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Kathryn Winglee, Andrew N. Hill, Robert Belknap, Jason E. Stout, Tracy Ayers
Clinical Microbiology and Infection, 17.02.2022
Tilføjet 17.02.2022
Interferon-γ release assays (IGRAs), including T-SPOT.TB (TSPOT) and QuantiFERON Gold In-Tube (QFT), are important diagnostic tools for tuberculosis infection, yet little work has been done to study the performance of these tests in populations prioritized for tuberculosis testing in the United States, especially other than healthcare personnel.
Læs mere Tjek på PubMedStuart G. Tangye, Klaus Warnatz
Immunity, 17.02.2022
Tilføjet 17.02.2022
The generation of memory B cells and plasma cells is complex and involves inputs from the microenvironment, notably from T follicular helper cells. In last month’s issue of Immunity, Yeh et al. and Song et al. refine our understanding of the B cell intrinsic and extrinsic requirements to generate effective humoral immunity in response to foreign antigens.
Læs mere Tjek på PubMedJue Feng, Joseph N. Pucella, Geunhyo Jang, Marcela Alcántara-Hernández, Samik Upadhaya, Nicholas M. Adams, Alireza Khodadadi-Jamayran, Colleen M. Lau, Marlon Stoeckius, Stephanie Hao, Peter Smibert, Aristotelis Tsirigos, Juliana Idoyaga, Boris Reizis
Immunity, 17.02.2022
Tilføjet 17.02.2022
The origin and lineage affiliation of plasmacytoid dendritic cells (pDCs) remain controversial. Feng et al. show that pDCs originate from the same pool of bone marrow progenitors as conventional dendritic cells (cDCs) and are clonally related to the cDC1 subset of cDCs.
Læs mere Tjek på PubMedHoward, M. J., Chambers, C. N. L., Mohr, N. M.
BMJ Open, 17.02.2022
Tilføjet 17.02.2022
Objective
Our objective was to assess the level of COVID-19 preparedness of emergency departments (EDs) in Aotearoa New Zealand (NZ) through the views of emergency medicine specialists working in district health boards around the country. Given the limited experience NZ hospitals have had with SARS-CoV-2, a comparison of current local practice with recent literature from other countries identifying known weaknesses may help prevent future healthcare worker infections in NZ.
Methods
We conducted a cross-sectional survey of NZ emergency specialists in November 2020 to evaluate preparedness of engineering, administrative policy and personal protective equipment (PPE) use.
Results
A total of 137 surveys were completed (32% response rate). More than 12% of emergency specialists surveyed reported no access to negative pressure rooms. N95 fit testing had not been performed in 15 (12%) of respondents. Most specialists (77%) work in EDs that cohort patients with COVID-19, about one-third (34%) do not use spotters during PPE doffing, and most (87%) do not have required space for physical distancing in non-patient areas. Initial PPE training, simulations and segregating patients were widespread but appear to be waning with persistent low SARS-CoV-2 prevalence. PPE shortages were not identified in NZ EDs, yet 13% of consultants do not plan to use respirators during aerosol-generating procedures on patients with COVID-19.
Conclusions
NZ emergency specialists identified significant gaps in COVID-19 preparedness, and they have a unique opportunity to translate lessons from other locations into local action. These data provide insight into weaknesses in hospital engineering, policy and PPE practice in advance of future SARS-CoV-2 endemic transmission.
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van Amstel, P., Bakx, R., van der Lee, J. H., van der Weide, M. C., Eekelen, R. v., Derikx, J. P. M., van Heurn, E. L. W., Gorter, R. R., CAPP collaborative study group, Rippen, Berkhof, Koot, van der Kuip, van Rijn, Bonjer, Jansen, Lijkwan, Boele van Hensbroek, Springer, van Eijck, Luyer, Jairam, de Widt, Knaapen, Keyzer-Dekker, Wijnen, Diepenhorst, Dreuning, Poelman, Verver, van Duijvendijk, van der Sande, Oosterhuis, Zijp, Pasveer, Groenendijk, van Vugt, Vles, Selles, Nieuwenhuijs, Hoffman, Leijtens, Vosbeek, van Rossem, Gaspersz, Bender, Corten, Consten, Seesing, Bijlsma, The, Janssen, Leijdekkers, Nijenhuis, Botden, Joosten, Bloemendaal, Blanken-Peeters, IJgosse, Meij-de Vries, Bruntink, Go, Pool, Oosterling, Derksen, van Geloven, Poels, Hulscher, den Boer, Hardon, Garssen, Wagner, Lutke Holzik, Decaestecker, Boerma, Schweitzer, Musters
BMJ Open, 17.02.2022
Tilføjet 17.02.2022
Introduction
In daily practice large heterogeneity in the treatment of children with complex appendicitis exists. Complex appendicitis can be divided into two subtypes; complex appendicitis with and without appendiceal mass and/or abscess. As complex appendicitis is associated with high morbidity and costs, identification of the optimal treatment strategy is essential. In this article, we present the study protocol for the CAPP (Complex Appendicitis in the Pediatric Population) study.
