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Malaria Journal, 25.06.2023
Tilføjet 25.06.2023
Abstract Background Ethiopia has a history of climate related malaria epidemics. An improved understanding of malaria–climate interactions is needed to inform malaria control and national adaptation plans. Methods Malaria–climate associations in Ethiopia were assessed using (a) monthly climate data (1981–2016) from the Ethiopian National Meteorological Agency (NMA), (b) sea surface temperatures (SSTs) from the eastern Pacific, Indian Ocean and Tropical Atlantic and (c) historical malaria epidemic information obtained from the literature. Data analysed spanned 1950–2016. Individual analyses were undertaken over relevant time periods. The impact of the El Niño Southern Oscillation (ENSO) on seasonal and spatial patterns of rainfall and minimum temperature (Tmin) and maximum temperature (Tmax) was explored using NMA online Maprooms. The relationship of historic malaria epidemics (local or widespread) and concurrent ENSO phases (El Niño, Neutral, La Niña) and climate conditions (including drought) was explored in various ways. The relationships between SSTs (ENSO, Indian Ocean Dipole and Tropical Atlantic), rainfall, Tmin, Tmax and malaria epidemics in Amhara region were also explored. Results El Niño events are strongly related to higher Tmax across the country, drought in north-west Ethiopia during the July–August–September (JAS) rainy season and unusually heavy rain in the semi-arid south-east during the October–November–December (OND) season. La Niña conditions approximate the reverse. At the national level malaria epidemics mostly occur following the JAS rainy season and widespread epidemics are commonly associated with El Niño events when Tmax is high, and drought is common. In the Amhara region, malaria epidemics were not associated with ENSO, but with warm Tropical Atlantic SSTs and higher rainfall. Conclusion Malaria–climate relationships in Ethiopia are complex, unravelling them requires good climate and malaria data (as well as data on potential confounders) and an understanding of the regional and local climate system. The development of climate informed early warning systems must, therefore, target a specific region and season when predictability is high and where the climate drivers of malaria are sufficiently well understood. An El Niño event is likely in the coming years. Warming temperatures, political instability in some regions, and declining investments from international donors, implies an increasing risk of climate-related malaria epidemics.
Læs mere Tjek på PubMedMalaria Journal, 25.06.2023
Tilføjet 25.06.2023
Abstract Background Ivermectin (22,23-dihydroavermectin B1a: H2B1a) is an endectocide used to treat worm infections and ectoparasites including lice and scabies mites. Furthermore, survival of malaria transmitting Anopheles mosquitoes is strongly decreased after feeding on humans recently treated with ivermectin. Currently, mass drug administration of ivermectin is under investigation as a potential novel malaria vector control tool to reduce Plasmodium transmission by mosquitoes. A “post-ivermectin effect” has also been reported, in which the survival of mosquitoes remains reduced even after ivermectin is no longer detectable in blood meals. In the present study, existing material from human clinical trials was analysed to understand the pharmacokinetics of ivermectin metabolites and feeding experiments were performed in Anopheles stephensi mosquitoes to assess whether ivermectin metabolites contribute to the mosquitocidal action of ivermectin and whether they may be responsible for the post-ivermectin effect. Methods Ivermectin was incubated in the presence of recombinant human cytochrome P450 3A4/5 (CYP 3A4/5) to produce ivermectin metabolites. In total, nine metabolites were purified by semi-preparative high-pressure liquid chromatography. The pharmacokinetics of the metabolites were assessed over three days in twelve healthy volunteers who received a single oral dose of 12 mg ivermectin. Blank whole blood was spiked with the isolated metabolites at levels matching the maximal blood concentration (Cmax) observed in pharmacokinetics study samples. These samples were fed to An. stephensi mosquitoes, and their survival and vitality was recorded daily over 3 days. Results Human CYP3A4 metabolised ivermectin more rapidly than CYP3A5. Ivermectin metabolites M1–M8 were predominantly formed by CYP3A4, whereas metabolite M9 (hydroxy-H2B1a) was mainly produced by CYP3A5. Both desmethyl-H2B1a (M1) and hydroxy-H2B1a (M2) killed all mosquitoes within three days post-feeding, while administration of desmethyl, hydroxy-H2B1a (M4) reduced survival to 35% over an observation period of 3 days. Ivermectin metabolites that underwent deglycosylation or hydroxylation at spiroketal moiety were not active against An. stephensi at Cmax levels. Interestingly, half-lives of M1 (54.2 ± 4.7 h) and M4 (57.5 ± 13.2 h) were considerably longer than that of the parent compound ivermectin (38.9 ± 20.8 h). Conclusion In conclusion, the ivermectin metabolites M1 and M2 contribute to the activity of ivermectin against An. stephensi mosquitoes and could be responsible for the “post-ivermectin effect”.