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Establishing the value of regional cooperation and a critical role for regional organisations in managing future health emergencies
Get PDFThe COVID-19 pandemic revealed the failures of global, multilateral cooperation to respond and adapt to health emergencies while observing the principles of solidarity and equity. This response has raised the question of whether the global architecture for health emergencies is fit for purpose. In this Health Policy, amid proposals to reform this architecture, we consider the potential value of regional cooperation and the role regional organisations might play in delivering effective and equitable solutions to the challenges posed by public health emergencies. Drawing on our multidisciplinary perspectives and diverse experience of geographical regions, we explore the value of regional cooperation, the role of regional organisations, where they could have the greatest impact, and the major factors affecting regional cooperation and regional organisations in managing public health emergencies. As the COVID-19 pandemic reshapes our approach to health emergencies, leveraging and integrating the capabilities of regional organisations will be crucial for improving preparedness and response efforts globally.</p
Malaria infection prevalence and diagnostic performance of the Abbott Bioline Malaria Ag P.f/Pan rapid test in rural populations of Central Cameroon
Get PDFIn Cameroon, the management of uncomplicated malaria cases in the communities and in low-resource health facilities rely on the use of reliable rapid diagnostic tests (RDTs). This work was undertaken to determine the trend in human malaria infection in rural settings of Central Cameroon and assess the diagnostic performance of Abbott Bioline Malaria Ag P.f/Pan RDT recommended by the National Malaria Control Programme (NMCP). Cross-sectional surveys were conducted in March 2022 and May 2024. Plasmodium infection was detected using RDT and microscopy techniques, and with real-time PCR for validation of discordant results. Sensitivity (Se), specificity (Sp), positive and negative predictive values, positive and negative likelihood ratios (LR + and LR-), accuracy and agreement were calculated to assess the performance of the RDT. Plasmodium infection prevalence was 64.9% and 71.7% by microscopy and RDT, respectively, Plasmodium falciparum being the predominant species (microscopy:97.48%). With microscopy as reference, the RDT showed high sensitivity (Se:93.37%; CI:91.15%-95.77%) and low specificity (Sp: 68.50%; CI:62.40%-74.17%) for the detection of P. falciparum infection. The positive and negative predictive values were respectively 84.43% (CI:81.01%-87.46%) and 85.71% (CI:80.13%-90.22%). The RDT showed a small positive likelihood ratio (LR + = 2.96; CI:2.47-3.5734), a good negative likelihood ratio (LR-=0.09; CI:0.06–0.13) and moderate agreement (k = 0.652; CI:0.593–0.710; P < 0.001) with microscopy. The RDT showed higher sensitivity (81.48% vs. 48.14%), accuracy (0.75 and vs. 0.50), and agreement (AC1 = 0.715 vs. 0.371) than microscopy. The Abbott Bioline Malaria Ag P.f/Pan RDT demonstrated a high level of agreement with the most sensitive qPCR technique compared to microscopy. These findings further support its use as a reliable malaria diagnostic tool in the highly endemic setting of Central Cameroon.</p
The association between systemic inflammation and albuminuria among people living with HIV: A cross-sectional study from Botswana
Get PDFTreated human immunodeficiency virus (HIV) is associated with persistent systemic inflammation, even after many years of sustained viral suppression following initiation of antiretroviral therapy (ART). Albuminuria is common among people living with HIV (PLWH), but the impact of persistent systemic inflammation on outcome of albuminuria is not well understood. Thawed serum samples from PLWH who participated in an albuminuria prevalence study in Gaborone, Botswana, between January 2020 and March 2022, were selected randomly for a cross-sectional study of the link between inflammation and albuminuria. Systemic inflammation (interleukin [IL] 1β, IL 6, and soluble cluster of differentiation-163 [sCD163]) was assessed using enzyme linked immunosorbent assay, and albuminuria was reported as urinary albumin-creatinine ratio (ACR) (mg/g), as obtained from the parent study. The association between systemic inflammation and albuminuria was first explored by ACR quartiles, graphically using simple linear models, and then using general additive models for the adjusted analysis. The study population comprised 715 ART treated PLWH, with a mean age of 49.9 (SD 10.7) years, median HIV disease duration of 13.5 (IQR 8.7-16.7) years, and 398/715 (55.7%) were male. The relationship between log transformed ACR and sCD163 was linear, with regression coefficient β=0.10, P-value=.02 but was nonlinear for log transformed IL-1β and IL-6, β=0.10, P -value=.82 and β=-0.04, P-value=.36, respectively. In the final adjusted general additive models, sCD163 was not associated with ACR, P-value=.137. IL-1β, IL-6, and sCD163 were not associated with ACR among ART treated PLWH. Novel strategies to identify inflammatory pathways that may promote albuminuria among PLWH should consider other innovative and sensitive markers of both systemic and organ specific inflammation.</p
