Vaccine-masked spread of SARS-CoV2 in an elderly care home, and how to prevent a spill-over into the general population.

Aim: The vaccination campaign against SARS-CoV2 in Germany started at the peak of the second wave. An outbreak in an elderly care home occurred in our county at the time of the second vaccination. We describe a package of measures to control the outbreak and to prevent a spill over into the general population. Subjects and methods: After outbreak confirmation, a package of measures such as quarantine of the elderly care home, staff and visitors, and their households was implemented. By sequential testing, quarantine measures were lifted. Surveillance of staff and residents by rapid antigen test and symptom monitoring was used in parallel. Results: The outbreak was on-going for around 17 days until it was noticed by a symptomatic external staff member as index case. A total of 23 out of 96 residents (24.0%) and nine out of 114 staff (7.9%) were infected. Three residents died. Effective first-dose vaccine coverage was 85.4% in residents, 27.4% in internal, and 10.5% in external staff. Given the long latency period, the use of household quarantine prevented a spill over into the public. Already 16 days after notification of the index case the outbreak could be declared over. Conclusions: Interferences between vaccination coverage and outbreak characteristics in regard to an extended latency period were observed. Household quarantine of case as well as contact households is of increased importance in the era of vaccination to prevent further spread into the general population until population-based control measures and lockdowns can be lifted.

Household quarantine of second degree contacts is an effective non-pharmaceutical intervention to prevent tertiary cases in the current SARS-CoV pandemic.

BACKGROUND: Given the characteristics of SARS-CoV2 with regard to transmission before the onset of symptoms and varying manifestation indices according to age, isolation and quarantine have limited efficacy in the current pandemic. Household quarantine in second degree contacts (Hh-Q2°) outside the case household has so far only been addressed by modellers. In the literature there is no publication based on field data. METHODS: In a retrospective cohort study on real field data from a county health department (CHD), all PCR-confirmed cases and related contact persons put into quarantine were analysed. Hh-Q2° was used in our CHD from the onset of the pandemic. RESULTS: From 9 March to 8 December 2020, 353 PCR-confirmed cases were registered in the CHD Ploen, Northern Germany: 225 (63.7%) primary, 107 (30.3%) secondary and 21 (5.9%) tertiary cases. The 107 secondary cases resulted out of 470 (22.8%) close or 1°contacts and 21 tertiary cases out of 179 (11.7%) indirect or 2°contacts put into quarantine. The efficacy of Hh-Q2° was 51.5% (11.7%/22.8%) of that of quarantine in 1°contacts; 16.4% of all converted cases in quarantined persons were ascertained by Hh-Q2°. One in ten 1°contacts in households with tertiary cases remained asymptomatic. CONCLUSION: The impact of Hh-Q2° in preventing further spread of SARS-CoV2 was considerable. With half the conversion rate in 2°contacts compared to 1°contacts, the efficacy of Hh-Q2° is substantial. Hh-Q2° should definitely be used routinely to control the spread of SARS-CoV2 more efficiently and national authorities should include it in their guidelines.

Open flanks in the management of tuberculosis in Germany under the pressure of migration.

To prevent transmission is the ultimate goal of any TB control strategy. So far, asylum seekers/immigrants are only actively screened for TB after arrival in Germany, if admitted to mass accommodation facilities. The current TB control strategy in Germany is assessed by a SWOT-analysis (strengths, weaknesses, opportunities and threats) including the impact of active case finding, environmental case finding (ECF) also known as contact tracing, passive case finding (PCF) and effective TB treatment. According to the number-needed-to-screen (NNS), asylum seekers from most countries and unaccompanied minors would have to be screened for active TB by a chest radiograph at entry independently of the type of accommodation. This would include children between 10 and 15 years of age and a follow-up for at least 3 to 5 years, with a denser follow-up in the first year. ECF and PCF only contribute little to a proactive reduction of the pre-patency period. The available data on the epidemiology and the NNS of TB in migrants are sufficient to come up with a more powerful control strategy for TB in migrants in Germany to close the existing open flanks. It is time for action.

[Outbreaks of Scabies in Schools and Use of Ivermectin]. / Fallhäufungen von Skabies an Schulen und Einsatz von Ivermectin.

BACKGROUND: At Pentecost 2017 outbreaks of scabies occurred in three schools in Ploen County. Several classes were supposed to go on an excursion or had returned from an excursion with symptomatic kids. METHODS: Rapid investigation, on site outbreak confirmation, home visits of the environment of the index cases, simultaneous mass treatment and post exposure prophylaxis (PEP) with Ivermectin according to the outbreak characteristics were applied. RESULTS: The index case of school A was ill since 5 months, but was misdiagnosed as eczema. Not all cases were linked to this index case. The entire school was treated in three steps within a 10-day period: step 1 began 48 h after notification. The attack rate was 6.4% (19 out of 298 pupils). A total of 93% of the kids and 100% of the teaching staff were treated. For school B with two sporadic and independent cases, an alert warning was issued. In school C, the two classes with cases were treated and according to the contact pattern two further classes were physically examined: 7 out of 39 (18%) of the kids were symptomatic, but none in the contact classes. CONCLUSIONS: The endemicity of scabies appears to be much higher than previously assumed. With the use of Ivermectin, the local public health department could act quickly and demonstrate that interventional public health is possible. However, several obstacles had to be overcome, but parents and teachers were cooperative and thankful.

