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Blood culture time to positivity in pediatric patients with bloodstream infection in rural Gambia.
Get PDFOBJECTIVES: There is a lack of data on the time to blood culture positivity (TTP) in pediatric populations in low-income countries. We aimed to assess the host and pathogen factors associated with TTP in children aged under 5 years in rural Gambia. METHODS: Between September 2019 and December 2023, we collected blood cultures from children under 5 years with suspected bloodstream infections. We determined the TTP from the time of culture incubation to when bacterial growth was first detected. RESULTS: Overall, 547 invasive bacteria pathogens were evaluated. The median TTP was 19.2 hours and 70%, 76%, 89%, and 96% of cases had TTP at 24, 36, 48, and 72 hours, respectively. Streptococcus pneumoniae had the shortest median TTP (17.4 hours), whereas Neisseria species had the longest (45 hours). TTP was dependent on the pathogen and independent of age, sex, temperature, clinical outcome, nutritional status, and length of hospital stay. Gram-positive bacteria had shorter TTP than gram-negative bacteria (18.6 vs 19.6 hours, P < 0.01). CONCLUSIONS: In rural Gambia, most blood cultures from pediatric patients would turn positive within 48 hours of incubation. A maximum of 48 hours of observation after the commencement of antibiotic therapy in hospitalized children may be sufficient for clinicians to receive feedback on blood culture results
Imported malaria in Cabo Verde (2010–2024): Risks to post-elimination stability
Get PDFCabo Verde was officially certified malaria-free by the World Health Organization (WHO), following sustained public health interventions and strategic malaria elimination efforts. The country’s National Strategic Plan (2020–2024) emphasized strengthening epidemiological and entomological surveillance at the archipelago’s entry points (e.g., ports and airports), alongside early diagnosis and case investigation to prevent local transmission. However, imported malaria cases remain a persistent threat and challenge to prevent malaria reintroduction to maintain the elimination status. Therefore, this study aims to analyze imported malaria cases in Cabo Verde from 2010 to 2024, characterizing their locations, origins, epidemiological trends and spatial distribution. The findings aim to support evidence-based decision-making to prevent post-certification disease reintroduction. This study used an ecological time-series approach analyzing all confirmed imported malaria cases reported between 2010 and 2024 in Cabo Verde. Data was collected in collaboration with the National Malaria Control Program and the Integrated Surveillance and Response Service. Incidence, mortality, and case fatality rates were calculated. Joinpoint Regression Analysis was performed to assess time trends, and Holt-Winters additive models were applied for time-series forecasting. Spatial data visualization was also conducted. A total of 383 imported malaria cases were reported. A significant increase trend was observed from 2020 to 2024 (annual percentage change - APC): + 25.75%). Forecast models estimate approximately 80 imported cases annually in 2025 and 2026 (-23.1 to 80). Most cases were reported in Santiago Island (68.9%), particularly in Praia (80.5%). The most common sources of imported infection were Guinea-Bissau (N = 90; 23,5%), Angola (N = 73; 19.1%), Senegal (49; 15.4%, and Nigeria (29; 7.6%). Malaria reintroduction risks persist in Cabo Verde, necessitating continuous surveillance and prevention efforts. Understanding the epidemiological trends and future projections is essential for maintaining Cabo Verde’s malaria-free status. Vigilance and strategic interventions, including fast and correct case identification, treatment, and follow-up of imported cases, are some actions that need to be reinforced. Accurate policies, leadership capacity, and necessary resources are key requirements for maintaining and sustaining the elimination
Acceptability of the R21/Matrix-M malaria vaccine alongside existing malaria interventions in the trial context.
