Refining the hospitalization rate: A mixed methods approach to differentiate primary COVID-19 from incidental cases.

Purpose: Until now, the Hospitalization Rate (HR) served as an indicator (among others) for the COVID-19 associated healthcare burden. To ensure that the HR accomplishes its full potential, hospitalizations caused by COVID-19 (primary cases) and hospitalizations of patients with incidental positive SARS-CoV-2 test results (incidental cases) must be differentiated. The aim of this study was to synthesize the existing evidence on differentiation criteria between hospitalizations of primary cases and incidental cases. Methods: An online survey of the members of the German Network University Medicine (NUM) was conducted. Additionally, senior clinicians with expertise in COVID-19 care were invited for qualitative, semi-structured interviews. Furthermore, a rapid literature review was undertaken on publications between 03/2020 and 12/2022. Results: In the online survey (n=30, response rate 56%), pneumonia and acute upper respiratory tract infections were the most indicative diagnoses for a primary case. In contrast, malignant neoplasms and acute myocardial infarctions were most likely to be associated with incidental cases. According to the experts (n=6), the diagnosis, ward, and type of admission (emergency or elective), low oxygen saturation, need for supplemental oxygen, and initiation of COVID-19 therapy point to a primary case. The literature review found that respiratory syndromes and symptoms, oxygen support, and elevated levels of inflammatory markers were associated with primary cases. Conclusion: There are parameters for the differentiation of primary from incidental cases to improve the objective of the HR. Ultimately, an updated HR has the potential to serve as a more accurate indicator of the COVID-19 associated healthcare burden.

Factors Affecting Physical Activity in People with Dementia: A Systematic Review and Narrative Synthesis.

Physical activity (PA) has positive effects on the physical and cognitive functioning of people with dementia. Knowledge about what limits and stimulates people with dementia to participate in PA is essential to promote effective PA implementation and enhance PA levels. Previous reviews primarily included opinion-based studies, using data from interviews, focus groups or dyads. By including implementation studies, we aimed to elaborate on previous reviews by identifying new barriers to PA and new facilitators and motivators for PA. We conducted systematic searches in Pubmed, PsychInfo and Web of Science for studies published up to the 21st of September 2021. Search terms were related to the population of people with dementia, PA interventions and implementation outcomes. Studies were included if PA participation was investigated during actual PA implementation. No restrictions were made regarding study design, date of publication, PA type or outcome measures. Studies not implementing PA or not evaluating the implementation were excluded. Based on 13 empirical studies, we identified 35 barriers, 19 facilitators and 12 motivators. Of these, 21 barriers, 11 facilitators and 4 motivators were not identified by previous reviews. New factors are related to the support for people with dementia from informal and formal caregivers, e.g., revealing the importance of a trusting relationship. Furthermore, support for staff from the institution or an external party is needed to overcome doubts about PA, for example, related to safety and effects. New factors also suggested specific recommendations for the content and organization of the PA intervention, for instance, related to how to give instructions. Overall, factors affecting PA identified with opinion-based or implementation studies are complementary. Our extended overview shows the complexity of PA implementation and may help to personalize PA, develop implementation strategies, facilitate actual PA implementation and free up resources needed for effective implementation.

Epidemiology and outcomes of vancomycin-resistant enterococcus infections: a systematic review and meta-analysis.

Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however, remains fragmented. We aimed to summarize recent studies on VRE epidemiology and outcomes in hospitals, long-term-care facilities (LTCFs) and nursing homes worldwide based on current epidemiological reports. We searched MEDLINE/PubMed, the Cochrane Library, and Web of Science for observational studies, which reported on VRE faecium and faecalis infections in in-patients published between January 2014 and December 2020. Outcomes were incidence, infection rate, mortality, length of stay (LOS), and healthcare costs. We conducted a meta-analysis on mortality (PROSPERO registration number: CRD42020146389). Of 681 identified publications, 57 studies were included in the analysis. Overall quality of evidence was moderate to low. VRE incidence was rarely and heterogeneously reported. VRE infection rate differed highly (1-55%). The meta-analysis showed a higher mortality for VRE faecium bloodstream infections (BSIs) compared with VSE faecium BSIs (risk ratio, RR 1.46; 95% confidence interval (CI) 1.17-1.82). No difference was observed when comparing VRE faecium vs VRE faecalis BSI (RR 1.00, 95% CI 0.52-1.93). LOS was higher in BSIs caused by E. faecium vs E. faecalis. Only three studies reported healthcare costs. In contrast to previous findings, our meta-analysis of included studies indicates that vancomycin resistance independent of VRE species may be associated with a higher mortality. We identified a lack of standardization in reporting outcomes, information regarding healthcare costs, and state-of-the-art microbiological species identification methodology, which may inform the set-up and reporting of future studies.

