Nyt fra tidsskrifterne
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Klik på knappen for at kopiere eller tryk på linket nedenfor.
Kopieret til udklipsholder!
Ingen søgeord valgt.
45 emner vises.
Marshall, H., Ward, J., Wang, B., Andraweera, P., McMillan, M., Flood, L., Bell, C., Sisnowski, J., Krause, V., Webby, R., Childs, E., Gunathilake, M., Egoroff, N., Leong, L., Lawrence, A., Baird, R., Freeman, K., Menouhos, D., Whiley, D. M., Karnon, J., van Hal, S., Lahra, M. M.
BMJ Open, 8.05.2024
Tilføjet 8.05.2024
IntroductionThe effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. Methods and analysesThis observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4–7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. Ethics and disseminationThe protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.
Læs mere Tjek på PubMedSalamun, J., Da Silva, T., Ustero, P., Gosmain, Y., Guessous, I., Calmy, A., Spechbach, H.
BMJ Open, 8.05.2024
Tilføjet 8.05.2024
IntroductionSARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) is a well-established, widely available vasoactive and angioprotective drug interacting with heparan sulphate, with the potential to interfere with the uptake of SARS-CoV-2 by epithelial cells. The CADOVID trial aims to evaluate the efficacy and safety of CaD in reducing the SARS-CoV-2 viral load in non-hospitalised adult patients diagnosed with COVID-19, confirmed by a positive SARS-CoV-2 PCR, including its efficacy to reduce the impact of persistent COVID-19 symptoms. Methods and analysisThis is a randomised, placebo-controlled, double-blind, monocentric phase II trial. Enrolment began in July 2022. A total of 74 adult patients will be randomly allocated to the CaD arm or the placebo group with a 1:1 ratio, respectively. Participants in the intervention arm will receive two capsules of CaD 500 mg two times per day and the placebo arm will receive two matching capsules of mannitol 312.5 mg two times per day, with a treatment period of 7 days for both arms, followed by a 77-day observational period without treatment administration. Participants will be asked to complete secured online questionnaires using their personal smartphone or other electronic device. These include a COVID-19 questionnaire (assessing symptoms, temperature measurement, reporting of concomitant medication and adverse events), a COVID-19 persistent symptoms’ questionnaire and the Short Form 12-Item (SF-12) survey. SARS-CoV-2 PCR testing will be performed on nasopharyngeal swabs collected on days 1, 4, 8 and 21. The primary endpoint is the reduction from baseline of SARS-CoV-2 viral load determined by RT-PCR at day 4. Ethics and disseminationThis trial has received approval by the Geneva Regional Research Ethics Committee (2022-00613) and Swissmedic (701339). Dissemination of results will be through presentations at scientific conferences and publication in scientific journals. Trial registration number NCT05305508; Clinicaltrials.gov; Swiss National Clinical Portal Registry (SNCTP 000004938).
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Prior to September 2021, 55,000–90,000 hospital inpatients in England were identified as having a potentially nosocomial SARS-CoV-2 infection. This includes cases that were likely missed due to pauci- or asymptomatic infection. Further, high numbers of healthcare workers (HCWs) are thought to have been infected, and there is evidence that some of these cases may also have been nosocomially linked, with both HCW to HCW and patient to HCW transmission being reported. From the start of the SARS-CoV-2 pandemic interventions in hospitals such as testing patients on admission and universal mask wearing were introduced to stop spread within and between patient and HCW populations, the effectiveness of which are largely unknown. Materials/methods Using an individual-based model of within-hospital transmission, we estimated the contribution of individual interventions (together and in combination) to the effectiveness of the overall package of interventions implemented in English hospitals during the COVID-19 pandemic. A panel of experts in infection prevention and control informed intervention choice and helped ensure the model reflected implementation in practice. Model parameters and associated uncertainty were derived using national and local data, literature review and formal elicitation of expert opinion. We simulated scenarios to explore how many nosocomial infections might have been seen in patients and HCWs if interventions had not been implemented. We simulated the time period from March-2020 to July-2022 encompassing different strains and multiple doses of vaccination. Results Modelling results suggest that in a scenario without inpatient testing, infection prevention and control measures, and reductions in occupancy and visitors, the number of patients developing a nosocomial SARS-CoV-2 infection could have been twice as high over the course of the pandemic, and over 600,000 HCWs could have been infected in the first wave alone. Isolation of symptomatic HCWs and universal masking by HCWs were the most effective interventions for preventing infections in both patient and HCW populations. Model findings suggest that collectively the interventions introduced over the SARS-CoV-2 pandemic in England averted 400,000 (240,000 – 500,000) infections in inpatients and 410,000 (370,000 – 450,000) HCW infections. Conclusions Interventions to reduce the spread of nosocomial infections have varying impact, but the package of interventions implemented in England significantly reduced nosocomial transmission to both patients and HCWs over the SARS-CoV-2 pandemic.