Sidst opdateret 24.11.2018
Klik på linket nedenfor, tryk derefter Ctrl + C eller højreklik for at kopiere det.
Nedenfor kan du finde abstracts fra de nyeste artikler indenfor udvalgte internationale tidsskrifter med infektionsmedicinsk relevans. Du kan under "Yderligere søgekriterier" vælge tidsskrifter, hvor langt tilbage i tiden og rækkefølge.
Vælg eventuelt et eller flere søgeord til at afgrænse søgningen. Match, hvis mindst 1 ord er fundet. Benyt semikolon mellem hvert ord.
Vælg et eller flere tidsskrifter fra listen.
Alle | Ingen
Vælg hvor mange dage tilbage i tiden, der skal vælges artikler fra.
Vælg, hvordan resultaterne skal sorteres.
Ingen søgeord valgt. Opdateret for 25 dage siden.44 emner vises.
Escota, Gerome; Baker, Jason; Bush, Tim; Conley, Lois; Brooks, John T.; Patel, Pragna; Powderly, William; Presti, Rachel; Overton, E. Turner; for the CDC (Centers for Disease Control and Prevention)-SUN (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy) Inv
Studies among HIV-uninfected persons (mostly in their sixth decade of life) show that detectable coronary artery calcium (CAC) is independently associated with low bone mineral density (BMD), suggesting a possible common pathogenic mechanism.
We assessed the relationship between CAC and BMD, which has not been well described among younger to middle-aged HIV-infected persons.
We studied participants with baseline CAC and BMD measures from a prospective cohort of HIV-infected persons enrolled in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) during 2004-2006. We used logistic regression to assess the association between detectable CAC (>0 Agatston score) and BMD (g/cm2, T-score), and adjusted for known traditional and HIV-related risk factors.
Among 472 participants (76% male, 30% non-Hispanic black, median age 41 years, 71% with HIV RNA
Antoine Grillon, Xavier Argemi, Jeannot Gaudias, Cécile Ronde-Ousteau, Cyril Boeri, Jean-Yves Jenny, Yves Hansmann, Nicolas Lefebvre, François Jehl
Tricya Nunes Vieira Bueloni, Daniel Marchi, Camille Caetano, Ricardo de Souza Cavalcante, Marcela Lara Mendes Amaral, Daniela Ponce
Haemodialysis (HD) is the most widely used dialysis therapy in the world, and vascular access represents an important risk factor for bacteraemia, hospitalisation and mortality (Brazilian dialysis census, 2016; Niyyar, 2012; Lok and Mokrzycki, 2011; Al-Balas et al., 2017; Vascular Access 2006 Work Group, 2006). In particular, catheter-related bloodstream infections (CR-BSI) is a severe complication that requires hospitalisation, systemic antibiotic therapy and removal, reinsertion or replacement of catheters (The NIH, 2016; Lee, 2017; Sequeira et al., 2017).
Yu, H., Lin, H., Xie, L., Tang, L., Chen, J., Zhou, Z., Ni, J., Zhong, G.
Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice, which is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed a CD4+ T cell-mediated protective immunity and CD8+ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8+ T cells were evaluated, we surprisingly found that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice mentioned above and suggesting that chlamydial infection is able to activate pathogenic mechanisms that is independent of CD8+ T cells. We further found that depletion of CD4+ T cells from CD8+ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4+ T cells became pathogenic in mice genetically deficient in CD8+ T cells. Since depletion of CD4+ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8+ T cell-deficient mice, we propose that in the absence of CD8+ T cells, some CD4+ T cells may remain protective (as in C57BL/6J) while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms depending upon host genetics and infection conditions. The CD8+ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4+ T cells promote chlamydial pathogenicity.
Ana Paula Silva Champs, Valéria Maria de Azeredo Passos, Guilherme Carvalho, Sandhi Maria Barreto, Carla Meirelles, Paulo Caramelli
Myelopathy is a well-established long-term clinical manifestation of HTLV-1 infection. Besides motor dysfunction, cognitive impairment may be another consequence of HTLV-1 infection. Moreover, inflammatory markers may be associated with cognitive impairment in these patients. The present study compared the cognitive performance of HAM/TSP patients with healthy controls and investigated the associations between cognitive performance, proviral load and blood inflammatory markers.
Dastgheyb, Raha M.; Sacktor, Ned; Franklin, Donald; Letendre, Scott; Marcotte, Thomas; Heaton, Robert; Grant, Igor; McArthur, Justin; Rubin, Leah H.; Haughey, Norman J.
The presentation of cognitive impairments in HIV-infected individuals has transformed since the introduction of antiretroviral therapies (ART). Although the overall prevalence of cognitive impairments has not changed considerably, frank dementia is now infrequent, and milder forms of cognitive impairments predominate. Mechanistic insights to the underlying causes of these residual cognitive impairments have been elusive, in part due to the heterogenous etiology of cognitive dysfunction in this population. Here we sought to categorize longitudinal change in HIV-infected patients based on the performance in specific cognitive domains.
This study consisted of 193 participants from the CHARTER cohort with detailed demographic, clinical and neuropsychological testing data obtained from two study visits interspersed by ∼6 months. Cognitive testing assessed executive function, learning and delayed recall, working memory, verbal fluency, speed of information processing, and motor skills. Change scores were calculated for each domain between the two study visits. Dimension reduction and clustering was accomplished by principal component analysis of change scores and k-means clustering to identify cognitive domains that group together, as well as groups of subjects with similar patterns of change.
