Antimicrobial Agents and Chemotherapy
● American Society for Microbiology
Preprints posted in the last 7 days, ranked by how well they match Antimicrobial Agents and Chemotherapy's content profile, based on 167 papers previously published here. The average preprint has a 0.11% match score for this journal, so anything above that is already an above-average fit.
Mapahla, L.; Kleinschmidt, I.; Silal, S. P.
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Artemisinin partial resistance has not yet been reported in southern Africa. Therefore, the magnitude of the spread of artemisinin partial resistance in this region is yet to be quantified. Using a two strain metapopulation modelling framework, we explored possible spread of artemisinin partial resistance in eight connected countries with high level of human movement. We explored three scenarios in which artemisinin partial resistance may first enter circulation: low malaria transmission level country; high malaria transmission level country and all countries and compared to an artemisinin partial resistance free scenario. Partial rank correlation coefficient sensitivity analysis was performed to identify key parameters that drive artemisinin partial resistance spread. Our model simulations show that high mobility between countries can increase the spread of mutations associated with delayed clearance. Suggesting that artemisinin partial resistance will be confirmed (>5% partial resistant cases) after 14 years of circulation if it is to appear in southern Africa. We confirm that human movement, both human-to-mosquito and mosquito-to-human probabilities of transmission, were significant and highly sensitive parameters in the spread of artemisinin partial resistance. Human mobility between countries can facilitate the spread of artemisinin partial resistance. More research is needed to identify strategies to preserve the efficacy of artemisinin-based combination therapies in the presence of partial artemisinin resistance, which may eventually lead to treatment failure and necessitate regimen replacement.
Saxe, G.; Shubov, A.; Smith, C. N.; Golshan, S.; Shekhtman, T.; Wilson, S.; Slater, D.; Bair, Z. J.; Beathard, C.; Davis, R. A.; MacElhern, L.; Kao, L. K.; Senowitz, P.; Gosnell, N.; Buchholz, D.; Aguilar-Carreno, H.
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Use of fungal mycelia, which has antiviral properties, constitutes a novel strategy for addressing existing and newly emerging viral diseases. We evaluated safety and feasibility of fungal mycelia (Fomitopsis officinalis and Trametes versicolor, FoTv) for treatment of COVID-19 and assessed its antiviral effects and potential to reduce symptoms. In a randomized, double-blind, placebo-controlled, dual site (UCSD/UCLA medical centers) clinical trial we examined non-hospitalized patients who contracted mild-to-moderate COVID-19 [≤] 96 hours, and experienced symptom onset [≤] nine days, before enrollment. FoTv was safe, well-tolerated, and feasible for COVID-19 treatment. Minor differences in biochemical markers were observed between groups (26 FoTv, 24 Placebo). FoTv significantly reduced the number and severity of symptoms, particularly sore throat/cough, and in vitro SARS-CoV-2 (pseudovirus) cellular infection. In conclusion, FoTv was safe and reduced COVID-19 symptoms and cellular viral infection. Future studies should investigate therapeutic benefits of fungal mycelia for SARS-CoV-2 and other viruses. Clinicaltrials.gov registration:NCT04667247.
Munyangi wa Nkola, J.; Akilimali Zalagile, P.; Lukuke Mbutshu, H.; Kabala Munyemo, S.; Ramazani Bin Eradi, I.; CAMARA, A.
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Background: Artemisinin-based combination therapies remain the mainstay of malaria control strategies; nevertheless, the advent of genetic markers linked to partial artemisinin resistance in Plasmodium falciparum has elicited substantial concern across African settings. To assess the prevalence, geographic distribution, and clinical associations of these molecular markers, we undertook a systematic review and meta-analysis of observational cohort studies.Methods: We conducted a search of cohort studies published between January 2015 and June 2025, following PRISMA 2020 guidelines. We queried databases including PubMed/MEDLINE, Scopus, Web of Science, and CINAHL. Eligibility required prospective enrollment of patients, longitudinal monitoring (therapeutic efficacy studies), and pfkelch13 propeller domain genotyping.Results: A meta-analytical synthesis of 888 isolates from six core prospective cohorts revealed a pooled prevalence of 6% (95% CI: 2.1%-11.8%) for validated pfkelch13 mutations. A profound geographic dichotomy was identified: while West and Central African cohorts maintained a 0% prevalence, East African hotspots showed significant expansion, with prevalence reaching 12.8% in Rwanda and up to 25.5% in Northern Uganda; high statistical heterogeneity (, ) reflects this biological divergence. Conclusions: These findings highlight the established and expanding presence of artemisinin partial resistance in East Africa. Standardized surveillance is essential to adapt malaria control policies across the continent. Keywords: Africa; artemisinin resistance; clinical indicators; pfkelch13 gene; molecular markers; partial resistance; Plasmodium falciparum.