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins——nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Early prediction of mortality in individuals with HIV (PWH) has perpetually posed a formidable challenge. With the widespread integration of machine learning into clinical practice, some researchers endeavor to formulate models predicting the mortality risk for PWH. Nevertheless, the diverse timeframes of mortality among PWH and the potential multitude of modeling variables have cast doubt on the efficacy of the current predictive model for HIV-related deaths. To address this, we undertook a systematic review and meta-analysis, aiming to comprehensively assess the utilization of machine learning in the early prediction of HIV-related deaths and furnish evidence-based support for the advancement of artificial intelligence in this domain. Methods We systematically combed through the PubMed, Cochrane, Embase, and Web of Science databases on November 25, 2023. To evaluate the bias risk in the original studies included, we employed the Predictive Model Bias Risk Assessment Tool (PROBAST). During the meta-analysis, we conducted subgroup analysis based on survival and non-survival models. Additionally, we utilized meta-regression to explore the influence of death time on the predictive value of the model for HIV-related deaths. Results After our comprehensive review, we analyzed a total of 24 pieces of literature, encompassing data from 401,389 individuals diagnosed with HIV. Within this dataset, 23 articles specifically delved into deaths during long-term follow-ups outside hospital settings. The machine learning models applied for predicting these deaths comprised survival models (COX regression) and other non-survival models. The outcomes of the meta-analysis unveiled that within the training set, the c-index for predicting deaths among people with HIV (PWH) using predictive models stands at 0.83 (95% CI: 0.75–0.91). In the validation set, the c-index is slightly lower at 0.81 (95% CI: 0.78–0.85). Notably, the meta-regression analysis demonstrated that neither follow-up time nor the occurrence of death events significantly impacted the performance of the machine learning models. Conclusions The study suggests that machine learning is a viable approach for developing non-time-based predictions regarding HIV deaths. Nevertheless, the limited inclusion of original studies necessitates additional multicenter studies for thorough validation.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. Case presentation We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. Conclusions The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Sepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis. Methods PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated. Results The sensitivity of PSP was 0.88 (95% CI: 0.77–0.94), and the pooled specificity was 0.78 (95% CI: 0.65–0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60). Conclusions This study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia. Methods A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I2 statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed. Results Twenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]). Conclusions This study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. Methods After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants’ receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. Results 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1–14.3%), and 8.9% (95%CI 5.6–12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12–5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38–13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07–3.87). Conclusion We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). Methods This Swedish nationwide population-based cohort study (2006–2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. Results Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40–18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16–9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84–4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31–3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Chile rapidly implemented an extensive COVID-19 vaccination campaign, deploying a diversity of vaccines with a strategy that prioritized the elderly and individuals with comorbidities. This study aims to assess the direct impact of vaccination on the number of COVID-19 related cases, hospital admissions, ICU admissions and deaths averted during the first year and a half of the campaign. Methods Via Chile’s transparency law, we obtained access to weekly event counts categorized by vaccination status and age. Integrating this data with publicly available census and vaccination coverage information, we conducted a comparative analysis of weekly incidence rates between vaccinated and unvaccinated groups from December 20, 2020 to July 2, 2022 to estimate the direct impact of vaccination in terms of the number of cases, hospitalizations, ICU admissions and deaths averted, using an approach that avoids the need to explicitly specify the effectiveness of each vaccine deployed. Results We estimated that, from December 20, 2020 to July 2, 2022 the vaccination campaign directly prevented 1,030,648 (95% Confidence Interval: 1,016,975-1,044,321) cases, 268,784 (95% CI: 264,524-273,045) hospitalizations, 85,830 (95% CI: 83,466-88,194) ICU admissions and 75,968 (95% CI: 73,909-78,028) deaths related to COVID-19 among individuals aged 16 years and older. This corresponds to a reduction of 26% of cases, 66% of hospital admissions, 70% of ICU admissions and 67% of deaths compared to a scenario without vaccination. Individuals 55 years old or older represented 67% of hospitalizations, 73% of ICU admissions and 89% of deaths related to COVID-19 prevented. Conclusions This study highlights the role of Chile\'s vaccination campaign in reducing COVID-19 disease burden, with the most substantial reductions observed in severe outcomes.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Abstract South Korea’s remarkable success in controlling the spread of COVID-19 during the pre-Omicron period was based on extensive contact tracing and large-scale testing. Here we suggest a general criterion for tracing and testing based on South Korea’s experience, and propose a new framework to assess tracing and testing. We reviewed papers on South Korea’s response to COVID-19 to capture its concept of tracing and testing. South Korea expanded its testing capabilities to enable group tracing combined with preemptive testing, and to conduct open testing. According to our proposed model, COVID-19 cases are classified into 4 types: confirmed in quarantine, source known, source unknown, and unidentified. The proportion of the first two case types among confirmed cases is defined as “traced proportion”, and used as the indicator of tracing and testing effectiveness. In conclusion, South Korea successfully suppressed COVID-19 transmission by maintaining a high traced proportion (> 60%) using group tracing in conjunction with preemptive testing as a complementary strategy to traditional contact tracing.