We identified four distinct cognitive change phenotypes that included declines in: 1) verbal fluency, 2) executive function 3) learning and recall, and 4) motor function, with approximately equal numbers of participants in each phenotype.
Each of the four cognitive change phenotypes identify deficits that imply perturbations in specific neural networks. Future studies will need to validate if cognitive change phenotypes are associated with alterations in associated neural pathways.
Co-Correspondence. Norman J. Haughey, Department of Neurology, The Johns Hopkins University School of Medicine. Pathology 517, 600 North Wolfe Street. Baltimore MD. 21287. email: email@example.com. Leah H. Rubin, Department of Neurology, The Johns Hopkins University School of Medicine. Meyer 6-109, 600 North Wolfe Street. Baltimore MD. 21287. email: firstname.lastname@example.org.
The authors report no conflicts of interest related to this work.
Study Funding: This work was supported by the National Institutes of Health awards AA0017408, MH077542, MH075673, AG034849 (NJH and JCM), MH071150 (NS), the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) was supported by awards N01 MH22005, HHSN271201000036C and HHSN271201000030C (IG, TM, SL).
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Zhonghua Liu, Chuanping Wang, Jie Yang, Bowen Zhou, Rui Yang, Rajesh Ramachandran, Derek W. Abbott, Tsan Sam Xiao
The molecular mechanisms for activation and regulation of gasdermin D (GSDMD) are poorly characterized. Liu et al. report the crystal structures of the full-length murine and human GSDMDs, which reveal distinct and common features of autoinhibition among gasdermin family members, as well as an overlapping surface for lipid binding and oligomerization.
Sanjay S. Patel, Svetlana Bizjajeva, Kelly Lindert, Esther Heijnen, Janine Oberye
Influenza represents a significant burden in children—a fact that became apparent during the 2017-2018 season, in which an epidemic led to the highest rate of influenza-related hospitalizations ever reported and an increase in deaths due to influenza among children and adults (Rolfes et al., 2019). Because children are not only susceptible to influenza but also can transmit the disease to other vulnerable members of their household, seasonal influenza vaccination is recommended for children ≥6 months of age in the United States (Grohskopf et al., 2017).
Nicholas M. Adams, Clair D. Geary, Endi K. Santosa, Dianne Lumaquin, Jean-Benoît Le Luduec, Rosa Sottile, Kattria van der Ploeg, Joy Hsu, Benjamin M. Whitlock, Benjamin T. Jackson, Orr-El Weizman, Morgan Huse, Katharine C. Hsu, Joseph C. Sun
NK cells are innate lymphocytes capable of “adaptive” responses after infection, but whether they undergo avidity selection is unknown. Adams et al. report that diversity in antigen receptor Ly49H expression drives NK cell functional heterogeneity during MCMV infection with high-avidity NK cells being selected to dominate the adaptive response.
Rogovskyy, A. S., Caoili, S. E. C., Ionov, Y., Piontkivska, H., Skums, P., Tsyvina, V., Zelikovsky, A., Waghela, S. D.
Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by Borreliella burgdorferi (Bb). No vaccine is available for humans. Dogmatically, Bb can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. However, our recent study has shown that the Bb spirochete is effectively cleared by anti-Bb antibodies of New Zealand White rabbits despite the surface expression of VlsE. Besides homologous protection, the rabbit antibodies also cross-protect against heterologous Bb and significantly reduced pathology of LD arthritis in persistently infected mice. Thus, this finding that NZW rabbits develop a unique repertoire of very potent antibodies targeting the protective surface epitopes, despite abundant VlsE, prompted us to identify specificities of the rabbit protective antibodies and their respective targets. By applying subtractive reverse vaccinology, which involved random peptide phage display libraries coupled with the next generation sequencing and our computational algorithms, repertoires of non-protective (early) and protective (late) rabbit antibodies were identified and directly compared. Consequently, putative surface epitopes that are unique to the rabbit protective sera have been mapped. Importantly, the relevance of newly identified protection-associated epitopes for their surface exposure has been strongly supported by prior empirical studies. This study is significant because it now allows us to systematically test the putative epitopes for their protective efficacy with an ultimate goal of selecting the most efficacious targets for development of a long-awaited LD vaccine.
Blais, N., Somers, D., Faubert, D., Labbe, S., Castado, C., Ysebaert, C., Gagnon, L.-P., Champagne, J., Gagne, M., Martin, D.
Non-typeable Haemophilus influenzae (NTHi) is a pathogen known for being a frequent cause of acute otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In the present study, a vaccine antigen has been developed based on the fusion of two known NTHi adhesive proteins, Protein E (PE) and pilin subunit (PilA). The quality of the combined antigen was investigated through functional, biophysical and structural analyses. It was shown that PE and PilA individual structures are not modified in the PE-PilA fusion and that PE-PilA assembles as a dimer in solution, reflecting PE dimerization. PE-PilA was found to bind vitronectin in ELISA, as isolated PE does. Disulfide bridges were conserved and homogeneous, which was determined by peptide mapping and Top-down analysis on PE, PilA and PE-PilA molecules. Finally, the PE-PilA crystal showed a PE entity with a 3D-structure similar to that of recently published isolated PE, while the structure of the PilA entity was similar to that of a 3D-model elaborated from two other type 4 pilin subunits.Taken together, our observations suggest that the two tethered proteins behave independently within the chimeric molecule and display structures similar to the respective isolated antigens, which are important characteristics for eliciting an optimal antibody-mediated immunity. PE and PilA can thus be further developed as a single fusion protein in a vaccine perspective, in the knowledge that tethering the two antigens does not perceptibly compromise the structural attributes offered by the individual antigens.
