Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations

With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib …

Immunogenicity of routinely used childhood vaccines when coadministered with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV).

Background The choice of non-typeable Haemophilus influenzae Protein D as main carrier protein in the candidate 10-valent pneumococcal conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals), was driven in part to avoid carrier-mediated suppression and possible bystander interference with coadministered vaccines. Immunogenicity data from 3 primary and 2 booster vaccination studies were assessed for possible impacts of PHiD-CV coadministration on immune responses to routinely administered childhood vaccines, in comparison to 7-valent pneumococcal conjugate vaccine (7vCRM) coadministration. Methods Randomized, controlled studies in which PHiD-CV or 7vCRM vaccines were coadministered with DTP…

Immunogenicity of a single dose of reduced-antigen acellular pertussis vaccine in a non-vaccinated adolescent population.

Abstract German adolescents ( n  = 123) without previous pertussis vaccination, no history of pertussis and low IgG-anti-pertussis-toxin (PT) levels received one dose of the Tdap vaccine Boostrix™. Blood samples were taken before, and 5–12 days and 29–49 days after vaccination. IgG- and IgA-anti-PT, IgG- and IgA-anti filamentous hemagglutinin, IgG-anti-pertactin, IgG-anti-tetanus-toxin, and IgG-anti-diphtheria-toxin were measured by ELISA. 88.6% of subjects had an immune response to PT, and all vaccinees had an immune response to at least one pertussis antigen 29–49 days after vaccination. IgA-anti-PT and IgA-anti-FHA responses were found in 43 and 81% of subjects, respectively. This study …

Anaphylaxie nach gleichzeitiger Impfung gegen Masern, Mumps, Röteln und Frühsommer-Meningoenzephalitis aufgrund einer Gelatineallergie

Most allergic reactions after vaccination occur in patients sensitive to egg protein. Therefore this subject is well investigated, and the majority of common vaccines today contain only traces of egg protein. In contrast, there is little knowledge of hypersensitivities to other substances frequently contained in vaccines, e. g. antibiotics, phenol, gelatin and different preservatives. Here we report the case of a boy who had an anaphylactic reaction after being vaccinated against measles, mumps, rubella (MMR), and tick-born encephalitis (TBE) simultaneously. Different tests finally revealed a hypersensitivity to gelatin. This should be kept in mind especially during emergency care, since ge…

Booster vaccination after neonatal priming with acellular pertussis vaccine.

After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/ Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.

Immunogenicity and reactogenicity of a bicomponent and a tricomponent acellular pertussis-diphtheria-tetanus (DTaP) vaccine in primary immunization and as second year booster: A double-blind, randomized trial

Abstract Objectives: To compare the immunogenicities and reactogenicities of bicomponent (B) (pertussis toxoid, filamentous hemagglutinin) and tricomponent (T) (pertussis toxoid, filamentous hemagglutinin, pertactin) acellular pertussis vaccines when coadministered with diphtheria and tetanus toxoids in primary (3, 4, and 5 mo) and booster (15–19 mo) vaccinations. Design and Methods: A randomized, double-blind study involving 175 children aged 12 to 18 weeks. Reactogenicity was based on diary cards, immunogenicity assessed by ELISA measurements of serum IgG antibodies. Results: There were no clinically relevant differences in local (B = 34.5; T=31.3%) and general (B = 43.9; T=41.8%) reactog…

Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults

Priming a population with a pre-pandemic vaccine is being considered to maximize the response upon subsequent vaccination with a true pandemic vaccine more closely matched to the causative pandemic strain. The present study explored this prime-boost concept by evaluating different primary schedules with the pre-pandemic A/Vietnam/1194/2004(NIBRG-14) vaccine, containing 3.75 microg of HA, followed by a 6-month booster with a vaccine formulated with 3.75 microg HA of either the same strain or with A/Indonesia/05/2005(IBCDC-RG2), a heterologous strain from a different clade. In this multicentre, open, randomized study (NCT00430521) we measured immune responses in four groups (N = 48-60) of adu…

