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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 the time of booster vaccination. Each participant had received three doses of a DTaP vaccine (Infanrixtrade mark, GlaxoSmithKline, Rixensart, Belgium; "reference DTaP") at age 3, 4, and 5 months as part of a previous clinical trial. More than 20,000 children were eligible for participation in the current study protocol at the time. In a first phase at a University hospital-based vaccination study center, nine sequential cohorts of 63-119 study subjects received one of nine different candidate vaccines. Patients and study personal were blinded with regard to which vaccine was currently in use. Reactogenicity was solicited from parents using diary cards. Blood was drawn prior to and 4 weeks after vaccination and immediately centrifuged. The serum was stored at -20 degrees C until serology was performed by ELISA tests. As soon as the first candidate vaccine with adequate reactogenicity and immunogenicity profile was identified in the first study phase, a second study phase was initiated in parallel, to evaluate the safety and reactogenicity of the respective candidate vaccine in private practices in large cohorts (1613-2095 study subjects per group)., Results: In the first study phase, DTaP with no aluminum induced the highest frequency of ETS and fever. All other candidate vaccines caused lower rates of local and general reactions than the reference DTaP. As a general rule, vaccines with less antigen induced fewer reactions, although there was no strict dose-response effect and the difference, e.g. between a one-tenth and a one-fifth DTaP dose (DTaP 1/5; DTaP 1/10) was not clinically relevant. Separate injections of Td and aP caused fewer general reactions than the respective TdaP combination and local reactions were higher at the aP than at the Td injection site. Again, as a general rule, reduced amounts of antigen induced lower antibody concentrations, although all vaccines induced "protective" anti-tetanus and anti-diphtheria antibody responses. A total of 92-100% of children showed seroresponses to pertussis antigens even when vaccinated with reduced amounts of the respective pertussis antigen. Elimination of aluminum from DTaP vaccine induced higher anti-tetanus-antibody concentrations and so did a reduction of the amount of diphtheria antigen. Additional examples for antigen interaction were increased antibody concentrations, observed with injection of Td and aP into different limbs. In the second study phase, all three vaccines evaluated (one with a reduced amount of diphtheria antigen, TdaP; one with reduced amounts of all antigens, tdap; and one with a fifth dose of the reference vaccine (DTaP 1/5)) were safe and had an acceptable reactogenicity profile in a total of 4871 study subjects., Conclusions: Local reactions due to DTaP booster doses in the second year of life can be reduced by reducing the amount of antigen in the respective vaccine while an adequate immunogenicity is maintained. Aluminum-free vaccines induced ETS and fever most commonly. Any changes in vaccine composition should lead to a full evaluation of the new product. more...

Background: In Germany, Haemophilus influenzae type b (Hib), polio and hepatitis B (HBV) vaccines have been combined with diphtheria, tetanus and acellular pertussis vaccines. We examined whether the use of combination vaccines has improved the timing of these vaccinations., Methods: Vaccination information was obtained from representative nationwide telephone interviews about 2701 children born from 1996 through 2003 in Germany. We assessed up-to-date vaccination as the percentage of children vaccinated by 3, 5 and 15 months for the first dose, full primary series and full immunization, respectively. We compared results over periods when different combination vaccines were used. We also compared median age at first dose, full priming and full immunization for children receiving different types of combination vaccines., Results: During the study period, monovalent vaccines were replaced by higher-valent combination vaccines. With the change from mono- to 4-, 5- and 6-valent vaccines, up-to-date vaccination increased for Hib, polio and HBV. Median age at immunization improved by 0.5 month for Hib, 0.4 month for polio and 0.9 month for HBV at the first dose and 2.2 months for Hib, 3.2 months for polio and 1.4 months for HBV at full immunization when comparing hexavalent with monovalent vaccines. Median age for 4-5-valent vaccines was intermediate. The difference between monovalent and 6-valent vaccines remained significant after stratifying/adjusting for the effect of birth cohorts., Conclusion: Combination vaccines are usually advocated for reducing the number of injections. In Germany, however, the use of combination vaccines has also significantly improved timeliness of immunizations. more...

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 dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens., Results: Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41 IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever >or=38.0 degrees C following each vaccination was reported more frequently in the PCV7 group (28.3-50.0%) than in the Control group (15.6-33.6%) whereas fever >39.0 degrees C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8-2.7%; Control, 1.6-4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever., Conclusion: DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12-15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children. more...

Influenza is often regarded as an illness of the elderly portion of the population because most of the excess mortality associated with influenza epidemics occurs in that age group. However, evidence derived from a large number of clinical studies carried out in different countries and various settings has clearly demonstrated that the burden of influenza is also substantial in children. The attack rates of influenza during annual epidemics are consistently highest in children, and young children are hospitalized for influenza-related illnesses at rates comparable to those for adults with high-risk conditions. Especially among children younger than 3 years of age, influenza frequently predisposes the patient to bacterial complications such as acute otitis media. Children also serve as the main transmitters of influenza in the community. A safe and effective vaccine against influenza has been available for decades, but the vaccine is rarely used even for children with high-risk conditions. Despite several existing problems related to influenza vaccination of children, the current evidence indicates that the advantages of vaccinating young children would clearly outweigh the disadvantages. Considering the total burden of influenza in children, children younger than 3 years of age should be regarded as a high-risk group for influenza, analogously with the age-based definition of high risk among persons 65 years of age or older. Annual influenza vaccination should be recommended to all children from 6 months to 3 years of age. more...

Background: The Charcot-Marie-Tooth (CMT) disorders are a group of hereditary motor and sensory neuropathies characterized clinically by peripheral muscle wasting and weakness. We hypothesized that unknown involvement of the muscle used for monitoring neuromuscular block may account for the conflicting reports about the effect of nondepolarizing neuromuscular agents in these patients. The aim of this study was to compare onset and recovery from mivacurium-induced neuromuscular block on the adductor pollicis and orbicularis oculi muscles., Methods: We used mivacurium 0.2 mg.kg(-1) in five children (aged 7-12 years) with CMT type I undergoing propofol-fentanyl-oxygen-air anesthesia for orthopedic surgery. Using acceleromyography, neuromuscular transmission was monitored in parallel in the eye and thumb muscles, and onset and duration times were recorded., Results: Following bolus administration of 0.2 mg.kg(-1) of mivacurium the onset time ranged between 135 and 240 s and 75 and 165 s in the eye and in the thumb, respectively. The recovery time varied between 5.3 and 16 min and 6 and 31.3 min in the eye and in the thumb, respectively., Conclusions: In our small series of patients with CMT the clinical duration of mivacurium-induced neuromuscular block was similar to data known from children without neuromuscular disease. more...

