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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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: ETRAMP11.2 (PVX&#95;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., (© 2023. The Author(s).)

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., Competing Interests: All authors declare that they have no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Competing Interests: We declare no competing interests.

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., (© 2023. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

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., (© 2022. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

Nursing home (NH) residents and staff have been severely affected by the COVID-19 pandemic. The aim of this study was to examine the use of weekly saliva RT-qPCR testing for SARS-CoV-2 detection among NH workers as a strategy to control disease transmission within NHs in Belgium. From 16 November to 27 December 2020, a voluntary and anonymous weekly screening was implemented in a cohort of 50,000 workers across 572 NHs in the Walloon region of Belgium to detect asymptomatic cases of SARS-CoV-2 via saliva RT-qPCR testing and using the Diagenode saliva sample collection device. Positive workers were isolated to avoid subsequent infections in residents and other staff. RT-qPCR testing was based on pooled saliva sampling techniques from three workers, followed by individual testing of each positive or inconclusive pool. The majority of NHs (85%) and 55% of their workers participated. Pooling did not affect sensitivity as it only induced a very decrease in sensitivity estimated as 0.33%. Significant decreases in the prevalence (34.4-13.4%) and incidence of NHs with either single (13.8-2%) or multiple positive workers (3.7-0%) were observed over time. In addition, deaths among NH residents and NH worker absences decreased significantly over time. Weekly saliva RT-qPCR testing for SARS-CoV-2 demonstrated large-scale feasibility and efficacy in disrupting the chain of transmission. Implementation of this testing strategy in NHs could also be extended to other settings with the aim to control viral transmission for maintaining essential activities., (© 2021 Wiley-VCH GmbH.)

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., (© 2022. The Author(s).)

Background: Since the beginning of the ongoing conflict in Yemen, >23 000 air strikes and >100 000 fatalities have been recorded. Data from Yemen Data Project linked >1300 child fatalities and >900 child injuries to air raids. However, there is little literature on the effect of the protracted armed conflict on the pattern of child mortality using data from small-scale surveys. We aimed to identify the pattern of the death rate for children aged <5 years ('under-5') and its relationship with human insecurity in Yemen., Methods: We created a human insecurity index (i.e. severely insecure vs insecure) for the 22 governorates in Yemen from 2015 to 2019, using data from the Armed Conflict Location and Event Database. We matched this insecurity index with the corresponding under-5 mortality data from the Complex Emergency Database. We analysed the relationship between the under-5 death rate (U5DR) and the insecurity level using a Bayesian finite mixture model in order to account for unobserved heterogeneity in clustered finite subsets of a population., Results: We extracted 72 surveys and 77.8% (n = 56) were included in this study. The mean of the recall period for mortality was 106 days with a standard deviation of 93 days. We identified two subpopulations: Subpopulation I-high average number of child deaths and Subpopulation II-low average number of child deaths. The log posterior mean of the U5DR is 1.10 (95% credible intervals: 0.36, 1.82) in the severely insecure group in Subpopulation I and 3-fold the estimate in Subpopulation II. However, in Subpopulation II, we found no association between the insecurity level and the U5DR., Conclusion: The pattern of child deaths is crucial in understanding the relationship between human insecurity and the U5DR., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Disability-adjusted life years (DALYs) combine the impact of morbidity and mortality and can enable comprehensive, and comparable, assessments of direct and indirect health harms due to COVID-19. Our aim was to estimate DALYs directly due to COVID-19 in Scotland, during 2020; and contextualise its population impact relative to other causes of disease and injury., Methods: National deaths and daily case data were used. Deaths were based on underlying and contributory causes recorded on death certificates. We calculated DALYs based on the COVID-19 consensus model and methods outlined by the European Burden of Disease Network. DALYs were presented as a range, using a sensitivity analysis based on Years of Life Lost estimates using: cause-specific; and COVID-19 related deaths. All COVID-19 estimates were for 2020., Results: In 2020, estimates of COVID-19 DALYs in Scotland ranged from 96,500 to 108,200. Direct COVID-19 DALYs were substantial enough to be framed as the second leading cause of disease and injury, with only ischaemic heart disease having a larger impact on population health. Mortality contributed 98% of total DALYs., Conclusions: The direct population health impact of COVID-19 has been very substantial. Despite unprecedented mitigation efforts, COVID-19 developed from a single identified case in early 2020 to a condition with an impact in Scotland second only to ischaemic heart disease. Periodic estimation of DALYs during 2021, and beyond, will provide indications of the impact of DALYs averted due to the national rollout of the vaccination programme and other continued mitigation efforts, although new variants may pose significant challenges., (© 2022. The Author(s).)