Mwenda, M.; Oliveira, R.; Mambwe, B.; Chiyesu, C.; Bohmeier, B.; Mosler, K.; Phiri, M.; Sinyoolo, A.; Chiposa, V.; Namonje, T.; Munsanje, M.; Ilunga, M.; Chirwa, C.; Mwape, I.; Mumba, D.; Coppee, R.; Stoica, M.-A.; Veiga, M. I.; Drakeley, C.; Pearson, R.; Verity, R.; Chirwa, J.; Mockenhaupt, F. P.; Vvn Loon, W.; Portugal, S.; Simulundu, E.; Bwalya, S.; Miller, J. M.; Chilengi, R.; Fanaka, C.; Bridges, D. J.; Hawela, M.; Hendry, J. A.
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Background Artemisinin derivatives are central to first-line treatment of both uncomplicated and severe Plasmodium falciparum malaria. Emerging artemisinin partial resistance in East Africa threatens to spread across the continent. Methods In two cross-sectional studies in Zambia in 2024, we genotyped the artemisinin resistance-associated gene Pfkelch13. In Kaoma, western Zambia, we evaluated the percentage of patients with day-3 parasite positivity following treatment with artemisinin-based combination therapy, and ex vivo parasite susceptibility to dihydroartemisinin (the active metabolite of artemisinin). We also assessed longitudinal changes in Pfkelch13 mutation prevalence in Kaoma using isolates collected from 2018 through 2026. Results We identified a novel mutation, Pfkelch13 A724E, in 52% (113 of 217) of isolates from Western Province, 51% (94 of 184) of isolates from North-Western Province, and 11.7% (229 of 1,949) of isolates country-wide. In Kaoma, 28% (21 of 75) of patients carrying Pfkelch13 A724E mutant parasites before treatment were parasite positive on day 3, compared with 0% (0 of 23) of patients with the wild-type allele (P=0.003). Within day-3 positive patients, the proportion of A724E mutant parasites increased significantly after treatment (P = 0.013). The prevalence of Pfkelch13 A724E in Kaoma increased steadily from 0% (95% confidence interval [CI], 0 to 22%) in 2018 to 79% (95% CI, 73 to 85%) in 2026. Conclusions A novel Pfkelch13 mutation conferring partial resistance to artemisinin is spreading in Zambia. Additional clinical evaluations are urgently needed in the region. (Funded by the Gates Foundation, INV-048316).
Xu, Q.; Wang, S.; Sun, H.; Wei, X.; Zhong, J.; Cai, J.
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Background: This study aimed to evaluate real-world adverse event (AE) signals of EV to provide evidence-based guidance for its safe clinical application. Methods: Data from the FDA Adverse Event Reporting System (FAERS) database from the period of 2019 Q1-2025 Q3 were analyzed. Disproportionality analysis algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), were utilized to mine safety signals.The time to onset (TTO) was evaluated using the Weibull distribution model. Results: Among 11,697,906 reports, 4,177 EV-treated patients experienced 14,511 AEs. The most common System Organ Classes (SOCs) were skin and subcutaneous tissue disorders (18.23%), general disorders and administration site conditions (13.17%).Multi-algorithm consensus identified 179 positive signals. Alongside known toxicities (rash, peripheral neuropathy, hyperglycemia), potential new signals emerged, including dysgeusia, atypical skin lesions, and myelosuppression. Median TTO was 14 days, with the Weibull {beta} of 0.736, confirming an "early failure" profile. Subgroup analysis revealed toxicity heterogeneity: patients aged [≥]65 and females exhibited stronger signals for fatal severe cutaneous adverse reactions, while patients aged < 65 and males showed higher susceptibility to neurological and metabolic toxicities. Conclusions: The real-world safety profile of EV confirms known toxicities, reveals new risks (e.g., dysgeusia), and shows toxicity concentrated in the first treatment cycle. Clinical practice requires proactive monitoring during the first two weeks using demographic-specific strategies: vigilance for fatal skin toxicity in elderly and female patients, and close follow-up of neurological and metabolic indicators in younger and male populations.
