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47 ud af 47 tidsskrifter valgt, ingen søgeord valgt, emner højest 7 dage gamle, sorteret efter nyeste først.
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Infection, 18.05.2024
Tilføjet 18.05.2024
Abstract Purpose Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management. Methods Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment. Results Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38–8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31–12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47–2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65–8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27–0.70]). Conclusion Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens.
Læs mere Tjek på PubMedSubhajit Chatterjee, Gabriel J. Starrett
Journal of Medical Virology, 18.05.2024
Tilføjet 18.05.2024
Seoyeon Kyung, Yejun Son, Minji Kim, Jiseung Kang, Lee Smith, Hayeon Lee, Dong Keon Yon
Journal of Medical Virology, 18.05.2024
Tilføjet 18.05.2024
BMC Infectious Diseases, 18.05.2024
Tilføjet 18.05.2024
Abstract Background The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China. Methods From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed. Results Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed
Læs mere Tjek på PubMedBMC Infectious Diseases, 18.05.2024
Tilføjet 18.05.2024
Abstract Background Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission. Methods Retrospective study conducted over a period of 6 years (2013–2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF). Results A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease. Conclusions The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 18.05.2024
Tilføjet 18.05.2024
Abstract The study of how micro-organisms detect and respond to different stresses has a long history of producing fundamental biological insights while being simultaneously of significance in many applied microbiological fields including infection, food and drink manufacture, and industrial and environmental biotechnology. This is well illustrated by the large body of work on acid stress. Numerous different methods have been used to understand the impacts of low pH on growth and survival of micro-organisms, ranging from studies of single cells to large and heterogeneous populations, from the molecular or biophysical to the computational, and from well-understood model organisms to poorly defined and complex microbial consortia. Much is to be gained from an increased general awareness of these methods, and so the present review looks at examples of the different methods that have been used to study acid resistance, acid tolerance, and acid stress responses, and the insights they can lead to, as well as some of the problems involved in using them. We hope this will be of interest both within and well beyond the acid stress research community.
Læs mere Tjek på PubMedDhrumi Shah, Sriram Varahan
Trends in Microbiology, 18.05.2024
Tilføjet 18.05.2024
Enterococcus faecalis is a Gram-positive opportunistic pathogen that is primarily associated with various infections, including bacteremia, endocarditis, peritonitis, surgical site infections, and catheter-associated urinary tract infections (CAUTIs). E. faecalis exists as a commensal organism in the gastrointestinal (GI) tract of animals, including insects, birds, reptiles, and mammals. Under specific conditions, including antibiotic-induced dysbiosis and severe inflammatory diseases in the GI tract, E.
Læs mere Tjek på PubMedAzadeh Nasuhidehnavi, George S. Yap
Trends in Parasitology, 18.05.2024
Tilføjet 18.05.2024
Polymeric guanylate-binding proteins (GBPs) physically dismember the vacuole membrane formed by Toxoplasma gondii while nitric oxide (NO) poisons and inhibits parasite replication within interferon (IFN)-γ activated macrophages. Zhao et al. report a novel mechanism for synergy between these classical microbicidal and microbistatic effectors in cell-autonomous immunity to the intracellular parasites.
Læs mere Tjek på PubMedMuge Cevik, Lindsay C Thompson, Caryn Upton, Valéria Cavalcanti Rolla, Mookho Malahleha, Blandina Mmbaga, Nosipho Ngubane, Zamzurina Abu Bakar, Mohammed Rassool, Ebrahim Variava, Rodney Dawson, Suzanne Staples, Umesh Lalloo, Cheryl Louw, Francesca Conradie, Marika Eristavi, Anastasia Samoilova, Sergey N Skornyakov, Niyanda Elias Ntinginya, Frederick Haraka, George Praygod, Harriett Mayanja-Kizza, Janice Caoili, Vincent Balanag, Margareth Pretti Dalcolmo, Timothy McHugh, Robert Hunt, Priya Solanki, Anna Bateson, Angela M Crook, Stella Fabiane, Juliano Timm, Eugene Sun, Melvin Spigelman, Derek J Sloan, Stephen H Gillespie, SimpliciTB Consortium
Lancet Infectious Diseases, 18.05.2024
Tilføjet 18.05.2024
For DS-TB, BPaMZ successfully met the primary efficacy endpoint of sputum culture conversion. The regimen did not meet the key secondary efficacy endpoint due to adverse events resulting in treatment withdrawal. Our study demonstrated the potential for treatment-shortening efficacy of the BPaMZ regimen for DS-TB and DR-TB, providing clinical validation of a murine model widely used to identify such regimens. It also highlights that novel, treatment-shortening TB treatment regimens require an acceptable toxicity and tolerability profile with minimal monitoring in low-resource and high-burden settings.
Læs mere Tjek på PubMedSeyed Hossein Karimi, Khaled Abdelaziz, Heidi Spahany, Jake Astill, David Trott, Blake Wang, Alice Wang, John Parkinson, Shayan Sharif
PLoS One Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
by Seyed Hossein Karimi, Khaled Abdelaziz, Heidi Spahany, Jake Astill, David Trott, Blake Wang, Alice Wang, John Parkinson, Shayan Sharif
Læs mere Tjek på PubMedThe PLOS ONE Editors
PLoS One Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Yu Liang, Anzhou Ma
PLoS One Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
by Yu Liang, Anzhou Ma Perfluorooctane sulfonate (PFOS) is a prominent perfluorinated compound commonly found in the environment, known to pose various risks to human health. However, the removal of PFOS presents significant challenges, primarily due to the limited discovery of bacteria capable of effectively degrading PFOS. Moreover, single degradation bacteria often encounter obstacles in individual cultivation and the breakdown of complex pollutants. In contrast, microbial consortia have shown promise in pollutant degradation. This study employed a continuous enrichment method, combined with multiple co-metabolic substrates, to investigate a microbial consortium with the potential for PFOS degradation. By employing this methodology, we effectively identified a microbial consortium that demonstrated the capacity to reduce PFOS when exposed to an optimal concentration of methanol. The consortium predominantly comprised of Hyphomicrobium species (46.7%) along with unclassified microorganisms (53.0%). Over a duration of 20 days, the PFOS concentration exhibited a notable decrease of 56.7% in comparison to the initial level, while considering the exclusion of adsorption effects. Furthermore, by comparing the predicted metabolic pathways of the microbial consortium with the genome of a known chloromethane-degrading bacterium, Hyphomicrobium sp. MC1, using the KEGG database, we observed distinct variations in the metabolic pathways, suggesting the potential role of the unclassified microorganisms. These findings underscore the potential effectiveness of a \'top-down\' functional microbial screening approach in the degradation of stubborn pollutants.