Sarcopenia of kidney transplant recipients as a predictive marker for reduced graft function and graft survival after kidney transplantation.

PURPOSE: The association between sarcopenia of kidney transplant recipients and outcome after kidney transplantation (KT) has not yet been fully understood and is still considered controversial. The aim of our study was to analyze the impact of pre-transplant sarcopenia on graft function, postoperative complication rates, and survival of the patients after renal transplantation. METHODS: In this retrospective single-center study, all patients who underwent KT (01/2013-12/2017) were included. Demographic data, rejection rates, delayed graft function, and graft and patient survival rates were analyzed. Sarcopenia was measured in computed tomography images by the sex-adjusted Hounsfield unit average calculation (HUAC). RESULTS: During the study period, 111 single KTs (38 women and 73 men) were performed. Living donor kidney transplants were performed in 48.6%. In total, 32.4% patients had sarcopenia. Sarcopenic patients were significantly older (59.6 years vs. 49.8 years; p < 0.001), had a higher body mass index (BMI = 27.6 kg/m2 vs. 25.0 kg/m2; p = 0.002), and were more likely to receive deceased donor kidneys (72.2% vs. 41.3%; p = 0.002). Interestingly, 3 years after KT, the creatinine serum levels were significantly higher (2.0 mg/dl vs. 1.5 mg/dl; p = 0.001), whereas eGFR (39.9 ml/min vs. 53.4 ml/min; p = 0.001) and graft survival were significantly lower (p = 0.004) in sarcopenic transplant recipients. Sarcopenic patients stayed in hospital significantly longer postoperatively than those who were non-sarcopenic. CONCLUSIONS: At the time of kidney transplantation, sarcopenia was found to predict reduced long-term graft function and diminished graft survival after KT. The early identification of sarcopenic patients can not only enable an optimized selection of recipients, but also the initiation of pre-habilitation programs during the waiting period.

[Current WSES-AAST guidelines on anorectal emergencies-Summary and comments]. / Aktuelle WSES-AAST-Leitlinie zu anorektalen Notfällen ­ Zusammenfassung und Kommentar.

In 2019, the World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST) generated consensus recommendations for the treatment of anorectal emergencies in Parma, Italy, and published a guideline in 2021. This is the first global guideline dealing with this important topic for surgeons' everyday work. Seven anorectal emergencies were discussed and the guideline recommendations were given according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

[Summary and comments on the WSES guidelines on open abdomen in trauma and non-trauma patients]. / Zusammenfassung und Kommentar zur WSES-Leitlinie Abdomen apertum bei Trauma- und Nichttraumapatienten.

The first edition of the World Society of Emergency Surgeons (WSES) guidelines on the indications and treatment of open abdomen in trauma as well as in non-trauma patients was published at the end of 2018. Publications from 1980 to 2017 were included in the evaluation. Based on the GRADE system each publication was checked for its evidence and evaluated in a Delphi process. In this article the aspects of the guidelines are presented and commented on.

Morgagni-Larrey diaphragmatic hernia repair in adult patients: a retrospective single-center experience.

