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Geographical Differences in SARS-CoV-2 Antibody Response Dynamics and Neutralisation Profiles to Mild COVID-19: Lessons from a UK-Uganda Comparison.
Get PDFBackground: The global SARS-CoV-2 pandemic revealed stark variability in clinical outcomes across populations, underscoring the need for region-tailored vaccination strategies. To inform standardised global immunisation efforts, this study compared longitudinal binding antibody responses and neutralisation capacities in mild COVID-19 cases from Uganda and the United Kingdom (UK). Methods: IgG responses to spike (S) and nucleocapsid (N) proteins, along with IgM responses to S and receptor-binding domain (RBD) proteins, were assessed in 29 Ugandan and 14 UK participants over 84 and 82 days, respectively. Antibody levels were quantified using a validated enzyme-linked immunosorbent assay (ELISA), alongside pseudovirus neutralisation assays targeting the D614G variant. Results: Ugandan participants exhibited higher early IgG and IgM levels, particularly against spike and RBD, with a rapid onset of responses that waned quickly. UK participants showed a slower but sustained increase in IgG and IgM levels. Neutralisation titres revealed elevated responses in 16.4% of Ugandan participants (>2000) compared to 4.5% of UK participants, suggesting a greater sensitivity to viral neutralisation. Conversely, 31.8% of UK participants exhibited low titres (<25) compared to 14.8% of Ugandan participants, indicating differences in resistance mechanisms. Neutralisation correlated strongly with spike and receptor-binding domain IgG in the UK cohort but showed weaker correlations in Ugandan participants. Conclusions: These findings highlight distinct population-level immune responses, suggesting that geographic factors shaped the quality and durability of SARS-CoV-2 immunity. Tailored vaccination strategies are essential to optimise immunity across diverse populations and improve global epidemic preparedness
Effect of universal no-cost coverage on use of long-acting reversible contraception and all prescription contraception: population based, controlled, interrupted time series analysis.
Get PDFOBJECTIVE: To estimate effects of a policy introducing universal, no-cost public coverage for prescription contraception on use in British Columbia, Canada. DESIGN: Population based, controlled, interrupted time series analysis. SETTING: 10 Canadian provinces. PARTICIPANTS: Prescription medications dispensed to reproductive aged (15-49 years) female residents of British Columbia, Canada, compared with a synthetic control derived from the nine other Canadian provinces and a population based cohort of 859 845 female individuals in British Columbia (age 15-49 years) between 1 April 2021 and 30 June 2024. INTERVENTION: Introduction of a universal contraception coverage policy in April 2023, where the public insurer pays 100% of prescription costs. OUTCOME MEASURES: Number of monthly dispensations for long-acting reversible contraception (LARC) and number of monthly dispensations for all forms of prescription contraception (including LARC), percentage of reproductive aged female residents using LARC and using all forms of prescription contraception, and the proportion of people using prescription contraception who use LARC (LARC market share). Segmented regression models were used to estimate policy effects by comparing the expected outcome values after 15 months of the policy (ie, the counterfactual, derived from trends before the policy and changes in the control) with the observed values, with 95% confidence intervals (CIs) estimated using bootstrapping. RESULTS: In April 2021, 3249 (95% CI 3066 to 3391) LARC prescriptions were dispensed in British Columbia, with a declining slope trend of -17 (-30 to -7) fewer dispensed per month before the policy. Monthly LARC dispensations increased by 1050 (942 to 1487) immediately after British Columbia's policy change and saw a steady increasing trend after the policy introduction. An additional 1273 (963 to 1698) monthly LARC prescriptions were dispensed 15 months after policy implementation compared with the expected volume, representing an estimated 1.49-fold (1.34 to 1.77) increase. Dispensations for all prescription contraception (including LARC) increased by 1981 (356 to 3324) per month, representing a 1.04-fold (1.01 to 1.07) increase. Among the 859 845 female residents aged 15-49 years in the population, 9.1% were using LARC in April 2021. 15 months after the policy, 11 375 (10 273 to 13 013) more individuals were using LARC than expected without the policy, representing an additional 1.3% (1.2% to 1.5%) of the population. The policy led to an additional 1.7% (1.5% to 2.3%) of the population using any prescription contraception. 15 months after the policy, the LARC market share was 1.9% (1.2% to 2.3%) higher than expected. CONCLUSIONS: Universal, no-cost public coverage in British Columbia increased prescription contraception use overall, driven by increased LARC use. As such, cost seems to be an important contributor to contraception use and method selection at the population level
Observational study of antibiotic prescribing patterns by age and sex in primary care in England: why we need to take this variation into account to evaluate antibiotic stewardship and predict AMR variation.
