• The assessment of childhood maltreatment and its associations with affective symptoms in adulthood: Results of the German National Cohort (NAKO).

      Klinger-König, Johanna; Streit, Fabian; Erhardt, Angelika; Kleineidam, Luca; Schmiedek, Florian; Schmidt, Börge; Investigators, Nako; Wagner, Michael; Deckert, Jürgen; Rietschel, Marcella; et al. (Taylor and Francis, 2022-03-18)
      Overall, 21,131 participants (27.5%) reported at least one type of childhood maltreatment; 14,017 participants (18.3%) reported exactly one type and 250 participants (0.3%) reported all five types of childhood maltreatment. Small differences regarding age (mean absolute deviation around the mean (MAD)=0.47), sex (MAD = 0.07) and education (MAD = 0.82) were observed. The severity of childhood maltreatment was associated with more severe symptoms of depression (β = 0.23), anxiety (β = 0.21) and perceived stress (β = 0.23) in adulthood, validated particularly for emotional abuse and emotional neglect.
    • Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

      Langer, Susan; Horn, Johannes; Gottschick, Cornelia; Klee, Bianca; Purschke, Oliver; Caputo, Mahrrouz; Dorendorf, Evelyn; Meyer-Schlinkmann, Kristin Maria; Raupach-Rosin, Heike; Karch, André; et al. (MDPI, 2022-01-05)
      Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.
    • Referral of presumptive TB among operators of community medicine outlets.

      Kwabla, M P; Amuasi, J H; Krause, G; Klett-Tammen, C J; Castell, S; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Ingenta connect, 2021-12-01)
      BACKGROUND: Case detection is an important part of TB control programmes. In 2007, the TB programme in Ghana join the WHO´s public-private partnership with community medicine outlet operators to increase referral of persons with presumptive TB for laboratory investigation. Information on factors likely to influence referral is scarce in Ghana. We assessed these factors among pharmacists and over-the-counter (OTC) medicine sellers.METHODS: In 2019-2020, we conducted computer-assisted telephone interviews among community pharmacists and OTC medicine sellers in the Eastern Region of Ghana. We used a structured questionnaire and collected data on respondents´ sociodemographics and professional characteristics. We used logistic regression to investigate characteristics associated with self-reported referral of presumptive TB cases.RESULTS: Of all respondents who completed the interviews, 68.7% (321/467) reported having ever referred a presumptive TB case and 72.1% (336/466) had received specific training. Associated factors of presumptive TB referral were having received specific training (OR 2.7, 95% CI 1.5-4.9); performing both dispensing and managerial functions (OR 2.8, 95% CI 1.4-5.5); operating from OTC shop (OR 6.2, 95% CI 1.6-23.4) and the availability of a TB laboratory within walking distance (OR 3.3, 95% CI 1.2-9.5).CONCLUSION: Interviewees largely support TB referral. However, a significant proportion does not follow the strategy closely. We recommend more specific TB training courses.
    • Carbapenem-Resistant spp. as an Emerging Concern in the Hospital-Setting: Results From a Genome-Based Regional Surveillance Study.