Khan, P. Y.; Govender, I.; McCreesh, N.; Sithole, M.; Mkwanzai, E.; Sweeney, S.; Ording-Jespersen, G.; Wong, E. B.; Hanekom, W.; Houben, R. M. G. J.; White, R. G. M. G. J.; Smit, T.; Smith, M. J.; Fielding, K.; Grant, A. D.
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Background Tuberculosis remains the leading infectious cause of death worldwide. In the WHO African region, declining incidence has coincided with antiretroviral therapy (ART) scale-up, though whether this reflects reduced progression to disease or reduced transmission is unclear. We evaluated how ART and symptom status influence within-household Mycobacterium tuberculosis complex (MTBC) transmission risk. Methods We conducted a case-contact household study in rural South Africa, enrolling index adults with bacteriologically-confirmed pulmonary tuberculosis. MTBC immunoreactivity was measured in all child household contacts (aged 2-14 years) as a proxy measure of within-household transmission. We assessed the influence of index person ART status and symptom status, and explored effect-measure modification of the association between index person HIV status and transmission risk by sex. Results Among 755 child contacts of 296 index persons, effective ART was not associated with within-household MTBC transmission risk (risk ratio [RR], 1.07; 95% CI, 0.66-1.74). Among PLHIV engaged in ART care, WHO TB four-symptom screen (WHO4SS) status was not associated with transmission risk (RR, 0.80; 95% CI, 0.43-1.47), although absence of reported cough reduced risk (RR, 0.61; 95% CI, 0.38-0.96). A pronounced interaction between sex and HIV status was observed: HIV-negative women had the highest within-household MTBC transmission risk (30.5% vs. 14.3% in women with HIV) whereas risks were similar between HIV-positive and HIV-negative men. Conclusions We found no evidence that effective ART or WHO4SS status influenced within-household MTBC transmission risk, though confidence intervals were wide. Absence of reported cough was associated with lower risk, and transmission risk was highest among child contacts of HIV-negative women. These findings suggest reported cough is a useful marker of transmission risk and that routine tuberculosis screening within ART care may reduce transmission from PLHIV; intensified efforts are nonetheless needed to achieve earlier tuberculosis detection in HIV-negative individuals.
Forrer, A.; Obie, E. D.; Bong, R. A.; Ekanya, R.; Njouendou, A. J.; Nji, T. M.; Amuam, A.; Eyong, E. M.; Ndzeshang, B. L.; Nkimbeng, D. A.; Fombad, F. F.; Teghen, S.; Suireng, A.; Ashu, E. E.; Hamill, L.; Enyong, P.; Turner, J. D.; Wanji, S.; Taylor, M. J.
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Abstract Introduction Onchocerciasis is targeted for elimination with community-directed treatment with ivermectin (CDTI). Alternative strategies are needed in areas where transmission persists despite long-term CDTI and/or are co-endemic with loiasis. This study assessed the efficacy of 35-day treatment with 100mg doxycycline on Wolbachia density at 6 months and microfilaridermia and palpable nodules at 30 months post-treatment. Methods A treatment follow-up study was conducted in 20 high-transmission onchocerciasis communities in a co-endemic loiasis area of South-West Cameroon. Community-based directly observed treatment with 100mg doxycycline was administered to community members aged [≥]9 years. Wolbachia clearance at 6-months and treatment efficacy on microfilaridermia and palpable nodules were assessed at 30-months post treatment. Factors associated with reductions in microfilaridermia post treatment, including adherence to doxycycline treatment were assessed with mixed-effects logistic regression. Results Over 92% (2835/3080) of eligible participants took 35 days of 100mg doxycycline over 5 or 6 weeks. This regimen achieved a 62.8% microfilaridermia reduction and 99% palpable nodule reduction in the 720 participants included at follow-up. Wolbachia depletion was observed in 92% of skin samples at 6 months post treatment. The most important factor associated with microfilaridermia after 30 months was having missed at least 7 doxycycline consecutive doses (OR 3.11, 95%CI: 1.17-8.26). Incomplete treatment to a lesser extent was not associated with reduced efficacy at follow-up. Conclusion This large-scale community intervention shows that a 5-week treatment with 100mg doxycycline is feasible and has high curative efficacy against adult O. volvulus as measured by the dramatic reduction in the proportion of palpable nodules at 30-months post treatment. The high efficacy shows the tremendous potential of anti-Wolbachia drugs as part of the arsenal for onchocerciasis elimination and paves the way for the next generation of anti-Wolbachia drugs with shorter treatment courses, which will facilitate the implementation of alternative strategies to accelerate onchocerciasis elimination.
