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Exploring the IS-capades of Klebsiella pneumoniae: insertion sequences drive metabolic loss in obscure sub-lineages.
Get PDFIntroduction. Klebsiella pneumoniae is an opportunistic pathogen that causes a wide spectrum of infections within healthcare settings and the community. Four K. pneumoniae sub-lineages, defined using core gene multi-locus sequence types, are known to cause distinct infections of the nasal and/or upper respiratory passages: SL91 and SL10031 (also referred to as subspecies ozaenae), SL10032 (subspecies rhinoscleromatis) and SL82. These sub-lineages have also demonstrated reduced carbon source utilization, which, in other species, has been linked with high loads of insertion sequences (ISs).Methods. We performed comparative genomics, analysed IS composition and loads and constructed genome-scale metabolic models for available public sequences from these four sub-lineages. These were then compared with other sub-lineages from the wider K. pneumoniae population.Results. The four focal sub-lineages displayed significantly higher IS loads (median range, 88-120 per genome) than other K. pneumoniae sub-lineages (median range, 12-73). Notably, each K. pneumoniae sub-lineage had unique IS profiles, consistent with distinct evolutionary trajectories of IS acquisition and expansion. Across sub-lineages, higher IS loads were inversely associated with the number of metabolic model genes per genome (R2=0.16; P<0.001), as well as predicted aerobic substrate utilization for phosphorus sources (R2=0.39; P<0.001), as per a second-degree polynomial regression model (n=1,664 genomes). Additionally, the four IS-dense sub-lineages displayed a combination of convergent, sub-lineage-specific substrate utilization losses, including the parallel loss of 3-phospho-d-glycerate, d-glycerate-2-phosphate and phosphoenolpyruvate utilization as carbon/phosphorus sources. Finally, inspection of IS insertion sites demonstrated frequent and non-destructive insertion next to transcriptional, carbohydrate and amino acid metabolism genes.Conclusions. IS accumulation in K. pneumoniae was significantly associated with reduced metabolic substrate usage, consistent with an inverse relationship between IS load and metabolic capacity. Despite these losses, the affected lineages still demonstrate substantial metabolic breadth, consistent with early-stage, ongoing reductive evolution
Level and determinants of district primary healthcare system technical efficiency in Ghana: two-stage stochastic frontier analysis.
Get PDFBACKGROUND: Primary healthcare (PHC) is critical towards achieving Universal Health Coverage (UHC). In Ghana, PHC is organised at the district level and plays a key role in the country's pursuit of UHC. However, many districts face challenges not only with limited resources but also with how effectively they are used. We examined how efficiently districts in Ghana use their health resources and what factors are associated with this efficiency. METHODS: We used a two-step stochastic frontier analysis model using data from 181 districts. The output variable was a composite coverage index derived from eight PHC service indicators for 2021, primarily reflecting maternal and child health and infectious disease services. Input variables included district health expenditure for 2020/2021 and the number of health facilities and clinical staff in 2021. We then assessed the associations between efficiency scores generated by the model and health systems, socioeconomic and demographic factors, such as health facility type, insurance coverage, literacy level, Gini coefficient, poverty incidence, urbanisation and population density. RESULTS: On average, districts operated at 87% efficiency, with scores ranging from 65% to 99%. Two factors were associated with the efficiency. First, districts with a higher proportion of PHC facilities tended to use resources more efficiently (coeff=0.151; 95% CI=0.041 to 0.261). Second, districts with greater income inequality were less efficient, measured by the Gini coefficient (coeff=-0.858; 95% CI=-1.146 to -0.252). CONCLUSION: Districts in Ghana have the potential to improve PHC outputs by about 13% on average by better use of existing resources and addressing determinants of efficiency. Findings suggest that districts with a higher proportion of PHC facilities and lower income inequality tend to be more efficient. These patterns highlight the value of strengthening PHC infrastructure and pursuing equity-focused policies as part of strategies to enhance efficiency in district health systems
Geospatial analysis of the impact of Cameroonian Anglophone Crisis conflict intensity on antenatal care utilisation.
No full textBACKGROUND: Adequate antenatal care (ANC) is often unrealised in sub-Saharan Africa (SSA). This is exemplified in the Cameroonian Anglophone Crisis, an ongoing armed civil conflict. Conflict intensity varies nationally, causing differential impacts on healthcare access. This study aimed to quantify the impact of the conflict's intensity on ANC use and identify its geographical variations.
METHODS: We analysed live births from the 2011 and 2018 Cameroonian Demographic and Health Surveys and the 2022 Cameroonian Malaria Indicator Survey. Conflict intensity was measured as the proportion of Anglophone Crisis-related deaths occurring in each division, using Armed Conflict Location & Event Data Project (ACLED) data. Associations between conflict intensity and the proportion of live births attending at least one (ANC1) and at least four (ANC4) ANC visits were assessed using multiple linear regression and geographically weighted regression.
