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BMC Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and gene polymorphism’s influence on the IL-17A serum levels. In this research, 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum levels and malaria outcomes. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P
Læs mere Tjek på PubMedBMC Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract Purpose To compare the outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PKP) in the management of medically unresponsive Acanthamoeba keratitis (AK). Methods This retrospective study included 27 eyes of BB-DALK and 24 eyes of PKP from a tertiary ophthalmology care centre. Glucocorticoid eye drops were subsequently added to the treatment plan 2 months postoperatively based on the evaluation using confocal laser scanning microscopy. The clinical presentations, best-corrected visual acuity (BCVA), postoperative refractive outcomes, graft survival, and Acanthamoeba recurrence were analyzed. Results The AK patients included in the study were in stage 2 or stage 3, and the percentage of patients in stage 3 was higher in the PKP group (P = 0.003). Clinical presentations were mainly corneal ulcers and ring infiltrates, and endothelial plaques, hypopyon, uveitis and glaucoma were more common in the PKP group (P = 0.007). The BCVA and the graft survival rate showed no statistically significant differences between the two groups at 1 year after surgery. However, 3 years postoperatively, the BCVA of 0.71 ± 0.64 logMAR, the graft survival rate of 89.5%, and the endothelial cell density of 1899 ± 125 cells per square millimeter in the BB-DALK group were significantly better than those of the PKP group (P = 0.010, 0.046, and 0.032, respectively). 3 eyes (11.1%) in the BB-DALK group and 2 eyes (8.3%) in the PKP group experienced Acanthamoeba recurrence, but the rates showed no statistically significant difference between the two groups (P = 1.000). In the PKP group, immune rejection and elevated intraocular pressure were observed in 5 and 6 eyes, respectively. Conclusion Corneal transplantation is recommended for AK patients unresponsive to antiamoebic agents. The visual acuity and graft survival can be maintained after BB-DALK surgery. Acanthamoeba recurrence is not related to the surgical approach performed, whereas complete dissection of the infected corneal stroma and delayed prescribing of glucocorticoid eye drops were important to prevent recurrence.
Læs mere Tjek på PubMedBMC Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract Background The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis. Methods This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated. Results In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674–0.823), and 0.601 (95% CI: 0.524–0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025–6.891) was an independent risk factor for 28-day mortality. Conclusions The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.
Læs mere Tjek på PubMedKenneth W. NickersonDaniel J. GutzmannCory H. T. BooneRuvini U. PathiranaAudrey L. Atkin1School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA2Department of Biology and Chemistry, Texas A&M International University, Laredo, Texas, USA, Corrella S. Detweiler
Microbiology and Molecular Biology Reviews, 5.03.2024
Tilføjet 5.03.2024
Christopher J. HarmerRuth M. Hall1School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia, Corrella S. Detweiler
Microbiology and Molecular Biology Reviews, 5.03.2024
Tilføjet 5.03.2024
Christian R. Voolstra, Jean-Baptiste Raina, Melanie Dörr, Anny Cárdenas, Claudia Pogoreutz, Cynthia B. Silveira, Amin R. Mohamed, David G. Bourne, Haiwei Luo, Shady A. Amin, Raquel S. Peixoto
Nat Rev Microbiol, 5.03.2024
Tilføjet 5.03.2024
Nada RezaAlessandro GeradaKatharine E. StottAlex HowardMike SharlandWilliam Hope1Department of Antimicrobial Pharmacodynamics and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom2Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom3Centre for Neonatal and Paediatric Infection, Institute for Infection and Immunity, St George’s, University of London, London, United Kingdom, Graeme N. Forrest
Clinical Microbiology Reviews, 4.03.2024
Tilføjet 4.03.2024
Haibo SuShufeng WengLiulin LuoQin SunTaiyue LinHuixia MaYumo HeJing WuHonghai WangWenhong ZhangYing Xua State Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of Chinab Department of Intensive Care Unit, the Second Affiliated Hospital, GMU-GIBH Joint School of Life Science, Guangzhou Medical University, Guangzhou, People’s Republic of Chinac Shanghai Sci-Tech Inno Center for Infection & Immunity, Shanghai, People’s Republic of Chinad Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of Chinae Shanghai Clinical Research Center for Infectious Disease (Tuberculosis), Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China
Emerg Microbes Infect, 4.03.2024
Tilføjet 4.03.2024
Elena Cama, Loren Brener, Timothy Broady, Robyn Horwitz, Defeng Jin, Hoang Minh Khoi Vu, K. O. E. Wu, Carla Treloar
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by Elena Cama, Loren Brener, Timothy Broady, Robyn Horwitz, Defeng Jin, Hoang Minh Khoi Vu, K. O. E. Wu, Carla Treloar Research has shown that there are significant gaps in hepatitis B knowledge among migrant communities who are at risk of hepatitis B, such as Chinese and Vietnamese communities. Many students studying within Australia come from countries with high prevalence of hepatitis B. However, there is very little research examining hepatitis B knowledge, screening, or vaccination among university students in Australia or worldwide. The aim of this paper was to measure both levels of and demographic differences in hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia. Online surveys were completed by 112 Chinese- and 95 Vietnamese-identifying students in Australia, measuring knowledge of hepatitis B, engagement in screening and vaccination, and demographic characteristics. Results show that although engagement in screening and vaccination for hepatitis B was high, there were significant gaps in knowledge around transmission of hepatitis B. There were also some key demographic differences in screening and knowledge. For instance, those born in Australia were more likely to have been screened compared to those born Mainland China, Hong Kong, or Vietnam. Chinese students born in Australia had lower levels of knowledge compared to those born in Mainland China or Hong Kong. Among both samples, knowing someone living with hepatitis B was associated with higher levels of knowledge. Findings underscore the need for education-based interventions to address the significant gaps that exist in knowledge around hepatitis B, with a specific need for culturally appropriate resources in a range of languages to cater to the diverse communities who may be at risk of hepatitis B.
