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42 emner vises.
Infection, 10.05.2024
Tilføjet 10.05.2024
Abstract Purpose The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. Methods The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. Results In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug–drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. Conclusion As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.
Læs mere Tjek på PubMedInfection, 10.05.2024
Tilføjet 10.05.2024
Abstract Purpose To assess the Xpert MTB/XDR assay’s efficiency in promptly detecting resistance to isoniazid, fluoroquinolones, ethionamide, and second-line injectable drugs among tuberculosis (TB) patients. Methods From August 2020 to July 2021, TB suspected patient samples were enrolled at a tertiary care center for our study. We conducted mycobacterial culture, phenotypic DST using proportion method in liquid culture at WHO-recommended concentrations, and the line probe assay (LPA). Simultaneously, the Index test, Xpert MTB/XDR, was performed following the manufacturer’s instructions. Results Among 360 samples, 107 were excluded due to incomplete information. Resistance to isoniazid, levofloxacin and moxifloxacin was found in 45/251, 21/251 and 20/251 samples, respectively by phenotypic DST. The diagnostic accuracy of Index test, taking phenotypic DST as a reference standard, was 95.8%, 99.04%, and 99.05% for isoniazid, levofloxacin, and moxifloxacin, respectively. The Index test assay demonstrated a specificity of 99.1% for detecting SLID resistance, yielding a diagnostic accuracy of 99.2. Comparing the Index test with LPA revealed a significant enhancement in sensitivity for detecting isoniazid resistance (86.7% vs. 82.2%). Conclusions The Index test exhibited promising outcomes in identifying resistance to isoniazid and fluoroquinolones, surpassing the performance of the LPA. This could be valuable for promptly initiating treatment in cases of drug-resistant tuberculosis.
Læs mere Tjek på PubMedInfection, 10.05.2024
Tilføjet 10.05.2024
Abstract Purpose Early diagnosis of surgical site infections (SSIs) could prevent surgical revision. Inflammatory markers (IMs), such as procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), seem more accurate in diagnosing SSI than C-reactive protein (CRP) and white blood cell (WBC) count. The aim was to compare the predictive values of CRP, WBC count, PCT, IL-6, and TNF-α in SSI detection. Methods A total of 130 patients undergoing dorsal spondylodesis from 2019 to 2024 were enrolled in a prospective diagnostic study at a maximum care spine center. IMs were measured preoperatively and on the postoperative days (PODs) 1, 2, 3, 5, and 7. Patients with high suspicion of SSI underwent revision surgery. SSI was diagnosed when the microbiological evidence was positive. Patients were divided a posteriori into the non-infection and infection groups. Results IMs of 118 patients (66.9 ± 13.0 years, 61.0% females) were measured. Fifteen of the 118 patients (12.7%) developed an SSI. The groups differed with respect to existing hypertension, number of instrumented segments, region of surgery, CRPPOD1,7, PCTPOD7, and IL-6POD3,5,7. Binary logistic regression for SSI detection including these parameters showed an area under the curve (AUC) of 0.88 (95% CI 0.79–0.98; P
Læs mere Tjek på PubMedInfection, 10.05.2024
Tilføjet 10.05.2024
Abstract Background and Aim A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis. Methods 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR. Results The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality. Conclusion FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.
Læs mere Tjek på PubMedDe kyi, Yujia Xiao, Xia Wang, Shuwen Feng, Yuxin Wang, Lihong Liao, Shouyi Wang, Youping Deng, Junwen Zheng, Dongchi Zhao
International Journal of Infectious Diseases, 10.05.2024
Tilføjet 10.05.2024
The sharp increase in mycoplasma pneumoniae (MP) infection among children in mainland China in 2023 has raised concerns about a traditional infectious disease epidemic[1]. However, it is still impossible to accurately judge the epidemic scale, the infected objectives and the clinical outcome[2]. Until the mid-2023, strong regional epidemics occurred in northern China, mycoplasma pneumoniae pneumonia (MPP) in children attracted the attention of the World Health Organization[3].
Læs mere Tjek på PubMedAurélien Dinh, Clara Duran, Jacques Ropers, Frédérique Bouchand, Laurène Deconinck, Morgan Matt, Olivia Senard, Aurore Lagrange, Guillaume Mellon, Ruxandra Calin, Sabrina Makhloufi, Victoire de Lastours, Emmanuel Mathieu, Jean-Emmanuel Kahn, Elisabeth Rouveix, Julie Grenet, Jennifer Dumoulin, Thierry Chinet, Marion Pépin, Véronique Delcey, Sylvain Diamantis, Daniel Benhamou, Virginie Vitrat, Marie-Christine Dombret, Bertrand Renaud, Yann-Erick Claessens, José Labarère, Jean-Pierre Bedos, Philippe Aegerter, Anne-Claude Crémieux, the Pneumonia Short Treatment (PTC) Study Group
Clinical Microbiology and Infection, 9.05.2024
Tilføjet 9.05.2024
In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP).
Læs mere Tjek på PubMedMurphy, M., Dutton, R., Gezahegne, K., Jones, N., Seager, J., Baird, S.
BMJ Open, 9.05.2024
Tilføjet 9.05.2024
ObjectiveTo understand the relationship between the COVID-19 pandemic and menstrual hygiene management (MHM) among adolescent girls in Ethiopia and to explore which girls were most affected by pandemic disruptions. DesignTwo rounds of data from surveys and interviews were collected with adolescent girls immediately prior to and during the COVID-19 pandemic. The primary analysis is cross-sectional, controlling for pre-COVID-19 covariates. SettingThe setting was three zones in two regions of Ethiopia: East Hararghe and East Shewa Zones in Oromia and South Gondar Zone in Amhara. Data were collected in December 2019–March 2020 and September 2020–February 2021. Participants742 adolescent girls, ages 11–25 years. Outcome measuresFour primary outcomes were explored (1) the number of challenges girls experienced; (2) adolescent-identified challenges managing menstrual hygiene; (3) adolescent-identified difficulties accessing MHM products and (4) adolescent-identified difficulties accessing soap or water. ResultsGirls who were more vulnerable to COVID-19 were more likely to have worse MHM outcomes. An SD increase in household vulnerability to COVID-19 was associated with an 8.7 percentage point increase in the likelihood that the respondent had difficulty getting MHM products (p
Læs mere Tjek på PubMedJohnson, D. R., Ghosh, D., Wagner, B. D., Carlton, E. J.
