Acta Tropica

Successive dengue virus (DENV) outbreaks can progressively reshape population immunity influencing disease expression and diagnostic performance. Objectives The aim was to evaluate the impact of secondary infections across sequential outbreaks on clinical severity, serotype dynamics and diagnostic concordance. Methods This retrospective study analyzed 976 febrile-stage samples from three sequential outbreaks in Misiones, Argentina. For serotyping and clinical analyses, 869 viremic samples confirmed by at least one direct method were included (2016: n=512; 2019: n=148; 2024: n=209). Additionally, 318 samples, including 107 non-viremic cases, were used to compare NS1 rapid diagnostic tests (NS1 Ag) and RT-PCR. Viral serotyping and clinical and laboratory markers of disease severity were evaluated. Results Secondary infections increased from 31.05% (2016) to 43.24% (2019) and 53.87% (2024) (p<0.0010). Serotype distribution shifted from DENV-1 predominance in 2016 (95.12%), DENV-1/DENV-4 co-circulation in 2019 (60.71%/39.29%), and DENV-2 predominance in 2024 (97.60%). Secondary infections were associated with more severe disease manifestations, particularly in 2024, with higher hematocrit (p=0.0120) and hemoglobin (p=0.0080), lower white blood cells (p=0.020) and platelet counts (p=0.0030), and elevated AST (p=0.0007) and ALT (p=0.0130). Concordance between NS1 Ag and RT-PCR was lower in secondary infections (k=0.457 vs k=0.759, p=0.0013). Conclusions The rising frequency of secondary infections may affect both clinical severity and diagnostic performance during outbreaks. The clinical impact was more evident in 2024, likely associated with the introduction of a new serotype. These findings highlight the need for optimized surveillance and diagnostic strategies to improve case detection and patient management during epidemics.

Background Rabies is a zoonotic neglected public health problem associated with animal bites, especially domestic carnivores claiming 59,000 deaths annually predominantly in developing countries of Africa and Asia. There is a high risk of exposure among rural communities endemic with animal rabies where adoption of prevention strategies is minimal. This study determined the prevalence of suspected rabies exposure, associated factors, and delayed post-exposure care-seeking among animal-bite human cases in Busia district, Uganda. Methods: This was a cross-sectional study that involved 332 consecutively sampled animal bite human cases that occurred within the period 2023 to 2024. Data for the bite cases from records were collected using a data abstraction tool. In addition, interviewer-administered semi-structured questionnaires were used to collect data on sociodemographic, animal-related and environmental characteristics. Approximate bite locations were collected using Global Positioning System (GPS) coordinates via Kobo collect. Analysis was carried out in STATA 17 using mixed effects modified Poisson regression for factors associated with suspected rabies exposure. Results: The median age of the bite cases was 18 (IQR: 9-36) with the male gender predominantly affected. The prevalence of suspected rabies exposure was 53.6% (95% Confidence interval - CI: 46.8-60.3). Factors associated were urban versus (vs) rural residence (adjusted prevalence ratio-aPR: 1.04, 95%CI: 1.00-1.08), being bitten by a stray animal (aPR: 1.28, 95% CI: 1.22-1.35) and wild animal (aPR: 1.22, 95% CI: 1.14-1.30) vs domestic animal, vaccination status of the biting animal i.e. vaccinated vs unvaccinated (aPR: 0.76, 95% CI: 0.69-0.85), provoked vs unprovoked bites (aPR: 0.82, 95% CI: 0.79-0.86), and distance to nearest river ([&ge;]5km) vs <5km (aPR: 0.93, 95% CI: 0.87-0.99). The prevalence of delayed post-exposure seeking was 23.0% (95% CI: 16.5-31.1) among the suspected rabies exposures. Conclusion: The study reveals a high prevalence of suspected rabies exposure. Factors associated are multidimensional i.e. are of human, animal and environmental origin. The one health paradigm should be emphasized during routine surveillance of rabies-related cases. The study observed that 1 in 5 bite cases delayed to seek care post bite exposure. We recommend collaborations between sectors, routine vaccination and awareness campaigns, and monitoring of wild carnivore populations and environmental dynamics in rabies-related surveillance.