Læs mere Tjek på PubMedMenghao Teng, Jiachen Wang, Xiaochen Su, Ye Tian, Jiqing Wang, Yingang Zhang
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by Menghao Teng, Jiachen Wang, Xiaochen Su, Ye Tian, Jiqing Wang, Yingang Zhang Background Previous studies have indicated a heightened susceptibility to cataract and glaucoma among rheumatoid arthritis (RA) patients, while it remains uncertain whether RA is causally associated with cataract and glaucoma. A two-sample mendelian randomization (MR) analysis was used to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations. Methods In the European population, genome-wide association study (GWAS) summary statistics for cataract (372,386 individuals) and glaucoma (377,277 individuals) were obtained from the FinnGen consortium (R9), while RA summary data were derived from a meta-analysis of GWAS encompassing 97173 samples. In the East Asian population, summary data for cataract (212453 individuals), glaucoma (212453 individuals), and RA (22515 individuals) were sourced from the IEU Open GWAS project. Inverse-variance weighted (IVW, random-effects) method served as the primary analysis, complemented by MR‒Egger regression, weighted median, weighted mode and simple mode methods. Additionally, various sensitivity tests, including Cochran’s Q test, MR‒Egger intercept, MR pleiotropy Residual Sum and Outlier test and leave-one-out test were performed to detect the heterogeneity, horizontal pleiotropy and stability of the analysis results. Results Following stringent screening, the number of selected instrumental variables ranged from 8 to 56. The IVW results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019–1.064; P = 2.08×10−4) and glaucoma (OR = 1.029, 95% CI = 1.003–1.057; P = 2.94×10−2) in European populations, and RA displayed a positive association with cataract (OR = 1.021, 95% CI = 1.004–1.039; P = 1.64×10−2) in East Asian populations. Other methods also supported those results by IVW, and sensitivity tests showed that our analysis results were credible and stable. Conclusions This study revealed a positive causality between RA and the increased risk of cataract and glaucoma, which provides guidance for the early prevention of cataracts and glaucoma in patients with RA and furnishes evidence for the impact of RA-induced inflammation on ophthalmic diseases.
Læs mere Tjek på PubMedGetaneh Alemu, Arancha Amor, Endalkachew Nibret, Abaineh Munshea, Melaku Anegagrie
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by Getaneh Alemu, Arancha Amor, Endalkachew Nibret, Abaineh Munshea, Melaku Anegagrie Background Schistosoma mansoni and S. haematobium infections have been public health problems in Ethiopia, S. mansoni being more prevalent. To reduce the burden of schistosomiasis, a national school-based prazequantel (PZQ) mass drug administration (MDA) program has been implemented since November 2015. Nevertheless, S. mansoni infection is still a major public health problem throughout the country. Reduced efficacy of PZQ is reported by a few studies in Ethiopia, but adequate data in different geographical settings is lacking. Hence, this study aimed to assess the efficacy and safety of PZQ for the treatment of S. mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia. Methods A school-based single-arm prospective cohort study was conducted from February to June, 2023 among 130 S. mansoni-infected school-aged children (SAC). Forty-two, 37, and 51 S. mansoni-infected SAC were recruited from purposely selected schools located in low, moderate, and high transmission districts, respectively. School-aged children who were tested positive both by Kato Katz (KK) using stool samples and by the point of care circulating cathodic antigen (POC-CCA) test using urine samples at baseline were treated with a standard dose of PZQ and followed for 21 days for the occurrence of adverse events. After three weeks post-treatment, stool and urine samples were re-tested using KK and POC-CCA. Then the cure rate (CR), egg reduction rate (ERR), and treatment-associated adverse events were determined. The data were analyzed using SPSS version 21. Results Out of the total 130 study participants, 110 completed the follow-up. The CR and ERR of PZQ treatment were 88.2% (95%CI: 82.7–93.6) and 93.5% (95%CI: 85.4–98.5), respectively, by KK. The CR of PZQ based on the POC-CCA test was 70.9% (95%CI: 62.7–79.1) and 75.5% (95%CI: 67.3–83.6) depending on whether the interpretation of ‘trace’ results was made as positive or negative, respectively. After treatment on the 21st day, 78 and 83 participants tested negative both by KK and POC-CCA, with respective interpretations of ‘trace’ POC-CCA test results as positive or negative. The CR in low, moderate and high transmission settings was 91.7%, 91.2% and 82.5%, respectively (p = 0.377) when evaluated by KK. The CR among SAC with a light infection at baseline (95.7%) by KK was higher than that of moderate (81.5%) and heavy (64.3%) infections (χ2 = 12.53, p = 0.002). Twenty-six (23.6%) participants manifested at least one adverse event. Eleven (10.0%), eight (7.3%), six (5.5%), and three (2.7%) participants complained about abdominal pain, nausea, headache, and anorexia, respectively. All adverse events were mild, needing no intervention. Occurrence of adverse events was slightly higher in high endemic areas (32.5%) than moderate (23.5%) and low endemic areas (p = 0.279). Conclusions A single dose of 40 mg/kg PZQ was efficacious and safe for the treatment of S. mansoni infection when it was evaluated by the KK test, but a lower efficacy was recorded when it was evaluated by the POC-CCA test. However, the POC-CCA test’s specificity, clearance time of CCA from urine after treatment, and interpretation of weakly reactive (trace) test results need further research.
Læs mere Tjek på PubMedMarcel Schrijvers-Gonlag, Christina Skarpe, Riitta Julkunen-Tiitto, Antonio B. S. Poléo
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by Marcel Schrijvers-Gonlag, Christina Skarpe, Riitta Julkunen-Tiitto, Antonio B. S. Poléo Herbivory can be reduced by the production of defense compounds (secondary metabolites), but generally defenses are costly, and growth is prioritized over defense. While defense compounds may deter herbivory, nutrients may promote it. In a field study in boreal forest in Norway, we investigated how simulated herbivory affected concentrations of phenolics (generally a defense) and the carbon/nitrogen (C/N) ratio in annual shoots of bilberry (Vaccinium myrtillus), a deciduous clonal dwarf shrub whose vegetative and generative parts provide forage for many boreal forest animals. We measured concentrations of total tannins, individual phenolics, nitrogen and carbon following several types and intensities of herbivory. We identified 22 phenolics: 15 flavonoids, 1 hydroquinone and 6 phenolic acids. After high levels of herbivory, the total tannin concentration and the concentration of these 22 phenolics together (called total phenolic concentration) were significantly lower in bilberry annual shoots than in the control (natural herbivory at low to intermediate levels). Low-intensive herbivory, including severe defoliation, gave no significantly different total tannin or total phenolic concentration compared with the control. Many individual phenolics followed this pattern, while phenolic acids (deterring insect herbivory) showed little response to the treatments: their concentrations were maintained after both low-intensive and severe herbivory. Contrary to our predictions, we found no significant difference in C/N ratio between treatments. Neither the Carbon:Nutrient Balance hypothesis nor the Optimal Defense hypotheses, theories predicting plant resource allocation to secondary compounds, can be used to predict changes in phenolic concentrations (including total tannin concentration) in bilberry annual shoots after herbivory: in this situation, carbon is primarily used for other functions (e.g., maintenance, growth, reproduction) than defense.