Health system drivers of antimicrobial resistance: a qualitative exploration of implications for infection prevention and control in hospitals and long-term care facilities in Merseyside
Get PDFBackgroundAntimicrobial resistance (AMR) transmission is shaped by a complex interplay of health system factors, many of which remain underexplored or insufficiently addressed. This study investigates concrete systemic transmission drivers in hospitals and long-term care facilities (LTCFs) for older adults in Merseyside, UK.MethodsQualitative data were collected through semi-structured interviews with 37 purposively selected participants across hospitals, LTCFs, community settings, and ambulance services. Interviews were informed by the WHO Health System Building Blocks framework and explored AMR transmission pathways and drivers, barriers to infection prevention and control (IPC) practices, and intervention strategies. Thematic analysis was conducted using NVivo 12.ResultsThree key perceived transmission points were identified: prolonged waits in overcrowded hospital areas, inter-facility transfers, and shared spaces within LTCFs and hospital wards. Contributing systemic AMR drivers included inadequate infrastructure, fragmented communication during care transitions, staff turnover, training gaps. Less recognised yet significant risks included the lack of consistent cleaning teams across wards; generic IPC guidelines ill-suited to specific care contexts; and weak administrative oversight of environmental hygiene. While AMR screening was widely recognised as problematic, its cost-effectiveness and clinical utility remain unclear. Communication failures during transfers emerged as an immediately addressable issue, while infrastructure deficits and workforce instability posed more persistent, systemic challenges.ConclusionAddressing AMR in care settings requires a context-specific, multi-component approach prioritising effective infection risk communication at care interfaces, tailored IPC protocols, and stable staffing. While long-term investment in infrastructure, screening and workforce is essential, immediate progress is possible through low-resource measures such as improved infection risk information systems and context-specific IPC guidelines
Leishmaniasis in the United Kingdom: Experience of a national multidisciplinary team meeting in a non-endemic setting
Get PDFIntroduction: Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. Disease phenotypes are heterogenous, and diagnosis is frequently delayed. Treatment is often challenging, and international guidelines recommend consultation with experts. The UK Leishmaniasis Multidisciplinary Team (UKLMDT) meeting provides an accessible online forum for clinicians to discuss cases of leishmaniasis, facilitating access to expertise and enabling local care for patients where possible.Methods: Three years of UKLMDT discussions, from its inception in November 2021 to October 2024, were reviewed using electronic patient records. An anonymous feedback questionnaire was sent to referrers. Data regarding treatment outcomes for patients discussed up to June 2024 were gathered using a separate questionnaire completed by their responsible clinician. Results: The UKLMDT contributed to 139 patient discussions involving 80 patients over in total over the study period. Just over half of individuals (45/80; 56.2 %) had cutaneous leishmaniasis, a quarter had visceral leishmaniasis (20/80; 25 %) and a tenth had mucosal leishmaniasis (8/80; 10 %). Seven patients (8.8 %) were found not to have leishmaniasis. In total, 24/80 (30 %) of patients were immunocompromised, but only in four cases (5 %) was HIV the cause of immunosuppression. All visceral leishmaniasis cases were acquired in Europe, and the majority acquired their disease in Spain. Leishmania donovani complex was the commonest causative agent overall, including in visceral and mucosal disease, whereas Leishmania Viannia subgenus was commonest in cutaneous leishmaniasis. Patients with mucosal or visceral leishmaniasis were more frequently immunosuppressed than those with cutaneous leishmaniasis. Outcomes and feedback on the UKLMDT were generally positive. Discussion: The experience of the UKLMDT specialist forum provides insight into leishmaniasis in the UK, a non-endemic setting. Key findings include that southern Europe is the primary destination where UK-based leishmaniasis is acquired, and that Leishmania donovani complex (most likely Leishmania infantum) in immunosuppressed hosts is an important cause of mucosal leishmaniasis in Europe. The UKLMDT offers equitable access to expertise for a rare disease in the UK, as well as serving as a model for national provision of multidisciplinary advice for other rare diseases.</p