Get PDFBACKGROUND: The R21/Matrix-M malaria vaccine has been shown to provide high protective efficacy against malaria in a phase III trial, and has been recommended for use by WHO. The vaccine will soon be deployed at scale in sub-Saharan Africa. This study aimed to understand the caregiver and community acceptability of the R21/Matrix-M vaccine alongside existing malaria prevention interventions, according to the communities of participants in the seasonal R21/Matrix-M phase III trial in Mali. METHODS: Qualitative data were collected to assess the acceptability of the R21/Matrix-M vaccine alongside the three R21/Matrix-M or control vaccine priming injections given in the first year of the trial. A total of 33 in-depth interviews (IDIs), 12 focus group discussions (FGDs) and 45 exit interviews at the trial clinics were conducted with caregivers of trial participants, 18 IDIs and 8 FGDs were conducted with community members, 13 IDIs with community health workers and 8 IDIs with trial field staff. Data were coded using the constructs from Sekhon's theoretical framework on acceptability. RESULTS: Acceptability of the R21/Matrix-M vaccine was driven mainly by the high burden of malaria in the highly seasonal study area and consequent demand for a malaria vaccine, a perceived high efficacy of the R21/Matrix-M vaccine, and a high level of trust and confidence in the trial and trial team. These perceptions of the acceptability of the R21/Matrix-M vaccine led to a reduced perceived importance of seasonal malaria chemoprevention (SMC) among some caregivers, while others viewed R21/Matrix-M, SMC and insecticide-treated nets as complementary. CONCLUSIONS: The R21/Matrix-M vaccine was acceptable to caregivers and communities of participants in the R21/Matrix-M phase III trial in Mali. Implementation research is needed to evaluate and ensure co-coverage of complementary malaria control interventions, including SMC in seasonal settings, in the face of the scale-up of R21/Matrix-M and other malaria vaccines
Optimised medical therapy alone versus optimised medical therapy plus revascularisation for asymptomatic or low-to-intermediate risk symptomatic carotid stenosis (ECST-2): 2-year interim results of a multicentre randomised trial.
Get PDFBACKGROUND: Carotid revascularisation, comprising either carotid endarterectomy or stenting, is offered to patients with carotid stenosis to prevent stroke based on the results of randomised trials conducted more than 30 years ago. Since then, medical therapy for stroke prevention has improved. We aimed to assess whether patients with asymptomatic and symptomatic carotid stenosis with a low or intermediate predicted risk of stroke, who received optimised medical therapy (OMT), would benefit from additional revascularisation. METHODS: The Second European Carotid Surgery Trial (ECST-2) is a multicentre randomised trial with blinded outcome adjudication, which was conducted at 30 centres with stroke and carotid revascularisation expertise in Europe and Canada. Patients aged 18 years or older with asymptomatic or symptomatic carotid stenosis of 50% or greater, and a 5-year predicted risk of ipsilateral stroke of less than 20% (estimated using the Carotid Artery Risk [CAR] score), were recruited. Patients were randomly assigned to either OMT alone or OMT plus revascularisation (1:1) using a web-based system. The primary outcome for this 2-year, interim analysis was a hierarchical outcome composite of: (1) periprocedural death, fatal stroke, or fatal myocardial infarction; (2) non-fatal stroke; (3) non-fatal myocardial infarction; or (4) new silent cerebral infarction on imaging. Analysis was by intention-to-treat using the win ratio-ie, each patient in the OMT alone group was compared as a pair with each patient in the OMT plus revascularisation group, with a win declared for the patient with a better outcome within the pair (a tie was declared if neither patient in the pair had a better outcome). The win ratio was calculated as the number of wins in the OMT alone group divided by the number of wins in the OMT plus revascularisation group. This trial is registered with the ISRCTN Registry (ISRCTN97744893) and is ongoing. FINDINGS: Between March 1, 2012, and Oct 31, 2019, 429 patients were randomly assigned to OMT alone (n=215) or OMT plus revascularisation (n=214). One patient allocated to OMT alone withdrew consent within 48 h and was not considered further. The median age of patients was 72 years (IQR 65-78); 296 (69%) were male and 133 (31%) female. No benefit was recorded in favour of either treatment group with respect to the primary hierarchical outcome assessed 2 years after randomisation, with 5228 (11·4%) wins for the OMT alone group, 5173 (11·3%) wins for the OMT plus revascularisation group, and 35 395 (77·3%) ties between groups (win ratio 1·01 [95% CI 0·60-1·70]; p=0·97). For OMT alone versus OMT plus revascularisation, four versus three patients had periprocedural death, fatal stroke, or fatal myocardial infarction; 11 versus 16 had non-fatal stroke; seven versus five had non-fatal myocardial infarction; and 12 versus seven had new silent cerebral infarction on imaging. One periprocedural death occurred in the OMT plus revascularisation group, which was attributed to decompensated aortic stenosis 1 week after carotid endarterectomy. INTERPRETATION: No evidence for a benefit of revascularisation in addition to OMT was found in the first 2 years following treatment for patients with asymptomatic or symptomatic carotid stenosis of 50% or greater with a low or intermediate predicted stroke risk (assessed by the CAR score). The results support treating patients with asymptomatic and low or intermediate risk symptomatic carotid stenosis with OMT alone until further data from the 5-year analysis of ECST-2 and other trials become available. FUNDING: National Institute for Health and Care Research; Stroke Association; Swiss National Science Foundation; Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-Being; Leeds Neurology Foundation
Using an analogue-digital hybrid clinical data management platform during a two-dose preventive Ebola virus vaccine trial in Goma, the Democratic Republic of the Congo.
