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Impact of a community-led intervention on the uptake of childhood vaccines in Liverpool: A protocol for a synthetic control evaluation
Full text linkIntroduction: Vaccines are our best defence against infectious diseases, yet uptake of childhood immunisation programmes has consistently declined in the UK, with growing concerns around socioeconomic inequalities. Liverpool, in particular, demonstrated some of the lowest uptake rates in England since 2019. In response, the Health Equity Liverpool Project (HELP) implemented a hyper-localised community-led initiative between September 2023 and June 2024 to tackle vaccine hesitancy. Activities included outreach events and school-based engagement across nine sites within Liverpool. Despite promising qualitative evidence, the intervention’s impact on childhood vaccine uptake has not yet been quantified. We aim to evaluate the population level impact of the HELP intervention on the uptake of five childhood vaccines (first and second doses of the measles, mumps, and rubella vaccine (MMR1, MMR2), 6-in-1 vaccine (diphtheria, tetanus, pertussis, polio, haemophilus influenzae type b (Hib) and hepatitis B), pneumococcal conjugate vaccine booster dose (PCV), and rotavirus vaccine) using synthetic control methods. Methods and Analysis: We will analyse publicly available quarterly vaccine uptake data (between April 2019 and March 2025) from the Cover of Vaccination Evaluated Rapidly (COVER) programme for general practices (GPs) in England. The intervention group will be defined as practices located within a 1 km radius of the intervention sites. A synthetic control group will be constructed using non-intervention GPs matched on pre-intervention vaccine uptake, and linked demographic, socioeconomic, and healthcare capacity covariates. Primary outcomes are the uptake of MMR1 and MMR2 vaccines. Secondary outcomes include the uptake of 6-in-1, PCV, and rotavirus vaccines. Average treatment effects will be estimated as the post-intervention difference in uptake between intervention and synthetic control groups. Sensitivity analyses will examine spillover effects, alternative spatial definitions of exposure, the biasing effect of concurrent interventions, and the feasibility of analysis at small area neighbourhood level.Ethics and Dissemination: This study will be conducted as part of the ReCITE project, which has received ethical approval from the Liverpool School of Tropical Medicine Research Ethics Committee (Reference: 24-018) and is funded by the UK Arts and Humanities Research Council (Project Number: AH/Z505341/1). Findings will be shared with the project funder and submitted for publication in a peer-reviewed journal.<br/
Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia: A meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage
Full text linkBackground: Klebsiella pneumoniae causes ∼20% of sepsis in neonates, with ∼40% crude mortality. A vaccine administered to pregnant women, protecting against =70% of K. pneumoniae infections, could avert ∼400,000 cases and ∼80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine-targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. Methods and findings: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and =70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n=14 types). We estimate the top-5 (O1αβ,2α O1αβ,2β, O2α, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ∼99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. Conclusions: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover =70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.</p
Effectiveness and safety of Bufei granules in treatment of preserved ratio impaired spirometry:Study protocol for a randomized controlled trial
No full textIntroduction: Early identification and monitoring of preserved ratio impaired spirometry (PRISm) population and suitable intervention can reduce the incidence rate of chronic obstructive pulmonary disease (COPD) and delay the disease process. Although Traditional Chinese medicine (TCM) has been used to treat COPD for many years, few data are available for the PRISm population. This study aims to evaluate the efficacy and safety of Bufei granules in preventing progression from PRISm to COPD. Methods: This is a multicenter, randomized, double-blind, placebo-controlled trial targeting the PRISm population. One thousand one hundred PRISm patients will be randomly divided into two groups, with the experimental group receiving Bufei granules and the control group receiving placebo granules. The treatment regimen is to take one packet after meals, twice