Taylor, A. R.; Foo, Y. S.; White, M. T.
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Background: Reliable inference of Plasmodium vivax recurrence states - relapse, recrudescence and reinfection (the ``3Rs'') - improves estimates of antimalarial efficacy. The R package Pv3Rs features a Bayesian model designed for P. vivax molecular correction, i.e., using parasite genetic data to infer recurrence states. The model is an extension of a prototype built to analyse microsatellite data from the Vivax History (VHX) and Best Primaquine Dose (BPD) trials. Methods: We re-analysed data from 212 VHX and BPD trial participants (493 recurrences) using Pv3Rs, comparing results with those from the prototype and with genetic relatedness estimated using Dcifer, a tool for estimating relatedness based on identity-by-descent. Posterior recurrence state probabilities were computed using both uniform and time-to-event priors: artificial but equal prior probabilities facilitate posterior interpretation, while time-to-event priors leverage all available information and enable re-computation of failure rates. Relatedness estimates were used to identify and correct instances of model misspecification. Results: The Pv3Rs model generated posterior probabilities for all recurrences and was able to jointly model data on all episodes per participant for 89% of participants, compared with 73% using the prototype. Recurrence state probabilities were broadly consistent across methods, though the Pv3Rs model elevated reinfection probabilities slightly. Relatedness estimates exposed various outliers consistent with half-sibling parasites and/or genotyping errors. Outlier correction impacted some per-participant failure probabilities, but reinfection-adjusted radical-cure failure rates of high-dose primaquine remained near 3%, in line with previous findings. Conclusion: Re-analysis of VHX and BPD P. vivax genetic data restates earlier reinfection-adjusted efficacy estimates. It demonstrates the increased computational capability and misspecification sensitivity of Pv3Rs, highlighting a need for careful analyses. Using relatedness-based diagnostics alongside model-based inference, we were able to harness the advantages of model-based inference and provide a framework for future P. vivax molecular correction.
Sevilla-Parra, G.; Bravo-Garcia, F.; Mier y Teran Guevara, M.; Montes-Garcia, A.; Schäfer, A.; Ochoa-Rodriguez, N.; Bienvenu Caballero, M.; Gonzalez Zenteno, S. G.; Pena-Ayala, A.; Tinajero-Nieto, L.; Torres-Valdez, E.; Martinez, D.; Hernandez-Ledesma, A. L.; Medina-Rivera, A.; Alpizar-Rodriguez, D.
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Objective: To characterize pregnancy outcomes and menstrual irregularities in Mexican women with systemic lupus erythematosus (SLE) and identify clinical factors associated with adverse pregnancy outcomes and early-onset menopause. Methods: We conducted a cross-sectional study of women with SLE enrolled in the Mexican Lupus Registry (LupusRGMX) between May 2021 and September 2024. Clinical and reproductive data were collected using standardized questionnaires. Menopause was defined as the absence of menstruation for [≥]12 consecutive months, and early menopause as onset before age 40. Univariable and multivariable logistic regression analyses were used to identify factors associated with pregnancy complications and early menopause. Results: A total of 210 women were included. Median age was 38 years (IQR 29-46) and median disease duration was 4 years (IQR 1-10). Among women with a history of pregnancy (47%), full-term delivery predominated (61%), while pregnancy loss occurred in 26% and preterm delivery in 13%. Pregnancy complications were reported in 9.6%, most commonly preeclampsia (6.7%). Younger maternal age was independently associated with pregnancy complications (OR 0.89, 95% CI 0.83-0.95) and adverse outcomes (OR 0.95, 95% CI 0.92-0.98). Higher disease activity was associated with complications in univariable analysis. Most pregnancies (68.3%) occurred before diagnosis. Early menopause was observed in 6.2% and independently associated with longer disease duration and older age. Conclusion: Younger maternal age was independently associated with adverse pregnancy outcomes, whereas disease activity showed an association in univariable analysis. Most pregnancies occurred prior to SLE diagnosis. Early menopause was associated with longer disease duration, suggesting impact of cumulative disease burden on ovarian function.