Close to 50% of all bird species are reservoirs of potentially pathogenic fungi, including those listed as priority by the World Health Organization. In Malawi, data on diversity, pathogenic potential, and ecological avian sources of medically important yeast are scarce. A cross-sectional study using a descriptive approach was conducted in Blantyre, Southern Malawi, to characterise medically important yeasts recovered from environments contaminated with excreta/guano from synanthropic pigeons. A total of 20 samples were collected from 4 peri-urban areas, which yielded 71 yeast isolates. To assess the pathogenic potential of the environmental isolates, we compared their phenotypic virulence traits with those of 21 clinical yeast isolates collected from referral hospital laboratories. Pichia kudriavzevii (39%) and Candida orthopsilosis (30%) were the commonly isolated species in the pigeon-guano-contaminated environments. Candida parapsilosis sensu stricto (29%) and Candida albicans (24%) constituted most of the clinical yeast isolates. Half of the species isolated in the pigeon-guano-contaminated environments were also identified among the clinical isolates. A majority of the environmental isolates showed virulence traits similar to or stronger than clinical isolates. The findings underscore the critical need for integrated surveillance under the One Health framework, especially in bird-inhabited spaces close to human settlements.

Background: Sexual and gender minorities (SGM), including men who have sex with men (MSM) and transgender women, often face stigma, legal constraints, and limited access to sexual and reproductive health services. These conditions restrict prevention and care, increasing vulnerability to HIV and human papillomavirus (HPV) infections. While strong HIV-HPV interaction is documented in high-income settings, evidence from low- and middle-income countries remains limited. This study examines the burden, co-infection dynamics, and progression of HPV infection and anal dysplasia among MSM and transgender women in Pakistan. Methods: A cross-sectional study was conducted between September 2015 and October 2016 among men who have sex with men (MSM) and transgender women recruited from sexual health and antiretroviral therapy centers in Karachi. Eligible participants were aged [&ge;]18 years and self-reported anal sex within the past 6 months (N=298). Two anal specimens were collected for HPV DNA detection and genotyping using PCR, and anal squamous intraepithelial lesions (ASIL) were assessed cytologically using the Bethesda classification. Associations were estimated using Cox proportional hazards regression algorithms to derive prevalence ratios (PRs). Results: Among participants, 44% (n=133) were living with HIV. Overall HPV prevalence was 65.1%, rising to 87% among HIV-positive individuals compared to 48% among those without HIV ({chi}{superscript 2}p[&le;]0.001). Likewise 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV ({chi}{superscript 2}p[&le;]0.001). HIV infection was strongly associated with HPV acquisition (adjusted PR 2.81, 95% CI 2.16-3.82). Among HPV-positive participants (n=194), 58.8% were co-infected with HIV. High-risk HPV was highly prevalent among those living with HIV (83.2% vs. 35.3% ({chi}{superscript 2}p[&le;]0.001)), with HPV16 as the dominant oncogenic type. Multiple HPV infections were more common among HIV-positive individuals ({chi}{superscript 2}p[&le;]0.001), and HIV seropositivity was 3.43 (95% CI: 2.55-3.51) times higher among those with high-risk HPV. Co-infected participants demonstrated prolonged smoking, longer duration of sex work, high-intensity sex work with limited condom negotiation, and higher prevalence of anal warts (all p<0.05). Anal dysplasia (ASIL) was present in 35% of participants and was higher among HIV-positive individuals (42.4% vs. 28.1%, p<0.001). HIV-HPV co-infection was independently associated with ASIL (adjusted PR 1.75, 95% CI 1.07-2.88), while high-risk HPV further amplified this risk (PR 3.04, 95% CI 1.75-5.26). Conclusion: These findings demonstrate a biological continuum in HIV-positive MSM and transgender women, where HIV increases HPV acquisition, persistence, and multiplicity, accelerating progression to anal dysplasia. This reflects a syndemic shaped by biological interaction and structural vulnerability. Integrating HPV screening and vaccination within HIV services is essential to interrupt progression to cancer in this high-risk population.