Læs mere Tjek på PubMedGennaro Esposito, Yamanappa Hunashal, Mathias Percipalle, Federico Fogolari, Tomas Venit, Ainars Leonchiks, Kristin C. Gunsalus, Fabio Piano, Piergiorgio Percipalle
PLoS One Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
by Gennaro Esposito, Yamanappa Hunashal, Mathias Percipalle, Federico Fogolari, Tomas Venit, Ainars Leonchiks, Kristin C. Gunsalus, Fabio Piano, Piergiorgio Percipalle The interaction between SARS-CoV-2 non-structural protein Nsp9 and the nanobody 2NSP90 was investigated by NMR spectroscopy using the paramagnetic perturbation methodology PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation). The Nsp9 monomer is an essential component of the replication and transcription complex (RTC) that reproduces the viral gRNA for subsequent propagation. Therefore preventing Nsp9 recruitment in RTC would represent an efficient antiviral strategy that could be applied to different coronaviruses, given the Nsp9 relative invariance. The NMR results were consistent with a previous characterization suggesting a 4:4 Nsp9-to-nanobody stoichiometry with the occurrence of two epitope pairs on each of the Nsp9 units that establish the inter-dimer contacts of Nsp9 tetramer. The oligomerization state of Nsp9 was also analyzed by molecular dynamics simulations and both dimers and tetramers resulted plausible. A different distribution of the mapped epitopes on the tetramer surface with respect to the former 4:4 complex could also be possible, as well as different stoichiometries of the Nsp9-nanobody assemblies such as the 2:2 stoichiometry suggested by the recent crystal structure of the Nsp9 complex with 2NSP23 (PDB ID: 8dqu), a nanobody exhibiting essentially the same affinity as 2NSP90. The experimental NMR evidence, however, ruled out the occurrence in liquid state of the relevant Nsp9 conformational change observed in the same crystal structure.
Læs mere Tjek på PubMedSalman Khan, Arghya Das, Deepali Vashisth, Anwita Mishra, Ashima Jain Vidyarthi, Raghav Gupta, Nazneen Nahar Begam, Babita Kataria, Sushma Bhatnagar
PLoS One Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
by Salman Khan, Arghya Das, Deepali Vashisth, Anwita Mishra, Ashima Jain Vidyarthi, Raghav Gupta, Nazneen Nahar Begam, Babita Kataria, Sushma Bhatnagar NDM-producing carbapenem-resistant bacterial infections became a challenge for clinicians. Combination therapy of aztreonam and ceftazidime-avibactam is a prudent choice for these infections. However, there is still no recommendation of a practically feasible method for testing aztreonam and ceftazidime-avibactam synergy. We proposed a simple method for testing aztreonam and ceftazidime-avibactam synergy and compared it with reference broth micro-dilution and other methods. Carbapenem-resistant Enterobacterales clinical isolates were screened for the presence of the NDM gene by the Carba R test. NDM harbouring isolates were tested for aztreonam and ceftazidime-avibactam synergy by broth microdilution (reference method), E strip-disc diffusion, double disc diffusion, and disc replacement methods. In the newly proposed method, the MHA medium was supplemented with ceftazidime-avibactam (corresponding to an aztreonam concentration of 4μg/ml). The MHA medium was then inoculated with the standard inoculum (0.5 McFarland) of the test organism. An AZT disc (30 μg) was placed on the supplemented MHA medium, and the medium was incubated overnight at 37°C. Aztreonam zone diameter on the supplemented MHA medium (in the presence of ceftazidime-avibactam) was compared with that from a standard disc diffusion plate (without ceftazidime-avibactam), performed in parallel. Interpretation of synergy was based on the restoration of aztreonam zone diameter (in the presence of ceftazidime-avibactam) crossing the CLSI susceptibility breakpoint, i.e., ≥ 21 mm. Of 37 carbapenem-resistant NDM-producing isolates, 35 (94.6%) were resistant to aztreonam and tested synergy positive by the proposed method. Its sensitivity and specificity were 97.14% and 100%, respectively. Cohen’s kappa value showed substantial agreement of the reference method with the proposed method (κ = 0.78) but no other methods. The proposed method is simple, easily interpretable, and showed excellent sensitivity, specificity, and agreement with the reference method. Therefore, the new method is feasible and reliable for testing aztreonam synergy with avibactam in NDM-producing Enterobacterales.