Methods and analysis
This nation-wide, multi-centre, comparative, non-randomised prospective cohort study includes all children <18 years old with a preoperative suspicion of complex appendicitis, which is based on imaging confirmed acute appendicitis and predefined criteria regarding the severity of appendicitis. Eligible patients are recruited in more than 30 hospitals. Open appendectomy will be compared with laparoscopic appendectomy for children without appendiceal mass and/or abscess and initial non-operative treatment (ie, intravenous antibiotics with or without percutaneous drainage) to direct appendectomy for children with appendiceal mass and/or abscess. Based on historical data supplied by the participating hospitals and an inclusion period of 2 years and 9 months, a sample size of 1308 patients is aimed. Primary outcome is the proportion of patients experiencing any complication at 3 months follow-up. Reported complications will be assessed by an independent adjudication committee. Secondary outcomes include, but are not limited to, quality of life, and (in)direct costs. To adjust for baseline differences and selection bias, outcomes will be compared after propensity score analysis (inverse probability weighting and stratification).
Ethics and dissemination
The Medical Ethics Review Committee of the Amsterdam UMC, location AMC, declared that the Medical Research involving Human Subjects Act (WMO) did not apply to this study. Therefore, no official approval was required by national law. Study results will be presented in peer-reviewed scientific journals and at (inter)national conferences.
Trial registration numbers
NCT04755179; NL9371.
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Bhandari, D., Ozaki, A., Suzuki, T., Kotera, Y., Shrestha, S., Horiuchi, S., Miyachi, T., Tabuchi, T.
BMJ Open, 17.02.2022
Tilføjet 17.02.2022
Objectives
The detrimental impacts of abuse on victims’ well-being are well documented globally, including Japan. The ongoing COVID-19 pandemic may increase the incidence of abuse in the community, creating an additional burden amid the crisis. However, the incidence of abuse in Japan during COVID-19 remains to be evaluated. Accordingly, our study aimed to assess the incidence of physical and verbal abuse among the general population in Japan and to identify the associated factors of abuse during COVID-19.
Design and setting
We used the data obtained from a nationwide, cross-sectional internet survey conducted in Japan between August and September 2020. Sampling weights were used to calculate national estimates, and multivariable logistic regression was performed to identify the associated factors for physical and verbal abuse.
Results
Out of the total 25 482 participants, 965 (3.8 %) reported experiencing physical abuse and 1941 (7.6%) verbal abuse from April 2020 to September 2020. The incidence of physical and verbal abuse was higher among female participants. Participants who lived in areas where the ‘state of emergency’ was enforced were more likely to suffer from physical abuse. Similarly, vulnerable participants such as those below age 18, with low income, bad family relationships, and disabled people were more likely to experience both physical and verbal abuse. Participants suffering from COVID-19-related symptoms, who had poor health status and widows/divorcees were more likely to be verbally abused. Furthermore, those who did not follow preventive behaviours such as wearing masks in public places, abusing drugs and drinking alcohol in high amounts were also more likely to experience abuse.
Conclusion
The impact of abuse was found disproportionately greater in more vulnerable groups of the population. Pandemic has reinforced the existing social inequalities, which need to be addressed timely to prevent precarious repercussions.
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Sutan, R., Batarfi, S. A., Ismail, H., Bin-Ghouth, A. S.
BMJ Open, 17.02.2022
Tilføjet 17.02.2022
Introduction
Although immunisation prevents the death of millions of infants and children each year, the vaccination coverage of routine childhood vaccination does not reach its target. The reasons for low vaccination uptake can be related to both demand and supply side determinants. The prevalence of vaccine hesitancy is increasing globally. However, data on vaccine hesitancy in low-income Arabic countries are scarce. To investigate this issue in Yemen, an Arabic low-income country, we aim to examine the link between vaccine hesitancy and the immunisation status of children living in Costal Hadhramout, Yemen, from the perspective of their parents and healthcare providers.
Methods and analysis
We will use a mixed-method research design. The study will be conducted in Costal Hadhramout in three phases. Phase 1 will involve a situational analysis using secondary data from records of the national expanded immunisation programme in Costal Hadhramout to examine the trend for previous years. Phase 2 will be a quantitative study aimed at assessing the prevalence of vaccination status of children aged <2 years and the determinants of parental vaccine hesitancy perception through a validated questionnaire. Lastly, phase 3 will be a qualitative study that explores vaccine hesitancy in Yemen using in-depth interviews and focus group discussions with parents and healthcare providers, respectively.
Ethics and dissemination
The study has been approved by the Research Committee of the Faculty of Medicine, University Kebangsaan Malaysia. The findings will be disseminated via publication in peer-reviewed academic journals, academic conferences and public presentations.
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Widbiller, M., Weiler, R., Knüttel, H., Galler, K. M., Buchalla, W., Scholz, K. J.
BMJ Open, 17.02.2022
Tilføjet 17.02.2022
Introduction
Primary goal of restorative caries therapy is to preserve pulp vitality and the dentition. Whereas the conventional approach of complete caries removal aims at the elimination of all affected substances without regard to losses of hard tissue or pulp vitality, the innovative concept of selective caries removal (SCR) is characterised by a targeted and non-invasive excavation. It presents a lower risk of accidental pulp exposure, which reportedly has a positive effect on tooth survival. Although clinical data show the benefits of SCR, knowledge about the biological processes during this procedure in the pulp-dentine complex of permanent teeth is scarce. Hence, the aim of this work is to systematically scope the existing literature and map the existing evidence according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guideline. This protocol details the scoping review’s methodological and analytical approaches.
