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Oxford Centre for Tropical Medicine and Global Health
Piloting the options assessment toolkit with national malaria programme leaders from the Asia-Pacific countries: a meeting report.
Plasmodium vivax malaria remains a major challenge in the Asia-Pacific region, where National Malaria Programmes (NMPs) will need to determine optimal radical cure strategies given the availability of novel options, such as high-dose primaquine and tafenoquine. The Options Assessment Toolkit (OAT) was developed to assist NMPs to make decisions on the optimal combination of G6PD testing and radical cure drug regimen. This study reports on the piloting of OAT with NMP representatives during the APMEN Vivax Working Group Annual Meeting in December 2022. A total of 23 NMP representatives from 13 Asia-Pacific countries participated in facilitated discussions. Thematic analysis of qualitative data revealed that NMPs found the OAT useful and timely for structuring malaria policy discussions. However, concerns were raised regarding mismatches between OAT-generated scenarios and country-specific contexts, the inclusion of political and economic factors, and the feasibility of implementing expert-suggested options. Many NMPs expressed enthusiasm for single-dose tafenoquine, but preferred to await WHO recommendations before considering policy changes. Overall, the OAT was well received as a tool for initiating policy discussions on P. vivax radical cure. The OAT represents an important step toward accelerating evidence-based policy change in malaria-endemic countries, with further refinements enhancing its utility.
Why should we be concerned by internalised racism in global health?
Internalised racism constitutes an adoption of beliefs about one's inferiority, weaknesses or shortcomings as a function of racial hierarchy affecting one's identity and self-worth, thoughts, emotions and behaviours. Internalised racism stems from widely known and discussed institutional racial discrimination, which perpetuates epistemic injustice, social injustice and health inequities in global health. In this article, reflecting on our experiential knowledge from working on global health, we engage with relevant literature to (1) highlight the concepts associated with internalised racism, (2) explore the potential impacts of internalised racism on individuals, organisations and global health and (3) propose strategies to redress and mitigate its impact on global health practice.
Spatial distribution and population structure of the invasive Anopheles stephensi in Kenya from 2022 to 2024.
This study analyzes the distribution, genetic diversity, and spread of Anopheles stephensi in Kenya following initial detection in December 2022. A total of 114 larval and 33 adult An. stephensi samples were confirmed in 7 of 18 surveyed counties majorly along transportation routes. Genetic analyses revealed three distinct genetic compositions with different levels of genetic diversity, suggesting multiple introductions into the country. The genetic composition of mosquitoes in most counties resembled southern Ethiopian populations, while those from Turkana showed a unique haplotype. A species distribution model predicts a more extensive range than currently observed, with low precipitation and minimal seasonal temperature variations as key factors influencing distribution. Challenges in adult sampling were noted, with larval sampling revealing co-occurrence with native Anopheles species. The findings have implications for surveillance and control strategies, emphasizing the need for continued monitoring, refined sampling techniques to inform bionomics, and cross-border collaboration.
Vaccine effects on in-hospital COVID-19 outcomes.
Here, we posit that studies comparing outcomes of patients hospitalized with COVID-19 by vaccination status are important descriptive epidemiologic studies, but contrast two groups that are not comparable with regard to causal analyses. We use the principal stratification framework to show that these studies can estimate a causal vaccine effect only for the subgroup of individuals who would be hospitalized with or without vaccination. Further, we describe the methodology for, and present sensitivity analyses of, this effect. Using this approach can change the interpretation of studies only reporting the standard analyses that condition on observed hospital admission status - that is, analyses comparing outcomes for all hospitalised COVID-19 patients by vaccination status.
Iron deficiency causes aspartate-sensitive dysfunction in CD8+ T cells.
Iron is an irreplaceable co-factor for metabolism. Iron deficiency affects >1 billion people and decreased iron availability impairs immunity. Nevertheless, how iron deprivation impacts immune cell function remains poorly characterised. We interrogate how physiologically low iron availability affects CD8+ T cell metabolism and function, using multi-omic and metabolic labelling approaches. Iron limitation does not substantially alter initial post-activation increases in cell size and CD25 upregulation. However, low iron profoundly stalls proliferation (without influencing cell viability), alters histone methylation status, gene expression, and disrupts mitochondrial membrane potential. Glucose and glutamine metabolism in the TCA cycle is limited and partially reverses to a reductive trajectory. Previous studies identified mitochondria-derived aspartate as crucial for proliferation of transformed cells. Despite aberrant TCA cycling, aspartate is increased in stalled iron deficient CD8+ T cells but is not utilised for nucleotide synthesis, likely due to trapping within depolarised mitochondria. Exogenous aspartate markedly rescues expansion and some functions of severely iron-deficient CD8+ T cells. Overall, iron scarcity creates a mitochondrial-located metabolic bottleneck, which is bypassed by supplying inhibited biochemical processes with aspartate. These findings reveal molecular consequences of iron deficiency for CD8+ T cell function, providing mechanistic insight into the basis for immune impairment during iron deficiency.