BMJ Open, 9.05.2024
Tilføjet 9.05.2024
ObjectivesTo assess whether increasing levels of hospital stress—measured by intensive care unit (ICU) bed occupancy (primary), ventilators in use and emergency department (ED) overflow—were associated with decreasing COVID-19 ICU patient survival in Colorado ICUs during the pre-Delta, Delta and Omicron variant eras. DesignA retrospective cohort study using discrete-time survival models, fit with generalised estimating equations. Setting34 hospital systems in Colorado, USA, with the highest patient volume ICUs during the COVID-19 pandemic. Participants9196 non-paediatric SARS-CoV-2 patients in Colorado hospitals admitted once to an ICU between 1 August 2020 and 1 March 2022 and followed for 28 days. Outcome measuresDeath or discharge to hospice. ResultsFor Delta-era COVID-19 ICU patients in Colorado, the odds of death were estimated to be 26% greater for patients exposed every day of their ICU admission to a facility experiencing its all-era 75th percentile ICU fullness or above, versus patients exposed for none of their days (OR: 1.26; 95% CI: 1.04 to 1.54; p=0.0102), adjusting for age, sex, length of ICU stay, vaccination status and hospital quality rating. For both Delta-era and Omicron-era patients, we also detected significantly increased mortality hazard associated with high ventilator utilisation rates and (in a subset of facilities) states of ED overflow. For pre-Delta-era patients, we estimated relatively null or even protective effects for the same fullness exposures, something which provides a meaningful contrast to previous studies that found increased hazards but were limited to pre-Delta study windows. ConclusionsOverall, and especially during the Delta era (when most Colorado facilities were at their fullest), increasing exposure to a fuller hospital was associated with an increasing mortality hazard for COVID-19 ICU patients.
Læs mere Tjek på PubMedBaye, T., Kassaw, A. T., Gebrie, D., Girmaw, F., Ashagrie, G.
BMJ Open, 9.05.2024
Tilføjet 9.05.2024
BackgroundTuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO’s End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain. ObjectiveTo conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings. MethodsWe will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted. Ethics and disseminationEthical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals. PROSPERO registration numberCRD42023443260.
Læs mere Tjek på PubMedBMC Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Background Several models have been used to predict outbreaks during the COVID-19 pandemic, with limited success. We developed a simple mathematical model to accurately predict future epidemic waves. Methods We used data from the Ministry of Health, Labour and Welfare of Japan for newly confirmed COVID-19 cases. COVID-19 case data were summarized as weekly data, and epidemic waves were visualized and identified. The periodicity of COVID-19 in each prefecture of Japan was confirmed using time-series analysis and the autocorrelation coefficient, which was used to investigate the longer-term pattern of COVID-19 cases. Outcomes using the autocorrelation coefficient were visualized via a correlogram to capture the periodicity of the data. An algorithm for a simple prediction model of the seventh COVID-19 wave in Japan comprised three steps. Step 1: machine learning techniques were used to depict the regression lines for each epidemic wave, denoting the “rising trend line”; Step 2: an exponential function with good fit was identified from data of rising straight lines up to the sixth wave, and the timing of the rise of the seventh wave and speed of its spread were calculated; Step 3: a logistic function was created using the values calculated in Step 2 as coefficients to predict the seventh wave. The accuracy of the model in predicting the seventh wave was confirmed using data up to the sixth wave. Results Up to March 31, 2023, the correlation coefficient value was approximately 0.5, indicating significant periodicity. The spread of COVID-19 in Japan was repeated in a cycle of approximately 140 days. Although there was a slight lag in the starting and peak times in our predicted seventh wave compared with the actual epidemic, our developed prediction model had a fairly high degree of accuracy. Conclusion Our newly developed prediction model based on the rising trend line could predict COVID-19 outbreaks up to a few months in advance with high accuracy. The findings of the present study warrant further investigation regarding application to emerging infectious diseases other than COVID-19 in which the epidemic wave has high periodicity.
Læs mere Tjek på PubMedBMC Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Background and objectives Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references. Methods A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug. Results Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01–9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74–9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15–32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98–57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43–52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26]. Conclusion Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir’s potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.
Læs mere Tjek på PubMedBMC Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Background Diarrhea poses a significant threat to the lives of children in The Gambia, accounting for approximately 9% of all deaths among children under the age of five. Addressing and reducing child mortality from diarrhea diseases is crucial for achieving the Sustainable Development Goal (SDG) 3, specifically target 3.2, which aims to eliminate preventable deaths in newborns and children under the age of five by 2030. Thus, this research aims to assess the prevalence and contextual factors associated with diarrhea among under-five children in The Gambia. Methods This research employed secondary data from the 2019/20 Gambia Demographic Health Survey (GDHS). The study initially involved 8,362 women aged between 15 and 49 years. Of these, 6,929 women with children under five were included in this analysis. Data were analyzed using STATA with cross-tabulation and model fitting. Multilevel logistic regression was applied to accommodate the hierarchical structure of the demographic health survey data. The model comparison parameters were BIC, AIC, deviance, and LLR. Variables with a p-value less than 0.05 were selected for multivariable analysis. The statistical significance of the factors was determined using an adjusted odds ratio with a 95% confidence interval (CI) and a p-value of less than 0.05. Results The prevalence of diarrhea in under-five children was 53.2% in males and 46.8% in females. In the final model, Kerewan (aOR = 0.58; 95% CI = 0.33–0.98) and Basse (aOR = 0.59; 95% CI = 0.35–0.98) have significantly lower odds of childhood diarrhea compared to Banjul, female children show slightly lower, yet significant, odds of diarrhea compared to males (aOR = 0.96; 95% CI = 0.86–0.98), deliveries at government health centers are associated with higher odds of childhood diarrhea compared to home births (aOR = 1.24; 95% CI = 1.01–1.52). Mothers with post-secondary education had significantly lower odds of having children with diarrhea than those without any education (aOR = 0.50; 95% CI = 0.26–0.99) after controlling for confounders. Conclusion The study findings indicate that several factors significantly impact the risk of childhood diarrhea in The Gambia. These factors include region of residence, sex of the child, place of delivery, and education level of the mother. The study suggests that existing interventions aimed at improving child health outcomes in the country should take into consideration these influential factors. Addressing these modifiable factors can enhance the effectiveness of interventions and promote better health outcomes for children in Gambia.