Læs mere Tjek på PubMedDavid Dye, John W. Cain
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by David Dye, John W. Cain Wolbachia is an endosymbiont bacterium present in many insect species. When Wolbachia-carrying male Aedes aegypti mosquitoes mate with non-carrier females, their embryos are not viable due to cytoplasmic incompatibility. This phenomenon has been exploited successfully for the purpose of controlling mosquito populations and the spread of mosquito-borne illnesses: Wolbachia carriers are bred and released into the environment. Because Wolbachia is not harmful to humans, this method of mosquito control is regarded as a safer alternative to pesticide spraying. In this article, we introduce a mathematical framework for exploring (i) whether a one-time release of Wolbachia carriers can elicit a sustained presence of carriers near the release site, and (ii) the extent to which spatial propagation of carriers may allow them to establish fixation in other territories. While some prior studies have formulated mosquito dispersal models using advection-reaction-diffusion PDEs, the predictive power of such models requires careful ecological mapping: advection and diffusion coefficients exhibit significant spatial dependence due to heterogeneity of resources and topography. Here, we adopt a courser-grained view, regarding the environment as a network of discrete, diffusively-coupled “habitats”—distinct zones of high mosquito density such as stagnant ponds. We extend two previously published single-habitat mosquito models to multiple habitats, and calculate rates of migration between pairs of habitats using dispersal kernels. Our primary results are quantitative estimates regarding how the success of carrier fixation in one or more habitats is determined by: the number of carriers released, sizes of habitats, distances between habitats, and the rate of migration between habitats. Besides yielding sensible and potentially useful predictions regarding the success of Wolbachia-based control, our framework applies to other approaches (e.g., gene drives) and contexts beyond the realm of insect pest control.
Læs mere Tjek på PubMedMiyoko Massago, Mamoru Massago, Pedro Henrique Iora, Sanderland José Tavares Gurgel, Celso Ivam Conegero, Idalina Diair Regla Carolino, Maria Muzanila Mushi, Giane Aparecida Chaves Forato, João Vitor Perez de Souza, Thiago Augusto Hernandes Rocha, Samile Bonfim, Catherine Ann Staton, Oscar Kenji Nihei, João Ricardo Nickenig Vissoci, Luciano de Andrade
PLoS One Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
by Miyoko Massago, Mamoru Massago, Pedro Henrique Iora, Sanderland José Tavares Gurgel, Celso Ivam Conegero, Idalina Diair Regla Carolino, Maria Muzanila Mushi, Giane Aparecida Chaves Forato, João Vitor Perez de Souza, Thiago Augusto Hernandes Rocha, Samile Bonfim, Catherine Ann Staton, Oscar Kenji Nihei, João Ricardo Nickenig Vissoci, Luciano de Andrade Smoking cessation is an important public health policy worldwide. However, as far as we know, there is a lack of screening of variables related to the success of therapeutic intervention (STI) in Brazilian smokers by machine learning (ML) algorithms. To address this gap in the literature, we evaluated the ability of eight ML algorithms to correctly predict the STI in Brazilian smokers who were treated at a smoking cessation program in Brazil between 2006 and 2017. The dataset was composed of 12 variables and the efficacies of the algorithms were measured by accuracy, sensitivity, specificity, positive predictive value (PPV) and area under the receiver operating characteristic curve. We plotted a decision tree flowchart and also measured the odds ratio (OR) between each independent variable and the outcome, and the importance of the variable for the best model based on PPV. The mean global values for the metrics described above were, respectively, 0.675±0.028, 0.803±0.078, 0.485±0.146, 0.705±0.035 and 0.680±0.033. Supporting vector machines performed the best algorithm with a PPV of 0.726±0.031. Smoking cessation drug use was the roof of decision tree with OR of 4.42 and importance of variable of 100.00. Increase in the number of relapses also promoted a positive outcome, while higher consumption of cigarettes resulted in the opposite. In summary, the best model predicted 72.6% of positive outcomes correctly. Smoking cessation drug use and higher number of relapses contributed to quit smoking, while higher consumption of cigarettes showed the opposite effect. There are important strategies to reduce the number of smokers and increase STI by increasing services and drug treatment for smokers.
Læs mere Tjek på PubMedMalaria Journal, 4.03.2024
Tilføjet 4.03.2024
Abstract Background Insecticide-treated nets (ITNs) contributed significantly to the decline in malaria since 2000. Their protective efficacy depends not only on access, use, and net integrity, but also location of people within the home environment and mosquito biting profiles. Anopheline mosquito biting and human location data were integrated to identify potential gaps in protection and better understand malaria transmission dynamics in Busia County, western Kenya. Methods Direct observation of human activities and human landing catches (HLC) were performed hourly between 1700 to 0700 h. Household members were recorded as home or away; and, if at home, as indoors/outdoors, awake/asleep, and under a net or not. Aggregated data was analysed by weighting hourly anopheline biting activity with human location. Standard indicators of human-vector interaction were calculated using a Microsoft Excel template. Results There was no significant difference between indoor and outdoor biting for Anopheles gambiae sensu lato (s.l.) (RR = 0.82; 95% CI 0.65–1.03); significantly fewer Anopheles funestus were captured outdoors than indoors (RR = 0.41; 95% CI 0.25–0.66). Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400–0700 h for An. gambiae and 0300–0700 h for An. funestus. The study population away from home peaked at 1700–1800 h (58%), gradually decreased and remained constant at 10% throughout the night, before rising again to 40% by 0600–0700 h. When accounting for resident location, nearly all bites within the peri-domestic space (defined as inside household structures and surrounding outdoor spaces) occurred indoors for unprotected people (98%). Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning. Conclusion While use of an ITN was estimated to prevent most vector bites in this context, results suggest gaps in protection, particularly in the early hours of the morning when biting peaks and many people are awake and active. Assessment of additional human exposure points, including outside of the peri-domestic setting, are needed to guide supplementary interventions for transmission reduction.