Methods and analysis
First, a structure was established (phase I) as basis for a systematic scoping of literature (phase II). In the course of phase I, a total of 100 systematic reviews related to selective caries removal were searched in MEDLINE and information or theories on the biological processes were extracted. During the entire procedure, two reviewers independently screened the articles, and controversies were mediated by vote of a third reviewer. Eventually, it became apparent that different biological explanations can be organised into four categories: pulp response, cavity seal, remaining bacteria and cavity liner. Based on this structure, a search for original publications (phase II) will be performed and retrieved evidence will be assembled using a predefined conceptual framework.
Ethics and dissemination
As primary data will not be included in this study, ethical approval is not required. Findings will be disseminated through peer-reviewed publications, conference presentations and summaries for key stakeholders.
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Emerging Infectious Diseases, 17.02.2022
Tilføjet 17.02.2022
Ashley York
Nat Rev Microbiol, 17.02.2022
Tilføjet 17.02.2022
Nature Reviews Microbiology, Published online: 17 February 2022; doi:10.1038/s41579-022-00707-yA recent study provides evidence of non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-associated anosmia.
Læs mere Tjek på PubMedKeith Sacco, Riccardo Castagnoli, Svetlana Vakkilainen, Can Liu, Ottavia M. Delmonte, Cihan Oguz, Ian M. Kaplan, Sara Alehashemi, Peter D. Burbelo, Farzana Bhuyan, Adriana A. de Jesus, Kerry Dobbs, Lindsey B. Rosen, Aristine Cheng, Elana Shaw, Mikko S. Vakkilainen, Francesca Pala, Justin Lack, Yu Zhang, Danielle L. Fink, Vasileios Oikonomou, Andrew L. Snow, Clifton L. Dalgard, Jinguo Chen, Brian A. Sellers, Gina A. Montealegre Sanchez, Karyl Barron, Emma Rey-Jurado, Cecilia Vial, Maria Cecilia Poli, Amelia Licari, Daniela Montagna, Gian Luigi Marseglia, Francesco Licciardi, Ugo Ramenghi, Valentina Discepolo, Andrea Lo Vecchio, Alfredo Guarino, Eli M. Eisenstein, Luisa Imberti, Alessandra Sottini, Andrea Biondi, Sayonara Mató, Dana Gerstbacher, Meng Truong, Michael A. Stack, Mary Magliocco, Marita Bosticardo, Tomoki Kawai, Jeffrey J. Danielson, Tyler Hulett, Manor Askenazi, Shaohui Hu, Jason Barnett, Xi Cheng, Krishnaveni Kaladi, Vasudev Kuram, Joseph Mackey, Neha M. Bansal, Andrew J. Martins, Boaz Palterer, Helen Matthews, Uma Mudunuri, Marshall Nambiar, Andrew J. Oler, Andre Rastegar, Smilee Samuel, Conrad Shyu, Varsha Waingankar, Sarah Weber, Sandhya Xirasagar, Yazmin Espinosa, Camila Astudillo, Cecilia Piñera, Ricardo González, Maria De Filippo, Martina Votto, Lorenza Montagna, Jeffrey I. Cohen, Helen C. Su, Douglas B. Kuhns, Michail S. Lionakis, Thomas M. Snyder, Steven M. Holland, Raphaela Goldbach-Mansky, John S. Tsang, Luigi D. Notarangelo
Nature, 17.02.2022
Tilføjet 17.02.2022
Nature Medicine, Published online: 17 February 2022; doi:10.1038/s41591-022-01724-3Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.
Læs mere Tjek på PubMedJin‐Qiu Zhou, Gong‐Xiang Liu, Xiao‐ Li Huang, Hua‐Tian Gan
Journal of Medical Virology, 17.02.2022
Tilføjet 17.02.2022
Stefano Pascarella, Martina Bianchi, Marta Giovanetti, Daniele Narzi, Roberto Cauda, Antonio Cassone, Massimo Ciccozzi
Journal of Medical Virology, 17.02.2022
Tilføjet 17.02.2022
Matthew M. Hernandez, Mariawy Riollano‐Cruz, Mary C. Boyle, Radhika Banu, Paras Shrestha, Brandon Gray, Liyong Cao, Feng Chen, Huanzhi Shi, Daniel E. Paniz‐Perez, Paul A. Paniz‐Perez, Aryan L. Rishi, Jacob Dubinsky, Dylan Dubinsky, Owen Dubinsky, Sophie Baine, Lily Baine, Suzanne Arinsburg, Ian Baine, Juan David Ramirez, Carlos Cordon‐Cardo, Emilia Mia Sordillo, Alberto E. Paniz‐Mondolfi
Journal of Medical Virology, 16.02.2022
Tilføjet 17.02.2022
Gail Brenda Cross, Claire M. Naftalin, Jinghao Nicholas Ngiam, Natasha Bagdasarian, Chek Meng Poh, Yun Shan Goh, Wan Ni Chia, Siti Naqiah Amrun, Sai Meng Tham, Hazel Teng, Rawan Alagha, Shoban Krishna Kumar, Shaun Shi Yan Tan, Lin Fa Wang, Paul Anantharajah Tambyah, Laurent Renia, Dale Fisher, Lisa F.P. Ng
Journal of Medical Virology, 16.02.2022
Tilføjet 17.02.2022
Michael C. McGee, Weishan Huang
Journal of Medical Virology, 16.02.2022
Tilføjet 17.02.2022
Shu Yuan, Si‐Cong Jiang, Zhong‐Wei Zhang, Yu‐Fan Fu, Feng Zhu, Zi‐Lin Li, Jing Hu
Journal of Medical Virology, 16.02.2022
Tilføjet 17.02.2022
Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
New England Journal of Medicine, 16.02.2022
Tilføjet 17.02.2022
New England Journal of Medicine, 16.02.2022
Tilføjet 17.02.2022
Jennifer Hammond, Heidi Leister-Tebbe, Annie Gardner, Paula Abreu, Weihang Bao, Wayne Wisemandle, MaryLynn Baniecki, Victoria M. Hendrick, Bharat Damle, Abraham Simón-Campos, Rienk Pypstra, James M. Rusnak
New England Journal of Medicine, 16.02.2022
Tilføjet 17.02.2022