Læs mere Tjek på PubMedInfection, 17.05.2024
Tilføjet 17.05.2024
Bradford BeckenKhalid M. DousaJohn L. JohnsonSteven M. HollandRobert A. Bonomo1Division of Pediatric Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA2Department of Internal Medicine and Infectious Diseases, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA3Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA4Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA5Department of Internal Medicine, CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA, Cesar A. Arias
Antimicrobial Agents And Chemotherapy, 17.05.2024
Tilføjet 17.05.2024
L. M. MinukS. K. BrodeM. MehrabiM. K. SharmaM. StobartH. SoualhineT. K. Marras1Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada2Division of Respirology, Department of Medicine, University Health Network, Mount Sinai Hospital, Toronto, Ontario, Canada3Division of Respiratory Medicine, West Park Healthcare Centre, Toronto, Ontario, Canada4Division of Respirology, Department of Medicine, Toronto Western Hospital, Toronto, Ontario, Canada5National Reference Centre for Mycobacteriology, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada6Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada7McGill International TB Centre, McGill University, Montreal, Quebec, Canada, Sean Wasserman
Antimicrobial Agents And Chemotherapy, 17.05.2024
Tilføjet 17.05.2024
Journal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Maternal priming with Bacille Calmette-Guérin (BCG) has been associated with reduced mortality in male offspring. We investigated this association in a cohort of healthy BCG-vaccinated neonates.Methods Observational study within a randomized controlled trial comparing different BCG strains conducted in Guinea-Bissau from 2017-2020. As part of trial inclusion procedures, on the day of discharge from the maternity ward, maternal BCG scar status was evaluated by visual inspection, followed by offspring BCG and polio vaccination. Through mortality data collected at telephone interviews at six weeks and six months of age, we assessed all-cause mortality risk in Cox Proportional Hazards models adjusted for maternal schooling and BCG strain, providing adjusted Mortality Rate Ratios (aMRRs).Results 64% (11,070/17,275) of mothers had a BCG scar, which for females and overall was not associated with neither admission risk, admission severity nor all-cause mortality. By six months of age, the mortality rate (MR) was 4.1 (200 deaths/4,919 person-years) for the maternal BCG scar cohort and 5.2 (139 deaths/2,661 person-years) for no maternal scar, aMRR=0.86 (0.69-1.06). In males, six-month MRs were 4.3 (109/2,531) for maternal BCG scar vs 6.3 (87/1,376) for no scar, the maternal scar/no scar aMRR being 0.74 (0.56-0.99). In females, six-month MRs were 3.8 (91/2,388) vs 4.0 (52(1,286), the aMRR being 1.04 (0.74-1.47), p for interaction with sex=0.16.Conclusion While we cannot rule out an association in females, being born to a mother with a BCG scar reduced the risk of death during early infancy for BCG-vaccinated males, reproducing findings from previous studies.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Quantifying the risk of SARS-CoV-2 transmission in indoor settings is crucial for developing effective non-vaccine prevention strategies and policies. However, summary evidence on the transmission risks in settings other than households, schools, elderly care and healthcare facilities is limited. We conducted a systematic review to estimate the secondary attack rates (SARs) of SARS-CoV-2 and the factors modifying transmission risk in community indoor settings.Methods We searched Medline, Scopus, Web of Science, WHO COVID-19 Research Database, MedrXiv, and BiorXiv from January 1, 2020, to February 20, 2023. We included articles with original data for estimating SARS-CoV-2 SARs. We estimated the overall and setting-specific SARs using the inverse variance method for random-effects meta-analyses.Results We included 34 studies with data on 577 index cases, 898 secondary cases, and 9173 contacts. The pooled SAR for community indoor settings was 20.4% (95% confidence interval [CI] 12.0–32.5%). The setting-specific SARs were highest for singing events (SAR 44.9%, 95% CI 14.5–79.7%), indoor meetings and entertainment venues (31.9%, 10.4–65.3%), and fitness centers (28.9%, 9.9–60.1%). We found no difference in SARs by index case, viral, and setting-specific characteristics.Conclusions The risk of SARS-CoV-2 transmission was highest in indoor settings where singing and exercising occurred. Effective mitigation measures such as assessing and improving ventilation should be considered to reduce the risk of transmission in high-risk settings. Future studies should systematically assess and report the host, viral, and setting-specific characteristics that may modify the transmission risks of SARS-CoV-2 and other respiratory viruses in indoor environments.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Drug-resistant shigellosis is increasing, particularly among men who have sex with men (MSM). During July–October 2022, an extended-spectrum beta-lactamase producing Shigella sonnei cluster of 9 patients was identified in Chicago, of whom 8 were MSM and 6 were festival attendees. The cluster also included 4 domestic travelers to Chicago. Sexual health care for MSM should include shigellosis diagnosis and prevention.
Læs mere Tjek på PubMedWang, J., Jiang, C., Wang, S., Feng, L., Zhang, Y., Guo, Y., Liu, G., Li, X., Zhang, G., Zhu, X., Ren, F., Guan, L., Chen, J., Gao, Y., Chen, M., Darwish, N., Mottaz, S. C., Horcajada, M. N., Bonnet, N., Dogra, S. K., Wang, D.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
PurposeThe Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process. ParticipantsThe recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively. Findings to dateThe age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study. Future plansData collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0–3 years and investigate the contribution of dietary factors in the process. Trial registration numberChiCTR2100049972
Læs mere Tjek på PubMedYiryuo, L., Kpekura, S., Osman, W., Kukeba, M. W., Mumuni, N. D., Mwinbam, M. M., Dery, A.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
BackgroundFamily caregivers of children living with HIV/AIDS in most cases are found to be overwhelmed and under-resourced, yet they are believed to be the primary source of support for children living with HIV/AIDS. Family caregivers experience different challenges that affect their children’s antiretroviral therapy (ART) adherence. AimThis study explored the lived experiences of family caregivers of children living with HIV/AIDS who sought ART services for these children at the St Joseph’s Hospital of Jirapa, Ghana. MethodUsing a qualitative phenomenology design and a semistructured in-depth interview guide and using purposive sampling, data were gathered from 13 family caregivers of children living with HIV/AIDS receiving ART treatment at St Joseph’s Hospital, Jirapa following ethical approval. All interviews were audio-taped and transcribed verbatim. Reflexive thematic analysis was used to analyse the transcribed data. FindingsSix themes were generated: five challenges and one support. Family caregivers of children living with HIV/AIDS experienced: (1) Financial challenges, (2) Human-related challenges, (3) Challenges at HIV testing and counselling (HTC) centres, (4) Challenges with transportation, (5) Challenges in disclosing children’s HIV status to them and (6) Support received from HTC and their family members. Conclusion and recommendationFamily caregivers of children living with HIV/AIDS experience daunting challenges in their quest to care for their children. Governmental and non-governmental HIV/AIDS programme support should include small business skills training and acquisition including capital to help set up small-scale businesses for such caregivers to reduce their financial challenges. Access to ART at clinics closer to caregivers is also key to promoting adherence. Family and community support has been recognised as key to enhancing ART adherence. Education of caregivers on policy regarding disclosure of the HIV/AIDS status of children, the need to work to reduce the time spent by caregivers at HTC, and ensuring privacy by limiting access to HTCs to only caregivers and their children, are important to enhancing adherence.
