A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.

Primary microcephaly (MCPH) is an autosomal recessive disorder characterized by head circumference of at least two standard deviations below the mean. Biallelic variants in the kinetochore gene KNL1 is a known cause of MCPH4. KNL1 is the central component of the KNL1-MIS12-NSL1 (KMN) network, which acts as the signaling hub of the kinetochore and is required for correct chromosomal segregation during mitosis. We identified biallelic KNL1 variants in two siblings from a non-consanguineous family with microcephaly and intellectual disability. The two siblings carry a frameshift variant predicted to prematurely truncate the transcript and undergo nonsense mediated decay, and an intronic single nucleotide variant (SNV) predicted to disrupt splicing. An in vitro splicing assay and qPCR from blood-derived RNA confirmed that the intronic variant skips exon 23, significantly reducing levels of the canonical transcript. Protein modeling confirmed that absence of exon 23, an inframe exon, would disrupt a key interaction within the KMN network and likely destabilize the kinetochore signaling hub, disrupting mitosis. Therefore, this splicing variant is pathogenic and, in trans with a frameshift variant, causes the MCPH phenotype associated with KLN1. This finding furthers the association of splicing variants as a common pathogenic variant class for KNL1.

Standardised reporting of burden of disease studies: the STROBOD statement.

BACKGROUND: The burden of disease (BOD) approach, originating with the Global Burden of Disease (GBD) study in the 1990s, has become a cornerstone for population health monitoring. Despite the widespread use of the Disability-Adjusted Life Year (DALY) metric, variations in methodological approaches and reporting inconsistencies hinder comparability across studies. To tackle this issue, we set out to develop guidelines for reporting DALY calculation studies to improve the transparency and comparability of BOD estimates. METHODS AND FINDINGS: The development of the STROBOD statement began within the European Burden of Disease Network, evolving from initial concepts discussed in workshops and training sessions focused on critical analysis of BOD studies. In 2021, a working group was formed to refine the preliminary version into the final Standardised Reporting of Burden of Disease studies (STROBOD) statement, consisting of 28 items structured across six main sections. These sections cover the title, abstract, introduction, methods, results, discussion, and open science, aiming to ensure transparency and standardization in reporting BOD studies. Notably, the methods section of the STROBOD checklist encompasses aspects such as study setting, data inputs and adjustments, DALY calculation methods, uncertainty analyses, and recommendations for reproducibility and transparency. A pilot phase was conducted to test the efficacy of the STROBOD statement, highlighting the importance of providing clear explanations and examples for each reporting item. CONCLUSIONS: The inaugural STROBOD statement offers a crucial framework for standardizing reporting in BOD research, with plans for ongoing evaluation and potential revisions based on user feedback. While the current version focuses on general BOD methodology, future iterations may include specialized checklists for distinct applications such as injury or risk factor estimation, reflecting the dynamic nature of this field.

Etiology-specific incidence and mortality of diarrheal diseases in the African region: a systematic review and meta-analysis.

BACKGROUND: Diarrheal diseases substantially affect public health impact in low- and middle-income countries (LMIC), particularly in Africa, where previous studies have indicated a lack of comprehensive data. With a growing number of primary studies on enteric infections in Africa, this study aimed to estimate the incidence and mortality of diarrheal pathogens across all ages in Africa in the year 2020. We also explored different methodological assumptions to allow comparison with other approaches. METHODS: Through a systematic review and meta-analysis of data from African LMICs, we estimated the etiology proportions for diarrheal diseases and deaths. We combined the etiology proportions with incidence data collected from a population survey in Africa from 2020 and mortality data from the Global Health Observatory of WHO. RESULTS: We estimated 1,008 billion diarrhea cases (95% UI 447 million-1,4 billion) and 515,031 diarrhea deaths (95% UI 248,983-1,007,641) in the African region in 2020. In children under five, enteroaggregative E. coli (EAEC) (44,073 cases per 100,000 people, 95% UI 18,818 - 60,922) and G. lamblia (36,116 cases per 100,000 people, 95% UI 15,245 - 49,961) were the leading causes of illness. Enteroinvasive E. coli (EIEC) (155 deaths per 100,000 people, 95% UI 106.5-252.9) and rotavirus (61.5 deaths per 100,000 people, 95% UI 42.3-100.3) were the primary causes of deaths. For children over five and adults, Salmonella spp. caused the largest number of diarrheal cases in the population of children ≥ 5 and adults (122,090 cases per 100,000 people, 95% UI 51,833 - 168,822), while rotavirus (16.4 deaths per 100,000 people, 95% UI 4.2-36.7) and enteroaggregative E. coli (EAEC) (14.6 deaths per 100,000 people, 95% UI 3.9-32.9) causing the most deaths. Geographically, the highest incidence of diarrhea was in Eastern Africa for children under five (114,389 cases per 100,000 people, 95% UI 34,771 - 172,884) and Central Africa for children over five and adults (117,820 cases per 100,000 people, 95% UI 75,111-157,584). Diarrheal mortality was highest in Western Africa for both children below five and above (children < 5: 194.5 deaths per 100,000 people, 95% UI 120-325.4; children ≥ 5 and above: 33.5 deaths per 100,000 people, 95% UI 12.9-75.1). CONCLUSION: These findings provide new information on the incidence and mortality of sixteen pathogens and highlight the need for surveillance and control of diarrheal infectious diseases in Africa. The cause-specific estimates are crucial for prioritizing diarrheal disease prevention in the region.