O'Malley, K. J., Bowling, J. D., Barry, E. M., Hazlett, K. R. O., Reed, D. S.
Inhalation of Francisella tularensis (Ft) causes pneumonic tularemia in humans, a severe disease with a 30-60% mortality rate. Reproducible delivery of aerosolized virulent bacteria in relevant animal models is essential for evaluating medical countermeasures. Here we developed optimized protocols for infecting New Zealand White (NZW) rabbits with aerosols containing Ft. We evaluated relative humidity, aerosol exposure technique, and bacterial culture conditions to optimize spray factor (SF), a central metric of aerosolization. This optimization reduced both inter- and intra-daily variability and were applicable to multiple isolates of Ft. Further improvements in the accuracy and precision of the inhaled pathogen dose were achieved through enhanced correlation of bacterial culture OD and CFU. Plethysmograph data collected during exposures found that respiratory function varied considerably between rabbits, was not a function of weight, and did not improve with acclimation to the system. Vaccine Strain (LVS)-vaccinated rabbits were challenged via aerosol with human-virulent Ft SCHU S4 that had been cultivated in either Mueller Hinton Broth (MHB) or Brain Heart Infusion (BHI) broth. LVS-vaccinated animals challenged with MHB-SCHU S4 experienced short febrile periods (median: 3.2 days), limited weight loss (< 5%), and longer median survival times (~18 d) that were significantly different than unvaccinated controls. In contrast, LVS-vaccinated rabbits challenged with BHI SCHU S4 experienced longer febrile periods (median: 5.5 days), greater weight loss (> 10%), and median survival times that were not significantly different than unvaccinated controls. These studies highlight the importance of careful characterization and optimization of protocols for aerosol challenge with pathogenic agents.
Svahn, S. L., Gutierrez, S., Ulleryd, M. A., Nookaew, I., Osla, V., Beckman, F., Nilsson, S., Karlsson, A., Jansson, J.-O., Johansson, M. E.
Neutrophils are the most abundant circulating leukocytes in humans and are essential for the defense against invading pathogens. As many other cells of an organism, neutrophils can be highly influenced by the diet. We have previously described that mice fed a diet rich in polyunsaturated fatty acids (HFD-P) present higher frequency of neutrophils in bone marrow compared with mice fed a diet rich in saturated fatty acids (HFD-S). Interestingly, such increase correlated with improved survival to bacteria-induced sepsis. In this study we aimed to investigate the effects of dietary polyunsaturated and saturated fatty acids on neutrophil homeostasis. We found that HFD-P specifically induced accumulation of neutrophils in the marginal pools of spleen and liver. The accumulation of neutrophils in spleen was a result of a dual effect of polyunsaturated fatty acids on neutrophil homeostasis. Firstly, polyunsaturated fatty acids enhanced the recruitment of neutrophils from the circulation into the spleen via chemokine secretion. Secondly, they delayed neutrophil cell death in the spleen. Interestingly, these effects were not observed in mice fed a diet rich in saturated fatty acids, suggesting that the type of fat rather than the amount of fat mediates the alterations in neutrophil homeostasis. In conclusion, our results show that dietary polyunsaturated fatty acids have a strong modulatory effect on neutrophil homeostasis that may have future clinical applications.
Simon Grassmann, Ludwig O. Pachmayr, Justin Leube, Lorenz Mihatsch, Immanuel Andrae, Sophie Flommersfeld, Jennifer Oduro, Luka Cicin-Sain, Matthias Schiemann, Michael Flossdorf, Veit R. Buchholz
Upon infection, T cell clones harboring TCRs of distinct antigen affinity undergo differential expansion. Whether NK cells show similar clonal dynamics is not clear. By using retrogenic color-barcoding and single-cell adoptive transfers, Grassmann et al. show that NK cells adapt to cytomegalovirus infection by differential expansion of individual clones that heritably express distinct levels of virus-specific activating receptor Ly49H.
Jéssica Vespa Presa, Maria Grabriela Abalos, Rodrigo Sini de Almeida, Alejandro Cane
Juliana Komuczki, Selma Tuzlak, Ekaterina Friebel, Tom Hartwig, Sabine Spath, Philip Rosenstiel, Ari Waisman, Lennart Opitz, Mohammed Oukka, Bettina Schreiner, Pawel Pelczar, Burkhard Becher
GM-CSF is a critical cytokine in the development of tissue inflammation. Komuzcki et al. use a fate-mapping and reporter system to demonstrate that GM-CSF production by CNS-infiltrating T helper cells is crucial for phagocyte invasion and neuroinflammation. Pathogenicity was lost in the absence of GM-CSF expression despite the presence of IFN-γ- and IL-17-producing T helper cells in the CNS.
Abhay Kumar, Manisha Biswal, Kamran Zaman, Navneet Sharma, Vikas Suri, Ashish Bhalla
Lysien I. Zambrano, Itzel Carolina Fuentes-Barahona, Ramon Jeremías Soto-Fernández, Concepción Zuniga, José Cláudio da Silva, Alfonso J. Rodriguez-Morales
Despite the enormous magnitude of Zika virus (ZIKV) infection epidemics in the Americas, (Musso et al., 2018) studies describing its many consequences, such as the Congenital Zika Syndrome (CZS) (Alvarado-Socarras et al., 2018) or the Guillain-Barré syndrome (GBS) (Villamil-Gomez et al., 2017), lack in many countries across the region. That mainly includes reports from Central America countries, such as Honduras. This country was affected by ZIKV with epidemic during 2016-2017 (Zambrano et al., 2019).
