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V. Eric Kerchberger
American Journal of Respiratory and Critical Care Medicine , 16.02.2024
Tilføjet 16.02.2024
American Journal of Respiratory and Critical Care Medicine, Volume 209, Issue 4, Page 351-352, February 15, 2024.
Læs mere Tjek på PubMedErik H. A. Michels, Brent Appelman, Justin de Brabander, Rombout B. E. van Amstel, Christine C. A. van Linge, Osoul Chouchane, Tom D. Y. Reijnders, Alex R. Schuurman, Titia A. L. Sulzer, Augustijn M. Klarenbeek, Renée A. Douma, Lieuwe D. J. Bos, W. Joost Wiersinga, Hessel Peters-Sengers, Tom van der Poll
American Journal of Respiratory and Critical Care Medicine , 16.02.2024
Tilføjet 16.02.2024
American Journal of Respiratory and Critical Care Medicine, Volume 209, Issue 4, Page 402-416, February 15, 2024.
Læs mere Tjek på PubMedBMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
BMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
Abstract Background Leishmania infantum is the major causative agent of visceral leishmaniasis in Mediterranean regions. Isoenzyme electrophoresis (IE), as a biochemical technique, is applied in the characterization of Leishmania species. The current study attempted to investigate the isoenzyme patterns of logarithmic and stationary promastigotes and axenic amastigotes (amastigote-like) of L. infantum using IE. The antioxidant activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) was also checked in the aforementioned forms. Method After L. infantum cultivation and obtaining logarithmic and stationary promastigotes, axenic amastigotes were achieved by incubation of stationary promastigotes at 37 °C for 48 h. The lysate samples were prepared and examined for six enzymatic systems including glucose-6-phosphate dehydrogenase (G6PD), nucleoside hydrolase 1 (NH1), malate dehydrogenase (MDH), glucose-phosphate isomerase (GPI), malic enzyme (ME), and phosphoglucomutase (PGM). Additionally, the antioxidant activity of SOD and GPX was measured. Results GPI, MDH, NH1, and G6PD enzymatic systems represented different patterns in logarithmic and stationary promastigotes and axenic amastigotes of L. infantum. PGM and ME showed similar patterns in the aforementioned forms of parasite. The highest level of SOD activity was determined in the axenic amastigote form and GPX activity was not detected in different forms of L. infantum. Conclusion The characterization of leishmanial-isoenzyme patterns and the measurement of antioxidant activity of crucial antioxidant enzymes, including SOD and GPX, might reveal more information in the biology, pathogenicity, and metabolic pathways of Leishmania parasites and consequently drive to designing novel therapeutic strategies in leishmaniasis treatment.
Læs mere Tjek på PubMedBMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
Abstract Background In Japan, carbapenem-resistant Enterobacterales (CRE) infections were incorporated into the National Epidemiological Surveillance of Infectious Diseases (NESID) in 2014, necessitating mandatory reporting of all CRE infections cases. Subsequently, pathogen surveillance was initiated in 2017, which involved the collection and analysis of CRE isolates from reported cases to assess carbapenemase gene possession. In this surveillance, CRE is defined as (i) minimum inhibitory concentration (MIC) of meropenem ≥2 mg/L (MEPM criteria) or (ii) MIC of imipenem ≥2 mg/L and MIC of cefmetazole ≥64 mg/L (IPM criteria). This study examined whether the current definition of CRE surveillance captures cases with a clinical and public health burden. Methods CRE isolates from reported cases were collected from the public health laboratories of local governments, which are responsible for pathogen surveillance. Antimicrobial susceptibility tests were conducted on these isolates to assess compliance with the NESID CRE definition. The NESID data between April 2017 and March 2018 were obtained and analyzed using antimicrobial susceptibility test results. Results In total, 1681 CRE cases were identified during the study period, and pathogen surveillance data were available for 740 (44.0%) cases. Klebsiella aerogenes and Enterobacter cloacae complex were the dominant species, followed by Klebsiella pneumoniae and Escherichia coli. The rate of carbapenemase gene positivity was 26.5% (196/740), and 93.4% (183/196) of these isolates were of the IMP type. Meanwhile, 315 isolates were subjected to antimicrobial susceptibility testing. Among them, 169 (53.7%) fulfilled only the IPM criteria (IPM criteria-only group) which were susceptible to meropenem, while 146 (46.3%) fulfilled the MEPM criteria (MEPM criteria group). The IPM criteria-only group and MEPM criteria group significantly differed in terms of carbapenemase gene positivity (0% vs. 67.8%), multidrug resistance rates (1.2% vs. 65.8%), and mortality rates (1.8% vs 6.9%). Conclusion The identification of CRE cases based solely on imipenem resistance has had a limited impact on clinical management. Emphasizing resistance to meropenem is crucial in defining CRE, which pose both clinical and public health burden. This emphasis will enable the efficient allocation of limited health and public health resources and preservation of newly developed antimicrobials.