      Yao, Yancheng; Falgenhauer, Linda; Falgenhauer, Jane; Hauri, Anja M; Heinmüller, Petra; Domann, Eugen; Chakraborty, Trinad; Imirzalioglu, Can; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Frontiers, 2021-11-11)
      The rise of Carbapenem-resistant Enterobacterales (CRE) represents an increasing threat to patient safety and healthcare systems worldwide. Citrobacter spp., long considered not to be a classical nosocomial pathogen, in contrast to Klebsiella pneumoniae and Escherichia coli, is fast gaining importance as a clinical multidrug-resistant pathogen. We analyzed the genomes of 512 isolates of 21 CRE species obtained from 61 hospitals within a three-year-period and found that Citrobacter spp. (C. freundii, C. portucalensis, C. europaeus, C. koseri and C. braakii) were increasingly detected (n=56) within the study period. The carbapenemase-groups detected in Citrobacter spp. were KPC, OXA-48/-like and MBL (VIM, NDM) accounting for 42%, 31% and 27% respectively, which is comparable to those of K. pneumoniae in the same study. They accounted for 10%, 17% and 14% of all carbapenemase-producing CRE detected in 2017, 2018 and 2019, respectively. The carbapenemase genes were almost exclusively located on plasmids. The high genomic diversity of C. freundii is represented by 22 ST-types. KPC-2 was the predominantly detected carbapenemase (n=19) and was located in 95% of cases on a highly-conserved multiple-drug-resistance-gene-carrying pMLST15 IncN plasmid. KPC-3 was rarely detected and was confined to a clonal outbreak of C. freundii ST18. OXA-48 carbapenemases were located on plasmids of the IncL/M (pOXA-48) type. About 50% of VIM-1 was located on different IncN plasmids (pMLST7, pMLST5). These results underline the increasing importance of the Citrobacter species as emerging carriers of carbapenemases and therefore as potential disseminators of Carbapenem- and multidrug-resistance in the hospital setting.
    • A mathematical model of how non-adherence to HIV management guidelines for infected newborns contribute to the spread of HIV/AIDS

      Apenteng, Ofosuhene O.; Kwabla, Mavis Pearl; Ismail, Noor Azina; Gold, Kafilah Lola; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Routledge, 2021-11-11)
      Each year, millions of children are born with human immunodeficiency virus (HIV), a quarter of whom adhere poorly to HIV treatment guidelines. This study uses a simple mathematical model to investigate the basic dynamic processes by which infected newborns under treatment progress to AIDS and contribute to its spread. The results indicate that the disease-free steady state is unstable, raising substantial concern from the public health point of view. The results show that the fraction of newborns who fail to adhere to the HIV management guidelines (30%) significantly contributes to the spread of HIV. However, the rate of HIV-positive newborns under treatment therapy is significant. This study agrees that only a small proportion of HIV-positive newborns adhere to management guidelines. These analyses should yield significant knowledge to advance our understanding of HIV infection in the early stages of life.
    • Reducing burden from respiratory infections in refugees and immigrants: a systematic review of interventions in OECD, EU, EEA and EU-applicant countries.

      Lambert, Jan-Frederic; Stete, Katarina; Balmford, James; Bockey, Annabelle; Kern, Winfried; Rieg, Siegbert; Boeker, Martin; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2021-08-26)
      Background: Respiratory diseases are a major reason for refugees and other immigrants seeking health care in countries of arrival. The burden of respiratory diseases in refugees is exacerbated by sometimes poor living conditions characterised by crowding in mass accommodations and basic living portals. The lack of synthesised evidence and guideline-relevant information to reduce morbidity and mortality from respiratory infections endangers this population. Methods: A systematic review of all controlled and observational studies assessing interventions targeting the treatment, diagnosis and management of respiratory infections in refugees and immigrants in OECD, EU, EEA and EU-applicant countries published between 2000 and 2019 in MEDLINE, CINAHL, PSYNDEX and the Web of Science. Results: Nine of 5779 identified unique records met our eligibility criteria. Seven studies reported an increase in vaccine coverage from 2 to 52% after educational multilingual interventions for respiratory-related childhood diseases (4 studies) and for influenza (5 studies). There was limited evidence in one study that hand sanitiser reduced rates of upper respiratory infections and when provided together with face masks also the rates of influenza-like-illness in a hard to reach migrant neighbourhood. In outbreak situations of vaccine-preventable diseases, secondary cases and outbreak hazards were reduced by general vaccination strategies early after arrival but not by serological testing after exposure (1 study). We identified evidence gaps regarding interventions assessing housing standards, reducing burden of bacterial pneumonia and implementation of operational standards in refugee care and reception centres. Conclusions: Multilingual health literacy interventions should be considered to increase uptake of vaccinations in refugees and immigrants. Immediate vaccinations upon arrival at refugee housings may reduce secondary infections and outbreaks. Well-designed controlled studies on housing and operational standards in refugee and immigrant populations early after arrival as well as adequate ways to gain informed consent for early vaccinations in mass housings is required to inform guidelines.
    • Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis.

