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Improving meningitis surveillance and diagnosis with machine learning: Insights from São Paulo.
Get PDFINTRODUCTION: Meningitis, an inflammatory condition of the membranes surrounding the brain and spinal cord, can be caused by various agents. Bacterial meningitis is particularly severe due to its high morbidity and mortality rates. This study aims to develop machine learning (ML) models to classify the aetiology of bacterial meningitis using data from the Notifiable Diseases Information System (SINAN) in São Paulo State, Brazil.
METHODS: Data were collected from the SINAN database, including sociodemographic variables, clinical symptoms, and cerebrospinal fluid (CSF) analyses. Five ML models Random Forest, LightGBM, XGBoost, CatBoost, and AdaBoost were applied to classify meningitis cases into bacterial, fungal, viral, and other types. Models were evaluated using metrics such as AUC-ROC, accuracy, precision, recall, F1-score, and MCC.
RESULTS: The CatBoost model demonstrated superior performance, achieving an AUC-ROC of 0.95 for binary classification (bacterial vs. non-bacterial) and 0.85 for multiclass classification (Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae). XGBoost and LightGBM also showed promising results with AUC-ROC scores of 0.94 and 0.92, respectively, for binary classification. The CatBoost model exhibited high sensitivity and reasonable specificity, highlighting its applicability in the rapid and accurate diagnosis of meningitis. SHAP analysis identified variables such as leukocyte count and the presence of petechiae as influential predictors in the models.
CONCLUSION: ML algorithms, particularly CatBoost, XGBoost, and LightGBM, proved highly effective in the differential diagnosis of meningitis, offering a valuable tool for the rapid identification of meningitis types and bacterial serogroups. These techniques can be integrated into public health protocols to improve meningitis outbreak responses and optimize patient treatment
Effect of repurposed simvastatin on disability progression in secondary progressive multiple sclerosis (MS-STAT2): a phase 3, randomised, double-blind, placebo-controlled trial.
Get PDFBACKGROUND: Despite the success of immune modulation in the treatment of relapsing multiple sclerosis, disability progression is a major problem driven by multiple mechanisms. Comorbidities (eg, vascular risk) and ageing are thought to augment these neurodegenerative pathologies. In the phase 2b MS-STAT trial of simvastatin (80 mg) versus placebo in secondary progressive multiple sclerosis (SPMS), the adjusted difference in brain atrophy rate between groups was -0·254% per year: a 43% reduction. In this phase 3 MS-STAT2 trial, we aimed to assess the efficacy of simvastatin versus placebo in slowing the progression of disability in SPMS.
METHODS: This phase 3, randomised, double-blind, parallel group, placebo-controlled clinical trial was conducted at 31 neuroscience centres and district general hospitals in the UK. Participants aged 18-65 years with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) of between 4·0 and 6·5 were eligible and randomly assigned (1:1) to oral simvastatin (80 mg) or matched placebo for up to 4·5 years, based on a minimisation algorithm within an independent and secure online randomisation service. All participants, site investigators, and the trial coordinating team were masked to treatment allocation. The primary outcome was time to 6-month EDSS confirmed disability progression (an increase of at least 1 point if EDSS score at baseline visit was less than 6·0 or an increase of 0·5 point if EDSS score at baseline visit was 6·0 or more) assessed in all randomly assigned participants (intention-to-treat analysis) without imputation. This study is registered with ClinicalTrials.gov (NCT03387670) and is on the ISRCTN registry (ISRCTN82598726). The study is completed.
FINDINGS: Between May 10, 2018, and July 26, 2024, 1079 patients were screened for eligibility and 964 participants were randomly assigned, with 482 (50%) in the placebo group and 482 (50%) in the simvastatin group. Of all 964 participants, 704 (73%) were female and 260 (27%) were male, with a mean age of 54 years (SD 7). 173 (36%) of 482 participants in the placebo group and 192 (40%) of 482 participants in the simvastatin group had 6-month confirmed disability progression (adjusted hazard ratio 1·13 [95% CI 0·91 to 1·39], p=0·26). Although no emergent safety issues were seen, there was one serious adverse reaction (rhabdomyolysis) in the simvastatin group. 12 (2%) of 482 participants in the placebo group and five (1%) of 482 participants in the simvastatin group had a cardiovascular serious adverse event.