Nguyen, Huyen; Thorball, Christian W.; Fellay, Jacques; Böni, Jürg; Yerly, Sabine; Perreau, Matthieu; Klimkait, Thomas; Kusjeko, Katharina; Bachmann, Nadine; Chaudron, Sandra E.; Paioni, Paolo; Thurnheer, Maria Christine; Battegay, Manuel; Cavassini, Matthias; Vernazza, Pietro; Bernasconi, Enos; Günthard, Huldrych F.; Kouyos, Roger; the Swiss HIV Cohort Study
HIV’s capacity to escape immune recognition by Human Leukocyte Antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA Class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to host HLA type, and could better improve therapeutic strategies against HIV.
Materials and Methods:
301-325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA Class I data was compiled at three specificity levels: four-digit, two-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as two measures: the proportion of transmission pairs which are HLA-concordant as well as the average percentage of allele matches within all clusters. These measures were compared to the mean value across randomizations with randomly assorted individuals.
We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs.0.251, p-value=0.009; supertype clusters: 0.659 vs. 0.611, p-value=0.002; supertype pairs: 0.655 vs. 0.608, p-value=0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men (MSM) but not other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, though this yielded no significant pattern.
The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.
Corresponding Author: Huyen Nguyen Division of Infectious Diseases and Hospital Epidemiology University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich Fax: + 41 44 63 4496 Phone: +41 44 253 01 88 Email: Huyen.email@example.com
** Shared authorship.
Conferences: Conference on Retroviruses and Opportunistic Infections (CROI)Boston, 4-7 March 2018.
Conflicts of Interest and Source of Funding: HFG has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Sandoz and Mepha; and travel reimbursement from Gilead. MB has received research or educational grants by Abb Vie AG, Gilead Sciences Switzerland Sàrl, Janssen-Cilag AG, MSD Merck Sharp & Dohme AG and ViiV Healthcare GmbH. EB has received fees for his institution for participation to advisory board from MSD, Gilead Sciences, ViiV Healthcare, Abbvie and Janssen. MC has received research and travel grants for his institution from ViiV and Gilead. The remaining authors have no competing interests to declare.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Ilker Uçkay, Panayiotis Christofilopoulos
Januel, Edouard; Godin, Ophelia; Moulignier, Antoine; Lescure, François-Xavier; Savatovsky, Julien; Lamirel, Cédric; Valin, Nadia; Tubiana, Roland; Canestri, Ana; Roux, Pascal; Sadik, Jean-Claude; Salomon, Laurence; Katlama, Christine; Yazdanpanah, Yazdan; Pialoux, Gilles; Girard, Pierre-Marie; dominique Costagliola, ; Assoumou, Lambert; for the Microvascular Brain Retina And Kidney (MicroBREAK) Study Group
Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral-drug class could be associated with an increasing risk of CSVD.
The MicroBREAK-2 case–control study (NCT02210130) enrolled PLHIVs ≥50 years old, treated with combined antiretroviral therapy (cART) for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex and year of HIV diagnosis (±5 years). Multivariable conditional logistic-regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV-transmission group.
Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs’ median age was 57.6 years and median HIV-diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class.
No deleterious effect of ART-class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.
Conflicts of Interest and Source of Funding: This work was supported by the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales. A.M. reports consultancy fees and/or non-financial support from Biogen Idec, Novartis, Gilead, MSD, Teva, and Merck-Serono, outside the submitted work. J.S. reports consultancy fees from Bayer Pharmaceutical, Medtronic, Philips Healthcare, Gilead, Novartis, Sanofi, IRIS (Institut de Recherche Servier), and non-financial support from GE Healthcare and Bayer Pharmaceutical, outside the submitted work. F.-X.L. reports consultancy fees from MSD and Gilead, outside the submitted work. C.L. reports consultancy fees and/or non-financial support from Allergan, Thea, and Alcon, outside the submitted work. P.R. reports non-financial support from General Electrics, outside the submitted work. C.K. reports grants and/or consultancy fees from Merck-Sharp-Dome, Bristol-Myers-Squibb, from ViiV Healthcare, from Gilead Sciences, and Janssen Pharmaceuticals, outside the submitted work. Y.Y. reports consultancy fees from Abbvie, BMS, Gilead, MSD, Roche, Johnson&Johnson, ViiV Healthcare and Pfizer, from Janssen for board membership and payment for development of educational presentations, outside the submitted work. G.P. reports grants or consultancy fees from Gilead, Abbvie, BMS, Viiv, GSK, Janssen, and Nephrotek, outside the submitted work. P.-M.G. reports grants and/or consultancy fees from BMS, Janssen, Gilead, Viiv Healthcare, and Abbvie, outside the submitted work. D.C. reports grants from Janssen-Cilag (2017-2018), Merck-Sharp & Dohme-Chibret (2015-2017), ViiV (2015), personal fees from Janssen-Cilag (2016, 2018), Merck-Sharp & Dohme-Chibret (2015, 2017) for lectures, personal fees from ViiV (2015) for travel/accommodations/meeting expenses, personal fees from Gilead France from 2011 until December 2015 for French HIV board, personal fees from Innavirvax (2015 and 2016) and Merck Switzerland (2017) for consultancy all outside the submitted work. E.J. L.A., O.G., N.V., R.T., A.C., J.-C.S., L.S. have nothing to disclose.