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractWe evaluated the performance of rapid antigen (RAg) and antibody (RAb) microfluidic diagnostics with serial sampling of 71 participants at six visits over two months following SARS-CoV-2 infection. Rapid tests showed strong agreement with laboratory references (KAg = 81.0%; KAb = 87.8%). RAg showed substantial concordance to both virus growth in culture and PCR-positivity 0-5 days since symptom onset (KAg-culture = 60.1% and KAg-PCR = 87.1%). PCR concordance to virus growth in culture was similar (KPCR-culture = 70.0%), though agreement between RAg and culture was better overall (KAg-culture = 45.5% vs. KPCR-culture = 10.0%). Rapid antigen and antibody testing by microfluidic immunofluorescence platform are highly accurate for characterization of acute infection.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractBackgroundWhile antiretroviral therapy (ART) has improved outcomes for people with HIV (PWH), brain dysfunction is still evident. Immune activation and inflammation remain elevated in PWH on ART contributing to morbidity and mortality. Previous studies demonstrated reduced functional and structural changes in PWH; however, the underlying mechanisms remain elusive.MethodsOur cohort consists of ART-adherent, virologically suppressed PWH (n=173;
Læs mere Tjek på PubMedJournal of Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractType I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response, therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We sought to assess the pathogenicity of emerging wildtype filovirus infections in IFNAR-/- mice since filovirus models using immunocompetent mice require a mouse-adapted viral strain. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (i.n.) or intraperitoneal (i.p.) route and compared virus loads at early and late timepoints after infection. No signs of disease and no viral RNA were detected after i.n. infection regardless of LLOV dose. In contrast, i.p. infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early timepoint. The low-dose LLOV and BOMV groups achieved higher viral loads at the late timepoint. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 25.06.2023
Tilføjet 25.06.2023
AbstractOver the past few decades, the interest in lactic acid bacteria (LAB) has been steadily growing. This is mainly due to their industrial use, their health benefits as probiotic bacteria and their ecological importance in host-related microbiota. Phage infection represents a significant risk for the production and industrial use of LAB. This created the need to study the various means of defense put in place by LAB to resist their viral enemies, as well as the countermeasures evolved by phages to overcome these defenses. In this review, we discuss defense systems that LAB employ to resist phage infections. We also describe how phages counter these mechanisms through diverse and sophisticated strategies. Furthermore, we discuss the way phage-host interactions shape each other\'s evolution. The recent discovery of numerous novel defense systems in other bacteria promises a new dawn for phage research in LAB.
Læs mere Tjek på PubMedBMC Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
Abstract Background The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread over the world and caused tremendous impacts on global health. Understanding the mechanism responsible for the spread of this pathogen and the impact of specific factors, such as human mobility, will help authorities to tailor interventions for future SARS-CoV-2 waves or newly emerging airborne infections. In this study, we aim to analyze the spatio-temporal transmission of SARS-CoV-2 in Belgium at municipality level between January and December 2021 and explore the effect of different levels of human travel on disease incidence through the use of counterfactual scenarios. Methods We applied the endemic-epidemic modelling framework, in which the disease incidence decomposes into endemic, autoregressive and neighbourhood components. The spatial dependencies among areas are adjusted based on actual connectivity through mobile network data. We also took into account other important factors such as international mobility, vaccination coverage, population size and the stringency of restriction measures. Results The results demonstrate the aggravating effect of international travel on the incidence, and simulated counterfactual scenarios further stress the alleviating impact of a reduction in national and international travel on epidemic growth. It is also clear that local transmission contributed the most during 2021, and municipalities with a larger population tended to attract a higher number of cases from neighboring areas. Conclusions Although transmission between municipalities was observed, local transmission was dominant. We highlight the positive association between the mobility data and the infection spread over time. Our study provides insight to assist health authorities in decision-making, particularly when the disease is airborne and therefore likely influenced by human movement.