Læs mere Tjek på PubMedBMC Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract We report a very rare case of Listeria multiple brain abscesses manifested as delirium, which represented diagnostic and therapeutic challenges overcome only by the close cooperation between Infectious Diseases and Neuroradiology, without which a satisfactory outcome would not be achieved. An elderly man presented with confusion and drowsiness with a background of type-II diabetes mellitus. Although computed tomography of the brain only showed frontal lobe oedema, contrast magnetic resonance (MR) imaging showed numerous irregular rim-enhancing lesions containing central diffusion restriction, suggesting multiple pyogenic cerebral abscesses of unclear aetiology. Thereafter, Listeria monocytogenes was isolated from blood cultures, suggesting this as the causative organism. Deemed unsuitable for neurosurgical drainage, the patient received medical management with a protracted course of antibiotics. This case was extremely challenging, due to 1) the impossibility of source control, 2) the small number of effective antibiotics available to treat this condition, and 3) the inevitable antibiotic side-effects, derived from long-term exposure. A successful outcome was only possible thanks to strict close multidisciplinary follow up, requiring frequent MR imaging and a judicious antibiotic choice, including monitoring of their side-effects. Due to the rarity of this condition, there is lack of guidance on its management, hence the importance of multidisciplinary involvement with very close imaging and antibiotic monitoring.
Læs mere Tjek på PubMedPin-Xian DuShen-Shin ChangTzong-Shiann HoHsi-Chang ShihPei-Shan TsaiGuan-Da Syua Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwanb Division of Transplantation, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwanc Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwand Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwane Department of Pediatrics, Tainan Hospital, Ministry of Health and Welfare, Yunlin, Taiwanf Department of Pediatrics, National Cheng Kung University Hospital Dou-Liou Branch, College of Medicine, National Cheng Kung University, Yunlin, Taiwang Department of Pharmacology and Molecular Sciences, JohnsHopkins University School of Medicine, Baltimore, USAh International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwani Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
Virulence, 9.05.2024
Tilføjet 9.05.2024
Rosita Rotella, José M. Soriano, Isabel Peraita‐Costa, Agustín Llopis‐González, María Morales‐Suarez‐Varela
Tropical Medicine & International Health, 9.05.2024
Tilføjet 9.05.2024
Muhammad Ijaz, Muhammad Jawad Sabir, Muhammad Umar Javed, Arslan Ahmed, Hamza Rasheed, Ali Abdullah Jabir
Tropical Medicine & International Health, 9.05.2024
Tilføjet 9.05.2024
Clinical Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract In this randomised, controlled study in 14 low- and middle-income countries, individuals taking dolutegravir with darunavir/ritonavir for 48 weeks had a greater increase in systolic and diastolic blood pressure than individuals taking two nucleoside reverse transcriptase with darunavir/ritonavir. The difference remained significant after controlling for confounding factors including weight gain.
Læs mere Tjek på PubMedElena Vázquez, Oscar de Gregorio-Vicente, Vicente Soriano, Carmen Álvarez-Domínguez, Octavio Corral, Víctor Moreno-Torres
International Journal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Although most cases of listeriosis are sporadic, Listeria monocytogenes (LM) is an important cause of major epidemic outbreaks from contaminated food worldwide [1]. Despite its relatively low prevalence, LM is an important health treat given the high mortality rate and the growing of risk populations, such as the elderly, immunosuppressed individuals, pregnant women, unborn babies and newborn infants [1,2].
Læs mere Tjek på PubMedBai, Francesca; Bono, Valeria; Borghi, Lidia; Bonazza, Federica; Falcinella, Camilla; Vitaletti, Virginia; Miraglia, Federica; Trunfio, Mattia; Calcagno, Andrea; Cusato, Jessica; Vegni, Elena; Monforte, Antonella D’arminio; Marchetti, Giulia
AIDS, 9.05.2024
Tilføjet 9.05.2024
Background: HIV-associated neurocognitive disorders (HAND) still affects persons living with HIV (PLWH) and their pathogenesis isn’t completely understood. We aimed to explore the association between plasma and CSF markers of blood-brain barrier (BBB) impairment and HAND in untreated PLWH. Design: Cross-sectional study. Methods: We enrolled untreated PLWH, who underwent blood exams and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, TJs: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria). Results: Twenty-one patients (21/78, 26,9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4+ T-cells and increased CD4+ T-cell exhaustion (lower CD4+CD127+ and CD4+CD45RA+ T cells percentages), in comparison to subjects without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15), but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules weren’t associated with HAND, but with a poor performance in different cognitive domains. Conclusions: By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PLWH. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedBrickman, Cristina E.; Agnello, Melissa; Imam, Nabeel; Camejo, Pamela; Pino, Rodolfo; Carroll, Lauren N.; Chein, Aung; Palefsky, Joel M.