Læs mere Tjek på PubMedKento TominagaShogo OzakiShohei SatoTsutomu KatayamaYuki NishimuraKimiho OmaeWataru IwasakiaDepartment of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, JapanbDepartment of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, JapancDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, JapandDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-0882, JapaneAtmosphere and Ocean Research Institute, The University of Tokyo, Chiba 277-8564, JapanfInstitute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, JapangCollaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedAlexandra BlancoRobert A. CoronadoNeha ArunKelly MaRoy D. DarCollin KiefferaDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801bDepartment of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedDan PollackTakashi NozoeEdo KussellaDepartment of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10003bDepartment of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, JapancResearch Center for Complex Systems Biology, The University of Tokyo, Tokyo 153-8902, JapandUniversal Biology Institute, The University of Tokyo, Tokyo 113-0033, JapaneDepartment of Physics, New York University, New York, NY 10003
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedJosé L. FachiBlanda Di LucciaSusan GilfillanHao-Wei ChangChristina SongJiye ChengMarina CellaMarco Aurelio VinoloJeffrey I. GordonMarco ColonnaaDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110bDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305cClinical Biomarkers and Diagnostics, Amgen Inc., South San Francisco, CA 94080dEdison Family Center for Genome Sciences and Systems Biology, and the Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110eDepartment of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, Sao Paulo 13083-862, Brazil
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedDaisuke KobayashiYusuke InoueRyosuke SuzukiMami MatsudaHiroshi ShimodaAstri Nur FaizahYoshihiro KakuKeita IshijimaYudai KurodaKango TatemotoMilagros Virhuez-MendozaMichiko HaradaAyano NishinoMizue InumaruKenzo YonemitsuRyusei KuwataAi TakanoMamoru WatanabeYukiko HigaKyoko SawabeKen MaedaHaruhiko IsawaaDepartment of Medical Entomology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, JapanbManagement Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, JapancDepartment of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, JapandJoint Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi City, Yamaguchi 753-8515, JapaneDepartment of Virology II, National Institute of Infectious Diseases, Musashimurayama City, Tokyo 208-0011, JapanfFaculty of Veterinary Medicine, Okayama University of Science, Imabari City, Ehime 794-8555, Japan
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedDongHo KimMichael A. CianfroccoKristen J. VerheyGregory A. SmithaDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611bLife Sciences Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109cDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedRachel L. PatersonMarco P. La MannaVictoria Arena De SouzaAndrew WalkerDawn Gibbs-HoweRakesh KulkarniJoannah R. FergussonNitha Charles MulakkalMauro MonteiroWilawan BunjobpolMarcin DembekMagdalena Martin-UrdirozTressan GrantClaire BarberDiana J. Garay-BaqueroLiku Bekele TezeraDavid LowneCamille Britton-RivetRobert PengellyNatalia ChepisiukPraveen K. SinghAmanda P. WoonAlex S. PowleslandMichelle L. McCullyNadia CaccamoMariolina SalioGiusto Davide BadamiLucy DorrellAndrew KnoxRoss RobinsonPaul ElkingtonFrancesco DieliMarco LeporeSarah LeonardLuis F. GodinhoaImmunocore Ltd., Abingdon, Oxfordshire OX14 4RY, United KingdombDepartment of Biomedicine, Neurosciences and Advanced Diagnostic, University of Palermo, Palermo 90127, ItalycCentral Laboratory of Advanced Diagnosis and Biomedical Research, Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone, University of Palermo, Palermo 90127, ItalydNational Institute for Health and Care Research, Biomedical Research Centre and Institute for Life Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, United Kingdom
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedRichard J. LamontaDepartment of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY 40202
Proceedings of the National Academy of Sciences, 8.05.2024
Tilføjet 8.05.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 19, May 2024.