Læs mere Tjek på PubMedBMC Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
Abstract Background No research has been conducted to assess whether antibiotic prophylaxis prescribing differs by dental setting. Therefore, the goal of this study was to compare the prescribing of antibiotic prophylaxis in Veterans Affairs (VA) and non-Veterans Affairs settings. Methods This was a retrospective study of veteran and non-veteran dental patients with cardiac conditions or prosthetic joints between 2015–2017. Multivariable log binomial regression analysis was conducted to compare concordant prescribing by setting with a sub-analysis for errors of dosing based on antibiotic duration (i.e., days prescribed). Results A total of 61,124 dental visits that received a prophylactic antibiotic were included. Most were male (61.0%), and 55 years of age or older (76.2%). Nearly a third (32.7%) received guideline concordant prophylaxis. VA dental settings had a lower prevalence of guideline concordant prescribing compared to non-VA settings in unadjusted results (unadjusted prevalence ratio [uPR] = 0.92, 95% CI: 0.90–0.95). After adjustment, prevalence of guideline concordant prescribing was higher in those with prosthetic joints in the VA setting (adjusted prevalence ratio [aPR] = 1.73, 95% CI: 1.59–1.88), with no difference identified in those without a prosthetic joint (aPR = 0.99, 95% CI: 0.96–1.01). Concordance of dosing was higher in VA compared to non-VA settings (aPR = 1.11, 95% CI: 1.07–1.15). Conclusions VA has a higher prevalence of guideline concordant prescribing among those with prosthetic joints and when assessing dosing errors. Though the presence of an integrated electronic health record (EHR) may be contributing to these differences, other system or prescriber-related factors may be responsible. Future studies should focus on to what extent the integrated EHR may be responsible for increased guideline concordant prescribing in the VA setting.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
Clinical Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
Clinical Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractBackgroundDeath within a specified time window following a positive SARS-CoV-2 test is used by some agencies for attributing death to COVID-19. With omicron variants, widespread immunity, and asymptomatic screening, there is cause to re-evaluate COVID-19 death attribution methods and develop tools to improve case ascertainment.MethodsAll patients who died following microbiologically-confirmed SARS-CoV-2 in the Veterans Health Administration (VA) and at Tufts Medical Center (TMC) were identified. Records of selected vaccinated VA patients with positive tests in 2022, and of all TMC patients with positive tests in 2021-22, were manually reviewed to classify deaths as COVID-19-related (either directly caused by or contributed to), focused on deaths within 30 days. Logistic regression was used to develop and validate a surveillance model for identifying deaths in which COVID-19 was causal or contributory.ResultsAmong vaccinated VA patients who died within 30 days after a positive test in January-February, 2022, death was COVID-19-related in 103/150 (69%) of cases (55% causal, 14% contributory). In June-August, 2022, death was COVID-19-related in 70/150 (47%) of cases (22% causal, 25% contributory). Similar results were seen among the 71 patients who died at TMC. A model including hypoxemia, remdesivir, and anti-inflammatory drugs had PPV 0.82-0.95 and NPV 0.64-0.83.ConclusionsBy mid-2022, “death within 30 days” did not provide an accurate estimate of COVID-19-related death in two US healthcare systems with routine admission screening. Hypoxemia and use of antiviral and anti-inflammatory drugs – variables feasible for reporting to public health agencies - would improve classification of death as COVID-19-related.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractBackgroundMany community-acquired pleural infections are caused by facultative and anaerobic bacteria from the human oral microbiota. The epidemiology, clinical characteristics, pathogenesis and etiology of such infections are little studied.The aim of the present prospective multicenter cohort study was to provide a thorough microbiological and clinical characterization of such oral-type pleural infections, and to improve our understanding of the underlying etiology and associated risk factors.MethodsOver a 2-year period, we included 77 patients with community-acquired pleural infection, whereof 63 (82%) represented oral-type pleural infections. Clinical and anamnestic data were systematically collected, and patients were offered a dental assessment by an oral surgeon. Microbial characterizations were done using next-generation sequencing. Obtained bacterial profiles were compared to microbiology data from previous investigations on odontogenic infections, bacteremia after extraction of infected teeth, and community-acquired brain abscesses.ResultsFrom the oral-type pleural infections, we made 267 bacterial identifications representing 89 different species. Streptococcus intermedius and/or Fusobacterium nucleatum were identified as a dominant component in all infections. We found a high prevalence of dental infections among patients with oral-type pleural infection and demonstrate substantial similarities between the microbiology of such pleural infections and that of odontogenic infections, odontogenic bacteremia and community-acquired brain abscesses.ConclusionOral-type pleural infection is the most common type of community-acquired pleural infection. Current evidence supports hematogenous seeding of bacteria from a dental focus as the most important underlying etiology. Streptococcus intermedius and Fusobacterium nucleatum most likely represent key pathogens necessary for establishing the infection.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractBackgroundEvidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assess the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compare the effectiveness and safety of C-BA vs. third-generation cephalosporin monotherapy.MethodsRetrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and one-year mortality.ResultsA total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9 %, and 190 (20.9 %) patients developed acute kidney injury. Heart failure (OR 6.06; 95% CI 1.37-26.87; P = .018), central nervous system emboli (OR 9.83; 95% CI 2.17-44.49; P = .003) and intracardiac abscess (OR 13.47; 95% CI 2.24-81.08; P = 0.004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR 1.01; 95% CI 0.26-3.96; P = .982).ConclusionsOur findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.06.2023
