Malaria infection among adults residing in a highly endemic region from the Democratic Republic of the Congo.

BACKGROUND: Adults infected with Plasmodium spp. in endemic areas need to be re-evaluated in light of global malaria elimination goals. They potentially undermine malaria interventions but remain an overlooked aspect of public health strategies. METHODS: This study aimed to estimate the prevalence of Plasmodium spp. infections, to identify underlying parasite species, and to assess predicting factors among adults residing in an endemic area from the Democratic Republic of Congo (DRC). A community-based cross-sectional survey in subjects aged 18 years and above was therefore carried out. Study participants were interviewed using a standard questionnaire and tested for Plasmodium spp. using a rapid diagnostic test and a nested polymerase chain reaction assay. Logistic regression models were fitted to assess the effect of potential predictive factors for infections with different Plasmodium spp. RESULTS: Overall, 420 adults with an estimated prevalence of Plasmodium spp. infections of 60.2% [95% CI 55.5; 64.8] were included. Non-falciparum species infected 26.2% [95% CI 22.2; 30.5] of the study population. Among infected participants, three parasite species were identified, including Plasmodium falciparum (88.5%), Plasmodium malariae (39.9%), and Plasmodium ovale (7.5%) but no Plasmodium vivax. Mixed species accounted for 42.3% of infections while single-species infections predominated with P. falciparum (56.5%) among infected participants. All infected participants were asymptomatic at the time of the survey. Adults belonging to the "most economically disadvantaged" households had increased risks of infections with any Plasmodium spp. (adjusted odds ratio, aOR = 2.87 [95% CI 1.66, 20.07]; p < 0.001), compared to those from the "less economically disadvantaged" households. Conversely, each 1 year increase in age reduced the risk of infections with any Plasmodium spp. (aOR = 0.99 [95% CI 0.97, 0.99]; p = 0.048). Specifically for non-falciparum spp., males had increased risks of infection than females (aOR = 1.83 [95% CI 1.13, 2.96]; p = 0.014). CONCLUSION: Adults infected with malaria constitute a potentially important latent reservoir for the transmission of the disease in the study setting. They should specifically be taken into account in public health measures and translational research.

Multimorbidity and frailty are associated with poorer SARS-CoV-2-related outcomes: systematic review of population-based studies.

BACKGROUND: Estimating the risks and impacts of COVID-19 for different health groups at the population level is essential for orienting public health measures. Adopting a population-based approach, we conducted a systematic review to explore: (1) the etiological role of multimorbidity and frailty in developing SARS-CoV-2 infection and COVID-19-related short-term outcomes; and (2) the prognostic role of multimorbidity and frailty in developing short- and long-term outcomes. This review presents the state of the evidence in the early years of the pandemic. It was conducted within the European Union Horizon 2020 program (No: 101018317); Prospero registration: CRD42021249444. METHODS: PubMed, Embase, World Health Organisation COVID-19 Global literature on coronavirus disease, and PsycINFO were searched between January 2020 and 7 April 2021 for multimorbidity and 1 February 2022 for frailty. Quantitative peer-reviewed studies published in English with population-representative samples and validated multimorbidity and frailty tools were considered. RESULTS: Overall, 9,701 records were screened by title/abstract and 267 with full text. Finally, 14 studies were retained for multimorbidity (etiological role, n = 2; prognostic, n = 13) and 5 for frailty (etiological role, n = 2; prognostic, n = 4). Only short-term outcomes, mainly mortality, were identified. An elevated likelihood of poorer outcomes was associated with an increasing number of diseases, a higher Charlson Comorbidity Index, different disease combinations, and an increasing frailty level. DISCUSSION: Future studies, which include the effects of recent virus variants, repeated exposure and vaccination, will be useful for comparing the possible evolution of the associations observed in the earlier waves.

Sociodemographic and socioeconomic disparities in COVID-19 vaccine uptake in Belgium: a nationwide record linkage study.

