Biomedical subjects
Publications and source records attributed to Johannes Forster.
A longitudinal study of health care-associated transmission of rotaviruses (RVs) in pediatric inpatients 0-48 months old in Austria, Germany, and Switzerland showed that almost one third of all cases occurred in patients 2 months old or younger. The effectiveness of vaccination against RV from 2 months of age onward remains to be evaluated.
BACKGROUND: Interleukin 8 (IL8) belongs to the family of chemokines. It mediates the activation and migration of neutrophils from peripheral blood into tissue and hereby plays a pivotal role in the initiation of inflammation. Thus it is important in inflammatory lung diseases like bronchial asthma or severe infections by Respiratory Syncytial Virus (RSV). IL8 acts through binding to the IL8-Receptor alpha (IL8RA). For both genes association with asthma has been described. In addition, IL8 has been found in association with RSV bronchiolitis. The aim of our study was to test both genes for association with asthma and severe RSV infections. In addition we were interested in whether a common genetic background of both diseases exists in regards to these genes. METHODS: We genotyped the two IL8 promotor polymorphisms -251A/T and -781C/T and the three amino acid variants M31R, S276T and R335C in IL8RA on 322 children with asthma, 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP for calculations of haplotypes. RESULTS: We found association of the IL8 polymorphism -781C/T as well as IL8 haplotypes with asthma (p = 0.011 and p = 0.036, respectively). In addition, direct comparison of the asthmatic population with the RSV population revealed significant differences, both for -781C/T alone (p = 0.034) and IL8 haplotypes (p = 0.005). The amino acid variants in IL8RA were evenly distributed in between all three populations. CONCLUSION: We conclude from our data that IL8 might play a role in the genetic predisposition to asthma and that these effects are different or even opposite to the effects on severe RSV diseases. Furthermore, IL8RA is unlikely to play a major role in the genetics of either disease.
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Surfactant protein C is part of the surfactant complex lining up the alveoles and thereby inhibiting collapse of the airways. In addition it is involved in innate immune responses. Rare polymorphisms within surfactant protein C have been linked to sporadic paediatric lung diseases, like proteinosis or interstitial lung diseases. One study in the Finnish population described association of common polymorphisms with neonatal respiratory syndrome. Other common lung diseases have not yet been investigated for association with this gene. The aim of this study was to test surfactant protein C for association with bronchial asthma and with severe respiratory syncytial virus associated diseases in infancy. The two common amino acid variants Asn138Thr and Asn186Ser were genotyped on 322 children with asthma, 131 children with severe respiratory syncytial virus associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage's trend test; haplotypes were calculated with FAMHAP and FASTEHPLUS. Polymorphisms were in Hardy-Weinberg equilibrium and in tight linkage equilibrium in all populations. Single polymorphisms showed no association with the diseases, however, surfactant protein C haplotypes were associated with severe respiratory syncytial virus associated diseases (p = 0.013). Furthermore, an inverse haplotype distribution was found between children with asthma and respiratory syncytial virus infection (p = 0.00025). The results of our study might suggest opposing roles of surfactant Protein C in the genetic predisposition for respiratory syncytial virus associated diseases vs. asthma. The causal mechanism for this observation has still to be shown.
Respiratory syncytial virus (RSV) infection has been implicated in the pathogenesis of bronchial asthma. In both diseases, interleukin (IL)-4 and IL-13 play important roles. By investigating IL4 and IL13 polymorphisms in 131 children with severe RSV infection and 270 control subjects, we found an association between IL13 polymorphism -1112C/T and severe RSV infection (P = .026). Furthermore, certain haplotypes showed an even stronger association with severe RSV infection (P = .0008). The results suggest that there is a common genetic background in children with severe RSV infection and bronchial asthma. More studies are needed to clarify whether RSV infection provokes asthma or whether RSV infection occurs in children who are genetically predisposed to a pronounced T helper 2 immune response and subsequently develop bronchial asthma.