Læs mere Tjek på PubMedMalaria Journal, 4.03.2024
Tilføjet 4.03.2024
Abstract Background The malaria incidence data from a malaria prevention study from the Rift Valley, Central Ethiopia, were reanalysed. The objective was to investigate whether including an administrative structure within the society, which may have required consideration in the protocol or previous analysis, would provide divergent outcomes on the effect measures of the interventions. Methods A cluster-randomized controlled trial lasting 121 weeks with 176 clusters in four groups with 6071 households with 34,548 persons was done: interventions combining indoor residual spraying (IRS) and insecticide-treated nets (ITNs), IRS alone, ITNs alone and routine use. The primary outcome was malaria incidence. A multilevel negative binomial regression model was employed to examine the impact of the kebele (smallest administrative unit) and the proximity of homes to the primary mosquito breeding sites as potential residual confounders (levels). The study also assessed whether these factors influenced the effect measures of the interventions. Results The study\'s initial findings revealed 1183 malaria episodes among 1059 persons, with comparable effects observed across the four intervention groups. In the reanalysis, the results showed that both ITN + IRS (incidence rate ratio [IRR] 0.63, P
Læs mere Tjek på PubMedJournal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Abstract Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Abstract Background Critical illness induces immune disorders associated with an increased risk of hospital-acquired pneumonia (HAP) and acute respiratory distress syndrome (ARDS). Torque Teno Virus (TTV), from the Anelloviridae family, are proposed as a biomarker to measure the level of immunosuppression. Our objective was to describe the kinetics of TTV DNA loads and their association with critical-illness related complications.Methods We performed a longitudinal study in 115 brain-injured patients from a prospective cohort, collected endotracheal and blood samples at three time points (T1, T2, T3) during the two weeks post-admission in intensive care unit, and measured viral DNA loads using the TTV R-gene® kit (Biomerieux) and a pan-Anelloviridae in house qRT-PCR.Results TTV DNA was detected in the blood of 69, 71, and 64% of brain-injured patients at T1, T2 and T3 respectively. Time-associated variations of TTV and Anellovirus (AV) DNA loads were observed. Using a linear mixed-effects model, we found that HAP and ARDS were associated with lower blood AV DNA loads.Conclusion Our results show that HAP or ARDS in critically ill patients are associated to changes in AV DNA loads, and should be evaluated further as a biomarker of immune disorders leading to these complications.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Abstract Background Polyomavirus nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV-haufen-test, centering around the detection of three-dimensional PyV aggregates in the urine, might provide crucial diagnostic information.Methods A multistep experimental design. Hypothesis: PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney specific protein; PyV-haufen are kidney-specific-disease-markers.Results Investigative step A showed colocalization of uromodulin with aggregated PyV (i) in ten kidneys with PyVN by immunohistochemistry, (ii) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (iii) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). Investigative step B: In in-vitro experiments only high uromodulin concentrations of ≥ 1.25 mg/mL aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2 -19.6 µg/mL). Investigative step C: 0/11 (0%) uromodulin KO-/- mice with histologic signs of PyVN showed urinary PyV-haufen shedding compared to 10/14 (71%) WT+/+ mice.Conclusion PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intra-renal disease, i.e. definitive PyVN.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Abstract Introduction People living with the human immunodeficiency virus (PWH) have microvascular disease. Since perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels.Methods Subcutaneous small arteries were dissected with or without (+ or -) PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged
Læs mere Tjek på PubMedJournal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Abstract Background The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges.Methods We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 non-neurosyphilis and 10 neurosyphilis patients. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 non-neurosyphilis, 51 untreated neurosyphilis, and 31 post-treatment neurosyphilis patients were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman\'s analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve.Results A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis were positive correlations with WBC counts, RPR titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an AUC of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR.Conclusions CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.
Læs mere Tjek på PubMedAnna Shmakova, Ivan Tsimailo, Yana Kozhevnikova, Laurence Gérard, David Boutboul, Eric Oksenhendler, Edouard Tuaillon, Aurélie Rivault, Diego Germini, Yegor Vassetzky, Bruno Beaumelle
International Journal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Human immunodeficiency virus (HIV) infection affects ∼38.4 million people worldwide (http://www.who.int/hiv/en/). The implementation of combination antiretroviral therapy (cART) largely decreased mortality and prolonged the lifespan of individuals with HIV [1]. However, people with HIV still face increased risks of different comorbidities. cART effectively controls viral replication but does not eliminate latently infected cells, posing challenges in achieving a cure [1].
Læs mere Tjek på PubMedCED Rees, BMC Swift, P Haldar
International Journal of Infectious Diseases, 4.03.2024
Tilføjet 4.03.2024
Tuberculosis (TB), an aerosol transmitted infection caused by Mycobacterium tuberculosis (Mtb), remains the commonest cause of death globally, from an infectious bacterial disease. Nine years on from the launch of the WHO\'s END-TB strategy, disease incidence rates are stubbornly unchanged [1]. While this represents, in part, a reversal of improving trends caused by the COVID-19 pandemic, it also reflects the fragility and inadequacy of healthcare systems to sustain TB control [2]. Although multifactorial, a key reason for this is the ineffectiveness of existing clinical tools to meet the two key objectives of the END-TB strategy – (i) early diagnosis and treatment of TB disease (to limit onward transmission); and (ii) disease prevention through screening for asymptomatic TB infection (TBI).
Læs mere Tjek på PubMedJournal of Medical Virology, 3.03.2024
Tilføjet 3.03.2024
BMC Infectious Diseases, 3.03.2024
Tilføjet 3.03.2024
Abstract Background Human herpesviruses are widespread among the human population. The infections often occur unnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence varies among subpopulations and with time. The aim of this study was to describe the seroprevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish population over a time period of several decades. Methods Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old men and 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibodies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linear regression analysis was used to differentiate between other factors such as age and gender. Results Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1 and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus (p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the prevalence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women, and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011). Conclusions The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virus decreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a child and adolescent.
Læs mere Tjek på PubMedGuido Werner, Hege Vangstein Aamot, Natacha Couto
Trends in Microbiology, 3.03.2024
Tilføjet 3.03.2024
Genome-based diagnostics provides relevant information to guide patient treatment and support pathogen and resistance surveillance. Recently, Coll et al. introduced a curated database for predicting antimicrobial resistance (AMR) from Enterococcus faecium genomics data, offering excellent predictive values for susceptibility to important antimicrobials. Challenges to predict resistance to last-resort antimicrobials remain.