Unlabelled: In Germany, a low coverage with hepatitis B and measles vaccines and a considerable delay in administration of all recommended vaccines were previously apparent. Whether there have been improvements and whether there are regional differences within Germany is not known. Using representative nationwide telephone interviews on 2,701 children born 1996-2003, we assessed vaccination coverage for the first dose or full primary series (2/3 doses, depending on vaccine used) at 24 months of age. The proportions vaccinated with the first dose, full priming and full immunisation (2/3 doses plus booster in the 2nd year of life) until the end of the recommended age (3, 5 and 15 months, respectively, for diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib) and hepatitis B vaccines (DTPPolioHibHep), and 15 for the first measles, mumps and rubella dose (MMR) were used as indicators of compliance with national guidelines. Coverage for polio, Hib and hepatitis B vaccines increased, while coverage for the first MMR dose remained constantly low at about 70%. Vaccination coverage differed substantially among the German states and was highest for the new states. Compliance with national guidelines increased from 2.5% to 15% for the full primary DTPPolioHibHep series, from 16.2% to 44.7% for the first MMR dose and from 1.0% to 19.3% for the full immunisation with all recommended vaccines (DTPPolioHibHepMMR)., Conclusion: Vaccination coverage at 24 months and compliance with national guidelines has improved for most vaccines in Germany. However, improving coverage for measles, mumps, rubella and eliminating the regional disparities remain a major challenge for the public health sector. more...

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. more...

Background: To determine the response to mivacurium, we prospectively studied onset time and complete spontaneous recovery from mivacurium-induced neuromuscular block in patients with Duchenne muscular dystrophy (DMD)., Methods: Twelve boys with DMD, age 5-14 yr, seven of them wheelchair-bound, ASA II-III, and 12 age- and sex-matched controls (ASA I) were enrolled in the study. Anaesthesia was induced with fentanyl 2-3 microg kg(-1) and propofol 3-4 mg kg(-1) titrated to effect, and maintained by continuous i.v. infusion of propofol 8-12 mg kg(-1) and remifentanil as required. The lungs were ventilated with oxygen in air. Neuromuscular transmission was assessed by acceleromyography using train-of-four (TOF) stimulation every 15 s. After baseline readings, a single dose of mivacurium 0.2 mg kg(-1) was given. The following variables were recorded: (i) lag time; (ii) onset time; (iii) peak effect; (iv) recovery of first twitch from the TOF response to 10, 25 and 90% (T(10), T(25), T(90)) relative to baseline; (v) recovery index (time between 25 and 75% recovery of first twitch); and (vi) recovery time (time between 25% recovery of first twitch and recovery of TOF ratio to 90%). For comparison between the groups the Mann-Whitney U-test was applied., Results: There were no differences between the groups in lag time, onset time and peak effect. However, all recorded recovery indices were significantly (P<0.05) prolonged in the DMD group. The median (range) for time points T(10), T(25) and T(90) in the DMD and control group was 12.0 (8-16) vs 8.4 (5-15) min, 14.1 (9-20) vs 10.5 (7-17) min and 26.9 (15-40) vs 15.9 (12-23) min, respectively. The recovery index and recovery time were similarly prolonged in the DMD group., Conclusions: These results support the assumption that mivacurium-induced neuromuscular block is prolonged in patients with DMD. more...

The Directigen Flu A+B enzyme immunoassay and the Abbott TestPack RSV enzyme immunoassay were each compared with a multiplex RT-PCR ELISA by testing 635 nasopharyngeal aspirates collected from children aged < 16 years who had been hospitalised with acute respiratory tract infection during the epidemic season 2002-2003. In this study, the sensitivity of the Directigen Flu A+B assay was unacceptably low (29.3% and 10.0%, respectively) for the detection of influenza A and B viruses. The sensitivity of the Abbott TestPack RSV assay (77.4%) was acceptable and in agreement with the multiplex RT-PCR ELISA. more...

Background: Lower respiratory tract infections (LRI) inflict a high burden of disease in children worldwide. Longitudinal, descriptive epidemiological data on different forms of LRI are urgently needed to differentiate this burden, compare population-based incidence rates between countries and to recognize trends., Patients and Methods: From July 1996 to June 2000, all children hospitalized with LRI, i. e. laryngo-tracheo-bronchitis (LTB), bronchitis, wheezing bronchitis-bronchiolitis (WBB), bronchopneumonia and pneumonia, in the municipal area of Kiel, Schleswig-Holstein, Germany, were analyzed by cross-sectional studies. Naso-pharyngeal aspirates (NPA) were analyzed by an in-house 9-valent multiplex-RT-PCR., Results: In the 4-year observational period, 1 072 children aged 0 to 16 years (median 23 months) were hospitalized with LRI: 12 % (median 28 months) with LTB, 11 % (median 17 months) with bronchitis, 28 % (median 13 months) with WBB, 26 % (median 26 months) with bronchopneumonia and 22 % (median 47 months) with pneumonia. The prevalence of chronic underlying conditions (20 %) and low gestational age (13 %) varied in the different forms of LRI. The cumulative incidence rate of LRI rose steadily over the 4 years. The highest fraction was contributed by WBB, while pneumonia declined. The highest incidence rate ratio was attributable to respiratory syncytial virus (RSV, 0.46) and to children under 2 years of age., Conclusions: LRI, especially obstructive forms of LRI, are increasing in Germany as described earlier for the USA, UK and Sweden. The major burden is carried by children under 2 years. RSV is the single pathogen with the highest impact. more...