Læs mere Tjek på PubMedAbbas YadegarHaggai Bar-YosephTanya Marie MonaghanSepideh PakpourAndrea SeverinoEd J. KuijperWiep Klaas SmitsElisabeth M. TerveerSukanya NeupaneAli Nabavi-RadJavad SadeghiGiovanni CammarotaGianluca IaniroEstello Nap-HillDickson LeungKaren WongDina Kao1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran2Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel3Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel4National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom5Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom6School of Engineering, Faculty of Applied Sciences, UBC, Okanagan Campus, Kelowna, British Columbia, Canada7Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy8Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy9Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy10Center for Microbiota Analysis and Therapeutics (CMAT), Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands11Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada12Department of Medicine, Division of Gastroenterology, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada, Christopher Staley
Clinical Microbiology Reviews, 8.05.2024
Tilføjet 8.05.2024
Lorenzo Subissi, James Richard Otieno, Nathalie Worp, Homa Attar Cohen, Bas B. Oude Munnink, Laith J. Abu-Raddad, Erik Alm, Amal Barakat, Wendy S. Barclay, Jinal N. Bhiman, Leon Caly, Meera Chand, Mark Chen, Ann Cullinane, Tulio de Oliveira, Christian Drosten, Julian Druce, Paul Effler, Ihab El Masry, Adama Faye, Elodie Ghedin, Rebecca Grant, Bart L. Haagmans, Christian Happi, Belinda L. Herring, Emma B. Hodcroft, Juniorcaius Ikejezie, Victoria Katawera, Zyleen Alnashir Kassamali, Yee-Sin Leo, Gabriel M. Leung, Rebecca J. Kondor, Marco Marklewitz, Jairo Mendez-Rico, Nada M. Melhem, Vincent Munster, Karen Nahapetyan, Dhamari Naindoo, Djin-Ye Oh, Thomas P. Peacock, Malik Peiris, Zhibin Peng, Leo L. M. Poon, Andrew Rambaut, Senjuti Saha, Yinzhong Shen, Marilda M. Siqueira, Erik Volz, Sofonias K. Tessema, Volker Thiel, Henda Triki, Sylvie van der Werf, Karin von Eije, Jane Cunningham, Marion P. G. Koopmans, Anne von Gottberg, Anurag Agrawal, Maria D. Van Kerkhove
Nature, 8.05.2024
Tilføjet 8.05.2024
Infectious Disease Modelling, 8.05.2024
Tilføjet 8.05.2024
Publication date: Available online 7 May 2024 Source: Infectious Disease Modelling Author(s): J. Vanderlocht, S. Møgelmose, K. Van Kerckhove, P. Beutels, N. Hens
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Universal coverage with insecticide-treated nets (ITNs) is important for malaria control and elimination. The emergence and intensification of insecticide resistance threatens progress made through the deployment of these interventions and has required the development of newer, more expensive ITN types. Understanding malaria prevention behaviour, including barriers and facilitators to net access and use, can support effective decision-making for the promotion and distribution of ITNs. Methods In-depth interviews and focus group discussions were conducted in 3 to 4 villages per district, in 13 districts across Burkina Faso, Mozambique, Nigeria and Rwanda from 2019 to 2022. Interviews were conducted in the local language, translated and transcribed in English, French or Portuguese. Transcripts were coded and analysed using Nvivo and ATLAS.ti. Results ITNs were obtained from mass distribution campaigns, antenatal care and immunization visits, and purchased on the private market in some locations. While there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets. Conclusions ITNs remain an important malaria control intervention. To ensure adequate and increased net access, distribution campaigns should consider family structures, available sleeping spaces, and other bed sharing preferences when identifying the number of nets needed for distribution. In addition, campaigns should allow for multiple options for net distribution points and timing to accommodate households remote to health services. Continuous distribution channels and complimentary distribution through the private sector could help fill gaps in coverage. Solutions are needed for outdoor malaria transmission, including alternative designs for ITNs, and improving access to complementary personal protective measures.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background The direct membrane feeding assay (DMFA), whereby gametocyte-infected blood is collected from human donors and from which mosquitoes feed through a membrane, is proving essential for assessing parameters influencing Plasmodium transmission potential in endemic countries. The success of DMFAs is closely tied to gametocyte density in the blood, with relatively high gametocytaemia ensuring optimal infection levels in mosquitoes. As transmission intensity declines with control efforts, the occurrence of asymptomatic individuals with low gametocyte densities, who can significantly contribute to the infectious reservoir, is increasing. This poses a limitation to studies relying on the experimental infection of large numbers of mosquitoes with natural isolates of Plasmodium. A simple, field-applicable method is presented for improving parasite infectivity by concentrating Plasmodium falciparum gametocytes. Methods Anopheles gambiae received one of the following 5 blood treatments through DMFA: (i) whole blood (WB) samples from naturally-infected donors; (ii) donor blood whose plasma was replaced with the same volume of Plasmodium-naive AB + serum (1:1 control); (iii) plasma replaced with a volume of malaria-naïve AB + serum equivalent to half (1:1/2), or to a