PURPOSE: Morgagni-Larrey congenital diaphragmatic hernia (MLH) is rare in adult patients and surgery is performed infrequently. The evidence regarding the most beneficial treatment modality is low. Nevertheless, with increasing experience in minimally-invasive surgery, the literature proves the laparoscopic approach as being safely feasible. However, knowledge on the disease as well as treatment options are based on single surgeon's experiences and small case series in the literature. METHODS: Retrospective single-center analysis on adult patients (≥ 18 years) with MLH from 01/2003 to 06/2019 regarding symptoms, hernia sac contents, surgical technique and perioperative outcome. RESULTS: 4.0% of diaphragmatic hernia repair procedures were performed for MLH (n = 11 patients). 27.3% of these patients were asymptomatic. Dyspnea or gastrointestinal symptoms were frequently observed (both in 45.5% of the patients). Colon transversum (63.6%), omentum majus (45.5%) and/or stomach (27.3%) were the most common hernia sac contents. Correct diagnosis was achieved preoperatively in 10/11 patients by cross-sectional imaging. All procedures were performed by trans-abdominal surgery (laparotomy in four and laparoscopy in seven patients). All hernias were reinforced by mesh after primary closure. No differences were observed in the perioperative outcome between patients who underwent hernia repair by laparotomy versus laparoscopy. Pleural complications requiring drainage were the most common postoperative complications. CONCLUSION: MLH repair seems to be safely feasible by laparoscopic surgery. The benefit of mesh augmentation in MLH repair is not clear yet. In contrast to the current literature, all patients in this study received mesh augmentation after primary closure of the hernia. This should be evaluated in larger patient cohorts with long-term follow-up.

[Guidelines for the Management of Community Acquired Pneumonia in Children and Adolescents (Pediatric Community Acquired Pneumonia, pCAP) - Issued under the Responsibility of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Pulmonology (GPP)]. / S2k-Leitlinie Management der ambulant erworbenen Pneumonie bei Kindern und Jugendlichen (pädiatrische ambulant erworbene Pneumonie, pCAP).

The present guideline aims to improve the evidence-based management of children and adolescents with pediatric community-acquired pneumonia (pCAP). Despite a prevalence of approx. 300 cases per 100 000 children per year in Central Europe, mortality is very low. Prevention includes infection control measures and comprehensive immunization. The diagnosis can and should be established clinically by history, physical examination and pulse oximetry, with fever and tachypnea as cardinal features. Additional signs or symptoms such as severely compromised general condition, poor feeding, dehydration, altered consciousness or seizures discriminate subjects with severe pCAP from those with non-severe pCAP. Within an age-dependent spectrum of infectious agents, bacterial etiology cannot be reliably differentiated from viral or mixed infections by currently available biomarkers. Most children and adolescents with non-severe pCAP and oxygen saturation > 92 % can be managed as outpatients without laboratory/microbiology workup or imaging. Anti-infective agents are not generally indicated and can be safely withheld especially in children of young age, with wheeze or other indices suggesting a viral origin. For calculated antibiotic therapy, aminopenicillins are the preferred drug class with comparable efficacy of oral (amoxicillin) and intravenous administration (ampicillin). Follow-up evaluation after 48 - 72 hours is mandatory for the assessment of clinical course, treatment success and potential complications such as parapneumonic pleural effusion or empyema, which may necessitate alternative or add-on therapy.

[COVID-19 in hospitalized children and adolescents]. / COVID-19 bei hospitalisierten Kindern und Jugendlichen: Ein systematischer Review zu publizierten Fallserien (Stand 31.03.2020) und erste Daten aus Deutschland.

BACKGROUND: The clinical knowledge about the course, complications and treatment of COVID-19 in children and adolescents is so far limited. AIM: This systematic review summarizes the current scientific evidence regarding the clinical presentation of COVID-19 in hospitalized children based on available case series from China. In addition, first data from a nationwide pediatric hospital survey conducted by the German Society for Pediatric Infectious Diseases (DGPI) are presented. METHODS: This study evaluated 12 case series from China with 6-2143 children infected with SARS-CoV­2, which were identified by a literature search in PubMed up to 31 March 2020. The database of the German nationwide DGPI COVID-19 survey was accessed on 6 April 2020. RESULTS: The median patient age in the case series was between 2 and 7 years and 18-45% were infants <1 year of age. The duration of hospital stay was 5-20 days. Most commonly reported symptoms were fever and cough; in 40-100% of cases involvement of the lower respiratory tract was reported, usually confirmed by computed tomography (CT). Severe and critical courses of disease were reported in up to 8% of the children including 2 fatalities. So far the German DGPI COVID-19 survey reported 33 hospitalized children up to 6 April 2020, mostly with upper airway infections. Of these children, 45% were infants and 32% had an underlying medical condition. So far 3 children (9%) needed admission to an intensive care unit. CONCLUSION: COVID-19 in hospitalized children usually presented as an uncomplicated febrile upper airway infection or mild pneumonia. Severe cases or fatalities rarely occurred in children. Information on neonates and children with underlying chronic conditions as well as on therapeutic and preventive measures are urgently needed.