Research Electronic Data Capture (REDCap) for Population-Based Data Collection in Low- and Middle-Income Countries: Opportunities, Challenges, and Solutions.
Health research requires high-quality data, and population-based health research comes with specific opportunities and challenges for data collection. Electronic data capture can mitigate some of the challenges of working with large populations in multiple, sometimes difficult-to-reach, locations. This viewpoint paper aims to describe experiences during the implementation of two mixed methods studies in Vietnam, Nepal, and Indonesia, focusing on understanding lived experiences of the COVID-19 pandemic across 3 countries and understanding knowledge and behaviors related to antibiotic use in Vietnam. We present the opportunities, challenges, and solutions arising through using Research Electronic Data Capture (REDCap) for designing, collecting, and managing data. Electronic data capture using REDCap made it possible to collect data from large populations in different settings. Challenges related to working in multiple languages, unstable internet connections, and complex questionnaires with nested forms. Some data collectors lacked the digital skills to comfortably use REDCap. To overcome these challenges, we included regular team meetings, training, supervision, and automated error-checking procedures. The main types of errors that remained were incomplete and duplicate records due to disruption during data collection. However, with immediate access to data, we were able to identify and troubleshoot these problems quickly, while data collection was still in progress. By detailing our lessons learned-such as the importance of iterative testing, regular intersite meetings, and customized modifications-we provide a roadmap for future projects to boost productivity, enhance data quality, and effectively conduct large-scale population-based research. Our suggestions will be beneficial for research teams working with electronic data capture for population-based data.
Clinicians’ use of metaphoric language in conversations with families of critically ill patients in the intensive care unit
Objectives: During conversations with families of critically ill patients in intensive care units (ICUs), clinicians’ metaphoric language use may facilitate families’ understanding, but also has potential drawbacks. We sought to obtain insights regarding how ICU clinicians use metaphors regarding patients’ disease and treatment trajectory. Methods: We identified clinicians’ metaphor use in N=101 audio-recorded neonatal, pediatric, and adult ICU family conversations about life-sustaining treatments. Using qualitative content analyses, each metaphor's semantic domain, disease phase, and dialogical function were coded. Overarching themes and patterns were analyzed. Results: Journey metaphors (N = 140 in N = 54 conversations) most frequently referred to the semantic domains boundary, path and bridge. Although most functioned to convey clinical information (72 %), metaphors were mainly presented in an emotionally charged way, serving to manage families’ perceptions. As patients’ conditions deteriorated, metaphors more often functioned to prepare families for medical limits. Metaphors were sometimes potentially unclear. Others suggested high patient agency, starkly contrasting with patients’ unconscious state. Conclusions: Metaphors related to ICU patients’ disease and treatment trajectory are common. They may clarify information or strengthen clinicians’ arguments but can also cause confusion and thereby hinder decision-making. Practice implications: Enhancing clinicians’ awareness about their metaphor use may promote more effective information exchange and decision-making.
Pathogen-specific host response in critically ill patients with blood stream infections: a nested case–control study
Background: Knowledge of the contribution of the pathogen to the heterogeneity of the host response to infection is limited. We aimed to compare the host response in critically ill patients with a bloodstream infection (BSI). Methods: RNA profiles were determined in blood obtained between one day before and after a positive blood culture. Differential expression and pathway analyses were performed on independent patients’ samples by RNA sequencing (discovery) or microarray (validation). Additional patients were included for the discovery and validation of transcriptome classifiers of pathogen-specific BSIs. Twenty biomarkers reflecting key host response pathways were measured in blood. Findings: We included 341 patients, among which 255 with BSI, 25 with viral infection and 61 non-infectious controls. The cultured pathogen explained 41·8% of the blood transcriptomic variance in patients with BSI. Gene set enrichment analysis showed a global resemblance between monomicrobial BSIs caused by Streptococcus, Staphylococcus aureus and Escherichia coli, which were clearly different from BSI caused by coagulase-negative staphylococci or Enterococcus. BSI by Streptococcus was associated with the highest number of differentially expressed genes, indicating strong innate and adaptive immune activation. An eight-gene streptococcal classifier performed well across different Streptococcus species, and was validated in external cohorts. Plasma biomarker profiling showed that E. coli BSI was associated with the strongest response in the cytokine and systemic inflammation domain, and S. aureus BSI with the strongest endothelial cell activation. Interpretation: The causative pathogen explains a substantial part of the heterogeneity of the host response in critically ill patients with BSI. Funding: Center for Translational Molecular Medicine and the European Commission.