INTERPRETATION: The MS-STAT2 trial did not show a treatment effect of simvastatin in slowing disability progression in SPMS. Simvastatin use in multiple sclerosis should be confined to existing vascular indications.
FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme, UK Multiple Sclerosis Society, and the US National Multiple Sclerosis Society
Characterization of an IL-8 cleavage inhibition assay to determine the functionality of anti-SpyCEP antibodies in human sera.
Get PDFExposure to Group A Streptococcus leads to a broad spectrum of disease and sequelae, as the bacterium employs a wide range of virulence factors to facilitate colonization of the host, propagation and onward transmission, disrupting both innate and adaptive immune responses. The protease SpyCEP has a crucial role in contributing to bacterial immune evasion by impairing neutrophil recruitment and killing of bacteria through the cleavage of interleukin-8 (IL-8). Given this critical function, SpyCEP represents a key vaccine antigen and quantifying functional anti-SpyCEP antibodies represents not only an important marker of vaccine efficacy, but also a tool to dissect the natural immune response. Here, we report the development and characterization of an IL-8 cleavage inhibition assay to measure the function of anti-SpyCEP antibodies in human sera. The assay was demonstrated to be sensitive, highly specific, linear and reproducible, and suitable for evaluating the function of anti-SpyCEP antibodies induced in humans in vaccine clinical trials and in observational studies of natural immunity
Evolution of child acute malnutrition during war in the Gaza Strip, 2023-2024: retrospective estimates and scenario-based projections.
Get PDFNutritional status has been compromised by ongoing war and restrictions on food deliveries in the Gaza Strip. We developed a mathematical model that outputs retrospective estimates and scenario-based projections of acute malnutrition prevalence among children given caloric intake and other factors. We present here the model and its application to the crisis in Gaza. We extended an existing mechanistic model for weight change as a function of energy balance, calibrating it to represent variability in growth curves observed in pre-war Gaza. We simulated open cohorts of children exposed to time-varying caloric intake, infant exclusive breast-feeding prevalence, incidence of infectious disease and coverage of malnutrition treatment, while allowing for adult caloric sacrifice to supplement child intake in times of food scarcity. The model accurately replicates growth standards, pre-war growth patterns and expected parameter dependencies. It suggests that a considerable increase in acute malnutrition occurred in northern Gaza during early 2024. Projections for late 2024 include a serious nutritional emergency if relatively pessimistic assumptions are made about food availability. The model may hold considerable promise for informing decisions in humanitarian response but requires further validation and development
Evaluating predictive values of umbilical cord arterial lactate for adverse newborn outcomes among term-births in northern Uganda: A cross sectional analytical study.
Get PDFOBJECTIVE: Birth asphyxia is one of the leading causes of death for neonates worldwide. Lack of an objective cost effective test to predict poor newborn outcomes at birth affects the ability to respond appropriately. This study determined predictive values of umbilical cord arterial lactate in relation to adverse neonatal outcomes.
METHODS: This was a cross-sectional analytical study conducted between March 2018 and March 2019 at two hospitals in Northern Uganda. A total of 2655 women admitted for birth and their newborns were recruited. At birth, umbilical cord arterial blood was tested for lactate using the Nova Biomedical StatStrip Xpress meter. Apgar scores were assessed at 5 min by trained research midwives. Area under the receiver operator characteristics curve (AUROC) was calculated relating umbilical arterial lactate (UAL) levels and four outcomes. We modeled the best lactate cutoff level associated with the highest AUROC for the four outcomes.
RESULTS: The estimated AUROC for lactate was: 88.42% for Apgar score <7 at 5 min, 83.35% for resuscitation with bag and mask, 84.55% for oxygen therapy after resuscitation and 87.72% for admission to neonatal care unit. The UAL cutoff value of 5.5 mmol/L was associated with the best AUROC of between 75.81% to 81.75% for the four adverse outcomes with no significant differences when adjusted for infectious disease parameters. The sensitivity, specificity, PPV, and NPV were; 78.95%, 86.48%, 23.54%, and 98.73% for Apgar scores <7 at 5 min, 64.40%, 88.11%, 36.59%, and 95.87% for resuscitation with bag and mask, 67.17%, 87.20%, 30.23%, and 96.99% for oxygen therapy after resuscitation, and 77.17%, 86.15%, 22.27%, and 98.65% for admission to the special care unit, respectively.