Victoria Hall, Sarah Foulkes, Ferdinando Insalata, Peter Kirwan, Ayoub Saei, Ana Atti, Edgar Wellington, Jameel Khawam, Katie Munro, Michelle Cole, Caio Tranquillini, Andrew Taylor-Kerr, Nipunadi Hettiarachchi, Davina Calbraith, Noshin Sajedi, Iain Milligan, Yrene Themistocleous, Diane Corrigan, Lisa Cromey, Lesley Price, Sally Stewart, Elen de Lacy, Chris Norman, Ezra Linley, Ashley D. Otter, Amanda Semper, Jacqueline Hewson, Silvia D’Arcangelo, Meera Chand, Colin S. Brown, Tim Brooks, Jasmin Islam, Andre Charlett, Susan Hopkins
New England Journal of Medicine, 16.02.2022
Tilføjet 17.02.2022
Ariel Hammerman, Ruslan Sergienko, Michael Friger, Tanya Beckenstein, Alon Peretz, Doron Netzer, Shlomit Yaron, Ronen Arbel
New England Journal of Medicine, 16.02.2022
Tilføjet 17.02.2022
Maarten Versteven
Frontiers in Immunology, 26.10.2022
Tilføjet 17.02.2022
Dendritic cell (DC) vaccines have proven to be a valuable tool in cancer immune therapy. With several DC vaccines being currently tested in clinical trials, knowledge about their therapeutic value has been significantly increased in the past decade. Despite their established safety, it has become clear that objective clinical responses are not yet robust enough, requiring further optimization. Improvements of this advanced therapy medicinal product encompass, among others, regulating their immune stimulating capacity by in situ gene engineering, in addition to their implementation in combination therapy regimens. Previously, we have reported on a superior monocyte-derived DC preparation, including interleukin-15, pro-inflammatory cytokines and immunological danger signals in the culture process. These so-called IL-15 DCs have already proven to exhibit several favorable properties as cancer vaccine. Evolving research into mechanisms that could further modulate the immune response towards cancer, points to programmed death-1 as an important player that dampens anti-tumor immunity. Aiming at leveraging the immunogenicity of DC vaccines, we hypothesized that additional implementation of the inhibitory immune checkpoint molecules programmed death-ligand (PD-L)1 and PD-L2 in IL-15 DC vaccines would exhibit superior stimulatory potential. In this paper, we successfully implemented PD-L silencing at the monocyte stage in the 3-day IL-15 DC culture protocol resulting in substantial downregulation of both PD-L1 and PD-L2 to levels below 30%. Additionally, we validated that these DCs retain their specific characteristics, both at the level of phenotype and interferon gamma secretion. Evaluating their functional characteristics, we demonstrate that PD-L silencing does not affect the capacity to induce allogeneic proliferation. Ultimately designed to induce a durable tumor antigen-specific immune response, PD-L silenced IL-15 DCs were capable of surpassing PD-1-mediated inhibition by antigen-specific T cells. Further corroborating the superior potency of short-term IL-15 DCs, the combination of immune stimulatory components during DC differentiation and maturation with in situ checkpoint inhibition supports further clinical translation.
Læs mere Tjek på PubMedChristina König, Jörn Grensemann, Patrick Czorlich, Eckhard Schlemm, Stefan Kluge, Sebastian G. Wicha
Clinical Microbiology and Infection, 16.02.2022
Tilføjet 17.02.2022
In difficult to treat infections such as nosocomial ventriculitis, meropenem exposure in the infected compartment is often uncertain but crucial for antibacterial effects. The aim of this study was to investigate the cerebrospinal fluid (CSF) penetration of meropenem in patients with nosocomial ventriculitis and to derive a nomograph to predict effective meropenem doses as a function of clinical parameters.
Læs mere Tjek på PubMedJohan Van Laethem, Sabine D. Allard
Clinical Microbiology and Infection, 16.02.2022
Tilføjet 17.02.2022
We read the latest systematic review and meta-analysis of Langford et al. with great interest [1]. The authors provide a high quality review concerning the incidence and microbiological predictors of respiratory and bloodstream bacterial infections in COVID-19 patients. Among other exclusion criteria, they chose to exclude editorials and letters, studies in which bacterial infection was only presumed or suspected and studies in which serology was used as a bacterial infection diagnostic approach.
Læs mere Tjek på PubMedVarpu Marjomäki, Malin Flodström-Tullberg
Trends in Microbiology, 16.02.2022
Tilføjet 17.02.2022
Coxsackie B virus (CVB) was first isolated in the late 1940s in Coxsackie, New York, and is now known to be widespread worldwide. Infections are common and show some seasonal variation as infections are more common during the summer and early fall. The virus particle is small, nonenveloped, and contains a positive single-stranded RNA genome. The virus attaches to a cellular receptor (often the Coxsackie-adenovirus receptor, CAR) on the cell surface and is then internalized via endocytic vesicles after which the virus uncoats and the RNA genome is delivered across the endosomal membrane into the cytoplasm.