      Strengert, Monika; Becker, Matthias; Ramos, Gema Morillas; Dulovic, Alex; Gruber, Jens; Juengling, Jennifer; Lürken, Karsten; Beigel, Andrea; Wrenger, Eike; Lonnemann, Gerhard; et al. (Elsevier, 2021-08-12)
      Background: Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. Methods: We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay. Findings: Patients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. Interpretation: Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity. Funding: Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.
    • Assessing excess mortality in times of pandemics based on principal component analysis of weekly mortality data-the case of COVID-19.

      Vanella, Patrizio; Basellini, Ugofilippo; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer Nature, 2021-08-09)
      The COVID-19 outbreak has called for renewed attention to the need for sound statistical analyses to monitor mortality patterns and trends over time. Excess mortality has been suggested as the most appropriate indicator to measure the overall burden of the pandemic in terms of mortality. As such, excess mortality has received considerable interest since the outbreak of COVID-19 began. Previous approaches to estimate excess mortality are somewhat limited, as they do not include sufficiently long-term trends, correlations among different demographic and geographic groups, or autocorrelations in the mortality time series. This might lead to biased estimates of excess mortality, as random mortality fluctuations may be misinterpreted as excess mortality. We propose a novel approach that overcomes the named limitations and draws a more realistic picture of excess mortality. Our approach is based on an established forecasting model that is used in demography, namely, the Lee-Carter model. We illustrate our approach by using the weekly age- and sex-specific mortality data for 19 countries and the current COVID-19 pandemic as a case study. Our findings show evidence of considerable excess mortality during 2020 in Europe, which affects different countries, age, and sex groups heterogeneously. Our proposed model can be applied to future pandemics as well as to monitor excess mortality from specific causes of death.
    • Effect modification of the association between comorbidities and severe course of COVID-19 disease by age of study participants: a systematic review and meta-analysis.

      Fernández Villalobos, Nathalie Verónica; Ott, Jördis Jennifer; Klett-Tammen, Carolina Judith; Bockey, Annabelle; Vanella, Patrizio; Krause, Gérard; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2021-06-30)
      Adjusting the protecting group strategy, from an alkyl ether to a bidentate ketal at the carbohydrate backbone of uridine, facilitates a switchable diastereoselective α- or β-C4'/C5'-spirocyclopropanation. Using these spirocyclopropanated nucleosides as key intermediates, we synthesized a variety of C4'-methylated d-ribose and l-lyxose-configured uridine derivatives by a base-mediated ring-opening of the spirocyclopropanol moiety. Investigations of antiviral activity against the human respiratory syncytial virus were carried out for selected derivatives, showing moderate activity.
    • Der Einfluss des Klimawandels auf die Ausbreitung von Infektionserkrankungen – am Beispiel der Lyme-Borreliose

      Lotto-Batista, Martín; Behrens, Christiane; Castell, Stefanie; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Medizinisch Wissenschaftliche Verlagsgesellschaft, 2021-06-07)
      Durch Zecken übertragene Erkrankungen gehören zu den häufigsten klimasensitiven Infektionserkrankungen auf der Nordhalbkugel. Lyme-Borreliose weist dabei die höchste Prävalenz unter diesen Erkrankungen in Europa, wo Ixodes ricinus (Gemeiner Holzbock) sehr verbreitet ist, auf. Mit fortschreitendem Klimawandel ändern sich die Bedingungen für die Verbreitung von Zeckenpopulationen, zum einen aufgrund von Temperatur- oder Niederschlagsver- änderungen, zum anderen wegen Änderungen in der Landnutzung sowie im menschlichen Verhalten. Während für Nordeuropa eine vermehrte Ausbreitung der Zecken erwartet wird, könnten vermehrte Trockenheit und Hitzeepisoden einen Rückgang der Zeckenpopulationen in mittleren und südlichen Regionen, die gegenwärtig Risikogebiete sind, bewirken. Folglich könnte Deutschland von den schlechteren Bedingungen für das Überleben von Zecken profitieren. Dennoch ist das komplexe System, das zur Entwicklung der Borreliose-Fallzahlen beiträgt, flexibel genug, um diesen Klimaeffekten entgegenzuwirken. Weitere Forschungsarbeiten sind notwendig, um die Auswirkungen des Klimawandels auf das Risiko von Borreliose in Deutschland vorhersagen zu können. Wenn immer mehr detailliertere Klimaprojektionen verfügbar werden, sollten Vorhersagen, die zu verbesserten oder regional spezifischeren Public Health-Empfehlungen in naher Zukunft sichtbar sein.
    • Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection.