BACKGROUND: Recent studies have identified important social inequalities in SARS-CoV-2 infections and related COVID-19 outcomes in the Belgian population. The aim of our study was to investigate the sociodemographic and socioeconomic characteristics associated with the uptake of COVID-19 vaccine in Belgium. METHODS: We conducted a cross-sectional analysis of the uptake of a first COVID-19 vaccine dose among 5 342 110 adults (≥18 years) in Belgium on 31 August 2021. We integrated data from four national data sources: the Belgian vaccine register (vaccination status), COVID-19 Healthdata (laboratory test results), DEMOBEL (sociodemographic/socioeconomic data) and the Common Base Register for HealthCare Actors (individuals licensed to practice a healthcare profession in Belgium). We used multivariable logistic regression analysis for identifying characteristics associated with not having obtained a first COVID-19 vaccine dose in Belgium and for each of its three regions (Flanders, Brussels and Wallonia). RESULTS: During the study period, 10% (536 716/5 342 110) of the Belgian adult population included in our study sample was not vaccinated with a first COVID-19 vaccine dose. A lower COVID-19 vaccine uptake was found among young individuals, men, migrants, single parents, one-person households and disadvantaged socioeconomic groups (with lower levels of income and education, unemployed). Overall, the sociodemographic and socioeconomic disparities were comparable for all regions. CONCLUSIONS: The identification of sociodemographic and socioeconomic disparities in COVID-19 vaccination uptake is critical to develop strategies guaranteeing a more equitable vaccination coverage of the Belgian adult population.

The landscape of drug resistance in Plasmodium falciparum malaria in the Democratic Republic of Congo: a mapping systematic review.

CONTEXT: The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country. METHODS: A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science). RESULTS: We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine-pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN-GE mutants (i.e., parasites carrying the PfDHFR N51I-C59R-S108N and PfDHPS A437G-K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates. CONCLUSIONS: Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.

Trajectories of health behaviors during the COVID-19 pandemic: a longitudinal analysis of handwashing, mask wearing, social contact limitations, and physical distancing.

AIM: This study aimed to investigate the associations between health behavior adherence and psychological factors during the COVID-19 pandemic, with a particular focus on identifying trajectories of handwashing, mask wearing, social contact limitations, and physical distancing. METHODS: We employed a multi-trajectory group-based approach to analyze data from 6026 Belgian residents, including 60% women, with an average age of 52.65. Data were collected over six waves spanning from April 2021 to December 2021. RESULTS: Participants were categorized into trajectory groups based on persistently low (11.9%), moderate-low (20.9%), moderate-high (39.1%), and high (28.1%) levels of adherence to the specified health behaviors. Our findings indicate a declining trend in health behavior adherence over the study period. Additionally, we observed that females, older individuals, and those with prior COVID-19 infection had a higher likelihood of belonging to trajectory groups characterized by the highest levels of health behavior adherence. Similarly, individuals with positive vaccination intentions, a heightened perception of consequences, and increased health anxiety demonstrated greater adherence to health behaviors over time. Furthermore, our investigation into the relationship between health behaviors and mental health revealed that participants in trajectory groups with higher levels of adherence to social contact limitations and physical distancing reported increased feelings of loneliness and decreased life satisfaction. CONCLUSIONS: The COVID-19 pandemic has reshaped our lives, and while vaccines have marked progress, maintaining health behaviors is crucial for virus prevention. To address potential mental health challenges from sanitary measures, policies and communication should promote health behaviors while acknowledging their psychological impact.

COVID-19 contact tracing at work in Belgium - how tracers tweak guidelines for the better.

BACKGROUND: When conducting COVID-19 contact tracing, pre-defined criteria allow differentiating high-risk contacts (HRC) from low-risk contacts (LRC). Our study aimed to evaluate whether contact tracers in Belgium followed these criteria in practice and whether their deviations improved the infection risk assessment. METHOD: We conducted a retrospective cohort study in Belgium, through an anonymous online survey, sent to 111,763 workers by email. First, we evaluated the concordance between the guideline-based classification of HRC or LRC and the tracer's classification. We computed positive and negative agreements between both. Second, we used a multivariate Poisson regression to calculate the risk ratio (RR) of testing positive depending on the risk classification by the contact tracer and by the guideline-based risk classification. RESULTS: For our first research question, we included 1105 participants. The positive agreement between the guideline-based classification in HRC or LRC and the tracer's classification was 0.53 (95% CI 0.49-0.57) and the negative agreement 0.70 (95% CI: 0.67-0.72). The type of contact tracer (occupational doctors, internal tracer, general practitioner, other) did not significantly influence the results. For the second research question, we included 589 participants. The RR of testing positive after an HRC compared to an LRC was 3.10 (95% CI: 2.71-3.56) when classified by the contact tracer and 2.24 (95% CI: 1.94-2.60) when classified by the guideline-based criteria. CONCLUSION: Our study indicates that contact tracers did not apply pre-defined criteria for classifying high and low risk contacts. Risk stratification by contact tracers predicts who is at risk of infection better than guidelines only. This result indicates that a knowledgeable tracer can target testing better than a general guideline, asking for a debate on how to adapt the guidelines.