BACKGROUND: The clinical relevance of infections with the novel human coronavirus NL63 (HCoV-NL63) has not been investigated systematically. We therefore determined its association with disease in young children with lower respiratory tract infection (LRTI). METHODS AND FINDINGS: Nine hundred forty-nine samples of nasopharyngeal secretions from children under 3 y of age with LRTIs were analysed by a quantitative HCoV-NL63-specific real-time PCR. The samples had been collected from hospitalised patients and outpatients from December 1999 to October 2001 in four different regions in Germany as part of the prospective population-based PRI.DE study and analysed for RNA from respiratory viruses. Forty-nine samples (5.2%), mainly derived from the winter season, were positive for HCoV-NL63 RNA. The viral RNA was more prevalent in samples from outpatients (7.9%) than from hospitalised patients (3.2%, p = 0.003), and co-infection with either respiratory syncytial virus or parainfluenza virus 3 was observed frequently. Samples in which only HCoV-NL63 RNA could be detected had a significantly higher viral load than samples containing additional respiratory viruses (median 2.1 x 10(6) versus 2.7 x 10(2) copies/ml, p = 0.0006). A strong association with croup was apparent: 43% of the HCoV-NL63-positive patients with high HCoV-NL63 load and absence of co-infection suffered from croup, compared to 6% in the HCoV-NL63-negative group, p < 0.0001. A significantly higher fraction (17.4%) of samples from croup patients than from non-croup patients (4.2%) contained HCoV-NL63 RNA. CONCLUSION: HCoV-NL63 infections occur frequently in young children with LRTI and show a strong association with croup, suggesting a causal relationship.
Data on the economic burden of lower respiratory tract infections (LRTI) in young children are lacking in Germany. The objective of the cost-of-illness study was to estimate the economic impact of community-acquired LRTI and nosocomial LRTI as well as of infections due to respiratory syncytial virus (RSV), parainfluenza viruses (PIV) and influenza viruses (IV). The economic analysis is part of the PRIDE study, a prospective, multi-centre, population-based epidemiological study on the impact of LRTI in children aged 0 to 36 months in Germany. The analysis includes children with community-acquired infections (1329 cases treated as outpatients, 2039 cases treated as inpatients) and nosocomial infections (90 cases). Medical services consumed were generated by chart abstraction and parental expenses data by telephone interviews within four weeks after physician visit or hospitalisation. Costs were evaluated from following perspectives: third party payer, parent and society. Total costs for outpatient treatment are Euro 123 per LRTI case. Stratified by virus type, total costs per case are Euro 163 (RSV), Euro 100 (PIV) and Euro 223 (IV). Total costs per hospitalised LRTI case amount to Euro 2579. Stratified by virus type, total costs per case are Euro 2772 (RSV), Euro 2374 (PIV) and Euro 2597 (IV). Total costs per nosocomial case are Euro 2814. Economic burden due to LRTI is Euro 213 million annually. It is concluded that treatment of LRTI in children up to age three causes a considerable economic burden in Germany. Presented results are the first data describing the economic burden of LRTI in young children assessed by means of the incidence data for Germany. This cost-of-illness study provides basic data for further decision-making, focusing on the economic assessment of preventive strategies for RSV, PIV and IV infections.
The role of suspected or confirmed neonatal sepsis in modifying the risk of atopic disease during childhood was assessed. Children with early-onset neonatal sepsis were identified from a cohort of neonates, hospitalized between 1990 and 1995. Of 196 individuals, 140 were recruited (71.4%). Pre- and postnatal history was ascertained from neonatal medical records. Based on clinical symptoms and a positive blood culture or at least three of initially defined laboratory or bacteriological criteria, they were stratified in either confirmed neonatal sepsis (CS) or suspected sepsis (SS) group. A control group (C) comprised children who were never hospitalized during infancy (n = 696). Primary end-point was the development of atopic dermatitis, bronchial asthma or allergic rhinitis during childhood (mean age 8.4 yr, range 5.7-12.4). CS and SS children had a higher prevalence of atopic dermatitis (CS 15.7%, SS 21.4%) compared with controls (C 5.2%, p < 0.001). Similarly, children with SS (7.1%), but not with CS (4.3%) had significantly more often a doctor's diagnosis of bronchial asthma compared to controls (1.9%, p = 0.02). No difference in the prevalence of allergic rhinitis was observed (CS 4.3%, SS 10%, C 8.3%). After adjusting for parental history of atopic disease and demographic factors, no significant difference for the risk to develop atopic dermatitis, asthma or allergic rhinitis among the groups was calculated in children with normal birth weight (>2500 g). Our data failed to show a possible link between hospital admission with SS and development of atopic disease.
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UNLABELLED: Population-based incidence data from Europe on the disease burden of lower respiratory tract infections (LRTI) due to respiratory syncytial viruses (RSV), parainfluenza viruses (PIV) and influenzaviruses (IV) are lacking, especially with respect to the disease burden. In a 2-year prospective multicentre study of children aged <3 years in Germany, we registered population-based cases as outpatients (n=2386), inpatients (n=2924), and nosocomially-acquired (n=141). Nasopharyngeal secretions were tested for viral RNA. The annual incidence for physician visits per 100 children for all LRTI was 28.7, RSV 7.7, PIV 3.8 and IV 1.1. Annual hospitalisation rates per 10(5) children were for all LRTI 2941, RSV 1117, PIV 261 and IV 123. Annual nosocomial cases per 10(5) hospital days were for all LRTI 79, RSV 29, PIV 9 and IV 1.5. All five children (0.27%) who died had an underlying disease and four were nosocomially acquired. CONCLUSION: Hospitalisation rates due to lower respiratory tract infections in healthy children were similar to those reported elsewhere; the rates for outpatient visits were approximately ten times higher.