AIDS, 9.05.2024
Tilføjet 9.05.2024
Objectives: Anal cancer risk is elevated in men who have sex with men living with HIV (MSMLWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool. We also sought to determine whether changes in the anal microbiome are associated with HSIL among MSMLWH. Design: Cross-sectional comparison of the microbiome of the anal canal with the microbiome of stool in MSMLWH and cross-sectional comparison of the anal microbiome of MSMLWH with anal HSIL with the anal microbiome of MSMLWH without anal HSIL. Methods: Sterile swabs were used to sample the anus of MSMLWH for microbiome and HPV testing, followed by high-resolution anoscopy. Stool samples were mailed from home. 16S sequencing was used for bacterial identification. Measures of alpha diversity, beta diversity and differential abundance analysis were used to compare samples. Results: 166 anal samples and 103 matching stool samples were sequenced. Beta diversity showed clustering of stool and anal samples. Of hr-HPV-positive MSMLWH, 31 had HSIL and 13 had no SIL. Comparison of the microbiome between these revealed 28 different species. The highest-fold enrichment among MSMLWH/hr-HPV/HSIL included pro-inflammatory and carcinogenic Prevotella, Parasuterella, Hungatella, Sneathia and Fusobacterium species. The anti-inflammatory Anaerostipes caccae showed the greatest reduction among MSMLWH/hr-HPV/HSIL. Conclusions: The anal microbiome is distinct from stool. A pro-inflammatory and carcinogenic environment may be associated with anal HSIL. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedDerseh, Nebiyu Mekonnen; Agimas, Muluken Chanie; Tesfie, Tigabu Kidie
AIDS, 9.05.2024
Tilføjet 9.05.2024
Objective: This study was aimed at developing a risk score prediction model for bacteriologically confirmed TB among HIV-infected adults receiving antiretroviral therapy in Ethiopia. Methods: An institutional-based retrospective follow-up study was conducted among 569 HIV-infected adults on ART. We used demographic and clinical prognostic factors to develop a risk prediction model. Model performance was evaluated by discrimination and calibration using the area under the receiver operating characteristic (AUROC) curve and calibration plot. Bootstrapping was used for internal validation. A decision curve analysis was used to evaluate the clinical utility. Results: Opportunistic infection, functional status, anemia, isoniazid preventive therapy, and WHO clinical stages were used to develop risk prediction. The AUROC curve of the original model was 87.53% (95% CI: 83.88–91.25) and the calibration plot (p-value = 0.51). After internal validation, the AUROC curve of 86.61% (95% CI: 82.92–90.29%) was comparable with the original model, with an optimism coefficient of 0.0096 and good calibration (p-value = 0.10). Our model revealed excellent sensitivity (92.65%) and negative predictive value (NPV) (98.60%) with very good specificity (70.06%) and accuracy (72.76%). After validation, accuracy (74.85%) and specificity (76.27%) were improved, but sensitivity (86.76%) and NPV (97.66%) were relatively reduced. The risk prediction model had a net benefit up to 7.5 threshold probabilities. Conclusion: This prognostic model had very good performance. Moreover, it had very good sensitivity and excellent NPV. The model could help clinicians use risk estimation and stratification for early diagnosis and treatment to improve patient outcomes and quality of life. JOURNAL/aids/04.03/00002030-990000000-00483/figure1/v/2024-04-24T104332Z/r/image-jpeg Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedCatling, Finneas J. R.; Nagendran, Myura; Festor, Paul; Bien, Zuzanna; Harris, Steve; Faisal, A. Aldo; Gordon, Anthony C.; Komorowski, Matthieu
Critical Care Explorations, 9.05.2024
Tilføjet 9.05.2024
Large randomized trials in sepsis have generally failed to find effective novel treatments. This is increasingly attributed to patient heterogeneity, including heterogeneous cardiovascular changes in septic shock. We discuss the potential for machine learning systems to personalize cardiovascular resuscitation in sepsis. While the literature is replete with proofs of concept, the technological readiness of current systems is low, with a paucity of clinical trials and proven patient benefit. Systems may be vulnerable to confounding and poor generalization to new patient populations or contemporary patterns of care. Typical electronic health records do not capture rich enough data, at sufficient temporal resolution, to produce systems that make actionable treatment suggestions. To resolve these issues, we recommend a simultaneous focus on technical challenges and removing barriers to translation. This will involve improving data quality, adopting causally grounded models, prioritizing safety assessment and integration into healthcare workflows, conducting randomized clinical trials and aligning with regulatory requirements.
Læs mere Tjek på PubMedAngriman, Federico; Saoraya, Jutamas; Lawler, Patrick R.; Shah, Baiju R.; Martin, Claudio M.; Scales, Damon C.; on behalf of the Sepsis Canada Network
Critical Care Explorations, 9.05.2024
Tilføjet 9.05.2024
OBJECTIVES: We assessed the association of preexisting diabetes mellitus with all-cause mortality and organ support receipt in adult patients with sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008–2019). POPULATION: Adult patients (18 yr old or older) with a first sepsis-related hospitalization episode. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure of interest was preexisting diabetes (either type 1 or 2). The primary outcome was all-cause mortality by 90 days; secondary outcomes included receipt of invasive mechanical ventilation and new renal replacement therapy. We report adjusted (for baseline characteristics using standardization) risk ratios (RRs) alongside 95% CIs. A main secondary analysis evaluated the potential mediation by prior metformin use of the association between preexisting diabetes and all-cause mortality following sepsis. Overall, 503,455 adults with a first sepsis-related hospitalization episode were included; 36% had preexisting diabetes. Mean age was 73 years, and 54% of the cohort were females. Preexisting diabetes was associated with a lower adjusted risk of all-cause mortality at 90 days (RR, 0.81; 95% CI, 0.80–0.82). Preexisting diabetes was associated with an increased risk of new renal replacement therapy (RR, 1.53; 95% CI, 1.46–1.60) but not invasive mechanical ventilation (RR, 1.03; 95% CI, 1.00–1.05). Overall, 21% (95% CI, 19–28) of the association between preexisting diabetes and reduced risk of all-cause mortality was mediated by prior metformin use. CONCLUSIONS: Preexisting diabetes is associated with a lower risk of all-cause mortality and higher risk of new renal replacement therapy among adult patients with sepsis. Future studies should evaluate the underlying mechanisms of these associations.
Læs mere Tjek på PubMedJelte Elsinga, Temmy Sunyoto, Letizia di Stefano, Pier Francesco Giorgetti, Htet Aung Kyi, Chiara Burzio, Ximena Campos Moreno, Chiedozie K Ojide, Nnennaya Ajayi, Richard Ewah, Emeka O Ogah, Chioma Dan-Nwafor, Anthony Ahumibe, Chinwe Lucia Ochu, Adebola Olayinka, Sylvie Jonckheere, Pascale Chaillet, Michel van Herp
Lancet Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings.