Læs mere Tjek på PubMedMcManus, C., Mifflin, N., Rivera, R., Vause, S., Tran, T., Ostroff, M., Harrowell, L., Frost, S., Alexandrou, E.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
ObjectivesTo compare catheter-related outcomes of individuals who received a tunnelled femorally inserted central catheter (tFICC) with those who received a peripherally inserted central catheter (PICC) in the upper extremities. DesignA propensity-score matched cohort study. SettingA 980-bed tertiary referral hospital in South West Sydney, Australia. ParticipantsIn-patients referred to the hospital central venous access service for the insertion of a central venous access device. Primary and secondary outcome measuresThe primary outcome of interest was the incidence of all-cause catheter failure. Secondary outcomes included the rates of catheters removed because of suspected or confirmed catheter-associated infection, catheter dwell and confirmed upper or lower extremity deep vein thrombosis (DVT). ResultsThe overall rate of all-cause catheter failure in the matched tFICC and PICC cohort was 2.4/1000 catheter days (95% CI 1.1 to 4.4) and 3.0/1000 catheter days (95% CI 2.3 to 3.9), respectively, and when compared, no difference was observed (difference –0.63/1000 catheter days, 95% CI –2.32 to 1.06). We found no differences in catheter dwell (mean difference of 14.2 days, 95% CI –6.6 to 35.0, p=0.910); or in the cumulative probability of failure between the two groups within the first month of dwell (p=0.358). No significant differences were observed in the rate of catheters requiring removal for confirmed central line-associated bloodstream infection (difference 0.13/1000 catheter day, 95% CI –0.36 to 0.63, p=0.896). Similarly, no significant differences were found between the groups for confirmed catheter-related DVT (difference –0.11 per 1000 catheter days, 95% CI –0.26 to 0.04, p=1.00). ConclusionThere were no differences in catheter-related outcomes between the matched cohort of tFICC and PICC patients, suggesting that tFICCs are a possible alternative for vascular access when the veins of the upper extremities or thoracic region are not viable for catheterisation.
Læs mere Tjek på PubMedSu, J., Chen, P., Yang, Y., Gao, Z., Bi, Z., Feng, M.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
PurposeThe administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case–control study was conducted. MethodsClinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally. ResultsA total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p
Læs mere Tjek på PubMedYip, S. W. S., Weinberg, L., Gooi, J., Sivenayagam, S., Coulson, T. G., Barnett, S. A., Knight, S. R., Ludski, J., Lee, D. K.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
IntroductionExtrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD. It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes. Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps. Methods and analysisThis scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care. Ethics and disseminationEthics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.
Læs mere Tjek på PubMedMills, N., Farrar, N., Warnes, B., Ashton, K. E., Harris, R., Rogers, C. A., Lim, E., Elliott, D.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
ObjectivesRecruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent. DesignA multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period. SettingSecondary thoracic cancer care. ResultsRespiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment. ConclusionsWith bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible. Trial registration numberISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.
Læs mere Tjek på PubMedRake, E. A., Meinders, M. J., Brand, G., Dreesens, D., Kremer, J. A. M., Elwyn, G., Aarts, J. W. M.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
ObjectivesPatients’ preferences, values and contexts are important elements of the shared decision-making (SDM) process. We captured those elements into the concept of ‘personal perspective elicitation’ (PPE), which reflects the need to elicit patients’ preferences, values and contexts in patient–clinician conversations. We defined PPE as: ‘the disclosure (either elicited by the clinician or spontaneously expressed by the patient) of information related to the patient’s personal preferences, values and/or contexts potentially relevant to decision-making’. Our goal was to operationalise the concept of PPE through the evaluation of preferences, values and contexts and explore how PPE occurs in clinical encounters. DesignCross-sectional study: observational coding based on a novel coding scheme of audio-recorded outpatient clinical encounters where encounter patient decision aids were applied. SettingWe audio-recorded patient–clinician interactions at three Dutch outpatient clinics. PPE was analysed using a novel observational coding scheme, distinguishing preferences, contexts and four Armstrong taxonomy value types (global, decisional, external and situational). We measured SDM using the Observer OPTION5. ParticipantsTwenty patients who suffered from psoriasis or ovarian cysts; four clinicians. ResultsWe included 20 audio-recordings. The mean Observer OPTION5 score was 57.5 (SD:10.1). The audio-recordings gave a rich illustration of preferences, values and contexts that were discussed in the patient–clinician interactions. Examples of identified global values: appearance, beliefs, personality traits. Decisional values were related to the process of decision-making. External values related to asking advice from for example, the clinician or significant others. An identified situational value: a new job ahead. Contexts related to how the illness impacted the life (eg, sexuality, family, sports, work life) of patients. ConclusionsThe operationalisation of PPE, an important aspect of SDM, explores which preferences, values and contexts were discussed during patient–clinician interactions where an ePDA was used. The coding scheme appeared feasible to apply but needs further refinement.