Tilføjet 25.06.2023
AbstractBackgroundFew studies have comprehensively evaluated the risk of lung cancer in tuberculosis (TB) survivors with consideration of smoking status and chronic obstructive pulmonary disease (COPD). Furthermore, little is known about lung cancer risk factors in TB survivors.MethodsThis population-based cohort study enrolled TB survivors (n=75,467) between 2010 and 2017 and 1:1 age- and sex-matched controls. Subjects were followed up for one year from the date of TB diagnosis to the date of the incident lung cancer, death, or Dec, 2018, whichever came first. The risk of lung cancer was evaluated according to smoking and COPD status. Additionally, We evaluated the risk factors for lung cancer and developed an individualized lung cancer prediction model for TB survivors.ResultsDuring a median follow-up duration of 4.8 years, the incident lung cancer risk was 1.72-fold higher in TB survivors than in the controls. Among TB survivors, those who were current smokers with ≥20 pack-years showed the highest risk of lung cancer (adjusted hazard ratio [aHR]=6.78) compared to never-smoker, non-TB controls. TB survivors with COPD had a higher risk (aHR=2.43) than non-COPD, non–TB controls. Risk factors for lung cancer in TB survivors were pulmonary TB, age>60 years, smoking, and the presence of COPD or asthma. The individualized lung cancer risk model showed good discrimination (c-statistic=0.827).ConclusionsPrevious TB infection is an independent risk factor independent of smoking status or amount and COPD. Closer monitoring of TB survivors, especially heavy smokers or those with COPD, is needed for early lung cancer diagnosis.
Læs mere Tjek på PubMedAnn M. ArvinaStanford University School of Medicine, Stanford, California, USA
Microbiology and Molecular Biology Reviews, 24.06.2023
Tilføjet 24.06.2023
Rebekah M. Dedrick, Lawrence Abad, Nathaniel Storey, Ari M. Kaganovsky, Bailey E. Smith, Haley A. Aull, Madison Cristinziano, Anna Morkowska, Saraswathi Murthy, Michael R. Loebinger, Graham F. Hatfull, Giovanni Satta
Clinical Microbiology and Infection, 24.06.2023
Tilføjet 24.06.2023
Mycobacterium abscessus complex is responsible for 2.6%–13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option.Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCC), the likelihood of patient-to-patient transmission and the presence of prophages.
Læs mere Tjek på PubMedCremonese, C., Souza, F. N., Palma, F. A. G., Sodre, J. F. A., Brito, R. L., Ribeiro, P. d. S., Santana, J. O., Coelho, R. H., Ticona, J. P. A., Nazare, R. J., de Oliveira, D., Silva, C. Q., Eyre, M. T., Mendes, V. d. A., Knee, J., Ristow, P., Stauber, C. E., Lopez, Y. A. A., Giorgi, E., Diggle, P. J., Reis, M. G. G., Cumming, O., Ko, A., Costa, F.
BMJ Open, 24.06.2023
Tilføjet 24.06.2023
IntroductionLeptospirosis is a globally distributed zoonotic and environmentally mediated disease that has emerged as a major health problem in urban slums in developing countries. Its aetiological agent is bacteria of the genus Leptospira, which are mainly spread in the urine of infected rodents, especially in an environment where adequate sanitation facilities are lacking, and it is known that open sewers are key transmission sources of the disease. Therefore, we aim to evaluate the effectiveness of a simplified sewerage intervention in reducing the risk of exposure to contaminated environments and Leptospira infection and to characterise the transmission mechanisms involved. Methods and analysisThis matched quasi-experimental study design using non-randomised intervention and control clusters was designed to assess the effectiveness of an urban simplified sewerage intervention in the low-income communities of Salvador, Brazil. The intervention consists of household-level piped sewerage connections and community engagement and public involvement activities. A cohort of 1400 adult participants will be recruited and grouped into eight clusters consisting of four matched intervention-control pairs with approximately 175 individuals in each cluster in baseline. The primary outcome is the seroincidence of Leptospira infection assessed through five serological measurements: one preintervention (baseline) and four postintervention. As a secondary outcome, we will assess Leptospira load in soil, before and after the intervention. We will also assess Leptospira exposures before and after the intervention, through transmission modelling, accounting for residents\' movement, contact with flooding, contaminated soil and water, and rat infestation, to examine whether and how routes of exposure for Leptospira change following the introduction of sanitation. Ethics and disseminationThis study protocol has been reviewed and approved by the ethics boards at the Federal University of Bahia and the Brazilian National Research Ethics Committee. Results will be disseminated through peer-reviewed publications and presentations to implementers, researchers and participating communities. Trial registration numberBrazilian Clinical Trials Registry (RBR-8cjjpgm).