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.

The global burden of neglected zoonotic diseases: Current state of evidence.

The majority of emerging infectious diseases are zoonoses, most of which are classified as "neglected". By affecting both humans and animals, zoonoses pose a dual burden. The disability-adjusted life year (DALY) metric quantifies human health burden since it combines mortality and morbidity. This review aims to describe and analyze the current state of evidence on neglected zoonotic diseases (NZDs) burden and start a discussion on the current understanding of the global burden of NZDs. We identified 26 priority NZDs through consulting three international repositories for national prioritization exercises. A systematic review of global and national burden of disease (BoD) studies was conducted using pre-selected databases. Data on diseases, location and DALYs were extracted for each eligible study. A total of 1887 records were screened, resulting in 74 eligible studies. The highest number of BoD was found for non-typhoidal salmonellosis (23), whereas no estimates were found for West Nile, Marburg and Lassa fever. Geographically, the highest number of studies was performed in the Netherlands (11), China (5) and Iran (4). The number of BoD retrieved mismatched the perceived importance in national prioritization exercises. For example, anthrax was considered a priority NZD in 65 countries; however, only one national study estimating BoD was retrieved. By summing the available global estimates, the selected NZDs caused at least 21 million DALYs per year, a similar order of magnitude to (but less than) the burden due to foodborne disease (included in the Foodborne Disease Burden Epidemiology Reference Group). The global burden of disease landscape of NZDs remains scattered. There are several priority NZDs for which no burden estimates exist, and the number of BoD studies does not reflect national disease priorities. To have complete and consistent estimates of the global burden of NZDs, these diseases should be integrated in larger global burden of disease initiatives.

Childhood Bacterial Meningitis Surveillance in Southern Vietnam: Trends and Vaccination Implications From 2012 to 2021.

Background: This retrospective hospital-based surveillance aimed to assess the epidemiology, causative pathogens trend, and serotypes distribution of pneumococcal meningitis among children aged under 5 years with bacterial meningitis in Southern Vietnam after the introduction of pentavalent vaccine in the Expanded Program on Immunization (EPI). Methods: From 2012 to 2021, cerebrospinal fluid samples were collected from children aged under 5 years with suspected bacterial meningitis at Children's Hospitals 1 and 2 in Ho Chi Minh City. Probable bacterial meningitis (PBM) cases were identified using biochemistry and cytology. Real-time polymerase chain reaction was used to confirm cases of confirmed bacterial meningitis (CBM) caused by Streptococcus pneumoniae, Haemophilus influenzae, or Neisseria meningitidis. Streptococcus pneumoniae serotyping was performed. Results: Of the 2560 PBM cases, 158 (6.2%) were laboratory-confirmed. The CBM proportion decreased during the 10-year study and was associated with age, seasonality, and permanent residence. Streptococcus pneumoniae was the most common pathogen causing bacterial meningitis (86.1%), followed by H influenzae (7.6%) and N meningitidis (6.3%). The case-fatality rate was 8.2% (95% confidence interval, 4.2%-12.2%). Pneumococcal serotypes 6A/B, 19F, 14, and 23F were the most prevalent, and the proportion of pneumococcal meningitis cases caused by the 10-valent pneumococcal conjugate vaccine (PCV) serotypes decreased from 96.2% to 57.1% during the PCV eras. Conclusions: Streptococcus pneumoniae is the most frequent causative agent of bacterial meningitis in children aged under 5 years in Southern Vietnam over the last decade. Policymakers may need to consider introducing PCVs into the EPI to effectively prevent and control bacterial meningitis.

Reduced polymorphism of Plasmodium vivax early transcribed membrane protein (PvETRAMP) 11.2.