quarter (1:1/4), of the initial plasma volume; and (v) donor blood whose plasma was fully removed (RBC). The experiment was repeated 4 times using 4 distinct wild parasite isolates. Seven days post-infection, a total of 1,095 midguts were examined for oocyst presence. Results Substituting plasma with reduced amounts (1:1/2 and 1:1/4) of Plasmodium-naive AB + serum led to a 31% and 17% increase of the mosquito infection rate and to a 85% and 308% increase in infection intensity compared to the 1:1 control, respectively. The full removal of plasma (RBC) reduced the infection rate by 58% and the intensity by 64% compared to the 1:1 control. Reducing serum volumes (1:1/2; 1:1/4 and RBC) had no impact on mosquito feeding rate and survival when compared to the 1:1 control. Conclusions Concentrating gametocytic blood by replacing natural plasma by lower amount of naive serum can enhance the success of mosquito infection. In an area with low gametocyte density, this simple and practical method of parasite concentration can facilitate studies on human-to-mosquito transmission such as the evaluation of transmission-blocking interventions.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Malaria vaccine introduction in endemic countries is a game-changing milestone in the fight against the disease. This article examines the inequity in the global pharmaceutical research, development, manufacturing, and trade landscape. The role of inequity in hindering progress towards malaria elimination is explored. The analysis finds that transformational changes are required to create an equity-enabling environment. Addressing the inequity is critical to maximizing the public health impact of vaccines and attaining sustainability. Avenues to catalyze progress by leveraging malaria vaccines and messenger ribonucleic acid (mRNA) technology are discussed.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Studies on haemosporidian diversity, including origin of human malaria parasites, malaria\'s zoonotic dynamic, and regional biodiversity patterns, have used target gene approaches. However, current methods have a trade-off between scalability and data quality. Here, a long-read Next-Generation Sequencing protocol using PacBio HiFi is presented. The data processing is supported by a pipeline that uses machine-learning for analysing the reads. Methods A set of primers was designed to target approximately 6 kb, almost the entire length of the haemosporidian mitochondrial genome. Amplicons from different samples were multiplexed in an SMRTbell® library preparation. A pipeline (HmtG-PacBio Pipeline) to process the reads is also provided; it integrates multiple sequence alignments, a machine-learning algorithm that uses modified variational autoencoders, and a clustering method to identify the mitochondrial haplotypes/species in a sample. Although 192 specimens could be studied simultaneously, a pilot experiment with 15 specimens is presented, including in silico experiments where multiple data combinations were tested. Results The primers amplified various haemosporidian parasite genomes and yielded high-quality mt genome sequences. This new protocol allowed the detection and characterization of mixed infections and co-infections in the samples. The machine-learning approach converged into reproducible haplotypes with a low error rate, averaging 0.2% per read (minimum of 0.03% and maximum of 0.46%). The minimum recommended coverage per haplotype is 30X based on the detected error rates. The pipeline facilitates inspecting the data, including a local blast against a file of provided mitochondrial sequences that the researcher can customize. Conclusions This is not a diagnostic approach but a high-throughput method to study haemosporidian sequence assemblages and perform genotyping by targeting the mitochondrial genome. Accordingly, the methodology allowed for examining specimens with multiple infections and co-infections of different haemosporidian parasites. The pipeline enables data quality assessment and comparison of the haplotypes obtained to those from previous studies. Although a single locus approach, whole mitochondrial data provide high-quality information to characterize species pools of haemosporidian parasites.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Malaria is a potentially life-threatening disease caused by Plasmodium protozoa transmitted by infected Anopheles mosquitoes. Controlled human malaria infection (CHMI) trials are used to assess the efficacy of interventions for malaria elimination. The operating characteristics of statistical methods for assessing the ability of interventions to protect individuals from malaria is uncertain in small CHMI studies. This paper presents simulation studies comparing the performance of a variety of statistical methods for assessing efficacy of intervention in CHMI trials. Methods Two types of CHMI designs were investigated: the commonly used single high-dose design (SHD) and the repeated low-dose design (RLD), motivated by simian immunodeficiency virus (SIV) challenge studies. In the context of SHD, the primary efficacy endpoint is typically time to infection. Using a continuous time survival model, five statistical tests for assessing the extent to which an intervention confers partial or full protection under single dose CHMI designs were evaluated. For RLD, the primary efficacy endpoint is typically the binary infection status after a specific number of challenges. A discrete time survival model was used to study the characteristics of RLD versus SHD challenge studies. Results In a SHD