Get PDFBACKGROUND: The drivers of antimicrobial resistance (AMR) likely vary substantially by different demographics. However, few complete, open, national detailed data exist on how antibiotic use (ABU) varies by both age and sex. Here, we aimed to describe the variation in ABU and consider how these age- and sex-specific patterns influence targets and methods for AMR control.
METHODS: Prescriptions of all antibiotics from general practices in England for 2015-23 disaggregated by 5 year age bands and sex were analysed at the national and Integrated Care Board (ICB) level. A descriptive analysis of the relative rates of ABU by age and sex was conducted, followed by an evaluation of comparison metrics of prescription levels between regions. ABU by age and sex were compared with global AWaRe targets, and ABU by age-group was correlated against influenza vaccination introduction, to evaluate the impact of such vaccines on ABU.
RESULTS: From a total of 249 578 795 prescriptions (across 9 years), 63% were given to women and the most prescribed were amoxicillin, nitrofurantoin and flucloxacillin sodium. Prescriptions per 100 000 population varied substantially across sex, age, geographical region, season, year, COVID-19 pandemic period and drug. Most antibiotics were prescribed more to women across most age bands (84% of antibiotics had more prescriptions to females across 50% of age bands). We show how this variation requires a more nuanced approach to comparing ABU across geographies and highlight that AWaRe targets are not met uniformly [prescribing in men aged 11-20 does not fulfil the Access, Watch and Reserve (AWaRe) 80% Access target]. We also show the impact on ABU of time-sensitive interruptions (38% of antibiotics showed a seasonal pattern in the absence of disruptions), including differential age-targeted influenza vaccination, COVID-19 restrictions and a shortage of amoxicillin due to a group A Streptococcus outbreak. However, we found few open data to link age- and sex-specific ABU to relevant AMR.
CONCLUSIONS: These detailed differences in ABU across England suggest that there should be large variation in AMR burden by age and sex. Linkage of this ABU data with similarly detailed open-access AMR data is now needed for better intervention design
Identifying acute kidney injury in children: comparing electronic alerts with health record data.
Get PDFBACKGROUND: Electronic (e-)alerts for rising serum creatinine values are increasingly used as clinical indicators of acute kidney injury (AKI). The aim of this study was to investigate to what degree AKI episodes, as identified using e-alerts, correlated with coding for AKI in the hospital record for a national cohort of hospitalised children and examine whether coding corresponded with 30-day mortality after an AKI episode.
METHODS: A cross-section of AKI episodes based on alerts issued for children under 18 years in England during 2017 were linked to hospital records. Multivariable logistic regression was used to examine patient and clinical factors associated with AKI coding. Agreement between coding and 30-day mortality was examined at hospital level.
RESULTS: 6272 AKI episodes in 5582 hospitalised children were analysed. Overall, coding was poor (19.7%). Older age, living in the least deprived quintile (odds ratio (OR) 1.4, 95% Confidence Interval (CI) 1.1, 1.7) and higher peak AKI stage (stage 1 reference; stage 2 OR 2.0, 95% CI 1.7, 2.4; stage 3 OR 8.6, 95% CI 7.1, 10.6) were associated with higher likelihood of coding in the hospital record. AKI episodes during birth admissions were less likely to be coded (OR 0.4, 95% CI 0.3, 0.5). No correlation was seen between coding and 30-day mortality.
CONCLUSIONS: The proportion of AKI alert-identified episodes coded in the hospital record is low, suggesting under-recognition and underestimation of AKI incidence. Understanding the reasons for inequalities in coding, variation in coding between hospitals and how alerts can enhance clinical recognition is needed
Genome-wide analysis and longitudinal study of Klebsiella pneumoniae in Portugal: Tracing the evolution and spread of carbapenem resistance.