First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of Noncoding RNAs and Metabolic Pathways.

Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein-protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding RNAs (ncRNAs), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncRNAs. An integrative miRNA-mRNA analysis revealed crucial biological processes associated with metabolism, oxidation reactions of lipids and carbohydrates, and methylation-dependent chromatin silencing. In particular, four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) played a pivotal role in the network, potentially targeting multiple protein-coding transcripts, including CCND1 and CAMK2B. In summary, our transcriptome analysis highlighted disrupted embryonic development as well as metabolic pathways, particularly those involving lipids, emphasizing the emerging role of ncRNAs as epigenetic regulators in hepatoblastomas. These findings provide insights into the complexity of the hepatoblastoma transcriptome and identify potential targets for future therapeutic interventions.

DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development.

DNA methylation may be involved in the development of osteosarcomas. Osteosarcomas commonly arise during the bone growth and remodeling in puberty, making it plausible to infer the involvement of epigenetic alterations in their development. As a highly studied epigenetic mechanism, we investigated DNA methylation and related genetic variants in 28 primary osteosarcomas aiming to identify deregulated driver alterations. Methylation and genomic data were obtained using the Illumina HM450K beadchips and the TruSight One sequencing panel, respectively. Aberrant DNA methylation was spread throughout the osteosarcomas genomes. We identified 3146 differentially methylated CpGs comparing osteosarcomas and bone tissue samples, with high methylation heterogeneity, global hypomethylation and focal hypermethylation at CpG islands. Differentially methylated regions (DMR) were detected in 585 loci (319 hypomethylated and 266 hypermethylated), mapped to the promoter regions of 350 genes. These DMR genes were enriched for biological processes related to skeletal system morphogenesis, proliferation, inflammatory response, and signal transduction. Both methylation and expression data were validated in independent groups of cases. Six tumor suppressor genes harbored deletions or promoter hypermethylation (DLEC1, GJB2, HIC1, MIR149, PAX6, and WNT5A), and four oncogenes presented gains or hypomethylation (ASPSCR1, NOTCH4, PRDM16, and RUNX3). Our analysis also revealed hypomethylation at 6p22, a region that contains several histone genes. Copy-number changes in DNMT3B (gain) and TET1 (loss), as well as overexpression of DNMT3B in osteosarcomas provide a possible explanation for the observed phenotype of CpG island hypermethylation. While the detected open-sea hypomethylation likely contributes to the well-known osteosarcoma genomic instability, enriched CpG island hypermethylation suggests an underlying mechanism possibly driven by overexpression of DNMT3B likely resulting in silencing of tumor suppressors and DNA repair genes.

Animal sources of antimicrobial-resistant bacterial infections in humans: a systematic review.