Læs mere Tjek på PubMedSunkersing, D., Ramasawmy, M., Alwan, N. A., Clutterbuck, D., Mu, Y., Horstmanshof, K., Banerjee, A., Heightman, M.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
ObjectiveTo investigate current care for people with Long COVID in England. DesignIn-depth, semistructured interviews with people living with Long COVID and Long COVID healthcare professionals; data analysed using thematic analysis. SettingNational Health Service England post-COVID-19 services in six clinics from November 2022 to July 2023. Participants15 healthcare professionals and 21 people living with Long COVID currently attending or discharged (18 female; 3 male). ResultsHealth professionals and people with lived experience highlighted the multifaceted nature of Long COVID, including its varied symptoms, its impact on people’s lives and the complexity involved in managing this condition. These impacts encompass physical, social, mental and environmental dimensions. People with Long COVID reported barriers in accessing primary care, as well as negative general practitioner consultations where they felt unheard or invalidated, though some positive interactions were also noted. Peer support or support systems proved highly valuable and beneficial for individuals, aiding their recovery and well-being. Post-COVID-19 services were viewed as spaces where overlooked voices found validation, offering more than medical expertise. Despite initial challenges, healthcare providers’ increasing expertise in diagnosing and treating Long COVID has helped refine care approaches for this condition. ConclusionLong COVID care in England is not uniform across all locations. Effective communication, specialised expertise and comprehensive support systems are crucial. A patient-centred approach considering the unique complexities of Long COVID, including physical, mental health, social and environmental aspects is needed. Sustained access to post-COVID-19 services is imperative, with success dependent on offering continuous rehabilitation beyond rapid recovery, acknowledging the condition’s enduring impacts and complexities.
Læs mere Tjek på PubMedFrith, M., Boyd, J., Savira, F., Senyel, D., Norman, R., Jones, J., Robinson, S.
BMJ Open, 17.05.2024
Tilføjet 17.05.2024
IntroductionTelehealth service provision and uptake has rapidly increased since the COVID-19 pandemic, allowing healthcare to be delivered safely and reducing non-essential face-to-face (F2F) contact. In Australia, the expansion of subsidisation of telehealth during COVID has led to its permanent installation within Australian primary care in 2022. However, little is known about consumer preferences and experiences with these services, particularly in relation to allied health practice (AHP). Previous studies on telehealth services have focused on general practice rather than allied health (AH) and broader primary care. Given that AH professionals make up a large proportion of the Australian healthcare workforce, the purpose of this study is to explore consumer preferences and experiences with telehealth AHP healthcare. Methods and analysisThis study uses a mixed methods research design that incorporates three independent but interrelated phases. Phase 2 of the study will use a focus group methodology to discuss consumer attitudes and experiences via a semistructured interview format. Phase 3 involves a discrete choice experiment (DCE) involving a large online survey conducted across the general population. The DCE will be informed by the qualitative findings from phases 1 and 2. The experiment aims to elicit consumer preferences in relation to AH services delivered through telehealth or F2F consultations, based on several hypothetical scenarios and preferences over several different dimensions. Ethics and disseminationEthics approval has been obtained from La Trobe University (approval number HEC23404). Findings will be disseminated as reports, presentations and peer-reviewed journal articles.
Læs mere Tjek på PubMedBMC Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Screening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV) care. The uptake of TPT during the coronavirus disease 2019 (COVID-19) period has not been adequately assessed in Addis Ababa City Administration. This study aimed at assessing TPT uptake status among People living with HIV (PLHIV) newly initiated on antiretroviral therapy during the COVID-19 period at all public hospitals of Addis Ababa City Administration, Ethiopia. Methods A retrospective data review was conducted from April-July 2022. Routine District Health Information System 2 database was reviewed for the period from April 2020-March 2022. Proportion and mean with standard deviation were computed. Logistic regression analysis was conducted to assess factors associated with TPT completion. A p-value of
Læs mere Tjek på PubMedBMC Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Antimicrobial resistance (AMR) represents a significant threat to global health with Neisseria gonorrhoea emerging as a key pathogen of concern. In Australia, the Australian Gonococcal Surveillance Program (AGSP) plays a critical role in monitoring resistance patterns. However, antibiotic susceptibility test (AST) uptake – a crucial component for effective resistance surveillance – remains to be a limiting factor. The study aims to model the processes involved in generating AST tests for N. gonorrhoea isolates within the Australian healthcare system and assess the potential impact of systematic and policy-level changes. Methods Two models were developed. The first model was a mathematical stochastic health systems model (SHSM) and a Bayesian Belief Network (BBN) to simulate the clinician-patient dynamics influencing AST initiation. Key variables were identified through systematic literature review to inform the construction of both models. Scenario analyses were conducted with the modification of model parameters. Results The SHSM and BBN highlighted clinician education and the use of clinical support tools as effective strategies to improve AST. Scenario analysis further identified adherence to guidelines and changes in patient-level factors, such as persistence of symptoms and high-risk behaviours, as significant determinants. Both models supported the notion of mandated testing to achieve higher AST initiation rates but with considerations necessary regarding practicality, laboratory constraints, and culture failure rate. Conclusion The study fundamentally demonstrates a novel approach to conceptualising the patient-clinician dynamic within AMR testing utilising a model-based approach. It suggests targeted interventions to educational, support tools, and legislative framework as feasible strategies to improve AST initiation rates. However, the research fundamentally highlights substantial research gaps in the underlying understanding of AMR.
