Efficient maturation and cytokine production of neonatal DCs requires combined proinflammatory signals

Specific functional properties of dendritic cells (DCs) have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs). Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNgamma, CD40L, TNFalpha, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNgamma proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.     

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 vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, ≥95% of vaccinees had anti-Hib antibody concentrations ≥0.15 μg/ml and there was a marked booster response (>100-fold) in all groups. Conclusions Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity. Received: 13 June 1997 / Accepted in revised form: 4 September 1997     

Meningokokkenimpfungen

In Germany vaccination with conjugated meningococcus C (MenC) vaccine is part of the national immunization program. Polysaccharide and conjugate vaccines against meningococci A, C, W₁₃₅ and Y are available and used according to the recommendations of the standing committee (STIKO). Since 2013 a new recombinant 4-component meningococcus B vaccine (4CMenB) has been approved. The strain coverage of this vaccine in Europe is approximately 80?%. Immunogenicity and safety data for various vaccine schedules were generated in several studies as well as for co-administration with routine vaccines which leads to higher fever rates. No recommendations from the STIKO are currently available for 4CMenB vaccines.     

Granulocyte function in premature infants before the 34th week of pregnancy and in mature newborn infants]

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 experimental conditions applied, the capacity to produce O2-radicals following vigorous stimulation (E. coli) is comparable between neutrophils of preterm/term neonates and healthy adults. However, unstimulated or weakly stimulated (fMLP) neutrophils of preterm and term neonates show a statistically higher O2-radical production as neutrophils of the control group. The production of oxygen radicals increases during the first 10 days of the life. The capability of neutrophils to phagocytose E. coli is significantly lower in newborns (preterm and term) compared to the adult controls. CONCLUSIONS: The values reported here for phagocytosis and O2-radical production utilizing a commercially available test system may serve as "preliminary normal values" for neonates. No differences were found between the groups of neonates with and without infection. Impaired neutrophil-phagocytosis possibly contributes to the increased risk of preterm and term neonates to acquire bacterial infections. The increased spontaneous O2-radical production, on the other hand, may play a role for the development of so called "free radical diseases" such as ROP or BPD. However, our results cannot add further proof to this hypothesis.     

Lymphadenitis colli due to non-tuberculous mycobacteria (NTM): a case-series and review of the literature

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 laboratory (30) cases. Additionally we screened the literature on "Lymphadenitis colli in children due to NTM". RESULTS: A total of 51 cases of Lymphadenitis due to NTM could be identified. The illness occurs typically in young children up to six years of age. The most frequent cause were species of the Mycobacterium avium-intracellulare-scrofulaceum complex. Except for the local diagnosis of a cervical Lymphadenitis other clinical symptoms are missing, just as specific laboratory parameters with a subacute or chronic course. The tuberculin skin test can be false positive. The diagnosis is confirmed by biopsy and histology as well as through microbiological tests. CONCLUSIONS: The best treatment is complete surgical excision, whereas the importance of additional or exclusive treatment with Clarithromycin, Rifabutin and other antibiotics could not be clarified completely. But in patients with AIDS Rifabutin and other drugs could perhaps be useful, even for prophylaxis. Also if complete excision is impossible, treatment with certain drugs (Clarithromycin or Azithromycin in combination with Rifampicin) will be recommended. It still remains in question if NTM infections in children are really increasing.     

Griscelli syndrome: a case report

BACKGROUND: Griscelli syndrome is a rare disorder with poor prognosis. It is characterized by silver-grey hair or strands of silver-grey hair in childhood, and variable cellular immunodeficiency. The course of the untreated disease is fatal. Recurrent episodes of fever and lymphohistocytic infiltration of organs lead to hepatosplenomegaly, lymphadenopathy, pancytopenia, and progressive neurological impairment. Prognosis on morbidity and lethality depends on an early diagnosis. PATIENT: The girl we report on suffers from Griscelli syndrome. She developed normally and only her grey strands of hair, grey eyebrows, and eyelids were conspicuous. With the age of 4 years, she presented with a first episode of illness. RESULTS: Cytostatic treatment seemed to ameliorate the course of the disease although further accelerated phases could not be prevented. The only therapeutic option is a bone marrow transplantation, which we conferred upon our patient. CONCLUSION: The finding of grey hairs in childhood should alert clinicians to consider Griscelli syndrome since an early diagnosis is life and health saving.     

The efficacy of intranasal live attenuated influenza vaccine in children 2 through 17 years of age: a meta-analysis of 8 randomized controlled studies

Background

Nine randomized controlled clinical trials, including approximately 26,000 children aged 6 months to 17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza illness compared with placebo or trivalent inactivated influenza vaccine (TIV). The objective of the current analysis was to integrate available LAIV efficacy data in children aged 2-17 years, the group for whom LAIV is approved for use.

Methods

A meta-analysis was conducted using all available randomized controlled trials and a fixed-effects model. Cases caused by drifted influenza B were analyzed as originally classified and with all antigenic variants classified as dissimilar.

Results

Five placebo-controlled trials (4 were 2-season trials) and 3 single-season TIV-controlled trials were analyzed. Compared with placebo, year 1 efficacy of 2 doses of LAIV was 83% (95% CI: 78, 87) against antigenically similar strains; efficacy was 87% (95% CI: 78, 93), 86% (95% CI: 79, 91), and 76% (95% CI: 63, 84) for A/H1N1, A/H3N2, and B, respectively. Classifying B variants as dissimilar, efficacy against all similar strains was 87% (95% CI: 83, 91) and 93% (95% CI: 83, 97) against similar B strains. Year 2 efficacy was 87% (95% CI: 82, 91) against similar strains. Compared with TIV, LAIV recipients experienced 44% (95% CI: 28, 56) and 48% (95% CI: 38, 57) fewer cases of influenza illness caused by similar strains and all strains, respectively. LAIV efficacy estimates for children from Europe, the United States, and Middle East were robust and were similar to or higher than those for the overall population.

Conclusions

In children aged 2-17 years, LAIV demonstrated high efficacy after 2 doses in year 1 and revaccination in year 2, and greater efficacy compared with TIV. This meta-analysis provides precise estimates of LAIV efficacy among the approved pediatric age group.