Simplifying medicine dosing for children by harmonising weight bands across therapeutic areas.
Generally, dose recommendations for children are expressed as fixed dosing increments related to bodyweight, known as weight bands. The weight bands recommended in WHO treatment guidelines vary between diseases, leading to complexity and potential dosing errors when treating children for multiple diseases simultaneously. The introduction of a harmonised weight banding approach for orally administered drugs across disease areas could streamline dosing for young children, but implementing such an approach would require changes in current dosing recommendations. In this Health Policy, we describe the process we conducted to: identify therapeutic areas for harmonisation of weight bands; propose a harmonised weight-banding system to align with current use of weight bands in antibiotic guidance; and simulate the expected effect of dose adjustments due to weight-band harmonisation. Each step of this process, along with the effect and feasibility of weight-band harmonisation was discussed with clinical, policy, and pharmacology experts convened by WHO, representing four therapeutic areas: tuberculosis, HIV, malaria, and hepatitis C. Dosing according to harmonised weight bands across the targeted therapeutic areas was found to be feasible and should be considered for implementation by WHO disease programmes through their appropriate normative processes.
Handheld Spatially Offset Raman Spectroscopy for rapid non-invasive detection of ethylene glycol and diethylene glycol in medicinal syrups.
We investigate the potential of Spatially Offset Raman Spectroscopy (SORS) as a rapid, non-invasive screening tool deployable in the field to detect diethylene glycol (DEG) and ethylene glycol (EG) in medicinal syrups within closed containers. Measurements were performed on neat propylene glycol (PG) and glycerol, key components of many medicinal syrups, as well as marketed medicinal syrup formulations spiked with DEG and EG at various concentration levels to assess the technique's limit of detection in real-life samples. SORS was able to detect these down to ∼0.5 % concentration level in neat PG for both DEG and EG compounds and ∼1 % concentration level for DEG and EG in neat glycerol. The DEG and EG detection thresholds for the marketed formulations measured through original bottles was ∼1 %, for Benylin (active ingredient: Glycerol) and Piriteze (active ingredient: Cetirizine Hydrochloride). For Calpol (active ingredient: Paracetamol) the detection limit was higher, ∼2 % for EG and ∼5 % for DEG. Although not reaching the International Pharmacopeial 0.1 % detection threshold currently required for purity checks for human consumption, the method can still be used to detect products where DEG or EG has been wrongly used instead of PG or glycerol or if present in large quantities. The technique could also be used for raw material identification testing to ensure no mislabelling has occurred in pre-production stages and as a screening device in distribution chains to detect major deviations from permitted content in non-diffusely scattering, clear formulations, to help prevent serious adverse outcomes, such as acute renal failure and deaths.
Unveiling sub-populations in critical care settings: a real-world data approach in COVID-19.
BackgroundDisease presentation and progression can vary greatly in heterogeneous diseases, such as COVID-19, with variability in patient outcomes, even within the hospital setting. This variability underscores the need for tailored treatment approaches based on distinct clinical subgroups.ObjectivesThis study aimed to identify COVID-19 patient subgroups with unique clinical characteristics using real-world data (RWD) from electronic health records (EHRs) to inform individualized treatment plans.Materials and methodsA Factor Analysis of Mixed Data (FAMD)-based agglomerative hierarchical clustering approach was employed to analyze the real-world data, enabling the identification of distinct patient subgroups. Statistical tests evaluated cluster differences, and machine learning models classified the identified subgroups.ResultsThree clusters of COVID-19 in patients with unique clinical characteristics were identified. The analysis revealed significant differences in hospital stay durations and survival rates among the clusters, with more severe clinical features correlating with worse prognoses and machine learning classifiers achieving high accuracy in subgroup identification.ConclusionBy leveraging RWD and advanced clustering techniques, the study provides insights into the heterogeneity of COVID-19 presentations. The findings support the development of classification models that can inform more individualized and effective treatment plans, improving patient outcomes in the future.