[The Plöner Model for the School Entry Screening is a Role Model for the Future]. / Das Plöner Modell zur Schuleingangsuntersuchung ist richtungsweisend für die Zukunft.

BACKGROUND: The Plöner Model is a stepwise-selective model, similar to the one practised in all of Bavaria since 2008. It was already developed in 2002/2003 for the school entry screening and has been in use since then. Such models are intermittently criticized since not each child is seen by a doctor. METHODS: The procedure and data of the Plöner Model are analyzed and put into a wider context within Germany and beyond. The current programs in place are therefore categorized into 3 groups and compared with regard to public heath ethics criteria. The primary endpoint is the need for special schooling or assistance. RESULTS: From 2003 to 2016, 1475-1045 children per year before school entry were checked by the pediatric health team of the county health department consisting of 2.1 full time equivalents of medical assistants and 1.5 fulltime equivalent pediatricians having other routine duties. Applying a stepwise-selective model, for children with special needs, 45-60 min instead of the usual 15 min per child were available. The roster consisting of a questionnaire for parents with a comment section for the daycare staff, a health and developmental check by the medical assistants and a detailed catalogue of inclusion criteria allowed to only examine 28-41% of the cohort by a pediatrician. The percentage of children needing further special care was within the mean of the entire cohort of the federal state of Schleswig-Holstein. CONCLUSION: A stepwise-selective procedure is warranted for the sake of efficiency and public health ethics. The required certainty (true positive and true negative) is guaranteed by the Plöner Model. Any program, either to examine all children by a doctor or moving parts of the school entry screening into the fourth year of life, require a continued critical evaluation and professional guidance.

A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects.

BACKGROUND: Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. METHODS: MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. RESULTS: Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of 1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]). CONCLUSIONS: One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. No cases of myopericarditis were observed following vaccinations with MVA. The safety, reactogenicity and immunogenicity were similar to that seen in younger (18-55 year old) healthy populations as investigated in other MVA trials. The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT00857493.

RSV--a substantial slice of the airway disease burden and the way to a vaccine.

BACKGROUND: The impact of an active RSV vaccine in the future will depend on the true fraction of airway diseases attributable to RSV as the causal pathogen, since many pathogens contribute to the airway disease burden at the same time. This attributable slice of the airway disease burden can vary between populations, regions and seasons, and by the incidence of co-infections. Furthermore, potential future vaccine effectiveness will depend on several characteristics such as prevention of vaccine escape mutants and earliest possible time of vaccination. AIMS AND METHODS: To analyse the disease burden attributable to RSV and review recently published, high-quality epidemiological data from all parts of the world. The development of an active RSV vaccine is illustrated and hurdles in delivery are described. RESULTS: RSV is estimated to be responsible for up to 22% of severe lower respiratory tract infections in children under 5 years of age. First lifetime RSV infections occur at a very early age, mainly in infants and toddlers, in a seasonal pattern, and lead to bacterial co-infections in about one-third of patients. The development of an active RSV vaccine faces several hurdles such as incomplete natural immunity, high variability of RS viruses, selection of the best antigens, choosing the proper vaccine technology platform, and lack of an immune correlate of protection. Added to this is the long way a clinical development programme has to go before it is possible from a regulatory point of view to test a vaccine candidate in a considerable number of RSV-naive children. CONCLUSION: An active RSV vaccine is urgently needed, but, given experience in the 1960s with the formalin-inactivated vaccines, and the long and complicated process involved in development, considerable support and flexibility by regulatory bodies and substantial funds are needed. The slice of up to 22% of the ARI disease burden in the first 5 years of life, which is potentially preventable by an active vaccine, is substantial, and the endeavour worthwhile.

Are meteorological parameters associated with acute respiratory tract infections?

BACKGROUND: Information on the onset of epidemics of acute respiratory tract infections (ARIs) is useful in timing preventive strategies (eg, the passive immunization of high-risk infants against respiratory syncytial virus [RSV]). Aiming at better predictions of the seasonal activity of ARI pathogens, we investigated the influence of climate on hospitalizations for ARIs. METHODS: Samples obtained from 3044 children hospitalized with ARIs in Mainz, Germany, were tested for pathogens with a multiplex reverse-transcriptase polymerase chain reaction enzyme-linked immunosorbent assay from 2001 through 2006. Hospitalizations for ARIs were correlated with meteorological parameters recorded at the University of Mainz. The frequency of hospitalization for RSV infection was predicted on the basis of multiple time series analysis. RESULTS: Influenza A, RSV, and adenovirus were correlated with temperature and rhinovirus to relative humidity. In a time series model that included seasonal and climatic conditions, RSV-associated hospitalizations were predictable. CONCLUSIONS: Seasonality of certain ARI pathogens can be explained by meteorological influences. The model presented herein is a first step toward predicting annual RSV epidemics using weather forecast data.