Læs mere Tjek på PubMedBMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
Abstract Background The magnitude of MDR-TB cases was noticeable in Egypt. However, the last national survey was 11-years ago. The current survey was conducted to determine the prevalence of rifampicin resistance among sputum smear-positive pulmonary tuberculosis patients in Egypt. Methods A national health facility-based cross-sectional study was conducted in 14 randomly selected governorates in Egypt between August 2020 and September 2021. All presumptive TB cases, either new or previously treated according to WHO definitions, with no gender, age, or nationality limitations, and provided informed consent were included in the study. Each patient completed a case report form (CRF). The CRF included socio-demographic and clinical data. Sputum samples were collected according to standard techniques and cultured on Lowenstein-Jensen (L-J) medium. Gene X-pert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. The prevalence of RR was calculated using crude, cluster, and weighted methods. Factors associated with RR were analyzed by bivariate and multivariate techniques. Results Among the total 849 presumptive TB patients enrolled in the study, 710 (83.6%) patients were subjected to Gene X-pert testing (MTB/RIF). The crude prevalence of RR was 3.32% (95% CI: 1.89–4.76%) among the new cases and 9.46% (95% CI: 2.63–16.29%) among the retreated cases with an overall estimate of 3.99%; (95% CI: 2.51–5.47%). By cluster analysis the overall prevalence of RR was 5.01% (95% CI: 2.90–7.13). Factors associated with the prevalence of RR were co-morbidity with bronchial asthma, drug abuse and history of contact with a family member with TB. Conclusion The prevalence of RR among either new or retreated cases TB patients was lower than the previous Egyptian rates in 2010–2012. The strongest predictor associated with RR was comorbidity with bronchial asthma.
Læs mere Tjek på PubMedBMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
Abstract Hand foot and mouth disease (HFMD) is caused by a variety of enteroviruses, and occurs in large outbreaks in which a small proportion of children deteriorate rapidly with cardiopulmonary failure. Determining which children are likely to deteriorate is difficult and health systems may become overloaded during outbreaks as many children require hospitalization for monitoring. Heart rate variability (HRV) may help distinguish those with more severe diseases but requires simple scalable methods to collect ECG data. We carried out a prospective observational study to examine the feasibility of using wearable devices to measure HRV in 142 children admitted with HFMD at a children’s hospital in Vietnam. ECG data were collected in all children. HRV indices calculated were lower in those with enterovirus A71 associated HFMD compared to those with other viral pathogens. HRV analysis collected from wearable devices is feasible in a low and middle income country (LMIC) and may help classify disease severity in HFMD.
Læs mere Tjek på PubMedBMC Infectious Diseases, 16.02.2024
Tilføjet 16.02.2024
Abstract Background Fear of a global public health issue and fresh infection wave in the persistent COVID-19 pandemic has been enflamed by the appearance of the novel variant Omicron BF.7 lineage. Recently, it has been seeing the novel Omicron subtype BF.7 lineage has sprawled exponentially in Hohhot. More than anything, risk stratification is significant to ascertain patients infected with COVID-19 who the most need in-hospital or in-home management. The study intends to understand the clinical severity and epidemiological characteristics of COVID-19 Omicron subvariant BF.7. lineage via gathering and analyzing the cases with Omicron subvariant in Hohhot, Inner Mongolia. Methods Based upon this, we linked variant Omicron BF.7 individual-level information including sex, age, symptom, underlying conditions and vaccination record. Further, we divided the cases into various groups and assessed the severity of patients according to the symptoms of patients with COVID-19. Clinical indicators and data might help to predict disadvantage outcomes and progression among Omicron BF.7 patients. Results In this study, in patients with severe symptoms, some indicators from real world data such as white blood cells, AST, ALT and CRE in patients with Omicron BF.7 in severe symptoms were significantly higher than mild and asymptomatic patients, while some indicators were significantly lower. Conclusions Above results suggested that the indicators were associated with ponderance of clinical symptoms. Our survey emphasized the value of timely investigations of clinical data obtained by systemic study to acquire detailed information.
Læs mere Tjek på PubMedFang WangHongmin SunChenbo KangJun YanJingnan ChenXuequan FengBin Yanga TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, Chinab Intensive Care Unit, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen, Chinac Tianjin First Central Hospital, Nankai University, Tianjin, China
Virulence, 15.02.2024
Tilføjet 15.02.2024
David A. PotterZhijun GuoJianxun LeiEmmanuel S. AntonarakisaDepartment of Medicine, Division of Hematology, Oncology, and Transplantation and Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455bMasonic Cancer Center, Minneapolis, MN 55455
Proceedings of the National Academy of Sciences: Immunology and Inflammation, 15.02.2024
Tilføjet 15.02.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 9, February 2024.
Læs mere Tjek på PubMedRasmus IversenLudvig M. SollidaNorwegian Centre for Coeliac Disease Research, Institute of Clinical Medicine, University of Oslo, Oslo 0372, NorwaybDepartment of Immunology, Oslo University Hospital, Oslo 0372, Norway
Proceedings of the National Academy of Sciences: Immunology and Inflammation, 15.02.2024
Tilføjet 15.02.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 9, February 2024.