Maternal health during pregnancy is critical for favorable birth outcomes and long-term wellbeing of both mothers and infants. Women in rural, malaria-endemic regions face unique biological and socioeconomic challenges that may increase the risk of adverse pregnancy outcomes (APOs). This study investigated the incidence and determinants of APOs among pregnant women attending antenatal care at Webuye sub-County Hospital in Western Kenya, a rural malaria-endemic setting. We conducted a retrospective cohort analysis utilizing previously collected data of 300 women enrolled during early pregnancy and followed through delivery. Maternal demographic, clinical, and infection-related factors were assessed, and associations with APOs were evaluated using chi-square tests and multivariable logistic regression. Maternal age and gestational age at enrollment were significantly associated with malaria history (P<0.001). Maternal BMI abnormality (124.5/1000 pregnancies), anemia (99.3/1000), fetal or neonatal death (81.3/1000), and preterm birth (43.8/1000) were observed (all P<0.001), suggesting a substantial burden. Younger mothers (<20 years) and older mothers (>35 years) were significantly more likely to develop anemia (P =0.026), and prior malaria infection further increased anemia risk (P =0.02). Abnormal urinalysis findings indicative of urinary tract infection were significantly associated with low birthweight (P =0.031). No significant associations were found between APOs and infant sex, parity, gravidity, or maternal ABO blood type. These findings highlight a substantial burden of APOs in this rural population, exceeding national and global estimates. Strengthening malaria prevention, nutritional support, urinary infection screening, and encouraging early antenatal care attendance are critical to improving maternal and neonatal outcomes. Targeted interventions for adolescent and older mothers, along with enhanced point-of-care diagnostics, may reduce preventable complications in similar resource-limited, malaria-endemic settings.

Abstract Background: The sanitation crisis poses a significant public health risk, leading to diseases like diarrhea, cholera, and typhoid, which impede children's health and development in developing countries like Uganda. Improving sanitation infrastructure is crucial for safeguarding child health and future generations. However, the link between sanitation and children's health is complex, influenced by various factors. This investigation in Gulu scrutinizes the correlation between sanitation practices and child well-being, considering moderating factors such as age, climate, and consistent water accessibility. Methods: The study used a convergent parallel design with equal priority. The Social Ecological Model, Social Learning Theory, and Diffusion of Innovations Model guided it. Researchers collected data from 10 health facilities and 317 households, using purposive and simple random sampling. They used sampling proportions proportional to village size within strata. The researcher analyzed quantitative data using SPSS with factor analysis, structural equation modeling, and multivariate analysis. To analyze qualitative data, they used DQA Minor Lite software, which facilitated thematic analysis. Results: The finding shows 56.8% of households had low socio-economic status. Sanitation was poor; 24.9% household had improved latrines, 20.5% had handwashing facilities with soap, and 68.1% used basic anal cleansing. For nutrition, 38.5% of children were malnourished by MUAC; by Z-scores, 28.7% were stunted, 16.4% underweight, 13.6% wasted. Diarrhea affected 62% of children. Climate worsened sanitation: 48.3% had latrines collapse from floods, and 63.4% of waterborne diseases occurred in both dry and wet seasons. Moderation analysis on childhood diarrhea shows that sociocultural factors ({beta} = -0.20, p < 0.001), sanitation ({beta} = -0.15, p < 0.001), and health system response ({beta} = -0.18, p < 0.001) reduced diarrhea. Climate change increased risk ({beta} = 0.15, p < 0.001) and moderated sanitation effects ({beta} = 0.01, p < 0.05). Models explained 10-14% variance. Age and water access had no moderating effect. While childhood malnutrition shows that sociocultural factors ({beta} = -0.43, p < 0.001) and health system response ({beta} = -0.13, p < 0.001) reduced malnutrition. Sanitation had no effect ({beta} = 0.01, p > 0.05). Age increased malnutrition risk ({beta} = 0.28, p < 0.01) and moderated sociocultural effects ({beta} = 0.16, p < 0.001), but not sanitation. The model explained 21% variance, R{superscript 2} = 0.21, p < 0.001. Conclusion: Sociocultural improvements and health system responses lower both diarrhea and malnutrition. Climate worsens diarrhea and alters sanitation's impact. Age worsens malnutrition and changes sociocultural effects. These findings are valuable for policymakers, healthcare professionals, and researchers