Læs mere Tjek på PubMedDan Huang, Rong Xia, Chengyi Chen, Jingqiu Liao, Linxing Chen, Dongsheng Wang, Pedro J.J. Alvarez, Pingfeng Yu
Trends in Microbiology, 3.03.2024
Tilføjet 3.03.2024
Bacteriophages (phages) play a vital role in ecosystem functions by influencing the composition, genetic exchange, metabolism, and environmental adaptation of microbial communities. With recent advances in sequencing technologies and bioinformatics, our understanding of the ecology and evolution of phages in stressful environments has substantially expanded. Here, we review the impact of physicochemical environmental stress on the physiological state and community dynamics of phages, the adaptive strategies that phages employ to cope with environmental stress, and the ecological effects of phage–host interactions in stressful environments. Specifically, we highlight the contributions of phages to the adaptive evolution and functioning of microbiomes and suggest that phages and their hosts can maintain a mutualistic relationship in response to environmental stress. In addition, we discuss the ecological consequences caused by phages in stressful environments, encompassing biogeochemical cycling. Overall, this review advances an understanding of phage ecology in stressful environments, which could inform phage-based strategies to improve microbiome performance and ecosystem resilience and resistance in natural and engineering systems.
Læs mere Tjek på PubMedImmunity, 2.03.2024
Tilføjet 2.03.2024
Publication date: Available online 1 March 2024 Source: Immunity Author(s): Julia Lederhofer, Yaroslav Tsybovsky, Lam Nguyen, Julie E. Raab, Adrian Creanga, Tyler Stephens, Rebecca A. Gillespie, Hubza Z. Syeda, Brian E. Fisher, Michelle Skertic, Christina Yap, Andrew J. Schaub, Reda Rawi, Peter D. Kwong, Barney S. Graham, Adrian B. McDermott, Sarah F. Andrews, Neil P. King, Masaru Kanekiyo
Læs mere Tjek på PubMedMalaria Journal, 2.03.2024
Tilføjet 2.03.2024
Abstract Background Neonicotinoids are potential alternatives for controlling pyrethroid-resistant mosquitoes, but their efficacy against malaria vector populations of sub-Saharan Africa has yet to be investigated. The aim of the present study was to test the efficacy of four neonicotinoids against adult populations of the sibling species Anopheles gambiae and Anopheles coluzzii sampled along an urban-to-rural gradient. Methods The lethal toxicity of three active ingredients for adults of two susceptible Anopheles strains was assessed using concentration–response assays, and their discriminating concentrations were calculated. The discriminating concentrations were then used to test the susceptibility of An. gambiae and An. coluzzii mosquitoes collected from urban, suburban and rural areas of Yaoundé, Cameroon, to acetamiprid, imidacloprid, clothianidin and thiamethoxam. Results Lethal concentrations of neonicotinoids were relatively high suggesting that this class of insecticides has low toxicity against Anopheles mosquitoes. Reduced susceptibility to the four neonicotinoids tested was detected in An. gambiae populations collected from rural and suburban areas. By contrast, adults of An. coluzzii that occurred in urbanized settings were susceptible to neonicotinoids except acetamiprid for which 80% mortality was obtained within 72 h of insecticide exposure. The cytochrome inhibitor, piperonyl butoxide (PBO), significantly enhanced the activity of clothianidin and acetamiprid against An. gambiae mosquitoes. Conclusions These findings corroborate susceptibility profiles observed in larvae and highlight a significant variation in tolerance to neonicotinoids between An. gambiae and An. coluzzii populations from Yaoundé. Further studies are needed to disentangle the role of exposure to agricultural pesticides and of cross-resistance mechanisms in the development of neonicotinoid resistance in some Anopheles species.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Objective To evaluate the impact of hepatitis C virus (HCV) infection and treatment status on COVID-19-related hospitalizations in Georgia.Methods We analyzed 2020-2021 Georgian health-registry data for COVID-19-positive individuals and categorized by HCV infection and treatment status. Logistic regression was used to assess the strengths of the associations.Results Treated HCV individuals had lower odds of COVID-19-related hospitalization compared to anti-HCV-negatives, while untreated HCV-viremic and anti-HCV-positive non-viremic individuals had higher odds.Conclusions HCV treatment prior to COVID-19 infection was associated with lower odds of COVID-19-related hospitalization, highlighting the benefits of HCV management in the context of the pandemic.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Adverse outcomes of viral respiratory tract infections (RTI) have been reported in recipients of allogeneic hematopoietic cell transplantation. Using a laboratory-developed multiparameter PCR in a consecutive series of 242 patients, we found the highest incidence of viral RTI in the pre-engraftment phase. The occurrence of multiple episodes of viral RTI or viral pneumonia was significantly associated with a higher hazard of non-relapse mortality in the first year after transplantation. We observed a 90-day mortality of 19.7% after viral RTI, which was significantly different between patient groups stratified according to the ISI score.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19).Methods This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity.Results aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways.Conclusions Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Background Early risk assessment is needed to stratify Staphylococcus aureus infective endocarditis (SA-IE) risk among Staphylococcus aureus bacteraemia (SAB) patients to guide clinical management. The objective of this study is to develop a novel risk score independent of subjective clinical judgment and can be used early at the time of blood culture positivity.Methods We conducted a retrospective big data analysis from territory-wide electronic data and included hospitalized patients with SAB between 2009 and 2019. We applied a random forest risk scoring model to select variables from an array of parameters, according to the statistical importance of each feature in predicting SA-IE outcome. The data was divided into derivation and validation cohorts. The areas under the curve of the receiver operating characteristic (AUCROC) were determined.Results We identified 15,741 SAB patients, among them 4.18% had SA-IE. The AUCROC was 0.74 (95%CI 0.70-0.76), with a negative predictive value of 0.980 (95%CI 0.977–0.983). The four most discriminatory features were age, history of infective endocarditis, valvular heart disease, and being community-onset.Conclusion We developed a novel risk score with good performance as compared to existing scores and can be used at the time of SAB and prior to subjective clinical judgment.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 2.03.2024
Tilføjet 2.03.2024
Abstract Sepsis is characterised by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility to identify integrative patterns from clinical parameters, plasma biomarkers and extensive phenotyping of blood immune cells. Whilst no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90 day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90 day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical and clinical parameters.