Increase in Streptococcus pneumoniae serotype 3 associated parapneumonic pleural effusion/empyema after the introduction of PCV13 in Germany.

INTRODUCTION: Pediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs). METHODS: In a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped. RESULTS: S. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1-4.3 years] vs. median 5.6 years [IQR 3.8-8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1. CONCLUSION: Following the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3.

Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions/empyema in Germany, 2010-2017: a nationwide surveillance study.

OBJECTIVES: Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants. METHODS: Children <18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting >7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae. RESULTS: The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34%), 541 bacteria (>40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87%); these were most frequently Streptococcus pneumoniae (41%), Streptococcus pyogenes (19%) and Staphylococcus aureus (6%). Serotype 3 accounted for 45% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95%CI 12-16) and 18 (95%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95%CI 1.5-3.2) by 2016/17 (p 0.205). CONCLUSIONS: In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.

Whole-genome sequencing enabling the detection of a colistin-resistant hypermutating Citrobacter werkmanii strain harbouring a novel metallo-ß-lactamase VIM-48.

Citrobacter spp. harbouring metallo-ß-lactamases (MBLs) have been reported from various countries and different sources, but their isolation from clinical specimens remains a rare event in Europe. MBL-harbouring Enterobacteriaceae are considered a major threat in infection control as therapeutic options are often limited to colistin. In this study, whole-genome sequencing was applied to characterise five clinical isolates of multidrug-resistant Citrobacter werkmanii obtained from rectal swabs. Four strains possessed a class 1 integron with a novel blaVIM-48 MBL resistance gene and the aminoglycoside acetyltransferase gene aacA4, whilst one isolate harboured a blaIMP-8 MBL. Resistance to colistin evolved in one strain isolated from a patient who had received colistin orally for 8 days. Genomic comparison of this strain with a colistin-susceptible pre-treatment isolate from the same patient revealed 66 single nucleotide polymorphisms (SNPs) and 26 indels, indicating the presence of a mutator phenotype. This was confirmed by the finding of a SNP in the mutL gene that led to a significantly truncated protein. Additionally, an amino acid change from glycine to serine at position 53 was observed in PmrA. Mutations in the pmrA gene have been previously described as mediating colistin resistance in different bacterial species and are the most likely reason for the susceptibility change observed. To the best of our knowledge, this is the first description of a colistin-resistant Citrobacter spp. isolated from a human sample. This study demonstrates the power of applying next-generation sequencing in a hospital setting to trace and understand evolving resistance at the level of individual patients.

Vacuum-assisted closure therapy of paradoxical reaction in tuberculous lymphadenopathy caused by Mycobacterium africanum.

A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli with a positive PCR for Mycobacterium tuberculosis complex. After debridement, vacuum-assisted closure therapy was performed for 6 weeks. Five months after the beginning of antituberculous therapy, a second paradoxical reaction occurred, with painful swelling of two contralateral supraclavicular lymph nodes. Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the culture was negative. Antituberculous treatment was continued, and additional treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks was introduced, resulting in a decrease in lymphadenopathy. Antituberculous treatment was continued for a total of 9 months. The outcome was favorable, no further lymphadenopathy occurred over the following 6 months.

[Varicella Vaccination Coverage and Possible Factors Influencing Parental Vaccination Decisions in Munich Area 2009-2011 after Introduction of Routine Varicella Vaccination]. / Entwicklung der Varizellen-Impfraten und mögliche Einflussfaktoren auf die Impfentscheidung der Eltern im Raum München in den Jahren 2009­2011 nach Einführung der allgemeinen Varizellenimpfung.

