METHODOLOGY/PRINCIPAL FINDINGS: Using in silico tools, we designed and expressed four novel P. knowlesi protein products to address the distinct lack of suitable serosurveillance tools: PkSERA3 antigens 1 and 2, PkSSP2/TRAP and PkTSERA2 antigen 1. Antibody prevalence to these antigens was determined by ELISA for three time-points post-treatment from a hospital-based clinical treatment trial in Sabah, East Malaysia (n = 97 individuals; 241 total samples for all time points). Higher responses were observed for the PkSERA3 antigen 2 (67%, 65/97) across all time-points (day 0: 36.9% 34/92; day 7: 63.8% 46/72; day 28: 58.4% 45/77) with significant differences between the clinical cases and controls (n = 55, mean plus 3 SD) (day 0 p<0.0001; day 7 p<0.0001; day 28 p<0.0001). Using boosted regression trees, we developed models to classify P. knowlesi exposure (cross-validated AUC 88.9%; IQR 86.1-91.3%) and identified the most predictive antibody responses.
CONCLUSIONS/SIGNIFICANCE: The PkSERA3 antigen 2 had the highest relative variable importance in all models. Further validation of these antigens is underway to determine the specificity of these tools in the context of multi-species infections at the population level.
METHODS: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.
RESULTS: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.
CONCLUSION: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
METHODS: This point prevalence survey (PPS) was conducted in 13 hospitals among 7 different cities of Pakistan. The survey included all inpatients receiving an antibiotic on the day of PPS. A web-based application was used for data entry, validation, and reporting as designed by the University of Antwerp (www.global-pps.com).
RESULTS: Out of 1954 patients, 1516 (77.6%) were treated with antibiotics. The top three most reported indications for antibiotic use were prophylaxis for obstetrics or gynaecological indications (16.5%), gastrointestinal indications (12.6%) and lower respiratory tract infections (12.0%). The top three most commonly prescribed antibiotics were ceftriaxone (35.0%), metronidazole (16.0%) and ciprofloxacin (6.0%). Out of the total indications, 34.2% of antibiotics were prescribed for community-acquired infections (CAI), 5.9% for healthcare-associated infections (HAI), and 57.4% for either surgical or medical prophylaxis. Of the total use for surgical prophylaxis, 97.4% of antibiotics were given for more than one day.
CONCLUSIONS: Unnecessary prophylactic antibiotic use is extremely high, and broad-spectrum prescribing is common among hospitals in Pakistan. There is an urgent need to work on the national action plan of Pakistan on antibiotic resistance to address this.
Objective: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics.
Methods: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions.
Results: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions.
Conclusions: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.
METHODS: A comparative cross sectional study design involving 379 pregnant women was used to assess the prevalence of anaemia and low intake of dietary nutrients in pregnant women living in rural and urban areas in the Ashanti region of Ghana. Anaemia status and mid upper arm circumference (MUAC) were used as proxy for maternal nutritional status. Haemoglobin measurements were used to determine anaemia prevalence and the dietary diversity of the women were determined with a 24-hour dietary recall and a food frequency questionnaire.
RESULTS: Overall, anaemia was present in 56.5% of the study population. Anaemia prevalence was higher among rural residents than urban dwellers. Majority of the respondents had inadequate intakes of iron, zinc, folate, calcium and vitamin A. The mean dietary diversity score (DDS) of the study population from the first 24-hour recall was 3.81 ± 0.7. Of the 379 women, 28.8% met the minimum dietary diversity for women (MDD-W). The independent predictors of haemoglobin concentration were, gestational age, maternal age and dietary diversity score. Such that respondents with low DDS were more likely to be anaemic than those with high DDS (OR = 1.795, p = 0.022, 95% CI: 1.086 to 2.967).
CONCLUSIONS: A large percentage of pregnant women still have insufficient dietary intakes of essential nutrients required to support the nutritional demands during pregnancy. Particularly, pregnant women resident in rural areas require interventions such as nutrition education on the selection and preparation of diversified meals to mitigate the effects of undernutrition.