Impfung von allergischen Kindern

Hilfs- und Konservierungsstoffe, Reste von Kulturmedien, aber auch die Antigene eines Impfstoffs selbst konnen eine allergische Reaktion auslosen. Deren Behandlung sollte daher bei einer Impfung stets gewahrleistet sein. Bei Kindern mit allergischen Erkrankungen wird aus Angst vor schwerwiegenden Reaktionen oft nicht geimpft. Fur Kinder mit einer Huhnereiweisallergie (HEA) wird haufig befurchtet, dass sie auf einen Impfstoff mit Spuren von Huhnereiweis (MMR, Influenza) allergisch oder gar anaphylaktisch reagieren. Fur die MMR-Impfung ist mittlerweile gesichert, dass Kinder mit HEA kein erhohtes Anaphylaxierisiko haben und somit eine Hauttestung vor der Impfung oder fraktionierte Gaben unnot…

Adjustable tourniquet to manipulate pulmonary blood flow after Norwood operations

Abstract Background . Survival after first-stage palliative Norwood operations for single ventricle with systemic outflow obstruction is mainly dependent on a balanced ratio of pulmonary blood flow to systemic blood flow. Here we report the clinical results using a modified technique that allows a controlled systemic-to-pulmonary shunt flow to prevent pulmonary overcirculation. Methods . From 1995 to 1998, of 26 infants undergoing first-stage palliative Norwood operations, 7 had placement of an adjustable tourniquet around a modified right Blalock-Taussig shunt. Results . Hospital survival was 20 of 26 patients (77%). All 7 patients in whom snaring of the shunt was indicated survived. Two p…

An assessment of prime‐boost vaccination schedules with AS03A‐adjuvanted prepandemic H5N1 vaccines: a randomized study in European adults

Please cite this paper as: Gillard et al. (2012) An assessment of prime‐boost vaccination schedules with AS03A‐adjuvanted prepandemic H5N1 vaccines: a randomized study in European adults. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00349.x. Background  Long‐term persistence of immune response and safety of an H5N1 prepandemic influenza vaccine adjuvanted with AS03 (an α‐tocopherol oil‐in‐water emulsion‐based adjuvant system) was evaluated using various prime‐boost schedules that mimicked potential pandemic scenarios (NCT00430521). Methods  Five hundred and twelve healthy adults aged 18–60 years received primary vaccination with one or two doses (0, 21 days schedule…

Safety of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussis-containing vaccine.

Objective The safety of a booster dose of a reduced-antigen-content tetanus–diphtheria–acellular pertussis (Tdap) vaccine was evaluated in adolescents previously vaccinated with five doses of acellular pertussis–containing vaccine. Study design Adolescents (n = 319) previously vaccinated with either 5 doses of diphtheria–tetanus–acellular pertussis (DTaP) (n = 193) or 4 doses of DTaP plus another acellular pertussis–containing vaccine received one dose each of Tdap and hepatitis A vaccine in a double-blinded, randomized, crossover trial. Rates of adverse events (AEs) after vaccination with Tdap versus hepatitis A and rates of local AEs among adolescents vaccinated with Tdap (sixth acellular…

Evaluation der augenärztlichen Versorgung ehemaliger früh- und reifgeborener Kinder im Alter von 4 bis 10 Jahren in Deutschland – Ergebnisse der Wiesbaden Prematurity Study (WPS)

Zusammenfassung Hintergrund Ziele der vorliegenden Untersuchung waren die Evaluation ophthalmologischer Nachsorgeuntersuchungen ehemaliger früh- und reifgeborener Kinder im Alter von 4 bis 10 Jahren und der Vergleich mit den deutschen Leitlinien. Methodik In der prospektiven Wiesbaden Prematurity Study (WPS) wurden 503 Kinder, davon 239 Frühgeborene (FG) mit Gestationsalter (GA) ≤ 32 Wochen und 264 Reifgeborene (RG) mit GA ≥ 37 Wochen (Kontrollgruppe) im Alter von 4 bis 10 Jahren inklusive Refraktionsmessung und orthoptischem Status untersucht. Anisometropie war definiert als Refraktionsunterschied von ≥ 1 dpt sphärischem Äquivalent. Die Eltern wurden zusätzlich gefragt, ob nach der Entlass…

Pneumokokken und Pneumokokkenimpfstoffe

An assessment of prime-boost vaccination schedules with AS03A-adjuvanted prepandemic H5N1 vaccines: a randomized study in European adults

