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head of the department: Prof. Krause

Recent Submissions

  • Patient satisfaction & use of health care: a cross-sectional study of asylum seekers in the Freiburg initial reception centre.

    Bockey, Annabelle J; Janda, Aleš; Braun, Cornelia; Müller, Anne-Maria; Stete, Katarina; Kern, Winfried V; Rieg, Siegbert R; Lange, Berit; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (BMC, 2020-08-03)
    Background: In response to a high number of incoming asylum seekers and refugees (AS&R) in Germany, initial reception centres were established to provide immediate shelter, food and health support. This study evaluates the satisfaction with and use of the health care available at the Freiburg initial reception centre (FIRC) where an integrated health care facility (ICF) was set up in 2015. Methods: We assessed use and satisfaction with health services available to resident AS&R within and outside the FIRC in a cross-sectional design. Data were collected in 2017 using a questionnaire with both open and closed ended items. Results: The majority of 102 included participants were young (mean age 24.2; 95%CI 22.9-25.5, range 18-43) males (93%), from Sub-Saharan Africa (92%). High use frequencies were reported from returning patients of the ICF; with 56% fortnightly use and 19% daily use reported. The summary of satisfaction scores indicated that 84% (CI95 76-89%) of respondents were satisfied with the ICF. Multivariate analysis showed female gender and non-English speaking as risk factors for low satisfaction. Outside the FIRC, the satisfaction scores indicated that 60% of participants (95%CI 50-69%) were satisfied with the health care received. Conclusion: Our study shows that AS&R residing in the FIRC are generally satisfied with the services at the ICF, though strategies to enhance care for females and non-English speakers should be implemented. Satisfaction with health care outside of the FIRC was not as high, indicating the need to improve quality of care and linkage to regular health care services.
  • The Surveillance Outbreak Response Management and Analysis System (SORMAS): Digital Health Global Goods Maturity Assessment.

    Tom-Aba, Daniel; Silenou, Bernard Chawo; Doerrbecker, Juliane; Fourie, Carl; Leitner, Carl; Wahnschaffe, Martin; Strysewske, Maté; Arinze, Chinedu Chukwujekwu; Krause, Gerard; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (JMIR publications, 2020-04-29)
    Background: Digital health is a dynamic field that has been generating a large number of tools; many of these tools do not have the level of maturity required to function in a sustainable model. It is in this context that the concept of global goods maturity is gaining importance. Digital Square developed a global good maturity model (GGMM) for digital health tools, which engages the digital health community to identify areas of investment for global goods. The Surveillance Outbreak Response Management and Analysis System (SORMAS) is an open-source mobile and web application software that we developed to enable health workers to notify health departments about new cases of epidemic-prone diseases, detect outbreaks, and simultaneously manage outbreak response. Objective: The objective of this study was to evaluate the maturity of SORMAS using Digital Square's GGMM and to describe the applicability of the GGMM on the use case of SORMAS and identify opportunities for system improvements. Methods: We evaluated SORMAS using the GGMM version 1.0 indicators to measure its development. SORMAS was scored based on all the GGMM indicator scores. We described how we used the GGMM to guide the development of SORMAS during the study period. GGMM contains 15 subindicators grouped into the following core indicators: (1) global utility, (2) community support, and (3) software maturity. Results: The assessment of SORMAS through the GGMM from November 2017 to October 2019 resulted in full completion of all subscores (10/30, (33%) in 2017; 21/30, (70%) in 2018; and 30/30, (100%) in 2019). SORMAS reached the full score of the GGMM for digital health software tools by accomplishing all 10 points for each of the 3 indicators on global utility, community support, and software maturity. Conclusions: To our knowledge, SORMAS is the first electronic health tool for disease surveillance, and also the first outbreak response management tool, that has achieved a 100% score. Although some conceptual changes would allow for further improvements to the system, the GGMM already has a robust supportive effect on developing software toward global goods maturity.
  • 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.
  • Anosmia in COVID-19 patients.

    Hornuss, D; Lange, B; Schröter, N; Rieg, S; Kern, W V; Wagner, D; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2020-05-22)
    No abstract available.
  • CSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD.