Læs mere Tjek på PubMedRubens L. Monte-Neto, Christopher Fernandez-Prada, Nilmar S. Moretti
Trends in Parasitology, 16.02.2022
Tilføjet 17.02.2022
The selection of Leishmania hybrids in axenic culture was considered rare until recently, when Louradour and Ferreira et al., demonstrated that induced DNA damage facilitates genetic exchange, resulting in full genome tetraploid progenies in vitro. Meiosis-related gene homologues HAP2, GEX1, and RAD51 were found to be involved, opening new avenues for functional genomic studies.
Læs mere Tjek på PubMedHedberg, Pontus; Ternhag, Anders; Giske, Christian G.; Strålin, Kristoffer; Özenci, Volkan; Johansson, Niclas; Spindler, Carl; Hedlund, Jonas; Mårtensson, Johan; Nauclér, Pontus
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Objectives:
Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic.
Design:
Retrospective cohort study.
Setting:
Karolinska University Hospital, Stockholm, Sweden.
Patients:
All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020.
Interventions:
None.
Measurements and Main Results:
The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5–18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26–37) for COVID-19 and 34 (95% CI, 32–36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29–0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15–1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14–2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI.
Conclusions:
COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Drs. Hedberg and Ternhag shared first authorship.
Dr. Hedberg had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Hedberg, Ternhag, Mårtensson, and Nauclér were involved in study concept and design. Dr. Hedberg was involved in acquisition, analysis, or interpretation of data. Drs. Hedberg, Ternhag, and Nauclér were involved in drafting of the article. Dr. Nauclér was involved statistical analysis. All authors involved in critical revision of the article for important intellectual content.
Supported, in part, by grants from the Swedish Innovation Agency (Vinnova), Region Stockholm, and Emil och Wera Cornells Stiftelse.
Dr. Hedberg received funding from the Swedish Innovation Agency (Vinnova), Region Stockholm, and Emil och Wera Cornell Stiftelse; he was supported by Karolinska Institutet (combined clinical studies and PhD training program). Dr. Ternhag’s institution received funding from the Swedish Innovation Agency (Vinnova). The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: pontus.naucler@ki.se
Copyright © by 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedFossali, Tommaso; Pavlovsky, Bertrand; Ottolina, Davide; Colombo, Riccardo; Basile, Maria Cristina; Castelli, Antonio; Rech, Roberto; Borghi, Beatrice; Ianniello, Andrea; Flor, Nicola; Spinelli, Elena; Catena, Emanuele; Mauri, Tommaso
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Objectives:
Prone positioning allows to improve oxygenation and decrease mortality rate in COVID-19–associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT).
Design:
Experimental, physiologic study.
Setting:
Patients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU.
Patients:
Twenty-one intubated patients with moderate or severe C-ARDS.
Interventions:
First, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position).
Measurements and Main Results:
Prone position induced recruitment in the dorsal part of the lungs (12.5% ± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (–6.9% ± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ± 15 vs 45 ± 18 mL/cm H2O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ± 0.16 vs 1.30 ± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3–23.4] vs 4.3 [0.7–6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching.
Conclusions:
Several changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Drs. Fossali, Spinelli, and Mauri designed the study. All authors participated to data collection and analysis. All authors participated to article redaction and revision and approved the final version of this article.
The present study was supported by institutional funding of the Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy (ricerca corrente 2020).
Dr. Mauri received funding from the Department of Anesthesia, Critical Care and Emergency, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy (ricerca corrente 2020). Dr. Mauri’s institution received funding from Fisher and Paykel and Draeger; he received funding from Fisher and Paykel, Draeger, and BBraun. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: tommaso.fossali@asst-fbf-sacco.it
Copyright © by 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedLayba, Cathline; Wallace, David J.
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Cardinale, Michael; Boussen, Salah; Cungi, Pierre-Julien; Esnault, Pierre; Mathais, Quentin; Bordes, Julien; Meaudre, Eric; Goutorbe, Philippe
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Objectives:
ICUs have had to deal with a large number of patients with acute respiratory distress syndrome COVID-19, a significant number of whom received prone ventilation, which is a substantial consumer of care time. The selection of patients that we have to ventilate in prone position seems interesting. We evaluate the correlation between the percentage of collapsed dependent lung areas in the supine position, monitoring by electrical impedance tomography and the oxygenation response (change in PaO2/FIO2 ratio) to prone position.
Design:
An observational prospective study.
Setting:
From October 21, 2020, to 30 March 30, 2021. At the Sainte Anne military teaching Hospital and the Timone University Hospital.
Patients:
Fifty consecutive patients admitted in our ICUs, with COVID-19 acute respiratory distress syndrome and required mechanical, were included. Twenty-four (48%) received prone ventilation. Fifty-eight prone sessions were investigated.
Interventions:
An electrical impedance tomography recording was made in supine position, daily and repeated just before and just after the prone session. The daily dependent area collapse was calculated in relation to the previous electrical impedance tomography recording. Prone ventilation response was defined as a PaO2/FIO2 ratio improvement greater than 20%.
