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Ren H, Liu Y, Zhou J, et al.
AbstractBackgroundTrans-translation is a ribosome rescue system that plays an important role in bacterial tolerance to environmental stresses. It is absent in animals, making it a potential treatment target. However, its role in antibiotic tolerance in Pseudomonas aeruginosa remains unknown.MethodsThe role and activity of trans-translation during antibiotic treatment were examined with a trans-translation–deficient strain and a genetically modified trans-translation component gene, respectively. In vitro assays and murine infection models were used to examine the effects of suppression of trans-translation.ResultsWe found that the trans-translation system plays an essential role in P. aeruginosa tolerance to azithromycin and multiple aminoglycoside antibiotics. We further demonstrated that gentamicin could suppress the azithromycin-induced activation of trans-translation. Compared with each antibiotic individually, gentamicin and azithromycin combined increased the killing efficacy against planktonic and biofilm-associated P. aeruginosa cells, including a reference strain PA14 and its isogenic carbapenem-resistance oprD mutant, the mucoid strain FRD1, and multiple clinical isolates. Furthermore, the gentamicin-azithromycin resulted in improved bacterial clearance in murine acute pneumonia, biofilm implant, and cutaneous abscess infection models.ConclusionsCombination treatment with gentamicin and azithromycin is a promising strategy in combating P. aeruginosa infections.
Laurens M, Berry A, Travassos M, et al.
AbstractDirect venous inoculation (DVI) of 3.2x103 aseptic, purified, cryopreserved, vialed Plasmodium falciparum (Pf) strain NF54 sporozoites, PfSPZ Challenge (NF54), has been used for controlled human malaria infection (CHMI) in the U.S., 4 European and 6 African countries. In non-immunes, this results in 100% infection rates. We conducted a double blind, randomized, dose escalation study to assess the infectivity of the 7G8 clone of Pf (PfSPZ Challenge [7G8]). Results showed dose-dependent infectivity from 43% for 8x102 PfSPZ to 100% for 4.8x103 PfSPZ. PfSPZ Challenge (7G8) will allow for more complete assessment by CHMI of anti-malarial vaccines and drugs.
Schwarz T, McPhee R, Launay O, et al.
AbstractBackgroundRespiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life.MethodsThis randomized, observer-blind, multi-center, phase II study (NCT02956837) evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy non-pregnant 18–45-year-old women. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30µg, 60µg, or 120µg of RSV-F protein engineered to preferentially maintain a pre-fusion conformation (RSV-PreF vaccine) or placebo.ResultsThirty days post-vaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75, 4.42 and 4.36fold; RSV-B neutralizing antibody GMTs 2.36, 2.54 and 2.76fold; and palivizumab competing antibody (PCA) concentrations 11.69, 14.38 and 14.24fold compared to baseline levels in the 30µg, 60µg and 120µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at Day 30 were significantly higher with the 120µg compared to the 30µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered RSV-PreF vaccine-related.ConclusionsThe three formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, non-pregnant women.
Checkmahomed L, M’hamdi Z, Carbonneau J, et al.
AbstractBackgroundBaloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence.MethodsInfluenza A/Quebec/144147/2009 (H1N1)pdm09 and A/Switzerland/9715293/2013 (H3N2) recombinant viruses and their I38T PA mutants were compared in single and competitive infection experiments in ST6GalI-MDCK cells and C57/BL6 mice. Virus titers in cell culture supernatants and lung homogenates were determined by virus yield assays. Ratios of wild-type (WT) and I38T mutant were assessed by digital RT-PCR.ResultsI38T substitution did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses. In competition experiments, a 50:50% mixture evolved to 70:30% (WT/mutant) for A(H1N1) and 88:12% for A(H3N2) viruses after a single cell passage. The I38T substitution remained stable after 4 passages in vitro. In mice, the WT and its I38T mutant induced similar weight loss with comparable lung titers in both viral subtypes. The mutant virus tended to predominate over the WT in mouse competition experiments.ConclusionThe fitness of baloxavir-resistant I38T PA mutants appears relatively unaltered in seasonal subtypes warranting surveillance for its dissemination.
Direk Limmathurotsakul, Susanna Dunachie, Keiji Fukuda, Nicholas A Feasey, Iruka N Okeke, Alison H Holmes, Catrin E Moore, Christiane Dolecek, H Rogier van Doorn, Nandini Shetty, Alan D Lopez, Sharon J Peacock, Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC)
Estimating the global burden of disease from infections caused by pathogens that have acquired antimicrobial resistance (AMR) is essential for resource allocation and to inform AMR action plans at national and global levels. However, the scarcity of robust and accepted methods to determine burden is widely acknowledged. In this Personal View, we discuss the underlying assumptions, characteristics, limitations, and comparability of the approaches used to quantify mortality from AMR bacterial infections.
Oyong D, Wilson D, Barber B, et al.
AbstractBackgroundComplement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterised for P. vivax malaria. Plasmodium vivax merozoite Surface Protein-3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.MethodsPlasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days following drug treatment. Complement-fixing antibodies and IgM and IgG, targeting three distinctive regions of PvMSP3α were measured by ELISA.ResultsSeroprevalence of complement-fixing antibodies was highest against PvMSP3α Central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q-fixation and both purified IgG and IgM were capable of mediating C1q-fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Functional antibodies increased following acute infection to 7 days after treatment, however rapidly waned by day 28.ConclusionOur study demonstrates PvMSP3α antibodies acquired during P. vivax infection can mediate complement-fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.
Riou C, Jhilmeet N, Rangaka M, et al.
AbstractThe reconstitution of Mycobacterium tuberculosis (Mtb)-antigen-specific CD4 T cells in a cohort of HIV-infected persons starting antiretroviral treatment (ART) in high TB endemic area is described. Restoration of the antigen-specific CD4 T cell subsets mirrored the overall CD4 T cell compartment. Activation (assessed by HLA-DR expression) decreased during ART but remained elevated compared to HIV-uninfected persons. Despite known Mtb sensitisation determined by IGRA, 12/23 participants had no Mtb-specific CD4 T cells detectable by flow cytometry, combined with overall elevated T cell activation and memory differentiation, suggesting heightened turnover. Our data suggest early ART initiation to maintain polyfunctional immune memory responses.
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 anbefaler Professor Thomas Benfield artiklen"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."?
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