Ernandez, J.; Najafi, A.; Roehrborn, C. G.; Lerner, L. B.
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PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [≥] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by <12 months, 1-3 years, and >3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.
Sahal, K.; Amin, S. M. A.; Mostafa, T.; Wang, S.; Colucci, B.; Shafoyat, M. U.; Yuan, Z. -m.; Cheng, G.
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Mosquito-borne diseases continue to pose significant public health challenges worldwide, particularly in densely populated regions of South Asia and parts of North America experiencing increasing vector prevalence due to climate and environmental changes. Commercial mosquito repellents are widely used as a primary preventive measure; however, their efficacy, safety, and public health impacts vary depending on formulation, active ingredients, environmental conditions, and user practices. This study presents a comparative evaluation of commonly used mosquito repellent products in South Asia and North America, including coils, vaporizers, sprays, creams, and Natural repellents. The research aims to assess repellent efficacy against major mosquito vectors, evaluate potential health and respiratory effects associated with prolonged exposure, and analyze consumer awareness and usage patterns across different regions. Laboratory-based efficacy testing and field observations were conducted to compare protection duration, repellency rate, and environmental performance under varying climatic conditions. Safety assessments included analysis of chemical composition, indoor air quality impact, and reported adverse health symptoms among users. The findings indicate significant differences in effectiveness and safety profiles among product categories and geographical regions. Synthetic repellents generally demonstrated higher repellency duration, while herbal formulations showed improved safety and environmental compatibility. The study highlights the importance of standardized evaluation protocols, regulatory oversight, and public awareness in promoting safe and effective mosquito control strategies. These findings may support policymakers, healthcare professionals, and manufacturers in improving mosquito repellent technologies and reducing the burden of mosquito-borne diseases globally.
Wang, M.; Zhao, T.; Wang, H.; Hou, S.; Fu, Y.
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Introduction: To investigate the epidemiological characteristics of chronic kidney diseases (CKD) in China in 2021 and its trends between 1990 and 2021, in the context of significant population growth and lifestyle changes over the past 30 years that have likely influenced the CKD spectrum. Methods: Data on CKD prevalence, mortality, disability-adjusted life-years (DALY), and risk factors were obtained from the Global Burden of Disease Study 2021. The estimated decadal percentage changes were calculated to evaluate changes in trends in prevalence, mortality and disease burden. Results: In 2021, an estimated 118.4 (95% UI 109.4 to 127.5) million people in China were affected by CKD, contributing to 204 230 (95% UI 164 736 to 246 372) deaths and 6.13 (95% UI 5.18 to 7.21) million DALY. Although CKD due to diabetes mellitus and hypertension accounted for less than a quarter of all cases, they were responsible for over 90% of CKD-related deaths. Over the past three decades, CKD mortality and DALY rates have steadily increased, although the prevalence has stabilized in the last decade. Diabetes mellitus type 2 and hypertension have emerged as key drivers of CKD burden in China. Conclusions: The CKD burden in China shows a dual pattern of rising incidence and high mortality from diabetes and hypertension-related chronic kidney disease, alongside persistently high years lived with disability from glomerulonephritis and other causes.
Lum, J.; Jordan, A.; Knigh, P.; Hisamoto, K.