      Jombart, Thibaut; Ghozzi, Stéphane; Schumacher, Dirk; Taylor, Timothy J; Leclerc, Quentin J; Jit, Mark; Flasche, Stefan; Greaves, Felix; Ward, Tom; Eggo, Rosalind M; et al. (The Royal Society, 2021-05-31)
      As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.
    • Needs for an Integration of Specific Data Sources and Items - First Insights of a National Survey Within the German Center for Infection Research.

      Jakob, Carolin E M; Stecher, Melanie; Fuhrmann, Sandra; Wingen-Heimann, Sebastian; Heinen, Stephanie; Anton, Gabriele; Behnke, Michael; Behrends, Uta; Boeker, Martin; Castell, Stefanie; et al. (IOS Press, 2021-05-24)
      State-subsidized programs develop medical data integration centers in Germany. To get infection disease (ID) researchers involved in the process of data sharing, common interests and minimum data requirements were prioritized. In 06/2019 we have initiated the German Infectious Disease Data Exchange (iDEx) project. We have developed and performed an online survey to determine prioritization of requests for data integration and exchange in ID research. The survey was designed with three sub-surveys, including a ranking of 15 data categories and 184 specific data items and a query of available 51 data collecting systems. A total of 84 researchers from 17 fields of ID research participated in the survey (predominant research fields: gastrointestinal infections n=11, healthcare-associated and antibiotic-resistant infections n=10, hepatitis n=10). 48% (40/84) of participants had experience as medical doctor. The three top ranked data categories were microbiology and parasitology, experimental data, and medication (53%, 52%, and 47% of maximal points, respectively). The most relevant data items for these categories were bloodstream infections, availability of biomaterial, and medication (88%, 87%, and 94% of maximal points, respectively). The ranking of requests of data integration and exchange is diverse and depends on the chosen measure. However, there is need to promote discipline-related digitalization and data exchange.
    • Effectiveness of Trainings of General Practitioners on Antibiotic Stewardship: Methods of a Pragmatic Quasi-Experimental Study in a Controlled Before-After Design in South-East-Lower Saxony, Germany (WASA).

      Gornyk, Daniela; Scharlach, Martina; Buhr-Riehm, Brigitte; Klett-Tammen, Carolina Judith; Eberhard, Sveja; Stahmeyer, Jona Theodor; Großhennig, Anika; Smith, Andrea; Meinicke, Sarah; Bautsch, Wilfried; et al. (Frontiers, 2021-04-22)
      Introduction: Antibiotic resistance is a serious threat to global public health. It reduces the effectiveness of treatments for serious bacterial infections and thus increases the risk of fatal outcomes. Antibiotic prescriptions are often not in line with clinical evidence-based guidelines. The process of emergence of resistant bacteria can be slowed down by adherence to guidelines. Yet this adherence seems to be lacking in primary health care. Methods and Analysis: This pragmatic quasi-experimental study using a controlled before-after design was carried out in South-East-Lower Saxony in 2018-2020. The voluntary attendance of interactive trainings with condensed presentation of current guidelines for general practitioners (GP) on antibiotic management for urinary and respiratory tract infections is regarded as intervention. Those GP not attending the trainings constitute the control group. Data were collected via questionnaires; routine health records are provided by a statutory health insurance. The primary outcome is the proportion of (guideline-based) prescriptions in relation to the relevant ICD-10 codes as well as daily defined doses and the difference in proportion of certain prescriptions according to guidelines before and after the intervention as compared to the control group. Further outcomes are among others the subjectively perceived risk of antibiotic resistance and the attitude toward the guidelines. The questionnaires to assess this are based on theory of planned behavior (TPB) and health action process approach (HAPA). Variations over time and effects caused by measures other than WASA (Wirksamkeit von Antibiotika-Schulungen in der niedergelassenen Aerzteschaft-Effectiveness of antibiotic management training in the primary health care sector) training are taken into account by including the control group and applying interrupted time series analysis. Ethics and Dissemination: The study protocol and the data protection concept respectively were reviewed and approved by the Ethics Committee of the Hannover Medical School and the Federal Commissioner for Data Protection and Freedom of Information. Trial Registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013951, identifier DRKS00013951.
    • Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity.