Læs mere Tjek på PubMedPankaj Sharma, Xiaolong Zhang, Kevin Ly, Yuxiang Zhang, Yu Hu, Adam Yongxin Ye, Jianqiao Hu, Ji Hyung Kim, Mumeng Lou, Chong Wang, Quinton Celuzza, Yuji Kondo, Keiko Furukawa, David R. Bundle, Koichi Furukawa, Frederick W. Alt, Florian Winau
Science, 15.02.2024
Tilføjet 15.02.2024
Kelvin J. Y. Wu, Ben I. C. Tresco, Antonio Ramkissoon, Elena V. Aleksandrova, Egor A. Syroegin, Dominic N. Y. See, Priscilla Liow, Georgia A. Dittemore, Meiyi Yu, Giambattista Testolin, Matthew J. Mitcheltree, Richard Y. Liu, Maxim S. Svetlov, Yury S. Polikanov, Andrew G. Myers
Science, 15.02.2024
Tilføjet 15.02.2024
Janet D. Siliciano, and Robert F. Siliciano
Science, 15.02.2024
Tilføjet 15.02.2024
Clinical Infectious Diseases, 15.02.2024
Tilføjet 15.02.2024
Abstract Background Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses (ARI) in children. RSV can be broadly categorized into two major subtypes (A and B). RSV subtypes have been known to co-circulate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established.Methods During 2016–2020, children
Læs mere Tjek på PubMedFlorian M. Wagenlehner, Leanne B. Gasink, Paul C. McGovern, Greg Moeck, Patrick McLeroth, MaryBeth Dorr, Aaron Dane, Tim Henkel
New England Journal of Medicine, 15.02.2024
Tilføjet 15.02.2024
New England Journal of Medicine, Volume 390, Issue 7, Page 611-622, February 2024.
Læs mere Tjek på PubMedEric A. Meyerowitz, Shambo Guha Roy, Anne M. Neilan, Douglas S. Ross, Grace K. Mahowald
New England Journal of Medicine, 15.02.2024
Tilføjet 15.02.2024
New England Journal of Medicine, Volume 390, Issue 7, Page 653-660, February 2024.
Læs mere Tjek på PubMedJana K. Dickter, Ahmed Aribi, Angelo A. Cardoso, Sara Gianella, Ketevan Gendzekhadze, Shirley Li, Ye Feng, Antoine Chaillon, Gregory M. Laird, Diana L. Browning, Justine A. Ross, Deepa D. Nanayakkara, Alfredo Puing, Rodica Stan, Lily L. Lai, Sue Chang, Trilokesh D. Kadambi, Sandra Thomas, Monzr M. Al Malki, Ryo Nakamura, Joseph Alvarnas, Randy A. Taplitz, Sanjeet S. Dadwal, Stephen J. Forman, John A. Zaia
New England Journal of Medicine, 15.02.2024
Tilføjet 15.02.2024
New England Journal of Medicine, Volume 390, Issue 7, Page 669-671, February 2024.
Læs mere Tjek på PubMedNew England Journal of Medicine, 15.02.2024
Tilføjet 15.02.2024
New England Journal of Medicine, Volume 390, Issue 7, Page 671-673, February 2024.
Læs mere Tjek på PubMedMona Sadat Larijani, Amir Javadi, Seyed Ebrahim Eskandari, Delaram Doroud, Fatemeh Ashrafian, Mohammad Banifazl, Ali Khamesipour, Anahita Bavand, Amitis Ramezani
Journal of Medical Virology, 15.02.2024
Tilføjet 15.02.2024
Layla Honorato, Noely Evangelista Ferreira, Renan Barros Domingues, Carlos Senne, Fernando Brunale Vilela de Moura Leite, Márcio Vega dos Santos, Gustavo Bruniera Peres Fernandes, Heuder Gustavo Oliveira Paião, Lucy Santos Vilas Boas, Antonio Charlys da Costa, Tânia Regina Tozetto‐Mendoza, Steven S. Witkin, Maria Cássia Mendes‐Correa
Journal of Medical Virology, 15.02.2024
Tilføjet 15.02.2024
Richterman, Aaron; Sinha, Pranay; Ivers, Louise C; Gross, Robert; Rantleru, Tumelo; Tamuhla, Neo; Bisson, Gregory P.