Get PDFBACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has high incidence in Portugal, causing severe and often fatal infections. OBJECTIVES: Characterize the evolutionary history and epidemiology of CRKP in Portugal over a 40-year period. METHODS: WGS was performed using the Illumina platform. In silico multilocus sequence typing, surface antigen characterization, and resistance gene detection were subsequently carried out. Core and pan-genome analyses were conducted using Roary. Genomic clusters (GCs) were identified based on a 21-SNP threshold. To estimate the divergence times of the most prevalent sequence types (ST) in the dataset, Bayesian evolutionary analysis was performed using BEAST. RESULTS: Nineteen GCs harboring carbapenemases were identified. The blaKPC-3 gene was the most prevalent carbapenemase, linked to strains circulating in both hospital and community settings, with dissemination patterns at regional, interregional, and international levels. ST15 was the most established sequence type in Portugal, with nine distinct GCs identified in both clinical and environmental samples. Towards the end of 2010s, ST147 and ST13 were responsible for significant outbreaks associated with blaKPC-3. CONCLUSIONS: This study underscores the value of genomic-based surveillance in understanding the evolution of high-risk clones coupled with the spread of AMR determinants. The data obtained highlights a shift in ST predominance across the country from an ST15-dominated period and strongly associated with ESBL dissemination, to the emergence of ST147 and ST13 CRKP clones, the latter associated with international transmission. This work further stresses the importance of cross-border surveillance efforts to monitor the emergence and dissemination of CRKP strains and inform risk assessment and prevention
Towards the Development of a Conceptual Framework of the Determinants of Pre-eclampsia: A Hierarchical Systematic Review of Biomarkers.
Get PDFBACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. There are several determinants of individual pregnant women's risk of developing pre-eclampsia, including biomarkers and ultrasound markers. OBJECTIVE: A conceptual framework to collate and summarise the extensive body of literature on biomarkers (including ultrasound markers) associated with pre-eclampsia, through a hierarchical systematic literature review. SEARCH STRATEGY: Medline, Embase, Health Technology Assessments, Database of Abstracts of Reviews of Effects, Cochrane Library were searched until April 2024. SELECTION CRITERIA: Reviews and cohort studies (> 100 participants) reporting biomarkers associated with pre-eclampsia were included. DATA COLLECTION AND ANALYSIS: Studies were screened by title, then abstract and full text. Evidence was prioritised from umbrella reviews, followed by systematic reviews and then observational studies. Associations were assessed for strength of association and quality of evidence using GRADE. MAIN RESULTS: The biomarker domain included 40 individual determinants of pre-eclampsia. Of these, there were 18 biomarkers with definite or probable associations based on moderate-strong quality evidence across markers of angiogenic imbalance, fetal-placental unit function, inflammatory and immune markers, and physiological markers. Vascular endothelial growth factor, human chorionic gonadotropin, inhibin-A, maternal serum placental protein-13, and interferon-gamma had definite associations based on high-quality evidence. CONCLUSION: Biomarkers associated with the development of pre-eclampsia highlight the multi-factorial aetiology of the syndrome. The addition of biomarkers, including ultrasound, will optimise the prediction of pre-eclampsia and enable individualised risk stratification
Thirty years after the Cairo declaration on population & development: have family planning measurements caught up?
Get PDFINTRODUCTION: The 1994 International Conference on Population Development (ICPD) initiated the transition of family planning (FP) programmes from focusing on population control to promoting human rights and women's empowerment. The indicators used to measure success of FP programmes, however, continue to focus on estimating modern contraceptive uptake. Contraceptive Prevalence Rate (CPR) and unmet need are the main indicators used. We aim to assess the views of those working within the FP community from the Global North and South on the use of current indicators for FP programmes. While there have been calls for new measures, understanding the barriers to changing existing ones is essential for adopting and implanting these new measures. METHODS: We conducted semi-structured interviews with 31 participants from five distinct groups; academics, NGO workers, government officials, funding agency workers and advocates. Participants were working in countries worldwide, including both the Global North and South; the latter were mostly based in Francophone West Africa. Interviews explored several themes including FP targets and indicators. We applied a thematic analysis. RESULTS: Participants' views ranged from those who believed in the need to eradicate current indicators from FP programmes to those expressing contentment with current indicators and their benefit in measuring success. Most of the participants acknowledged the benefit of indicators in assessing progress or as a starting point, yet they identified multiple limitations to their use, including the possibility of implicit coercion, skewing training to focus on long-acting reversible contraceptives (LARCs) promotion, and prioritising modern contraceptive methods over natural ones. Some expressed anxiety that challenging the status quo could lead to funding cuts. Participants identified challenges in adopting new indicators and emphasised that funding for FP programs remains largely concentrated among international agencies based in the Global North, which results in maintaining certain traditional demographic approaches. CONCLUSION: Current indicators affect the understanding of success of FP programmes and influence how FP services translate on the ground. We provide international stakeholders' perspectives on the barriers to be overcome to support development of new indicators, including non-use of contraception as a success as long as it is a full, free and informed choice
Shigella-trained pro-inflammatory macrophages protect zebrafish from secondary infection.