* The MicroBREAK Study Group members are listed in the Acknowledgment section.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Linghua Yu, Jin He, Linlin Wang, Huixing Yi
Melvyn T. Chow, Aleksandra J. Ozga, Rachel L. Servis, Dennie T. Frederick, Jennifer A. Lo, David E. Fisher, Gordon J. Freeman, Genevieve M. Boland, Andrew D. Luster
Chow et al. find the CXCR3 chemokine system is not required for CD8+ T cell migration into the tumor, but rather for the enhancement of the intratumoral CD8+ T cell response in the context of PD-1 blockade. The CXCR3 chemokine system might serve as a biomarker for sensitivity to PD-1 blockade and a target for improving clinical outcomes.
Olatunde Olayanju, Aliasgar Esmail, Jason Limberis, Phindile Gina, Keertan Dheda
Banerjee, S. K., Huckuntod, S. D., Mills, S. D., Kurten, R. C., Pechous, R. D.
Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Key to the progression of infection is activity of the Plasminogen activator protease Pla. Deletion of Pla results in decreased Y. pestis bacterial burden in the lung and failure to progress into the lethal pro-inflammatory phase of disease. While a number of putative functions have been attributed to Pla, its precise role in the pathogenesis of pneumonic plague is yet to be defined. Here, we show that Pla facilitates type 3 secretion into primary alveolar macrophages, but not the commonly used THP-1 cell line. We also establish human precision-cut lung slices as a platform for modeling early host/pathogen interactions during pneumonic plague, and solidify the role of Pla in promoting optimal type 3 secretion using primary human tissue with relevant host-cell heterogeneity. These results position Pla as a key player in the early host/pathogen interactions that define pneumonic plague, and showcase the utility of human precision-cut lung slices as a platform to evaluate pulmonary infection by bacterial pathogens.
Even though prosthetic valve endocarditis due to coagulase-negative staphylococci (CoNS) is widely documented and attracts global attention, native valve endocarditis due to CoNS has been also described lately and may warrant closer attention due to the relative increased incidence.
We describe a 35-year-old male patient who is a former resident of a long-term health-care facility with multiple co-morbidities, diagnosed with native aortic valve S. capitis endocarditis and underwent conservative antimicrobial treatment with full recovery and no recurrence after 6 months’ follow-up. In addition, we reviewed the English literature on all reported cases of S. capitis endocarditis.
Infective endocarditis due to S. capitis has thus far been described in 13 patients. All but three had involved native valves with two infected prosthetic valves and a single case of infection in an implanted transvenous pacemaker. Although the number of cases of endocarditis due to S. capitis is small, early removal of either a prosthetic valve or infected pacemaker would appear prudent, while native valve endocarditis could successfully be treated with appropriate antimicrobials alone.
Staphylococcus capitis is classified as coagulase-negative staphylococci with the inherent ability to cause debilitating native valve endocarditis and is usually managed conservatively.
Billings, Erik; Kijak, Gustavo H.; Sanders-Buell, Eric; Ndembi, Nicaise; O'Sullivan, Anne Marie; Adebajo, Sylvia; Kokogho, Afoke; Milazzo, Mark; Lombardi, Kara; Baral, Stefan; Nowak, Rebecca; Ramadhani, Habib; Gramzinski, Robert; Robb, Merlin L.; Michael, Nelson L.; Charurat, Manhattan E.; Ake, Julie; Crowell, Trevor A.; Tovanabutra, Sodsai; for the MHRP Viral Sequencing Core and the TRUST/RV368 Study Group
HIV-1 circulating recombinant forms (CRF) containing subtype B are uncommon in sub-Saharan Africa. Prevalent infections observed during enrollment of a prospective study of men who have sex with men (MSM) from Lagos, Nigeria revealed the presence of a family of subtype B and CRF02_AG recombinants. This report describes the HIV-1 genetic diversity within a high-risk, high-prevalence, and previously undersampled cohort of Nigerian MSM.
Between 2013 and 2016, 672 MSM were enrolled at the Lagos site of the TRUST/RV368 study. Prevalent HIV-1 infections were initially characterized via pol sequencing and phylogenetic subtyping analysis. Samples demonstrating the presence of subtype B were further characterized by near full-length sequencing, phylogenetic, and Bayesian analyses.
Within this cohort, HIV-1 prevalence was 59%. The major subtype was CRF02_AG (57%), followed by CRF02/B recombinants (15%), subtype G (13%), and smaller amounts of A1, B, and other recombinants. Nine clusters of closely related pol sequences indicate ongoing transmission events within this cohort. Among the CRF02_AG/B, a new CRF was identified and termed CRF95_02/B. Shared risk factors and Bayesian phylogenetic inference of the new CRF95_02B and the similarly structured CRF56_cpx, indicate a Nigerian or West African origin of CRF56_cpx prior to its observation in France.
With high HIV-1 prevalence, new strains, and multiple transmission networks, this cohort of Nigerian MSM represents a previously hidden reservoir of HIV-1 strains, including the newly-identified CRF95_02B and closely-related CRF56_cpx. These strains will need to be considered during vaccine selection and development in order to optimize the design of a globally effective HIV-1 vaccine.