Background: Antimicrobial resistance is the world's silent pandemic. The public knowledge, attitudes, and practices (KAP) about antibiotic usage are strongly related to the growing problem in Nepal. Methods: A cross-sectional descriptive survey was done to 263 respondents. Information on KAP regarding antibiotics, primary healthcare sources, and demography was collected through a questionnaire. To identify health literacy gaps and characteristics that contribute to improper antibiotic use, this study assessed these variables across an age group from 18 to 60 years. Descriptive statistics analysis was performed to analyze the data. Results: The majority of respondents were between the ages of 18 and 39 (85.1%), female (63.1%), and had at least a bachelor's degree (67.8%). Significant misunderstandings about antibiotics remained, even though 77.6% of respondents correctly recognized antibiotics as effective against bacteria; 44.1% incorrectly believed that antibiotics cure viral diseases, and 87.8% felt that antibiotics should be stopped right away if adverse effects develop. In practice, 52.9% acknowledged quitting antibiotics as soon as symptoms improved, despite 89.4% consulting doctors. Additionally, 43% of respondents said they have taken antibiotics without a prescription, frequently due to pharmacist recommendations (21.67%) and financial or geographical constraints. The main sources of information were doctors (11.07%) and pharmacist-doctor combinations (14.88%), yet 81.8% of respondents said they had never heard of the phrase antimicrobial resistance. Conclusion: There is a significant lack between theoretical understanding and practical application, despite the high levels of fundamental knowledge toward the prohibition of non-prescription sales. Self-medication and early withdrawal are still common inappropriate practices. It is crucial to implement focused teaching initiatives that highlight the differences between bacterial and viral diseases as well as the risks associated with leftover medicine. It is advised to use digital platforms for younger demographics and to strengthen the role of pharmacists in order to reduce AMR.

This work focuses on the global and partial identification problem for fractional differential equations. We provide a general numerical procedure based on global and local optimization algorithms with two refinements for biological systems that ensure solution positivity and homogeneous parameter units. The method is applied to a new fractional model of Dengue outbreak called the Fractional Homogeneous Nishiura (FHN) model, calibrated using data of newly infected people in Cape Verde. We show that our identification method yields a better fit between data and model solutions than previous approaches and that our FHN model captures the dynamics of Dengue more closely than existing systems.

Background: Persons with disabilities, particularly deaf individuals, remain a largely overlooked population in sexual and reproductive health (SRH) programming globally, with this gap especially pronounced in low- and middle-income countries. Deafness imposes substantial barriers to accessing information and services that are routinely available to hearing peers, further exacerbated in the post-COVID-19 era. This study assessed deaf adolescents' knowledge of and access to SRH education and services in Wakiso District, Uganda, and explored systemic, institutional, community, and adolescent-level factors shaping access. Methods: A mixed-methods cross-sectional study was conducted at Wakiso Secondary School for the Deaf from July 2022 to January 2023. Quantitative data were collected from 70 consecutively sampled deaf adolescents aged 13-19 years using a structured questionnaire. Qualitative data were gathered through key informant interviews (KIIs) with four purposively selected stakeholders and a focus group discussion (FGD) with deaf adolescent students. Qualitative data were analysed thematically. Results: The mean participant age was 17 years (SD {+/-}1.8); 65.7% were female. A large majority (88.6%) had heard of SRH components, and 98.6% perceived a need for SRH education or services. However, 84.3% reported challenges accessing these services at least 85% of the time. No participant had ever received SRH education or services through a formal health facility. The FGD revealed that adolescents' conceptualisation of SRH was narrow, centred on body hygiene and HIV prevention, while service-seeking was reactive and symptom-driven. Five cross-cutting themes emerged from the KIIs and were reinforced by FGD findings: communication barriers; inadequate and inaccessible services; family and community isolation; existing platforms and positive practices; and negative provider attitudes and limited capacity. The school nurse emerged as the sole functional SRH access point for most participants. Conclusion: Despite high awareness and near-universal perceived need, deaf adolescents in Uganda face profound multilevel barriers to SRH access. Structural, psychosocial, and knowledge-related barriers interact to exclude this population from formal health services. Findings call for disability-responsive SRH integration into health systems, training of health workers in accessible communication, community capacity building, and co-design of SRH programmes with deaf adolescents.