Læs mere Tjek på PubMedBMC Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Early in the host-response to infection, neutrophils release calprotectin, triggering several immune signalling cascades. In acute infection management, identifying infected patients and stratifying these by risk of deterioration into sepsis, are crucial tasks. Recruiting a heterogenous population of patients with suspected infections from the emergency department, early in the care-path, the CASCADE trial aimed to evaluate the accuracy of blood calprotectin for detecting bacterial infections, estimating disease severity, and predicting clinical deterioration. Methods In a prospective, observational trial from February 2021 to August 2022, 395 patients (n = 194 clinically suspected infection; n = 201 controls) were enrolled. Blood samples were collected at enrolment. The accuracy of calprotectin to identify bacterial infections, and to predict and identify sepsis and mortality was analysed. These endpoints were determined by a panel of experts. Results The Area Under the Receiver Operating Characteristic (AUROC) of calprotectin for detecting bacterial infections was 0.90. For sepsis within 72 h, calprotectin’s AUROC was 0.83. For 30-day mortality it was 0.78. In patients with diabetes, calprotectin had an AUROC of 0.94 for identifying bacterial infection. Conclusions Calprotectin showed notable accuracy for all endpoints. Using calprotectin in the emergency department could improve diagnosis and management of severe infections, in combination with current biomarkers. Clinical trial registration number DRKS00020521
Læs mere Tjek på PubMedBMC Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background In recent years, there has been a growing interest in phage therapy as an effective therapeutic tool against colibacillosis caused by avian pathogenic Escherichia coli (APEC) which resulted from the increasing number of multidrug resistant (MDR) APEC strains. Methods In the present study, we reported the characterization of a new lytic bacteriophage (Escherichia phage AG- MK-2022. Basu) isolated from poultry slaughterhouse wastewater. In addition, the in vitro bacteriolytic activity of the newly isolated phage (Escherichia phage AG- MK-2022. Basu) and the Escherichia phage VaT-2019a isolate PE17 (GenBank: MK353636.1) were assessed against MDR- APEC strains (n = 100) isolated from broiler chickens with clinical signs of colibacillosis. Results Escherichia phage AG- MK-2022. Basu belongs to the Myoviridae family and exhibits a broad host range. Furthermore, the phage showed stability under a wide range of temperatures, pH values and different concentrations of NaCl. Genome analysis of the Escherichia phage AG- MK-2022. Basu revealed that the phage possesses no antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and any E. coli virulence associated genes. In vitro bacterial challenge tests demonstrated that two phages, the Escherichia phage VaT-2019a isolate PE17 and the Escherichia phage AG- MK-2022. Basu exhibited high bactericidal activity against APEC strains and lysed 95% of the tested APEC strains. Conclusions The current study findings indicate that both phages could be suggested as safe biocontrol agents and alternatives to antibiotics for controlling MDR-APEC strains isolated from broilers.
Læs mere Tjek på PubMedM. Molemans, L. Kayaert, Q. Olislagers, S. Abrahams, N. Berkowitz, E. Mohr‐Holland, D. McKelly, R. Wood, F. van Leth, S. Hermans
Tropical Medicine & International Health, 17.05.2024
Tilføjet 17.05.2024
Benedikt LitzJulia Sehl-EwertAngele BreithauptAnja LandmesserFlorian PfaffAurore RomeySandra Blaise-BoisseauMartin BeerMichael Eschbaumera Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germanyb Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germanyc Animal Health Laboratory, Foot-and-Mouth Disease Reference Laboratory, Virology JRU, ANSES, INRAE, ENVA, Paris-Est University, Maisons-Alfort, France
Emerg Microbes Infect, 17.05.2024
Tilføjet 17.05.2024
Alison SchaeferBing YangHolly A. SchroederDimple HaritMike S. HumphryLarry ZeitlinKevin J. WhaleyJacques RavelWilliam A. FischerSamuel K. Laia UNC/NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC, USAb Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAc Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USAd Mapp Biopharmaceutical, Inc., San Diego, CA, USAe Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USAf Division of Pulmonary and Critical Care Medicine, School of Medicine, Chapel Hill, NC, USAg Department of Microbiology & Immunology; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Emerg Microbes Infect, 17.05.2024
Tilføjet 17.05.2024
Malaria Journal, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014–2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed. Methods Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR. Results Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found. Conclusions Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa.
Læs mere Tjek på PubMedMalaria Journal, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Sporozoite invasion of hepatocytes is an essential step in the Plasmodium life-cycle and has similarities, at the cellular level, to merozoite invasion of erythrocytes. In the case of the Plasmodium blood-stage, efforts to identify host–pathogen protein–protein interactions have yielded important insights including vaccine candidates. In the case of sporozoite-hepatocyte invasion, the host–pathogen protein–protein interactions involved are poorly understood. Methods To gain a better understanding of the protein–protein interaction between the sporozoite ligands and host receptors, a systematic screen was performed. The previous Plasmodium falciparum and human surface protein ectodomain libraries were substantially extended, resulting in the creation of new libraries comprising 88 P. falciparum sporozoite protein coding sequences and 182 sequences encoding human hepatocyte surface proteins. Having expressed recombinant proteins from these sequences, a plate-based assay was used, capable of detecting low affinity interactions between recombinant proteins, modified for enhanced throughput, to screen the proteins for interactions. The novel interactions identified in the screen were characterized biochemically, and their essential role in parasite invasion was further elucidated using antibodies and genetically manipulated Plasmodium parasites. Results A total of 7540 sporozoite-hepatocyte protein pairs were tested under conditions capable of detecting interactions of at least 1.2 µM KD. An interaction between the human fibroblast growth factor receptor 4 (FGFR4) and the P. falciparum protein Pf34 is identified and reported here, characterizing its affinity and demonstrating the blockade of the interaction by reagents, including a monoclonal antibody. Furthermore, further interactions between Pf34 and a second P. falciparum rhoptry neck protein, PfRON6, and between human low-density lipoprotein receptor (LDLR) and the P. falciparum protein PIESP15 are identified. Conditional genetic deletion confirmed the essentiality of PfRON6 in the blood-stage, consistent with the important role of this protein in parasite lifecycle. Pf34 was refractory to attempted genetic modification. Antibodies to Pf34 abrogated the interaction and had a modest effect upon sporozoite invasion into primary human hepatocytes. Conclusion Pf34 and PfRON6 may be members of a functionally important invasion complex which could be a target for future interventions. The modified interaction screening assay, protein expression libraries and P. falciparum mutant parasites reported here may be a useful tool for protein interaction discovery and antigen candidate screening which could be of wider value to the scientific community.
Læs mere Tjek på PubMedMalaria Journal, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing. Methods Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples. Results Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack. Conclusion The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide.
Læs mere Tjek på PubMedMalaria Journal, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Malaria is a major public health concern in Ethiopia, where more than half of the population lives in malaria risk areas. While several studies have been conducted in different eco-epidemiological settings in Ethiopia, there is a notable scarcity of data on the prevalence of malaria in the Gindabarat district. Therefore, this study aimed to analyse 10-year trend of malaria prevalence in Gindabarat district, West Shawa Zone of Oromia, Western Ethiopia. Methods A retrospective laboratory record review was conducted at Gindabarat General Hospital and Gindabarat District Health Office from September 2011 to August 2020. The retrieved data included the date of examination, age, sex and laboratory results of the blood smears, including the Plasmodium species identified. Data were summarized and presented in the form of tables, figures, and frequencies to present the results. The data were analysed using SPSS (version 25.0) and Microsoft Excel. Results Over the course of 10 years, a total of 11,478 blood smears were examined in the public health facilities in the district. Of the total blood smears examined, 1372 (11.95%) were microscopically confirmed malaria. Plasmodium falciparum, Plasmodium vivax and mixed infections (P. falciparum and P. vivax) accounted for 70.77%, 20.55% and 8.67% of the cases, respectively. Malaria prevalence was significantly higher among individuals aged ≥ 15 years (12.60%, x2 = 13.6, df = 2, p = 0.001) and males (14.21%, x2 = 59.7, df = 1, p = 0.001). The highest number of malaria cases was recorded from September to November. Conclusion Malaria remains a public health problem in the district. P. falciparum was the most predominant parasite species in the area. Malaria prevalence was significantly higher among individuals aged ≥ 15 years and males. There was a remarkable fluctuation in the number of malaria cases in different months and years. In the study area malaria cases peaked in 2015 and 2017 then decreasing from 2017 to 2019, with sharp increase in 2020. Moreover, this study showed malaria cases were reported in all seasons and months, but the highest was observed from September to November. Strengthening malaria control activities is essential to further reduce the burden of malaria and pave the way for the anticipated elimination.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on non-nucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics.Methods We conducted a prospective cohort study of PWH ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24- and 48- weeks later. The primary endpoint was viral suppression (500 copies/mL.Results We enrolled 500 participants (median age of 47 years; 41% women). At 48-weeks after TLD transition, 94% of participants were in care with a VL 500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events.Conclusions High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Vaccines and vaccine boosting have blunted excess morbidity and mortality from SARS-CoV-2 infection suffered by older nursing home residents (NHR). However, the impact of repeated vaccination on the T cell response based on biological sex and prior infection of NHR remain understudied.Methods We examined T cell responses to mRNA vaccines to SARS-CoV-2 in a cohort of NHR and healthcare workers (HCW) over 2 years. We used IFN-γ ELIspot and flow cytometry to assess T cell response before, two weeks and 6 months after the initial series and each of two booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T cell effector function.Results We show that prior SARS-CoV-2 infection and female sex contribute to higher T cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations and suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T cell response to mRNA vaccination.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown.Methods 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform.Results 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7.Conclusion Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background The cell envelope of Staphylococcus aureus contains two major secondary cell wall glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Both the CP and the WTA are attached to the cell wall and play distinct roles in S. aureus colonization, pathogenesis, and bacterial evasion of host immune defenses.Objective We aimed to investigate whether CP interferes with WTA-mediated properties.Methods Strains with natural heterogeneous expression of CP, strains with homogeneous high CP expression and CP-deficient strains were compared to WTA deficient controls regarding WTA dependent phage binding, cell adhesion, IgG deposition, and virulence in vivo.Results WTA-mediated phage adsorption, specific antibody deposition and cell adhesion were negatively correlated with CP expression. WTA, but not CP, enhanced the bacterial burden in a mouse abscess model, while CP overexpression resulted in intermediate virulence in vivo.Conclusions CP protects the bacteria from WTA-dependent opsonization and phage binding. This protection comes at the cost of diminished adhesion to host cells. The highly complex regulation and mostly heterogeneous expression of CP has probably evolved to ensure the survival and optimal physiological adaptation of the bacterial population as a whole.