BACKGROUND: In a hospital-based study by Martinello (2002), specific G gene genotypes of respiratory syncytial virus subgroup A virus were associated with an increased severity of illness. AIM: We sought to confirm the association of G genotypes with disease severity in a population-based study. MATERIAL AND METHODS: Ninety-one type A respiratory syncytial viruses (identified in the 1999/2000 season by polymerase chain reaction and cell culture), collected in a German multicenter study (PRI.DE) were analyzed for G gene diversity (amino acids 1-165). Disease severity was classified according to World Health Organization criteria for pneumonia in outpatients and by a bronchiolitis score (Rodriguez, 1997) in inpatients. Multiple regression analysis was used to explain disease severity. RESULTS: Three clusters were identified (cluster 1, n = 35; cluster 2,n = 35; cluster 3, n = 21). Sixty-seven patients had severe disease. After controlling for other variables, illness severity was significantly greater for cluster 2 viruses (odds ratio, 7.0; 95% confidence interval, 1.6 49), compared with viruses in other clusters. Other known risk factors (male gender, age) were not associated with disease severity. Our cluster 2 is genetically distinct from the virulent genotype in Martinello's study. DISCUSSION: Previously reported associations between G genotypes and disease severity in hospitalized patients can be generalized across the spectrum of illnesses including outpatients. The association seems not to be linked to a specific G gene structure. Rather G gene diversity in combination with the susceptibility of the host cohort may form the basis of such associations. Because of the magnitude of the effect, the underlying mechanisms warrant further investigation.
Most lower respiratory tract infections (LRTIs) in children under the age of 3 years are due to respiratory syncytial virus (RSV). Epidemiological, host, and viral factors eventually account for the severity of LRTIs, but they do not completely explain it. Human metapneumovirus (hMPV) was recently identified in children with LRTIs. In a population-based prospective multicenter study (the PRI.DE study, conducted in Germany over 2 years), we tested 3,369 nasopharyngeal secretions from children younger than 3 years of age with LRTIs for RSV A and B, influenza viruses (IVs) A and B, and parainfluenza viruses (PIVs) 1 to 3. Of the children requiring intensive care (n = 85), 18% had hMPV infections, and 60% of these children were infected with hMPV in combination with RSV. We did not detect hMPV in a randomly selected subset of RSV-positive nasopharyngeal secretions (n = 120) from children not requiring intensive care support. hMPV was detected in <1% of virus-negative samples from patients without intensive care support (n = 620). Our data support the hypothesis that coinfections with RSV and hMPV are more severe than infections with either RSV or hMPV alone, at least in children younger than 3 years of age.
Several studies have demonstrated that early intervention may modulate the natural course of atopic disease. The objective of this study was to prevent sensitization to house dust mite and food allergens, as well as development of atopic symptoms, during infancy. To achieve this we employed the combination of an educational package with the use of mite allergen-impermeable mattress encasings. A multi-center European, population-based, randomized controlled study of children at increased atopic risk [study on the prevention of Allergy in Children in Europe (SPACE)] was performed in five countries (Austria, Germany, Greece, Great Britain, Lithuania) and included three cohorts of schoolchildren, toddlers and newborns. We report on the newborn cohort. A total of 696 newborns were included in Austria, Great Britain and Germany. Inclusion criteria were a positive history of parental allergy and a positive skin-prick test or specific immunoglobulin E (IgE) of >or= 1.43 kU/l against at least one out of a panel of common aeroallergens in one or both parents. At 1 year of age the overall sensitization rate against the tested allergens [dust mite allergens: Dermatophagoides pteronyssinus and D. farinae (Der p and Der f, respectively)] and food allergens (egg, milk) in the prophylactic group was 6.21% vs. 10.67% in the control group. The prevalence of sensitization against Der p was 1.86% in the prophylactic group vs. 5% in the control group. In conclusion, we demonstrated, in a group of newborns at risk for atopic diseases, that the sensitization rate to a panel of aero- and food allergens could be effectively decreased through the use of impermeable mattress encasings and the implementation of preventive measures that were easy to perform.