Læs mere Tjek på PubMedThe PLOS ONE Editors
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
José Ferreira Saraiva, Nercy Virginia Rabelo Furtado, Ahana Maitra, Dario P. Carvalho, Allan Kardec Ribeiro Galardo, José Bento Pereira Lima
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
by José Ferreira Saraiva, Nercy Virginia Rabelo Furtado, Ahana Maitra, Dario P. Carvalho, Allan Kardec Ribeiro Galardo, José Bento Pereira Lima Entomological research is vital for shaping strategies to control mosquito vectors. Its significance also reaches into environmental management, aiming to prevent inconveniences caused by non-vector mosquitoes like the Mansonia Blanchard, 1901 mosquito. In this study, we carried out a five-year (2019–2023) monitoring of these mosquitoes at ten sites in Porto Velho, Rondônia, using SkeeterVac SV3100 automatic traps positioned between the two hydroelectric complexes on the Madeira River. Throughout this period, we sampled 153,125 mosquitoes, of which the Mansonia genus accounted for 54% of the total, indicating its prevalence in the region. ARIMA analysis revealed seasonal patterns of Mansonia spp., highlighting periods of peak density. Notably, a significant decreasing trend in local abundance was observed from July 2021 (25th epidemiological week) until the end of the study. Wind speed was observed to be the most relevant meteorological factor influencing the abundance of Mansonia spp. especially in the Joana D’Arc settlement, although additional investigation is needed to comprehensively analyze other local events and gain a deeper understanding of the ecological patterns of this genus in the Amazon region.
Læs mere Tjek på PubMedRahmat Dapari, Muhammad Fahmi Mohd Fadzil, Muhammad Yazid Hanzir, Jamal Sham Mohamed Jais, Nur Fatin Safarudin, Adila Albar
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
by Rahmat Dapari, Muhammad Fahmi Mohd Fadzil, Muhammad Yazid Hanzir, Jamal Sham Mohamed Jais, Nur Fatin Safarudin, Adila Albar Introduction Workers in the construction industry frequently work in construction sites with numerous areas that can potentially accumulate water, such as tanks, wet cement surfaces, or water puddles. These water collection sites become ideal breeding grounds for mosquito infestation, which leads to a higher prevalence of mosquito-borne diseases, especially malaria and dengue among construction workers. Despite that numerous factors have been identified in controlling vector-borne diseases, the specific factors that influence mosquito control at construction sites have yet to be explored. Aims This systematic review aims to determine the factors associated with mosquito control among construction workers. Methods Primarily, articles related to factors associated with mosquito control among construction workers were collected from two different online databases (ScienceDirect and EBSCOhost). Two independent reviewers were assigned to screen the titles and abstracts of the collected data, stored in Microsoft Excel, against the inclusion and exclusion criteria. Afterwards, the quality of the included articles was critically assessed using the Mixed Method Appraisal Tool (MMAT). Of the 171 articles identified, 4 were included in the final review. Results Based on the thorough evaluation, mosquito-related knowledge, practical mosquito prevention measures, and Larval Source Management (LSM) were identified as vital factors associated with mosquito control among construction workers. The significant association between mosquito-related knowledge and control practices indicates higher knowledge linked to effective practices, particularly among female workers and those who were recently infected with malaria. Concurrently, there were notable challenges regarding sustainable preventive measures and larval control methods in construction settings. Conclusion Implementing effective mosquito control, including knowledge and practice on mosquito control together with vector control, is highly required to suppress the expanding mosquito population. It is recommended that employers provide continuous mosquito control education and training to their employees and reward them with incentives, while employees should comply with the guidelines set by their employers to ensure successful mosquito control and reduce the spread of mosquito-borne diseases in the construction industry.
Læs mere Tjek på PubMedBenjamín Quiroz-Martínez, Pablo Hernández-Alcántara, David Alberto Salas de León, Vivianne Solís-Weiss, María Adela Monreal Gómez, León Felipe Álvarez Sánchez
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
by Benjamín Quiroz-Martínez, Pablo Hernández-Alcántara, David Alberto Salas de León, Vivianne Solís-Weiss, María Adela Monreal Gómez, León Felipe Álvarez Sánchez The spatial patterns of taxonomic diversity of annelid polychaete species from the continental shelf in the Southern Gulf of Mexico were examined in this study. We used taxonomic distinctness and its spatial variations to explore the diversity patterns and how they change between Southern Gulf of Mexico regions. In addition, using taxonomic distinctness as a dissimilarity measure and Ward’s Clustering, we characterized three distinct faunal assemblages. We also investigated patterns of richness, taxonomic distinctness, and distance decay of similarity between sampling stations as a ß-diversity measure. Finally, we examined the spatial relationships between polychaete assemblages and environmental variables to test the relative importance of spatial and environmental components in annelid polychaete community structure from the Southern Gulf of Mexico. We used a combination of eigenvector-based multivariate analyses (dbMEMs) and distance-based redundancy analysis (dbRDA) to quantify the relative importance of these explanatory variables on the spatial variations of taxonomic distinctness. The significance level of spatial and environmental components to the distribution of polychaete species showed that the combined effect of spatial processes and sediment characteristics explained a higher percentage of the variance than those parameters could alone.