Corresponding Author: Sodsai Tovanabutra, PhD 503 Robert Grant Avenue, Room 2N25 Silver Spring, MD 20910 USA Tel: 301-319-9993 Email: firstname.lastname@example.org
* Current affiliation: Children’s National Hospital, Washington, DC, USA
** Current affiliation: GSK Vaccines, Rockville, MD, USA
This work was presented in part at the 2018 Conference on Retroviruses and Opportunistic Infections in Boston, MA, USA, March 4-7, 2018.
Funding Statement: This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174]; the National Institutes of Health [R01 MH099001, R01 AI120913, R01 MH110358]; Fogarty Epidemiology Research Training for Public Health Impact in Nigeria program [D43TW010051]; and the President’s Emergency Plan for AIDS Relief through a cooperative agreement between the Department of Health and Human Services/Centers for Disease Control and Prevention, Global AIDS Program, and the Institute for Human Virology-Nigeria [NU2GGH002099].
The authors report no conflicts of interest related to this work.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Argita D. Salindri, Jann-Yuan Wang, Hsien-Ho Lin, Matthew J. Magee
Philip S. Watson, Patricia L. Novy, Leonard R. Friedland
A Balkhair, Z Al-Muharrmi, B Al'Adawi, I Al Busaidi, HB Taher, T Al-Siyabi, M Al Amin, KS Hassan
Extrapulmonary infections due to M. xenopi, particularly osteoarticular localizations, are rare. The purpose of this paper is to describe a case of prosthetic hip infection and to review the published literature on cases of M. xenopi osteoarticular infections.
Literature search was performed in the following databases: MEDLINE (PubMed), Embase, Central (the Cochrane Library 2019, Issue 1), LILACS (BIREME) (Latin American and Caribbean Health Science Information database) and Clinical Trials databases (14th August 2018). We included all case reports and case series on adult patients diagnosed with bone or joint infection by M. xenopi for whom the treatment and outcome were specified.
We retrieved 30 cases published between 1982 and 2012, among which 25 (83.3%) were reported from Europe. The two most common infection sites were spine (12/30, 40%) and knee (9/30, 30%). Risk factors for infection were previous invasive procedures (11/30, 36.7%), autoimmune disease (8/30, 26.7%), AIDS (4/30, 13.3%) and other comorbidities (2/30, 6.7%); five patients had no past medical history. All patients were treated with antibiotic combinations, but composition and duration of regimens hugely varied. Surgical intervention was performed in 16 patients (53.3%). Only 11 patients obtained full recovery of articular mobility after treatment.
This work highlights the difficulties in diagnosing and treating M. xenopi osteoarticular infections. Globally, evidence supporting the best practice for diagnosis and treatment of this infection is scanty.
Fritz Matthieu, Taty Taty Raphaël, Portella Chantale, Guimbi Christ, Mankou Michel, M. Leroy Eric, Becquart Pierre
In January 2019, an outbreak of Chikungunya virus fever was reported in a rural region near Pointe-Noire, Republic of the Congo. Molecular and phylogenetic analysis of this new CHIKV strain demonstrated the presence of the A226 V substitution and a surprisingly close relation with Aedes aegypti-associated Central Africa chikungunya strains. These results, combined with the preponderance of Aedes albopictus in the outbreak area, suggest a recent vector-host switch facilitated by the emergence and spread of the A226 V mutation from a related CHIKV strain previously circulating in Aedes aegypti.
Carrie E Barnes, C Raina MacIntyre
Antimicrobial resistance (AMR) is an important factor for consideration in pandemic preparedness. Any reduction in treatability poses a potential risk to national and international security and economic stability when applied to pandemic-related pathogens (McArthur and Tsang, 2017). Increasing AMR among pathogens responsible for the development of community-acquired pneumonia (CAP) (e.g. Streptococcus pneumoniae and Haemophilus influenzae) (Adam, 2002) is especially concerning given their propensity to cause bacterial infections secondary to viral influenza.
Ye, C., Li, Q., Li, X., Park, C. G., He, Y., Zhang, Y., Wu, B., Xue, Y., Yang, K., Lv, Y., Ying, X.-l., Ding, H.-h., Cai, H., Alkraiem, A. A., Njiri, O., Tembo, J., Huang, H.-p., Li, A.-y., Gong, J., Qin, J., Cheng, B., Wei, X., Sun, Z., Zhang, S.-s., Zhang, P., Zheng, G.-x., Li, W., Kan, B., Yan, M., Xiding, X., Huo, X., Zeng, Y., Peng, H., Fu, Y., Klena, J. D., Skurnik, M., Jiang, L.-y., Chen, T.
Salmonella typhimurium, a Gram-negative bacterium, can cause infectious diseases ranging from gastroenteritis to systemic dissemination and infection. However, the molecular mechanisms underlying this bacterial dissemination have yet to be elucidated. A study indicated that using the lipopolysaccharide (LPS) core as a ligand, S. typhimurium was able to bind human DC-SIGN (hCD209a), a HIV receptor that promotes viral dissemination by hijacking antigen-presenting cells (APCs). In this study, we showed that S. typhimurium interacted with CD209s, leading to the invasion of APCs and potentially the dissemination to regional lymph nodes, spleen and liver in mice. Shielding of the exposed LPS core through the expression of O-antigen reduces dissemination and infection. Thus, we propose that similar to HIV, S. typhimurium may also utilize APCs via interactions with CD209s as a way to disseminate to the lymph nodes, spleen and liver to initiate host infection.