Get PDFClinical trials in settings with intermittent or non-existent internet and power connectivity, for example during humanitarian emergencies, present challenges in the synchronisation of data across different sites, in addition to accessing a centralised database in real-time. To overcome these, we designed a novel hybrid analogue/digital data management system which was deployed during the rapid implementation of a Phase III evaluation of a two-dose preventative vaccine for Ebola virus disease in Goma, Democratic Republic of the Congo, from 2019 to 2022. We provided study participants with an Enhanced Participant Record Card (EPRC) that served as eligibility for, and confirmation of, vaccination and was used in combination with Open Data Kit (ODK) electronic case report forms to create an off-grid study participant management system. To understand the utility of the EPRC, we analysed data from 15,327 study participants who received both vaccines and various types of prompts or reminders to return for dose 2, including home visits, telephone calls, or short messaging service (SMS). A total of 53% participants referred to the date on the EPRC as a prompt to return for dose 2 and 36.1% mentioned this as the only prompt. A multivariable generalised linear mixed-effects model showed that those who were not working, those aged 45-64 years or who had a chronic medical condition identified prior to receiving dose 2 were more likely to use the date on the EPRC as a prompt. Our findings demonstrate the utility of this system in the facilitation of decentralised data collection in off-grid locations that may be useful for future trials in complex humanitarian settings. Clinical Trials Registration Number: ClinicalTrials.gov NCT01128790
Disparities in the access and provision of mental health services as part of primary health care: a case study of Ga-South district in the Greater Accra region.
Get PDFMental illness can be as debilitating as physical ailments, yet many mental health patients lack access to quality mental health care in low- and middle-income countries. This study aimed to identify and characterize disparities in access to mental health care, as well as challenges in service provision, in the Ga-South district of Ghana. A qualitative case study design was used, employing purposive and snowball sampling to recruit participants. Sixteen in-depth interviews were conducted with 17 participants, which included one interview with 2 participants. The participants were mental health patients, caregivers of mental health patients, mental health advocates, health promotion officers, and psychiatric nurses in the Ga-South district of Ghana. The findings reveal that stigma, inadequate support, deficiencies in diagnosis and referral, and high treatment costs create substantial disparities in mental health care access. Stigma around mental health constrains both the provision of mental health care by nurses and healthcare-seeking efforts by patients. Diagnosis and referrals of mental health cases are sometimes deficient in the district, with some medical officers and midwives diagnosing mental health conditions inadequately before referrals to psychiatrists. Nurses on the wards also struggle to manage mental health cases, even after receiving mental health training from their facilities. Findings also reveal that some healthcare professionals sometimes exhibit apathy toward mental health issues. The cost of services and medications for patients is also high which prevents patients from seeking care. Additionally, a critical shortage of psychiatrists results in inadequate patient follow-up. The study underscores the urgent need for comprehensive reforms in mental health care delivery to promote inclusion and address disparity issues. It is necessary to ensure equitable access to quality mental health services by addressing workforce shortages and financial barriers, as well as enhancing awareness, training, and efforts to reduce stigma. Prioritizing these reforms will help to create a healthcare system that effectively supports mental health, promoting healthier communities and improving overall health outcomes
Projections of heat related mortality under combined climate and socioeconomic adaptation scenarios for England and Wales
Get PDFThis study projects heat-related mortality in England and Wales at Government region level under combined climate and socioeconomic scenarios, focusing on the implications of different pathways on adaptive capacity and resilience. Using UK specific climate projections and socioeconomic narratives, and employing a timeseries regression analysis we estimated the impacts of consistent pairs of Representative Concentration Pathways (RCPs) and Shared Socioeconomic Pathways (SSPs) on future heat-related health burdens. Our findings indicate significant increases in heat-related mortality under high emissions scenarios, with the highest burden observed in the RCP8.5-SSP5 scenario (2050s: 10,317, 2060s: 19,478, 2070s: 34,027), due to combined high temperatures and population growth and ageing in this scenario. Conversely, the lowest burden is seen under RCP2.6-SSP1 (2050s: 3,007, 2060s: 4,004, 2070s: 4,592), reflecting effective adaptation and lower warming levels. These values represent an increases from a baseline of 634 annual heat related deaths (1981–2021). The contribution of individual drivers, regional variations and the impact of potential power outages during heatwaves were also examined. These projections highlight the combined role of mitigation and adaptation, with a focus on resilience, in response to climate change and demonstrate that adaptation beyond the observed bounds will be required to limit heat related mortality to the baseline level even under low emission scenarios
Heterogeneity in diagnostic criteria for chronic kidney disease of undetermined etiology (CKDu): a systematic review of the literature.