Læs mere Tjek på PubMedDoo Ri Park, Bo Ram Choi, Changhwan Yeo, Jee Eun Yoon, Eun Young Hong, Seung Ho Baek, Yoon Jae Lee, In-Hyuk Ha
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
by Doo Ri Park, Bo Ram Choi, Changhwan Yeo, Jee Eun Yoon, Eun Young Hong, Seung Ho Baek, Yoon Jae Lee, In-Hyuk Ha Osteoarthritis is the most prevalent type of degenerative arthritis. It is characterized by persistent pain, joint dysfunction, and physical disability. Pain relief and inflammation control are prioritised during osteoarthritis treatment Mume Fructus (Omae), a fumigated product of the Prunus mume fruit, is used as a traditional medicine in several Asian countries. However, its therapeutic mechanism of action and effects on osteoarthritis and articular chondrocytes remain unknown. In this study, we analyzed the anti-osteoarthritis and articular regenerative effects of Mume Fructus extract on rat chondrocytes. Mume Fructus treatment reduced the interleukin-1β-induced expression of matrix metalloproteinase 3, matrix metalloproteinase 13, and a disintegrin and metalloproteinase with thrombospondin type 1 motifs 5. Additionally, it enhanced collagen type II alpha 1 chain and aggrecan accumulation in rat chondrocytes. Furthermore, Mume Fructus treatment regulated the inflammatory cytokine levels, mitogen-activated protein kinase phosphorylation, and nuclear factor-kappa B activation. Overall, our results demonstrated that Mume Fructus inhibits osteoarthritis progression by inhibiting the nuclear factor-kappa B and mitogen-activated protein kinase pathways to reduce the levels of inflammatory cytokines and prevent cartilage degeneration. Therefore, Mume Fructus may be a potential therapeutic option for osteoarthritis.
Læs mere Tjek på PubMedHuiyang Zhang, Zhiyong Wang, Zhenjin Li, Xiaotong Liu, Kai Wang, Shichang Sun, Silong Cheng, Zhenhai Gao
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
by Huiyang Zhang, Zhiyong Wang, Zhenjin Li, Xiaotong Liu, Kai Wang, Shichang Sun, Silong Cheng, Zhenhai Gao Winter wheat is one of the most important crops in the world. It is great significance to obtain the planting area of winter wheat timely and accurately for formulating agricultural policies. Due to the limited resolution of single SAR data and the susceptibility of single optical data to weather conditions, it is difficult to accurately obtain the planting area of winter wheat using only SAR or optical data. To solve the problem of low accuracy of winter wheat extraction only using optical or SAR images, a decision tree classification method combining time series SAR backscattering feature and NDVI (Normalized Difference Vegetation Index) was constructed in this paper. By synergy using of SAR and optical data can compensate for their respective shortcomings. First, winter wheat was distinguished from other vegetation by NDVI at the maturity stage, and then it was extracted by SAR backscattering feature. This approach facilitates the semi-automated extraction of winter wheat. Taking Yucheng City of Shandong Province as study area, 9 Sentinel-1 images and one Sentinel-2 image were taken as the data sources, and the spatial distribution of winter wheat in 2022 was obtained. The results indicate that the overall accuracy (OA) and kappa coefficient (Kappa) of the proposed method are 96.10% and 0.94, respectively. Compared with the supervised classification of multi-temporal composite pseudocolor image and single Sentinel-2 image using Support Vector Machine (SVM) classifier, the OA are improved by 10.69% and 5.66%, respectively. Compared with using only SAR feature for decision tree classification, the producer accuracy (PA) and user accuracy (UA) for extracting the winter wheat are improved by 3.08% and 8.25%, respectively. The method proposed in this paper is rapid and accurate, and provide a new technical method for extracting winter wheat.
Læs mere Tjek på PubMedAliyu Dantani Abdullahi, Kridsada Unban, Chalermpong Saenjum, Pratthana Kodchasee, Napapan Kangwan, Hathairat Thananchai, Kalidas Shetty, Chartchai Khanongnuch
PLoS One Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
by Aliyu Dantani Abdullahi, Kridsada Unban, Chalermpong Saenjum, Pratthana Kodchasee, Napapan Kangwan, Hathairat Thananchai, Kalidas Shetty, Chartchai Khanongnuch Bacterial pathogens have remained a major public health concern for several decades. This study investigated the antibacterial activities of Miang extracts (at non-neutral and neutral pH) against Bacillus cereus TISTR 747, Escherichia coli ATCC 22595, Salmonella enterica serovar Typhimurium TISTR 292 and Streptococcus mutans DMST 18777. The potential of Polyvinylpolypyrrolidone (PVPP)-precipitated tannin-free Miang extracts in growth-inhibition of the cariogenic Streptococcus mutans DMST 18777 and its biofilms was also evaluated. The tannin-rich fermented extracts had the best bacterial growth inhibition against S. mutans DMST 18777 with an MIC of 0.29 and 0.72 mg/mL for nonfilamentous fungi (NFP) Miang and filamentous-fungi-processed (FFP) Miang respectively. This observed anti-streptococcal activity still remained after PVPP-mediated precipitation of bioactive tannins especially, in NFP and FFP Miang. Characterization of the PVPP-treated extracts using High performance liquid chromatography quadrupole-time of flight-mass spectrometry (HPLC-QToF-MS) analysis, also offered an insight into probable compound classes responsible for the activities. In addition, Crystal violet-staining also showed better IC50 values for NFP Miang (4.30 ± 0.66 mg/mL) and FFP Miang (12.73 ± 0.11 mg/mL) against S. mutans DMST 18777 biofilms in vitro. Homology modeling and molecular docking analysis using HPLC-MS identified ligands in tannin-free Miang supernatants, was performed against modelled S. mutans DMST 18777 sortase A enzyme. The in silico analysis suggested that the inhibition by NFP and FFP Miang might be attributed to the presence of ellagic acid, flavonoid aglycones, and glycosides. Thus, these Miang extracts could be optimized and explored as natural active pharmaceutical ingredients (NAPIs) for applications in oral hygienic products.