Please cite this paper as: Gillard et al. (2012) An assessment of prime-boost vaccination schedules with AS03A-adjuvanted prepandemic H5N1 vaccines: a randomized study in European adults. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00349.x. Background  Long-term persistence of immune response and safety of an H5N1 prepandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based adjuvant system) was evaluated using various prime-boost schedules that mimicked potential pandemic scenarios (NCT00430521). Methods  Five hundred and twelve healthy adults aged 18–60 years received primary vaccination with one or two doses (0, 21 days schedule…

Disease Burden of Rotavirus Gastroenteritis in Children Residing in Germany: A Retrospective, Hospital-based Surveillance.

Background Representative, population-based epidemiologic data for gastroenteritis caused by rotavirus (RV) are rare. RV vaccines were first licensed in Europe in 2006 and recommended in 5 western federal states in 2008 or thereafter. This study establishes a baseline for assessing the impact of vaccination and delineates the RV disease burden in Germany today. Methods Nationwide data obtained from hospitals for children 0 to 10 years of age and transferred to the Federal Statistical Office were analyzed retrospectively. Acute gastroenteritis cases because of RV were identified by the International Classification of Diseases code (ICD-10) combined with the referring diagnosis-related group …

Pneumokokken und Pneumokokkenimpfstoffe

Die 3 Bakterien Streptococcus pneumoniae, Neisseria meningitidis und Haemophilus influenzae haben gemeinsam, dass ihre Kapsel der wichtigste Pathogenitatsfaktor ist, dass sie den Nasopharynx des Menschen kolonisieren konnen und dass sie mit jeweils unterschiedlicher Haufigkeit verantwortlich sind fur ▸,invasive Infektionskrankheiten“ — Bakteriamie, Sepsis, Meningitis — wie auch fur lokale Infektionskrankheiten im Bereich der Atemwege, allen voran fur Otitis media und Pneumonie.

Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses

Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver…

Assessment of nine candidate DTP-vaccines with reduced amount of antigen and/or without adjuvant as a fourth (booster-) dose in the second year of life

Abstract Background The incidence of local reactions to diphtheria-, tetanus and acellular pertussis (DTaP-) vaccines in infants and toddlers increases with each subsequent dose, and entire thigh swellings (ETS) have been reported. Lowering the amount of antigen or of adjuvant may decrease the reactogenicity of DTaP while maintaining a protective immune response. Objectives Following priming with three doses of a DTaP vaccine during infancy, the safety, reactogenicity and immunogenicity of nine different candidate DTaP-vaccines with reduced amounts of antigen and/or adjuvant given as fourth (booster) dose were evaluated. Methods Study participants were healthy infants aged 15–27 months at t…

Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children

The present extension study, conducted in children originally vaccinated at 12–14 mo or 3–5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development.   Exploratory comparisons showed that (…

Lymphadenitis colli durch nichttuberkulöse Mykobakterien (NTM) im Kindesalter - Eine Fallserie und Literaturübersicht

Objective Lymphadenitis colli due to NTM should always be considered in children with cervical Lymphadenitis. For Germany there is a lack of data concerning the incidence, the epidemiology, the diversity and frequency of the different bacteria, the diagnosis, the clinical manifestation and the medical treatment. Methods By means of a questionnaire, which was retrospective for 1985 to 1994 and was sent to 277 children's hospitals in Germany, we collected data on Lymphadenitis colli in Germany. In our study we also incorporated cases from the "National Laboratory for Mycobacteria" in Borstel as well as six cases from our hospital in Mainz. Therefore our data includes both clinical (28) and la…

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 antibodi…

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

Abstract OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 dos…

Antibody persistence and booster response 68 months after vaccination at 2–10 years of age with one dose of MenACWY-TT conjugate vaccine

Abstract Background We evaluated antibody persistence up to 68 months (M) post-vaccination with a quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) or a licensed monovalent MenC conjugate vaccine (MenC-CRM 197 ) and subsequent booster responses to MenACWY-TT in healthy European children. Methods In the initial study (NCT00674583), healthy children, 2–10 years of age, were randomized to receive a single dose of either MenACWY-TT or MenC-CRM 197 . In the follow-up study, we present the persistence at 32, 44, 56, and 68 M post-vaccination, overall and stratified by age (2–5 and 6–10 years), and the immunogenicity and safety of MenACWY-TT administ…