Acceptability and feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing using SD Biosensor by village malaria workers in Cambodia: a qualitative study.
IntroductionPlasmodium vivax is the predominant cause of malaria in the Greater Mekong Subregion. To ensure safe treatment with primaquine, point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing was rolled out in Cambodia at the health facility level, although most malaria patients are diagnosed in the community. The current study aims to explore the acceptability and feasibility of implementing community-level G6PD testing in Cambodia.MethodsSemistructured interviews and focus group discussions (FGD) were conducted. Across eight study sites in three provinces, 142 respondents, including policymakers, programme officers, healthcare providers and patients, participated in 67 interviews and 19 FGDs in 2022 and 2023. Data were analysed thematically using an adapted framework derived from Bowen et al's feasibility framework and Sekhon et al's acceptability framework.ResultsAll stakeholders attributed value to the intervention. Acknowledging an intervention's different values can help discern policy implications for an intervention's successful implementation. Building and maintaining confidence in the device, end users, infrastructure and health systems were found to be key elements of acceptability. In general, health centre workers and village malaria workers (VMWs) had confidence that VMWs could conduct the test and administer treatment given appropriate initial training, monthly refresher training and the test's repeated use. More is required to build policymakers' confidence, while some implementation challenges, including the test's regulatory approval, stability above 30°C and cost, need to be overcome.ConclusionImplementation of G6PD testing at the community level in Cambodia is an acceptable and potentially feasible option but requires addressing implementation challenges and building and maintaining confidence among stakeholders.
Intravenous Rehydration for Severe Acute Malnutrition with Gastroenteritis.
BackgroundInternational recommendations advise against the use of intravenous rehydration therapy in children with severe acute malnutrition because of the concern about fluid overload, but evidence to support this concern is lacking. Given the high mortality associated with the current recommendations, the adoption of intravenous rehydration strategies might improve outcomes.MethodsWe conducted a factorial, open-label superiority trial in four countries in Africa. Children 6 months to 12 years of age with severe acute malnutrition with gastroenteritis and dehydration underwent randomization in a 2:1:1 ratio to one of three rehydration strategies: oral rehydration, plus intravenous boluses for shock; a rapid intravenous strategy that consisted of lactated Ringer's solution (100 ml per kilogram of body weight) administered over a period of 3 to 6 hours, with boluses for shock; or a slow intravenous strategy that consisted of the same solution administered over a period of 8 hours, with no boluses. The primary end point was death at 96 hours.ResultsA total of 272 children underwent randomization; 138 were assigned to the oral strategy, 67 to the rapid intravenous strategy, and 67 to the slow intravenous strategy. Participants were followed for 28 days. A nasogastric tube was used for oral rehydration in 126 of 135 participants (93%) in the oral group and in 82 of 126 (65%) in the intravenous groups. Intravenous boluses were administered at admission in 12 participants (9%) in the oral group, 7 (10%) in the rapid intravenous group, and none in the slow intravenous group. At 96 hours, 11 participants (8%) in the oral group and 9 (7%) in the intravenous groups (5 in the rapid group and 4 in the slow group) had died (risk ratio, 1.02; 95% confidence interval [CI], 0.41 to 2.52; P = 0.69). At 28 days, 17 participants (12%) in the oral group and 14 (10%) in the intravenous groups had died (hazard ratio, 0.85; 95% CI, 0.41 to 1.78). Serious adverse events occurred in 32 participants (23%) in the oral group, 14 (21%) in the rapid intravenous group, and 10 (15%) in the slow intravenous group. No evidence of pulmonary edema, heart failure, or fluid overload was noted.ConclusionsAmong children with severe acute malnutrition and gastroenteritis, no evidence of a difference in mortality at 96 hours was noted between oral and intravenous rehydration strategies. (Funded by the Joint Global Health Trials scheme and others; GASTROSAM Current Controlled Trials number, ISRCTN76149273.).