Læs mere Tjek på PubMedJonsson-Oldenbüttel, Celia; Ghosn, Jade; van der Valk, Marc; Florence, Eric; Vera, Francisco; De Wit, Stéphane; Rami, Agathe; Bonnet, Fabrice; Hocqueloux, Laurent; Hove, Kai; Ait-Khaled, Mounir; DeMoor, Rebecca; Bontempo, Gilda; Latham, Christine L.; Gutner, Cassidy A.; Iyer, Supriya; Gill, Martin; Czarnogorski, Maggie; D’Amico, Ronald; van Wyk, Jean
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. Here, we report Month 12 clinical outcomes in patient study participants (PSPs) in the CARISEL study. Setting: CARISEL is a Phase 3b implementation–effectiveness study. Methods: CARISEL was designed as a two-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, the study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through Month 12 included: the proportion of PSPs with plasma HIV-1 RNA ≥50 copies/mL and
Læs mere Tjek på PubMedBarth, Shannon K.; Monroe, Anne K.; Houston, Patricia; Benator, Debra; Horberg, Michael; Castel, Amanda D.; On behalf of the DC Cohort Executive Committee
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: Studies on the incidence of COVID-19 among persons with HIV (PWH) present varied results. Few studies have investigated the impact of COVID-19 infection on health and socioeconomic factors or COVID-19 stigma. We sought to measure the incidence and severity of COVID-19 infection among a cohort of PWH, characterize associated risk factors and impact, and document perceptions of COVID-19-related stigma. Methods: Data for this cross-sectional study come from the COVID-19 survey of participants in the DC Cohort longitudinal study from October 30, 2020 through December 31, 2022. Survey results were linked to electronic health records, including HIV labs and COVID test results. We conducted analyses comparing demographic, socioeconomic, HIV measures, and stigma among those with and without self-reported COVID-19. Results: Out of 1,972 survey respondents, 17% self-reported COVID-19 infection, with greatest incidence in the Omicron wave of the pandemic. We found statistically significant differences by age, employment status, essential worker status, education, and household income. Longer duration of HIV diagnosis was associated with greater incidence of COVID-19. PWH who were overweight or obese had greater incidence of COVID-19 compared to those who were not. Over 40% of PWH with COVID-19 reported experiencing at least one form of COVID-19-related stigma. Conclusion: We observed a high incidence of COVID-19 infection among PWH in DC. Further, a substantial proportion of PWH with COVID-19 reported experiencing COVID-19 related stigma. These findings add to the existing literature on COVID-19 co-infection among PWH and highlight the need for awareness and support for those experiencing COVID-19 stigma. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedJi, Cheng; Chen, Liting; Kaypaghian, Marina
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Garrett, Nigel; Dintwe, One; Monaco, Cynthia L.; Jones, Megan; Seaton, Kelly E.; Church, E. Chandler; Grunenberg, Nicole; Hutter, Julia; deCamp, Allan; Huang, Yunda; Lu, Huiyin; Mann, Philipp; Robinson, Samuel T.; Heptinstall, Jack; Jensen, Ryan L.; Pantaleo, Giuseppe; Ding, Song; Koutsoukos, Marguerite; Hosseinipour, Mina C.; Van Der Meeren, Olivier; Gilbert, Peter B.; Ferrari, Guido; Andersen-Nissen, Erica; McElrath, M. Juliana; Tomaras, Georgia D.; Gray, Glenda E.; Corey, Lawrence; Kublin, James G.; on behalf of the HVTN 108 and HVTN 111 Study Teams
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Despite progress in HIV prevention and treatment, an estimated 1.3 million people were newly infected with HIV in 2022,1 highlighting the urgent need for an effective vaccine. To date, the RV144 trial remains the only HIV vaccine trial that has demonstrated partial efficacy against acquisition.2 The Pox-Protein Public-Private Partnership (P5) was established with the aims of improving on RV144 by developing a vaccine capable of protecting against a broader diversity of HIV strains and achieving a better understanding of immune responses associated with preventing HIV infection.3 Vaccine concepts in the P5 program have focused on clade C immunogens, targeting predominant strains of East and Southern Africa, where approximately half of the 39 million people living with HIV reside.1 Despite progress in HIV prevention and treatment, an estimated 1.3 million people were newly infected with HIV in 2022,1 highlighting the urgent need for an effective vaccine. To date, the RV144 trial remains the only HIV vaccine trial that has demonstrated partial efficacy against acquisition.2 The Pox-Protein Public-Private Partnership (P5) was established with the aims of improving on RV144 by developing a vaccine capable of protecting against a broader diversity of HIV strains and achieving a better understanding of immune responses associated with preventing HIV infection.3 Vaccine concepts in the P5 program have focused on clade C immunogens, targeting predominant strains of East and Southern Africa, where approximately half of the 39 million people living with HIV reside.1 The RV144 regimen, originally designed to protect against subtype B/E strains, was adapted to incorporate clade C antigens and adjuvanted with MF59®.4 This regimen demonstrated adequate immunogenicity in the HVTN100 phase 1/2a trial,5 and was further evaluated in the HVTN702 efficacy trial in South Africa, but ultimately discontinued due to non-efficacy.6 In parallel, the P5 designed the correlates program: a series of phase 1/2a trials to evaluate vaccine candidates based on favorable immune profiles of putative correlates of protection. These trials employed novel prime-boost and co-administration regimens, varied protein doses, and used new adjuvants and vaccine delivery systems, with an emphasis on shared immunological endpoints to allow for cross-study comparisons. Preclinical studies have shown promising immune responses using DNA/protein combination vaccines.7,8 A comparison of responses between HVTN100 (ALVAC) and HVTN111 (DNA) trials indicated that DNA priming with a protein boost led to increased antibody and cellular responses compared to priming with the canarypox vector.9 In the HVTN105 trial, both a DNA prime-protein boost and a co-administration regimen induced potent and durable V1/V2 binding antibody responses (a known correlate of lower HIV-1 infection risk in RV144), with co-administration inducing early antibody responses.10 Furthermore, in the HVTN096 trial, including gp120 Env protein at the priming stage, co-administered with either NYVAC or DNA, elicited earlier and even greater antibody responses.11 The adjuvant system 01 (AS01) has been successfully tested in vaccine trials for other infectious diseases including malaria,12 shingles,13,14 and tuberculosis.15 Some HIV vaccine studies have also used AS01 and have shown that it contributes to the induction of robust and persistent cellular and humoral responses.16,17 MF59® has likewise been used in several licensed vaccines and pre-clinical studies,18 inducing strong and durable T-cell memory and humoral responses. MF59® was also used in HVTN studies with ALVAC 5 and was therefore chosen for comparison with AS01B in this trial. Thus, the aim of the HVTN108 trial was to evaluate the safety and immunogenicity of the DNA vaccine with different HIV clade C protein doses, adjuvanted with MF59® or AS01B, and dosed in prime-boost or co-administration regimens. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedHernandez, Alexandra L.; Hilton, Joan F.; Weatherly, Christopher Scott; Berry-Lawhorn, J. Michael; Jay, Naomi; Brickman, Cristina; Wang, Chia-ching J; Kauffman, Jason; Calderon, Joanne; Farhat, Sepideh; Costa, Maria DA; Akha, Arezou Sadighi; Darragh, Teresa; Palefsky, Joel M.