Measurement and Main Results:
The main outcome was the correlation between dependent area collapse and the oxygenation response to prone ventilation. Dependent area collapse was correlated with oxygenation response to prone ventilation (R2 = 0.49) and had a satisfactory prediction accuracy of prone response with an area under the curve of 0.94 (95% CI, 0.87–1.00; p < 0.001). Best Youden index was obtained for a dependent area collapse greater than 13.5 %. Sensitivity of 92% (95% CI, 78–97), a specificity of 91% (95% CI, 72–97), a positive predictive value of 94% (95% CI, 88–100), a negative predictive value of 87% (95% CI, 78–96), and a diagnostic accuracy of 91% (95% CI, 84–98).
Conclusions:
Dependent lung areas collapse (> 13.5%), monitored by electrical impedance tomography, has an excellent positive predictive value (94%) of improved oxygenation during prone ventilation.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Drs. Cardinale and Philippe designed the study. Drs. Cardinale wrote the article and is its guarantor. Drs. Cardinale, Salah, Pierre-Julien, Pierre, and Quentin managed the data collection. All of the authors have contributed to writing the article and approved the final article.
Presented, in part, at the French Society of Anesthesia and Intensive Care, Paris, France, September 2021.
Study Approvals: Protection to Persons Committee in Ile de France, 20 October 2020 (N°2020-A02823-36) and The Sainte Anne Military Teaching Hospital’s ethics committee (N° 0011873-2020-21).
This work was performed at Intensive care Unit, Sainte Anne Military Teaching Hospital, Toulon, France; Intensive Care Unit, Timone University Hospital, Marseille, France.
The authors have disclosed that they do not have any potential conflicts of interest.
ClinicalTrials.gov: NCT04603755.
For information regarding this article, E-mail: mickaelcardinale@hotmail.fr
Copyright © by 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedBenghanem, Sarah; Cariou, Alain; Diehl, Jean-Luc; Marchi, Angela; Charpentier, Julien; Augy, Jean-Loup; Hauw-Berlemont, Caroline; Gavaret, Martine; Pène, Frédéric; Mira, Jean-Paul; Sharshar, Tarek; Hermann, Bertrand
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Objectives:
Describe the prevalence of acute cerebral dysfunction and assess the prognostic value of an early clinical and electroencephalography (EEG) assessment in ICU COVID-19 patients.
Design:
Prospective observational study.
Setting:
Two tertiary critical care units in Paris, France, between April and December 2020.
Patients:
Adult critically ill patients with COVID-19 acute respiratory distress syndrome.
Interventions:
Neurologic examination and EEG at two time points during the ICU stay, first under sedation and second 4–7 days after sedation discontinuation.
MEASUREMENTS AND MAIN RESULTS:
Association of EEG abnormalities (background reactivity, continuity, dominant frequency, and presence of paroxystic discharges) with day-28 mortality and neurologic outcomes (coma and delirium recovery). Fifty-two patients were included, mostly male (81%), median (interquartile range) age 68 years (56–74 yr). Delayed awakening was present in 68% of patients (median awakening time of 5 d [2–16 d]) and delirium in 74% of patients who awoke from coma (62% of mixed delirium, median duration of 5 d [3–8 d]). First, EEG background was slowed in the theta-delta range in 48 (93%) patients, discontinuous in 25 patients (48%), and nonreactive in 17 patients (33%). Bifrontal slow waves were observed in 17 patients (33%). Early nonreactive EEG was associated with lower day-28 ventilator-free days (0 vs 16; p = 0.025), coma-free days (6 vs 22; p = 0.006), delirium-free days (0 vs 17; p = 0.006), and higher mortality (41% vs 11%; p = 0.027), whereas discontinuous background was associated with lower ventilator-free days (0 vs 17; p = 0.010), coma-free days (1 vs 22; p < 0.001), delirium-free days (0 vs 17; p = 0.001), and higher mortality (40% vs 4%; p = 0.001), independently of sedation and analgesia.
Conclusions:
Clinical and neurophysiologic cerebral dysfunction is frequent in COVID-19 ARDS patients. Early severe EEG abnormalities with nonreactive and/or discontinuous background activity are associated with delayed awakening, delirium, and day-28 mortality.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Drs. Benghanem, Sharshar, and Hermann helped in concept and design. Drs. Benghanem and Hermann helped in acquisition, analysis, or interpretation of data. Drs. Benghanem, Cariou, Diehl, Sharshar, and Hermann drafted of the article. All authors contributed to critical revision of the article for important intellectual content.
Supported, in part, by the Département Médico-Universitaire Urgences-Réanimation of Assistance Publique - Hôpitaux de Paris Centre-Université de Paris.
Dr. Pène’s institution received funding from Alexion; he received funding from Gilead. Dr. Hermann’s institution received funding from the Département Médico-Universitaire Urgences-Réanimation of Assistance Publique - Hôpitaux de Paris Centre-Université de Paris. The remaining authors have disclosed that they do not have any potential conflicts of interest.
Work was performed at HEGP and Cochin hospitals, Assistance Publique – Hôpitaux de Paris (AP-HP).
Clinicaltrials.gouv registration: NCT04527198. Registration date: August 26, 2020, retrospectively registered.