How equitable, diverse and inclusive are UK primary care trials? A systematic review
BACKGROUND: Randomised Controlled Trials (RCTs) are central to our evidence-informed healthcare system and their findings greatly influence clinical guidelines. More trials are being delivered in primary care however, for the findings to be generalisable, they should be inclusive of the populations for which the intervention is targeted. The NIHR's INCLUDE project looked to address this by creating a framework to consider inclusivity throughout each step of the trial process, concluding at the end of 2021. The PRO EDI initiative looks to improve how equity, diversity and inclusion are handled in evidence synthesis, outlining characteristics about trial participants to guide data extraction. AIM: This systematic review aims to address the question 'How equitable, diverse and inclusive are UK primary care trials?' METHOD: This systematic review will be carried out in accordance with PRISMA guidelines and is pending registration on PROSPERO (submitted). MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched to identify any RCT conducted in the UK from January 2022 - September 2024. Covidence will be used to assist in the review. Preliminary searches have identified 4471 records for title and abstract screening. RESULTS: This work is ongoing, but we aim to present the prevalence of PRO EDI characteristics of trial participants in the UK primary care setting at the conference. CONCLUSION: With our findings we hope to describe the state of equity, diversity and inclusion of trial participants in UK primary care, in the post-INCLUDE framework period.
The genome sequence of varicella-zoster virus (<i>Varicellovirus humanalpha3</i>) obtained by metagenomics from a patient presenting with an exanthem rash.
Here, we report a partial genome sequence of varicella-zoster virus, recovered through metagenomic sequencing from a skin lesion sample collected from a 31-year-old male from Mombasa, Kenya, in August 2024. Phylogenetic analysis placed this isolate in varicella-zoster virus clade 5.
Identifying context-specific determinants to inform improvement of antimicrobial stewardship implementation in healthcare facilities in Asia: results from a scoping review and web-based survey among local experts.
International guidelines are available for the assessment and improvement of antimicrobial stewardship (AMS) programmes: an important strategy to address the escalating global antimicrobial resistance problem. However, existing AMS assessment tools lack contextual specificity for resource-limited settings, leading to limited applicability in Asia. This project aimed to identify relevant themes from current guidance documents to help develop a context-specific assessment tool that can be applied by healthcare facilities (HCFs) to improve local implementation.We performed a sequential approach of a scoping review to identify relevant assessment themes for Asia and an expert survey for getting feedback on the relevance of assessment stems developed from the scoping review. We reviewed English-language published documents discussing AMS implementation or assessment at HCFs globally and in Asia. Themes were derived through content analysis and classified following the predefined context dimensions to develop assessment stems, defined as containing one identified determinant that may influence implementation outcomes. The survey consisting of identified assessment stems was reviewed by 20 locally identified experts in Asia who rated the level of relevance of these stems in AMS implementation in the region.National leadership, training and technical support, and policy and guidance were the most commonly identified themes among 100 themes identified from 73 reviewed documents. From these themes, we developed 131 assessment stems for the expert survey. Of the 131 assessment stems, 117 (89%) were considered relevant for AMS implementation in Asia by at least 80% of respondents. These stems were included in the process of developing a global AMS assessment tool to support HCFs to improve their programmes.In conclusion, national leadership and support represent a distinct and important aspect affecting AMS implementation in HCFs in Asia. The identified assessment themes have substantial value for the formulation of locally relevant implementation strategies tailored to the Asian context.
Adolescent hope and optimism: A scoping review of measures and their psychometric properties.
There is much research examining adolescent hope and optimism, but there is limited information on the available measures, particularly the most frequently used measures and their psychometric properties. We conducted a scoping review to: (1) identify measures of hope and optimism for use among adolescents; (2) determine the most frequently used measures of adolescent hope and optimism; (3) document the psychometric properties of the identified measures. We searched five bibliographic databases and Open Grey for relevant articles published from database inception to 03 May 2023. The search included the key terms 'adolescents', 'optimism', 'hope' and 'measures'. We targeted adolescents aged 10-19 years without country or gender restrictions. We identified 86 measures of optimism and 64 measures of hope for use among adolescents from 803 eligible studies. Most of the included studies (n = 341, 42.5%) originated from North America. We identified 22 most frequently used measures used across 603 (75.1%) of the included studies, with 509 (84.4%) of them providing their psychometric properties. The reported validity of the tools included face, content, construct, criterion, convergent, discriminant, predictive validity and measurement invariance. There are several measures of adolescent hope and optimism. The most frequently used measures of these constructs demonstrated sound psychometric properties, especially reliability. However, most of the evidence originates from high-income countries. There is a need for development, cross-cultural adaptation and validation of these tools to other settings.ContributionHope and optimism are character strengths that have been consistently linked to positive health outcomes in adolescents. Based on increasing research on adolescent hope and optimism, there have been measures developed to assess these constructs but there is no study summarising the available measures, particularly regarding the most frequently used measures and their reliability and validity across contexts. This study aimed at filling this gap. Information on this will be useful to various stakeholders to make evidence-informed choice on selection of the most relevant instrument for use in adolescents in their contexts.