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Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefit in type 2 diabetes and obesity, with recent observational data suggesting favorable associations after transcatheter aortic valve replacement. Whether similar associations exist after surgical aortic valve replacement (SAVR) is unknown. Methods: Retrospective propensity-matched cohort analysis using the TriNetX U.S. Collaborative Network. Adults with type 2 diabetes or obesity (BMI [≥]30 kg/m2) undergoing SAVR were categorized by GLP-1 RA exposure (any use within 3 months before through 1 year after SAVR) versus no use. One-to-one matching was performed on 44 covariates. Primary outcomes were 1-year all-cause mortality, heart failure, acute kidney injury, acute myocardial infarction, cerebral infarction, and atrial fibrillation. Sensitivity analyses included 30-day landmark restriction and falsification outcomes. Results: After matching, 1,984 patients were retained per cohort. GLP-1 RA use was associated with lower 1-year risks of all-cause mortality (4.8% vs 10.4%; HR, 0.44; 95% CI, 0.34-0.56), acute kidney injury (6.9% vs 10.1%; HR, 0.65; 95% CI, 0.49-0.85), myocardial infarction (3.0% vs 5.1%; HR, 0.57; 95% CI, (0.40-0.82), heart failure (11.3% vs 15.7%; HR, 0.68; 95% CI, (0.51-0.90), and atrial fibrillation or flutter (10.1% vs 13.9%; HR, 0.69; 95% CI, 0.54-0.90; all P[≤]006). Cerebral infarction did not differ. In landmark analysis, mortality, heart failure, and acute kidney injury associations persisted; myocardial infarction and atrial fibrillation associations were attenuated. Falsification outcomes were null. Conclusions: Perioperative GLP-1 RA use was associated with lower 1-year cardiovascular event rates after SAVR. These hypothesis-generating findings support prospective randomized investigation.
Ma, X.; Gu, R.; Ma, W.; Xu, Q.; Wang, R.; Wang, W.; Liang, M.; Liu, X.; Yang, X.; Zhuang, L.; Zhang, W.; Zeng, X.; Xu, J.; Xu, X.; Wu, Z.; Xia, Y.; Liu, Y.; Zhou, J.; Zhu, X.; Wang, H.; Dong, Z.; Yang, W.; Dai, Y.; Pan, X.; Li, X.; Wang, Y.; Dong, X.; Wu, X.; Feng, Z.
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Background: Mucopolysaccharidosis type IIIB (MPS IIIB) is a devastating neurodegenerative lysosomal storage disorder caused by alpha-N-acetylglucosaminidase (NAGLU) deficiency. There is currently no approved therapy. We report the 3-month outcomes of a novel intracerebroventricular (ICV) gene therapy in a child with MPS IIIB. Methods: In an open-label, single-center, investigator-initiated trial (ChiCTR2600121466), a single dose of RDGT-101 (2.0E14; vg of an AAV9 vector encoding human NAGLU) was administered via ICV infusion. Primary outcomes were safety and tolerability. Secondary outcomes included serum NAGLU activity, urinary heparan sulfate (HS) excretion, and neurocognitive function. Exploratory analyses included hematological parameters. Results: The patient achieved serum NAGLU activity (17.06 nmol/mL/hour) approaching that of healthy controls (17.75 {+/-} 1.37 nmol/mL/hour) by Month 3, accompanied by a 58.4% reduction in urinary HS. Clinically, previously severe hand and toe contractures resolved, allowing for full extension. Neurocognitive improvements were observed, including clear articulation, logical conversation, and sustained eye contact. Hematological analyses revealed normalized red blood cell indices and improved iron utilization. No dose-limiting toxicities, serious adverse events, or clinically significant laboratory abnormalities were observed. Conclusions: A single ICV infusion of RDGT-101 was safe and well-tolerated in this patient with MPS IIIB. Early biochemical correction was accompanied by marked improvements in somatic, neurocognitive, and hematological parameters. These findings support further investigation of ICV AAV9 gene therapy for MPS IIIB.
Tsai, C.-H.; Chang, Y.-C.; Chang, C.-C.; Wu, W.-C.; Chang, Y.-Y.; Chen, U.-L.; Lee, B.-C.; Hung, C.-S.; Huang, K.-H.; Chueh, J. S.; Wu, V.-C.; Lin, Y.-H.