      Becker, Matthias; Strengert, Monika; Junker, Daniel; Kaiser, Philipp D; Kerrinnes, Tobias; Traenkle, Bjoern; Dinter, Heiko; Häring, Julia; Ghozzi, Stéphane; Zeck, Anne; et al. (NPG, 2021-02-19)
      The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.
    • Development of the reproduction number from coronavirus SARS-CoV-2 case data in Germany and implications for political measures.

      Khailaie, Sahamoddin; Mitra, Tanmay; Bandyopadhyay, Arnab; Schips, Marta; Mascheroni, Pietro; Vanella, Patrizio; Lange, Berit; Binder, Sebastian C; Meyer-Hermann, Michael; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BioMedCentral, 2021-01-28)
      Background: SARS-CoV-2 has induced a worldwide pandemic and subsequent non-pharmaceutical interventions (NPIs) to control the spread of the virus. As in many countries, the SARS-CoV-2 pandemic in Germany has led to a consecutive roll-out of different NPIs. As these NPIs have (largely unknown) adverse effects, targeting them precisely and monitoring their effectiveness are essential. We developed a compartmental infection dynamics model with specific features of SARS-CoV-2 that allows daily estimation of a time-varying reproduction number and published this information openly since the beginning of April 2020. Here, we present the transmission dynamics in Germany over time to understand the effect of NPIs and allow adaptive forecasts of the epidemic progression. Methods: We used a data-driven estimation of the evolution of the reproduction number for viral spreading in Germany as well as in all its federal states using our model. Using parameter estimates from literature and, alternatively, with parameters derived from a fit to the initial phase of COVID-19 spread in different regions of Italy, the model was optimized to fit data from the Robert Koch Institute. Results: The time-varying reproduction number (Rt) in Germany decreased to <1 in early April 2020, 2-3 weeks after the implementation of NPIs. Partial release of NPIs both nationally and on federal state level correlated with moderate increases in Rt until August 2020. Implications of state-specific Rt on other states and on national level are characterized. Retrospective evaluation of the model shows excellent agreement with the data and usage of inpatient facilities well within the healthcare limit. While short-term predictions may work for a few weeks, long-term projections are complicated by unpredictable structural changes. Conclusions: The estimated fraction of immunized population by August 2020 warns of a renewed outbreak upon release of measures. A low detection rate prolongs the delay reaching a low case incidence number upon release, showing the importance of an effective testing-quarantine strategy. We show that real-time monitoring of transmission dynamics is important to evaluate the extent of the outbreak, short-term projections for the burden on the healthcare system, and their response to policy changes.
    • The transplant cohort of the German center for infection research (DZIF Tx-Cohort): study design and baseline characteristics.