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Background Food insecurity and undernutrition are related but distinct concepts contributing to poor HIV and tuberculosis outcomes. Pathways linking them with immunologic profile, which may relate to clinical outcomes, remain understudied. Methods We analyzed data from a cohort study of 165 ART-naïve adults with advanced HIV and newly diagnosed tuberculosis in Botswana from 2009-2013. 29 plasma biomarkers were measured pre-ART and four weeks post-ART initiation. We used principal components analysis (PCA) and multivariable linear regression models to assess relationships between immunological profiles and food insecurity (based on the Household Food Insecurity Access Scale), undernutrition (Body Mass Index < 18.5 kg/m2), and clinical outcomes. Results PCA identified 5 principal components (PCs) with eigenvalues >1. After adjustment, food insecurity was associated with PC3 pre-ART (0.19 per increased category of severity, 95% CI 0.02 to 0.36) and post-ART (0.24, 95% CI 0.07 to 0.41). PC3 was driven by higher levels of IFN-α, IFN-γ, IL-12p40, VEGF, IL-1α, and IL-8, and decreased concentrations of IL-3. Undernutrition was associated with PC5 post-ART (0.49, 95% CI 0.16 to 0.82). PC5 was driven by higher levels of IL-8, MIP-1α, IL-6, and IL-10, and decreased concentrations in IP-10 and IFN-α. Post-ART PC3 (4.3 percentage point increased risk per increased score of 1, 95% CI 0.3 to 8.9) and post-ART PC5 (4.8, 95% CI 0.6 to 8.9) were associated with death in adjusted models. Discussion We identified two distinct immunologic profiles associated with food insecurity, undernutrition, and clinical outcomes in patients with advanced HIV and TB. Different pathophysiologic processes may link food insecurity and undernutrition with poor outcomes in this vulnerable patient population. Future studies should assess the impact of improving food access and intake on immune function and clinical outcomes. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedWeld, Ethel D.; Ogasawara, Ken; Fuchs, Edward J.; Louissaint, Nicolette; Caffo, Brian; Hendrix, Craig W.
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Background. Anal sex remains the greatest HIV transmission risk for men who have sex with men and carries substantial population attributable risk among women. Despite a growing array of HIV pre-exposure prophylaxis (PrEP) options, rectal microbicides remain desirable as on demand, non-systemic PrEP. Rectal microbicide product development for PrEP requires understanding the spatiotemporal distribution of HIV infectious elements in the rectosigmoid to optimize formulation development. Setting. Outpatient setting with healthy research participants. Methods. Six healthy men underwent simulated receptive anal sex with an artificial phallus fitted with a triple lumen catheter in the urethral position. To simulate ejaculation of HIV-infected semen, autologous seminal plasma laden with autologous blood lymphocytes from apheresis labeled with 111Indium-oxine (cell-associated) and 99mTechnetium-sulfur colloid (cell-free) as HIV surrogates were injected into the rectal lumen through the phallic urethra. Spatiotemporal distribution of each radioisotope was assessed using SPECT/CT over eight hours. Analysis of radiolabel distribution used a flexible principal curve algorithm to quantitatively estimate rectal lumen distribution. Results. Cell-free and cell-associated HIV surrogates distributed to a maximal distance of 15 and 16 cm, respectively, from the anorectal junction (∼19 and ∼20 cm from the anal verge), with a maximal signal intensity located 6 and 7 cm, respectively. There were no significant differences in any distribution parameters between cell-free and cell-associated HIV surrogate. Conclusions. Cell-free and cell-associated HIV surrogate distribution in the rectosigmoid can be quantified with spatiotemporal pharmacokinetic methods. These results describe the ideal luminal target distribution to guide rectal microbicide development. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedWandika, Brenda; Nyapara, Florence; Aballa, Calvince; Richardson, Barbra A.; Wamalwa, Dalton; John-Stewart, Grace; Inwani, Irene; Njuguna, Irene
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Introduction Adolescents living with HIV (ALH) have poorer adherence to antiretroviral therapy (ART) than adults. Many ALH in sub-Saharan Africa (SSA) are enrolled in boarding schools where stigma is pervasive and may impact adherence. Methods We collected sociodemographic data, school information, medical history, and viral load (VL) data from ALH age 14-19 in 25 HIV clinics in 3 counties in Kenya. Using generalized estimating equations, we compared ART adherence in ALH attending day and boarding schools. Results Of 880 ALH, 798 (91%) were enrolled in school, of whom 189 (24%) were in boarding schools. Of those in school, median age was 16 (IQR: 15, 18), 55% were female, 78% had a parent as a primary caregiver, and 74% were on DTG-based ART. Median age at ART initiation was 6 years (IQR 3, 10). Overall, 227 (29%) ALH self-reported missing ART when school was in session (40% in boarding and 25% in day school). After adjusting for sociodemographic and HIV care characteristics, ALH in boarding schools were significantly more likely to self-report missing ART than those in day schools (adjusted Prevalence Ratio (aPR): 1.47, 95% CI 1.18, 1.83, p=0.001). Among 194 ALH, only 60% had undetectable (
Læs mere Tjek på PubMedDe Wit, Stéphane; Bonnet, Fabrice; Osiyemi, Olayemi; Bisshop, Fiona; Olalla, Julian; Routy, Jean-Pierre; Wyen, Christoph; Moodley, Riya; Pappa, Keith; Wang, Ruolan; Oyee, James; Saggu, Parminder; Letang, Emilio; Wynne, Brian; Jones, Bryn; Smith, Kimberly Y.; Ait-Khaled, Mounir