BACKGROUND: ETRAMP11.2 (PVX_003565) is a well-characterized protein with antigenic potential. It is considered to be a serological marker for diagnostic tools, and it has been suggested as a potential vaccine candidate. Despite its immunological relevance, the polymorphism of the P. vivax ETRAMP11.2 gene (pvetramp11.2) remains undefined. The genetic variability of an antigen may limit the effectiveness of its application as a serological surveillance tool and in vaccine development and, therefore, the aim of this study was to investigate the genetic diversity of pvetramp11.2 in parasite populations from Amazonian regions and worldwide. We also evaluated amino acid polymorphism on predicted B-cell epitopes. The low variability of the sequence encoding PvETRAMP11.2 protein suggests that it would be a suitable marker in prospective serodiagnostic assays for surveillance strategies or in vaccine design against P. vivax malaria. METHODS: The pvetramp11.2 of P. vivax isolates collected from Brazil (n = 68) and Peru (n = 36) were sequenced and analyzed to assess nucleotide polymorphisms, allele distributions, population differentiation, genetic diversity and signature of selection. In addition, sequences (n = 104) of seven populations from different geographical regions were retrieved from the PlasmoDB database and included in the analysis to study the worldwide allele distribution. Potential linear B-cell epitopes and their polymorphisms were also explored. RESULTS: The multiple alignments of 208 pvetramp11.2 sequences revealed a low polymorphism and a marked geographical variation in allele diversity. Seven polymorphic sites and 11 alleles were identified. All of the alleles were detected in isolates from the Latin American region and five alleles were detected in isolates from the Southeast Asia/Papua New Guinea (SEA/PNG) region. Three alleles were shared by all Latin American populations (H1, H6 and H7). The H1 allele (reference allele from Salvador-1 strain), which was absent in the SEA/PNG populations, was the most represented allele in populations from Brazil (54%) and was also detected at high frequencies in populations from all other Latin America countries (range: 13.0% to 33.3%). The H2 allele was the major allele in SEA/PNG populations, but was poorly represented in Latin America populations (only in Brazil: 7.3%). Plasmodium vivax populations from Latin America showed a marked inter-population genetic differentiation (fixation index [Fst]) in contrast to SEA/PNG populations. Codon bias measures (effective number of codons [ENC] and Codon bias index [CBI]) indicated preferential use of synonymous codons, suggesting selective pressure at the translation level. Only three amino acid substitutions, located in the C-terminus, were detected. Linear B-cell epitope mapping predicted two epitopes in the Sal-1 PvETRAMP11.2 protein, one of which was fully conserved in all of the parasite populations analyzed. CONCLUSIONS: We provide an overview of the allele distribution and genetic differentiation of ETRAMP11.2 antigen in P. vivax populations from different endemic areas of the world. The reduced polymorphism and the high degree of protein conservation supports the application of PvETRAMP11.2 protein as a reliable antigen for application in serological assays or vaccine design. Our findings provide useful information that can be used to inform future study designs.

Impact of environmental nitrogen pollution on pollen allergy: A scoping review.

The current rise in the prevalence of allergies to aeroallergens is incompletely understood and attributed to interactions with environmental changes and lifestyle changes. Environmental nitrogen pollution might be a potential driver of this increasing prevalence. While the ecological impact of excessive nitrogen pollution has been widely studied and is relatively well understood, its indirect effect on human allergies is not well documented. Nitrogen pollution can affect the environment in various ways, including air, soil, and water. We aim to provide a literature overview of the nitrogen-driven impact on plant communities, plant productivity, and pollen properties and how they lead to changes in allergy burden. We included original articles investigating the associations between nitrogen pollution, pollen, and allergy, published in international peer-reviewed journals between 2001 and 2022. Our scoping review found that the majority of studies focus on atmospheric nitrogen pollution and its impact on pollen and pollen allergens, causing allergy symptoms. These studies often examine the impact of multiple atmospheric pollutants and not just nitrogen, making it difficult to determine the specific impact of nitrogen pollution. There is some evidence that atmospheric nitrogen pollution affects pollen allergy by increasing atmospheric pollen levels, altering pollen structure, altering allergen structure and release, and causing increased allergenic reactivity. Limited research has been conducted on the impact of soil and aqueous nitrogen pollution on pollen allergenic reactivity. Further research is needed to fill the current knowledge gap about the impact of nitrogen pollution on pollen and their related allergic disease burden.