Background and Objective: Germany introduced routine varicella vaccination for all infants aged 11-14 months in 2004; since 2009, a second dose was recommended for toddlers aged 15-23 months. In Bavaria, vaccination with combined MMRV vaccine has been routinely reimbursed since the introduction of the 2-dose vaccination schedule. We investigated varicella vaccination coverage and factors associated with parental acceptance of varicella vaccination in the area of Munich from 2009 to 2011, within the frame of the 'Bavarian Varicella Surveillance Project' (2006-2011). Method: Annual cross-sectional parent survey of random samples of 600 children aged 18-36 months in Munich on the child's vaccination status for varicella and measles, socio-demographic data and parental attitude towards varicella vaccination. Results: During 2009-2011, the first dose varicella vaccination (VV) coverage increased from 53% (2009) to 68% (2011) while the second dose VV increased from 29% (2009) to 59% (2011). First-dose measles vaccination coverage was 88-91% (2009-2011). In 2009, 51% of all vaccinated children received the combined MMRV vaccine as first dose; in 2011, 94% (p<0.001). In 2009, 27% of all parents considered varicella vaccination as superfluous. This percentage had decreased to 15% by 2011. Recommendation of varicella vaccination by the physician was the most important explanatory factor and was significantly associated with parental acceptance of varicella vaccination in 2009 to 2011 (adjusted OR 11.5; 95%CI 3.6-36.3 (2009), 26.7; 95%CI 5.4-132.2 (2010) and 12.7; 95%CI 3.9-41.4 (2011)). Conclusions: From 2009 to 2011, first dose VV coverage further increased by approximately 15% up to 68%, corresponding with the increased use of MMRV. Although parental acceptance had increased, first dose coverage for varicella was still considerably lower than coverage for measles in 2011. Physician's recommendation of VV was the only independent factor significantly associated with parental acceptance in all study years. A further increase in varicella vaccination coverage is necessary in order to avoid potential negative effects such as an increase in the mean age of children getting infected with varicella. Therefore, information campaigns for both parents and physicians are urgently needed.

Prevalence of antibodies against influenza A and B viruses in children in Germany, 2008 to 2010.

The prevalence of influenza A and B virus-specific IgG was determined in sera taken between 2008 and 2010 from 1,665 children aged 0-17 years and 400 blood donors in Germany. ELISA on the basis of whole virus antigens was applied. Nearly all children aged nine years and older had antibodies against influenza A. In contrast, 40% of children aged 0-4 years did not have any influenza A virus-specific IgG antibodies. Eightysix percent of 0-6 year-olds, 47% of 7-12 year-olds and 20% of 13-17 year-olds were serologically naïve to influenza B viruses. By the age of 18 years, influenza B seroprevalence reached approximately 90%. There were obvious regional differences in the seroprevalence of influenza B in Germany. In conclusion, seroprevalences of influenza A and influenza B increase gradually during childhood. The majority of children older than eight years have basal immunity to influenza A, while comparable immunity against influenza B is only acquired at the age of 18 years. Children aged 0-6 years, showing an overall seroprevalence of 67% for influenza A and of 14% for influenza B, are especially at risk for primary infections during influenza B seasons.

Incidence and clinical presentation of acute otitis media in children aged <6 years in European medical practices.

We conducted an epidemiological, observational cohort study to determine the incidence and complications of acute otitis media (AOM) in children aged <6 years. Data on physician-diagnosed AOM were collected from retrospective review of medical charts for the year preceding enrolment and then prospectively in the year following enrolment. The study included 5776 children in Germany, Italy, Spain, Sweden, and the UK. AOM incidence was 256/1000 person-years [95% confidence interval (CI) 243-270] in the prospective study period. Incidence was lowest in Italy (195, 95% CI 171-222) and highest in Spain (328, 95% CI 296-363). Complications were documented in <1% of episodes. Spontaneous tympanic membrane perforation was documented in 7% of episodes. Both retrospective and prospective study results were similar and show the high incidence during childhood in these five European countries. Differences by country may reflect true differences and differences in social structure and diagnostic procedures.

Prevalence of antibodies against hepatitis A virus among children and adolescents in Germany.