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Background: Switching to the 2-drug regimen dolutegravir/lamivudine demonstrated durable non-inferior efficacy vs continuing 3- or 4-drug tenofovir alafenamide–based regimens for maintaining virologic suppression in people with HIV-1 through Week 144 in TANGO. Setting: 134 centers, 10 countries. Methods: Adults with HIV-1 RNA 6 months and no history of virologic failure were randomized to switch from stable tenofovir alafenamide–based regimens to dolutegravir/lamivudine on Day 1 (early-switch group) for 196 weeks. Those randomized to continue tenofovir alafenamide–based regimens on Day 1 who maintained virologic suppression at Week 144 switched to dolutegravir/lamivudine at Week 148 (late-switch group). Efficacy, safety, and tolerability (including weight and biomarker changes) of dolutegravir/lamivudine in early-switch and late-switch groups were assessed through Week 196. Results: Overall, 369 participants switched to dolutegravir/lamivudine on Day 1 (early-switch) and 298 switched at Week 148 (late-switch). In the early-switch group, 83% (306/369) maintained virologic suppression through Year 4, and 3% (11/369) reported new adverse events between Weeks 144 and 196. The late-switch group at Week 196 and early-switch group at Week 48 had comparable proportions with virologic suppression (93% each) and similar safety profiles. No late-switch participants and 1 early-switch participant met confirmed virologic withdrawal criteria through Week 196, with no resistance-associated mutations observed. Treatment continued to be well tolerated long-term. Conclusion: Switching from tenofovir alafenamide–based regimens to dolutegravir/lamivudine showed durable efficacy, high barrier to resistance, and good tolerability through 4 years. These results support dolutegravir/lamivudine as a robust treatment for maintaining virologic suppression. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Læs mere Tjek på PubMedMehtani, Nicky J.; Strough, Alix; Strieff, Sarah; Zevin, Barry; Eveland, Joanna; Riley, Elise D.; Gandhi, Monica
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Background: Long-acting (LA) antiretrovirals may provide meaningful benefit to people who use drugs and people experiencing homelessness (PEH) who face disproportionate structural and psychosocial barriers in adhering to daily oral HIV antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP), but their use in these populations has not been studied. Setting: The Maria X. Martinez Health Resource Center is a low-barrier (e.g., no appointment) community-based clinic serving San Francisco PEH. Methods: A multidisciplinary care model with robust monitoring and outreach support was developed to provide LA-ART and LA-PrEP to eligible patients experiencing difficulties adhering to oral antiretrovirals. Feasibility was assessed by evaluating rates of HIV viremia and on-time injections among patients receiving LA antiretrovirals over the first 24 months of program implementation. Results: Between November 2021 and November 2023, 33 patients initiated LA-ART or LA-PrEP (median age, 37 years; 27% transgender/non-binary; 73% non-White; 27% street homeless; 52% sheltered homeless; 30% with opioid use disorder; 82% with methamphetamine use disorder). Among 18 patients with HIV, 14 initiated LA-ART injections with detectable viremia (median CD4 count, 340 cells/mm3; mean log10 viral load, 3.53; standard deviation [SD], 1.62), eight had never previously been virally suppressed, and all but one achieved or maintained virologic suppression (mean, 9.67 months; SD, 8.30). Among 15 LA-PrEP patients, all remained HIV-negative (mean, 4.73 months; SD, 2.89). Of 224 injections administered total, 8% were delayed >7 days. Discussion: The implementation of LA antiretrovirals is feasible in low-barrier, highly supportive clinical settings serving vulnerable PEH. Expansion of such programs will be critical to Ending the HIV Epidemic. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedÖzkaya, Hacer Deniz; Elazab, Khaled; Turan, Bülent; Nazlı, Arzu; Öztürk, Barçın; Pullukçu, Hüsnü; Gökengin, Deniz
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Background: Late diagnosis of HIV infection is a major global problem. In Turkiye, only 41% - 50% of people living with HIV (PLWH) are diagnosed, suggesting that many opportunities for HIV testing might be missed. Setting: The aim of this study is to determine the missed testing opportunities for HIV in healthcare settings in Turkiye and the predictors for missed opportunities (MOs). Methods: The study included patients with a new HIV diagnosis, presenting to care between January 2018 and December 2020. They were given a verbal questionnaire face to face, by a telephone call or an online meeting for visits to a healthcare setting within the year prior to their diagnosis. Electronic medical records were also examined. Results: The sample included 198 patients with at least one visit to any healthcare setting, with a total of 1677 visits. Patients had an indication for HIV testing in 51.3% (861/1677) of the visits; an HIV test was not offered in 77.9% (671/861) and was considered a MO. The highest number of MOs was in emergency departments (EDs) (59.8%) (180/301).The most common reason for visiting was constitutional symptoms and indicator conditions (ICs) (55.4%) (929/1677). University graduates and those with a CD4+T cell count
Læs mere Tjek på PubMedSkye OPSTEEN; Tim FRAM; Jacob K. FILES; Emily B. LEVITAN; Paul GOEPFERT; Nathaniel ERDMANN
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