study with the continuous time survival model, log-rank test and t-test are the most powerful and provide more interpretable results than Wilcoxon rank-sum tests and Lachenbruch tests, while the likelihood ratio test is uniformly most powerful but requires knowledge of the underlying probability model. In the discrete time survival model setting, SHDs are more powerful for assessing the efficacy of an intervention to prevent infection than RLDs. However, additional information can be inferred from RLD challenge designs, particularly using a likelihood ratio test. Conclusions Different statistical methods can be used to analyze controlled human malaria infection (CHMI) experiments, and the choice of method depends on the specific characteristics of the experiment, such as the sample size allocation between the control and intervention groups, and the nature of the intervention. The simulation results provide guidance for the trade off in statistical power when choosing between different statistical methods and study designs.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background In Nigeria, seasonal malaria chemoprevention (SMC) is typically administered door-to-door to children under five by community medicine distributors during high transmission seasons. While door-to-door distribution (DDD) is exclusively employed in Nigeria as part of standard operating procedures of SMC programmes, some households access SMC through non-DDD channels, such as fixed-point distributions, health facilities, and private purchase. However, analysis of access to SMC medicines through non-DDD has been limited, with little evidence of its outcomes on adherence to the three-day complete course of SMC medicines and caregiver actions in the event of adverse reactions to SMC medicines. Methods Data were obtained from SMC end-of-round coverage surveys conducted in Nigeria in 2021 and 2022, including 25,278 households for the analysis. The proportion of households accessing SMC medicine through non-DDD and the distribution of various non-DDD sources of SMC medicines were described. Multivariate random-effects logistic regression models were performed to identify predictors of accessing SMC medicines through non-DDD. The associations between non-DDD, and caregiver-reporting of adherence to complete administration of SMC medicines and caregiver actions in the event of adverse reactions to SMC medicines were also assessed. Results Less than 2% (314/24003) of households accessed SMC medicines through non-DDD in the states surveyed. Over 60% of non-DDD access was via health facility personnel and community medicine distributors from different locations. Variables associated with non-DDD access included heads of household being born in the local state (OR = 0.68, 95% CI 0.47 to 0.90), households residing in the study state since the first cycle of the SMC round (OR = 0.39, 95% CI 0.17 to 0.88), households with high wealth index (OR = 1.36, 95% CI 1.01 to 1.82), and caregivers hearing about date of SMC delivery in the previous cycle (OR = 0.18, 95%CI 0.14 to 0.24). Furthermore, non-DDD was associated with reduced SMC adherence and higher caregiver non-reporting of adverse reactions to SMC medicines in children compared with DDD. Conclusion This study provides evidence on the characteristics of households accessing SMC medicines through non-DDD and its potential negative outcomes on adherence to SMC medicine and adverse reaction reporting, underscoring potential implementation issues that may arise if non-DDD delivery models are adopted in SMC, particularly in places where DDD had been firstly used.
Læs mere Tjek på PubMedMalaria Journal, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Drug repurposing offers a strategic alternative to the development of novel compounds, leveraging the known safety and pharmacokinetic profiles of medications, such as linezolid and levofloxacin for tuberculosis (TB). Anti-malarial drugs, including quinolones and artemisinins, are already applied to other diseases and infections and could be promising for TB treatment. Methods This review included studies on the activity of anti-malarial drugs, specifically quinolones and artemisinins, against Mycobacterium tuberculosis complex (MTC), summarizing results from in vitro, in vivo (animal models) studies, and clinical trials. Studies on drugs not primarily developed for TB (doxycycline, sulfonamides) and any novel developed compounds were excluded. Analysis focused on in vitro activity (minimal inhibitory concentrations), synergistic effects, pre-clinical activity, and clinical trials. Results Nineteen studies, including one ongoing Phase 1 clinical trial, were analysed: primarily investigating quinolones like mefloquine and chloroquine, and, to a lesser extent, artemisinins. In vitro findings revealed high MIC values for anti-malarials versus standard TB drugs, suggesting a limited activity. Synergistic effects with anti-TB drugs were modest, with some synergy observed in combinations with isoniazid or pyrazinamide. In vivo animal studies showed limited activity of anti-malarials against MTC, except for one study of the combination of chloroquine with isoniazid. Conclusions The repurposing of anti-malarials for TB treatment is limited by high MIC values, poor synergy, and minimal in vivo effects. Concerns about potential toxicity at effective dosages and the risk of antimicrobial resistance, especially where TB and malaria overlap, further question their repurposing. These findings suggest that focusing on novel compounds might be both more beneficial and rewarding.