Bacterial antimicrobial resistance (AMR) is among the leading global health challenges of the century. Animals and their products are known contributors to the human AMR burden, but the extent of this contribution is not clear. This systematic literature review aimed to identify studies investigating the direct impact of animal sources, defined as livestock, aquaculture, pets, and animal-based food, on human AMR. We searched four scientific databases and identified 31 relevant publications, including 12 risk assessments, 16 source attribution studies, and three other studies. Most studies were published between 2012 and 2022, and most came from Europe and North America, but we also identified five articles from South and South-East Asia. The studies differed in their methodologies, conceptual approaches (bottom-up, top-down, and complex), definitions of the AMR hazard and outcome, the number and type of sources they addressed, and the outcome measures they reported. The most frequently addressed animal source was chicken, followed by cattle and pigs. Most studies investigated bacteria-resistance combinations. Overall, studies on the direct contribution of animal sources of AMR are rare but increasing. More recent publications tailor their methodologies increasingly towards the AMR hazard as a whole, providing grounds for future research to build on.

Burden of lung cancer and predicted costs of occupational exposure to hexavalent chromium in the EU - The impact of different occupational exposure limits.

BACKGROUND: Exposure to hexavalent chromium [Cr(VI)] occurs widely in occupational settings across the EU and is associated with lung cancer. In 2025, the occupational exposure limit is set to change to 5 µg/m3. Current exposure limits are higher, with 10 µg/m3 as a general limit and 25 µg/m3 for the welding industry. We aimed to assess the current burden of lung cancer caused by occupational exposure to Cr(VI) and to evaluate the impact of the recently established EU regulation by analysing different occupational exposure limits. METHODS: Data were extracted from the literature, the Global Burden of Disease 2019) study, and Eurostat. We estimated the cases of cancer attributable to workplace exposure to Cr(VI) by combining exposure-effect relationships with exposure data, and calculated related DALYs and health costs in scenarios with different occupational exposure limits. RESULTS: With current EU regulations, 253 cases (95%UI 250.96-255.71) of lung cancer were estimated to be caused by Cr(VI) in 2019, resulting in 4684 DALYs (95%UI 4683.57-4704.08). In case the welding industry adopted 10 µg/m3, a decrease of 43 cases and 797 DALYs from current values is expected. The predicted application of a 5 µg/m3 limit would cause a decrease of 148 cases and 2746 DALYs. Current costs are estimated to amount to 12.47 million euros/year (95%UI 10.19-453.82), corresponding to 39.97 million euros (95%UI 22.75-70.10) when considering costs per DALY. The limits implemented in 2025 would lead to a decrease of 23.35 million euros when considering DALYs, with benefits of introducing a limit value occurring after many decades. Adopting a 1 µg/m3 limit would lower costs to 1.04 million euros (95%UI 0.85-37.67) and to 3.33 million euros for DALYs (95%UI 1.89-5.84). DISCUSSION: Assessing different scenarios with different Cr(VI) occupational exposure limits allowed to understand the impact of EU regulatory actions. These findings make a strong case for adapting even stricter exposure limits to protect workers' health and avoid associated costs.

The increasing significance of disease severity in a burden of disease framework.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) - put simply, ill-health - is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.

The direct disease burden of COVID-19 in Belgium in 2020 and 2021.

BACKGROUND: Burden of disease estimates have become important population health metrics over the past decade to measure losses in health. In Belgium, the disease burden caused by COVID-19 has not yet been estimated, although COVID-19 has emerged as one of the most important diseases. Therefore, the current study aims to estimate the direct COVID-19 burden in Belgium, observed despite policy interventions, during 2020 and 2021, and compare it to the burden from other causes. METHODS: Disability-adjusted life years (DALYs) are the sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to disease. DALYs allow comparing the burden of disease between countries, diseases, and over time. We used the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs related to COVID-19. Estimates of person-years for (a) acute non-fatal disease states were calculated from a compartmental model, using Belgian seroprevalence, social contact, hospital, and intensive care admission data, (b) deaths were sourced from the national COVID-19 mortality surveillance, and (c) chronic post-acute disease states were derived from a Belgian cohort study. RESULTS: In 2020, the total number of COVID-19 related DALYs was estimated at 253,577 [252,541 - 254,739], which is higher than in 2021, when it was 139,281 [136,704 - 142,306]. The observed COVID-19 burden was largely borne by the elderly, and over 90% of the burden was attributable to premature mortality (i.e., YLLs). In younger people, morbidity (i.e., YLD) contributed relatively more to the DALYs, especially in 2021, when vaccination was rolled out. Morbidity was mainly attributable to long-lasting post-acute symptoms. CONCLUSION: COVID-19 had a substantial impact on population health in Belgium, especially in 2020, when COVID-19 would have been the main cause of disease burden if all other causes had maintained their 2019 level.

Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development.

Osteosarcoma (OS) is the most prevalent type of bone tumor, but slow progress has been achieved in disentangling the full set of genomic events involved in its initiation and progression. We assessed by NGS the mutational spectrum of 28 primary OSs from Brazilian patients, and identified 445 potentially deleterious SNVs/indels and 1176 copy number alterations (CNAs). TP53 was the most recurrently mutated gene, with an overall rate of ~60%, considering SNVs/indels and CNAs. The most frequent CNAs (~60%) were gains at 1q21.2q21.3, 6p21.1, and 8q13.3q24.22, and losses at 10q26 and 13q14.3q21.1. Seven cases presented CNA patterns reminiscent of complex events (chromothripsis and chromoanasynthesis). Putative RB1 and TP53 germline variants were found in five samples associated with metastasis at diagnosis along with complex genomic patterns of CNAs. PTPRQ, KNL1, ZFHX4, and DMD alterations were prevalent in metastatic or deceased patients, being potentially indicative of poor prognosis. TNFRSF11B, involved in skeletal system development and maintenance, emerged as a candidate for osteosarcomagenesis due to its biological function and a high frequency of copy number gains. A protein-protein network enrichment highlighted biological pathways involved in immunity and bone development. Our findings reinforced the high genomic OS instability and heterogeneity, and led to the identification of novel disrupted genes deserving further evaluation as biomarkers due to their association with poor outcomes.

Human health risk-benefit assessment of fish and other seafood: a scoping review.

Fish and other seafood are important sources of nutrients, but they are also sources of chemical contaminants that may cause adverse health effects. This article aimed to identify existing risk-benefit assessments (RBA) of fish, shellfish, and other seafood, compare methodologies, discuss differences and commonalities in findings, and identify limitations and ways forward for future studies. We conducted a scoping review of the scientific literature of studies in all languages published from 2000 through April 2019. We identified 106 RBA of fish and other seafood across Europe, Asia, North America, Africa, and at the global level. Studies were heterogeneous in terms of types of fish and other seafood considered, beneficial and adverse compounds assessed, and overall methodology. Collected data showed that a diet consisting of a variety of lean and fatty fish and other seafood is recommended for the overall population and that women of childbearing age and children should limit the consumption of fish and other seafood types that have a high likelihood of contamination. Our review emphasizes the need for evidence-based, up-to-date, and harmonized approaches in RBA in general.

Practicalities of implementing burden of disease research in Africa: lessons from a population survey component of our multi-partner FOCAL research project.

BACKGROUND: Collaborative research is being increasingly implemented in Africa to study health-related issues, for example, the lack of evidence on disease burden, in particular for the presumptive high load of foodborne diseases. The FOCAL (Foodborne disease epidemiology, surveillance, and control in African LMIC) Project is a multi-partner study that includes a population survey to estimate the foodborne disease burden in four African low- and middle-income countries (LMICs). Our multi-partner study team had members from seven countries, all of whom contributed to the project from the grant application stage, and who play(ed) specific roles in designing and implementing the population survey. MAIN TEXT: In this paper, we applied Larkan et al.'s framework for successful research partnerships in global health to self-evaluate our project's collaboration, management, and implementation process. Our partnership formation considered the interplay and balance between operations and relations. Using Larkan et al.'s seven core concepts (i.e., focus, values, equity, benefit, communication, leadership, and resolution), we reviewed the process stated above in an African context. CONCLUSION: Through our current partnership and research implementing a population survey to study disease burden in four African LMICs, we observed that successful partnerships need to consider these core concepts explicitly, apply the essential leadership attributes, perform assessment of external contexts before designing the research, and expect differences in work culture. While some of these experiences are common to research projects in general, the other best practices and challenges we discussed can help inform future foodborne disease burden work in Africa.

Disability adjusted life years associated with COVID-19 in Denmark in the first year of the pandemic.

