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Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study.
In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127-0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 .</p
Unraveling social health inequalities during COVID-19 in Belgium: the vital role of data linkages
Background
During the COVID-19 crisis, data linkages were set up to efficiently monitor the outbreak and identify vulnerable population groups. Yet, considerable technical, administrative and data security issues have hindered the effectiveness of data linkages as a critical instrument during public health emergencies. This workshop aims to provide a practical demonstration of the challenges encountered in a Belgian data linkage during the COVID-19 crisis, along with the strategies implemented to overcome these challenges. This case study offers insights into the development of a highly sensitive linkage between COVID-19 hospital data and information related to social and health use in Belgium.
Methods
The HELICON data linkage is developed at the individual level to investigate the risk of COVID-19 hospitalization and the influence of various social and biomedical factors during and after the crisis. Data are drawn from data collections on hospitalization from the COVID-19 health surveillance (Sciensano), on the socioeconomic and sociodemographic context (Statistics Belgium), and on healthcare use and reimbursement (InterMutualistic Agency).
Results
A representative case-cohort study is established comprising 1,149,264 million randomly selected Belgians and 44,508 hospitalized patients. Annual follow-up is scheduled over a four-year span, allowing the investigation of pre- and post-pandemic health data from July 2020 to January 2026.
Conclusions
The HELICON data linkage took 3.5 years to complete. Among the many challenges, we were faced with complicated approval procedures, ambiguous data security guidelines, unclear cost estimates, and technical issues related to the analysis environment. Building on these experiences, we explore the strengths and weaknesses of data linkages as a research instrument during the COVID-19 pandemic and discuss which lessons should be drawn to for the post-pandemic era.</p
Surveillance de la mortalité toutes causes confondues en Belgique, Flandre, Wallonie et Bruxelles durant les hivers 2022-2023 et 2023-2024. Be-MOMO : the Belgian Mortality Monitoring
La période hivernale 2022-2023 a été marquée par une sous-mortalité au niveau de la Belgique, relativement faible (-0,3 % avec 203 décès de moins que prévu) et qui a été observée principalement chez les personnes entre 65 et 84 ans. Cette sous-mortalité a touché davantage les hommes, tandis qu’une surmortalité a été observée chez les femmes, affectant tous les groupes d’âge. Il y a des différences au niveau régional, avec une faible sous-mortalité en Wallonie (-0,3 % avec 80 décès en mois que prévu), mais une surmortalité, bien que faible, en Flandre (+0,3 % avec 115 décès supplémentaires) et à Bruxelles (+2,8 % avec 146 décès supplémentaires). Durant cette période, la Belgique a connu deux semaines consécutives de surmortalité (semaines 51 et 52, du 19 décembre 2022 au 1er janvier 2023) affectant l’ensemble de la population, coïncidant avec une chute des températures, la 9e vague de COVID-19, une épidémie de grippe, une épidémie de RSV, des infections au human metapneumovirus et un épisode de smog.
La période hivernale 2023-2024 a présenté une sous-mortalité modérée en Belgique (-2,0 %, soit 1 434 décès de moins que prévu). Cette sous-mortalité est plus importante que celle de l’hiver précédent. Il n’y a pas eu d’alerte de surmortalité sur l’ensemble d’une semaine pour toute la population en Belgique. Cette période hivernale se distingue par 14 semaines d’épidémie de RSV, qui fut suivie par une épidémie de grippe saisonnière relativement longue (11 semaines) et une vague de froid en janvier 2024.
Durant les périodes hivernales 2022-2023 et 2023-2024, un résumé hebdomadaire concernant la surveillance de la surmortalité par Be-MOMO était joint au bulletin sur les infections aiguës des voies respiratoires de Sciensano, et ainsi qu’au bulletin hebdomadaire de la surveillance épidémiologique du COVID-19 (jusqu’au 21 juillet 2023). </p
Surveillance épidémiologique de la rougeole (Morbillivirus) - 2023
La rougeole est l’une des maladies infectieuses les plus contagieuses et peut parfois entraîner des complications graves. En collaboration avec l’Organisation mondiale de la santé (OMS), tous les pays européens se sont engagés à éliminer la rougeole.