There is mounting evidence that HIV infection is a risk factor for severe presentations of COVID-19. We hypothesized that the persistent immune activation associated with chronic HIV infection contributes to worsened outcomes during acute COVID-19. The goals of this study were to provide an in-depth analysis of immune response to acute COVID-19 and investigate relationships between immune responses and clinical outcomes in an unvaccinated, sex and race-matched cohort of people with HIV (PWH, n=20) and people without HIV (PWOH, n=41). There is mounting evidence that HIV infection is a risk factor for severe presentations of COVID-19. We hypothesized that the persistent immune activation associated with chronic HIV infection contributes to worsened outcomes during acute COVID-19. The goals of this study were to provide an in-depth analysis of immune response to acute COVID-19 and investigate relationships between immune responses and clinical outcomes in an unvaccinated, sex and race-matched cohort of people with HIV (PWH, n=20) and people without HIV (PWOH, n=41). We performed flow cytometric analyses on peripheral blood mononuclear cells from PWH and PWOH experiencing acute COVID-19 (≤ 21 days post-symptom onset). PWH were younger (median 52 vs 65 years) and had milder COVID-19 (40% vs 88% hospitalized) compared to PWOH. Flow cytometry panels included surface markers for immune cell populations, activation and exhaustion surface markers (with and without SARS-CoV-2-specific antigen stimulation), and intracellular cytokine staining. We observed that PWH had increased expression of activation (e.g., CD137, OX40) and exhaustion (e.g., PD1, TIGIT) markers as compared to PWOH during acute COVID-19. When analyzing the impact of COVID-19 severity, we found that hospitalized PWH had lower non-classical (CD16+) monocyte frequencies, decreased expression of TIM3 on CD4+ T cells, and increased expression of PDL1 and CD69 on CD8+ T cells. Our findings demonstrate that PWH have increased immune activation and exhaustion as compared to a cohort of predominately older, hospitalized PWOH and raises questions on how chronic immune activation impacts acute disease and the development of post-acute sequelae. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRambiki, Ethel; Heller, Tom; Wallrauch, Claudia; Painschab, Matthew; Huwa, Jacquiline; Khalani, Jennipher; Rambiki, Kelvin
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Machavariani, Eteri; Miceli, Janet; Altice, Frederick L.; Fanfair, Robyn Neblett; Speers, Suzanne; Nichols, Lisa; Jenkins, Heidi; Villanueva, Merceditas
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Background: Re-engaging people with HIV (PWH) who are newly out-of-care remains challenging. Data-to-care (D2C) is a potential strategy to re-engage such individuals. Methods: A prospective randomized controlled trial compared a D2C strategy using a disease intervention specialist (DIS) vs standard-of-care (SOC) where 23 HIV clinics in 3 counties in Connecticut could re-engage clients using existing methods. Using a data reconciliation process to confirm being newly out-of-care, 655 participants were randomized to DIS (N=333) or SOC (N=322). HIV care continuum outcomes included re-engagement at 90 days, retention in care and viral suppression (VS) by 12 months. Multivariable regression models were used to assess factors predictive of attaining HIV care continuum outcomes. Results: Participants randomized to DIS were more likely to be re-engaged at 90 days (aOR=1.42, p=0.045). Independent predictors of re-engagement at 90 days were: age>40 years (aOR=1.84, p=0.012) and peri-natal HIV risk category (aOR=3.19, p=0.030). Predictors of retention at 12 months included: re-engagement at 90 days (aOR=10.31, p
Læs mere Tjek på PubMedReis, Karl; Wolf, Allison; Perumal, Rubeshan; Seepamore, Boitumelo; Guzman, Kevin; Ross, Jesse; Cheung, Ken; Amico, K. Rivet; Brust, James C.M.; Padayatchi, Nesri; Friedland, Gerald; Naidoo, Kogieleum; Daftary, Amrita; Zelnick, Jennifer; O’Donnell, Max
Journal of Acquired Immune Deficiency Syndromes, 15.02.2024
Tilføjet 15.02.2024
Introduction For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework. Methods Adults with MDR-TB and HIV initiating bedaquiline (BDQ) and receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa, were enrolled and followed through the end of MDR-TB treatment. Electronic dose monitoring devices (EDM) measured BDQ and ART adherence. Longitudinal focus groups were conducted and transcripts analyzed thematically to describe discrete treatment stage-specific and cross-cutting treatment challenges. Results 283 participants were enrolled and followed through treatment completion (median 17.8 months [IQR 16.5–20.2]). Thirteen focus groups were conducted. Most participants (82.7%, 234/283) maintained high adherence (mean BDQ adherence 95.3%; mean ART adherence 85.5%), but an adherence-challenged subpopulation with
Læs mere Tjek på PubMedJulia C. Berentschot, L. Martine Bek, Majanka H. Heijenbrok-Kal, Rita J.G. van den Berg-Emons, Gerard M. Ribbers, Joachim G.J.V. Aerts, Merel E. Hellemons
International Journal of Infectious Diseases, 15.02.2024
Tilføjet 15.02.2024
COVID-19, caused by SARS-CoV-2, has resulted in a worldwide pandemic, requiring hospitalization for respiratory insufficiency in numerous patients. Many of these patients suffer lingering and debilitating health problems that can persist for months or years,[1] commonly referred to as ‘long COVID’ or ‘post-COVID syndrome’. Long COVID comprises a wide range of symptoms, with dyspnea, fatigue, and neurocognitive symptoms among the most frequently reported, may negatively affect health-related quality of life, and more commonly affects patients after severe COVID-19.[1,2]
Læs mere Tjek på PubMedSatoshi Kutsuna, Hiroyuki Ohbe, Hiroki Matsui, Hideo Yasunaga
International Journal of Infectious Diseases, 15.02.2024
Tilføjet 15.02.2024
Legionnaires’ Disease is a type of pneumonia caused by Legionella spp. such as L. pneumophila, L. longbeachae and L. anisa., and accounts for 1–10% of community-acquired pneumonia cases 1. It is a severe form of pneumonia with a reported fatality rate of 6.4%4. Multiple reports have shown that a delay in the administration of appropriate antimicrobials is associated with worse prognosis in Legionnaires’ Disease 2.