BACKGROUND: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16 gene (A38G) was previously associated with asthma. OBJECTIVE: We evaluated the role of the CC16 SNP in pediatric asthma and asthma severity in 2 German study populations. METHODS: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the present study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1 was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. RESULTS: No association of the CC16*38A allele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC(20)FEV(1) values were significantly lower in individuals homozygous or heterozygous for the CC16*38A allele compared with those in subjects with the CC16*38GG genotype (P <.05 and P <.03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1 after exercise when homozygous for the CC16*38A allele compared with that seen in asthmatic patients with the *38AG or *38GG genotype (P <.04 and P =.006, respectively). CONCLUSION: We conclude that the CC16*A38G SNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children.
BACKGROUND: Influenza is recognized as an important disease in infants and children, but epidemiologic data on influenza in children are limited. METHODS: We analyzed German epidemiologic data from three sources: a population-based study in children 0 to 3 years of age [Paediatric Respiratory Infection in Germany (PRIDE) study]; a multicenter hospital-based survey of children 0 to 16 years of age (www.pid-ari.net); and a sentinel study (Deutsche Arbeitsgemeinschaft Influenza) comparing influenza activity and numbers of consultations for respiratory infections in children and adults. RESULTS: In 1996 to 2001, the PID-ARI-net and the PRIDE studies showed that the rate of influenza-associated hospitalizations was approximately 120/100 000 children (0 to 5 and 0 to 3 years of age, respectively). Children born prematurely and those with underlying cardiac or pulmonary disease were at increased risk of hospitalization. The mean duration of hospital stay was 6.3 days, which is equal to the mean length of hospitalization for respiratory syncytial virus infections in continental Europe. Few nosocomial infections were reported. The outpatient consultation rate per year for lower respiratory tract illness caused by influenza virus was 1.1/100 children. CONCLUSION: Direct and indirect epidemiologic evidence indicates that influenza is a significant health hazard for all children.
OBJECTIVE: To analyze prevalences of allergic sensitization and atopic disease in relation to vaccination coverage. METHODS: A German atopy risk-enhanced birth cohort of 1314 neonates who were born in 1990 in 5 German cities was studied. A total of 943 children participated in the follow-up visit at 5 years of age. Atopic symptoms and diagnoses (derived from structured interviews), total serum immunoglobulin E, and specific immunoglobulin E against 9 common allergens (CAP Radio-Allergo-Sorbent Test Fluoro-Enzyme Immunoassay) were evaluated. Children were grouped into dose percentiles according to cumulative doses of any vaccine given up to 5 years of age (<10%, 0-11 doses; 10%-50%, 12-14 doses; 51%-90%, 15-20 doses; >90%, 21-27 doses). RESULTS: The cumulative vaccine dose was inversely related to atopic dermatitis prevalences at 6 months (13.8%, 5.2%, 5.1%, and 4.5%), 2 years (16.9%, 10.9%, 7.4%, and 3.7%), 3 years (27.6%, 16.4%, 13.5%, and 4.5%), and 5 years (28.3%, 16.0%, 9.3%, and 11.9%). Asthma followed a similar pattern at age 3 (22.4%, 8.6%, 6.7%, and 6.3%), age 4 (20.0%, 8.6%, 8.9%, and 8.1%), and age 5 (20.8%, 12.6%, 10.3%, and 5.5%). Allergic sensitization rates were inversely related to the cumulative vaccine dose at age 2 (37.5%, 29.1%, 23.8%, and 12.9%). CONCLUSION: Children with a higher vaccination coverage seemed to be transiently better protected against development of atopy in the first years of life.
OBJECTIVE: To evaluate the effectiveness of prevention measures against dust mite sensitization. DESIGN: European (England, Germany, Greece, Lithuania) multicenter prospective single-blind randomized control trial with a follow-up of 12 months. PARTICIPANTS: Toddlers and preschoolers, with at least 1 parent with atopic symptoms and sensitization, who initially were not sensitized to mite allergens. INTERVENTIONS: A combination of education and a simple preventive measure (mattress encasement) to reduce mite allergen exposure. SETTING: Community-based study. MAIN OUTCOME MEASURES: Sensitization to mite allergens (skin-prick test or specific immunoglobulin E). RESULTS: Of 636 children (mean age, 3.1 years) included in the study, 566 (89%) participated in the first-year follow-up. The incidence of sensitization to mite allergens was 10 (3%) of 330 in the intervention vs 20 (6.5%) of 306 in the control arm, including loss of follow-up (intention-to-treat principle). Allergic symptoms were more common in sensitized than in nonsensitized children and so was the prevalence of physician-diagnosed asthma, eczema, and food allergy. CONCLUSIONS: This simple, harmless, and inexpensive measure can be used in toddlers and preschoolers of parents with atopic disorders to reduce sensitization to mite allergens. With regard to clinical manifestations of atopy, follow-up studies are needed to determine the effectiveness of the intervention.