      Karch, André; Schindler, Daniela; Kühn-Steven, Andrea; Blaser, Rainer; Kuhn, Klaus A; Sandmann, Lisa; Sommerer, Claudia; Guba, Markus; Heemann, Uwe; Strohäker, Jens; et al. (Springer, 2021-01-25)
      Infectious complications are the major cause of morbidity and mortality after solid organ and stem cell transplantation. To better understand host and environmental factors associated with an increased risk of infection as well as the effect of infections on function and survival of transplanted organs, we established the DZIF Transplant Cohort, a multicentre prospective cohort study within the organizational structure of the German Center for Infection Research. At time of transplantation, heart-, kidney-, lung-, liver-, pancreas- and hematopoetic stem cell- transplanted patients are enrolled into the study. Follow-up visits are scheduled at 3, 6, 9, 12 months after transplantation, and annually thereafter; extracurricular visits are conducted in case of infectious complications. Comprehensive standard operating procedures, web-based data collection and monitoring tools as well as a state of the art biobanking concept for blood, purified PBMCs, urine, and faeces samples ensure high quality of data and biosample collection. By collecting detailed information on immunosuppressive medication, infectious complications, type of infectious agent and therapy, as well as by providing corresponding biosamples, the cohort will establish the foundation for a broad spectrum of studies in the field of infectious diseases and transplant medicine. By January 2020, baseline data and biosamples of about 1400 patients have been collected. We plan to recruit 3500 patients by 2023, and continue follow-up visits and the documentation of infectious events at least until 2025. Information about the DZIF Transplant Cohort is available at https://www.dzif.de/en/working-group/transplant-cohort .
    • Impact of non-pharmaceutical interventions targeted at COVID-19 pandemic on influenza burden - a systematic review.

      Fricke, Lara Marleen; Glöckner, Stephan; Dreier, Maren; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2020-12-03)
      Objectives: To better understand the impact of comprehensive COVID-19 targeted non-pharmaceutical interventions (NPIs) on influenza burden worldwide. Methods: We conducted a systematic literature search in selected databases (PubMed, WHO COVID-19), preprint servers (medRxiv, bioRxiv) and websites of European Public Health institutes. Documents that compared influenza estimates in the 2019/2020 season with previous seasons were included. Information synthesis was qualitative due to a high heterogeneity in the number and periods of comparative seasons, outcome measures and statistical methods. Results: We included 23 records reporting from 15 countries/regions as well as 8 reports from European Public Health agencies. Estimates in the 2019/2020 season based on influenza virus tests (4 out of 7 countries/regions), defined influenza cases (8 out of 9), influenza positivity rate (7 out of 8), and severe complications (1 out of 2) were lower than in former seasons. Results from syndromic indicators, such as influenza-like-illness (ILI), were less clear or even raised (4 out of 7) after the influenza season indicating a misclassification with COVID-19 cases. Conclusions: Evidence synthesis suggests that NPIs targeted at SARS-CoV-2-transmission reduce influenza burden as well. Low threshold NPIs need to be more strongly emphasized in influenza prevention strategies. Keywords: COVID-19; Flu; Influenza; Non-pharmaceutical interventions; SARS-CoV-2; Surveillance; Systematic review.
    • EventEpi-A natural language processing framework for event-based surveillance.

      Abbood, Auss; Ullrich, Alexander; Busche, Rüdiger; Ghozzi, Stéphane; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (PLOS, 2020-11-20)
      According to the World Health Organization (WHO), around 60% of all outbreaks are detected using informal sources. In many public health institutes, including the WHO and the Robert Koch Institute (RKI), dedicated groups of public health agents sift through numerous articles and newsletters to detect relevant events. This media screening is one important part of event-based surveillance (EBS). Reading the articles, discussing their relevance, and putting key information into a database is a time-consuming process. To support EBS, but also to gain insights into what makes an article and the event it describes relevant, we developed a natural language processing framework for automated information extraction and relevance scoring. First, we scraped relevant sources for EBS as done at the RKI (WHO Disease Outbreak News and ProMED) and automatically extracted the articles' key data: disease, country, date, and confirmed-case count. For this, we performed named entity recognition in two steps: EpiTator, an open-source epidemiological annotation tool, suggested many different possibilities for each. We extracted the key country and disease using a heuristic with good results. We trained a naive Bayes classifier to find the key date and confirmed-case count, using the RKI's EBS database as labels which performed modestly. Then, for relevance scoring, we defined two classes to which any article might belong: The article is relevant if it is in the EBS database and irrelevant otherwise. We compared the performance of different classifiers, using bag-of-words, document and word embeddings. The best classifier, a logistic regression, achieved a sensitivity of 0.82 and an index balanced accuracy of 0.61. Finally, we integrated these functionalities into a web application called EventEpi where relevant sources are automatically analyzed and put into a database. The user can also provide any URL or text, that will be analyzed in the same way and added to the database. Each of these steps could be improved, in particular with larger labeled datasets and fine-tuning of the learning algorithms. The overall framework, however, works already well and can be used in production, promising improvements in EBS. The source code and data are publicly available under open licenses.
    • Development and external validation of a clinical prediction model for MRSA carriage at hospital admission in Southeast Lower Saxony, Germany.