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Background: Primary aldosteronism (PA) is increasingly recognized as a common cause of hypertension. The 2025 Endocrine Society guideline introduced a simplified diagnostic framework, but its real-world clinical implications remain unclear. Methods: We conducted a multicenter retrospective cohort study of hypertensive patients undergoing PA testing in Taiwan. PA was defined biochemically according to the 2025 Endocrine Society criteria. Multivariable logistic regression identified factors associated with PA diagnosis and aldosterone-targeted therapy. Among patients with suppressed renin (?1 ng/mL/h), restricted cubic splines evaluated the adjusted association between renin and PA probability. Results: Among 18,766 patients undergoing PA testing, 6,760 (36.0%) met diagnostic criteria for PA. PA was associated with older age, female sex, lower potassium, resistant hypertension, and a higher antihypertensive medication burden. Among patients with suppressed renin, lower renin remained significantly associated with higher adjusted PA probability. However, only 39.0% of patients with PA received aldosterone-targeted therapy, including 28.2% who received mineralocorticoid receptor antagonist therapy within 6 months and 9.4% who underwent adrenalectomy during follow-up. Lower renin, higher aldosterone, lower potassium, and resistant hypertension were associated with aldosterone-targeted therapy, while younger patients with fewer comorbidities were more likely to undergo adrenalectomy. Conclusions: Using the updated diagnostic framework, PA was highly prevalent among hypertensive patients undergoing PA testing. Nevertheless, many patients who met these biochemical criteria did not receive aldosterone-targeted therapy in routine care. These findings highlight the potential treatment implications of broader PA recognition and support the development of practical pathways to guide MRA therapy, adrenalectomy referral, and individualized management.
Iggidr, Y.; Ruktanonchai, N. W.; Benhana, B.; Turbe, V.; Bauzile, B.; Ward, A.; Cohen, J.; Pothin, E.; Champagne, C.
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Malaria control programs are increasingly tailored at subnational scales; however, neighboring areas remain connected through human mobility, allowing parasite importation that may undermine independently timed interventions. Although the spatial targeting of control has been the focus of extensive research, the epidemiological consequences of temporal misalignment in intervention deployment across interconnected regions remain to be elucidated. We investigate how asynchronous timing of malaria interventions affects transmission dynamics using a two-patch susceptible-infected-susceptible metapopulation model. We compare synchronous and asynchronous intervention schedules and quantify their impact using measures of excess cumulative incidence attributable to asynchrony. The measure that will be used for this purpose is referred to as Asynchrony Induced Growth (AIG). Across a range of 10,000 parameter combinations, asynchronous implementation has been observed to result in a heightened incidence compared to synchronized deployment, though the impact is typically negligible in most endemic settings. Sensitivity analyses indicate that the impact is most significant when interventions are highly effective, infectious duration is brief, and transmission intensity approaches the elimination threshold. In such circumstances, asynchrony has the potential to substantially inflate case numbers, delay transmission interruption, or even prevent elimination entirely. In illustrative scenarios that reflect realistic settings, synchronizing interventions has been shown to avert large numbers of infections and shorten elimination timelines by years to decades. These findings demonstrate that, beyond spatial targeting, temporal coordination of interventions across connected areas can meaningfully enhance malaria control and elimination. Coordinated timing may be particularly valuable for cross-border or near-elimination programs and should be considered in operational planning and resource allocation.
Morris, H.; Pritt, B. S.
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Effective filtration and concentration of stool specimens is an essential pre-analytical step for reducing fecal debris and improving organism recovery using microscopy-based ova and parasite (O&P) examination. This study evaluated three commercially available fecal sedimentation-based filtration/concentration systems, ParaPak SpinCon (Meridian Bioscience), Mini Parasep SF (Apacor), and the newly-available ParadeviceReingenuity), for qualitative parasite detection and workflow logistics using conventional and artificial intelligence (AI)-assisted microscopy. Forty clinical stool specimens (20 parasite-positive and 20 parasite-negative) were processed with the 3 devices, and the resultant 120 wet mount and 120 trichrome stained smear preparations were examined using conventional microscopy. Trichrome-stained slides were also scanned at 40x magnification using a Hamamatsu NanoZoomerS360 flatbed digital slide scanner and images were analyzed using the Techcyte Fusion Human Fecal Trichrome AI algorithm. Positive and indeterminate digital findings were confirmed by conventional glass slide microscopy. Slides and digital images were reviewed in a blinded manner. Concordance was assessed among the 360 initial evaluations (microscopy and AI-assisted), and discrepant parasitology results were resolved through re-review and specimen reprocessing as needed. Final qualitative agreement across slide/image evaluations using all three concentration systems was 100%. Minor discrepancies in protozoan and white/red blood cell detection/identification were noted in 5 and 7 cases, respectively, and likely reflected sampling and observer variability. While the three concentration systems produced equivalent qualitative results, the Paradevice and Mini Parasep SF offered the most streamlined workflows. These findings support the Paradevice and Mini Parasep SF as efficient, analytically equivalent systems that are compatible with traditional and AI-assisted O&P workflows.