Background Oropouche virus (OROV) is an emerging vector-borne virus with rapidly expanding geographic range, increasing case counts, and growing evidence of severe outcomes including neuroinvasive disease and vertical transmission. Because OROV infection presents with nonspecific febrile illness that overlaps clinically with other viruses including dengue, zika, and chikungunya, accurate molecular diagnostics are essential for patient care and surveillance. Yet existing assays rely on single genomic targets and are vulnerable to detection failure as the virus evolves and reassorts. Methodology/Principal Findings To support diagnostic capacity, we developed and clinically validated a multiplexed qPCR assay targeting three regions of the OROV S segment, incorporating redundancy to preserve sensitivity across viral diversity while enabling robust clinical interpretation. The multiplex also includes an assay targeting RNaseP as an internal sample control to ensure adequate sample processing. We evaluated assay performance using both historical and contemporary OROV strains and validated the assay on contrived serum, plasma, and cerebrospinal fluid samples, assessing linearity, limit of detection (LOD), accuracy, specificity, precision, and sample stability. The assay met or exceeded all predefined acceptance criteria for clinical testing and achieved an LOD as low as 6 copies per reaction for contemporary outbreak strains. We further implemented a logic-based interpretation matrix that reduced false-positive risk while maintaining sensitivity near the analytical LOD. Conclusions/Significance Our assay sensitively and specifically detects OROV RNA in serum, plasma, and cerebrospinal fluid while incorporating safeguards against viral evolution and reassortment. The assay has been approved for use by CLIA at Nexus Medical Labs in 49 U.S. states, expanding access to timely OROV diagnostics in the United States and providing a durable framework for molecular detection of reassorting, rapidly evolving viruses as OROV continues to spread into new regions.

Methicillin-resistant Staphylococcus (MRS) infections are a significant public health concern. Anterior nares serve as a major reservoir and source of spread of MRS ssp. People living with HIV (PLWHIV) tend to be at higher risk of colonisation with MRS organisms due to frequent healthcare exposure. We assessed the prevalence of MRS nasal carriage and associated factors among PLWHIV at the HIV clinic of Kiruddu National Referral Hospital, Kampala, Uganda, from May to July 2024. Nasal swabs from 256 PLWHIV were cultured, and microbiological isolation was performed at MBN Clinical Laboratories. Prevalence was calculated as proportions, and logistic regression identified associations with clinical and socio-demographic factors (p < 0.05). Of 256 participants, 163 (63.7%) carried Staphylococcus, with 82 (32%) identified as MRS carriers (8.9% MRSA, 23% MRCoNS). Frequent hospital visits ([&ge;]3) (adjusted incidence risk ratio [A-IRR] = 1.18 x 107, p < 0.001), second-line antiretroviral therapy (ART) (A-IRR = 3.82, p = 0.041), and unsuppressed viral load (>1000 copies/mL) (adjusted odds ratio [AOR] = 11.3, 95% CI: 2.11-60.58, p = 0.005) were significantly associated with MRS carriage. Mask-wearing was protective against MRCoNS (A-IRR = 1.66, 95% CI: 1.06-2.58, p = 0.026). MRS isolates exhibited high resistance to erythromycin (81.7%) and trimethoprim-sulfamethoxazole (79.3%), but susceptibility to linezolid (93.9%). MRS nasal carriage is prevalent among PLWHIV. Individuals with frequent health care contact and those on second-line ART regimens are more susceptible to MRS colonization, while individuals who wear face masks and those with an undetectable HIV viral load are less susceptible. Antimicrobial Resistance (AMR) surveillance within HIV programs, enhanced infection control, ART adherence, and targeted screening for high-risk groups are critical to mitigate colonization.