Comparative effects of carrier proteins on vaccine-induced immune response

The efficacy of vaccines against major encapsulated bacterial pathogens -Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b (Hib) - has been significantly enhanced by conjugating the respective polysaccharides with different carrier proteins: diphtheria toxoid; non-toxic cross-reactive material of diphtheria toxin(197), tetanus toxoid, N. meningitidis outer membrane protein, and non-typeable H. influenzae-derived protein D. Hib, meningococcal, and pneumococcal conjugate vaccines have shown good safety and immunogenicity profiles regardless of the carrier protein used, although data are conflicting as to which carrier protein is the most immunogenic. Coadmini…

Immunogenicity and safety of two doses of tetravalent measles-mumps-rubella-varicella vaccine in healthy children.

Combination vaccines against common childhood diseases are widely used, provide an improved coverage, are more convenient and are more cost-effective than multiple injections. We conducted a study to evaluate the safety and immunogenicity of a combined measles-mumps-rubella-varicella (MMRV) candidate vaccine in comparison with the separate administration of licensed measles-mumps-rubella (MMR; Priorix) and varicella (V; Varilrix) vaccines.Healthy children 12-18 months of age received 2 doses of MMRV vaccine (3 lots) 6-8 weeks apart (MMRV group) or 1 dose of MMR vaccine administered concomitantly with 1 dose of varicella vaccine, followed by a second dose of MMR at 6-8 weeks later (MMR+V gro…

Axial Length and Anterior Segment Alterations in Former Preterm Infants and Full-Term Neonates Analyzed With Scheimpflug Imaging.

Purpose To compare the axial length and anterior segment alterations in preterm infants with and without retinopathy of prematurity with those of full-term infants. Methods The Wiesbaden Prematurity Study investigated 503 participants of former gestational age ≤32 weeks and gestational age ≥37 weeks now being aged 4 to 10 years. This study included 485 participants in the prospective controlled cross-sectional, hospital-based study with successful Pentacam Scheimpflug imaging. Anterior segment parameters, axial length measurements, and associated factors were analyzed. Results Corneal thickness did not differ between former preterm and full-term infants. Significant differences were found b…

MMR and MMRV vaccines.

Measles, mumps, rubella and varicella are viral infections which can implicate seriously long-term sequelae of infected individuals or even the unborn child. Vaccines against the individual diseases have long been available. Global measles vaccination is estimated to have prevented more than 20million deaths during 2000-2015. During the same time period, measles incidence decreased from 146 to 36 cases per million populations. Today vaccinations against measles, mumps, rubella and varicella are now carried out mainly with combination vaccines. These are today known as immunogenic and safe. MMRV had similar immunogenicity and overall safety profiles to MMR administered with or without varice…

Booster vaccination with hexavalent DTPa-HBV-IPV/Hib vaccine in the second year of life is as safe as concomitant DTPa-IPV/Hib + HBV administered separately

The safety and reactogenicity of a booster dose of GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine (N=4725) was compared with the separate administration of GSK Biologicals' DTPa-IPV/Hib and HBV vaccines (N=4474) in two open, randomized multicenter studies (A and B). Solicited symptoms occurring within 4 days of vaccination were recorded on diary cards and serious adverse events (SAEs) were collected throughout the study period. In Study A (N=1149), incidences of solicited symptoms were similar in both groups; there were no SAEs either reported within 4 days of vaccination or considered to be causally related to vaccination. In study B (N=8050), where fever was the only solicited sympt…

Inflammatory Characteristics of Monocytes from Pediatric Patients with Tuberous Sclerosis.

Objective  Therapeutic options for the tuberous sclerosis complex (TSC) syndrome showed varying outcomes. Malfunctional tsc1 / tsc2 genes leave mTOR uninhibited, a positive downstream modulator of the innate proinflammatory immune system, which has not yet been described in pediatric patients with TSC. Methods  Using polymerase chain reaction (PCR) gene expression levels of monocytes after cultivation with lipopolysaccharide (LPS) or with LPS + mTOR inhibitor rapamycin, patients with TSC ( n  = 16) were compared with healthy subjects ( n  = 20). Results  Compared with monocytes from healthy controls, LPS showed a more prominent gene expression pattern in patients with TSC (CCL24, CXCL10, IL…

A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children.

Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12-14 months) and 268 children (3-5 years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises …

Identification of an Immunogenic Medulloblastoma-Specific Fusion Involving EPC2 and GULP1

Medulloblastoma is the most common malignant brain tumor in children. Immunotherapy is yet to demonstrate dramatic results in medulloblastoma, one reason being the low rate of mutations creating new antigens in this entity. In tumors with low mutational burden, gene fusions may represent a source of tumor-specific neoantigens. Here, we reviewed the landscape of fusions in medulloblastoma and analyzed their predicted immunogenicity. Furthermore, we described a new in-frame fusion protein identified by RNA-Seq. The fusion involved two genes on chromosome 2 coding for the enhancer of polycomb homolog 2 (EPC2) and GULP PTB domain containing engulfment adaptor 1 (GULP1) respectively. By qRT-PCR …

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants.

Abstract Background To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). Methods Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12–15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each do…

Changes in lymphocyte subsets after cardiac surgery in children.

Children undergoing cardiopulmonary bypass (CPB) operations have an increased risk of developing severe infections. Impairment of the immune system may contribute to the development of sequelae such as capillary leaks, pulmonary dysfunction and auto-immune reactions. The objective of this study was to investigate the impact of cardiac surgery with CPB on the immune system of infants and young children. We conducted a prospective study to investigate the changes in circulating lymphocyte subpopulations in a sample of 21 consecutive infants and young children undergoing cardiac surgery for congenital heart disease. The following statistically significant (P<0.05) results were obtained: leucoc…

Corneal Aberrations in Former Preterm Infants: Results From The Wiesbaden Prematurity Study

Purpose To compare corneal aberrations in former preterm infants to that of full-term infants. Methods A prospective cross-sectional study was carried out measuring the corneal shape with Scheimpflug imaging in former preterm infants of gestational age (GA) ≤32 weeks and full-term infants with GA ≥37 weeks now being aged between 4 to 10 years. The main outcome measures were corneal aberrations including astigmatism (Zernike: Z2-2; Z22), coma (Z3-1; Z31), trefoil (Z3-3; Z33), spherical aberration (Z40) and root-mean square of higher-order aberrations (RMS HOA). Multivariable analysis was performed to assess independent associations of gestational age groups and of retinopathy of prematurity …

Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants.

Background Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Methods Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Results Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies…

Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy.

Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp 299 Gly and Thr 399 Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.

Identification of a novel compound heterozygote SCO2 mutation in cytochrome c oxidase deficient fatal infantile cardioencephalomyopathy

UNLABELLED Fatal infantile cardioencephalomyopathy (OMIM No. 604377) is a disorder of the mitochondrial respiratory chain and is characterised by neonatal progressive muscular hypotonia and cardiomyopathy because of severe Cytochrome c oxidase deficiency. Here we report a novel mutation in the Cytochrome c oxidase assembly gene SCO2 in an infant with fatal infantile cardioencephalomyopathy despite normal initial metabolic screening. CONCLUSION In newborns with unexplained muscular hypotonia and cardiomyopathy genetic testing of mitochondrial respiratory chain disorders might be helpful to establish a final diagnosis and guide treatment decisions.

Age-Dependent Association of Human Mannose-Binding Lectin Mutations With Susceptibility to Invasive Meningococcal Disease in Childhood

Mannose-binding lectin (MBL) is an important factor of the innate immune system, and MBL-initiated complement activation is an important early defense mechanism against various bacterial infections, including invasive meningococcal disease.In a pediatric cohort (ages 2-215 months) with invasive meningococcal disease, we investigated the overall and age-stratified frequency of 3 MBL exon 1 variations (C154T, G161A, G170A), previously shown to result in markedly decreased MBL plasma concentrations, by allele specific fluorescent hybridization probe real-time PCR assays and direct sequencing. Healthy age-matched volunteers with the same ethnic background and no history of meningococcal disease…

Detection of respiratory viral infections in neonates treated for suspicion of nosocomial bacterial sepsis: a feasibility study.