Jiang, X.; Fu, J.; Qu, C.; Huang, J.; Hu, X.
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To explore the safety of combined use of lidocaine/prilocaine aerosol and condoms of different materials, this study conducted compatibility tests between them. By observing changes in various physical properties of condom materials after exposure to the aerosol, the compatibility of different polymer materials with the aerosol was analyzed.The results showed that within 15 minutes of exposure to the aerosol, there was no significant difference in all physical properties of natural rubber latex condoms compared with the blank control group (P>0.05), indicating they can be used together. In contrast, obvious changes in physical properties of polyurethane condoms occurred within 5 minutes of exposure (P<0.05), and their performances failed to meet industrial application standards, so combined use is strictly prohibited.This study clarifies the compatibility differences between two mainstream condom materials and lidocaine/prilocaine aerosol, providing experimental evidence and theoretical references for rational matching in clinical and daily use as well as avoiding potential safety risks.
Bowers, A. S. A.; Henry, K.; McConnell, B.; Francis, C.; Thaxter-Nesbeth, K.
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Background Blood pressure (BP) regulation in individuals with sickle cell disease (SCD) is influenced by a complex interplay of genetic and physiological factors. While SCD has traditionally been associated with lower BP, there is an increased risk of hypertension. Emerging BP research suggests significant heterogeneity across genotypes, age groups, and sex. Objectives: This study investigated the longitudinal effects of population-level characteristics and continuous clinical and laboratory predictors on systolic (SBP) and diastolic blood pressure (DBP) in individuals with SCD, with emphasis on the interactions between baseline and predicted blood pressure slopes over time. Methods We retrospectively analyzed longitudinal data from a cohort of 2,739 patients with diverse SCD genotypes. Descriptive statistics were documented across sex, age range, genotype, health status and relative systemic hypertension risk categories (rHTN-risk). Linear mixed-effects models provided estimates of fixed- and random-effects of baseline BP and of time-related BP effects, respectively. Post-estimation margins provided contrasts of baseline-adjusted BP means and of pre-specified time effects on BP patterns. Results Males had significantly higher baseline SBP ({beta} = 6.64, p < 0.001) but lower baseline DBP ({beta} = -2.61, p < 0.001) compared with age-matched HbSS females. Baseline SBP was more unstable compared with baseline DBP and baseline DBP was more predictive of future BP trends than baseline SBP. Genotype was a consistent predictor of DBP (p < 0.05), but not of SBP. Similarly, we observed increased risks of relative diastolic hypertension across most genotypes, while the prevalence and magnitude of systolic hypertension was lower across all genotype compared with HbSS. Conclusions Blood pressure trajectories in SCD patients are not uniform and are significantly related to genotype, age group and sex over time. Baseline diastolic levels were less heterogenous and exhibited clear upward trajectories over time. These findings support the need for patient-specific BP surveillance in the care and management of SCD.
Topazian, H. M.; Morgan, C. E.; Goel, V.
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Use of zooprophylaxis as a malaria control strategy has been recommended historically, but a complex relationship exists between animal ownership and malaria infection, with mixed associations described in the literature. We sought to characterize this relationship spatially and temporally in malaria-endemic regions of Africa. We used data from 392,843 individuals from 66 Demographic and Health surveys from countries within Africa to investigate the association between household animal ownership and Plasmodium infection. We used Bayesian models with Integrated Nested Laplace Approximation to incorporate spatially varying coefficient processes, allowing the association of interest to vary over space, time, and within strata of vector species occurrence, land cover, and number of animals owned by households. Spatially varying intercept models showed that ownership of cattle, chickens/poultry, goats, horses/donkeys/mules, pigs, and sheep was broadly associated with malaria infection, with odds ratios ranging from 1.55 to 1.67. However, spatially varying slope models revealed considerable heterogeneity, with odds ratio estimates for all animal types demonstrating both protective and harmful effects varying from 0.33 to 3.33 both subnationally and across time. We found no evidence that modification by vector species, number of animals owned, and land cover fully explained the variation in estimates. Unobserved localized cultural, behavioral, or ecological factors likely modify the association between animal ownership and malaria prevalence. Further exploring the nature of this relationship over space and time will be important to understanding how context-specific One Health dynamics between humans, animals and the environment affect malaria prevention and control efforts.