Get PDFBACKGROUND: Chronic kidney disease (CKD) of undetermined etiology (CKDu) is an important public health problem. It is a diagnosis of exclusion and the diagnostic approach varies widely across geographies. We aimed to systematically examine criteria used to diagnose CKDu in published literature. METHOD: PubMed, Medline, Embase, and Web of Science were searched systematically for published studies and conference abstracts pertaining to CKDu using relevant search terms. Systematic reviews/meta-analyses and reviews were screened to identify additional studies. Findings are presented in tables and figures and discussed critically. RESULTS: 60 studies were identified which mention the definition used to diagnose CKDu. A combination of pre-specified estimated glomerular filtration rate (eGFR) and proteinuria/albuminuria cut-offs was used as diagnostic criteria in only 18 studies (30%), while another 11 studies (18.3%) relied solely on proteinuria/albuminuria cut-offs.Nineteen studies classified all CKD patients without any identifiable cause as CKDu irrespective of level of proteinuria/albuminuria. 18 studies excluded patients with significant proteinuria/albuminuria, although cut-offs used for exclusion varied. Limited studies mention the criteria used to exclude diabetes(n = 22) and hypertension(n = 23) related kidney disease, the two most common causes of CKD with wide variability. CONCLUSIONS: There is considerable variability in diagnostic criteria used to define CKDu in epidemiologic studies, especially in excluding proteinuria and other causes of kidney disease. Such heterogeneity may cause misclassification and erroneous estimation of disease burden making comparisons between studies difficult. CLINICAL TRIAL NUMBER: Not applicable
Incidence and forecasting of animal bites and trends in post-exposure prophylaxis (PEP) consumption in East Azerbaijan province
Get PDFRabies is one of the most common human and animal diseases threatening public health, and annually, many people in different parts of the world are treated for rabies. In Iran, challenges arise in obtaining rabies post-exposure prophylaxis (PEP), as these treatments are often imported, and there are problems with the procurement of vaccines and immunoglobulin. Thus, it is necessary to study the incidence of animal bites to inform PEP supply planning. This study analyzed data from 68,682 cases of animal bites registered at rabies prophylaxis centers in Tabriz, Iran. The cumulative incidence of animal bites and the rates of PEP consumption over the study years were calculated. The number of animal bites was forecasted using the Box-Jenkins time series model. From 2015 to 2022, the average annual incidence of animal bites in the covered population was 232 per 100,000 people. During this same period, the average yearly usage of rabies vaccines was 24,853 doses, totaling 1,136,238 units of antirabies immunoglobulin. The mean age of those bitten by an animal was 31.8 years (standard deviation=17.24), with 85% being male. The majority of bites were from dogs (80%), and 58% of the victims resided in rural areas. The average forecasted annual incidence rates for 2023 and 2024 are projected to be 289 and 311 per 100,000 people, respectively. The increasing trend in animal bites necessitates the urgent need for public health interventions, including expanding vaccine supply and implementing targeted education programs to mitigate the risk and financial burden of rabies in East Azerbaijan Province. In addition, managing stray animals, especially dogs, and strengthening the healthcare system and immunization program are essential to reducing the incidence of rabies
Evidence-Based Approaches to Quality Improvement: A Narrative Review of Integrating Bayesian Adaptive Trials Into Health Services.
Get PDFRATIONALE: Quality improvement (QI) in health service programmes aims to make small, incremental changes to increase reach and efficiency. Simple, low-risk programmatic changes can improve services, particularly when supported by robust evidence. However, in health service contexts, there is tension between the need for swift decision-making and the high research standards for conducting methodologically rigorous trials. Randomized trials are rarely used to evaluate these changes due to high costs and long timelines, especially when the changes are expected to result in marginal improvements. Instead, health service programmes frequently introduce changes informed by anecdotal evidence or less robust evaluation methods such as before-and-after comparisons. AIMS: In this paper, we present a narrative review of the concepts underlying Bayesian adaptive trial designs for conducting QI research, highlighting their use in the commercial sector and exploring opportunities for cross-industry learning and future application in healthcare settings. METHODS: Relevant studies were selected based on their contextual relevance to the topic, in keeping with the narrative review approach. RESULTS: Given that programmatic changes typically yield modest improvements, we recommend that adaptive trial designs can strike a balance between obtaining reliable results and avoiding overly large sample sizes. We review how interim analysis and early stopping can be integrated into trials, allowing the level of rigour to be adjusted according to the proramme specifications. CONCLUSION: Adaptive trial designs hold significant promise for enhancing the QI efforts. To ensure that adaptive trial designs can be successfully integrated into health service contexts, tradeoffs should be made between methodological rigour and resource constraints