There is a lack of knowledge concerning the frequency and significance of respiratory viral infections that occur in the neonatal intensive care unit. In the present study, all neonates with suspected nosocomial bacterial sepsis were screened for a panel of respiratory viruses. Respiratory viral infections were detected in 10% of these cases. This was comparable with the frequency of a blood-culture-proven sepsis.

Granulozytenfunktion bei Frühgeborenen ab der 34. Schwangerschaftswoche und bei reifen Neugeborenen

BACKGROUND Preterm and term neonates have an increased risk to develop severe bacterial infections. Impairment of neutrophil function may be responsible for this increased risk. Other diseases related to prematurity like retinopathia of prematurity (ROP) or broncho-pulmonary dysplasia (BPD) on the other hand may be due to poorly controlled O2-radical production. PATIENTS AND METHODS Blood samples of 112 premature (34 weeks of gestation and older) and term neonates were analysed. Blood samples of 23 healthy adults (18 to 50 years old) served as controls. O2-radical production and phagocytosis of neutrophils were determined by flow cytometry, using a commercial test system. RESULTS Under the …

Immunogenicity and reactogenicity of acellular pertussis booster vaccines in children: standard pediatric versus a reduced-antigen content formulation.

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 pre-school age. The dTpa vaccine was as immunogenic and possibly better tol…

Viral Infections in Neonates with Suspected Late-Onset Bacterial Sepsis—A Prospective Cohort Study

Objective The aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. Methods In a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. Using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial virus (RSV), influenza virus A and B, H1N1 virus, parainfluenza virus 1 to 4, metapneumovirus, coronavirus, and picornavirus. Stools were examined for adenovirus, rotavirus, norovirus, and enterovirus.…

Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine.

ABSTRACT We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [ www.ClinicalTrials.gov ]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM 197 plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharid…

Do We Know When, What and For How Long to Treat?

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric C…

Linezolidtherapie bei zwei Frühgeborenen mit nekrotisierender Enterokolitis und Infektion durch Vancomycin-resistente Enterokokken

The use of the antibiotic Linezolid in two premature babies with necrotizing enterocolitis and infection with vancomycin-resistant enterococcus is described. Therapy with Linezolid in cause of necrotizing enterocolitis is an exception. Actually there are no proven recommendations for the use in this age group. Despite the successfully results more investigations for the use of linezolid in newborns and prematures are necessary.

Neonatal vaccination with an acellular pertussis vaccine accelerates the acquisition of pertussis antibodies in infants

Objectives Because young infants are at highest risk of pertussis complications, this study assessed whether neonatal acellular pertussis (aP) vaccination could provide earlier immunity. Study design Neonates (n = 121) were randomly assigned (1:1) to receive either aP or hepatitis B vaccine (HBV) (controls) vaccine at birth, followed by vaccination with DTaP-HBV-IPV/Hib at 2, 4 and 6 months. Immune responses were measured. Reactogenicity was assessed for 7 days after each dose. Results The aP birth dose was followed by few adverse events. Reactogenicity of subsequent vaccine doses did not differ between groups. Seven serious adverse events were reported from each group; none were related to…

Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants.

The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC …

Immunogenicity of reduced antigen content tetanus–diphtheria–acellular pertussis vaccine in adolescents as a sixth consecutive dose of acellular pertussis-containing vaccine

Three hundred and nineteen adolescents aged 10-12 years who had been previously vaccinated with five doses of acellular pertussis-containing vaccines received single doses of Tdap (reduced-antigen-content tetanus, diphtheria, acellular pertussis) and hepatitis A vaccines in a double-blind crossover trial. Long-term antibody persistence following vaccination with Tdap at pre-school age was similar to that following vaccination with DTaP (diphtheria-tetanus-acellular pertussis). After the sixth dose booster, Tdap induced a vigorous immune response, consistent with protection against diphtheria, tetanus and pertussis diseases.

Pertussis-specific cell-mediated immunity in infants after vaccination with a tricomponent acellular pertussis vaccine.