INTRODUCTION: Cognitive trajectories may clarify how type 2 diabetes (T2D) and impaired fasting glucose (IFG) relate to dementia risk, but longitudinal associations remain unclear, particularly in the context of stroke. METHODS: Data from 5,631 dementia- and stroke-free older adults (mean age 75 years) from 7 international population-based cohorts were analyzed. Linear mixed-effects models estimated cognitive trajectories during stroke-free and post-stroke follow-up. Glucose status was defined by fasting glucose and prior T2D diagnosis. RESULTS: Over 6.6 years of follow-up (4.5% with incident stroke), T2D was associated with lower baseline cognitive performance compared with normal fasting glucose (-0.14 SD, 95% CI -0.21 to -0.07), but not with faster cognitive decline during stroke-free or post-stroke follow-up. IFG was not associated with lower cognitive performance or faster decline. DISCUSSION: In older adults, T2D was associated with persistently lower cognitive performance but not faster decline, suggesting adverse cognitive effects may be established before late life.

We present a compact pump-and-probe mid-infrared Optothermal Spectrometer (OTHES) equipped with Spatial Probing and Autocorrection (SPAC) optimized for robust intravital application in humans. SPAC-OTHES facilitates alignment stability and spectral comparability across different measurement sessions involving different skin types. Contrary to state-of-the-art, SPAC-OTHES uses camera-based beam detection and an auto-calibration mechanism that enables ca. 73% better spectral reproducibility in intravital measurements in human volunteers than non-calibrated readouts. Moreover, SPAC-OTHES has the potential to lower the glucose quantification error, as demonstrated here in artificial skin phantoms, where an improvement of 52% compared to conventional diode-based detection was observed. The compactness of OTHES, combined with reliable SPAC-readout, has the potential to accelerate commercialization and broad application of biosensors based on mid-infrared spectroscopy.

Background: Antenatal care (ANC) utilization is critical for improving maternal and neonatal health outcomes. Despite the World Health Organization recommendation of at least eight ANC contacts during pregnancy and the implementation of free maternal healthcare policies in Ghana, significant geographic and socioeconomic disparities in ANC utilization persist. This study therefore assessed the spatial distribution and geographically varying determinants of ANC utilization among women in Ghana. Methods: A cross sectional analytical study was conducted using women data from the 2022 Ghana Demographic and Health Survey. The analysis included women aged 15 to 49 years with an index child younger than five years preceding the survey. Descriptive statistics were computed using Stata version 18, while spatial analyses were conducted in QGIS version 3.44. Global Morans I was used to assess spatial autocorrelation, whereas Local Morans I and Getis Ord Gi analyses identified spatial clusters, hotspots, and coldspots of ANC utilization. Ordinary Least Squares (OLS) regression and Geographically Weighted Regression (GWR) models were fitted to assess global and local determinants of ANC utilization. Results: Overall, only 26.0% of women achieved adequate ANC utilization, while 74.0% reported inadequate ANC attendance. Adequate ANC utilization was higher among women with higher education (42.0%) and those from the richest households (41.3%) compared with women without formal education (19.1%) and those from the poorest households (17.6%). Regional disparities were observed, with Western (48.8%), Eastern (48.0%), and Greater Accra (47.3%) regions recording the highest ANC utilization, whereas Savannah (24.7%), Northern (25.8%), and North East (26.8%) regions recorded the lowest utilization levels. Global Morans I demonstrated significant positive spatial autocorrelation (Morans I = 0.457, p = 0.044), indicating geographic clustering of ANC utilization across Ghana. Getis Ord Gi analysis identified significant coldspots within Northern, Savannah, and North East regions, while Central Region demonstrated significant hotspot clustering. OLS regression showed that maternal education (B = 0.284, p = 0.003) and household wealth (B = 0.191, p = 0.011) positively influenced ANC utilization, whereas distance to health facility negatively influenced utilization (B = -0.156, p = 0.019). The GWR model demonstrated improved explanatory performance (Adjusted R-squared = 0.71), confirming substantial spatial heterogeneity in ANC determinants across Ghana. Conclusion: Adequate ANC utilization in Ghana remains low and geographically unequal. Maternal education, household wealth, and geographic accessibility significantly influence ANC utilization, with pronounced disparities concentrated within Northern Ghana. Spatially targeted maternal health interventions aimed at improving education, reducing socioeconomic inequalities, and enhancing healthcare accessibility are required to improve equitable ANC utilization across Ghana.