For information regarding this article, E-mail: bertrand.hermann@aphp.fr
Copyright © by 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedStockmann, Helena; Thelen, Philipp; Stroben, Fabian; Pigorsch, Mareen; Keller, Theresa; Krannich, Alexander; Spies, Claudia; Treskatsch, Sascha; Ocken, Michele; Kunz, Julius Valentin; Krüger, Anne; Khadzhynov, Dmytro; Kron, Susanne; Budde, Klemens; Eckardt, Kai-Uwe; Enghard, Philipp; Lehner, Lukas Johannes
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Objectives:
To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19–associated vasoplegic shock.
Design:
Prospective, randomized controlled pilot study.
Setting:
Eight ICUs at three sites of the tertiary-care university hospital Charité—Universitätsmedizin Berlin.
Patients:
COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis.
Interventions:
Randomization of 1:1 to receive CytoSorb for 3–7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change.
Measurements and Main Results:
The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4–5 d) and 4 days (IQR, 3–5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54–2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61–2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups.
Conclusions:
In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Drs. Enghard and Lehner contributed equally.
Supported, in part, by internal university funds only.
This work was performed at eight intensive care units at three sites of the Charité—Universitätsmedizin Berlin.
Dr. Enghard received honoraria from GlaxoSmithKline and AstraZeneca and filed two patents for novel urinary biomarkers outside the submitted work. Prof. Dr. Treskatsch received research funding and honoraria for workshops and lectures from Orionpharma, Edwards, Amomed, Cytosorbents, and Smith&Nephews all outside the submitted work. Prof. Dr. Spies received grants from Drägerwerk AG. KGaA; German Research Society; German Aerospace Center; Einstein Foundation Berlin; Federal Joint Committee (Gemeinsamer Bundesaussschuss [G-BA]); Inner University grants; Project Management Agency; Non-Profit Promoting Science and Education; European Society of Anesthesiology and Intensive Care; Baxter Deutschland GmbH; Cytosorbents Europe GmbH; Edwards Lifesciences Germany GmbH; Fresenius Medical Care; Grünenthal GmbH; Massimo Europe; Pfizer Pharma GmbH; Georg Thieme Verlag, Dr. F Köhler Chemie GmbH; Sintetica GmbH; Stifterverband für die deutsche Wissenschaft e.V./Philips; Stiftung Charié; Aguettant Deutschland GmbH; AbbVie Deutschland GmbH & KG; Amomed Pharma GmbH; InTouch Health; Copra System GmbH; Correvio GmbH; Max Plank Gesellschaft zur Förderung der Wissenschaften e.V.; Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin; Stifterverband für die Deutsche Wissenschaft e.V./Medtronic; Philipps ElectronicsNederland BV; and the Federal Ministry of Health, (Bundesministerium für Gesundheit [BMG]), the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung [BMBF]), German Research Society all outside the submitted work. In addition, Prof. Dr. Spies has different patents. Dr. Khadzhynov received fees for speaking at a symposium organized on behalf of Fresenius Medical Care AG, Germany. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: philipp.enghard@charite.de
Copyright © by 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedAnne O’Malley, Patricia
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Jaquet, Pierre; Legouy, Camille; Le Fevre, Lucie; Grinea, Alexandra; Sinnah, Fabrice; Franchineau, Guillaume; Patrier, Juliette; Marzouk, Mehdi; Wicky, Paul-Henri; Alexis Geoffroy, Pierre; Arnoult, Florence; Vledouts, Serafima; de Montmollin, Etienne; Bouadma, Lila; Timsit, Jean-François; Sharshar, Tarek; Sonneville, Romain
Critical Care Medicine, 14.02.2022
Tilføjet 17.02.2022
Objectives:
To describe 3–6-month neurologic outcomes of survivors of COVID-19–associated acute respiratory distress syndrome, invasively ventilated in the ICU.
Design:
A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020).
Setting:
Two academic hospital ICUs, Paris, France.
Patients:
Adult COVID-19–associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge.
Interventions:
Follow-up by face-to-face neurologic consultation.
Measures and Main Results:
The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6–5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome.
Conclusions:
COVID-19–associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Dr. Sonneville received grants from the French Ministry of Health, the French Society of Intensive Care Medicine and the European Society of Intensive Care Medicine. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: pierre.jaquet@aphp.fr
Copyright © by 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedEmerging Infectious Diseases, 2.02.2022
Tilføjet 17.02.2022
Malaria Journal, 16.02.2022
Tilføjet 17.02.2022
Abstract
Background
Achieving malaria elimination requires the targeting of the human reservoir of infection, including those patients with asymptomatic infection. The objective was to synthesise evidence on the accuracy of the rapid-onsite diagnostic tests (RDTs) and microscopy for the detection of asymptomatic malaria as part of the surveillance activities in Asian countries.
Methods
This was a meta-analysis of diagnostic test accuracy. Relevant studies that evaluated the diagnostic performance of RDTs and microscopy for detection of asymptomatic malaria were searched in health-related electronic databases. The methodological quality of the studies included was assessed using the QUADAS-2 tool.
Results
Ten studies assessing RDT and/or microscopy were identified. The diagnostic accuracies in all these studies were verified by PCR. Overall, the pooled sensitivities of RDT, as well as microscopy for detection of any malaria parasites in asymptomatic participants, were low, while their pooled specificities were almost ideal. For the detection of Plasmodium falciparum, pooled sensitivity by RDT (59%, 95%CI:16–91%) or microscopy (55%, 95%CI: 25–82%) were almost comparable. For detection of Plasmodium vivax, pooled sensitivity of RDT (51%, 95% CI:7–94%) had also the comparable accuracy of microscopy (54%, 95%CI,11–92%). Of note are the wide range of sensitivity and specificity.