Background: Because of the loss of chloroquine (CQ) effectiveness, the Democratic Republic of Congo (DRC)'s malaria treatment policy replaced CQ by sulfadoxine-pyrimethamine (SP) as first-line treatment of uncomplicated malaria in 2003, which in turn was replaced by artemisinin-based combination therapies (ACT) in 2005. The World Health Organization (WHO) recommends monitoring of anti-malarial drug resistance every 2 years. The study aimed to provide baseline data for biennial molecular surveillance of anti-malarial drug resistance by comparing data from a study conducted in 2019 to previously published data from a similar study conducted in 2017 in the DRC., Methods: From July to November 2019, a cross-sectional study was conducted in ten sites which were previously selected for a similar study conducted in 2017 across the DRC. P. falciparum malaria was diagnosed by a rapid diagnostic test (RDT) or by microscopy and dried blood samples (DBS) were taken from patients who had a positive test. Segments of interest in pfcrt and pfk13 genes were amplified by conventional PCR before sequencing., Results: Out of 1087 enrolled patients, 906 (83.3%) were PCR-confirmed for P. falciparum. Like in the 2017-study, none of the mutations known to be associated with Artemisinine (ART) resistance in Southeast Asia was detected. However, non-synonymous (NS) mutations with unknown functions were observed among which, A578S was detected in both 2017 and 2019-studies. The overall prevalence of pfcrt-K76T mutation that confers CQ-resistance was 22.7% in 2019-study compared to 28.5% in 2017-study (p-value = 0.069), but there was high variability between sites in the two studies. Like in 2017-study, the pfcrt 72-76 SVMNT haplotype associated with resistance to amodiaquine was not detected., Conclusion: The study reported, within 2 years, the non-presence of molecular markers currently known to be associated with resistance to ART and to AQ in P. falciparum isolated in the DRC. However, the presence of polymorphisms with as-yet unknown functions was observed, requiring further characterization. Moreover, an overall decrease in the prevalence of CQ-resistance marker was observed in the DRC, but this prevalence remained highly variable from region to region., (© 2022. The Author(s).)

Purpose: Health-related quality of life outcomes are increasingly used to monitor population health and health inequalities and to assess the (cost-) effectiveness of health interventions. The EQ-5D-5L has been included in the Belgian Health Interview Survey, providing a new source of population-based self-perceived health status information. This study aims to estimate Belgian population norms for the EQ-5D-5L by sex, age, and region and to analyze its association with educational attainment., Methods: The BHIS 2018 provided EQ-5D-5L data for a nationally representative sample of the Belgian population. The dimension scores and index values were analyzed using logistic and linear regressions, respectively, accounting for the survey design., Results: More than half of respondents reported problems of pain/discomfort, while over a quarter reported problems of anxiety/depression. The average index value was 0.84. Women reported more problems on all dimensions, but particularly on anxiety/depression and pain/discomfort, resulting in significantly lower index values. Problems with mobility, self-care, and usual activities showed a sharp increase after the age of 80 years. Consequently, index values decreased significantly by age. Lower education was associated with a higher prevalence of problems for all dimensions except anxiety/depression and with a significantly lower index value., Conclusion: This paper presents the first nationally representative Belgian population norms using the EQ-5D-5L. Inclusion of the EQ-5D in future surveys will allow monitoring over time of self-reported health, disease burden, and health inequalities., (© 2021. The Author(s).)