Læs mere Tjek på PubMedMishra, Shivangi; Gala, Jinay; Chacko, Jose
Critical Care Medicine, 15.02.2024
Tilføjet 15.02.2024
Objectives: Critically ill patients with tuberculosis carry high mortality. Identification of factors associated with mortality in critically ill tuberculosis patients may enable focused treatment. Data Sources: An extensive literature search of PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar was performed using Medical Subject Headings terms “tuberculosis,” “critical care,” “critical care outcome,” and “ICU.” We aimed to identify factors affecting mortality in critically ill tuberculosis patients. Study Selection: All the studies comparing factors affecting mortality between survivors and nonsurvivors in critically ill tuberculosis patients were included. The database search yielded a total of 3017 records, of which 17 studies were included in the meta-analysis. Data Extraction: Data were collected including the name of the author, year and country of publication, duration of the study, number of patients studied, type of tuberculosis, patient demography, smoking history, laboratory parameters, comorbidities, the requirement for mechanical ventilation, duration of ventilation, ICU and hospital length of stay (LOS), type of lung involvement, complications, and outcomes. Data Synthesis: The major factors that contributed to mortality in critically ill tuberculosis patients were age, platelet count, albumin, C-reactive protein (CRP), the requirement and duration of invasive mechanical ventilation, Pao2/Fio2 ratio, presence of acute respiratory distress syndrome, shock, hospital-acquired infections, renal replacement therapy, and ICU and hospital LOS. Conclusions: Patient age, platelet count, albumin and CRP levels, the requirement and duration of invasive mechanical ventilation, Pao2/Fio2 ratio, hospital-acquired infections, renal replacement therapy, and ICU LOS were variables associated with mortality.
Læs mere Tjek på PubMedArai, Riku; Murata, Nobuhiro; Fukamachi, Daisuke; Okumura, Yasuo; Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) Investigators
Critical Care Medicine, 15.02.2024
Tilføjet 15.02.2024
Objectives: This study aimed to investigate the current use and impact of pulmonary artery catheters (PACs) in patients with cardiogenic shock (CS) who underwent Impella support. Design: This was a prospective multicenter observational study between January 2020 and December 2021 that registered all patients with drug-refractory acute heart failure and in whom the placement of an Impella 2.5, CP, or 5.0 pump was attempted or successful in Japan. Setting: Cardiac ICUs in Japan. Patients: Between January 2020 and December 2021, a total of 3112 patients treated with an Impella were prospectively enrolled in the Japan registry for percutaneous ventricular assist device (J-PVAD). Among them, 2063 patients with CS were divided into two groups according to the PAC use. Interventions: None. Measurements and Main Results: The primary endpoint was the 30-day mortality, and the secondary endpoints were hemolysis, acute kidney injury, sepsis, major bleeding unrelated to the Impella, and ventricular arrhythmias within 30 days. PACs were used in 1358 patients (65.8%) who underwent an Impella implantation. The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) was significantly higher in the patients with PACs than in those without. Factors associated with PAC use were the prevalence of hypertension, out-of-hospital cardiac arrest, New York Heart Association classification IV, the lesser prevalence of a heart rate less than 50, and the use of any catecholamine. The primary and secondary endpoints did not significantly differ according to the PAC use. Focusing on the patients with VA-ECMO use, the 30-day mortality and hemolysis were univariately lower in the patients with PACs. Conclusions: The J-PVAD findings indicated that PAC use did not have a significant impact on the short-term outcomes in CS patients undergoing Impella support. Further prospective studies are required to explore the clinical implications of PAC-guided intensive treatment strategies in these patients.
Læs mere Tjek på PubMedBolanaki, Myrto; Winning, Johannes; Slagman, Anna; Lehmann, Thomas; Kiehntopf, Michael; Stacke, Angelika; Neumann, Caroline; Reinhart, Konrad; Möckel, Martin; Bauer, Michael
Critical Care Medicine, 15.02.2024
Tilføjet 15.02.2024
Objectives: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. Design: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. Setting: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). Patients: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. Interventions: None. Measurements and Main Results: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79–0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. Conclusions: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.