Conclusion
The findings of this meta-analysis suggest that RDTs and microscopy have limited sensitivity and are inappropriate for the detection of asymptomatic Plasmodium infections. Other methods including a combination of PCR-based strategies, Loop-Mediated Isothermal Amplification (LAMP) technique must be considered to target these infections, in order to achieve malaria elimination. However, more data is needed for the wide acceptance and feasibility of these approaches. Studies to explore the role of asymptomatic and sub-patent infections in the transmission of malaria are of critical importance and are recommended.
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Malaria Journal, 16.02.2022
Tilføjet 17.02.2022
Abstract
Background
Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation.
Methods
In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication.
Results
These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal.
Conclusions
Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
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Malaria Journal, 16.02.2022
Tilføjet 17.02.2022
Abstract
Background
Whole-genome sequencing (WGS) is becoming increasingly helpful to assist malaria control programmes. A major drawback of this approach is the large amount of human DNA compared to parasite DNA extracted from unprocessed whole blood. As red blood cells (RBCs) have a diameter of about 7–8 µm and exhibit some deformability, it was hypothesized that cheap and commercially available 5 µm filters might retain leukocytes but much less of Plasmodium falciparum-infected RBCs. This study aimed to test the hypothesis that such a filtration method, named 5WBF (for 5 µm Whole Blood Filtration), may provide highly enriched parasite material suitable for P. falciparum WGS.
Methods
Whole blood was collected from five patients experiencing a P. falciparum malaria episode (ring-stage parasitaemia range: 0.04–5.5%) and from mock samples obtained by mixing synchronized, ring-stage cultured P. falciparum 3D7 parasites with uninfected human whole blood (final parasitaemia range: 0.02–1.1%). These whole blood samples (50 to 400 µL) were diluted in RPMI 1640 medium or PBS 1× buffer and filtered with a syringe connected to a 5 µm commercial filter. DNA was extracted from 5WBF-treated and unfiltered counterpart blood samples using a commercial kit. The 5WBF method was evaluated on the ratios of parasite:human DNA assessed by qPCR and by sequencing depth and percentages of coverage from WGS data (Illumina NextSeq 500). As a comparison, the popular selective whole-genome amplification (sWGA) method, which does not rely on blood filtration, was applied to the unfiltered counterpart blood samples.
Results
After applying 5WBF, qPCR indicated an average of twofold loss in the amount of parasite template DNA (Pf ARN18S gene) and from 4096- to 65,536-fold loss of human template DNA (human β actin gene). WGS analyses revealed that > 95% of the parasite nuclear and organellar genomes were all covered at ≥ 10× depth for all samples tested. In sWGA counterparts, the organellar genomes were poorly covered and from 47.7 to 82.1% of the nuclear genome was covered at ≥ 10× depth depending on parasitaemia. Sequence reads were homogeneously distributed across gene sequences for 5WBF-treated samples (n = 5460 genes; mean coverage: 91×; median coverage: 93×; 5th percentile: 70×; 95th percentile: 103×), allowing the identification of gene copy number variations such as for gch1. This later analysis was not possible for sWGA-treated samples, as a much more heterogeneous distribution of reads across gene sequences was observed (mean coverage: 80×; median coverage: 51×; 5th percentile: 7×; 95th percentile: 245×).
Conclusions
The novel 5WBF leucodepletion method is simple to implement and based on commercially available, standardized 5 µm filters which cost from 1.0 to 1.7€ per unit depending on suppliers. 5WBF permits extensive genome-wide analysis of P. falciparum ring-stage isolates from minute amounts of whole blood even with parasitaemias as low as 0.02%.
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Kristjan E. Hjorleifsson, Solvi Rognvaldsson, Hakon Jonsson, Arna B. Agustsdottir, Margret Andresdottir, Kolbrun Birgisdottir, Ogmundur Eiriksson, Elias S. Eythorsson, Run Fridriksdottir, Gudmundur Georgsson, Kjartan R. Gudmundsson, Arnaldur Gylfason, Gudbjorg Haraldsdottir, Brynjar O. Jensson, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Kamilla S. Josefsdottir, Nina Kristinsdottir, Borghildur Kristjansdottir, Thordur Kristjansson, Droplaug N. Magnusdottir, Runolfur Palsson, Louise le Roux, Gudrun M. Sigurbergsdottir, Asgeir Sigurdsson, Martin I. Sigurdsson, Gardar Sveinbjornsson, Emil Aron Thorarensen, Bjarni Thorbjornsson, Marianna Thordardottir, Agnar Helgason, Hilma Holm, Ingileif Jonsdottir, Frosti Jonsson, Olafur T. Magnusson, Gisli Masson, Gudmundur L. Norddahl, Jona Saemundsdottir, Patrick Sulem, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Pall Melsted, Kari Stefansson
Clinical Microbiology and Infection, 16.02.2022
Tilføjet 17.02.2022
The spread of SARS-CoV-2 is dependent on several factors, both biological and behavioral. The effectiveness of non-pharmaceutical interventions can largely be attributed to changes in human behavior, but quantifying this effect remains challenging. Reconstructing the transmission tree of the third wave of SARS-CoV-2 infections in Iceland using contact tracing and viral sequence data from 2522 cases enables us to directly compare the infectiousness of distinct groups of persons.
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