George M. Varghese, Vijay Prakash Turaka, Jeshina Janardhanan, Sadhana Yadav, Kavitha M. Lakshmi, Vijayakumar TS, Bobby Cherayil
Tuberculosis (TB) continues to be a significant cause of morbidity and mortality worldwide. The recent annual report on TB by the World Health Organization (WHO) estimated 10 million new and recurrent TB cases globally, with India alone accounting for 27% of these cases, causing 1.3 million and 300,000 deaths in HIV negative and HIV positive individuals respectively (WHO, 2018). The progression from uninfected or latently infected to active tuberculosis is often insidious and has minimal symptoms in the initial months, resulting in delayed diagnosis and poor outcomes (Lui et al., 2014).
Zhidai Liu, Shan Liu, Yi Shu, Zuqun Yang, Bin Peng, Hongmei Xu, Qubei Li, Zhengxiu Luo, Jihong Dai, Enmei Liu, Zhou Fu, Lin Zou
NTM are ubiquitous bacteria that can cause colonisation and infection in immunocompetent and compromised hosts. The aim of this study was to elucidate the epidemiology of infection or colonisation with NTM for the metropolitan region of Frankfurt, Germany.
All patients from whom NTM were isolated within the period from 2006 to 2016 were included in this retrospective analysis. Patient data were retrieved using the local patient data management system. Different groups were formed according to clinical manifestations, underlying diseases and mycobacterial species. They were compared in regard to mortality, duration of infection/colonisation and their geographical origins.
A total of 297 patients with a median of 28 new patients each year were included. Most patients suffered from lung infection or colonisation (72.7%, n = 216), followed by disseminated mycobacteriosis (12.5%, n = 37). The majority were HIV-positive, suffering from malignoma or cystic fibrosis (29.3%, n = 87, 16.2%, n = 48, and 13.8%, n = 41, respectively). 17.2% of patients showed no predisposing condition (n = 51). Mycobacterium avium complex (MAC) species were most frequently isolated (40.7%, n = 121). Infection/colonisation was longest in CF patients (median of 1094 days). The mortality was highest in malignoma patients (52.4%), while CF patients had the lowest overall mortality rate (5.3%). But mortality analysis showed non-significant results within different mycobacterial species and clinical manifestations.
NTM remain rare but underestimated pathogens in lung and disseminated disease. MAC were the species most frequently isolated. Depending on species and underlying predispositions, the duration of infection/colonisation can be unexpectedly long.
Lilly, E. A., Yano, J., Esher, S. K., Hardie, E., Fidel, P. L., Noverr, M. C.
Polymicrobial intra-abdominal infections (IAI) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of polymicrobial IAI and demonstrated that co-infection with Candida albicans (Ca) with Staphylococcus aureus (Sa) results in 80-90% mortality in 48-72 h due to robust local and systemic inflammation. Surprisingly, inoculation with C. dubliniensis (Cd) and Sa resulted in minimal mortality and re-challenge of mice with lethal Ca/Sa conferred >90% protection up to 60 days post-inoculation. Protection was mediated by Gr-1+ polymorphonuclear leukocytes, indicating a novel form of trained innate immunity (TII). The purpose of this study was to determine the microbial requirements and spectrum of innate-mediated protection. In addition to Cd, several other low virulence Candida species (C. glabrata, C. auris, C. albicans efg1/ cph1/), and Saccharomyces cerevisiae conferred significant protection with or without Sa. For Cd-mediated protection, hyphal formation was not required, with protection conferred as early as 7 days after primary challenge, but not 120 days, and also following multiple lethal Ca/Sa re-challenges. This protection also extended to a lethal intravenous (i.v.) Ca challenge but had no effect in the Ca vaginitis model. Finally, studies revealed the ability of the low virulence Candida species that conferred protection to invade the bone marrow by 24 h post-primary challenge, with a positive correlation between femoral bone marrow fungal infiltration at 48 h and protection upon re-challenge. These results support and further extend the characterization of this novel TII in protection against lethal fungal-bacterial IAI and sepsis.
Seok Jun Mun, Si-Ho Kim, Jin Yang Baek, Kyungmin Huh, Sun Young Cho, Cheol-In Kang, Doo Ryeon Chung, Kyong Ran Peck
We describe the use of bacteriophage therapy in a 26-year-old cystic fibrosis (CF) patient awaiting lung transplantation.
The patient developed multidrug resistant (MDR) Pseudomonas aeruginosa pneumonia, persistent respiratory failure, and colistin-induced renal failure. We describe the use of intravenous bacteriophage therapy (BT) along with systemic antibiotics in this patient, lack of adverse events, and clinical resolution of infection with this approach. She did not have recurrence of pseudomonal pneumonia and CF exacerbation within 100 days following the end of BT and underwent successful bilateral lung transplantation 9 months later.
Given the concern for MDR P. aeruginosa infections in CF patients, BT may offer a viable anti-infective adjunct to traditional antibiotic therapy.
Llaguno, M., da Silva, M. V., Batista, L. R., da Silva, D. A. A., de Sousa, R. C., de Resende, L. A. P. R., da Silva, V. J. D., Lages Silva, E., Oliveira, C. J. F., Machado, J. R., Rodrigues, D. B. R., Correia, D., Rodrigues, V.