Wearable digital health technologies may complement traditional gait assessments in amyotrophic lateral sclerosis (ALS) by sensitively capturing real-world mobility changes. In this study, we validated six digital gait metrics derived from ankle-worn sensors in a natural history cohort of 182 individuals with ALS. Investigated metrics correspond to various aspects of gait, including volume, speed, intensity, similarity, variability, and fragmentation. Longitudinal analyses showed significant declines in step count, peak cadence, stride intensity, and stride similarity, with increasing stride duration variability and walking fragmentation over 52 weeks. Many participants exhibited greater relative change in the gait metrics than the self-reported ALS Functional Rating Scale-Revised (ALSFRS-RSE). Stratified analyses revealed that digital metrics captured significant functional decline even in participants with stable walking scores on the ALSFRS-RSE. These findings support the potential utility of these metrics for disease monitoring in ALS clinical care and trials.

Background: The rising prices of cancer medicines have intensified concerns about treatment access and health system sustainability particularly in low- and middle-income settings. Systematic facility level evidence on what medicines is actually available, at what prices, and at what cost to patients remains scarce, constraining evidence-based policy reform. Methods: Using adapted WHO/Health action international methodology, we conducted a cross-sectional survey of 52 cancer medicines across five therapeutic classes at five health facilities in Kisumu County, Kenya. Availability was measured as the proportion of facilities stocking each medicine. Affordability was assessed using days' wages required for the lowest-paid government worker to purchase standard treatment regimens, calculated per one chemotherapy cycle and maximum possible cycles. Results: Overall medicine availability was 48.1%, with marked inter-facility variation. Affordability analysis revealed severe financial barriers. The breast cancer AC regimen required 19.6-47.4 days' wages per full course; cervical cancer cisplatin, 19.8-49.2 days' wages; colorectal FOLFOX, 80.0-303.6 days' wages; and prostate docetaxel reached 437 days' wages at the highest-cost facility. The Social Health Authority's (SHA) KES 550,000 annual ceiling adequately covered cytotoxic regimens for common cancers at competitive prices but was exceeded by 24-116% for HER2-positive breast cancer requiring trastuzumab, with further strain for recurrent cervical and metastatic prostate cancers. Conclusions: Cancer medicines in Kisumu County are inconsistently available and highly variable in price resulting in inequitable access. We call for urgent retail price markup regulation, expanded pooled procurement through KEMSA, inclusion of priority targeted therapies on the Kenya Essential Medicines List, and SHA benefit packages redesigned around full-course regimen costs.

Objective Memory impairment is a frequent comorbidity of focal epilepsy, incompletely explained by seizure frequency or structural pathology. Ictal and postictal hippocampal dysfunction disrupt memory processes, but their cumulative impact remains poorly quantified. This study introduces cumulative hippocampal seizure-related burden metrics and examines their association with long-term memory consolidation. Methods Twenty consecutive patients undergoing stereo-EEG in Marseille (2016-2018) were prospectively included. Continuous stereo-EEG recordings between two memory assessments (30 minutes and one week post-encoding) were analysed. Hippocampal ictal involvement and durations were assessed using epileptogenicity markers and visual stereo-EEG analysis. The postictal period was quantified using permutation entropy. Cumulative hippocampal seizure-related burden metrics (ictal, postictal and combined: c-HipSZB) were computed across hippocampus-involving ictal events. Verbal and visual memory were assessed using standardized recall and recognition tasks. Associations were examined using univariate and multivariate analyses. Results Higher dominant-hemisphere hippocampal burden was associated with poorer one-week verbal memory (performance and retention), independently of most covariates. Higher c-HipSZB was associated with lower total recall performance (RT; free + cued) and RT retention ({beta} = -25.04 and -23.88; R2 = 0.57 and 0.53; p < 0.05) and accounted for the greatest variance in both outcomes (adjusted R2= 0.59 and 0.53; {beta} = -25.45 and -24.27; p < 0.01), particularly when adjusting for epilepsy duration. No robust associations were observed between non-dominant-hemisphere hippocampal seizure-related burden metrics and visual memory. Effects predominantly involved recall. Interpretation Cumulative ictal-postictal hippocampal dysfunction is a major determinant of impaired long-term verbal memory consolidation in focal epilepsy.