RESULTS: Between 2011 and 2022, North West and South West Cameroon experienced ANC4 compliance declines. North West also experienced an ANC1 decline, but South West experienced an ANC1 increase. There is no evidence for an association between ANC1 and conflict intensity (p = 0.403). There is strong evidence for a negative association between conflict intensity and ANC4 (p = 0.007). A 1% increase in conflict intensity is associated with a 1.14% (95% CI: 0.326, 1.963) decrease in ANC4. There is strong evidence for spatial variation of this relationship (p < 0.001).
CONCLUSIONS: There is strong evidence to suggest that the Anglophone Crisis has adversely impacted ANC use, with varying magnitudes nationwide. Targeted solutions are crucial to mitigate its impacts on sustained ANC use
Baseline determinants of adherence for drug-sensitive TB treatment in a South African prospective cohort: a focus on HIV infection and anti-retroviral therapy, clinical care access, and TB stigma.
No full textBACKGROUND: Inadequate adherence to tuberculosis (TB) treatment increases the risk of treatment failure and recurrence. Identifying factors contributing to poor adherence could refine targeting strategies and optimize resource distribution. We examined specific individual-level factors for TB treatment adherence among adults with drug-sensitive TB, including HIV status, antiretroviral therapy, time to access clinical care, and perceived stigma.
METHODS: Data are from the “TB Mate” cluster-randomized trial, which evaluated a TB treatment adherence intervention across 18 public health clinics in South Africa (PACTR201902681157721). Treatment adherence was measured using smart pillboxes, with pillbox opening recorded as a proxy for the dose taken. Adults in the control group, utilizing the pillbox in silent mode, were included in this analysis. We used logistic regression to model poor adherence (< 80% pillbox engagement), and negative binomial regression to model adherence as a count of pillbox engagement. Directed acyclic graphs informed confounder selection in the models.
RESULTS: Among 1,213 participants (nine clinics) in the control group, 61.2% (742) were male, the median age was 36 years, 63% (769) were living with HIV, with 66% (507/769) on antiretroviral therapy. The median time to access clinical care was 127 min and 95% (1151/1213) reported no perceived stigmatization upon starting TB treatment. Overall 51% (614) exhibited adherence below 80%, with a geometric mean pillbox engagement of 59.6%. Living with HIV was associated with poor adherence to TB treatment, with an adjusted odds ratio of 1.68 (95% confidence interval [CI] 1.27–2.22) for < 80% adherence and an adjusted rate ratio of 0.90 (0.83–0.97) for pillbox engagement, compared to being HIV-negative. Antiretroviral therapy, time to clinical care access, and perceived stigma showed no association with either measure of adherence.
CONCLUSIONS: The low adherence underscores the necessity for TB treatment support interventions, particularly among those living with HIV.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12304-4
Support for the wellbeing of frontline healthcare workers should be incorporated in health emergency preparedness planning.
Get PDFHealth system resilience requires a resilient and well workforce. During health crises, including pandemics and outbreaks of pathogens, frontline healthcare workers can face significant challenges, resulting in personal psychosocial costs for staff members, and organisational consequences for the health systems they work within. Here, we highlight that there is an urgent need to proactively incorporate organisational measures to protect and promote the wellbeing of frontline healthcare staff across all stages of response to health crises. Importantly, this not only involves specific emergency preparedness and planning efforts, but also supporting organisational-level everyday practices that foster staff wellbeing and health system resilience outside of crises
Epidemiologic features of depression and anxiety among homeless adults with healthcare access problems in London, UK: descriptive cross-sectional analysis.
Get PDFBACKGROUND: In England, 354 000 people were homeless on a given night in 2024. It has long been recognised that the physical and mental health of people who are homeless is poorer than for those who are stably housed. There are few peer-reviewed studies to inform health- and social care around depression or anxiety for people who are homeless in this setting. AIMS: To measure the symptoms of depression and anxiety among adults who are homeless and who have difficulty accessing healthcare, and to describe the distribution of symptoms across sociodemographic, health-related characteristics and indicators of social vulnerability. METHOD: We surveyed 311 adults between August and December 2021. We measured anxiety and depression symptoms using the four-item Patient Health Questionnaire (PHQ-4) score. We compared median PHQ-4 scores across strata of sociodemographic, social vulnerability and health-related characteristics, and tested for associations with the Kruskal-Wallis test. RESULTS: The median PHQ-4 score was 7 out of 12, with 38% having scores warranting clinical attention. While PHQ-4 scores were consistently high across a range of socioeconomic, social vulnerability and health-related characteristics, they were positively associated with young age; food insecurity; recent and historic abuse; joint, bone or muscle problems; and marijuana use. The most common barrier to accessing healthcare related to transportation (60%). CONCLUSIONS: People who are homeless and have difficulty accessing healthcare have high levels of depression and anxiety symptoms. Our findings support further coordination between health- and social care sectors
Epidemiology of sleep health and associations with mental health among in-school adolescents in Uganda: A cross-sectional mixed-methods study.