Læs mere Tjek på PubMedWrenger, J., Martin, D. D., Jenetzky, E.
BMJ Open, 24.06.2023
Tilføjet 24.06.2023
IntroductionVaccinations are considered to have a large impact on disease control, hence a multitude of vaccines in infancy is recommended. Retrospective studies suggest a possible relation between timing, kind or number of vaccines given in the first year of life and the subsequent incidence of allergic diseases. It must be clarified whether a causal relationship exists to ensure safety and reduce vaccine hesitancy. Methods and analysisDue to the high recommendation rate of vaccines, a long-term randomised controlled trial is not considered as ethically acceptable. Therefore, this study aims to observe prospectively the allergic incidence at the age of 5 years after various vaccine interventions in the early months of life. Parents of infants up to the age of 4–6 weeks will be recruited before the first recommended vaccination. Relevant prognostic factors for allergies, status of immunisation and general health will be evaluated up to the age of 5. Allergic symptoms will be assessed by the International Study of Asthma and Allergies in Childhood-questionnaire and a medical confirmation of the allergy is mandatory. The main objective is to compare the incidence of asthma, atopic dermatitis, rhinoconjunctivitis, food allergy or any of these atopies at the age of 5 between infants who were not vaccinated or were vaccinated according to recommendations in the first year of life. The sample size calculation with about 4000 participants can prove a 5% difference to the basic prevalence with about 80% power and global 5% alpha error for the five primary endpoints adjusting according to Bonferroni-Holm and assuming a rate of 10% not early vaccinated infants. Ethics and disseminationThe study was registered (DRKS00029677) and has received approval by the ethics committee of Universität Witten/Herdecke (no. 113/2022). The results will be published.
Læs mere Tjek på PubMedGutierrez, A., Rodriguez, B., Velasquez, K., Gutierrez, I., Garcia, S., Munez, E., Calderon-Parra, J., Callejas-Diaz, A., Ramos-Martinez, A., Fernandez-Cruz, A.
BMJ Open, 24.06.2023
Tilføjet 24.06.2023
IntroductionThe evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission tomography/CT with 18F-fluorodeoxyglucose (18F-FDG PET/CT) not only evaluates more than one body area in one session, but adds functional information to the anatomic data provided by usual imaging techniques and can potentially improve staging of IFI and monitoring of the response to therapy. Our objective is to analyse the impact of the systematic use of 18F-FDG PET/CT in IFI diagnostic and therapeutic management. Methods and analysisMulticentre prospective cohort study of IFI with performance of systematic 18F-FDG PET/CT at diagnosis and follow-up that will be carried out in 14 Spanish tertiary hospitals. It is planned to include 224 patients with IFI over a 2-year study period. Findings and changes in management before and after 18F-FDG PET/CT will be compared. Additionally, the association of initial quantitative 18F-FDG PET/CT parameters with response to therapy will be evaluated. The primary endpoint is to compare the yield of 18F-FDG PET/CT with standard management without 18F-FDG PET/CT in IFI at initial assessment (staging) and in monitoring the response to treatment. The impact of the results of 18F-FDG PET/CT on the diagnostic-therapeutic management of patients with IFI (added value), as well as the prognostic ability of different quantification parameters of 18F-FDG PET/CT will be secondary endpoints. Ethics and disseminationThe Clinical Research Ethics Committee of Puerta de Hierro-Majadahonda University Hospital approved the protocol of the study at the primary site. We plan to publish the results in high-impact journals. Trial registration number NCT05688592.