A multicenter, prospective, randomized, open-label, blinded endpoint trial of intravenous thrombolysis with tenecteplase for acute non-large vessel occlusion in extended time window (OPTION): Rationale and design
Get PDFBackground and Objectives: Recombinant human tenecteplase (TNK) tissue-type plasminogen activator (rhTNK-tPA, also named tenecteplase) is non-inferior to alteplase when given up to 4.5 hours after acute ischemic stroke (AIS) within 4.5 hours. Whether intravenous tenecteplase compared with supportive care improves the outcome of patients with AIS due to non-large vessel occlusion (non-LVO) between 4.5-24 hours is uncertain. The Tenecteplase for Acute Non-large vessel occlusion in the Extended Time Window (OPTION) trial aims to test the efficacy and safety of intravenous tenecteplase in patients presenting between 4.5-24 hours after symptom onset who have a non-LVO and evidence of salvageable tissue on perfusion imaging. Methods: OPTION is a multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) study. Patients with AIS due to non-LVO and evidence of salvageable brain tissue within 4.5-24 hour time window meeting eligibility criteria will be allocated in a 1∶1 ratio to tenecteplase or standard medical treatment. A target mismatch profile is defined as ischemic core volume <50 mL, a mismatch ratio ≥1.2, and a mismatch volume ≥10 mL. A total of 568 patients will provide >80% power to detect a 12% absolute difference in the proportion of patients achieving an excellent functional outcome (modified Rankin scale [mRS] 0-1 at 90 days) at the two-sided 0.05 significance level. The primary efficacy outcome is excellent functional outcome (mRS 0-1) at 90 days. Secondary efficacy outcomes include disability level (ordinal distribution of mRS) at 90 days, functional independence (mRS 0-2) at 90 days, reperfusion at 24 hours, infarct volume at 24 hours, early clinical response at 24 hours, the National Institutes of Health Stroke Scale (NIHSS) change from baseline at 7 days/discharge, health status and quality of life at 90 days. Safety outcomes include symptomatic intracranial hemorrhage within 36 hours, systemic bleeding within 90 days, and mortality within 90 days. Discussion: The OPTION trial (NCT05752916) will provide evidence regarding the efficacy and safety of tenecteplase 4.5 to 24 hours in patients with AIS due to non-LVO.</p
Maternal Dietary Anthocyanidin, Dietary Inflammatory Potential, and Risk of Small-for-Gestational-Age in China
Get PDFBackground: The interaction between anthocyanidin intake and dietary inflammatory potential might influence small-for-gestational-age (SGA), but the available evidence has been limited. This study aims to examine the associations of anthocyanidin with SGA and whether these associations change with dietary inflammatory potential. Methods: Data were derived from 2244 pregnant women enrolled in a community-based, randomized controlled trial between 2015 and 2019 in China. Anthocyanidin intake was calculated with the use of validated food-frequency questionnaires. The energy-adjusted dietary inflammatory index (EDII) was determined by aggregating data from 33 food parameters. Infant birth outcome measurements were obtained from hospital records. Associations were assessed by generalized estimating equations with adjustment for confounding factors.Results: During 39.7 gestational weeks of follow-up, 234 SGA cases occurred. The median intake of anthocyanidin was 28.7 mg/d. Higher consumption of total anthocyanidins (OR: 0.96, 95% CI: 0.95 to 0.97), cyanidin (OR: 0.96, 95% CI: 0.95 to 0.97), and peonidin (OR: 0.96, 95% CI: 0.96 to 0.97) subclasses was associated with a reduced risk of SGA. EDII was associated with an increased risk of SGA (OR: 1.08, 95% CI: 1.03 to 1.12). In addition, we observed that higher anthocyanidin intake was inversely associated with EDII (β: −0.40, 95% CI: −0.46 to −0.34). The inverse anthocyanidin-SGA association was mostly greater among women in the highest tertile of EDII (OR: 0.67, 95% CI: 0.65 to 0.68) compared with the lowest tertile. Conclusions: Higher anthocyanidin intake was inversely associated with SGA, especially among women with higher EDII scores.</p
Genomic Drivers of Pyrethroid Resistance Escalation in the Malaria Vector Anopheles funestus Across Africa