daily, for a period of two years. The main outcome is the incidence rate of COPD, and the secondary outcomes are lung function, COPD screening score, quality of life, clinical symptoms, 6-minute walking distance (6MWD), dyspnea score, biochemical indicators, and economic evaluation. Blood and urine routine tests, liver and kidney function tests, electrocardiogram, and chest computed tomography scans will be employed as safety indicators for the trial, with any adverse events occurring during the trial period being accurately recorded. The planned observation duration per patient is 2 years and will be followed up every 6 months. Discussion: This study will provide evidence to assess the efficacy and safety of Bufei granules in preventing progression from PRISm to COPD. It is expected that PRISm volunteers will show a reduced incidence rate and will exhibit improved lung function and quality of life. The data will be released after the research is completed. Trial registration: ClinicalTrials.gov registration number: NCT06375824.</p
Repeated biannual cross-sectional surveys in primary schools set baseline seasonal and spatial surveillance for malaria and schistosomiasis in the Shire Valley Transformation Programme (SVTP), Malawi
Full text linkControl of malaria and schistosomiasis among school children poses a key public health challenge in Chikwawa District, Malawi. Furthermore, anticipated environmental changes from the Shire Valley Transformation Programme (SVTP), a large-scale irrigation scheme, are expected to both alter transmission of malaria and schistosomiasis. To later inform future disease surveillance and appropriate control interventions, our study sought to establish comprehensive seasonal and spatial baseline epidemiological data. Four cross-sectional surveys were undertaken in 21 primary schools, covering two wet and two dry seasons. A total of 4176 children aged 7–13 years were examined using rapid diagnostic tests for malaria, urine reagent strips with egg-filtration microscopy for urogenital schistosomiasis, and urine-Circulating Cathodic Antigen (CCA) dipsticks for intestinal schistosomiasis. The overall prevalence was 10.8% (95% CI: 9.8–11.7%) for malaria, 36.5% (95% CI: 35.1–38.0%) for urogenital schistosomiasis, and 1.9% (95% CI: 1.5–2.4%) for intestinal schistosomiasis. Co-infection prevalence of malaria and urogenital schistosomiasis was 5.2% (95% CI: 4.5–5.9%). Macrohematuria was at 5.5% (95% CI: 4.8–6.2%) while microhematuria was at 26.2% (95% CI: 24.9–27.6%). Seasonal fluctuations were noted for malaria, whereas schistosomiasis was limited, although both diseases exhibited strong spatial heterogeneity. Alarmingly, malaria exceeded 25% and urogenital schistosomiasis surpassed 50% in certain schools, thus clearly demonstrating currently unmet public health needs. These are set to become further exacerbated by forthcoming SVTP-driven environmental change; hence, we provide critical evidence to guide the Malawi Ministry of Health in strengthening surveillance and preparing integrated disease control.</p
Selectivity screening of cytotoxicity evoked by viper venoms and their toxins after nanofractionation
Full text linkCytotoxicity is a major pathological effect that can occur during snakebite envenoming. To better understand the underlying biochemical and molecular mechanisms behind snake venom-induced cytotoxicity, it is essential to use appropriate in vitro tools for bioassaying cytotoxicity evoked by snake venoms. Identifying the toxins causing cytotoxicity is also important in this regard, particularly in the context of developing more effective snakebite treatments. Cytotoxicity induced by venom toxins can result in local pathologies in snakebite victims, which can result in long-term morbidity, and is frequently observed after bites by medically important vipers. In the present study, we optimized and applied an analytical cytotoxicity profiling platform for in vitro cytotoxicity assessment of viper venoms. Using four cell lines (RPTEC/TERT1, HepaRG, iPSC-EC, HaCat), we applied an imaging analysis assay together with resazurin reduction to identify the mechanisms of cytotoxicity at the level of cell necrosis, extracellular matrix (ECM) degradation and/or cell apoptosis. Strong cytotoxic peaks are consistent with ECM-associated cytotoxic effects, as reflected by pronounced reductions in cell area and monolayer integrity. These cytotoxicity bioassays were integrated into nanofractionation analytics and high throughput venomics, which allowed for the identification of viper venom cytotoxins at the biological and chemical levels. Venom profiling showed ECM degradation as the main cytotoxic mechanism, except for Daboia russelii, which induced necrosis and apoptosis in three cell lines. Cytotoxicity largely disappeared after reversed-phase separation, prompting use of non-denaturing SEC in nanofractionation analytics, which revealed strong cytotoxic peaks for Bothrops jararaca and Calloselasma rhodostoma in RPTEC/TERT1 cells. The methodology presented here combined analytical and biochemical tools allowing rapid cytotoxicity profiling of viper venom toxins in parallel with toxin identification.</p