Læs mere Tjek på PubMedYin Zhai, John P. Pribis, Sean W. Dooling, Libertad Garcia-Villada, P.J. Minnick, Jun Xia, Jingjing Liu, Qian Mei, Devon M. Fitzgerald, Christophe Herman, P.J. Hastings, Mauro Costa-Mattioli, Susan M. Rosenberg
Science Advances, 24.06.2023
Tilføjet 24.06.2023
Eugenio Paglino, Dielle J. Lundberg, Zhenwei Zhou, Joe A. Wasserman, Rafeya Raquib, Anneliese N. Luck, Katherine Hempstead, Jacob Bor, Samuel H. Preston, Irma T. Elo, Andrew C. Stokes
Science Advances, 24.06.2023
Tilføjet 24.06.2023
Zhiqiang Hu, Yingchao Xie, Jiansen Lu, Jianwu Yang, Jiahuan Zhang, Huaji Jiang, Hongyu Li, Yufeng Zhang, Dan Wu, Ke Zeng, Xiaochun Bai, Xiao Yu
Science Advances, 24.06.2023
Tilføjet 24.06.2023
Zhenzhen Wang, Zhenhua Li, Weiwei Shi, Dashuai Zhu, Shiqi Hu, Phuong-Uyen C. Dinh, Ke Cheng
Science Advances, 24.06.2023
Tilføjet 24.06.2023
Grischa Y. Chen, Natalia R. Thorup, Abigail J. Miller, Yao-Cheng Li, Janelle S. Ayres
Science Advances, 24.06.2023
Tilføjet 24.06.2023
Henry Kyobe Bosa, M. Kariuki Njenga, Misaki Wayengera, Bruce Kirenga, Winters Muttamba, Jeanette Dawa, Robert F. Breiman, Eric Osoro, Isaac Ngere, Francis Omaswa, Samuel Okware, Richard Kabanda, Henry Mwebesa, Diana Atwine, Yonas Tegegn Woldemariam, Jane Ruth Aceng
Nature, 24.06.2023
Tilføjet 24.06.2023
Susannah L. Woodd, Abdunoor M. Kabanywanyi, Andrea M. Rehman, Oona M. R. Campbell, Asila Kagambo, Warda Martiasi, Louise T. Day, Alexander M. Aiken, Wendy J. Graham
PLoS One Infectious Diseases, 24.06.2023
Tilføjet 24.06.2023
by Susannah L. Woodd, Abdunoor M. Kabanywanyi, Andrea M. Rehman, Oona M. R. Campbell, Asila Kagambo, Warda Martiasi, Louise T. Day, Alexander M. Aiken, Wendy J. Graham
Læs mere Tjek på PubMedRei Sakamoto, Ayumi Takada, Shinnosuke Yamakado, Haruki Tsuge, Etsuro Ito, Makoto Iwata
PLoS One Infectious Diseases, 24.06.2023
Tilføjet 24.06.2023
by Rei Sakamoto, Ayumi Takada, Shinnosuke Yamakado, Haruki Tsuge, Etsuro Ito, Makoto Iwata Follicular helper T (Tfh) cells are crucial for humoral immunity. Dysregulation of Tfh cell differentiation can cause infectious, allergic, and autoimmune diseases. To elucidate the molecular mechanisms underlying Tfh cell differentiation, we attempted to establish an in vitro mouse model of Tfh cell differentiation in the absence of other cell types. Various cytokines and cell surface molecules are suggested to contribute to the differentiation. We found that stimulating naïve CD4+ T cells with immobilized antibodies to CD3, ICOS, and LFA-1 in the presence of soluble anti-CD28 antibody, IL-6, and antibodies that block IL-2 signaling for 3 days induced the expression of Bcl6 and Rorc(γt), master regulator genes of Tfh and Th17 cells, respectively. TGF-β significantly enhanced cell proliferation and Bcl6 and Rorc(γt) expression. An additional 2 days of culture without immobilized antibodies selectively downregulated Rorc(γt) expression. These cells produced IL-21 and promoted B cells to produce IgG antibodies. Adding the aryl hydrocarbon receptor (AhR) antagonist CH-223191 to the T cell culture further downregulated Rorc(γt) expression without significantly affecting Bcl6 expression, and upregulated expression of a key Tfh marker, CXCR5. Although their CXCR5 expression levels were still not high, the CH-223191-treated cells showed chemotactic activity towards the CXCR5 ligand CXCL13. On the other hand, AhR agonists upregulated Rorc(γt) expression and downregulated CXCR5 expression. These findings suggest that AhR activity and the duration of T cell receptor stimulation contribute to regulating the balance between Tfh and Th17 cell differentiation. Although this in vitro system needs to be further improved, it may be useful for elucidating the mechanisms of Tfh cell differentiation as well as for screening physiological or pharmacological factors that affect Tfh cell differentiation including CXCR5 expression.
Læs mere Tjek på PubMedShun-Min Yao, Meng-Ling Wu, Ting-Hsuan Hung
PLoS One Infectious Diseases, 24.06.2023
Tilføjet 24.06.2023
by Shun-Min Yao, Meng-Ling Wu, Ting-Hsuan Hung Citrus Huanglongbing (HLB) is one of the most destructive diseases of citrus plants caused by the obligate and phloem-limiting bacterium Candidatus Liberibacter asiaticus (Las). Reliable detection methods are important for successful control of the disease. This study was aimed to develop a rapid and user-friendly on-site detection system for Las using the TaqMan probe-based insulated isothermal polymerase chain reaction (iiPCR) assay. The Las-specific on-site detection system could be completed within one hour by simple DNA extraction coupled with a portable POCKIT device, which can perform PCR amplification and automatically provide qualitative results derived from fluorescence signals. The sensitivity of the TaqMan probe-iiPCR assay could be as low as single copy of Las, comparable to a real-time PCR method. Further testing of the field citrus samples showed 100% agreement between the TaqMan probe-iiPCR assay and the real-time PCR method, and the on-site detection system also demonstrated a great performance of Las detection. With high specificity and sensitivity, the on-site detection system developed in this study becomes a simple, rapid and powerful tool for detecting Las in fields.