Background: A measles outbreak was recently observed in Coburg, Bavaria, in a population with vaccination rates of 76.5% in 5- to 6-year-old children in the years preceding the outbreak. Only a small proportion of children had received 2 vaccinations against measles. Vaccine effectiveness is estimated in a household contact study and also by a screening method., Methods: A household contact study was conducted in families with at least 1 measles case by standardized computer-assisted telephone interviews to assess secondary attack rate and to estimate vaccine effectiveness. Vaccine effectiveness was also estimated with Farrington's screening method with information from school entry examinations and from questionnaires of confirmed measles cases in the Coburg outbreak., Results: Thirty-eight children were primary cases. Of their contacts, 20 children were included in the study as secondary cases (1 vaccinated), and 23 children were contacts who did not develop measles (12 vaccinated once and 4 vaccinated twice), resulting in a vaccine effectiveness of 90% (95% confidence interval, 35-97%) for one vaccine dose. The proportion of the population vaccinated reached 81.5% during the outbreak and the proportion of the cases vaccinated was 10.9%, resulting in a vaccine effectiveness estimated using the screening method of 97.2% (95% confidence interval, 95.7-98.3%)., Conclusions: With the use of 2 approaches to estimate the effectiveness of measles vaccination, a consistently high vaccine effectiveness of 90% or above was shown during a measles outbreak in Western Europe. more...

Background: Elaborated data on the descriptive epidemiology of community-acquired pneumonia (CAP) are a prerequisite to estimate the impact of new vaccines., Patients and Methods: From July 1996 to June 2000, all children (0-16 years) admitted to one of the two pediatric hospitals in Kiel and being resident in the municipal area of Kiel were investigated by cross-sectional studies and prospective testing using a 9-valent in-house m-RT-PCR method., Results: In the 4-year period, 514 children were included (mean age 46, median 40 months): 279 were diagnosed with bronchopneumonia (BPN, median age 26 months), 235 with pneumonia (PN) (47 months); within the latter 69 cases had lobar PN (55 months), 41 atypical PN (51 months) and 28 parapneumonic effusions (74 months). An underlying chronic condition was present in 22.8 % and 10.1 % were born prematurely. The population-based incidence rates (per 100,000 per year) were on average 300 for children 0-16 years, 163 for BPN, 136 for PN, 53 for lobar PN, 24 for atypical PN and 16 for parapneumonic effusions. The rate was stable or slightly declined over the observation period. 61 % of infants and 45 % of children under 5 years of age have to be hospitalized having contracted CAP. The highest fraction of 34 and 25 %, respectively, was attributable to RSV. Viruses were not diagnosed significantly more often in BPN than in PN, if stratified by age., Conclusion: The incidence and the admission rate of severe CAP is lower than in the USA. The high rate of empyema warrants enhanced surveillance as an indicator for antibiotic resistance or changing impact of pneumococcal serotypes. Misclassification, also with ICD codes, is a major issue. Well analyzed epidemiological recruitment areas are a valid tool to generate precise data in Germany. more...

Background: Passive immunization with palivizumab is expensive and requires considerable logistic effort. So far 5 monthly injections from November to March are recommended. The RSV season onset and its duration, however, shows considerable variation. In many countries on the northern hemisphere a dual rhythm is described., Method: A web-based early warning system within the research network PID-ARI.net is in place since 2002. The surveillance data are published online weekly via www.pid-ari.net. This enables physicians to carry out interventions, like passive immunization for RSV, synchronously with the epidemiology of a given pathogen instead of a rigid schedule. The surveillance of PID-ARI.net is based on a 19 valent multiplex RT-PCR on naso-pharyngeal aspirates. The samples are provided by hospitals and offices in Freiburg, Mainz and Schleswig-Holstein (north, middle, south of Germany). Children with lower airway infections are prospectively enrolled., Results: In the time period from July 1999 to June 2003 with 20 months of recommended palivizumab application, 5 months (25 %) would have been not on target. In two seasons the start of the vaccine campaign would have been too early (waste of two months). In one season the application would have started one month too late and in two seasons the vaccine campaign would have been stopped two months too early leaving the vaccinees on risk for acquiring RSV., Conclusions: The web-based early warning system of PID-ARI.net is the first, pathogen-specific, comprehensive and fast surveillance-system for airway pathogens in Europe. It facilitates the epidemic-synchronous use of the passive immunization with palivizumab and by this increases its efficiency and should safe costs. more...

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines. more...

Background: Recently an increase in the number of invasive Haemophilus influenzae type b (Hib) cases was observed in the United Kingdom, which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis (DTaP) Hib vaccines. A study in Germany based on approximately 2 years of follow-up, estimated vaccine effectiveness (VE) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high., Objectives: To assess VE of DTaP-containing Hib vaccines against Hib in Germany with the use of extended follow-up of case surveillance and vaccine uptake., Subjects and Methods: Cases with confirmed systemic Hib infections in children born between June 1, 1996 and December 31, 1998 were ascertained by a nationwide active surveillance system from January 1998 through June 2002. A representative subcohort of 667 children born in the same time frame was randomly sampled in a nationwide vaccine coverage survey. VE was determined with a case-cohort approach of Cox regression with time-dependent covariates., Results: Thirty-six cases of Hib disease were reported. Of these, 10 were vaccinated with DTaP-containing Hib vaccines only and 20 were not vaccinated. Of the 10 vaccinated cases, 4 had received an incomplete primary series (1-2 doses), and 6 had received the full primary series (3 doses), 3 of whom also received the booster dose. VE of combination vaccines against invasive Hib infection was 89.6% [95% confidence interval (CI), 67.0-96.7] for an incomplete primary series, 96.7% (95% CI 87.7-99.1) for a full primary series and 98.5% (95% CI 94.5-99.6) for a booster dose (irrespective of priming)., Conclusion: Hib combination vaccines containing acellular pertussis antigens continue to be highly effective in Germany. more...

Purpose: The objective of this study was to assess the local and systemic tolerability of two batches of the Biken acellular pertussis (Pa) vaccine following administration of a single vaccine dose to adults with or without a history of prior pertussis immunization. The results from this study were compared to data from published literature., Patients and Methods: In a controlled, open-labeled double-blind trial, 518 healthy male and female adults with or without primary pertussis immunization were enrolled at three centers. All study participants had received one single dose (0.5 ml) of the Biken two-component (23.4 mg PT; 23.4 mg FHA) Pa vaccine deeply intramuscularly. Local and systemic adverse events were solicited for 4 days using diary cards. On two occasions, between day 4-7 and between day 12-16 postvaccination, vaccinees were reexamined. At the end of the observation period (day 28) vaccinees had to send a preprinted letter to the study center indicating their state of health., Results: One serious adverse event (acute appendicitis) occurred and was considered not to be related to the study vaccine. At the injection site, redness > 20 mm was observed in one subject (0.2%), and swelling > 20 mm was seen in ten subjects (1.98%). Edematous swelling occurred in three subjects (0.59%). In 27 subjects (5.34%) a "late-onset muscle mass swelling" could be palpated, usually occurring on day 6-12 postvaccination. 429 subjects (84.78%) experienced none or only slight tenderness on pressure during the. rst 4 days postvaccination, moderate tenderness on pressure was reported by 60 subjects (11.86%) and severe tenderness by 16 vaccinees (3.16%). Systemic side effects were rare: no fever > 38.5 degrees C was observed, and only seven subjects (1.39%) took antipyretics. Five patients (0.99%) experienced exhaustion or nausea. The vast majority of the participants (97.43%) would opt for the vaccination again., Conclusion: The study vaccine was safe and induced only infrequently and mostly mild, local or general symptoms that all resolved spontaneously. It was well tolerated and accepted in adults. more...

Unlabelled: In excess of 1 million young children die every year as a consequence of disease caused by Streptococcus pneumoniae, the vast majority in developing countries. Although the first vaccine against the Pneumococcus was produced before the First World War, licensure of the first vaccine with documented efficacy against severe infections in infants and young children did not occur until February 2000 in the United States. This conjugate vaccine consists of purified polysaccharide, from each of seven pneumococcal serotypes, chemically linked to a carrier protein. A high degree of efficacy of the new vaccine against potentially life-threatening infections has been shown in both poor and affluent countries. The vaccine's potential to protect from acute otitis media, however, is very limited, although encouraging indirect effects, such as reduced antibiotic prescriptions, have been reported. An inherent problem with the new pneumococcal conjugate vaccines is that, while more than 20 pneumococcal serotypes may cause invasive disease, only a more limited number of polysaccharides, 11 or so, can in practice be conjugated to carrier protein as part of a single vaccine formulation. Because of variation in the ranking of serotypes most commonly responsible for pneumococcal disease, by region, age and disease manifestation, compromise was required in selecting serotype-specific saccharides for inclusion., Conclusion: Complex conjugate technology comes at a price, and the present costs keep most of the world's children far out of reach of an effective vaccine. However, the pneumococcal conjugate vaccine is a highly functional weapon against deadly pneumococcal infections, and strenuous efforts are needed to maximise its accessibility to children most at risk. more...

Background: A multiplex reverse transcription (RT) polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) was previously developed to detect nine different microorganisms: enterovirus (EV), influenza virus type A (IVA) and type B (IVB), respiratory syncytial virus (RSV), parainfluenzavirus type 1 (PIV1) and type 3 (PIV3), adenovirus (AV), Mycoplasma pneumoniae (Mpn), Chlamydia pneumoniae (Cpn) in a single test. These organisms do not usually colonize the respiratory tract of humans, but, if present, it may be assumed they are involved in respiratory disease., Objectives and Study Design: The m-RT-PCR-ELISA was tested on (i) culture supernatants of unknown contents, (ii) by determining the analytical sensitivity of 10-fold serial dilutions of culture supernatants and (iii) by determining clinical sensitivity in a retrospective study on 411 clinical specimens. The specimens were re-tested in parallel by m-RT-PCR-ELISA versus the gold standard culture and immunfluorescence, and versus individual RT-PCR., Results: (i) The 9-valent m-RT-PCR-ELISA shows 83% to 100% concordant results on 103 culture supernatants containing different organisms. (ii) The analytical sensitivity was as follows: higher sensitivity of the 9-valent m-RT-PCR-ELISA in comparison to culture in the cases of PIV3, IVA and IVB (factor 10) and AV and EV (factor 100), and lower sensitivity in case of RSV and PIV1 (factor 10). (iii) The agreement with the gold standard in the kappa statistic was excellent for RSV (kappa = 0.937), IVA (kappa = 0.940), very good for PIV1 (kappa = 0.914), IVB (kappa = 0.907) and satisfactory for PIV3 (kappa = 0.410). For AV, EV and Mpn the m-RT-PCR-ELISA preliminary could be qualified as very good, based on the data derived on culture supernatants. Information about the validity for Cpn is limited., Conclusion: The m-RT-PCR-ELISA is a feasible, sensitive and specific method for detection of a broad spectrum of organisms. It is suitable for individual as well as epidemiological diagnosis. more...

This report highlights the importance of accurate interpretation of even small intraoperative capnography changes. In this case, an otherwise unexplained sudden small decrease in end-expiratory carbon dioxide tension (P(ET)CO2) led to the detection of a deep venous thrombus. During the surgery of a 34-year-old woman with a known carcinoma of the corpus uteri, who was scheduled for paraaortal lymphadenectomy, a sudden decrease in carbon dioxide tension occurred. In careful exploration of the surgical field to rule out a thromboembolic event, the surgeons noticed an induration of the right iliac vein. A consulting vascular surgeon exposed a right-sided, irregular, double-lumen, common iliac vein with a thrombus the tip of which floated in the inferior vena cava. Following complete thrombectomy, the procedure was accomplished without further adverse events. more...

Friedreich's ataxia is a rare hereditary neurodegenerative disease caused by a defect in the gene that encodes a mitochondrial protein called frataxin. We report the use of rocuronium 0.6 mg kg(-1) in two adolescent girls with Friedreich's ataxia undergoing propofol-sufentanil-oxygen-air anaesthesia for spinal surgery. Neuromuscular transmission was monitored using acceleromyography, and onset and recovery times were recorded. The clinical duration of rocuronium was comparable to that of children without neuromuscular disease (25% recovery T(1)=44 and 24 min for patients 1 and 2 respectively). more...

Background: Duration of hospitalization is influenced by many factors. It is an important parameter for quality of care. So far it is unknown, whether respiratory syncytial virus (RSV) etiology itself contributes to the time in hospital., Method: Children under 2 years of age admitted with a lower respiratory tract infection in 3 hospitals (1 tertiary and 2 secondary centers) in northern Germany were included in an unmatched, hospital-based case-control study. Cases were children tested positive for RSV by multiplex RT-PCR. One control group consisted of children tested negative for RSV in the multiplex-RT-PCR and a second control group consisted of patients in whom no PCR was done. Since only 4 to 5% in the latter group and thus 2% of the study population were misclassified, this group could be involved in the analysis., Results: The median days of hospitalization was 7 days; 9 days in the RSV-positive group, 8 and 6 days in the RSV-negative and non-PCR group, respectively. The time in hospital was diminishing over the 4 year observation period. Duration of hospitalization was best predicted by--young age, presence of an underlying condition, disease entity--being pneumonia or bronchiolitis, prematurity, earlier epidemiologic year and intercostal retractions. Not predictive were: RSV-etiology, center, duration of illness, wheezing, C-reactive protein level and consolidation on the chest x-ray (all on admission)., Conclusions: RSV-etiology is influencing the duration of hospitalization only indirectly via its predilection for the very young age and certain underlying conditions--not by RSV itself. In spite of considerable variation of patient populations between secondary and tertiary care facilities and locally different care practices, the treatment center pre se did not influence the duration of hospitalization significantly. Further rationalization of treatment is, however, possible. more...

To evaluate immune responses, safety and reactogenicity of the concomitant use of DTaP-IPV-Hib and the newly available 7-valent pneumococcal conjugate (7VPnC) vaccines when given as the primary immunization series in early infancy. A total of 231 healthy infants were enrolled at 11 German study centers and randomized to receive either 7VPnC plus DTaP-IPV-Hib vaccines concomitantly into opposite limbs at age 2, 3, 4 and 11-15 months (7VPnC group) or DTaP-IPV-Hib vaccine at the same ages plus a 7VPnC "catch-up vaccination" at ages 6, 7, 8 and 11-15 months (Control group). Blood samples were drawn before and 4 weeks after the first three vaccine doses and 4 weeks after the fourth dose. Local and general side effects (i.e. safety) were solicited by diary cards. Immune responses were determined by ELISA except for antibodies to polioviruses (neutralization assay). Post-dose 3, a significant antibody response against all seven pneumococcal vaccine-serotypes was observed in the 7VPnC group only. Post-dose 4 geometric mean concentrations (GMCs) were similar in both groups. GMCs for other vaccine antigens were comparable between groups except for diphtheria (higher in the 7VPnC group) and pertactin (lower in the 7VPnC group), although after three vaccine doses there was a 28-fold rise in GMCs from baseline. Both vaccines were generally well-tolerated although there were minor differences in the frequency of local reactions and somewhat more fever or drowsiness in the 7VPnC group. The use of DTaP-IPV-Hib and the 7VPnC vaccine was safe, well-tolerated and immunogenic when given concomitantly at age 2, 3 and 4 months or when given separately with 7VPnC as a catch-up vaccination at age 6, 7, 8 months and as a concomitant booster immunization at age 11-15 months. more...

Unlabelled: Community-acquired pneumonia (CAP) is of predominant interest in analysing the burden of airway diseases. No population-based incidence data for children in Germany exist. In retrospective cohort studies from 1999 to 2001, parents of an entire age-class (28,000-30,000) of 5- to 7-year-old children at school entry medical examination (S1) in a complete federal state (Schleswig-Holstein, population 2.77 million) were interviewed by the Children and Adolescent Service of the Public Health Service. CAP was defined as pneumonia diagnosed by a physician at the time it occurred. The proportion of children investigated (participation rate) was 82.0-86.1%. The CAP-positive rate was 6.7-7.4%, 6.9-8.2% of whom had recurrent CAP. The mean age at first CAP was 36.4-39.4 months (median 42 months). This resulted in a population-based incidence for the age groups 0-1 year and 0-5 years (under 5) of 1,664-1,932 and 1,369-1,690 per 100,000, respectively; 93.7-95.9% received antibiotics. For each percent of CAP, 458 days (1999), 312 days (2000) and 319 days (2001) of at least one parent's work were lost, respectively., Conclusions: Despite a relatively weak case definition, the population-based incidence of CAP before school entry was the same as recently reported form California and about 30-50% of that reported 20 to 40 years ago in the USA and Finland. more...

Despite the proven safety and efficacy of vaccines, common vaccine-preventable diseases such as measles are not yet controlled in all European countries. This is largely due to three factors. First, vaccination systems differ widely throughout Europe and they vary between highly centralised and totally decentralised systems. Both have advantages and disadvantages, but without doubt they can all work locally. "Harmonisation" in this field is neither a prerequisite nor a guarantee for success. Second, perception of vaccination--and this includes education of the public--is most crucial. In this field the media play an important part, but their ability or will to communicate complicated scientific matters in an appropriate way to the public is often insufficient. Third, political will may be the single most important factor for success in vaccination. Only if the European Union comes up with and implements common vaccination goals with firm deadlines can the best health through vaccination of all Europeans be accomplished. The system as well as the schedule used would then be of minor importance. more...

An unmatched, hospital-based case-control study was performed, to determine, whether respiratory syncytial virus (RSV) etiology in hospitalized young children can be predicted clinically. Children under 2 years of age admitted with a lower respiratory tract infection in three hospitals in northern Germany were included (one tertiary and two secondary centers). Cases were children tested positive for RSV by multiplex RT-PCR. One control group consisted of children tested negative for RSV in the multiplex-RT-PCR and a second control group consisted of patients in whom no PCR was done. A weighted backward stepwise logistic regression model was applied for multivariate analysis. RSV-etiology could be predicted with a sensitivity of 72.8% and a specificity of 73.2%. Young age, disease entity--pneumonia or bronchiolitis, center, intercostal retractions, absence of an underlying condition, low level of C-reactive protein, short duration of symptoms (all on admission), prematurity and epidemiologic year were predictive; anatomical infiltrates and wheezing were not. Pathogen specific diagnosis is necessary for individual therapy, allocation in observational studies or treatment trials and for surveillance of airway infections in children, since the positive predictive value is too low for an accurate diagnosis and decision making. Multivariate techniques are effective tools in complex clinical research for deconfounding. more...

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. more...

Several tests have been proposed to predict difficult laryngoscopy or intubation. The thyromental distance (TMD) is often used for these purposes but this measurement, used alone, is unreliable. This study tested the hypothesis that the ratio of the patient's height to TMD (ratio of height to TMD = RHTMD) would improve the accuracy of predicting difficult laryngoscopy compared with TMD alone. Two hundred and seventy patients were evaluated preoperatively using the TMD and RHTMD. The two tests were compared analyzing the area under the receiver operating characteristic curves (AUC). Difficult laryngoscopy occurred in 16 patients (5.9%). The AUC of RHTMD was significantly greater (P < 0.007) when compared to TMD, indicating a more accurate prediction by the RHTMD. A ratio of 25 for the RHTMD was found to be the optimal cut-off value to predict difficult laryngoscopy. When the sensitivity of both tests was 0.81, the RHTMD had a significantly greater specificity (0.91) than the TMD (0.73). Based on our results, we recommend that the RHTMD should be used instead of the TMD. more...

Since new vaccines and anti-viral drugs for influenza have become available, collation of actual and country-specific epidemiological data is essential. Since respiratory syncytial virus (RSV) is a well known paediatric airway pathogen and some epidemiological data exist already, a comparison between influenza and RSV seems warranted. From July 1996 to June 2001 the naso-pharyngeal aspirates (NPA) of children from birth to 16 years of age, admitted to one of the two paediatric hospitals in Kiel, Germany, were investigated by a nine-valent multiplex reverse transcriptase PCR assay. NPA were investigated in 60.8 % of 3,469 children admitted with an acute respiratory tract infection. Community-acquired or nosocomial infections (in parentheses) due to influenza A were diagnosed in 122 (10) children, due to influenza B in 14 (2) and due to RSV in 325 (24) cases. Patients with influenza A (median 752 days) and influenza B (median 966 days) were older than patients with RSV (median 168 days). The spectrum of disease presentation was broader in influenza than in RSV. In each winter, admissions with influenza were less common than those with RSV. Influenza B only occurred in 2 of the 5 years. The cumulative, population-based incidences per 100,000 children 0-16 (0-5, >5-16) years of age were 53 (123, 22) for influenza A, 16 (30, 9) for influenza B and 165 (453, 4) for RSV. Cardiac conditions and asthma were the major risk factors for admission to hospital with influenza A (RR 9.8, 4.1) and RSV (8.5, 2.1) infections. Underlying conditions were most common in influenza B. Low gestational age doubled the risk for admission to hospital with influenza A infection, but did not show a dose-effect relationship as in RSV. The burden of influenza-positive hospitalizations was about one third that of RSV. The incidence was similar to reports from the United States. Targeting children with underlying conditions, especially cardiac conditions and asthma in the German immunization programme is appropriate, as long as no policy for vaccination of the general paediatric population exists. more...

Background: In spite of a large amount of data from other countries, those on the burden of disease attributed to respiratory syncytial virus (RSV) in Germany are lacking and are urgently needed., Method: In a population-based cross-sectional study from July 1996 to June 1999 150 children from birth to 16 years of age hospitalized in Kiel and tested positive for RSV by polymerase chain reaction were investigated. Stepwise linear and logistic regression models were applied to predict a bacterial co-infection as well as the duration of hospitalization., Results: Pneumonia (54 %) and wheezing bronchitis (including bronchiolitis, 27 %) were the predominating diagnoses; 25 % had an underlying condition. Four patients needed nasal continuous airway pressure and one intermittent mandatory ventilation; none died. According to the surrogate markers CRP and immature neutrophil fraction, 20 % to 30 % were suspected to have a bacterial co-infection on admission; antibiotics were prescribed in 65 % of the patients. The average duration of hospitalization was 9 days and was best predicted by young age, the presence of an underlying condition, intercostal retractions and high CRP on admission., Conclusions: Bacterial co-infection is the major confounder in burden of disease analyses in RSV. The decision not to administer antibiotics to children hospitalized with RSV can be risky, particularly when there is considerable diagnostic uncertainty. Within the realm of current clinical practice, complications and deaths related to RSV are rare in Germany. more...

Background: In the US a pneumococcal conjugate vaccination program with a 7-valent conjugate vaccine was successfully implemented in 2000. How much invasive pneumococcal disease can potentially be prevented by the 7-valent (or 11-valent) vaccine in Europe?, Methods: Prospective, active surveillance of invasive pneumococcal disease in German children age <16 years was performed between 1997 and 2000. Age- and disease-specific coverage and incidence rates were assessed in children old enough to benefit from complete vaccination to estimate the annual number of cases potentially preventable., Results: A total of 1,743 cases were reported; 667 isolates were serotyped. Coverage of 7-valent (11-valent) conjugate vaccines in children age 6 months and older was age- and diagnosis-dependent, ranging from 10.5% (15.8%) to 78.3% (82.6%) for meningitis and from 13.6% (68.2%) to 75.0% (89.3%) for nonmeningitis invasive pneumococcal disease cases. Of an estimated annual number of 176 children with pneumococcal meningitis age 6 months or older, 112 (122) cases had serotypes included in the 7-valent (11-valent) conjugate vaccine compared with 181 (254) of 324 nonmeningitis invasive pneumococcal disease cases, with 37 of the 73 cases covered by the 11-valent vaccine only in children older than 5 years. Regarding meningitis in this age group the potential benefit was equally poor for both the 7-valent (12 of 37 cases) and the 11-valent vaccine (15 of 37 cases)., Conclusion: Coverage of the 7- and 11-valent conjugate vaccines depends markedly on age and disease. The additional potential benefit of the 11-valent compared with the 7-valent vaccine for pneumococcal meningitis was marginal. more...

Background: In recent surveillance data there are still many cases of measles and even local epidemics in Germany. We studied whether delayed measles vaccination contributes to this situation., Methods: Vaccine coverage data in children <3 years of age were assessed by a telephone survey. Three data sources for measles surveillance were analyzed: official measles notifications; sentinel data; and official hospital discharge diagnoses., Results: After the time recommended for completion of measles vaccination at Month 15, only 22% of German children had received their first vaccine dose. This percentage increased to 77% at the age of 24 months and to 87% at 36 months of age. According to all three surveillance instruments, the number of measles cases was highest in children age 1 to 4 years with a peak in the second year of life., Conclusions: More than 50% of measles cases in 1-year-old children would be prevented if presently observed vaccine coverage rates in the third year of life could be achieved 12 months earlier. Delayed measles vaccination is responsible for a large number of measles cases still occurring in the German population, where measles has not yet been eliminated. If vaccination were delivered according to the recommended time schedule, the incidence of measles would be considerably reduced. more...

Study Objective: To determine the influence of head and neck elevation beyond the "sniffing position" during difficult direct laryngoscopy., Design: Prospective case series, with each patient serving as her or his control., Setting: University hospital., Patients: 21 patients scheduled for general anesthesia and endotracheal intubation, all of whom presented with a laryngoscopic grade III view (Cormack & Lehane) during direct laryngoscopy in the sniffing position., Interventions: An assistant applied external laryngeal pressure with his left hand and elevated the patient's head and neck above the sniffing position with his right hand to improve laryngeal view., Measurements and Main Results: External laryngeal pressure and elevation of head and neck improved the laryngoscopic view in 19 of 21 patients to grade II (p = 0.001, Wilcoxon signed rank test). Beyond that, laryngoscopy with the neck maximally elevated enabled visualization of parts of the cords in six patients (30%)., Conclusions: Elevation of the head and neck beyond the sniffing position may improve visualization of glottic structures in cases of difficult direct laryngoscopy, leading to better intubation performance. more...

Background: Elaborate, long-term data on the rhythm, seasonality and severity of the yearly respiratory syncytial virus (RSV) epidemics in Germany are lacking., Patients and Methods: A longitudinal investigation was undertaken of children from birth to 16 years of age admitted with an RSV infection in the two pediatric hospitals in Kiel between July 1994 and June 2001. To compare the severity of the individual seasons, the incidences and the proportion of RSV-positive hospitalized children aged 0 to 2 years from the denominator area of Kiel were compared., Results: During the 7-year period, the nasopharyngeal aspirates of 2,367 children were investigated; RSV was detected in 384 (16.2%). The seasons from 1994/95 to 1996/97 started late (December to January) and ended between March and May. Since 1997/98 it seems that a late season is followed by an early season (start in September to October) in a 2-year pattern., Conclusion: No fixed rhythm of the RSV season can be identified as yet. Ascertainment bias is unlikely to explain the differences in rhythm. The incidence of RSV-positive hospitalizations seems to be increasing. more...

Background: To compare the antibody concentrations against Bordetella antigens in health care workers in a pediatric hospital with those of two different populations without professional contact with children., Methods: In a pediatric hospital 155 health care workers (135 female, 20 male), 292 male navy recruits after 3 months at sea and 146 regular blood donors (41 female, 105 male) were screened for antibodies of isotypes IgG and IgA to pertussis toxin (PT) and filamentous hemagglutinin (FHA) by enzyme-linked immunosorbent assay., Results: Pediatric health care workers were positive for IgG anti-PT in 88%, for IgA anti-PT in 52%, for IgG anti-FHA in 99% and for IgA anti-FRA in 84%. Relative numbers for blood donors and recruits were 86 and 80% for IgG anti-PT, 56 and 55% for IgA anti-PT, 100 and 98% for IgG anti-FHA and 92 and 82% for IgA anti-FHA, respectively. Reverse cumulative distribution of all antibodies except for IgA anti-FHA showed no differences among the three groups; 2% of pediatric personnel, 3% of blood donors and 3% of navy recruits, respectively, had IgG anti-PT > or = 100 enzyme-linked immunosorbent assay units/ml, indicating a recent contact to Bordetella pertussis., Conclusion: Antibodies to B. pertussis antigens, such as IgG/IgA anti-PT and IgG/IgA anti-FHA, were similarly distributed in all three groups. Our results suggest that exposures leading to measurable immune responses to pertussis antigens in German pediatric health care workers are not significantly more frequent than in other populations without professional contacts with children. more...

For the prevention of pertussis and invasive Haemophilus influenzae type b (Hib) infections, each with a peak for mortality and serious complications in the first year of life, early vaccination is important and needs adequate monitoring. In a 1999 national coverage survey the timing of uptake of these vaccines in German children was therefore assessed conventionally at defined age thresholds and with a new adaptation of the Kaplan-Meier (KM) method estimating immunization uptake over time by 1 minus the survival function s(t). Only 6% and 9% of children were vaccinated against pertussis and Hib in accordance with the national recommended primary vaccination schedule. Coverage levels for the primary vaccination course of 50% and 90% were attained for pertussis after 6.6 and 16.3 months respectively and for Hib after 7.0 and 24.3 months. These estimates were only possible with the KM method which proved useful to monitor vaccination programmes and will allow the comparison of vaccination uptake in different populations. more...

Unlabelled: We studied the effect of positive end-expiratory pressure (PEEP) release and positioning on the occurrence of venous air embolism (VAE). Eighteen consecutive patients (8 women, 10 men; ASA grade I-III) undergoing neurosurgery in the sitting position were studied. After induction of anesthesia ventilation was controlled with a PEEP of 5 cm H(2)O in an oxygen-air gas mixture. A transesophageal echocardiographic (TEE) probe was inserted. Preoperatively, a patent foramen ovale was excluded in all patients. TEE monitoring was performed during surgery, during PEEP release at the end of surgery with the patient still in the sitting position, and during change of the patient position into the supine position. The severity of VAE was differentiated as follows: grade 1 = only microbubbles; grade 2 = microbubbles and decrease of end-tidal carbon dioxide partial pressure (PETCO(2)) by more than 1.5 mm Hg; grade 3 = microbubbles combined with a decrease of PETCO(2) by more than 1.5 mm Hg, and a decrease of mean arterial blood pressure by at least 20 mm Hg. During surgery, VAE with a grade of 1, 2 or 3 occurred in 7, 4, and 2 patients, respectively. After PEEP release, VAE of grades 1, 2, and 3 were observed in 7, 2, and 1 patients, respectively. During repositioning from sitting to supine position, VAE of grades 1, 2, and 3 was observed in 6, 1, and 1 patients, respectively. The patient with VAE grade 3 needed inotropic support until 2 h after surgery to maintain sufficient blood pressure. No patient showed any sign of paradoxical arterial embolism or cardiac dysfunction. We conclude that VAE occurs not only during surgery in the sitting position, but also with release of PEEP and during repositioning to the supine position., Implications: This study shows that venous air embolism (VAE) occurs not only during surgery in the sitting position but also during positive end-expiratory pressure release and repositioning of the patient into the supine position. Continuous monitoring for VAE should be performed until the patient is returned to the supine position. more...

Detection of parvovirus B19 DNA offers diagnostic advantages over serology, particularly in persistent infections of immunocompromised patients. A rapid, novel method of B19 DNA detection and quantification is introduced. This method, a quantitative PCR assay, is based on real-time glass capillary thermocycling (LightCycler [LC]) and fluorescence resonance energy transfer (FRET). The PCR assay allowed quantification over a dynamic range of over 7 logs and could quantify as little as 250 B19 genome equivalents (geq) per ml as calculated for plasmid DNA (i.e., theoretically >or=5 geq per assay). Interrater agreement analysis demonstrated equivalence of LC-FRET PCR and conventional nested PCR in the diagnosis of an active B19 infection (kappa coefficient = 0.83). The benefit of the new method was demonstrated in an immunocompromised child with a relapsing infection, who required an attenuation of the immunosuppressive therapy in addition to repeated doses of immunoglobulin to eliminate the virus. more...

Objective: Varicella is a common infectious disease, usually benign and self-limited, and complications are believed to be rare. The purpose of this study was to describe the epidemiology of severe varicella complications in immunologically healthy children in Germany., Methods: Information on any admission of children with a severe complication associated with chickenpox was solicited throughout 1997 from all 485 pediatric hospitals in Germany using an established surveillance system. The case definition included nonimmunocompromised individuals who were up to 16 years of age and hospitalized with neurologic complications, bacterial superinfections, or hematologic complications., Results: The response rate to the surveillance questionnaire during the observation period was high: 93.4%. Of the 153 reported cases, 119 met the case definition. There was a seasonal distribution of reported complications with a peak in March. The majority of complications occurred in preschool-age children with a maximum age of 4 years. No gender predominance was found with a distribution of 56 female and 63 male patients. Multiple entries for complications were allowed. The most frequent complications were neurologic, which were reported in 73 children (61.3%); cerebellitis was the leading diagnosis (n = 48), followed by encephalitis (n = 22), meningitis (n = 2), and central facial palsy (n = 1). A total of 46 (38.6%) infectious complications were identified. Superinfections of the skin were present in 31 (26.0%), pyogenic arthritis was present in 5 (4.2%), osteomyelitis was present in 4 (3.3%), necrotizing fasciitis was present in 3 (2.5%), orbital cellulitis was present in 2 (1.6%), and pneumonia was present in 1 (0.8%). Streptococcus pyogenes was the leading cause of bacterial infections (18 cases [15.1%]), with invasive disease in 6 patients (8.4%) and linked to 4 of 8 cases with defect healing. Infectious complications were reported in the majority in younger children up to 4 years of age, whereas neurologic complications occurred more frequently in an older age range. Five children experienced thrombocytopenia or severe anemia. There was no bleeding disorder, no fatality, and no case of Reye syndrome reported during the 1-year observation period. In total, 8 (6.7%) of 119 patients reported having long-term sequelae, 6 attributable to infectious complications and 2 to persistent deficits after neurologic complications., Conclusion: This is the first prospective nationwide study of severe complications of varicella in immunologically healthy children. Related to 14 025 867 children up to the age of 16, a crude incidence of severe chickenpox complications of 0.85/100 000 could be calculated [corrected]. The actual hospitalization rate attributable to complicated chickenpox is probably much higher, because this calculation refers to a population theoretically at risk and not the truly susceptible individuals. The results of this study demonstrate considerable morbidity with a comparatively high rate of encephalitis, osteomyelitis, and pyogenic arthritis. Although infectious complications were present in only 38.6% of the reported cases, they contributed disproportionately to the cases with chronic sequelae. Looking at these cases in more detail, S pyogenes involvement was identified as the major risk factor for invasive disease with an unfavorable long-term outcome. varicella-zoster virus, chickenpox/epidemiology, chickenpox/complications, encephalitis, cellulitis, osteomyelitis, necrotizing fasciitis, group A beta-hemolytic streptococci, Europe. more...

While vaccines have virtually eliminated many infectious diseases in Germany, vaccination coverage in children, adolescents and adults is still unsatisfying. This situation is mainly due to inadequate remuneration of vaccination services, structural deficits in the health care system and a lack of motivation. Political support and leadership would most likely be able to change this situation. more...

Background: Since 1996 in Germany primary infant immunization against Haemophilus influenzae has been most commonly given in the form of diphtheria-tetanus toxoids-acellular pertussis/H. influenzae type b (DTaP/Hib) or diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b (DTaP-IPV/Hib) combination vaccines. These combination vaccines elicit lower anti-Hib antibody concentrations than the equivalent Hib conjugate administered as a separate injection, but the clinical relevance of this phenomenon is unknown., Methods and Findings: To assess the impact of DTaP/Hib combination vaccines on the incidence of invasive Hib disease in Germany, two independent surveillance systems, one hospital- and one laboratory-based, were used during 1998 and 1999 for detection of cases. Vaccination histories of all cases detected were obtained by telephone contact with parents or health care providers. During the 2-year study period invasive H. influenzae disease in the <5-year age group continued to fall, with a mean annual incidence of 1.01/100 000 children. National vaccination coverage rates revealed that only 70% of children given DTaP/Hib or DTaP-IPV/Hib received the recommended three doses in their first year of life, but the overall effectiveness of these vaccines was high at 97.5% (95% confidence interval, 96.3 to 98.4) for those who had received at least one dose. In subjects who received the full 3-dose schedule, effectiveness was 98.8% (95% confidence interval, 98.2 to 99.3)., Conclusion: Although it is well-documented that DTaP/Hib vaccines elicit lower anti-Hib titers than separate vaccines, such combinations are effective in reducing the incidence of invasive H. influenzae type b disease. more...