    Blennow, Kaj; Diaz-Lucena, Daniela; Zetterberg, Henrik; Villar-Pique, Anna; Karch, Andre; Vidal, Enric; Hermann, Peter; Schmitz, Matthias; Ferrer Abizanda, Isidro; Zerr, Inga; et al. (BMJ Publishing Group, 2019-05-16)
    Objective: To investigate whether cerebrospinal fluid (CSF) neurogranin concentrations are altered in sporadic Creutzfeldt-Jakob disease (CJD), comparatively with Alzheimer's disease (AD), and associated with neuronal degeneration in brain tissue. Methods: CSF neurogranin, total tau, neurofilament light (NFL) and 14-3-3 protein were measured in neurological controls (NCs, n=64), AD (n=46) and CJD (n=81). The accuracy of neurogranin discriminating the three diagnostic groups was evaluated. Correlations between neurogranin and neurodegeneration biomarkers, demographic, genetic and clinical data were assessed. Additionally, neurogranin expression in postmortem brain tissue was studied. Results: Compared with NC, CSF neurogranin concentrations were increased in CJD (4.75 times of NC; p<0.001, area under curve (AUC), 0.96 (95% CI 0.93 to 0.99) and AD (1.94 times of NC; p<0.01, AUC 0.73, 95% CI 0.62 to 0.82), and were able to differentiate CJD from AD (p<0.001, AUC 0.85, 95% CI 0.78 to 0.92). CSF tau was increased in CJD (41 times of NC) and in AD (3.1 times of NC), both at p<0.001. In CJD, neurogranin positively correlated with tau (r=0.55, p<0.001) and was higher in 14-3-3-positivity (p<0.05), but showed no association with NFL (r=0.08, p=0.46). CJD-MM1/MV1 cases displayed higher neurogranin levels than VV2 cases. Neurogranin was increased at early CJD disease stages and was a good prognostic marker of survival time in CJD. In brain tissue, neurogranin was detected in the cytoplasm, membrane and postsynaptic density fractions of neurons, with reduced levels in AD, and more significantly in CJD, where they correlated with synaptic and axonal markers. Conclusions: Neurogranin is a new biomarker of prion pathogenesis with diagnostic and prognostic abilities, which reflects the degree of neuronal damage in brain tissue in a CJD subtype manner. Keywords: alzheimer’s disease; cerebrospinal fluid; creutzfeldt-jakob disease; neurodegenerative dementias; neurofilament light; neurogranin; tau.
  • User Evaluation Indicates High Quality of the Surveillance Outbreak Response Management and Analysis System (SORMAS) After Field Deployment in Nigeria in 2015 and 2018.

    Tom-Aba, Daniel; Toikkanen, Salla E; Glöckner, Stephan; Adeoye, Olawunmi; Mall, Sabine; Fähnrich, Cindy; Denecke, Kerstin; Benzler, Justus; Kirchner, Göran; Schwarz, Norbert; et al.
    During the West African Ebola virus disease outbreak in 2014-15, health agencies had severe challenges with case notification and contact tracing. To overcome these, we developed the Surveillance, Outbreak Response Management and Analysis System (SORMAS). The objective of this study was to measure perceived quality of SORMAS and its change over time. We ran a 4-week-pilot and 8-week-implementation of SORMAS among hospital informants in Kano state, Nigeria in 2015 and 2018 respectively. We carried out surveys after the pilot and implementation asking about usefulness and acceptability. We calculated the proportions of users per answer together with their 95% confidence intervals (CI) and compared whether the 2015 response distributions differed from those from 2018. Total of 31 and 74 hospital informants participated in the survey in 2015 and 2018, respectively. In 2018, 94% (CI: 89-100%) of users indicated that the tool was useful, 92% (CI: 86-98%) would recommend SORMAS to colleagues and 18% (CI: 10-28%) had login difficulties. In 2015, the proportions were 74% (CI: 59-90%), 90% (CI: 80-100%), and 87% (CI: 75-99%) respectively. Results indicate high usefulness and acceptability of SORMAS. We recommend mHealth tools to be evaluated to allow repeated measurements and comparisons between different versions and users.
  • Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017.

    Troeger, Christopher E; GBD 2017 Influenza Collaborators; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2018-12-12)
    Background: Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza. Methods: We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza. Findings: Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000-200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16·4 deaths per 100 000 [95% UI 11·6-21·9]), and the highest rate among all ages was in eastern Europe (5·2 per 100 000 population [95% UI 3·5-7·2]). We estimated that influenza LRTIs accounted for 9 459 000 (95% UI 3 709 000-22 935 000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000-259 851 000). We estimated that 11·5% (95% UI 10·0-12·9) of LRTI episodes were attributable to influenza, corresponding to 54 481 000 (38 465 000-73 864 000) episodes and 8 172 000 severe episodes (5 000 000-13 296 000). Interpretation: This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed.
  • Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

    Roth, G.A.; GBD 2017 Causes of Death Collaborators; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2018-11-08)
    Background: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings: At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5-74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9-19·6), and injuries 8·0% (7·7-8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5-23·9), representing an additional 7·61 million (7·20-8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0-8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0-24·0) and the death rate by 31·8% (30·1-33·3). Total deaths from injuries increased by 2·3% (0·5-4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2-15·1) to 57·9 deaths (55·9-59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8-148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2-40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2-36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990-neonatal disorders, lower respiratory infections, and diarrhoeal diseases-were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation: Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade.
  • Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017.