Social inequalities and long-term health impact of COVID-19 in Belgium: protocol of the HELICON population data linkage.

INTRODUCTION: Data linkage systems have proven to be a powerful tool in support of combating and managing the COVID-19 pandemic. However, the interoperability and the reuse of different data sources may pose a number of technical, administrative and data security challenges. METHODS AND ANALYSIS: This protocol aims to provide a case study for linking highly sensitive individual-level information. We describe the data linkages between health surveillance records and administrative data sources necessary to investigate social health inequalities and the long-term health impact of COVID-19 in Belgium. Data at the national institute for public health, Statistics Belgium and InterMutualistic Agency are used to develop a representative case-cohort study of 1.2 million randomly selected Belgians and 4.5 million Belgians with a confirmed COVID-19 diagnosis (PCR or antigen test), of which 108 211 are COVID-19 hospitalised patients (PCR or antigen test). Yearly updates are scheduled over a period of 4 years. The data set covers inpandemic and postpandemic health information between July 2020 and January 2026, as well as sociodemographic characteristics, socioeconomic indicators, healthcare use and related costs. Two main research questions will be addressed. First, can we identify socioeconomic and sociodemographic risk factors in COVID-19 testing, infection, hospitalisations and mortality? Second, what is the medium-term and long-term health impact of COVID-19 infections and hospitalisations? More specific objectives are (2a) To compare healthcare expenditure during and after a COVID-19 infection or hospitalisation; (2b) To investigate long-term health complications or premature mortality after a COVID-19 infection or hospitalisation; and (2c) To validate the administrative COVID-19 reimbursement nomenclature. The analysis plan includes the calculation of absolute and relative risks using survival analysis methods. ETHICS AND DISSEMINATION: This study involves human participants and was approved by Ghent University hospital ethics committee: reference B.U.N. 1432020000371 and the Belgian Information Security Committee: reference Beraadslaging nr. 22/014 van 11 January 2022, available via https://www.ehealth.fgov.be/ehealthplatform/file/view/AX54CWc4Fbc33iE1rY5a?filename=22-014-n034-HELICON-project.pdf. Dissemination activities include peer-reviewed publications, a webinar series and a project website.The pseudonymised data are derived from administrative and health sources. Acquiring informed consent would require extra information on the subjects. The research team is prohibited from gaining additional knowledge on the study subjects by the Belgian Information Security Committee's interpretation of the Belgian privacy framework.

Addressing misclassification bias in vaccine effectiveness studies with an application to Covid-19.

Safe and effective vaccines are crucial for the control of Covid-19 and to protect individuals at higher risk of severe disease. The test-negative design is a popular option for evaluating the effectiveness of Covid-19 vaccines. However, the findings could be biased by several factors, including imperfect sensitivity and/or specificity of the test used for diagnosing the SARS-Cov-2 infection. We propose a simple Bayesian modeling approach for estimating vaccine effectiveness that is robust even when the diagnostic test is imperfect. We use simulation studies to demonstrate the robustness of our method to misclassification bias and illustrate the utility of our approach using real-world examples.

Lyme borreliosis in Belgium: a cost-of-illness analysis.

BACKGROUND: Lyme borreliosis (LB) is the most common tick-borne disease in Europe and North America, yet its economic burden remains largely unknown. This study aimed to estimate the economic cost associated with the different clinical manifestations of LB in Belgium. METHODS: An incidence approach and societal perspective were used to estimate the total cost-of-illness for LB in Belgium. Costs were calculated for patients with erythema migrans (EM) or disseminated/late LB, including patients who developed post-treatment Lyme disease syndrome (PTLDS). Direct medical, direct non-medical (transportation & paid help) and indirect non-medical costs (productivity losses) were included in the analysis. Ambulatory cost data were collected through a prospective cohort study from June 2016 to March 2020, in which patients with LB were followed up 6 to 12 months after diagnosis. Hospitalization costs were retrieved from the Minimal Clinical Data registry, a mandatory registry for all Belgian hospitals, linked to the Minimal Financial Data registry. Costs were expressed in 2019 euros. RESULTS: The total annual cost associated with clinical manifestations of LB in Belgium was estimated at €5.59 million (95% UI 3.82-7.98). Of these, €3.44 million (95% UI 2.05-5.48) or 62% was related to disseminated/late LB diagnoses and €2.15 million (95% UI 1.30-3.26) to EM. In general, direct medical costs and productivity losses accounted for 49.8% and 46.4% of the total costs, respectively, while direct non-medical costs accounted for only 3.8%. The estimated mean costs were €193 per EM patient and €5,148 per disseminated/late LB patient. While patients with PTLDS seemed to have somewhat higher costs compared to patients without PTLDS, the number of patients was too small to have representative estimates. CONCLUSIONS: We estimate the total annual direct medical costs, direct non-medical and indirect non-medical costs associated with LB to exceed €5.5 million per year, almost evenly distributed between EM (40%) and disseminated/late LB (60%). EM costs 26 times less per patient but occurs also 16 times more frequently than disseminated/late LB. The cost burden remains limited by comparison to other infectious diseases due to the relative lower incidence.