      Raschpichler, Gabriele; Raupach-Rosin, Heike; Akmatov, Manas K; Castell, Stefanie; Rübsamen, Nicole; Feier, Birgit; Szkopek, Sebastian; Bautsch, Wilfried; Mikolajczyk, Rafael; Karch, André; et al. (Nature publishing group (NPG), 2020-10-22)
      In countries with low endemic Methicillin-resistant Staphylococcus aureus (MRSA) prevalence, identification of risk groups at hospital admission is considered more cost-effective than universal MRSA screening. Predictive statistical models support the selection of suitable stratification factors for effective screening programs. Currently, there are no universal guidelines in Germany for MRSA screening. Instead, a list of criteria is available from the Commission for Hospital Hygiene and Infection Prevention (KRINKO) based on which local strategies should be adopted. We developed and externally validated a model for individual prediction of MRSA carriage at hospital admission in the region of Southeast Lower Saxony based on two prospective studies with universal screening in Braunschweig (n = 2065) and Wolfsburg (n = 461). Logistic regression was used for model development. The final model (simplified to an unweighted score) included history of MRSA carriage, care dependency and cancer treatment. In the external validation dataset, the score showed a sensitivity of 78.4% (95% CI: 64.7-88.7%), and a specificity of 70.3% (95% CI: 65.0-75.2%). Of all admitted patients, 25.4% had to be screened if the score was applied. A model based on KRINKO criteria showed similar sensitivity but lower specificity, leading to a considerably higher proportion of patients to be screened (49.5%).
    • The impact of implementing HIV prevention policies therapy and control strategy among HIV and AIDS incidence cases in Malaysia.

      Apenteng, Ofosuhene O; Osei, Prince P; Oduro, Bismark; Kwabla, Mavis Pearl; Ismail, Noor Azina (Elsevier, 2020-09-30)
      Malaysia is faced with a high HIV/AIDS burden that poses a public health threat. We constructed and applied a compartmental model to understand the spread and control of HIV/AIDS in Malaysia. A simple model for HIV and AIDS disease that incorporates condom and uncontaminated needle-syringes interventions and addresses the relative impact of given treatment therapy for infected HIV newborns on reducing HIV and AIDS incidence is presented. We demonstrated how treatment therapy for new-born babies and the use of condoms or uncontaminated needle-syringes impact the dynamics of HIV in Malaysia. The model was calibrated to HIV and AIDS incidence data from Malaysia from 1986 to 2011. The epidemiological parameters are estimated using Bayesian inference via Markov chain Monte Carlo simulation method. The reproduction number optimal for control of the HIV/AIDS disease obtained suggests that the disease-free equilibrium was unstable during the 25 years. However, the results indicated that the use of condoms and uncontaminated needle-syringes are pivotal intervention control strategies; a comprehensive adoption of the intervention may help stop the spread of HIV disease. Treatment therapy for newborn babies is also of high value; it reduces the epidemic peak. The combined effect of condom use or uncontaminated needle-syringe is more pronounced in controlling the spread of HIV/AIDS.