Background: A number of tick-borne pathogens circulate in the Belgian tick population in addition to the causative agent of Lyme borreliosis. However, so far, only a few patients with tick-borne diseases other than Lyme borreliosis have been reported in Belgium. The aim of this study was to investigate the occurrence of other human tick-borne infections in Belgium and their possible clinical manifestation., Methods: Patients with fever (> 37.5 °C) after a tick bite or those with erythema migrans (EM) were included in the study. EDTA-blood samples were screened for the presence of DNA from Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Anaplasma phagocytophilum, Neoehrlichia mikurensis, spotted fever group rickettsiae (genus Rickettsia), Babesia spp., Bartonella spp., Spiroplasma ixodetis and tick-borne encephalitis virus, using multiplex PCR methods. A questionnaire on, among others, demographics and clinical symptoms, was also filled in., Results: Over a period of 3 years, 119 patients with EM and 14 patients with fever after a recent tick bite were enrolled in the study. Three samples initially tested positive for N. mikurensis by quantitative PCR (qPCR), but the results could not be confirmed by other PCR methods, and repetition of the DNA extraction procedure and qPCR test was not successful. The qPCR test results for the other tick-borne pathogens were negative., Conclusions: In general, only a few patients with fever after a tick bite could be identified. Although no tick-borne pathogens were detected, their occurrence cannot be excluded based on the limited number of patients and the limitations inherent to current methodologies. This study underscores the possibility of false-positive PCR results and the necessity for the development of multiple independent tools for the sensitive and specific detection of emerging tick-borne pathogens., (© 2022. The Author(s).)

Background: The importance of assessing and monitoring the health status of a population has grown in the last decades. Consistent and high quality data on the morbidity and mortality impact of a disease represent the key element for this assessment. Being increasingly used in global and national burden of diseases (BoD) studies, the Disability-Adjusted Life Year (DALY) is an indicator that combines healthy life years lost due to living with disease (Years Lived with Disability; YLD) and due to dying prematurely (Years of Life Lost; YLL). As a step towards a comprehensive national burden of disease study, this study aims to estimate the non-fatal burden of cancer in Belgium using national data., Methods: We estimated the Belgian cancer burden from 2004 to 2019 in terms of YLD, using national population-based cancer registry data and international disease models. We developed a microsimulation model to translate incidence- into prevalence-based estimates, and used expert elicitation to integrate the long-term impact of increased disability due to surgical treatment., Results: The age-standardized non-fatal burden of cancer increased from 2004 to 2019 by 6 and 3% respectively for incidence- and prevalence-based YLDs. In 2019, in Belgium, breast cancer had the highest morbidity impact among women, followed by colorectal and non-melanoma skin cancer. Among men, prostate cancer had the highest morbidity impact, followed by colorectal and non-melanoma skin cancer. Between 2004 and 2019, non-melanoma skin cancer significantly increased for both sexes in terms of age-standardized incidence-based YLD per 100,000, from 49 to 111 for men and from 15 to 44 for women. Important decreases were seen for colorectal cancer for both sexes in terms of age-standardized incidence-based YLD per 100,000, from 105 to 84 for men and from 66 to 58 for women., Conclusions: Breast and prostate cancers represent the greatest proportion of cancer morbidity, while for both sexes the morbidity burden of skin cancer has shown an important increase from 2004 onwards. Integrating the current study in the Belgian national burden of disease study will allow monitoring of the burden of cancer over time, highlighting new trends and assessing the impact of public health policies., (© 2022. The Author(s).)

Early warning tools are crucial for the timely application of intervention strategies and the mitigation of the adverse health, social and economic effects associated with outbreaks of epidemic potential such as COVID-19. This paper introduces, the Epidemic Volatility Index (EVI), a new, conceptually simple, early warning tool for oncoming epidemic waves. EVI is based on the volatility of newly reported cases per unit of time, ideally per day, and issues an early warning when the volatility change rate exceeds a threshold. Data on the daily confirmed cases of COVID-19 are used to demonstrate the use of EVI. Results from the COVID-19 epidemic in Italy and New York State are presented here, based on the number of confirmed cases of COVID-19, from January 22, 2020, until April 13, 2021. Live daily updated predictions for all world countries and each of the United States of America are publicly available online. For Italy, the overall sensitivity for EVI was 0.82 (95% Confidence Intervals: 0.75; 0.89) and the specificity was 0.91 (0.88; 0.94). For New York, the corresponding values were 0.55 (0.47; 0.64) and 0.88 (0.84; 0.91). Consecutive issuance of early warnings is a strong indicator of main epidemic waves in any country or state. EVI's application to data from the current COVID-19 pandemic revealed a consistent and stable performance in terms of detecting new waves. The application of EVI to other epidemics and syndromic surveillance tasks in combination with existing early warning systems will enhance our ability to act swiftly and thereby enhance containment of outbreaks., (© 2021. The Author(s).)