Aetiological and prognostic roles of frailty, multimorbidity and socioeconomic characteristics in the development of SARS-CoV-2 health outcomes: protocol for systematic reviews of population-based studies.

INTRODUCTION: There is growing evidence that the impact of COVID-19 crisis may be stronger for individuals with multimorbidity, frailty and lower socioeconomic status. Existing reviews focus on few, mainly short-term effects of COVID-19 illness and patients with single chronic disease. Information is also largely missing for population representative samples.Applying population-based approach, the systematic reviews will have two objectives: (1) to evaluate the aetiological roles of frailty, multimorbidity and socioeconomic status on SARS-CoV-2 infection probability, hospitalisation, intensive care unit (ICU) admission, mechanical ventilation and COVID-19 related mortality among general population and (2) to investigate the prognostic roles of frailty, multimorbidity and socioeconomic characteristics on the risk of hospitalisation, ICU admission, mechanical ventilation, COVID-19 mortality, functioning, quality of life, disability, mental health and work absence. METHODS AND ANALYSIS: For this ongoing work, four databases were searched: PubMed, Embase, WHO COVID-19 Global literature on coronavirus disease and PsycINFO, for the period between January 2020 and April 7 2021. Peer-reviewed published literature in English and all types of population-based studies will be considered. Studies using standard tools to assess multimorbidity such as disease count, comorbidity indices or disease combinations will be retained, as well as studies with standard scales and scores for frailty or measurement of a socioeconomic gradient. Initial search included 10 139 articles, 411 for full-text reading. Results will be summarised by risk factor, objective and outcome. The feasibility of meta-analysis will be determined by the findings and will aim to better understand uncertainties of the results. Quality of studies will be assessed using standardised scales. ETHICS AND DISSEMINATION: The study will be based on published evidence, and it is exempt from the ethical approval. This work is part of the Population Health Information Research Infrastructure (PHIRI) project. Dissemination of the results will imply conference presentation, submission for scientific publication and PHIRI project report. PROSPERO REGISTRATION NUMBER: CRD42021249444.

The state of health in Belgium, 1990-2019: a benchmarking analysis based on the Global Burden of Disease 2019 study.

BACKGROUND: In a context of decreasing resources and growing health needs, evidence-based health and care policies are essential. This study aims to assess the health trends in Belgium between 1990 and 2019, to compare the Belgian health status to that of the EU-15 countries, and to identify the main drivers in trends over time and country differences within the EU-15. METHODS: We extracted estimates from the GBD 2019 study via the GBD results tool and visualization tools. We compared the Belgian health status with 14 European Union comparator countries between 1990 and 2019, and decomposed the time trends and country differences into the unique contributions of the different underlying causes of death and disability. RESULTS: Life expectancy (LE) in Belgium improved significantly between 1990 and 2019 for both men and women. Belgium age-standardised mortality rates dropped significantly for men (-40%) and women (-33%) between 1990 and 2019. Overall, Belgium age-standardised disability-adjusted life year (DALY) rates dropped by 23%. This decrease is mainly due to decreasing trends in age-standardised years of life lost (YLL) rates while age-standardised years lived with disability (YLD) rates remained stable. Compared to EU-15, Belgium's ranking in terms of age-standardised DALY rates worsened for both men and women in 2019. Self-harm and falls are major causes of disease burden, with DALY rates that are higher than in many other EU-15 countries, indicating a realistic potential for improvement. Lung cancer DALY rates remain worrisome for men, and even show an increasing trend for women. Increasing trends of headache disorders, drug use disorders, and diabetes, require further attention. CONCLUSION: Non-communicable diseases remain the main contributors for health burden in Belgium, with disability accounting for an increasingly larger share of the disease burden. Despite considerable improvements, Belgium's ranking for DALYs decreased between 1990 and 2019 compared to the EU-15. This study identified priority causes of disease burden based on their contributions to current evolutions and EU-15 differences. Since many of these causes are considered to be avoidable, primary and secondary prevention are crucial elements for reducing the burden of disease on the healthcare system.

Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016-2020).

BACKGROUND: Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors. METHODS: A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present. RESULTS: Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7-12.9) in EM patients and 20.9% (95% CI 6.8-64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98-12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes. CONCLUSIONS: In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.

Predictors of exceeding emergency under-five mortality thresholds using small-scale survey data from humanitarian settings (1999 - 2020): considerations for measles vaccination, malnutrition, and displacement status.

BACKGROUND: Quantifying the effect of measles containing vaccine (MCV) coverage and the prevalence of global acute malnutrition (GAM) on mortality levels in populations of displaced and crisis-affected resident children is important for intervention programming in humanitarian emergencies. METHODS: A total of 1597 surveys containing data on under-five death rate, population status (internally displaced, refugee, or crisis-affected resident), measles containing vaccine coverage, and global acute malnutrition were extracted from the Complex Emergency Database (CE-DAT). Under-five mortality rates were dichotomized to those exceeding critical levels or otherwise. A Bayesian multivariable mixed-effect logistic regression model was used to assess the association between an under-five death rate (U5DR) exceeding this threshold and population status (i.e., internally displaced, refugees or residents), GAM prevalence (proxy for food security), and MCV coverage. RESULTS: The prevalence of GAM, MCV and U5DR were higher in internally displaced children (IDC) with values of 14.6%, 69.9% and 2.07 deaths per 10 000 per day, respectively. Refugee populations had lower average under-five mortality rate (0.89 deaths per 10 000 per day), GAM of 12.0% and the highest measles containing vaccine coverage (80.0%). In crisis-affected residents the prevalence of GAM, MCV and average U5DR are 11.1%, 65.5% and 1.20 deaths per 10 000 per day respectively. In mixed-effect logistic model taking 2 deaths per 10 000 children less than five years old per as emergency threshold (Model III); MCV (AOR = 0.66, 95% Highest Density Interval (HDI): 0.57, 0.78), GAM (AOR = 1.79, 95% HDI: 1.52, 2.12) were associated with a reduction of the odds of U5DR exceeding critical level accounting for country-specific levels of variability. The odds of U5DR exceeding critical level (2/10000/day) in crisis-affected resident children and refugees were 0.36 (95% HDI: 0.22, 0.58) and 0.25(95% HDI: 0.11, 0.55) less than amongst IDP children adjusting for GAM and MCV. In considering country specific yearly median U5DR (model IV) the odds of U5DR exceeding twice the median U5DR were associated with MCV (AOR = 0.72, 95% HDI: 0.64, 0.82), GAM (AOR = 1.53, 95%HDI: 1.34, 1.76). The odds of U5DR exceeding critical level in crisis-affected resident children was 0.30(95% HDI: 0.20, 0.45) less than IDP children, after adjusting for MCV and GAM. We found no difference between the odds of U5DR exceeding twice the country level median U5DR in the refugee population compared to the IDPs. CONCLUSIONS: In this study vaccination coverage and global acute malnutrition (proxy for food security) were associated with U5DR exceeding critical level. The emergency threshold for IDPs and affected residents is significantly different and consistent across the different outcomes, whereas the result is inconsistent for IDPs and refugees. Continued improvement in measles vaccination coverage and reduction of malnutrition in humanitarian emergencies have the potential to minimize the deterioration of mortality level amongst children in emergency settings. To generate a robust understanding of the critical level of child mortality in displaced and affected resident populations, studies accounting for the impact of the duration of displacement, contextual factors in humanitarian settings, and the level of humanitarian assistance provided are needed.