Public health challenge of hybridization in urogenital schistosomiasis: New insights and one health perspectives from Malawi
Full text linkThe emergence of hybrid schistosomes resulting from interspecies mating between human and animal Schistosoma species is set to reshape the epidemiology of urogenital schistosomiasis in Malawi. Findings from the hybridization in urogenital schistosomiasis (HUGS) study in Malawi confirm the occurrence and circulation of S. haematobium × S. mattheei in humans, livestock and snails, from exemplar studies in Nsanje and Mangochi districts. Introgressed schistosomes complicate traditional diagnosis with atypical egg morphologies that defy standard microscopic identification, challenge current preventive chemotherapy strategies and raise concerns about long-term performance of mass drug administration considering zoonotic transmission inputs. With the recent completion of the multidisciplinary 4-year HUGS investigation, analysis of data reveals expanded infection risk among adults engaged in water-dependent occupations and highlights shared water bodies as key sites for human-animal-snail contact and hybrid emergence. This new One Health perspective introduces climate-driven ecological shifts, poor livestock management and lack of vector control strategies as circumstances that promote hybrid dispersal and environmental persistence. There is an urgent need to revise national schistosomiasis control strategies in Malawi, with incorporation of appropriate One Health dimensions. Looking ahead, better inclusion of hybrid schistosome surveillance into public health frameworks with intervention target indicators is needed to safeguard disease control gains and prevent future resurgence. This article is part of the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.</p
Exploring the importance and preference of sugar feeding behaviour of malaria vectors in sugar plantations of southern Malawi
Full text linkBackground Reliable tools are needed to control opportunistic outdoor biting and resting malaria vectors that remain beyond the reach of indoor targeted interventions. The attractive targeted sugar baits (ATSBs) have demonstrated effectiveness in some settings but have shown limited impact in other areas, in part due to differences in mosquito species’ preferences and the presence of competing natural sugar sources. We evaluated the sugar-feeding preferences of Anopheles gambiae in Chikwawa, southern Malawi, to inform context specific sugar-based vector control interventions. Methods Using three collection tools, CDC Light traps; Prokopack aspirator and the barrier screen, we collected 187 adult anophelines from the Illovo sugar plantations. Collected mosquitoes were subjected to cold anthrone tests in the laboratory to assess the presence of plant sugars in their gut. Additionally, 810 adult Anopheles gambiae s.l., reared in the insectary from wild caught larvae, were exposed in an olfactory-driven choice experiment to identify the most attractive available sugar source in the area. Sugar sources included guavas, melon, bananas, mango, marula and sugarcane. Results Over 40% (n = 74) of the collected Anopheles mosquitoes- including An. gambiae s.l., An. funestus, An. coustani and An. tenebrous were found to have fed on natural sugar sources. For the sugar attractiveness tests for An. gambiae s.l., guava was found to be twice as attractive (IRR = 1.97, 95% CI: 1.49–2.62, p < 0.001) as sugarcane (our reference fruit), followed by banana (IRR = 1.68, 95% CI: 1.26–2.24, P < 0.001), then mango, and melon (IRR = 1.49, 95% CI: 1.11–2.01, P = 0.008) and (IRR = 1.45, 95% CI: 1.08–1.96, P = 0.014) respectively. Conclusion Sugar feeding is a key activity for Anopheles mosquitoes and presents a potential target for control. Understanding local sugar source preferences will help tailor novel mosquito control intervention strategies such as the ATSBs to specific ecological contexts.</p
Exploring the larvicidal and repellent potentials of silver nanoparticles greenly synthesized using three Congolese plant extracts against Anopheles gambiae along with molecular docking analysis
