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Biomedical subjects

R de Groot

Publications and source records attributed to R de Groot.

At least 37 records · Page 2Linked to original sources
PubMed2002

Antibody avidity and immunoglobulin G isotype distribution following immunization with a monovalent meningococcal B outer membrane vesicle vaccine.

The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.

Antibodies, Bacterial↗
PubMed2001

Therapeutic immune reconstitution in HIV-1-infected children is independent of their age and pretreatment immune status.

OBJECTIVE: To evaluate long-term immune reconstitution of children treated with highly active antiretroviral therapy (HAART). METHODS: The long-term immunological response to HAART was studied in 71 HIV-1-infected children (aged 1 month to 18 years) in two prospective, open, uncontrolled national multicentre studies. Blood samples were taken before and after HAART was initiated, with a follow-up of 96 weeks, and peripheral CD4 and CD8 T cells plus naive and memory subsets were identified in whole blood samples. Relative cell counts were calculated in relation to the median of the age-specific reference. RESULTS: The absolute CD4 cell count and percentage and the CD4 cell count as a percentage of normal increased significantly (P < 0.001) to medians of 939 x 106 cells/l (range, 10-3520), 32% (range, 1-50) and 84% (range, 1-161), respectively, after 48 weeks. This increase was predominantly owing to naive CD4 T cells. There was a correlation between the increase of absolute naive CD4 T cell counts and age. However, when CD4 T cell restoration was studied as percentage of normal values, the inverse correlation between the increase of naive CD4 T cell count and age was not observed. In addition, no difference in immunological reconstitution was observed at any time point between virological responders and non-responders. CONCLUSIONS: Normalization of the CD4 cell counts in children treated with HAART is independent of age, indicating that children of all age groups can meet their CD4 T cell production demands. In general, it appears that children restore their CD4 T cell counts better and more rapidly than adults, even in a late stage of HIV-1 infection.

Adolescent↗
PubMed2001

Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults.

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 microg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-microg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced > or 2-fold and > or =4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A-specific responses were 89% and 67%. Furthermore, up to 71% of subjects had > or =2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults.

Adolescent↗
PubMed2001

Serum bactericidal activity and isotype distribution of antibodies in toddlers and schoolchildren after vaccination with RIVM hexavalent PorA vesicle vaccine.

A clinical phase II trial with the RIVM hexavalent OMV vaccine containing six different PorAs was carried out in toddlers (2-3 years) and schoolchildren (7-8 years) in The Netherlands. Children were vaccinated three times (0, 2, 8 months). Sera after two and three vaccinations were analysed for serum bactericidal activity (SBA) and isotype distribution in whole cell enzyme linked immunosorbent assay (ELISA). The SBA after vaccination against the six PorAs was significantly different. We investigated whether the age specific and PorA specific differences in SBA titers correlated with differences in PorA specific IgG isotype distribution. The SBA titers were higher in toddlers compared with schoolchildren. After vaccination, IgG1 antibodies dominated the response followed by IgG3 antibodies. IgG2 levels were low, whereas IgG4 was not detected. Irrespective of PorA, IgG total and isotype specific titers after two and three vaccinations were significantly higher in toddlers than in schoolchildren. A weak correlation was found between IgG total or IgG1 and SBA. Although the immunogenicity of the six PorAs is very different, the isotype distribution was similar for all six tested PorAs. We conclude that the RIVM hexavalent PorA vesicle vaccine induces bactericidal antibodies mainly of the IgG1 and IgG3 isotypes that are considered to be most important for protection against disease. The isotype distribution of the response is not age-dependent.

Antibodies, Bacterial↗
PubMed2001

Emergence of rifampin-resistant Streptococcus pneumoniae as a result of antimicrobial therapy for penicillin-resistant strains.

A multidrug-resistant strain of Streptococcus pneumoniae was isolated in The Netherlands during a nosocomial outbreak among 36 patients who mainly had chronic obstructive pulmonary disease. After the commencement of barrier nursing and short-term ceftriaxone-rifampin eradication therapy, the epidemic ceased. However, eradication therapy failed in 3 patients, and follow-up investigation of these patients showed the emergence of rifampin-resistant isolates.

Amino Acid Sequence↗
PubMed2001

Prevention of meningococcal serogroup B infections in children: a protein-based vaccine induces immunologic memory.

Immunologic memory against meningococci was studied in 177 children (100 children were 10-11 years old and 77 were 5-6 years old) 2.5 years after vaccination with hexavalent meningococcal outer membrane vesicle (OMV) vaccine or hepatitis B (HepB) vaccine. Children were revaccinated with monovalent P1.7(h),4 meningococcal OMV vaccine. Serum bactericidal antibodies (SBAs) were measured before revaccination and after 4-6 weeks. A minimum 4-fold increase in SBAs against serosubtype P1.7(h),4 was detected in 48.5% of the children after hexavalent meningococcal vaccine and in 8.9% after HepB vaccine. Of the initial responders given hexavalent meningococcal vaccine, 78% had > or =4-fold increase in SBAs against strain P1.4. Thus, immunologic memory is present in toddlers and school-aged children previously given 3 hexavalent meningococcal vaccinations. Booster vaccination with monovalent P1.7(h),4 meningococcal OMV vaccine induces a significant increase in SBAs against serosubtype P1.7(h),4 and cross-reactivity against other serosubtypes in the hexavalent vaccine.