Get PDFShigella is an important human pathogen that has no licensed vaccine. Despite decades of seminal work suggesting that its pathogenicity relies on inflammatory cell death of macrophages, the in vivo role of macrophages in controlling Shigella infection remains poorly understood. Here, we use a zebrafish model of innate immune training to investigate the antibacterial role of macrophages following a non-lethal Shigella infection. We found that macrophages are crucial for zebrafish larvae survival during secondary Shigella infection. Consistent with signatures of trained immunity, we demonstrate that bacteria are cleared during training and that protection is independent of the secondary infection site. We show that following Shigella training, macrophages have altered mono- and tri-methylation on lysine 4 in histone 3 (H3K4me1/me3) deposition and shift toward a pro-inflammatory state, characterized by increased tumor necrosis factor alpha (TNF-α) expression and antibacterial reactive oxygen species (ROS) production. We conclude that macrophages are epigenetically reprogrammed by Shigella infection to enhance pro-inflammatory and protective responses
A vaccine chatbot intervention for parents to improve HPV vaccination uptake among middle school girls: a cluster randomized trial.
Get PDFConversational artificial intelligence, in the form of chatbots powered by large language models, offers a new approach to facilitating human-like interactions, yet its efficacy in enhancing vaccination uptake remains under-investigated. This study assesses the effectiveness of a vaccine chatbot in improving human papillomavirus (HPV) vaccination among female middle school students aged 12-15 years across diverse socioeconomic settings in China, where HPV vaccination is primarily paid out-of-pocket. A school-based cluster randomized trial was conducted from 18 January to 31 May 2024. The study included 2,671 parents from 180 middle school classes stratified by socioeconomic setting, school and grade level in Shanghai megacity, and urban and rural regions of Anhui Province. Participants were randomly assigned to either the intervention group (90 classes, 1,294 parents), which engaged with the chatbot for two weeks, or the control group (90 classes, 1,377 parents), which received usual care. The primary outcome was the receipt or scheduled appointment of the HPV vaccine for participants' daughters. In intention-to-treat analyses, 7.1% of the intervention group met this outcome versus 1.8% of the control group (P < 0.001) over a two-week intervention period. In addition, there was a statistically significant increase in HPV vaccination-specific consultations with health professionals (49.1% versus 17.6%, P < 0.001), along with enhanced vaccine literacy (P < 0.001) and rumor discernment (P < 0.001) among participants using the chatbot. These findings indicate that the chatbot effectively increased vaccination and improved parental vaccine literacy, although further research is necessary to scale and sustain these gains. Clinical trial registration: NCT06227689
Multimorbidity and health system priorities in Zimbabwe: A participatory ethnographic study.
Get PDFMultimorbidity, increasingly recognised as a global health challenge, has recently emerged on the health agendas of many countries experiencing rapid epidemiological change, including in Africa. Yet with its conceptual origins in the global North, its meaning and possible utility in African contexts remains abstract. This study drew together policymakers, public health practitioners, academics, health informaticians, health professionals, and people living with multimorbidity (PLWMM) in Zimbabwe to understand: What is the transformative potential and possible limitations of elevating multimorbidity as a priority in this setting? To bring these different perspectives into conversation, we used a participatory ethnographic design that involved a health facility survey, participant-observation, in-depth interviews, audio-visual diaries, and participatory workshops. We found that multimorbidity was new to many respondents but generally viewed as a meaningful and useful concept. It captured the increasingly complex health profile of Zimbabwe's ageing population, foregrounded a range of challenges related to the 'vertical' organisation and uneven funding of different conditions, and revealed opportunities for integration across entrenched silos of knowledge and practice. However, with capacity and momentum to address multimorbidity concentrated within the HIV programme, there was concern that multimorbidity could itself become verticalized, undercutting its transformative potential. Participants agreed that responding to multimorbidity requires a decisive shift from vertical, disease-centred programming to restore the comprehensive primary care that undergirded Zimbabwe's once-renowned health system. It also means building a policy-enabling environment that values generalist (as well as specialist) knowledge, ground-level experience, and inclusive stakeholder engagement. We conclude that the 'learning' health system represents a promising conceptual lens for unifying these imperatives, providing a tangible framework for how knowledge, policy, and practice synergise within more self-reliant, person-centred health systems able to respond to complex health challenges like multimorbidity