Læs mere Tjek på PubMedDmitry A. Filatov, Mark Kirkpatrick
Trends in Microbiology, 15.02.2024
Tilføjet 15.02.2024
Marine phytoplankton play crucial roles in the Earth’s ecological, chemical, and geological processes. They are responsible for about half of global primary production and drive the ocean biological carbon pump. Understanding how plankton species may adapt to the Earth’s rapidly changing environments is evidently an urgent priority. This problem requires evolutionary genetic approaches as evolution occurs at the level of allele frequency change within populations driven by genetic drift and natural selection (microevolution). Plankters such as the coccolithophore Gephyrocapsa huxleyi and the cyanobacterium Prochlorococcus ‘marinus’ are among Earth’s most abundant organisms. In this opinion paper we discuss how evolution in astronomically large populations of superabundant microbes (SAMs) may act fundamentally differently than it does in the populations of more modest size found in well-studied organisms. This offers exciting opportunities to study evolution in the conditions that have yet to be explored and also leads to unique challenges. Exploring these opportunities and challenges is the goal of this article.
Læs mere Tjek på PubMedDipak Kathayat, Brian C. VanderVen
Trends in Microbiology, 15.02.2024
Tilføjet 15.02.2024
Mycobacterium tuberculosis (Mtb) replicates within host macrophages by adapting to the stressful and nutritionally constrained environments in these cells. Exploiting these adaptations for drug discovery has revealed that perturbing cAMP signaling can restrict Mtb growth in macrophages. Specifically, compounds that agonize or stimulate the bacterial enzyme, Rv1625c/Cya, induce cAMP synthesis and this interferes with the ability of Mtb to metabolize cholesterol. In murine tuberculosis (TB) infection models, Rv1625c/Cya agonists contribute to reducing relapse and shortening combination treatments, highlighting the therapeutic potential for this class of compounds. More recently, cAMP signaling has been implicated in regulating fatty acid utilization by Mtb. Thus, a new model is beginning to emerge in which cAMP regulates the utilization of host lipids by Mtb during infection, and this could provide new targets for TB drug development. Here, we summarize the current understanding of cAMP signaling in Mtb with a focus on our understanding of how cAMP signaling impacts Mtb physiology during infection. We also discuss additional cAMP-related drug targets in Mtb and other bacterial pathogens that may have therapeutic potential.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 15.02.2024
Tilføjet 15.02.2024
Abstract Tuberculosis (TB) remains one of the deadliest infectious diseases in human history, prevailing even in the 21st century. The causative agents of TB are represented by a group of closely-related bacteria belonging to the Mycobacterium tuberculosis complex (MTBC), which can be subdivided into several lineages of human- and animal-adapted strains, thought to have shared a last common ancestor emerged by clonal expansion from a pool of recombinogenic Mycobacterium canettii-like tubercle bacilli. A better understanding of how MTBC populations evolved from less virulent mycobacteria may allow for discovering improved TB control strategies and future epidemiologic trends. In this review, we highlight new insights into the evolution of mycobacteria at the genus level, describing different milestones in the evolution of mycobacteria, with focus on the genomic events that have likely enabled the emergence and the dominance of the MTBC. We also review the recent literature describing the various MTBC lineages and highlight their particularities and differences with focus on host preferences and geographic distribution. Finally, we discuss on putative mechanisms driving the evolution of tubercle bacilli and mycobacteria in general, by taking the mycobacteria-specific distributive conjugal transfer as an example.
Læs mere Tjek på PubMedMalaria Journal, 15.02.2024
Tilføjet 15.02.2024
Abstract Background South Africa set a target to eliminate malaria by 2023, with KwaZulu-Natal (KZN) Province the malaria-endemic province closest to achieving this goal. Objective two of the National Malaria Elimination Strategic Plan (NMESP) focused on strengthening surveillance systems to support the country’s elimination efforts. Regular evaluations of the malaria surveillance systems against the targets of the NMESP objective are crucial in improving their performance and impact. This study aimed to assess whether the malaria surveillance system in KwaZulu-Natal Province meets the NMESP surveillance objective and goals. Methods A mixed-methods cross-sectional study design was used to evaluate the malaria surveillance system, focusing on the District Health Information System 2 (DHIS2). The study assessed the data quality, timeliness, simplicity, and acceptability of the system. Key personnel from KZN’s Provincial malaria control programme were interviewed using self-administered questionnaires to evaluate their perception of the system\'s simplicity and acceptability. Malaria case data from January 2016 to December 2020 were extracted from the DHIS2 and evaluated for data quality and timeliness. Results The survey respondents generally found the DHIS2-based surveillance system acceptable (79%, 11/14) and easy to use (71%, 10/14), stating that they could readily find, extract, and share data (64%, 9/14). Overall data quality was good (88.9%), although some variables needed for case classification had low completeness and data availability. However, case notifications were not timely, with only 61% (2 622/4 329) of cases notified within 24 h of diagnosis. During the 5-year study period, the DHIS2 captured 4 333 malaria cases. The majority of cases (81%, 3 489/4 330) were categorized as imported, and predominately in males (67%, 2 914/4 333). Conclusion While the malaria surveillance system in KZN Province largely met the NMESP surveillance strategic goals, it failed to achieve the overarching surveillance objective of 100% notification of cases within 24 h of diagnosis. The majority of reported cases in KZN Province were classified as imported, emphasizing the importance of complete data for accurate case classification. Engaging with healthcare professionals responsible for case notification and disseminating aggregated data back to them is needed to encourage and improve notification timeliness.
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