The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher in vitro antigen-specific production of interferon (IFN-) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN- over interleukin (IL)-10 production in antigen-specific cultures was associated with cardiac involvement. A significant increase in the number of antigen-specific T helper 1 cells (T-Bet+IFN-+) and a significantly higher IFN-+/IL-10+ ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than those of cytotoxic T lymphocytes producing IFN-. Patients with cardiac Chagas disease had predominant CD25- and CD25low T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25high Tregs. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN- production (mostly from CD4+ T cells) relative to IL-10 production and Treg percentage. Patients with the indeterminate form of Chagas disease show a more balanced ratio of pro- and anti-inflammatory cytokines.
Kalisvar Marimuthu, Ng Oon-Tek, Natasha Bagdasarian, Paul A. Tambyah
Cuenot, E., Garcia-Garcia, T., Douche, T., Gorgette, O., Courtin, P., Denis-Quanquin, S., Hoys, S., Tremblay, Y. D. N., Matondo, M., Chapot-Chartier, M.-P., Janoir, C., Dupuy, B., Candela, T., Martin-Verstraete, I.
Clostridium difficile is the leading cause of antibiotic-associated diarrhea in adults. During infection, C. difficile must detect the host environment and induce an appropriate survival strategy. Signal transduction networks involving serine/threonine kinases (STKs) play key roles in adaptation, as they regulate numerous physiological processes. PrkC of C. difficile is a STK with two PASTA domains. We showed that PrkC is membrane associated and is found at the septum. We observed that deletion of prkC affects cell morphology with an increase in mean size, cell length heterogeneity, and presence of abnormal septa. When compared with the wild-type strain, a prkC mutant was able to sporulate and germinate but was less motile and formed more biofilm. Moreover, a prkC mutant was more sensitive to antimicrobial compounds that target the cell envelope such as the secondary bile salt deoxycholate, cephalosporins, cationic antimicrobial peptides, and lysozyme. This increased susceptibility was not associated with differences in peptidoglycan or polysaccharide II composition. However, the prkC mutant had less peptidoglycan and released more polysaccharide II into the supernatant. A proteomic analysis showed that the majority of C. difficile proteins associated with the cell wall were less abundant in the prkC mutant compared to the wild-type strain. Finally, in a hamster model of infection the prkC mutant had a colonization delay that did not significantly affect overall virulence.
Nance, Robin M; Vannappagari, Vani; Smith, Kimberly; Calingaert, Brian; Johannes, Catherine; Saltus, Catherine; Mayer, Kenneth H.; Whitney, Bridget M.; Rodriguez, Benigno; Moore, Richard D.; Eron, Joseph J.; Geng, Elvin; Mathews, W. Christopher; Mathews, W. Christopher; Mugavero, Michael J.; Saag, Michael S.; Kitahata, Mari M.; Delaney, Joseph A. C.; Crane, Heidi M
Guidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTI) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States.
We examined two groups of PLWH at eight clinics who initiated ART regimens (August 1, 2013–March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced.
The outcome in this longitudinal cohort study was VF, defined as a viral load of >400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models.
Among 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios (HRs) were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The HR for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95%CI:0.2-0.6) among previously treatment-naive PLWH and was 0.60 (95%CI:0.4-0.8) among treatment-experienced PLWH.
The proportion of previously treatment-naïve PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naïve and treatment-experienced PLWH.
Corresponding author: Heidi M. Crane Professor of Medicine Associate Director Clinical Epidemiology and Health Services Research Core, University of Washington Center for AIDS Research Harborview Medical Center 325 9th Ave, Box 359931 Seattle, WA 98106 email: email@example.com Telephone: 206-744-6649 Fax: 206-744-3693
Funding was provided by ViiV Healthcare who had input into protocol development. ViiV had no influence on data collection, analysis, or interpretation; writing, or decision to publish. CNICS is funded by the National Institutes of Health who had no role in study design or the manuscript. The corresponding author had access to data and bears responsibility for the manuscript. Additional support came from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health [CNICS R24 AI067039, UW CFAR NIAID Grant P30 AI027757; UNC CFAR grant P30 AI50410, JHU CFAR grant P30 AI094189, and UAB CFAR grant P30 AI027767].
The authors report no conflicts of interest related to this work.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Reply to Barner and Bruno-Murtha
23.09.2019Clinical Infectious Diseases Advance Access
False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers
21.09.2019Clinical Infectious Diseases Advance Access
Resistance of Influenza Virus to Antiviral Medications
20.09.2019Clinical Infectious Diseases Advance Access
Oseltamivir resistance in severe influenza A(H1N1)pdm09 pneumonia and acute respiratory distress syndrome: a French multicenter observational cohort study
20.09.2019Clinical Infectious Diseases Advance Access
Baloxavir marboxil in Japanese pediatric patients with influenza: safety and clinical and virologic outcomes
20.09.2019Clinical Infectious Diseases Advance Access
Hvorfor synes Professor Thomas Benfield, at du bør læse"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvorfor anbefaler Professor Niels Obel artiklen"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
Hvad synes Professor Thomas Benfield om"Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial."?
Hvad mener Professor Morten Sodemann om artiklen"Evidence-based clinical guidelines for immigrants and refugees."?
Hvorfor anbefaler Professor Niels Obel artiklen"Use of statins and risk of AIDS-defining and non-AIDS-defining malignancies among HIV-1 infected patients on antiretroviral therapy."?
Tilmeld dig vores nyhedsbrev og hold dig opdateret om nyt på hjemmesiden
© 2019 Dansk Selskab for Infektionsmedicin
version: 2.5.2 ● design: C P Fischer
Side indlæst på 0,107 s