    Dicker, Daniel; GBD 2017 Mortality Collaborators; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2018-11-08)
    Background: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing.
  • Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

    Kyu, Hmwe Hmwe; GBD 2017 DALYs and HALE Collaborators; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2019-06-22)
    Background: How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods: We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings: Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2). Interpretation: With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low SDI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health.
  • Population and fertility by age and sex for 195 countries and territories, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017.

    Murray, Christopher J.L.; GBD 2017 Population and Fertility Collaborators; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2018-11-08)
    Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10-54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10-14 years and 50-54 years was estimated from data on fertility in women aged 15-19 years and 45-49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4-52·0). The TFR decreased from 4·7 livebirths (4·5-4·9) to 2·4 livebirths (2·2-2·5), and the ASFR of mothers aged 10-19 years decreased from 37 livebirths (34-40) to 22 livebirths (19-24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3-200·8) since 1950, from 2·6 billion (2·5-2·6) to 7·6 billion (7·4-7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15-64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9-1·2) in Cyprus to a high of 7·1 livebirths (6·8-7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07-0·09) in South Korea to 2·4 livebirths (2·2-2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3-0·4) in Puerto Rico to a high of 3·1 livebirths (3·0-3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress.
  • A Single-Center Prospective Cohort Study on Postsplenectomy Sepsis and its Prevention.

    Rieg, Siegbert; Bechet, Lena; Naujoks, Kai; Hromek, Julia; Lange, Berit; Juzek-Küpper, Marc-Fabian; Stete, Katarina; Müller, Matthias C; Jost, Insa; Kern, Winfried V; et al. (Oxford University Press, 2020-02-13)
    A total of 459 asplenic patients were enrolled, and 426 patients were followed prospectively over a median period of 2.9 years. Pneumococcal vaccine uptake within 3 months of splenectomy or first diagnosis of asplenia was 27% vs 71% among delayed study entry and early study entry patients, respectively (P < .001). Forty-four episodes of severe sepsis or septic shock occurred in study patients: 22 after study entry and 22 before study entry. Streptococcus pneumoniae was more frequent among sepsis episodes that occurred before study entry (8/22) than after study entry (1/22 episodes). For episodes occurring after study entry, only a higher Charlson comorbidity index score was significantly associated with severe sepsis/septic shock postsplenectomy.
  • Seropositivity for pathogens associated with chronic infections is a risk factor for all-cause mortality in the elderly: findings from the Memory and Morbidity in Augsburg Elderly (MEMO) Study.

    Zeeb, Marius; Kerrinnes, Tobias; Cicin-Sain, Luka; Guzman, Carlos A; Puppe, Wolfram; Schulz, Thomas F; Peters, Annette; Berger, Klaus; Castell, Stefanie; Karch, André; et al. (Springer, 2020-07-09)
    Immunostimulation by chronic infection has been linked to an increased risk for different non-communicable diseases, which in turn are leading causes of death in high- and middle-income countries. Thus, we investigated if a positive serostatus for pathogens responsible for common chronic infections is individually or synergistically related to reduced overall survival in community dwelling elderly. We used data of 365 individuals from the German MEMO (Memory and Morbidity in Augsburg Elderly) cohort study with a median age of 73 years at baseline and a median follow-up of 14 years. We examined the effect of a positive serostatus at baseline for selected pathogens associated with chronic infections (Helicobacter pylori, Borrelia burgdorferi sensu lato, Toxoplasma gondii, cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1/2, and human herpesvirus 6) on all-cause mortality with multivariable parametric survival models. We found a reduced survival time in individuals with a positive serostatus for Helicobacter pylori (accelerated failure time (AFT) - 15.92, 95% CI - 29.96; - 1.88), cytomegalovirus (AFT - 22.81, 95% CI - 36.41; - 9.22) and Borrelia burgdorferi sensu lato (AFT - 25.25, 95% CI - 43.40; - 7.10), after adjusting for potential confounders. The number of infectious agents an individual was seropositive for had a linear effect on all-cause mortality (AFT per additional infection - 12.42 95% CI - 18.55; - 6.30). Our results suggest an effect of seropositivity for Helicobacter pylori, cytomegalovirus, and Borrelia burgdorferi sensu lato on all-cause mortality in older community dwelling individuals. Further research with larger cohorts and additional biomarkers is required, to assess mediators and molecular pathways of this effect.
  • Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention.