BACKGROUND: Burden of disease studies measure the public health impact of a disease in a society. The aim of this study was to quantify the direct burden of COVID-19 in the first 12 months of the epidemic in Denmark. METHODS: We collected national surveillance data on positive individuals for SARS-CoV-2 with RT-PCR, hospitalization data, and COVID-19 mortality reported in the period between 26th of February, 2020 to 25th of February, 2021. We calculated disability adjusted life years (DALYs) based on the European Burden of Disease Network consensus COVID-19 model, which considers mild, severe, critical health states, and premature death. We conducted sensitivity analyses for two different death-registration scenarios, within 30 and 60 days after first positive test, respectively. RESULTS: We estimated that of the 211,823 individuals who tested positive to SARS-CoV-2 by RT-PCR in the one-year period, 124,163 (59%; 95% uncertainty interval (UI) 112,782-133,857) had at least mild symptoms of disease. The total estimated disease burden was 30,180 DALYs (95% UI 30,126; 30,242), corresponding to 520 DALYs/100,000. The disease burden was higher in the age groups above 70 years of age, particularly in men. Years of life lost (YLL) contributed with more than 99% of total DALYs. The results of the scenario analysis showed that defining COVID-19-related fatalities as deaths registered up to 30 days after the first positive test led to a lower YLL estimate than when using a 60-days window. CONCLUSION: COVID-19 led to a substantial public health impact in Denmark in the first full year of the epidemic. Our estimates suggest that it was the the sixth most frequent cause of YLL in Denmark in 2020. This impact will be higher when including the post-acute consequences of COVID-19 and indirect health outcomes.

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review.

BACKGROUND: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. METHODS: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. RESULTS: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. CONCLUSIONS: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.

Burden of non-communicable disease studies in Europe: a systematic review of data sources and methodological choices.

BACKGROUND: Assessment of disability-adjusted life years (DALYs) resulting from non-communicable diseases (NCDs) requires specific calculation methods and input data. The aims of this study were to (i) identify existing NCD burden of disease (BoD) activities in Europe; (ii) collate information on data sources for mortality and morbidity; and (iii) provide an overview of NCD-specific methods for calculating NCD DALYs. METHODS: NCD BoD studies were systematically searched in international electronic literature databases and in grey literature. We included all BoD studies that used the DALY metric to quantify the health impact of one or more NCDs in countries belonging to the European Region. RESULTS: A total of 163 BoD studies were retained: 96 (59%) were single-country or sub-national studies and 67 (41%) considered more than one country. Of the single-country studies, 29 (30%) consisted of secondary analyses using existing Global Burden of Disease (GBD) results. Mortality data were mainly derived (49%) from vital statistics. Morbidity data were frequently (40%) drawn from routine administrative and survey datasets, including disease registries and hospital discharge databases. The majority (60%) of national BoD studies reported mortality corrections. Multimorbidity adjustments were performed in 18% of national BoD studies. CONCLUSION: The number of national NCD BoD assessments across Europe increased over time, driven by an increase in BoD studies that consisted of secondary data analysis of GBD study findings. Ambiguity in reporting the use of NCD-specific BoD methods underlines the need for reporting guidelines of BoD studies to enhance the transparency of NCD BoD estimates across Europe.

Health and Economic Burden of Seven Foodborne Diseases in Denmark, 2019.

We ranked seven foodborne pathogens in Denmark on the basis of their health and economic impact on society in 2019. We estimated burden of disease of infections with Campylobacter spp., Salmonella spp., Shiga toxin-producing Escherichia coli (STEC), Yersinia enterocolitica, Listeria monocytogenes, norovirus, and hepatitis A virus in terms of incidence, mortality, disability-adjusted life years (DALY), and economic burden in terms of direct and indirect health costs. These seven pathogens accounted for 268,372 cases, 98 deaths, and 3121 DALYs, and led to a total expenditure of 434 million Euro in 1 year in a country with 5.8 million citizens. Foodborne infections by Campylobacter, Salmonella, and norovirus caused the most DALYs, whereas Campylobacter, and norovirus and STEC had the higher costs. A combination of disease burden and cost of illness estimates is useful to inform policymaking and establish food safety priorities at the national level.

Integration of various dimensions in food-based dietary guidelines via mathematical approaches: report of a DGE/FENS Workshop in Bonn, Germany, 23-24 September 2019.