No full textChemical larvicides and repellents have long been used to combat Anopheles gambiae, the primary malaria vector. However, their prolonged application has raised significant concerns regarding environmental toxicity, human health risks, and the emergence of resistant mosquito populations. This study presents a sustainable alternative consisting of green-synthesized silver nanoparticles (AgNPs) derived from Lippia multiflora, Ocimum gratissimum, and Tetradenia riparia. These nanoparticles were characterized using several techniques, including UV–visible spectrophotometry, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FTIR) spectroscopy, revealing their spherical structure with diameters of 20–50 nm and stabilization by plant secondary metabolites. Aqueous suspensions of AgNPs derived from these three plants demonstrated dose-dependent larvicidal efficacy, achieving up to 95% mortality, while creams containing AgNPs from Lippia multiflora and Ocimum gratissimum exhibited an impressive 85% repellent efficiency. Molecular docking studies revealed that secondary metabolites used as capping agents enhanced larvicidal activity by inhibiting angiostensin converting enzyme of Anopheles gambiae (AnoACE2), further demonstrating the synergistic role of these metabolites in stabilising and boosting AgNPs efficacy. These findings highlight the potential of green-synthesized AgNPs as an eco-friendly and effective alternative to conventional chemical larvicides and repellents, addressing a pressing global need for sustainable mosquito control strategies. By leveraging the bioactivity of plant-derived compounds, this approach minimises environmental and health risks while offering high efficacy against malaria vectors. This research underscores the significant role of green nanotechnology in developing innovative solutions to vector control, paving the way for its integration into holistic malaria prevention programs and the fight against other mosquito-borne diseases.</p
Holiday hunger in India: experiences of food insecurity during the school summer holidays
No full textSchool feeding programs are widely used as safety nets and to realise food security. However, food is typically not served when schools are closed during school holidays. Consequently, children and their families may experience food insecurity or increased food insecurity in school holidays, known as holiday hunger. Outside of high-income countries, holiday hunger has received little attention. This study begins to expand the geographical focus in the literature by examining holiday hunger in India during the school summer break. I present primary data from household surveys and interviews conducted in four locations in Rajasthan. I show that many households experience increased food insecurity during the summer, including due to the absence of school meals, but that food insecurity was also high outside of the holidays. I conclude that policy makers and academics must give more attention to temporal lacunae in food provision.</p
The mediating effects of resilience and the symptoms of depression and anxiety on social frailty and quality of life in older heart failure patients
No full textObjectives: To investigate the relationship between social frailty (SF) and quality of life (QoL) in older heart failure individuals and to verify the mediating effect of resilience and the symptoms of depression and anxiety (DA) on this relationship. Methods: A cross-sectional study was implemented to collect data from 443 old HF patients from three tertiary hospitals based on convenient sampling. The measurement tools included a general information questionnaire, the Social Frailty Scale, the 10-item Connor-Davidson Resilience Scale, the Hospital Anxiety and Depression Scale, and the Minnesota Living with Heart Failure Questionnaire. The SPSS PROCESS Marco Plug-in was used to conduct mediation analysis. Results: The regression analysis showed that place of residence, the number of hospitalizations, and New York Heart Association (NYHA) classes were influencing factors of the QoL in older HF patients. The mediation analysis indicated that resilience and the symptoms of DA mediated the relationship between SF and QoL in older HF individuals, with mediating effect sizes of 45.95 % and 64.94 %, respectively. Conclusion: SF was significantly associated with QoL in older HF patients, and resilience and the symptoms of DA mediated the relationship. Interventions paying attention to reducing SF and the symptoms of DA or enhancing resilience are beneficial for improving the QoL in older HF individuals.</p