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSIL). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years of age, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). Setting: We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, California. Methods: 129 MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with biopsy of visible lesions. Results: Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (OR:45.1, 95% CI:15.8-129), other oncogenic HPV types (OR:5.95, 95% CI:2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. Conclusion: The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remain very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRohr, Julia K.; Manne-Goehler, Jennifer; Gómez-Olivé, F. Xavier; Kahn, Kathleen; Bärnighausen, Till W.
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background: As people with HIV grow older, stable engagement in care is essential for healthy aging. We evaluate the HIV care cascade for older adults in rural South Africa at two time points cross-sectionally and assess movement in the cascade over time. Setting: We evaluated cascade stage at Waves 1 (2014-2015) and 2 (2018-2019) of HAALSI, a population-based longitudinal cohort study in Mpumalanga Province, South Africa. Methods: Biomarker screening defined cascade stages (HIV+/No antiretroviral therapy [ART]; ART+/Unsuppressed viral load; ART+/Suppressed viral load). Between-wave probability of death, cascade progression, regression, cascade transitions, and sociodemographic predictors were assessed with Poisson regression. The impact of death was considered using the Fine and Gray competing risk model. Results: We observed higher prevalence of ART with viral suppression over time (50% in Wave 1 vs. 70% in Wave 2). Among those alive, the oldest age group (70+ yo) was most likely to have cascade progression (aRR for treatment initiation vs. 40-49 yo: 1.38 (95% CI: 1.02-1.86)). However, there was significant risk of death and cascade regression. Death between waves reached 40% for 70+ year olds who were ART+/Unsuppressed. In competing risk models, older age was associated with equivalent or less cascade progression. Conclusion: Older age groups who were unsuppressed on treatment and males had poorer cascade outcomes. Improvements observed in HIV treatment coverage over time for older adults must be interpreted in the context of high risk of death for older HIV-positive adults, especially among those failing treatment. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRoss, Jeremy L; Teeraananchai, Sirinya; Avihingsanon, Anchalee; Lee, Man Po; Ditangco, Rossana; Rajasuriar, Reena; Kim, Jung Ho; Gatechompol, Sivaporn; Chan, Iris; Echanis Melgar, Maria Isabel; Chong, Meng Li; Jiamsakul, Awachana; Sohn, Annette H.; Law, Matthew; Choi, Jun Yong; on behalf of the Substance use, Stigma, Depression and Disability (S2D2) study group of IeDEA Asia-Pacific
Journal of Acquired Immune Deficiency Syndromes, 9.05.2024
Tilføjet 9.05.2024
Background Mental health and substance use disorders are common among people living with HIV and are associated with high-risk sexual behaviors, such as unprotected sex and multiple sexual partners, but Asia-Pacific data are limited. Methods Adult PLHIV in care at five Asia-Pacific HIV clinics were enrolled at routine clinic visits between July 2019 and June 2020. Depression, substance use, sexual practice and socio-demographic data were collected using PHQ-9, ASSIST, and a study-specific questionnaire. Clinical data were accessed from medical records. Risk factors for medium- to high-risk sexual practices, defined based on total scores from the sexual practice questionnaire assessing number of sexual partners and condom use, were analyzed using logistic regression. Moderate to severe depression was defined as a PHQ-9 score >9, and moderate- to high-risk substance use as an ASSIST score >11 for alcohol or >4 for other substances. Results Among 723 participants, median age was 38 years, 89% were male, 99% were on ART and 37% had medium- to high-risk sexual practices. Medium- to high-risk sexual practices were more common among those
Læs mere Tjek på PubMedLouise Dahl HultqvistJens Bo AndersenCarl Martin NilssonCharlotte Uldahl JansenMorten RybtkeTim Holm JakobsenThomas Eiland NielsenKlaus QvortrupClaus MoserMichael GrazKatrine QvortrupTim Tolker-NielsenMichael Givskov1Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark2Department of Chemistry, Technical University of Denmark, Lyngby, Denmark3Department of Biomedical Sciences, CFIM, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark4Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, Anne-Catrin Uhlemann
Antimicrobial Agents And Chemotherapy, 9.05.2024
Tilføjet 9.05.2024
Journal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin improves the treatment of primary pneumonia or superinfection caused by amoxicillin-sensitive or -resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and -resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. Finally, we developed a mathematical model that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract Background Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs).Methods We used data from UK Biobank, The Trøndelag Health Study (HUNT), and Michigan Genomics Initiative (MGI) to conduct genome-wide association studies (GWASs) and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs.Results One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for the females, SCAMP1−AS1 for the males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (OR of 4.84, P = 4.50E-06 and OR of 2.79, P = 3.02E-05, respectively).Conclusions We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 9.05.2024
Tilføjet 9.05.2024
Abstract In an area endemic with Indian visceral leishmaniasis (VL), we performed direct xenodiagnosis to evaluate the transmission of Leishmania donovani from patients with VL–human immunodeficiency virus (HIV) coinfection to the vector sandflies, Phlebotomus argentipes. Fourteen patients with confirmed VL-HIV coinfection, with a median parasitemia of 42 205 parasite genome/mL of blood, were exposed to 732 laboratory-reared pathogen-free female P argentipes sandflies on their lower arms and legs. Microscopy revealed that 16.66% (122/732) of blood-fed flies were xenodiagnosis positive. Notably, 93% (13/14) of the VL-HIV group infected the flies, as confirmed by quantitative polymerase chain reaction and/or microscopy, and were 3 times more infectious than those who had VL without HIV.
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