CONCLUSION: Umbilical cord lactate point-of-care (POC) estimate of ≥5.5 mmol/L predicts adverse neonatal outcomes. This test may be used to trigger early interventions and intensified neonatal care complementing the clinical Apgar score assessment in settings like Uganda
Mainstreaming agrobiodiversity in planet-friendly school meals for children: a scoping review.
Get PDFThe global shift away from healthy, diverse, and sustainable diets threatens children's health and futures. Although school gardens and home-grown school feeding can reconnect children with nutritious, sustainably produced food, these interventions are often implemented separately and with little attention to agrobiodiversity, which is a cornerstone for sustainability and healthy diets. Via a scoping review of 124 articles from 35 countries, we identified wide-ranging and complementary benefits of these interventions beyond health and education. The benchmark of the species used in these interventions against cultivated, predicted, and listed edible plants shows that agrobiodiversity is underused. Despite fragmented and incomplete evidence, our research shows that these interventions can jointly drive profound transformation. Realising this potential demands systemic shifts toward holistic, rights-based approaches that overcome surmountable barriers and build objective, sustainable, and resilient food systems delivering planet-friendly school meals
Grimontia hollisae Sepsis in a 9-Month-Old Female Infant: A Case Report.
Get PDFGrimontia hollisae, an uncommon cause of sepsis, was identified in a 9-month-old infant in Africa without confirmed seafood consumption. Prompt diagnosis through blood culture and targeted antibiotic therapy ensured recovery, emphasizing the need for increased awareness, enhanced diagnostic tools, and active monitoring of emerging pathogens in tropical and resource-limited regions. We present a case report involving a 9-month-old infant who exhibited symptoms of acute gastroenteritis. The blood culture revealed G. hollisae. We treated the infant on empirical first-line antibiotics of IV ceftriaxone, IV gentamicin, zinc tablets, and syrup paracetamol for 5 days after which the child was discharged on oral metronidazole following resolution of symptoms. This case highlights the importance of G. hollisae in causing sepsis in infants in tropical settings. It also emphasizes the need for blood culture investigation and administering the appropriate antibiotics in the diagnosis of children presenting with suspected sepsis
Improving performance in radiation oncology: An international systematic review of quality improvement interventions.
Get PDFNational cancer audits and registers have highlighted significant national and international variation in patient care and outcomes. Quality Improvement (QI) is mandated in radiation oncology but the interventions designed to support QI in this field remain poorly understood. This paper seeks to assess the types of QI interventions in radiation oncology, the QI evaluation design and their impact on process of care measures and patient-related outcomes. MEDLINE and EMBASE were searched systematically for studies of QI interventions in radiation oncology between 2000 and 2024. The studies needed to identify the quantitative or qualitative impact of the QI intervention on process of care measures or patient-related outcomes. Study results were summarised using narrative synthesis and appraised using the Quality Improvement Minimum Quality Criteria Set (QI-MQCS). 26 papers were included in the analysis. The majority of studies were conducted in the USA (n = 13) and in Europe (n = 7), with only two studies conducted at a national level. Ten studies covered all tumour types, with six specifically focusing on head and neck cancers, two each on prostate and nasopharyngeal cancers, and one study each examining lung, cervical, rectal, and breast cancers. The aspects of care evaluated most frequently were those relating to reducing waiting times or increasing utilisation of radiotherapy as per guidelines (n = 15), followed by those seeking to reduce radiotherapy contouring variability (n = 5) and those involving the management of symptoms during or after radiotherapy treatment (n = 6). Only 42 % of studies reported funding, with the most frequent funding source being national, government or federal (n = 6). All QI interventions across the 26 studies were successful as they resulted in an improvement in a process or patient-related outcome measure. The studies scored between 10 and 15 out of 16, according to the QI-MQCS criteria. Despite substantial investments in cancer research and development, there is a scarcity of information on how to enhance the quality of care in radiation oncology. While there are examples of national cancer audits and registers in a number of countries, much of the research in QI interventions is being conducted in the USA. This situation underscores the need for more comprehensive, well-funded studies and improved training for clinicians to conduct high-quality improvement activities and research. There should be a greater emphasis on the substantial gains that can be achieved by improving existing care in terms of access and outcomes, rather than solely focusing on innovation
Evaluating the level of knowledge of HIV prevention methods and associated socio-demographic factors among adolescents before and after participating in health education in Nimule town of South Sudan.