Læs mere Tjek på PubMedLuisa Weisbrod, Luigi Capriotti, Marco Hofmann, Valerie Spieler, Herbert Dersch, Bernd Voedisch, Peter Schmidt, Susanne Knake
Frontiers in Immunology, 8.05.2024
Tilføjet 8.05.2024
The study of peptide repertoires presented by major histocompatibility complex (MHC) molecules and the identification of potential T-cell epitopes contribute to a multitude of immunopeptidome-based treatment approaches. Epitope mapping is essential for the development of promising epitope-based approaches in vaccination as well as for innovative therapeutics for autoimmune diseases, infectious diseases, and cancer. It also plays a critical role in the immunogenicity assessment of protein therapeutics with regard to safety and efficacy concerns. The main challenge emerges from the highly polymorphic nature of the human leukocyte antigen (HLA) molecules leading to the requirement of a peptide mapping strategy for a single HLA allele. As many autoimmune diseases are linked to at least one specific antigen, we established FASTMAP, an innovative strategy to transiently co-transfect a single HLA allele combined with a disease-specific antigen into a human cell line. This approach allows the specific identification of HLA-bound peptides using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Using FASTMAP, we found a comparable spectrum of endogenous peptides presented by the most frequently expressed HLA alleles in the world’s population compared to what has been described in literature. To ensure a reliable peptide mapping workflow, we combined the HLA alleles with well-known human model antigens like coagulation factor VIII, acetylcholine receptor subunit alpha, protein structures of the SARS-CoV-2 virus, and myelin basic protein. Using these model antigens, we have been able to identify a broad range of peptides that are in line with already published and in silico predicted T-cell epitopes of the specific HLA/model antigen combination. The transient co-expression of a single affinity-tagged MHC molecule combined with a disease-specific antigen in a human cell line in our FASTMAP pipeline provides the opportunity to identify potential T-cell epitopes/endogenously processed MHC-bound peptides in a very cost-effective, fast, and customizable system with high-throughput potential.
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Purpose To assess the Xpert MTB/XDR assay’s efficiency in promptly detecting resistance to isoniazid, fluoroquinolones, ethionamide, and second-line injectable drugs among tuberculosis (TB) patients. Methods From August 2020 to July 2021, TB suspected patient samples were enrolled at a tertiary care center for our study. We conducted mycobacterial culture, phenotypic DST using proportion method in liquid culture at WHO-recommended concentrations, and the line probe assay (LPA). Simultaneously, the Index test, Xpert MTB/XDR, was performed following the manufacturer’s instructions. Results Among 360 samples, 107 were excluded due to incomplete information. Resistance to isoniazid, levofloxacin and moxifloxacin was found in 45/251, 21/251 and 20/251 samples, respectively by phenotypic DST. The diagnostic accuracy of Index test, taking phenotypic DST as a reference standard, was 95.8%, 99.04%, and 99.05% for isoniazid, levofloxacin, and moxifloxacin, respectively. The Index test assay demonstrated a specificity of 99.1% for detecting SLID resistance, yielding a diagnostic accuracy of 99.2. Comparing the Index test with LPA revealed a significant enhancement in sensitivity for detecting isoniazid resistance (86.7% vs. 82.2%). Conclusions The Index test exhibited promising outcomes in identifying resistance to isoniazid and fluoroquinolones, surpassing the performance of the LPA. This could be valuable for promptly initiating treatment in cases of drug-resistant tuberculosis.
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Purpose Early diagnosis of surgical site infections (SSIs) could prevent surgical revision. Inflammatory markers (IMs), such as procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), seem more accurate in diagnosing SSI than C-reactive protein (CRP) and white blood cell (WBC) count. The aim was to compare the predictive values of CRP, WBC count, PCT, IL-6, and TNF-α in SSI detection. Methods A total of 130 patients undergoing dorsal spondylodesis from 2019 to 2024 were enrolled in a prospective diagnostic study at a maximum care spine center. IMs were measured preoperatively and on the postoperative days (PODs) 1, 2, 3, 5, and 7. Patients with high suspicion of SSI underwent revision surgery. SSI was diagnosed when the microbiological evidence was positive. Patients were divided a posteriori into the non-infection and infection groups. Results IMs of 118 patients (66.9 ± 13.0 years, 61.0% females) were measured. Fifteen of the 118 patients (12.7%) developed an SSI. The groups differed with respect to existing hypertension, number of instrumented segments, region of surgery, CRPPOD1,7, PCTPOD7, and IL-6POD3,5,7. Binary logistic regression for SSI detection including these parameters showed an area under the curve (AUC) of 0.88 (95% CI 0.79–0.98; P
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Background and Aim A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis. Methods 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR. Results The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality. Conclusion FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec). Methods A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality. Results Overall, 386 patients were included (363 [94%] with CP-Kp and 23 [6%] CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21–13.19). Conclusions HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE.