Background and Objective: Access to real-world electronic health records (EHRs) remains limited by privacy, governance and annotation constraints, hindering the development of clinical natural language processing models. Realistic synthetic progress notes may provide EHR-like corpora that preserve clinically rigorous information on diagnoses, treatments, symptoms, imaging, laboratory findings and therapeutic trajectories without relying directly on sensitive patient records. This study evaluates whether large language models (LLMs) can generate realistic Spanish prostate cancer progress notes from published case reports, preserving clinical content, temporality and hospital-style conventions.

People living with HIV (PLWH) are known to maintain a degree of immune deficiency despite efficient antiretroviral therapy and may exhibit diminished responses to vaccines. In this study, we assessed the immune response to SARS-CoV-2 infection and vaccines in two geographically distinct PLWH populations. PLWH and HIV-negative (HIV-) participants were recruited from Qu&bec City (QC), Canada, and Bobo-Dioulasso (BD), Burkina Faso, for two visits at 24-week intervals during the predominance of the Omicron variant, from May 2022 to September 2023. Blood samples were collected at each visit for the detection of antibodies against spike (anti-S) and nucleocapsid (anti-N) proteins of SARS-CoV-2 in platelet-free plasma. A total of 360 participants were enrolled. We detected anti-S antibodies in 99% of participants, indicating that nearly all had prior exposure to the SARS-CoV-2 spike antigen, either through vaccination or prior infection. Anti-S titers showed no difference between PLWH and HIV& participants in each location, while significantly higher titers were observed in participants from QC compared to BD. In contrast, anti-N antibodies, indicative of prior infection, were detected in 39% and 86% of the participants in QC and BD, respectively, suggesting that the virus circulated largely in the latter population. No difference in anti-N levels was observed between PLWH and HIV& participants in BD. However, participants in QC had significantly lower titers compared to HIV participants. Overall, this study shows that PLWH develop robust antibody responses to SARS-CoV-2 vaccination, comparable to those observed in HIV& participants. Significant geographic differences were observed in anti-S titers, irrespective of HIV status, with participants from QC displaying higher titers. In contrast, participants from BD had higher anti-N antibody prevalence and titers, reflecting more SARS-CoV-2 infections in BD than in QC. Finally, analysis of anti-S antibody titers against several circulating variants revealed significantly lower levels in unvaccinated participants and in those vaccinated with monovalent vaccines in BD. No significant difference was observed between monovalent and bivalent vaccines administered in QC. All authors have seen and approved the manuscript.

Rationale: Efficacious dose selection for anti-tuberculosis drugs has traditionally relied on achieving plasma exposures above the minimum inhibitory concentration, but this approach has not consistently aligned with clinical outcomes. Objectives: We sought to identify early pharmacokinetic-pharmacodynamic targets most predictive of clinical efficacious dose. Methods: We conducted a back-translational, pharmacokinetic-pharmacodynamic simulation-based analysis of 15 anti-tuberculosis drugs. Using pharmacokinetic data from multiple biological matrices and a range of pharmacodynamic metrics, we established candidate exposure-response targets for attainment. We systematically evaluated the predictive accuracy of each target pair against established clinical doses to formulate a decision-making framework linking key drug properties to the most predictive targets. Measurements and Main Results: Depending on the target used, projected clinical doses varied widely - both within and across compounds - highlighting the importance of target selection for dose projection and go/no-go decisions. In general, targeting cellular lesion-level drug exposures relative to in vivo preclinical potency provided an effective approach for early dose selection. However, for highly penetrating drugs, targeting site-of-action therapeutic exposures in the caseum was more predictive of clinical dose. Based on these findings, we developed a preliminary dose prediction tool that enables drug developers to estimate clinically relevant dose ranges of compounds using in vitro and early in vivo data. Conclusions: This work establishes and validates a simple, evidence-based framework to standardize early translational decision-making on dose selection of anti-tuberculosis candidates in development.