En 2023, 67 cas de rougeole ont été signalés, avec des diagnostics confirmés en laboratoire pour 54 cas, 12 cas liés à un cas confirmé en laboratoire et une personne enregistrée comme cas possible uniquement sur la base de ses symptômes.
Après des chiffres très bas en 2020-2022 en raison de la pandémie de COVID, on observe une nouvelle augmentation nette et alarmante, en particulier à la fin de l’année 2023. Plus de la moitié des infections (39 cas) a été enregistrée au cours du dernier trimestre, avec un pic de 31 infections au mois de novembre.
La majorité des cas (3⅚7) est survenue chez des enfants de moins de 10 ans, et en particulier chez des enfants de moins d’un an (n=8) qui sont encore trop jeunes pour être vaccinés.
Sur l’ensemble des cas, plus de la moitié n’était pas vaccinée (3⅚7) et l’information sur le statut vaccinal était manquante pour 15 cas. Des cas chez des personnes entièrement vaccinées sont possibles mais restent rares (n=4, tous >20 ans).
Quinze infections ont été contractées à l’étranger. Ces infections ont constitué le point de départ de 7 clusters, soit un total de 29 cas.
Pour 24 cas une hospitalisation était nécessaire.
L’OMS a accordé à la Belgique le statut de ‘rougeole eliminée’ pour les années 2020-2022. Cela ne signifie pas qu’il n’y a plus de cas de rougeole en Belgique, mais plutôt qu’aucune chaîne d’infection n’a duré plus de 12 mois et que l’incidence des cas non importés est faible (<1/1 million d’habitants).
Pour 2023 il n’y a pas encore de décision officielle de l’OMS. L’incidence des cas non importés était trop élevée (4,4/million d’habitants), mais la chaîne d’infections a toujours été interrompue avec succès : aucune chaîne n’a continué à circuler tout au long de l’année.
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Unravelling demographic and socioeconomic patterns of COVID-19 death and other causes of death: results of an individual-level analysis of exhaustive cause of death data in Belgium, 2020
Background
The COVID-19 pandemic led to significant excess mortality in 2020 in Belgium. By using microlevel cause-specific mortality data for the total adult population in Belgium in 2020, three outcomes were considered in this study aiming at predicting sociodemographic (SD) and socioeconomic (SE) patterns of (1) COVID-19 specific death compared to survival; (2) all other causes of death (OCOD) compared to survival; and (3) COVID-19 specific death compared to all OCOD.
Methods
Two complementary statistical methods were used. First, multivariable logistic regression models providing odds ratios and 95% confidence intervals were fitted for the three study outcomes. In addition, we computed conditional inference tree (CIT) algorithms, a non-parametric class of classification trees, to identify and rank by significance level the strongest predictors of the three study outcomes.
Results
Older individuals, males, individuals living in collectivities, first-generation migrants, and deprived SE groups experienced higher odds of dying from COVID-19 compared to survival; living in collectivities was identified by the CIT as the strongest predictor followed by age and sex. Education emerged as one of the strongest predictors for individuals not living in collectivities. Overall, similar patterns were observed for all OCOD except for first- and second-generation migrants having lower odds of all OCOD compared to survival; age group was identified by the CIT as the strongest predictor. Older individuals, males, individuals living in collectivities, first- and second-generation migrants, and individuals with lower levels of education had higher odds of COVID-19 death compared to all OCOD; living in collectivities was identified by the CIT as the strongest predictor followed by age, sex, and migration background. Education and income emerged as among the strongest predictors among individuals not living in collectivities.