Antibodies, Bacterial↗
PubMed2001

Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients.

A single base pair insertion/deletion (4G/SG) promoter polymorphism in the plasminogen-activator-inhibitor-1 (PAI-1) gene is thought to play a part in prognosis after severe trauma. We investigated the relation between outcome of severe trauma, PAI-1 concentrations, and PAP-1 genotype in 61 patients who had been severely injured. 11 (58%) of 19 patients with genotype 4G/4G did not survive, whereas only eight (28%) of 29 patients with heterozygous genotype 4G/SG, and two (15%) of 13 patients with genotype 5G/5G died. The PAI-1 4G allele is associated with high concentrations of PAI-1 in plasma and a poor survival rate after severe trauma.

Alleles↗
PubMed2001

Predictors of a normal chest x-ray in respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) accounts for the majority of lower respiratory tract infections (LRTI) in infants and young children. A chest x-ray is frequently performed in infants with LRTI caused by RSV. The aim of this study was to develop and validate a prediction model to estimate the probability for a normal chest x-ray in children with RSV infection. For this purpose, easy obtainable diagnostic parameters were used. This prediction model may be applied to decide which patients do not require a chest x-ray. The data of 287 children admitted with RSV infection or diagnosed as such in the outpatient department of the Sophia Children's Hospital between 1992-1996 were studied. The derivation set comprised 232 patients (1992-1995), and the validation set contained 55 patients (1995-1996). A chest x-ray was designated as normal when atelectasis, hyperinflation, or pulmonary infiltrates were absent. In order to develop a prediction model, patient history and clinical and laboratory variables were consecutively entered into a logistic regression model according to the diagnostic workup that was practiced at the time. Variables with P < or = 0.10 were retained in the model. The predictive accuracy of the multivariable models was examined using the area under receiver operating curve (ROC-area). In 202 (87%) patients from the derivation set, a chest x-ray was performed. A normal chest x-ray could be predicted by increasing age, increasing birth weight, presence of rhinitis, absence of retractions, and increasing arterial oxygen saturation. The ROC-area was 0.80 in the derivation and validation sets. This prediction model was transformed into a score chart. In conclusion, a normal chest x-ray can accurately be predicted, using a model including easily obtainable patient characteristics, and clinical and laboratory variables. This model may be a useful tool in deciding whether or not to perform a chest x-ray in patients with RSV infections.

Diagnosis, Differential↗
PubMed2001

Respiratory tract infections by Mycoplasma pneumoniae in children: a review of diagnostic and therapeutic measures.

UNLABELLED: This review discusses the current knowledge on laboratory tests and treatment of respiratory tract infections caused by Mycoplasma pneumoniae (MP) in children. MP infection is endemic in most areas of the world. The highest incidence is seen in children aged between 3 and 14 years. Most infections are mild and non-pneumonic. Parapneumonic complications of MP pneumonia are rare. Complications are described affecting the skin, central nervous system, kidneys, heart, muscles and the eyes. To diagnose an acute MP infection in children, a combination of PCR and IgM serology is sensitive and convenient. In both tests it is possible to obtain a result in 1 to 2 days. As a consequence, adequate antibiotic treatment can be prescribed to the child. Macrolides are the first choice in treatment of MP infection in children. CONCLUSION: The most sensitive and rapid test to diagnose a Mycoplasma pneumoniae infection in children is a combination of nasopharyngeal polymerase chain reaction and IgM enzyme immunoassay. The treatment of choice in children is a macrolide.

Anti-Bacterial Agents↗
PubMed2001

Reviewing Omenn syndrome.

UNLABELLED: Omenn syndrome is a form of severe combined immunodeficiency associated with high mortality. Early recognition is required in order to initiate life-saving therapy. This review provides information on the clinical symptoms, laboratory parameters and pathology of the disease, supporting early diagnosis in suspected patients. A literature search was performed using Medline, encompassing the period 1965-1999. Sixty-seven cases were identified and with the addition of a recently diagnosed patient at our hospital, 68 children were included. Median age at onset of symptoms was 4 weeks. Key symptoms were erythematous rash (98%), hepatosplenomegaly (88%), lymphadenopathy (80%), often accompanied by recurrent infections (72%) and alopecia (57%). An elevated WBC (55%) was frequently observed, due to eosinophilia and/or lymphocytosis. B-cell counts were significantly decreased whereas T-cell counts were elevated. A high serum IgE was another frequent finding (91%). Therapeutic options include bone marrow transplantation or cord blood stem cell transplantation; however, the mortality still was 46%. CONCLUSION: Omenn syndrome is a fatal disease if untreated. The mortality may be reduced when diagnosis is established early and treatment is initiated rapidly by using early compatible bone marrow transplantation or cord blood stem cell transplantation.