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Several influenza vaccine candidates aim to elicit antibodies against the conserved hemagglutinin stalk domain. Understanding the protective mechanism of these antibodies, which mediate broad neutralization and Fc-mediated functions, following seasonal vaccination is critical.Methods Plasma samples were obtained from a subset of pregnant women living with or without HIV-1 enrolled in a randomised trial (138 trivalent inactivated vaccine [TIV] and 145 placebo recipients). Twenty-three influenza-illness cases were confirmed within 6 months postpartum. We measured H1 stalk-specific antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD) and cellular cytotoxicity (ADCC) at enrolment and 1-month post-vaccination. The association between these Fc-mediated functions and protection against influenza-illness following vaccination was examined using multiple logistic regression analysis and risk reduction thresholds were defined by the score associated with the lowest odds of influenza-illness.Results Amongst TIV and placebo recipients, lower H1 stalk-specific ADCP and ADCD activity was detected for participants with confirmed influenza compared with individuals without confirmed influenza-illness 1-month post-vaccination. Pre-existing ADCP scores ≥250 reduced the odds of A/H1N1 infection (odds ratio 0.11; p=0.01) with an 83% likelihood of risk reduction. Following TIV, ADCD scores of ≥25 and ≥15 significantly reduced the odds against A/H1N1 (0.10; p=0.01) and non-group 1 (0.06; p=0.0004) influenza virus infections, respectively. These ADCD scores were associated with >84% likelihood of risk reduction. H1 stalk-specific ADCC potential was not associated with protection against influenza-illness.Conclusion H1 stalk-specific ADCD correlates with protection against influenza-illness following influenza vaccination during pregnancy. These findings provide insight into the protective mechanisms of HA stalk antibodies.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Data on antibiotic resistance of uropathogens for UTI recurrences are lacking.Methods In a retrospective cohort of adults at Kaiser Permanente Southern California with culture-confirmed index uncomplicated UTI (uUTI) between 01/2016 and 12/2020, we examined the number and characteristics of subsequent culture-confirmed UTIs through 2021.Results We identified 148,994 individuals with a culture-confirmed index uUTI (88% female, 44% Hispanic, mean age 51 years [s.d. 19]), of whom 19% developed a subsequent culture-confirmed UTI after a median 300 days (IQR: 126-627). The proportion of UTI due to E. coli was highest for index uUTI (79%) and decreased to 73% for sixth UTI (UTI 6) (p-for trend
Læs mere Tjek på PubMedJournal of Infectious Diseases, 17.05.2024
Tilføjet 17.05.2024
Abstract Background Monoclonal antibodies (mAbs) are utilized broadly to treat cancer and infectious diseases, and mAb exposure (serum concentration over time) is one predictor of overall treatment efficacy. Herein, we present findings from a clinical trial evaluating the pharmacokinetics (PK) of the long-acting mAb sotrovimab targeting SARS-CoV-2 in hematopoietic cell transplant (HCT) recipients.Methods All participants received an intravenous infusion of sotrovimab within one week prior to initiating the pre-transplant preparative regimen. The serum concentration of sotrovimab was measured longitudinally for up to 24 weeks post-transplant.Results Compared to non-HCT participants, we found that mAb clearance was 10% and 26% higher in autologous and allogeneic HCT recipients, respectively. Overall sotrovimab exposure was approximately 15% lower in HCT recipients compared to non-HCT recipients. Exposure was significantly reduced in HCT recipients who developed diarrhea and lower gastrointestinal (GI) graft-versus-host disease (GVHD) post-transplant.Conclusions These data show that sotrovimab exposure may be reduced in HCT recipients, possibly related to increased GI clearance in patients with GVHD. This phenomenon has implications for dose selection and duration of efficacy with sotrovimab and potentially other mAbs in this vulnerable patient population. Thus, mAb dose regimens developed in non-HCT populations may have to be optimized when applied to HCT populations.
Læs mere Tjek på PubMedPenelope A. Hancock, Eric Ochomo, Louisa A. Messenger
Trends in Parasitology, 17.05.2024
Tilføjet 17.05.2024
Insecticide resistance in malaria vector populations poses a major threat to malaria control, which relies largely on insecticidal interventions. Contemporary vector-control strategies focus on combatting resistance using multiple insecticides with differing modes of action within the mosquito. However, diverse genetic resistance mechanisms are present in vector populations, and continue to evolve. Knowledge of the spatial distribution of these genetic mechanisms, and how they impact the efficacy of different insecticidal products, is critical to inform intervention deployment decisions. We developed a catalogue of genetic-resistance mechanisms in African malaria vectors that could guide molecular surveillance. We highlight situations where intervention deployment has led to resistance evolution and spread, and identify challenges in understanding and mitigating the epidemiological impacts of resistance.
Læs mere Tjek på PubMedAlistair Antonopoulos, John S. Gilleard, Johannes Charlier
Trends in Parasitology, 17.05.2024
Tilføjet 17.05.2024
Helminth infections in grazing ruminants are a major issue for livestock farming globally, but are unavoidable in outdoor grazing systems and must be effectively managed to avoid deleterious effects to animal health, and productivity. Next-generation sequencing (NGS) technologies are transforming our understanding of the genetic basis of anthelmintic resistance (AR) and epidemiological studies of ruminant gastrointestinal parasites. They also have the potential to not only help develop and validate molecular diagnostic tests but to be directly used in routine diagnostics integrating species-specific identification and AR into a single test. Here, we review how these developments have opened the pathway for the development of multi-AR and multispecies identification in a single test, with widespread implications for sustainable livestock farming for the future.
Læs mere Tjek på PubMedMary Kefi, Victor Cardoso-Jaime, Sally A. Saab, George Dimopoulos
Trends in Parasitology, 17.05.2024
Tilføjet 17.05.2024
Malaria remains a persistent global public health challenge because of the limitations of current prevention tools. The use of transgenic mosquitoes incapable of transmitting malaria, in conjunction with existing methods, holds promise for achieving elimination of malaria and preventing its reintroduction. In this context, population modification involves the spread of engineered genetic elements through mosquito populations that render them incapable of malaria transmission. Significant progress has been made in this field over the past decade in revealing promising targets, optimizing genetic tools, and facilitating the transition from the laboratory to successful field deployments, which are subject to regulatory scrutiny. This review summarizes recent advances and ongoing challenges in ‘curing’ Anopheles vectors of the malaria parasite.
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