Læs mere Tjek på PubMedIda Peréa Monteiro, Camila Flávia Gomes Azzi, João Paolo Bilibio, Pedro Sadi Monteiro, Giordana Campos Braga, Nadjar Nitz
PLoS One Infectious Diseases, 24.06.2023
Tilføjet 24.06.2023
by Ida Peréa Monteiro, Camila Flávia Gomes Azzi, João Paolo Bilibio, Pedro Sadi Monteiro, Giordana Campos Braga, Nadjar Nitz Sexually transmitted infections (STIs) are among the most common public health problems worldwide, especially among adolescents and young adults, who account for almost 50% of all STI patients. Studies on the subject in the western Amazon are limited. This study aimed to evaluate the prevalence of STIs (chlamydia, gonorrhea, trichomoniasis, herpes simplex virus, syphilis, human immunodeficiency virus [HIV], hepatitis B, and hepatitis C) in adolescents treated at a family planning outpatient clinic in the western Amazon: Porto Velho, Rondônia, Brazil. A total of 196 adolescents were enrolled. During the gynecological examination, endocervical samples were collected to test for four STIs (chlamydia, gonorrhea, trichomoniasis, and herpes simplex virus), and blood samples were collected for the detection of HIV, syphilis, and hepatitis B and C. The mean age was 17.3 ± 1.5 years, the age at sexarche was 14.4 ± 1.6 years, and 54.6% of participants had their first sexual intercourse at 14 years or younger. Only 1.0% of the adolescents used condoms in all sexual relations, and 19.9% had casual partner(s) in the last year. In the evaluation of prevalence, we found that 32% of the adolescents had at least one STI, with the most prevalent being chlamydia (23%), followed by trichomoniasis (5.6%), herpes simplex (4.6%), and gonorrhea (3.1%). No positive cases of hepatitis B, hepatitis C, or HIV were detected, but 1% of the adolescents tested positive for syphilis. These indicators will support more effective health care strategies aimed at improving the quality of life of populations in this region of the western Amazon. In conclusion, our findings demonstrated high rates of STIs in the studied patients, reinforcing the need to expand epidemiological studies to implement more appropriate public policies and intervention strategies to prevent STIs in adolescents and other vulnerable populations in the western Amazon.
Læs mere Tjek på PubMedShay Perek, Udi Nussinovitch, Neta Sagi, Yori Gidron, Ayelet Raz-Pasteur
PLoS One Infectious Diseases, 24.06.2023
Tilføjet 24.06.2023
by Shay Perek, Udi Nussinovitch, Neta Sagi, Yori Gidron, Ayelet Raz-Pasteur Background Infective endocarditis (IE) is a disease that poses a serious health risk. It is important to identify high-risk patients early in the course of their treatment. In the current study, we evaluated the prognostic value of ultra-short heart-rate variability (HRV), an index of vagal nerve activity, in IE. Methods Retrospective analysis was performed on adult patients admitted to a tertiary hospital due to IE. A logistic regression (LR) was used to determine whether clinical, laboratory, and HRV parameters were predictive of specific clinical features (valve type, staphylococcal infection) or severe short-term complications (cardiac, metastatic infection, and death). The accuracy of the model was evaluated through the measurement of the area under the curve (AUC) of the receiver operating characteristic curve (ROC). An analysis of survival was conducted using Cox regression. A number of HRV indices were calculated, including the standard deviation of normal heart-beat intervals (SDNN) and the root mean square of successive differences (RMSSD). Results 75 patients, aged 60.3(±18.6) years old, were examined. When compared with published age- and gender-adjusted HRV norms, SDNN and RMSSD were found to be relatively low in our cohort (75%-76% lower than the median; 33%-41% lower than the 2nd percentile). 26(34.6%) patients developed a metastatic infection, with RMSSD
Læs mere Tjek på PubMedLiangchen Zhang, Guangli Yang
PLoS One Infectious Diseases, 24.06.2023
Tilføjet 24.06.2023
by Liangchen Zhang, Guangli Yang Social insurance is an essential component of a contemporary social security system since it protects people’s fundamental well-being, but it also incurs a heavy cost for businesses. If social security costs are excessively high, business profitability will suffer, and innovation will be discouraged. The most affected companies would be those in labor-intensive industries and medium-sized enterprises. Chinese businesses have suffered severe losses as a result of the COVID-19 outbreak. Given the circumstance, China enacted additional tax cuts and preferential social insurance premium plans. This article suggests a lower ratio of contribution as a strategy to cut the cost of social insurance premiums for businesses, given the growth of the social security fund in recent years and the proportion of participants to recipients in pension funds. It would be possible to increase firm profitability and lessen the impact of COVID-19 on industries by minimizing this operation burden. In order to compare the financial performance of state-owned manufacturers (SOMs) to that of their non-state-owned peers, who have a lower ratio of contribution, this study uses a multiple regression model. The ratio of contributions was inversely correlated with an enterprise’s financial performance. In other words, financial performance will improve as the ratio of contribution lowers; nevertheless, this effect is more pronounced in SOMs. The final section of this study proposed optimized approaches for social insurance premiums reform.