Læs mere Tjek på PubMedClinical Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Background Hematopoietic cell transplant (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have high morbidity from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are limited data on outcomes from SARS-CoV-2 infection shortly before cellular therapy and uncertainty whether to delay therapy.Methods We conducted a retrospective cohort study of patients with SARS-CoV-2 infection within 90 days prior to HCT or CAR-T therapy between January 2020 and November 2022. We characterized the kinetics of SARS-CoV-2 detection, clinical outcomes following cellular therapy, and impact on delays in cellular therapy.Results We identified 37 patients (n=15 allogeneic HCT, n=11 autologous HCT, n=11 CAR-T therapy) with SARS-CoV-2 infections within 90 days of cellular therapy. Most infections (73%) occurred between March and November 2022, when Omicron strains were prevalent. Most patients had asymptomatic (27%) or mild (68%) coronavirus disease 2019 (COVID-19). SARS-CoV-2 positivity lasted a median of 20.0 days [IQR, 12.5-26.25]. The median time from first positive SARS-CoV-2 test to cellular therapy was 45 days [IQR, 37.75-70]; one patient tested positive on the day of infusion. After cellular therapy, no patients had recrudescent SARS-CoV-2 infection or COVID-19-related complications. Cellular therapy delays related to SARS-CoV-2 infection occurred in 70% of patients for a median of 37 days. Delays were more common after allogeneic (73%) and autologous (91%) HCT compared to CAR-T cell therapy (45%).Conclusions Patients with asymptomatic or mild COVID-19 may not require prolonged delays in cellular therapy in the context of contemporary circulating variants and availability of antiviral therapies.
Læs mere Tjek på PubMedClinical Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Implementation of dedicated pediatric antimicrobial stewardship programs (ASPs) at two combined adult-pediatric hospitals with existing ASPs was associated with sustained decreases in pediatric antibiotic use (AU) out of proportion to declines seen in adult inpatient units. ASPs in combined hospitals may not detect excessive pediatric AU without incorporating pediatric expertise.
Læs mere Tjek på PubMedInfection, 2.03.2024
Tilføjet 2.03.2024
Infection, 2.03.2024
Tilføjet 2.03.2024
Abstract Purpose The massive increase of infections with Group A Streptococcus (GAS) in 2022–2023 coincided in Switzerland with a change of the recommendations for the management of GAS pharyngitis. Therefore, the objective of the present study was to investigate whether the clinical manifestations and management before hospitalization for GAS infection differed in 2022–2023 compared with 2013–2022. Methods Retrospective study of GAS infections requiring hospitalization in patients below 16 years. Preadmission illness (modified McIsaac score), oral antibiotic use, and outcome in 2022–2023 were compared with 2013–2022. Time series were compared with surveillance data for respiratory viruses. Results In 2022–2023, the median modified McIsaac score was lower (2 [IQR 2–3] vs. 3 [IQR 2–4], p =
Læs mere Tjek på PubMedMakumbi, S., Bajunirwe, F., Ford, D., Turkova, A., South, A., Lugemwa, A., Musiime, V., Gibb, D., Tamwesigire, I. K.
BMJ Open, 2.03.2024
Tilføjet 2.03.2024
ObjectivesTo examine the voluntariness of consent in paediatric HIV clinical trials and the associated factors. DesignMixed-methods, cross-sectional study combining a quantitative survey conducted concurrently with indepth interviews. Setting and participantsFrom January 2021 to April 2021, we interviewed parents of children on first-line or second-line Anti-retroviral therapy (ART) in two ongoing paediatric HIV clinical trials [CHAPAS-4 (ISRCTN22964075) and ODYSSEY (ISRCTN91737921)] at the Joint Clinical Research Centre Mbarara, Uganda. Outcome measuresThe outcome measures were the proportion of parents with voluntary consent, factors affecting voluntariness and the sources of external influence. Parents rated the voluntariness of their consent on a voluntariness ladder. Indepth interviews described participants’ lived experiences and were aimed at adding context. ResultsAll 151 parents randomly sampled for the survey participated (84% female, median age 40 years). Most (67%) gave a fully voluntary decision, with a score of 10 on the voluntariness ladder, whereas 8% scored 9, 9% scored 8, 6% scored 7, 8% scored 6 and 2.7% scored 4. Trust in medical researchers (adjusted OR 9.90, 95% CI 1.01 to 97.20, p=0.049) and male sex of the parent (adjusted OR 3.66, 95% CI 1.00 to 13.38, p=0.05) were positively associated with voluntariness of consent. Prior research experience (adjusted OR 0.31, 95% CI 0.12 to 0.78, p=0.014) and consulting (adjusted OR 0.25. 95% CI 0.10 to 0.60, p=0.002) were negatively associated with voluntariness. Consultation and advice came from referring health workers (36%), spouses (29%), other family members (27%), friends (15%) and researchers (7%). The indepth interviews (n=14) identified the health condition of the child, advice from referring health workers and the opportunity to access better care as factors affecting the voluntariness of consent. ConclusionsThis study demonstrated a high voluntariness of consent, which was enhanced among male parents and by parents’ trust in medical researchers. Prior research experience of the child and advice from health workers and spouses were negatively associated with the voluntariness of parents’ consent. Female parents and parents of children with prior research experience may benefit from additional interventions to support voluntary participation.
Læs mere Tjek på PubMedLim, L.-l., Williams, K., Francis, J. J., Wroth, M., Breen, J.