Get PDFINTRODUCTION: Adolescents in conflict-affected settings often face limited access to health information and other prevention resources, making them more vulnerable to HIV and other sexually transmitted infections. This study assessed adolescents' level of knowledge of at least three HIV prevention methods and sociodemographic characteristics among adolescents and associated with this knwoledge before and after participating in health education in the town of Nimule, South Sudan. MATERIALS AND METHODS: We collected and analysed baseline and endline data from 557 adolescents aged 10-17 aged recruited from HIV-affected households in Nimule town. The surveys were conducted between December 2020 and December 2022. Assent to participate for all participants was obtained from their caregivers while additional informed consent was obtained from adolescents aged 15-17 who were considered empowered minors by the South Sudan Ministry of Health. Adolescents were then recruited into 40 peer-led health clubs and completed a three-month comprehensive sexuality education curriculum developed by the South Sudan Ministry of Health. These participants were then followed up for 24 months, and an endline survey was conducted to collect comparabel data. Binay logistic regression analysis was used to assess the level of knowledge of at least three mIV prevention methods in line with UNAIDS conceptualisation of knowledge and associated sociodemographic factors. Associations were reported using adjusted odds ratios. RESULTS: Of the 768 adolescents enrolled, 557 were surveyed at baseline and endline with 301 (54.0%) being females and 276 (46.0%) males. The median age was 14 years (IQR: 11-16) at baseline and 15 years (IQR: 12-17) at the endline survey. The proportion of adolescents who knew at least three methods of HIV prevention increased from 465 (83.5%) at baseline to 556 (99.8%) at the endline survey. Unemployed adolescents had a 99% reduced chance of knowing at least three HIV prevention methods (aOR 0.01, 95% CI: 0.002-0.025, p < 0.001), whereas adolescents who self-rated their health as excellent had a 46% lower chance (aOR 0.56, 95% CI: 0.27-1.14, p < 0.025). CONCLUSIONS: The increase in knowledge of at least three methods of HIV prevention at the endline survey highlights the important role peer-led health education programs plays in closing gaps in HIV prevention among adolescents in conflict-affected settings like South Sudan
Comparative assessment of macrophage responses and antileishmanial efficacy in dynamic vs. Static culture systems utilizing chitosan-based formulations.
Get PDFThe discovery of novel anti-leishmanial compounds is essential due to the limitations of current treatments and the lack of new drugs in development. In this study, we employed the Quasi Vivo 900 medium perfusion system (QV900, Kirkstall Ltd, UK) to simulate physiological fluid flow, allowing us to compare macrophage responses and therapeutic outcomes under dynamic versus static conditions. After 24 hours, phagocytosis and macropinocytosis decreased in all cell types under flow conditions compared to static cultures. Under slow (1.45 x 10-9 m/s) and faster (1.23 x 10-7 m/s) flow conditions ((simulating in vivo lymphatic flow), phagocytosis decreased by around 42.55% and 56.98% in peritoneal macrophages (PEMs), 42.21% and 56.11% in bone marrow-derived macrophages (BMMs), and 49.75% and 63.32% in THP-1 cells, respectively. Similarly, macropinocytosis decreased by approximately 40.7% and 62.2% in PEMs, 34.8% and 60.9% in BMMs, and 33.3% and 59.3% in THP-1 cell line under this same conditions. In this study, we further assessed the impact of medium perfusion on drug efficacy and macrophage functions using a Leishmania major amastigote-macrophage assay. We evaluated the performance of both standard and nanoparticle-based drug formulations within dynamic and static culture systems. After 72 hours of medium perfusion, chitosan solution, blank chitosan-sodium tripolyphosphate (TPP) nanoparticles, and amphotericin B (AmB)-loaded chitosan-TPP nanoparticles exhibited a statistically significant reduction in antileishmanial activity by approximately 30-50% under slow flow conditions and 60-80% under faster flow conditions. In comparison, pure AmB showed a 40% decrease in efficacy at slow flow and a 67% decrease at faster flow, both statistically significant. These results highlighted the importance of considering fluid flow dynamics in in vitro studies for a more accurate simulation of in vivo conditions, potentially leading to better therapeutic strategies for cutaneous leishmaniasis (CL)