    Lemon, Stanley M; Ott, Jördis J; Van Damme, Pierre; Shouval, Daniel; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2017-09-05)
    Although epidemic jaundice was well known to physicians of antiquity, it is only in recent years that medical science has begun to unravel the origins of hepatitis A virus (HAV) and the unique pathobiology underlying acute hepatitis A in humans. Improvements in sanitation and the successful development of highly efficacious vaccines have markedly reduced the worldwide prevalence and incidence of this enterically-transmitted infection over the past quarter century, yet the virus persists in vulnerable populations and remains a common cause of food-borne disease outbreaks in economically-advantaged societies. Reductions in the prevalence of HAV have led to increases in the median age at which infection occurs, often resulting in more severe disease in affected persons and paradoxical increases in disease burden in some developing nations. Here, we summarize recent advances in the molecular virology of HAV, an atypical member of the Picornaviridae family, survey what is known of the pathogenesis of hepatitis A in humans and the host-pathogen interactions that typify the infection, and review medical and public health aspects of immunisation and disease prevention.
  • [Frequencies of musculoskeletal symptoms and disorders in the population-based German National Cohort (GNC)].

    Schmidt, Carsten Oliver; Günther, Klaus-Peter; Goronzy, Jens; Albrecht, Katinka; Chenot, Jean-François; Callhoff, Johanna; Richter, Adrian; Kasch, Richard; Ahrens, Wolfgang; Becher, Heiko; et al. (Springer, 2020-03-18)
    Background: Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy. Objectives: Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain, osteoporosis, osteoarthritis, and arthritis. Materials and methods: Data were collected from March 2014 to March 2017 in adults aged 20-75 years during the first half of the baseline survey of the GNC. The sample comprised 101,779 interviewed subjects, including 9370 subjects who underwent clinical musculoskeletal examinations. The interview included questions about specific musculoskeletal disorders. A clinical examination of the hand provided information about palpable swollen joints and pressure-sensitive joints. Resting pain of the knees and hips was also assessed by a clinical examination. Frequencies were standardized to the German standard population of the year 2011. Results: Having ever been diagnosed with recurrent back pain (22.5%) or osteoarthritis (20.6%) were the most common complaints reported in the interview; osteoporosis (2.9%) and rheumatoid arthritis (1.9%) were stated more seldom. According to the hand examination, 6.0% of all participants experienced pain in at least one finger joint. Resting pain was present in at least one knee among 8.2% and in at least one hip among 5.1% of the participants as assessed during the clinical examination. Women were more likely to report musculoskeletal disorders and symptoms than men. The proportion of adults affected by musculoskeletal diseases increased strongly with age. Conclusion: Musculoskeletal disorders and symptoms occur frequently. The burden of complaints and diagnoses is comparable to previous population-based surveys.
  • [Self-reported cancer in the German National Cohort (NAKO Gesundheitsstudie): assessment methods and first results] / Selbstberichtete Krebserkrankungen in der NAKO Gesundheitsstudie: Erfassungsmethoden und erste Ergebnisse.

    Nimptsch, Katharina; Jaeschke, Lina; Chang-Claude, Jenny; Kaaks, Rudolf; Katzke, Verena; Michels, Karin B; Franzke, Claus-Werner; Obi, Nadia; Becher, Heiko; Kuß, Oliver; et al. (Springer, 2020-03-16)
    Background: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. Objectives: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. Materials and methods: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. Results: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5‑year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. Conclusions: The NAKO is a rich data basis for future investigations of incident cancer.
  • [Self-reported infections in the German National Cohort (GNC) in the context of the current research landscape].

    Hassenstein, Max J; Aarabi, Ghazal; Ahnert, Peter; Becher, Heiko; Franzke, Claus-Werner; Fricke, Julia; Krause, Gérard; Glöckner, Stephan; Gottschick, Cornelia; Karch, André; et al.
    Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. Objectives The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. Methods As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. Results In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. Outlook The cross-sectional analyses of data and tools presented here – for example on determinants of susceptibility to self-reported infections – can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.
  • [Blood pressure measurement in the NAKO German National Cohort (GNC) - differences in methods, distribution of blood pressure values, and awareness of hypertension compared to other population-based studies in Germany].

    Schikowski, Tamara; Wigmann, Claudia; Fuks, Kateryna B; Schipf, Sabine; Heier, Margit; Neuhauser, Hannelore; Sarganas, Giselle; Ahrens, Wolfgang; Becher, Heiko; Berger, Klaus; et al. (Springer, 2020-03-13)
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  • [Design and quality control of the oral health status examination in the German National Cohort (GNC)].

    Holtfreter, Birte; Samietz, Stefanie; Hertrampf, Katrin; Aarabi, Ghazal; Hagenfeld, Daniel; Kim, Ti-Sun; Kocher, Thomas; Koos, Bernd; Schmitter, Marc; Ahrens, Wolfgang; et al. (Dpringer, 2020-03-12)
    BACKGROUND: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated. OBJECTIVES: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality. MATERIALS AND METHODS: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed. RESULTS: Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners. CONCLUSIONS: The results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC's overall assessment program. However, rigorous dental support of the study centres is required for quality management.

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