Bone Marrow Transplantation↗
PubMed2001

A newly discovered human pneumovirus isolated from young children with respiratory tract disease.

From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.

Adolescent↗
PubMed2001

Molecular characteristics of penicillin-binding protein genes of penicillin-nonsusceptible Streptococcus pneumoniae isolated in the Netherlands.

Recently, a nation-wide molecular epidemiologic survey of penicillin-nonsusceptible Streptococcus pneumoniae has been performed in the Netherlands. In the current study, we analyzed the genes pbp1a, pbp2b, and pbp2x from these clinical isolates at the molecular level, and identified the genetic composition of the penicillin-binding domains. The pneumococcal strains were selected on the basis of differences in restriction fragment length polymorphism (RFLP) patterns of the genes pbp1a, pbp2b, and pbp2x, and represented 8, 7, and 10 distinct patterns, respectively. The genetic heterogeneity observed by sequence analysis of the pbp gene parts was comparable with the heterogeneity of the entire pbp genes as deduced from RFLP analysis. Furthermore, the mutations in the pbp sequences of the Dutch isolates invariably matched with the mutations described in pbp sequences of penicillin-nonsusceptible pneumococci isolated in other countries. Finally, novel mosaic structures were identified indicating horizontal exchange of pbp gene parts among penicillin-nonsusceptible pneumococci.

Aminoacyltransferases↗
PubMed2001

Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections.

To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2001

Pharmacokinetics of the protease inhibitor indinavir in human immunodeficiency virus type 1-infected children.

The objective of this study was to evaluate the pharmacokinetics of indinavir in human immunodeficiency virus-infected children as part of a prospective, open, uncontrolled, multicenter study in The Netherlands. Human immunodeficiency virus type 1-infected children were monitored over 6 months of treatment with zidovudine (120 mg/m(2) every 8 h [q8h]), lamivudine (4 mg/kg of body weight q12h), and indinavir (33mg/kg of metabolic weight [MW] q8h). Four weeks after the start of treatment, the steady-state pharmacokinetics of indinavir were determined by high-pressure liquid chromatography. If patients had an indinavir area under the concentration-time curve (AUC) of below 10 or above 30 mg/liter. h, a dose increase or a dose reduction was made and pharmacokinetic measurements were repeated 4 weeks later. Nineteen patients started with the dose of 33 mg/kg of MW q8h. The median AUC (range) was 10.5 (2.8 to 51.0) mg/liter. h. The median AUC (range) in 17 children treated with 50 mg/kg of MW q8h was 20.6 (4.1 to 38.7) mg/liter. h. Finally, five patients had a dose increase to 67 mg/kg of MW q8h, resulting in a median AUC (range) of 36.6 (27.2 to 80.0) mg/liter. h. After 6 months of treatment, there were 11 children with an AUC of below 20 mg/liter. h, of whom 5 (45%) had a detectable viral load, while this was the case in none of the 11 children with an AUC of higher than 20 mg/liter. h. We conclude that the optimal dose of indinavir in children to obtain drug exposure similar to that observed in adult patients is 50 mg/kg of MW q8h, which approximates 600 mg/m(2) q8h. It would even be better to adjust the indinavir dose based on an AUC of greater than 20 mg/liter. h.

Adolescent↗
PubMed2001

Pneumococcal carriage in children in The Netherlands: a molecular epidemiological study.

In 1999, Engelen and coworkers investigated colonization in Amsterdam among 259 children attending 16 day-care centers (DCCs) and among 276 children who did not attend day-care centers (NDCCs). A 1.6- to 3.4-fold increased risk for nasopharyngeal colonization was observed in children attending DCCs compared with NDCC children, while no difference in antibiotic resistance was found between groups. The serotype and genotype distributions of 305 nasopharyngeal Streptococcus pneumoniae isolates of the latter study were investigated. The predominant serotypes in both the DCC and the NDCC groups included 19F (19 and 18%, respectively), 6B (14 and 16%, respectively), 6A (13 and 7%, respectively), 23F (9 and 7%, respectively), and 9V (7 and 7%, respectively). The theoretical vaccine coverage of the 7-valent conjugate vaccine was 59% for the DCC children and 56% for the NDCC group. Genetic analysis of the pneumococcal isolates revealed 75% clustering among pneumococci isolated from DCC attendees versus 50% among the NDCC children. The average pneumococcal cluster size in the DCC group was 3.8 and 4.6 isolates for two respective sample dates (range, 2 to 13 isolates per cluster), while the average cluster size for the NDCC group was 3.0 (range, 2 to 6 isolates per cluster). Similar to observations made in other countries, these results indicate a higher risk for horizontal spread of pneumococci in Dutch DCCs than in the general population. This study emphasizes the importance of molecular epidemiological monitoring before, during, and after implementation of pneumococcal conjugate vaccination in national vaccination programs for children.

Carrier State↗