In the past, food-based dietary guidelines (FBDGs) were derived nearly exclusively by using systematic reviews on diet-health relationships and translating dietary reference values for nutrient intake into foods. This approach neglects many other implications that dietary recommendations have on society, the economy and environment. In view of pressing challenges, such as climate change and the rising burden of diet-related diseases, the simultaneous integration of evidence-based findings from different dimensions into FBDGs is required. Consequently, mathematical methods and data processing are evolving as powerful tools in nutritional sciences. The possibilities and reasons for the derivation of FBDGs via mathematical approaches were the subject of a joint workshop hosted by the German Nutrition Society (DGE) and the Federation of European Nutrition Societies (FENS) in September 2019 in Bonn, Germany. European scientists were invited to discuss and exchange on the topics of mathematical optimisation for the development of FBDGs and different approaches to integrate various dimensions into FBDGs. We concluded that mathematical optimisation is a suitable tool to formulate FBDGs finding trade-offs between conflicting goals and taking several dimensions into account. We identified a lack of evidence for the extent to which constraints and weights for different dimensions are set and the challenge to compile diverse data that suit the demands of optimisation models. We also found that individualisation via mathematical optimisation is one perspective of FBDGs to increase consumer acceptance, but the application of mathematical optimisation for population-based and individual FBDGs requires more experience and evaluation for further improvements.

Burden of Disease Estimates of Seven Pathogens Commonly Transmitted Through Foods in Denmark, 2017.

Burden of disease metrics are increasingly established to prioritize food safety interventions. We estimated the burden of disease caused by seven foodborne pathogens in Denmark in 2017: Campylobacter, Salmonella, Shiga toxin-producing Escherichia coli, norovirus, Yersinia enterocolitica, Listeria monocytogenes, and Toxoplasma gondii. We used public health surveillance data and scientific literature to estimate incidence, mortality, and total disability-adjusted life year (DALY) of each, and linked results with estimates of the proportion of disease burden that is attributable to foods. Our estimates showed that Campylobacter caused the highest burden of disease, leading to a total burden of 1709 DALYs (95% uncertainty interval [UI] 1665-1755), more than threefold higher than the second highest ranked pathogen (Salmonella: 492 DALYs; 95% UI 481-504). Campylobacter still led the ranking when excluding DALYs attributable to nonfoodborne routes of exposure. The total estimated incidence was highest for norovirus, but this agent ranked sixth when focusing on foodborne burden. Salmonella ranked second in terms of foodborne burden of disease, followed by Listeria and Yersinia. Foodborne congenital toxoplasmosis was estimated to cause the loss of ∼100 years of healthy life, a burden that was borne by a low number of cases in the population. The ranking of foodborne pathogens varied substantially when based on reported cases, estimated incidence, and burden of disease estimates. Our results reinforce the need to continue food safety efforts throughout the food chain in Denmark, with a particular focus on reducing the incidence of Campylobacter infections.

Global and regional source attribution of Shiga toxin-producing Escherichia coli infections using analysis of outbreak surveillance data.

Shiga toxin-producing Escherichia coli (STEC) infections pose a substantial health and economic burden worldwide. To target interventions to prevent foodborne infections, it is important to determine the types of foods leading to illness. Our objective was to determine the food sources of STEC globally and for the six World Health Organization regions. We used data from STEC outbreaks that have occurred globally to estimate source attribution fractions. We categorised foods according to their ingredients and applied a probabilistic model that used information on implicated foods for source attribution. Data were received from 27 countries covering the period between 1998 and 2017 and three regions: the Americas (AMR), Europe (EUR) and Western-Pacific (WPR). Results showed that the top foods varied across regions. The most important sources in AMR were beef (40%; 95% Uncertainty Interval 39-41%) and produce (35%; 95% UI 34-36%). In EUR, the ranking was similar though with less marked differences between sources (beef 31%; 95% UI 28-34% and produce 30%; 95% UI 27-33%). In contrast, the most common source of STEC in WPR was produce (43%; 95% UI 36-46%), followed by dairy (27%; 95% UI 27-27%). Possible explanations for regional variability include differences in food consumption and preparation, frequency of STEC contamination, the potential of regionally predominant STEC strains to cause severe illness and differences in outbreak investigation and reporting. Despite data gaps, these results provide important information to inform the development of strategies for lowering the global burden of STEC infections.