Get PDFOBJECTIVES: Few studies have examined sleep health among African adolescents. We aimed to understand sleep health among Ugandan secondary school students. METHODS: We collected quantitative data in two schools through a survey with items on sleep health and insomnia (using the Cleveland Adolescent Sleepiness Questionnaire, Munich Chronotype Questionnaire and Insomnia Severity Index [ISI]) and mental health with the UNICEF Measuring Mental Health Among Adolescents and Young People at the Population Level (MMAPP) tool. We used regression models to assess characteristics associated with ISI score, and of sleep health with depression and anxiety. We conducted focus group discussions and in-depth interviews with students, parents, teachers, and officials. Quantitative and qualitative analyses were guided by the social ecological model of sleep health. RESULTS: The 358 participants generally reported poor sleep health (assessed by satisfaction, alertness, timing, efficiency and duration), especially among boarding students. The median sleep duration was 5.1 hours (interquartile range 4.2-6.2). Overall, 36 (10.1%) participants screened positive for moderate/severe insomnia (ISI ≥15), with higher prevalence among females than males (12.7% vs. 6.2%; p = .05). Qualitative interviews highlighted that individual (knowledge and attitudes), social-cultural (religious beliefs, family dynamics, academic demands, peer pressure), environmental (school and home conditions, technological influences), and societal factors (national school schedule guidelines) influenced sleep patterns. Depression and anxiety were associated with multiple dimensions of poor sleep health. CONCLUSIONS: Ugandan adolescents face substantial sleep challenges, which are associated with poor mental health. Evidence-based interventions should be adapted for specific social-ecological contexts to improve sleep and mental health in this population
(Un)sweetened deal? Young people's views on the South African Health Promotion Levy and food in Khayelitsha, Cape Town.
Get PDFOn 1 April 2018 the South African Health Promotion Levy on sugary beverages (HPL) came into effect with the goal of lowering the consumption of sugar sweetened beverages (SSBs) across the South African population. The Republic of South Africa, following the economic and nutrition transitions that occurred after the end of Apartheid, has one of the highest rates of obesity in sub-Saharan Africa. Within this context, this qualitative study examined the food choices and food access of young people living in one neighbourhood of Khayelitsha, Cape Town in 2019 during the period soon after the implementation of the HPL. Through seven focus group discussions, we spoke with 71 young people (18-34) about their lives in Khayelitsha, their understandings and perceptions of food choices, food access, health and the HPL. Using a critical theory approach, we assessed the role of on-going income inequalities and high rates of unemployment on the lives of young, low-income South Africans, as well as how this continued to impact their food access, choices, and awareness of health. At the time of this study, the HPL was not having the desired impact in shifting and lowering the consumption of SSBs amongst this population. We used this exploration of the individual experience of the HPL in Khayelitsha as a metric for a critical policy reflection over time; adding to the small number of qualitative studies on this topic, strengthening the evidence for the inclusion of social and historical context in assessing global health interventions in local settings
Randomised clinical trials of COVID-19 vaccines are not designed to study non-specific effects on rare mortality.
Get PDFWe write to the editorial team regarding the recently-published paper “Randomized clinical trials of COVID-19 vaccines: Do adenovirus-vector vaccines have beneficial non-specific effects? (1)” by Benn et al. We have a range of concerns regarding the data quality and the study methodology, that call into question the key findings. The study presents the results of a meta-analysis of nine randomised controlled trials (RCTs) and concludes that there are “marked differences” in the overall mortality impact of mRNA and adenovirus vector vaccines. However the data used in this study cannot possibly support such a claim and we detail below some of the shortcomings of the methodology used in Benn et al. 's manuscript
Collective disruption: consequences of parasitism for collective animal behaviour.
Get PDFHighly coordinated animal groups such as schooling fish, migrating birds and swarming insects are ubiquitous in nature, and these complex displays of collective behaviour emerge from local interactions between individuals. Although collective behaviours are known to confer benefits, they also come with the standard costs of group living, including increased risk of parasite infection. Notably, parasites can have profound effects on individual behaviour, which may in turn affect the inter-individual interactions that drive collective behaviour. Thus, given the commonness of parasites in animal populations and their widely appreciated effects on animal hosts, parasitism may be a key force shaping the ecology of collective behaviour. In this article, we use information transfer as a unifying theme to explore how the effects of parasites on individuals translate to the collective, focusing on four common collective behaviours: decision-making, collective movement, synchronization and construction. We also discuss the implications of parasite-altered collective behaviour for processes such as parasite transmission, wildlife conservation and animal culture