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Background Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence. Methods We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models. Results In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI 95% 30.7–39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, there was a lower risk of PCCs in males respect to females (adjusted OR = 0.64; CI 95% 0.99–3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI 95% 0.99–3.66). Notably, no viro-immunological variable modified the PCCs risk onset. Conclusions Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Purpose Patients hospitalized for community-acquired pneumonia (CAP) may have a higher risk of new-onset atrial fibrillation (NOAF). The C2HEST score was developed to evaluate the NOAF risk in the general population. Data on the value of the C2HEST score in acute patients admitted with CAP are lacking. We want to establish the predictive value of C2HEST score for NOAF in patients with CAP. Methods Patients with CAP enrolled in the SIXTUS cohort were enrolled. C2HEST score was calculated at baseline. In-hospital NOAF was recorded. Receiver-operating Characteristic (ROC) curve and multivariable Cox proportional hazard regression analysis were performed. Results We enrolled 473 patients (36% women, mean age 70.6 ± 16.5 years), and 54 NOAF occurred. Patients with NOAF were elderly, more frequently affected by hypertension, heart failure, previous stroke/transient ischemic attack, peripheral artery disease and hyperthyroidism. NOAF patients had also higher CURB-65, PSI class and CHA2DS2-VASc score. The C-index of C2HEST score for NOAF was 0.747 (95% confidence interval [95%CI] 0.705–0.786), higher compared to CURB-65 (0.611, 95%CI 0.566–0.655, p = 0.0016), PSI (0.665, 95%CI 0.621–0.708, p = 0.0199) and CHA2DS2-VASc score (0.696, 95%CI 0.652–0.737, p = 0.0762). The best combination of sensitivity (67%) and specificity (70%) was observed with a C2HEST score ≥ 4. This result was confirmed by the multivariable Cox analysis (Hazard Ratio [HR] for C2HEST score ≥ 4 was 10.7, 95%CI 2.0–57.9; p = 0.006), independently from the severity of pneumonia. Conclusion The C2HEST score was a useful predictive tool to identify patients at higher risk for NOAF during hospitalization for CAP. Clinical Trial Registration www.clinicaltrials.gov (NCT01773863)
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Purpose The aim was to analyse the clinical and economic impact of carbapenemase-producing Enterobacterales (CPE) infections. Methods Case–control study. Adult patients with CPE infections were considered cases, while those with non-CPE infections were controls. Matching criteria were age (± 5 years), sex, source of infection and microorganism (ratio 1:2). Primary outcome was 30-day mortality. Secondary outcomes were 90-day mortality, clinical failure, hospitalisation costs and resource consumption. Results 246 patients (82 cases and 164 controls) were included. Klebsiella pneumoniae OXA-48 was the most common microorganism causing CPE infections. CPE cases had more prior comorbidities (p = 0.007), septic shock (p = 0.003), and were more likely to receive inappropriate empirical and definitive antibiotic treatment (both p
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Abstract Purpose The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. Methods We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. Results We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73–0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. Conclusion With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. Clinical Trail registration The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).
Læs mere Tjek på PubMedInfection, 8.05.2024
Tilføjet 8.05.2024
Jun Miyata, Hirotomo Yamanashi, Yoshinori Dake, Kenichi Nobusue, Yusuke Doi, Yukiko Honda, Fumiaki Nonaka, Kazuhiko Arima, Mami Tamai, Daisuke Sasaki, Yuji Shimizu, Hiroo Hasegawa, Takashi Kitaoka, Katsunori Yanagihara, Kiyoshi Aoyagi, Atsushi Kawakami, Takahiro Maeda
Journal of Medical Virology, 8.05.2024
Tilføjet 8.05.2024
Juan Du, Qin‐Yi Ma, Shuai Wang, Wan‐Xue Zhang, Peng Wang, Yiguo Zhou, Ming Wei, Li Gu, Fuqiang Cui, Qing‐Bin Lu
Journal of Medical Virology, 8.05.2024
Tilføjet 8.05.2024
Piotr Rzymski, Dorota Zarębska‐Michaluk, Miłosz Parczewski, Agnieszka Genowska, Barbara Poniedziałek, Birute Strukcinskiene, Anna Moniuszko‐Malinowska, Robert Flisiak
Journal of Medical Virology, 8.05.2024
Tilføjet 8.05.2024
Daniela Loconsole, Francesca Centrone, Anna Sallustio, Daniele Casulli, Riccardo Zagaria, Davide Sacco, Vito Colella, Nelhudoff Albano, Desiree Caselli, Fabio Cardinale, Paola Giordano, Ignazio Lofù, Nicola Laforgia, Maria Chironna
International Journal of Infectious Diseases, 8.05.2024
Tilføjet 8.05.2024
Between 2022 and 2023, a new variant of Echovirus 11 (E11) caused fatal neonatal infections in Europe [1,2]. In France, nine cases occurred in premature infants from twin pregnancies, and seven of them died [1]. In April 2023, two cases of severe E11 neonatal infection in non-identical late-preterm twins were reported in Italy; the strain identified in these cases showed 99% nucleotide identity with the E11 strains reported in France [2].
Læs mere Tjek på PubMed