The aim of this study was to investigate pertussis-specific cell-mediated immunity in infants vaccinated with a tricomponent acellular vaccine. Infants were investigated during a primary vaccination schedule from the third month of life to the sixth month as well as before and after a booster at 15 to 24 months. This is the first report of specific cell-mediated immune responses to pertussis-related antigens in infants below the age of 12 months. Our data show that the vaccine induces T-cell responses specific for the vaccine components, detoxified pertussis toxin, filamentous hemagglutinin, and pertactin, that increase progressively over the course of the vaccination schedule. In contrast …

"Kinderkrankheiten" 2002

Prediction of pneumococcal conjugate vaccine effectiveness against invasive pneumococcal disease using opsonophagocytic activity and antibody concentrations determined by enzyme-linked immunosorbent assay with 22F adsorption.

ABSTRACT We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded we…

Cellular immune response of a varicella vaccine following simultaneous DTaP and VZV vaccination.

Abstract Background : Chickenpox and zoster are an important cause of morbidity among children and adults. The ability of a new, thermostable vaccine to induce varicella–zoster-virus (VZV)-specific humoral and cell mediated immunity when given simultaneously with diphtheria–tetanus-acellular pertussis vaccine (DTaP) as a booster dose in the second year of life was investigated. Methods : A new, temperature stable varicella vaccine (OKA-strain, SB-Biologicals, Rixensart, Belgium) was given simultaneously with a booster dose of DTaP vaccine. VZV-specific humoral and cell-mediated immunity was studied in the first 27 out of 232 vaccinated children at 16–28 months of age, from blood samples dra…

A combination vaccine against measles, mumps, rubella and varicella.

A new combination vaccine against measles, mumps, rubella and varicella (MMRV) from GlaxoSmithKline Biologicals has recently been approved in Europe. It combines the components from two well-established, live, attenuated vaccines against measles, mumps and rubella. This review presents a summary of the development of this MMRV vaccine from published clinical studies. Seroconversion rates and antibody titers after the first and second dose are similar to those observed after concomitant administration of the MMR and varicella vaccines. Furthermore, the clinical profile of this combination vaccine, in terms of injection- site and general tolerability, is similar to that of the component vacci…

Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe

OBJECTIVE—To obtain normal M mode (one dimensional) echocardiographic values in a substantial sample of normal infants and children.
DESIGN—Data were obtained over three years from a single centre in central Europe.
PATIENTS—2036 healthy infants and children aged one day to 18 years.
METHODS—In line with recommendations for standardising measurements from M mode echocardiograms, and using digital echocardiographic equipment, measurements were obtained of the following: right ventricular anterior wall thickness at end diastole, right ventricular end diastolic dimension, thickness of interventricular septum at end diastole and end systole, thickness of posterior wall of the left ventricle at …

The Interaction of Buccal Mucosal Epithelial Cells with E. coli Bacteria Enhances the Intraepithelial Calcium Flux and the Release of Prostaglandin E 2 (PgE 2 )

Mucosal epithelial cells contribute significantly to host defense mechanisms. Uroepithelial cells (UEC) from healthy donors suppress bacterial growth in vitro. Bacterial adherence to UEC has been shown to be a prerequisite. Similar results have been shown for buccal epithelial cells (BEC). The host response triggered by the host-parasite interaction seems to involve signal transduction and intracellular activation of second messengers. In this study the intraepithelial calcium flux was analyzed in individual BEC after bacterial contact. BEC were derived from scrapes of the buccal mucosa and labelled with fluo-3 (a calcium indicator). Thereafter the cells were analyzed immediately with a FAC…

Neue Entwicklungen bei Impfstoffen für Kinder und Jugendliche

Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants.

Safety, reactogenicity and immunogenicity of GSK Biologicals` hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix(R)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 it 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. (C) …

Effektivität einer universellen Varizellen-Schutzimpfung in Deutschland: Eine epidemiologische und gesundheitsökonomische Analyse

Varicella is a highly contagious viral disease which mainly affects young children and usually is perceived as infection with a mild disease course. However, there is increasing evidence indicating that the morbidity and mortality as well as the economic impact associated with varicella are significant. While universal childhood vaccination against varicella is currently not recommended in Germany, the availability of safe and efficacious vaccines offers the opportunity for preventive intervention. Detailed and reliable data on the consequences of varicella and the possible impact of a universal vaccination program are missing to date for Germany. In order to generate this information, we c…