Background: Increasing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) threatens its usefulness for intermittent preventive treatment in pregnancy (IPTp-SP). The prophylactic effects of IPTp-SP on maternal malaria and adverse pregnancy outcomes were evaluated in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo (DRC)., Methods: Laboring women (n = 844) and respective newborns were investigated. Blood samples collected from women were tested for malaria using rapid diagnostic test (RDT), blood smears examination, and real-time PCR. The hemoglobin level was measured by HemoCue© analyzer. A PCR-RFLP method was applied for detecting N51I, C59R, and S108N mutations on dhfr along with A437G and K540E mutations on dhps in P. falciparum positive samples. Logistic regression models assessed relationships between IPTp-SP uptake and pregnancy outcomes., Results: P. falciparum malaria was detected at delivery in 10.8% of women and was statistically associated with fever during the pregnancy (OR = 2.9 [1.5; 6.3]; p = 0.004) and maternal anemia (OR = 3.9 [2.4; 6.3]; p < 0.001). One out of five parasites was a quintuple mutant encoding dhfr mutations 51I, 59R, and 108 N along with dhps mutations 437G and 540E. The molecular profile of parasites (i.e., 32.6% of parasites carrying dhps K540E) was suitable with continued use of SP for IPTp. IPTp-SP uptake was not associated with reduced maternal malaria, fever reported in pregnancy, or fetal deaths (p > 0.05). Conversely, three or more doses of SP were associated with reduced maternal anemia at delivery (OR = 0.4 [0.2; 0.9]; p = 0.024), shortened gestation (OR = 0.4 [0.2; 0.8]; p = 0.009), and low-birth weights (OR = 0.2 [0.1; 0.5]; p < 0.001)., Conclusion: IPTp-SP was not associated with reduced maternal malaria in our study, but evidence was found of a prophylactic effect against adverse pregnancy outcomes. To counteract further loss of clinical effects of IPTp-SP in the study population, alternative strategies able to improve its anti-malarial efficacy such as combination of SP with partner molecules should be implemented., (Copyright © 2021. Published by Elsevier B.V.)

Beside diagnostic uncertainties due to the lack of a perfect gold standard test for Helicobacter pylori infection, the diagnosis and the prevalence estimation for this infection encounter particular challenges in Africa including limited diagnostic tools and specific genetic background. We developed and evaluated the accuracy of an enzyme-linked immunosorbent assay (ELISA) system tailored for H. pylori genetics in Africa (HpAfr-ELISA). Strains belonging to main genetic populations infecting Africans were exploited as sources for whole-cell antigens to establish in-house the ELISA system. A phase II unmatched case-control study explored the diagnostic accuracy of the HpAfr-ELISA using a training set of samples collected from dyspeptic patients from Kinshasa, the Democratic Republic of Congo (DRC) who had been tested with invasive standard tests (i.e., histology, culture, and rapid urease test) in 2017. Then the assay was cross-validated through a community-based survey assessing the prevalence of H. pylori and associated factors in 425 adults from Mbujimayi, DRC in 2018. Bayesian inferences were used to deal with statistical uncertainties of estimates (true prevalence, sensitivity, and specificity) in the study population. At its optimal cut-off-value 20.2 U/mL, the assay achieved an estimated sensitivity of 97.6% (95% credible interval [95%CrI]: 89.2; 99.9%) and specificity of 90.5% (95%CrI: 78.6; 98.5). Consistent outcomes obtained at repeated tests attested the robustness of the assay (negative and positive agreements always > 70%). The true prevalence of H. pylori was estimated 53.8% [95%CrI: 42.8; 62.7%]. Increasing age (adjusted odds ratio [aOR] > 1.0 [95% confidence interval (CI): > 1.0; 1.1]; p<0.001), overcrowding households (aOR = 3.2 [95%CI: 2.0; 5.1]; p<0.001), and non-optimal hand hygiene (aOR = 4.5 [95%CI: 2.0; 11.4]; p = 0.001) were independently associated with the H. pylori-seropositivity. The novel ELISA system has demonstrated good diagnostic accuracy and potential usefulness for management and mitigation strategies for H. pylori infection in African settings., Competing Interests: The authors have declared that no competing interests exist.