Conclusions
This study identified important SD and SE disparities in COVID-19 mortality, with living in collectivities highlighted as the strongest predictor. This underlines the importance of implementing preventive measures, particularly within the most vulnerable populations, in infectious disease pandemic preparedness to reduce virus circulation and the resulting lethality.</p
The importance of estimating the burden of disease from foodborne transmission of Trypanosoma cruzi
Chagas disease (ChD), caused by infection with the flagellated protozoan, Trypanosoma cruzi, has a complicated transmission cycle with many infection routes. These include vector-borne (via the triatomine (reduviid bug) vector defecating into a skin abrasion, usually following a blood meal), transplacental transmission, blood transfusion, organ transplant, laboratory accident, and foodborne transmission. Foodborne transmission may occur due to ingestion of meat or blood from infected animals or from ingestion of other foods (often fruit juice) contaminated by infected vectors or secretions from reservoir hosts. Despite the high disease burden associated with ChD, it was omitted from the original World Health Organization estimates of foodborne disease burden that were published in 2015. As these estimates are currently being updated, this review presents arguments for including ChD in new estimates of the global burden of foodborne disease. Preliminary calculations suggest a burden of at least 137,000 Disability Adjusted Life Years, but this does not take into account the greater symptom severity associated with foodborne transmission. Thus, we also provide information regarding the greater health burden in endemic areas associated with foodborne infection compared with vector-borne infection, with higher mortality and more severe symptoms. We therefore suggest that it is insufficient to use source attribution alone to determine the foodborne proportion of current burden estimates, as this may underestimate the higher disability and mortality associated with the foodborne infection route.</p
Replication Characteristics of African Swine Fever Virus (ASFV) Genotype I E70 and ASFV Genotype II Belgium 2018/1 in Perivenous Macrophages Using Established Vein Explant Model.
African Swine Fever Virus (ASFV), resulting in strain-dependent vascular pathology, leading to hemorrhagic fever, is an important pathogen in swine. The pathogenesis of ASFV is determined by the array and spatial distribution of susceptible cells within the host. In this study, the replication characteristics of ASFV genotype I E70 (G1-E70) and ASFV genotype II Belgium 2018/1 (G2-B18) in the environment of small veins were investigated in an established vein explant model. Immunofluorescence staining analysis revealed that perivenous macrophages (CD163 cells) were widely distributed in the explant, with most of them (approximately 2-10 cells/0.03 mm) being present close to the vein (within a radius of 0-348 µm). Upon inoculation with G1-E70 and G2-B18, we observed an increase in the quantity of cells testing positive for viral antigens over time. G1-E70 replicated more efficiently than G2-B18 in the vein explants (7.6-fold for the ear explant at 72 hpi). The majority of ASFV cells were CD163, indicating that macrophages are the primary target cells. Additional identification of cells infected with ASFV revealed the presence of vimentin, CD14, and VWF cells, demonstrating the cellular diversity and complexity associated with ASFV infection. By the use of this new vein explant model, the susceptibility of vascular and perivascular cells to an ASFV infection was identified. With this model, it will be possible now to conduct more functional analyses to get better insights into the pathogenesis of ASFV-induced hemorrhages.</p
Be.well.pro survey to measure work-related mental well-being of professionals from the healthcare and welfare sector
Background
The COVID-19 pandemic increased the already existing pressure on healthcare and welfare professionals, resulting in a growing shortage of staff.
Objective
The aim of the Be.well.pro survey is to monitor work-related mental well-being of healthcare and welfare professionals in Belgium. A first measurement in a national, representative sample will be conducted in November 2024. Based on the results, targeted measures can be taken in the future to strengthen this well-being. Here, we report on the results of the Be.well.pro pilot study conducted in 2022 - 2023.
Methods
The Be.well.pro survey was developed based on existing surveys and input from stakeholders. It was tested in a pilot study among 2960 respondents from eight Belgian regions with integrated care and/or mental health networks. Psychometric analyses and descriptive statistics were conducted.
Results
The be.well.pro survey has been (partly) validated and proved to be a useful monitoring instrument. Furthermore, some preliminary results could be established. If they were to leave their current job, 21,9% of the respondents would look for a job outside the healthcare or welfare sector, 18.1% would stay within the sector but with a different organization. Moreover, the average reported risk of burnout was 2.2 (1-5 scale), indicating the continued strain on the healthcare workforce in the aftermath of COVID-19.
Conclusion
This study shows the usability of the (partly) validated Be.well.pro survey to monitor work-related wellbeing healthcare and welfare professionals.
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