No temporal association between influenza outbreaks and invasive pneumococcal infections.

OBJECTIVE: To assess whether the influenza peak in populations precedes the annual peak for invasive pneumococcal infections (IPI) in winter. DESIGN: Ecological study. Active surveillance data on influenza A and IPI in children up to 16 years of age collected from 1997 to 2003 were analysed. SETTING: Paediatric hospitals in Germany. PATIENTS: Children under 16 years of age. RESULTS: In all years under study, the influenza A season did not appear to affect the IPI season (p = 0.49). Specifically, the influenza peak never preceded the IPI peak. CONCLUSION: On a population level there was no indication that the annual influenza epidemic triggered the winter increase in the IPI rate or the peak of the IPI distribution in children.

Diagnostic performance of a rapid antigen test for RSV in comparison with a 19-valent multiplex RT-PCR ELISA in children with acute respiratory tract infections.

A rapid and reliable diagnosis of respiratory syncytial virus (RSV) infection in childhood is very important for clinical management. In this study we compared a rapid antigen test (enzyme immunoassay, EIA) for the detection of RSV with a reverse transcriptase polymerase chain reaction (RT-PCR) [19-valent multiplex RT-PCR enzyme-linked immunosorbent assay (ELISA)] to assess the diagnostic performance. Furthermore the diagnostic value of the EIA in terms of age and season relation was analyzed. A total of 400 nasopharyngeal or tracheal secretions from pediatric patients with clinical signs of lower respiratory tract infection were included. The specimen had to be taken in a standardized manner within 72 h after admission. Specimens were tested in parallel with the EIA and the multiplex RT-PCR ELISA. The RT-PCR technique was used as the target assay. The EIA reached a sensitivity of 58% and a specificity of 90% for all samples tested. For patients < [corrected] 1 year the post-test probability for a positive EIA was 91% during the RSV season; a negative test result decreased disease probability from 53 to 25%. For older patients a positive test raised disease probability from 23 to 45% during the RSV season. Negative test results did not markedly change disease probability.

Ten years' experience with year-round active surveillance of up to 19 respiratory pathogens in children.

INTRODUCTION: Surveillance systems for acute respiratory infections (ARI) in children currently are often limited in terms of the panel of pathogens and the age range investigated or are only syndromic and at times only active in the winter season. METHODS: Within PID-ARI.net, a research network for ARI in children in Germany, an active, year-round surveillance system was formed in three regions from north to south for population-based analysis. Children from birth to 16 years of age were included and up to 19 noncolonizing airway pathogens were tested for with multiplex RT-PCR. RESULTS: In the 10-year period from July 1996 to June 2006, a total of 18,899 samples were tested. The positive rate increased with the size of the test panel to up to 72.9%. Picornaviruses (35-39%), paramyxoviruses (23-28%) and orthomyxoviruses (5.8-12.5%) comprised the highest fraction. Reoviruses and Legionella pneumophila were not found at all and Chlamydia pneumoniae and Bordetella parapertussis only rarely. Respiratory syncytial virus and parainfluenza virus (PIV) type 3 were anticyclical in rhythmicity with metapneumovirus and PIV1 and PIV2. The age medians per pathogen depended predominantly upon the attack rate and interepidemic intervals. CONCLUSION: Active surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical bacteria in children was highly overestimated in earlier studies.

Novel human metapneumovirus sublineage.

In a pediatric surveillance network, 287 (5.1%) of 5,580 specimens from patients with acute respiratory infections tested positive for human metapneumovirus (HMPV). Phylogenetic analysis of N- and F-gene sequences of identified HMPV showed that 30% belonged to a novel phylogenetic cluster.

Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease.

UNLABELLED: TIVES: We postulated a change of angiotensin II receptor subtype expression in patients with lone atrial fibrillation (AF) and AF with underlying mitral valve disease (MVD) both compared with sinus rhythm (SR). BACKGROUND: Atrial fibrillation is a progressive disease associated with electrical and structural remodeling. Angiotensin II (ANGII) is involved in the process of myocardial remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2 (AT(1) and AT(2)). METHODS: Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with or without underlying MVD. The AT(1) and AT(2) protein levels were measured by quantitative Western blotting techniques. RESULTS: The AT(1) protein level in the LA was significantly increased in patients with AF (all forms) compared with SR (p < 0.05), whereas AT(2) expression was not significantly altered. Comparison of the subgroups revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or without MVD. Additionally, investigations of ANGII receptor subtypes in the RA did not exhibit any significant changes either in AT(1) or in AT(2) in patients with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor subtype expression in LA. CONCLUSIONS: Atrial fibrillation is associated with an up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the AT(2) expression in the atrium. Because we found an enhanced expression of AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of AF in the LA.

Can respiratory syncytial virus etiology be diagnosed clinically? A hospital-based case-control study in children under two years of age.

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.

Population-based burden of pneumonia before school entry in Schleswig-Holstein, Germany.

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.