Læs mere Tjek på PubMedMalaria Journal, 24.06.2023
Tilføjet 24.06.2023
Abstract Background Malaria is a mosquito-borne disease that is one of the most serious public health issues globally and a leading cause of mortality in many developing countries worldwide. Knowing the prevalence of both symptomatic and asymptomatic malaria on a subnational scale allows for the estimation of the burden of parasitaemia present in the transmission system, enabling targeting and tailoring of resources towards greater impact and better use of available capacity. This study aimed to determine the PCR-based point prevalence of malaria infection, by parasite species, among three high-risk populations in Mondulkiri province, Cambodia: forest rangers, forest dwellers, and forest goers. Methods A cross-sectional survey was performed during the transmission season in November and December 2021. Blood samples collected on filter paper from participants (n = 1301) from all target groups were screened for Plasmodium spp using PCR. Results Malaria prevalence among all study participants was 6.7% for any Plasmodium species. Malaria prevalence in the forest ranger group was 8.1%, was 6.8% in forest goers, and 6.4% in forest dwellers; all infections were asymptomatic. Plasmodium vivax was detected in all participant groups, while the few Plasmodium falciparum infections were found in goers and dwellers. 81% of all infections were due to P. vivax, 9% were due to P. falciparum, 3% due to Plasmodium cynomolgi, and the rest (7%) remained undefined. Gender was associated with malaria infection prevalence, with male participants having higher odds of malaria infection than female participants (OR = 1.69, 95% CI 1.08–2.64). Passively collected malaria incidence data from the Cambodian government were also investigated. Health facility-reported malaria cases, based on rapid diagnostic tests, for the period Jan-Dec 2021 were 521 Plasmodium vivax (0.89% prevalence), 34 P. falciparum (0.06%) and four P. falciparum + mixed (0.01%)—a total of 559 cases (0.95%) for all of Mondulkiri. Conclusion This reservoir of asymptomatic parasitaemia may be perpetuating low levels of transmission, and thus, new strategies are required to realize the goal of eliminating malaria in Cambodia by 2025.
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.06.2023
Tilføjet 23.06.2023
Abstract Background . The Mycobacterium tuberculosis Beijing genotype is globally spread lineage with important medical properties that however vary among its subtypes. M. tuberculosis Beijing 14717-15-cluster was recently discovered as both multidrug-resistant, hypervirulent, and highly-lethal strain circulating in the Far Eastern region of Russia. Here, we aimed to analyze its pathogenomic features and phylogeographic pattern. Results . The study collection included M. tuberculosis DNA collected between 1996 and 2020 in different world regions. The bacterial DNA was subjected to genotyping and whole genome sequencing followed by bioinformatics and phylogenetic analysis. The PCR-based assay to detect specific SNPs of the Beijing 14717-15-cluster was developed and used for its screening in the global collections. Phylogenomic and phylogeographic analysis confirmed endemic prevalence of the Beijing 14717-15-cluster in the Asian part of Russia, and distant common ancestor with isolates from Korea (> 115 SNPs). The Beijing 14717-15-cluster isolates had two common resistance mutations RpsL Lys88Arg and KatG Ser315Thr and belonged to spoligotype SIT269. The Russian isolates of this cluster were from the Asian Russia while 4 isolates were from the Netherlands and Spain. The cluster-specific SNPs that significantly affect the protein function were identified in silico in genes within different categories (lipid metabolism, regulatory proteins, intermediary metabolism and respiration, PE/PPE, cell wall and cell processes). Conclusions . We developed a simple method based on real-time PCR to detect clinically significant MDR and hypervirulent Beijing 14717-15-cluster. Most of the identified cluster-specific mutations were previously unreported and could potentially be associated with increased pathogenic properties of this hypervirulent M. tuberculosis strain. Further experimental study to assess the pathobiological role of these mutations is warranted.
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