: The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days. RESULTS: Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05). CONCLUSIONS: The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers.