Can the booster interval for the tick-borne encephalitis (TBE) vaccine 'FSME-IMMUN' be prolonged? - A systematic review.

Tick-borne encephalitis (TBE) vaccines are effective and well tolerated. However, their acceptance and use by the public in endemic areas are suboptimal. To some extent this is due to the complicated dosing schedule requiring frequent boosters at variable intervals that even change with age. Simplification of the dosing schedule has failed so far as it is debated if the persistence of TBE virus (TBEV) antibodies is the only relevant factor for protection or if immune memory plays a decisive role as well. The objective here is to present the available evidence to determine the need for boosters and their interval after a primary series of three doses of FSME-IMMUN. A systematic literature review was conducted with a focus on serology, particularly seropersistence, immune memory, effectiveness, and vaccine breakthroughs (VB) of FSME-IMMUN. While after a 3-dose primary series seropositivity persisted for more than 10 years in >90% of younger subjects, it dropped to 37.5% in those 60 years or older. In contrast, field effectiveness of FSME-IMMUN remains high in irregularly vaccinated subjects and thus does not correlate well with the percentage of subjects achieving an arbitrarily defined threshold of persisting antibodies. FSME-IMMUN booster doses led to increases in antibody responses within 7 days. VB are rare and remain poorly understood. VB did not increase, and vaccine effectiveness did not significantly decrease with time since completion of the primary vaccination series or with the time since administration of the last vaccine dose. For all these reasons, data identified from this systematic review suggest that seropersistence alone does not explain the high effectiveness of FSME-IMMUN irrespective of the time since the last vaccine dose was administered. Induction of immunological memory characterized by a rapid and sustained secondary immune response is proving to be an alternative mechanism of action for protection against TBE. In this context Switzerland and Finland have adopted a longer booster interval (i.e., 10 years) following the three-dose primary immunization schedule without any evidence of harm at a population level. Longer booster intervals will likely drive up vaccine uptake. There is a lack of data to base an interval recommendation beyond 10 years.

Seropersistence and booster response following vaccination with FSME-IMMUN in children, adolescents, and young adults.

BACKGROUND: Tick-borne encephalitis (TBE) is a viral disease that can have a severe clinical course and considerable long-term morbidity. As no curative treatment exists, vaccination is the primary means of prevention. Long-term antibody seropersistence 2-5 years after the 3-dose primary immunization and 3-10 years after first booster was evaluated, as well as booster responses in children, adolescents and young adults. METHODS: Subjects who participated in these phase 4 prospective, open-label follow-up studies received all vaccinations with FSME-IMMUN. After 3-dose primary immunization, subjects were followed for 2-5 years. Overall, 205 out of 358 subjects (57%) received the first booster and 179 of these subjects (87%) enrolled in a further 10-year follow-up. Antibody seropersistence was assessed annually. Subjects with a TBE antibody titer below a pre-specified cut-off at the yearly blood draw received a booster. Seropositivity rates and geometric mean fold rises (GMFRs) were assessed. RESULTS: In children who received their 3-dose primary immunization between 1 and 15 years of age, the seropositivity rate 5 years after the 3rd dose was 84.9% by NT and 72.0% by ELISA. One month post-first booster, all subjects were seropositive by NT and 98.5% by ELISA. Response to first booster by GMFR ranged from 3.7 to 11.4. At 5 years post-first booster, seropositivity was 99.4% by NT and 97.5% by ELISA, and at 10 years, was 90.3% by NT and 87.7% by ELISA. Although seropositivity rates differed between age groups, all subjects (100%) who received a second booster responded with a robust increase of TBEV antibodies. DISCUSSION: Long-lasting seropersistence of TBEV antibodies after the 3-dose primary immunization and first booster was demonstrated as well as a competent immune memory response in those who received a first or second booster at any time during the 15-year follow-up. Therefore, an extension of FSME-IMMUN booster interval up to 10 years after the 3-dose primary immunization seems warranted. ClinicalTrials.gov Identifier: NCT00894686.

Pneumococcal empyema and complicated pneumonias: global trends in incidence, prevalence, and serotype epidemiology.

This review evaluates the serotype epidemiology of complicated pneumococcal pneumonia (CPP) during the period 1990-2012. PubMed and EMBASE were searched using the terms "empyema", "complicated pneumonia", "pleural infection", "necrotizing pneumonia", "pleural effusion", "parapneumonic effusion", "pneumatocele", or "lung abscess"; "pneumococcal" or "Streptococcus pneumoniae"; and "serotype" for studies on the epidemiology of complicated pneumonias published from January 1, 1990 to October 1, 2013. Studies with data on incidence and serotypes were included; reviews, case reports, and conference abstracts were excluded. Of 152 papers, 84 fitted the inclusion criteria. A few pneumococcal serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14, and 7F. CPP was a more common manifestation of pneumococcal disease among older (>2 years old) than younger children. The data support increases in both reported incidence rates and proportions of CPP in children and adults during the period 1990-2012; specific increases varied by geographic region. The proportions of serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas most studies show declines in serotype 14. Serotype 1 has been a predominant cause of CPP since 1990, while antibiotic resistance was infrequent among serotype 1 isolates. The reported incidence and proportions of CPP among pneumonia cases steadily increased from 1990 to 2012. Several factors might account for these increases, including enhanced disease detection due to a higher index of suspicion, more sophisticated diagnostic assays, and changes in the prevalence of serotypes with capacity to invade the pleural space that were not targeted by the 7-valent pneumococcal conjugate vaccine (PCV7).

Etomidate activates epileptic high frequency oscillations.

OBJECTIVE: The short acting anesthetic etomidate has been shown to provoke epileptic spikes and rarely seizures. Influence of etomidate on the occurrence of epileptic HFO (high frequency oscillations) however is unknown. An HFO inducing effect of etomidate would allow further validation of the substance as a provocation measure in presurgical evaluation as well as provide insights into the common mechanisms of HFO, spike and seizure generation. METHODS: We retrospectively analyzed EEG data from four patients who underwent etomidate activation during invasive video-EEG monitoring with subdural strip electrodes. Spikes were manually selected in raw data, HFO in band pass filtered data (80-250Hz). Rate and spatial distribution of HFO and spikes in three segments were compared: immediately after etomidate administration, as well as during slow wave sleep and while awake. RESULTS: Rates of HFO and spikes increased significantly after etomidate administration: Overall average rates of spikes were 9.7/min during sleep, 10/min while awake and 61.4/min after etomidate. Average HFO rates were 9.5/min during sleep, 8.3/min while awake and 24.4/min after etomidate (p<0.001, non-parametric ANOVA). Spatial distributions of HFO and spikes after administration of etomidate were consistent with the seizure onset zone (SOZ) and area of resection when available (SOZ: two patients; resection: one patient; no information: one patient). Except for spurious events, no additional HFO and spike foci were seen with activation. CONCLUSIONS: Etomidate administration activates spikes and HFO. Spatial distributions do not extend beyond electrodes showing spikes and HFO without Etomidate and seem consistent with the epileptic network. SIGNIFICANCE: Etomidate activation is a safe procedure to provoke not only epileptic spikes but also HFO, which were shown to have a high specificity for the SOZ.

Validation of a multiplex reverse transcriptase PCR ELISA for the detection of 19 respiratory tract pathogens.

INTRODUCTION: Since acute respiratory tract infections inflict a high burden of disease in children worldwide, a multiplex reverse transcription polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) to detect 19 different respiratory pathogens was developed and validated. METHODS: A total of 430 respiratory specimens were retrospectively tested in parallel by both the advanced 19-valent m-RT-PCR-ELISA as well as by culture or individual RT-PCR assays used in clinical routine. RESULTS: The mean (median) sensitivity of the m-RT-PCR-ELISA in the retrospective test was 93.3% (95.1%; range 83.3-100 %), and the mean (median) specificity was 99.8 and 100 % (range 98.6-100 %), respectively. The mean positive predictive value was 99.3 % (range 93.4-100 %) and the mean negative predictive value was 95.3 % (range 98.4-100 %). Feasibility and clinical value of the 19-valent method was prospectively shown on 16,231 incoming clinical specimens from patients between 0 and 16 years of age with acute respiratory tract infections admitted to pediatric hospitals or private practices from October 2003 to June 2010 in three regions in Germany (Kiel, Mainz, Freiburg; Freiburg to June 2007 only). At least one microorganism was detected in 10,765 of 16,231 (66.3 %) clinical specimens: 5,044 RV, 1,999 RSV, 1,286 AV, 944 EV, 737 seasonal IVA, 173 pandemic IVA H1N1-2009, 899 MPV, 518 CV, 383 PIV3, 268 PIV1, 259 Mpn, 205 IVB, 164 PIV2, 144 PIV4, 103 Bp, 29 Cpn and 29 Bpp, while reovirus and Lpn were not present in these specimens from a pediatric population. More than one organism could be detected in 13.4 % of the specimens. CONCLUSIONS: The m-RT-PCR-ELISA evaluated here improves the spectrum for diagnosing respiratory infections and is a feasible instrument for individual diagnostic and epidemiological studies.

Anesthesia in patients with neuromuscular disorders.

Neuromuscular disorders (NMDs) are a heterogeneous group of neurological and muscular diseases. Patients present with typical features such as wasting and weakness of skeletal muscles. However, despite these common clinical signs, underlying etiologies are nearly as multifaceted as the number of the diseases. For the anesthesiologist, it is very important to know the origin of a particular disease to select an appropriate anesthetic technique. Patients with NMDs are markedly sensitive to several anesthetics. Many reported anesthesia-related complications were caused by the administration of drugs like depolarizing and non-depolarizing muscle relaxants, volatile anesthetics, or respiratory and cardiovascular depressant agents.

Vaccination greatly reduces disease, disability, death and inequity worldwide.

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.

PID-ARI.net - a pediatric infectious diseases network on acute respiratory infections and the added value of a multilevel research network.

BACKGROUND: PID-ARI.net was one of three infectious disease epidemiological research networks funded by the German Ministry of Education and Research (BMBF). Its objectives were to strengthen the national initiative on infectious diseases epidemiology and to focus on a health care problem of high relevance. PATIENTS AND METHODS: A research network on the epidemiology of ARI in children was formed to generate data on several levels. Key structure was a centrally organized active surveillance system in three areas of Germany from north to south. RESULTS: In the 6 years of funding by the BMBF, an integrated research network with a known population denominator was formed. In the laboratory-based surveillance of up to 19 respiratory pathogens, 18,899 samples were analyzed. The added value is utilization of data on time, place, person and pathogen of a disease episode at several levels - from surveillance and online publication via a website to descriptive, analytical and molecular epidemiology and further specialized projects. Its wide age range including children up to 16 years of age, an extensive panel of pathogens, a known population denominator and the diversity of 3 distant geographical areas should considerably reduce vulnerability due to bias. CONCLUSIONS: Active surveillance systems for ARI are superior to passive systems. If a surveillance system such as the one used in PID-ARI.net is part of a research network which can utilize the data on several levels, the expenditure for such a system should be worthwhile and such a system would be an asset to any health care system.

Lower respiratory tract disease in children: constant pathogens - constant management?!

BACKGROUND: This study analyses the pathogens of acute lower respiratory tract infections (LRI) in children in a German community hospital over six years. Against this background the adoption of new diagnostic and therapeutic guidelines for the LRI management and of RSV-cases in particular is studied. METHODS: 1054 children aged zero to 36 months hospitalized with LRI were prospectively included in the surveillance studies "Parainfluenzavirus (PIV) and Respiratory syncytial virus (RSV) infections in Germany [PRI.de] 1999-2001" and the "pediatric infectious diseases network on acute respiratory tract infections" [PID-ARI.net] for the time period of October 2002 until June 2005. The nasopharyngeal aspirates (NPA) of these children had been analysed for RSV, PIV 1,2,3 and influenzavirus (IV)-A, -B. In 2003/2004 the national guideline on how to diagnose and treat RSV-disease (bronchiolitis) changed. Data on LRI cases severity and especially those regarding the clinical management of RSV-infections were compared to see differences following the release of the guideline. RESULTS: 84% of the children were between zero and 24 months old. 34% of the NPA specimens were positive for RSV, 7.7% for PIV 1,2,3 and 4.7% for IV-A, -B. Epidemiological findings did not differ substantially between the two studies. Clinical management of RSV-LRI, especially drug use, did not change except for the lower rate of x-ray examination (p<0.01). CONCLUSION: The spectrum of causing agents in LRI of children remained quite stable over of six years. Diagnostic and therapeutic concepts remain also stable in a situation where new guidelines were introduced, but not reinforced.

Varicella vaccination in Europe: are we ready for a universal childhood programme?

Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

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

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.

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

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.

Onset and duration of mivacurium-induced neuromuscular block in patients with Duchenne muscular dystrophy.

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.

The descriptive epidemiology of severe lower respiratory tract infections in children in Kiel, Germany.

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.

Comparison of the BD Directigen Flu A+B Kit and the Abbott TestPack RSV with a multiplex RT-PCR ELISA for rapid detection of influenza viruses and respiratory syncytial virus.

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.

Population-based incidence of severe pneumonia in children in Kiel, Germany.

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.

RSV-prevention in children guided by a web-based early warning system.

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.