BMJ Open, 2.03.2024
Tilføjet 2.03.2024
ObjectiveThe ‘To Dip or Not to Dip’ (TDONTD) intervention aims to reduce antibiotic prescribing for urinary tract infection (UTI) by reducing low-value dipstick testing. The aims of this study were to use a qualitative approach to (1) evaluate potential influences on the delivery of the TDONTD intervention in Australian residential aged care homes (RACHs) by identifying perceived barriers and enablers to delivery and acceptance; and (2) propose intervention strategies to address barriers and enhance enablers. DesignA qualitative before–after process evaluation of a multisite implementation study using interviews with nurse and pharmacist implementers. SettingThis study was conducted in 12 Australian RACHs. ParticipantsParticipants included 17 on-site nurse champions and 4 pharmacists (existing contracted providers). InterventionResources from England’s TDONTD intervention were adapted for an Australian context. Key resources delivered were case-based education, staff training video, clinical pathway and an audit tool. ResultsKey barriers to TDONTD were beliefs about nursing capabilities in diagnosing infection, beliefs about consequences (fear of missing infection) and social influences (pressure from family, doctors and hospitals). Key enablers were perceived increased nurse and carer knowledge (around UTI and asymptomatic bacteriuria), resources from a credible source, empowerment of nurse champions to apply knowledge and skills in delivering operational change initiatives, pharmacist-delivered education and organisational policy or process change. Of TDONTD’s key components, the clinical pathway substituted dipstick testing in diagnosing UTI, delivery of case-based education was enhanced by their attendance and support of the intervention and the antibiotic audit tool generated feedback that champions shared with staff. ConclusionsOur study confirms the core components of TDONTD and strategies to enhance delivery and overcome barriers. To further reduce barriers to TDONTD, broader advocacy work is required to raise awareness of dipstick testing as a low-value test in older persons and by linking it to healthcare professionals and consumer education.
Læs mere Tjek på PubMedYoung, A. M., Havens, J. R., Cooper, H. L. F., Fallin-Bennett, A., Fanucchi, L., Freeman, P. R., Knudsen, H., Livingston, M. D., McCollister, K. E., Stone, J., Vickerman, P., Freeman, E., Jahangir, T., Larimore, E., White, C. R., Cheatom, C., Community Staff, K., Design Team, K.
BMJ Open, 2.03.2024
Tilføjet 2.03.2024
IntroductionMany rural communities bear a disproportionate share of drug-related harms. Innovative harm reduction service models, such as vending machines or kiosks, can expand access to services that reduce drug-related harms. However, few kiosks operate in the USA, and their implementation, impact and cost-effectiveness have not been adequately evaluated in rural settings. This paper describes the Kentucky Outreach Service Kiosk (KyOSK) Study protocol to test the effectiveness, implementation outcomes and cost-effectiveness of a community-tailored, harm reduction kiosk in reducing HIV, hepatitis C and overdose risk in rural Appalachia. Methods and analysisKyOSK is a community-level, controlled quasi-experimental, non-randomised trial. KyOSK involves two cohorts of people who use drugs, one in an intervention county (n=425) and one in a control county (n=325). People who are 18 years or older, are community-dwelling residents in the target counties and have used drugs to get high in the past 6 months are eligible. The trial compares the effectiveness of a fixed-site, staffed syringe service programme (standard of care) with the standard of care supplemented with a kiosk. The kiosk will contain various harm reduction supplies accessible to participants upon valid code entry, allowing dispensing data to be linked to participant survey data. The kiosk will include a call-back feature that allows participants to select needed services and receive linkage-to-care services from a peer recovery coach. The cohorts complete follow-up surveys every 6 months for 36 months (three preceding kiosk implementation and four post-implementation). The study will test the effectiveness of the kiosk on reducing risk behaviours associated with overdose, HIV and hepatitis C, as well as implementation outcomes and cost-effectiveness. Ethics and disseminationThe University of Kentucky Institutional Review Board approved the protocol. Results will be disseminated in academic conferences and peer-reviewed journals, online and print media, and community meetings. Trial registration numberNCT05657106.
Læs mere Tjek på PubMedBMC Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
BMC Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Background The clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations. Therefore, we explored the variants associated with COVID-19 severity in the Guangdong population. Methods A total of 314 subjects were selected, of which the severe and critical COVID-19 patients were defined as “cases”, and the mild and moderate patients were defined as “control”. Twenty-two variants in interferon-related genes and FOXP4 were genotyped using the MassARRAY technology platform. Results IFN signaling gene MX1 rs17000900 CA + AA genotype was correlated with a reduced risk of severe COVID-19 in males (P = 0.001, OR = 0.050, 95%CI = 0.008–0.316). The AT haplotype comprised of MX1 rs17000900 and rs2071430 was more likely to protect against COVID-19 severity (P = 6.3E-03). FOXP4 rs1886814 CC genotype (P = 0.001, OR = 3.747, 95%CI = 1.746–8.043) and rs2894439 GA + AA genotype (P = 0.001, OR = 5.703, 95% CI = 2.045–15.903) were correlated with increased risk of severe COVID-19. Haplotype CA comprised of rs1886814 and rs2894439 was found to be correlated with adverse outcomes (P = 7.0E-04). FOXP4 rs1886814 CC (P = 0.0004) and rs2894439 GA + AA carriers had higher neutralizing antibody titers (P = 0.0018). The CA + AA genotype of MX1 rs17000900 tended to be correlated with lower neutralizing antibody titers than CC genotype (P = 0.0663), but the difference was not statistically significant. Conclusion Our study found a possible association between MX1 and FOXP4 polymorphisms and the severity of COVID-19. Distinguishing high-risk patients who develop severe COVID-19 will provide clues for early intervention and individual treatment strategies.
Læs mere Tjek på PubMedBMC Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Background HIV-1 CRF65_cpx strain carries drug-resistant mutations, which raises concerns about its potential for causing virologic failure. The CRF65_cpx ranks as the fourth most prevalent on Hainan Island, China. However, the origin and molecular epidemiology of CRF65_cpx strains in this area remain unclear. This study aims to estimate the spatial origins and dissemination patterns of HIV-1 CRF65_cpx in this specific region. Methods Between 2018 and 2021, a total of 58 pol sequences of the CRF65_cpx were collected from HIV-positive patients on Hainan Island. The available CRF65_cpx pol sequences from public databases were compiled. The HIV-TRACE tool was used to construct transmission networks. The evolutionary history of the introduction and dissemination of HIV-1 CRF65_cpx on Hainan Island were analyzed using phylogenetic analysis and the Bayesian coalescent-based approach. Results Among the 58 participants, 89.66% were men who have sex with men (MSM). The median age was 25 years, and 43.10% of the individuals had a college degree or above. The results indicated that 39 (67.24%) sequences were interconnected within a single transmission network. A consistent expansion was evident from 2019 to 2021, with an incremental annual addition of four sequences into the networks. Phylodynamic analyses showed that the CRF65_cpx on Hainan Island originated from Beijing (Bayes factor, BF = 17.4), with transmission among MSM on Hainan Island in 2013.2 (95%HPD: 2012.4, 2019.5), subsequently leading to an outbreak. Haikou was the local center of the CRF65_cpx epidemic. This strain propagated from Haikou to other locations, including Sanya (BF > 1000), Danzhou (BF = 299.3), Chengmai (BF = 27.0) and Tunchang (BF = 16.3). The analyses of the viral migration patterns between age subgroups and risk subgroups revealed that the viral migration directions were from "25–40 years old" to "17–24 years old" (BF = 14.6) and to "over 40 years old" (BF = 17.6), and from MSM to heterosexuals (BF > 1000) on Hainan Island. Conclusion Our analyses elucidate the transmission dynamics of CRF65_cpx strain on Hainan Island. Haikou is identified as the potential hotspot for CRF65_cpx transmission, with middle-aged MSM identified as the key population. These findings suggest that targeted interventions in hotspots and key populations may be more effective in controlling the HIV epidemic.