Since hepatitis A virus (HAV) infection during childhood is mostly asymptomatic, only seroprevalence studies can provide reliable information on incidence of HAV infection in children. The prevalence of anti-HAV antibodies was determined in sera taken in 2008 to 2010 from 1,645 children aged 0-17 years and in sera taken in 2010-2011 from 400 adult blood donors in Germany. For examination of trend over time, 715 sera collected between 1999 and 2006 from children at the age of 0-17 years within the federal state Thuringia were included. Antibody testing was carried out using the test kits ETI-AB-HAVK PLUS and ETI-HA-IGMK PLUS from DiaSorin. In children, the overall prevalence of antibodies was 10.8 %. After the seroprevalence declined from 8.8 % among the 0-2 year-olds to 2.4 % among the 3-4 year-olds, there was a significant increase to 20.5 % in the group of the 15-17 year-olds. Boys had with 12.7 % a significantly higher seroprevalence of anti-HAV antibodies compared to 8.8 % among girls. In adult blood donors, there was a HAV seroprevalence of 19.3 %. The likelihood of past infection or immunization within the age groups of children from 0 to 12 years differed significantly from that of adults. In conclusion, in Germany, only a small number of HAV infections occur in children, especially up to the age of 12 years. The proportion of susceptible children is greater than the proportion of susceptible adults. Thus, during outbreaks, the rate of infection among children would usually be higher than the rate among adults.

Compound heterozygosity of two functional null mutations in the ALPL gene associated with deleterious neurological outcome in an infant with hypophosphatasia.

Hypophosphatasia (HPP) is a heterogeneous rare, inherited disorder of bone and mineral metabolism caused by different mutations in the ALPL gene encoding the isoenzyme, tissue-nonspecific alkaline phosphatase (TNAP). Prognosis is very poor in severe perinatal forms with most patients dying from pulmonary complications of their skeletal disease. TNAP deficiency, however, may also result in neurological symptoms such as neonatal seizures. The exact biological role of TNAP in the human brain is still not known and the pathophysiology of neurological symptoms due to TNAP deficiency in HPP is not understood in detail. In this report, we describe the clinical features and functional studies of a patient with severe perinatal HPP which presented with rapidly progressive encephalopathy caused by new compound heterozygous mutations in the ALPL gene which result in a functional ALPL "knock out", demonstrated in vitro. In contrast, an in vitro simulation of the genetic status of his currently asymptomatic parents who are both heterozygous for one mutation, showed a residual in vitro AP activity of above 50%. Interestingly, in our patient, the fatal outcome was due to progressive encephalopathy which was refractory to antiepileptic therapy including pyridoxine, rather than hypomineralization and respiratory insufficiency often seen in HPP patients. The patient's cranial MRI showed progressive cystic degradation of the cortex and peripheral white matter with nearly complete destruction of the cerebrum. To our knowledge, this is the first MRI-based report of a deleterious neurological clinical outcome due to a progressive encephalopathy in an infant harboring a functional human ALPL "knock out". This clinical course of disease suggests that TNAP is involved in development and may be responsible for multiple functions of the human brain. According to our data, a certain amount of residual TNAP activity might be mandatory for normal CNS function in newborns and early childhood.

Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination.

Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines (aP) have a better safety profile with lower reactogenicity, although their short and long-term efficacy was found to be slightly lower. Up to now, no established serological parameter to predict long-term protection exists. IgG-anti-pertussis avidity possibly determines the effect of different pertussis vaccines and boosting intervals on long-term immunity. Thus, the avidity of a tetanus-diphtheria-aP booster at 10-14 years was tested in three groups of adolescents who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6, 15-18 months and 5-6 years of age, four doses of aP (4aP) or four doses of wcP (4wcP) at 2, 4, 6 and 15-18 months of age. Relative avidity index (RAI) of IgG-anti-pertussis toxin (PT) and IgG-anti-filamentous-hemagglutinin (FHA) was assessed by an adapted ELISA. RAI of IgG-anti-PT and of IgG-anti-FHA correlated positively with antibody concentrations in the pre-vaccination and in the post-vaccination analysis and significantly increased after adolescent booster with aP in all groups. Pre- and post-vaccination, the proportion of participants with IgG-anti-PT RAI>40% (moderate to high avidity) was significantly lower in the 4wcP group (52.9% and 88.9%) compared to the 5aP group (89.5% and 100.0%). In conclusion, TdaP in adolescence induces an increase of antibody avidity and, thus, is able to enhance the binding-quality of antibodies against pertussis. The study suggests including antibody avidity into serological studies on the humoral response to provide information about the long-term efficacy of the vaccine.