Get PDFAggravation of pyrethroid resistance threatens malaria control; yet, its molecular basis remains elusive. This study used a comprehensive multi-omics framework integrating 7-year gap temporal RNA-Seq, PoolSeq Whole Genome, and functional analyses, to uncover resistance escalation mechanisms in Anopheles funestus Africa-wide. Spatiotemporal analyses (2014–2021) reveal massive overexpression of novel genes (V-ATPase, tubulin alpha-1, transposase), alongside canonical resistance genes (P450s, cuticular proteins, chemosensory). Epigenetic regulators (histone H3/4, glycine N-methyltransferase) were greatly overexpressed in highly resistant mosquitoes, suggesting resistance modulation. P450-based signatures of selective sweep were detected with a drastic change in the rp1 and the P450 CYP9K1 in Central Africa. Noticeably, genomic variations at the cytochrome P450 reductase (CPR) gene were selected including a N70I mutation in Malawi [0% (2009)–80% (2021)] and a 5.9 kb promoter duplication in Ghana. Transgenic expression in Drosophila confirmed CPR-70I enhances pyrethroid resistance when co-expressed with P450-CYP6P9a, uncovering a novel CPR-mediated mechanism in intensely resistant mosquitoes. This study highlights novel candidate genes for marker development to track the spread of intensely resistant mosquitoes across Africa.</p
A Prospective Cohort Study Investigating the Prognostic Performance and Utility of 3 Severity of Illness Scores
Get PDFBackground: Mortality prediction is difficult in resource-constrained settings. Severity of illness scores have not been tested in hypoxemic adults in Africa. Research Question: How well do 3 severity of illness scores (Modified Early Warning Score [MEWS], quick Sequential Organ Failure Assessment [qSOFA], and Universal Vital Assessment [UVA]) and the ability to walk predict mortality in hypoxemic hospitalized adults in Africa? Study Design and Methods: All adults with hypoxemia on admission in 5 hospitals in Kenya, Malawi, and Rwanda between November 2022 and April 2023 were prospectively enrolled in the study. The capability of MEWS, qSOFA, UVA, and the ability to walk was evaluated to predict hospital mortality. In exploratory analyses, differences in disease severity and mortality were compared between sites. Results: A total of 24,724 admissions were screened; 1,732 of these were hypoxemic and had complete outcomes data. Median age was 52 years (interquartile range, 36-70 years), and hospital mortality was 35% (n = 615). Sites varied in the completeness of score variables (44%-99%). Increased odds of mortality were found using predefined thresholds for each score; UVA predicted best, with an OR of 3.40 (95% CI, 2.54-4.56). The area under the receiver-operating curves for MEWS, qSOFA, and UVA were 0.66 (95% CI, 0.62-0.69), 0.66 (95% CI, 0.63-0.69), and 0.69 (95% CI, 0.65-0.72), respectively, using complete case analysis; they were 0.61 (95% CI, 0.58-0.64), 0.65 (95% CI, 0.62-0.67), and 0.66 (95% CI, 0.64-0.69) with missing data imputed as normal. Inability to walk independently was also predictive of mortality (OR, 2.26; 95% CI, 1.62-3.15). UVA pairwise comparisons showed different mortality between 4 of 6 sites; these differences remained significant in 2 comparisons when adjusting for illness severity. Interpretation: In the largest prospective cohort of hypoxemic adults in Africa to date, MEWS, qSOFA, UVA, and ability to walk on admission had modest capability to predict hospital death. Missing data were common. Imputation of missing variables only slightly altered performance, and thus it is possible that scores could be simplified. UVA had the best predictive performance and may be cautiously used to aid clinical decision-making, quality improvement, research comparisons, and risk adjustment.</p
Photogrammetric Localisation of Electromagnetic Sensors for Detecting Anomalies in Heritage Internal Wood Structures
Get PDFThe strength estimation of built-in historical timber requires extensive investigation of internal wooden structures and properties, which cannot be mapped using only optical surveying methods. In most cases, additional equipment is required, including invasive techniques such as drilling resistance technology and sensitive methods such as ultrasonics or electromagnetic (EM) sensor technology. Thus, the localisation of a measuring device within a whole timber structure and the uniform registration of internal and external wooden structures is missing. In this article, we investigate the capability to localise the EM sensor, which will be used in future research activities for in-depth analysis of internal timber structures. The position of the EM sensor will be captured during the 3D timber imaging using different optical methods to provide a reference between the external wood surface and digitised internal structures. The data quality is compared and evaluated according to the measurement method using geometric features and visual expertise.</p