Læs mere Tjek på PubMedBMC Infectious Diseases, 2.03.2024
Tilføjet 2.03.2024
Abstract Objectives/Hypothesis To assess the efficacy of 0.23% povidone-iodine (PVP-I) nasal rinses and mouth washes on detectability of the coronavirus disease 2019 (COVID-19) virus and cycle threshold (Ct) values in nasopharyngeal swabs. Study design This was an open-label, prospective, randomized, placebo-controlled clinical trial. Setting The study was conducted in King Saud University Medical City, Riyadh, Saudi Arabia, from August 2021 to July 2022. Methods Participants diagnosed with SARS-CoV-2 were randomly assigned to one of three groups, with participants receiving either 0.23% PVP-I, 0.9% normal saline (NS) nasal rinses and mouth washes, or no intervention (control group). Nasopharyngeal swabs were taken 4, 8, 12, and 18 days after the first swab to measure the detectability of the virus and the Ct. Results A total of 19 participants were involved in this study. The mean viral survival was 9.8, 12, and 12.6 days for the PVP-I, NS, and control groups, respectively, with a statistically significant difference (p = 0.046). The Ct mean values were 23 ± 3.4, 23.5 ± 6.3, and 26.3 ± 5.9 at the time of recruitment and 25.2 ± 3.5, 15 ± 11.7, and 26.9 ± 6.4 after 4 days for the PVP-I, NS, and control groups, respectively. Conclusions When used continuously at a concentration of 0.23%, PVP-I showed promising results in terms of decreasing the pandemic burden by reducing the period of infectiousness and viral load. However, the use of PVP-I did not result in significantly different changes in the quality-of-life parameters in recently vaccinated and mild COVID-19 patients.
Læs mere Tjek på PubMedSergio P. Alpuche-Lazcano, Robert J. Scarborough and Anne Gatignol
Retrovirology, 2.03.2024
Tilføjet 2.03.2024
Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the cells that harbour them and on different...
Læs mere Tjek på PubMedWilson, Ira B.; Cole, Megan B.; Lee, Yoojin; Shireman, Theresa I.; Justice, Amy C.; Rahman, Momotazur
AIDS, 2.03.2024
Tilføjet 2.03.2024
Objective: To determine how aging impacts health care utilization in persons with HIV (PWH) compared to persons without HIV (PWoH). Design: Matched case-control study. Methods: We studied Medicaid recipients in the United States, aged 18-64 years, from 2001 to 2012. We matched each of 270,074 PWH to three PWoH by baseline year, age, gender, and zip code. Outcomes were hospital and nursing home days per month (DPM). Comorbid condition groups were cardiovascular disease, diabetes, liver disease, mental health conditions, pulmonary disease, and renal disease. We used linear regression to examine the joint relationships of age and comorbid conditions on the two outcomes, stratified by sex at birth. Results: We found small excesses in hospital DPM for PWH compared with PWoH. There were 0.03 and 0.07 extra hospital DPM for females and males, respectively, and no increases with age. In contrast, excess nursing home DPM for PWH compared with PWoH rose linearly with age, peaking at 0.35 extra days for females and 0.4 extra days for males. HIV-associated excess nursing home DPM were greatest for persons with cardiovascular disease, diabetes, mental health conditions, and renal disease. For PWH at age 55, this represents an 81% increase in the nursing home DPM for males, and a 110% increase for females, compared PWoH. Conclusions: Efforts to understand and interrupt this pronounced excess pattern of nursing home DPM among PWH compared to PWoH are needed and may new insights into how HIV and comorbid conditions jointly impact aging with HIV. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedWiseman, Robyn L.; Bigos, Kristin L.; Dastgheyb, Raha M.; Barker, Peter B.; Rubin, Leah H.; Slusher, Barbara S.
AIDS, 2.03.2024
Tilføjet 2.03.2024
Objectives : Cognitive impairment persists in virally-suppressed people with HIV (VS-PWH) especially in higher order domains. One cortical circuit, linked to these domains, is regulated by N-acetyl-aspartyl glutamate (NAAG), the endogenous agonist of the metabotropic glutamate receptor 3. The enzyme glutamate carboxypeptidase II (GCPII) catabolizes NAAG and is upregulated in aging and disease. Inhibition of GCPII increases brain NAAG and improves learning and memory in rodent and primate models. Design: As higher-order cognitive impairment is present in VS-PWH, and NAAG has not been investigated in earlier magnetic resonance spectroscopy studies (MRS), we investigated if brain NAAG levels measured by MRS were associated with cognitive function. Methods: We conducted a retrospective analysis of 7-Tesla MRS data from a previously published study on cognition in older VS-PWH. The original study did not separately quantify NAAG, therefore work for this report focused on relationships between regional NAAG levels in frontal white matter (FWM), left hippocampus, left basal ganglia and domain-specific cognitive performance in 40 VS-PWH after adjusting for confounds. Participants were >50 years of age, negative for affective and neurologic disorders, and had no prior 3-month psychoactive-substance use. Results: Higher NAAG levels in FWM were associated with better attention/working memory. Higher left basal ganglia NAAG related to better verbal fluency. There was a positive relationship between hippocampal NAAG and executive function which lost significance after correction for confounds. Conclusions: These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH. Conclusions: These data suggest brain NAAG serves as a biomarker of cognition in VS-PWH. Pharmacological modulation of brain NAAG warrants investigation as a therapeutic approach for cognitive deficits in VS-PWH. Graphical_abstract http://links.lww.com/QAD/D137 Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMed