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Wang, Q., Peng, K., Liu, Y., Xiao, X., Wang, Z., Li, R.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
The emergence and transmission of novel antimicrobial resistance genes pose a great threat to public health globally. Recently, the plasmid-encoding RND efflux pump TMexCD1-TOprJ1 in Klebsiella pneumoniae was reported to reduce the sensitivity of multiple antimicrobials. Herein, we identified a pandrug-resistant Proteus mirabilis isolate, which harbored the novel tmexCD3-toprJ3 gene cluster located on SXT/R391 ICE. This study expands current knowledge in transfer mechanism of tmexCD1-toprJ1-like gene clusters among P. mirabilis and warrant further genomic epidemiology investigations.
Læs mere Tjek på PubMedRehman, A., Jeukens, J., Levesque, R. C., Lamont, I. L.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Ciprofloxacin is one of the most widely used antibiotics for treating Pseudomonas aeruginosa infections. However P. aeruginosa acquires mutations that confer ciprofloxacin resistance, making treatment more difficult. Resistance is multifactorial, with mutations in multiple genes influencing the resistance phenotype. However the contributions of individual mutations and mutation combinations to the amounts of ciprofloxacin that P. aeruginosa can tolerate are not well understood. Engineering P. aeruginosa strain PAO1 to contain mutations in any one of the resistance-associated genes gyrA, nfxB, rnfC, parC and parE showed that only gyrA mutations increased the Minimum Inhibitory Concentration (MIC) for ciprofloxacin. Mutations in parC and parE increased the MIC of a gyrA mutant, making the bacteria ciprofloxacin resistant. Mutations in nfxB and rnfC increased the MIC, conferring resistance, only if both were mutated in a gyrA background. Mutations in all of gyrA, nfxB, rnfC and parC/E further increased the MIC. These findings reveal an epistatic network of gene-gene interactions in ciprofloxacin resistance. We used this information to predict ciprofloxacin resistance/susceptibility for 274 isolates of P. aeruginosa from their genome sequences. Antibiotic susceptibility profiles were predicted correctly for 84% of the isolates. The majority of isolates for which prediction was unsuccessful were ciprofloxacin resistant, demonstrating the involvement of additional as yet unidentified genes and mutations in resistance. Our data show that gene-gene interactions can play an important role in antibiotic resistance and can be successfully incorporated into models predicting resistance phenotype.
Læs mere Tjek på PubMedAbdelwahab, M. T., Court, R., Everitt, D., Diacon, A. H., Dawson, R., Svensson, E. M., Maartens, G., Denti, P.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Rationale
Clofazimine is classified as a WHO group B drug for the treatment of rifampicin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several anti-tubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation.
Objectives
To describe the effect of clofazimine exposure on QT prolongation
Methods
Fifteen adults drug-susceptible tuberculosis patients received clofazimine mono-therapy as 300 mg daily for three days followed by 100 mg daily in one arm of a 2-week, multi-arm early bactericidal activity trial in South Africa. Pre-treatment Fridericia-corrected QT (QTcF) (105 patients, 524 ECGs) and QTcF’s from the clofazimine-monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model.
Measurements and Main Results
Clofazimine was associated with significant QT prolongation described by an Emax function. We predicted clofazimine exposures using 100-mg daily doses and two-weeks loading with 200 and 300 mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (QTcF>30) were 2.52%, 11.6%, and 23.0% for 100, 200, and 300-mg daily doses, respectively. At steady state, the expected proportion with QTcF>30 ms was 23.7% and for absolute QTcF>450 ms was 3.42% for all simulated regimens.
Conclusions
The use of loading doses of 200 and 300 mg is not predicted to expose patients to increased risk of QT prolongation, compared to the current standard treatment, and is, therefore, an alternative option to achieve therapeutic concentrations faster.
Læs mere Tjek på PubMedKovacikova, K., Gonzalez, M. G., Jones, R., Reguera, J., Gigante, A., Perez-Perez, M.-J., Pürstinger, G., Moesslacher, J., Langer, T., Jeong, L. S., Delang, L., Neyts, J., Snijder, E. J., van Westen, G. J. P., van Hemert, M. J.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Chikungunya virus (CHIKV) nonstructural protein 1 (nsP1) harbours the methyltransferase (MTase) and guanylyltransferase (GTase) activities needed for viral RNA capping and represents a promising antiviral drug target. We compared the antiviral efficacy of nsP1 inhibitors belonging to the MADTP, CHVB and FHNA series [6’-fluoro-homoneplanocin A (FHNA), its 3’-keto form and 6'-β-Fluoro-homoaristeromycin]. Cell-based phenotypic cross-resistance assays revealed that the CHVB and MADTP series shared a similar mode of action that differed from that of the FHNA series. In biochemical assays with purified Semliki Forest virus and CHIKV nsP1, CHVB compounds strongly inhibited MTase and GTase activities, while MADTP-372 had a moderate inhibitory effect. FHNA did not directly inhibit enzymatic activity of CHIKV nsP1. The first of its kind molecular docking studies with the cryo-EM structure of CHIKV nsP1, which is assembled into a dodecameric ring, revealed that the MADTP and CHVB series bind at the SAM-binding site in the capping domain, where they would function as (non)competitive inhibitors. The FHNA series was predicted to bind at the secondary binding pocket in the Ring-Aperture Membrane-Binding and Oligomerization domain, potentially interfering with membrane binding and oligomerization of nsP1. Our cell-based and enzymatic assays, in combination with molecular docking and mapping of compound-resistance mutations to the nsP1 structure allowed us to group nsP1 inhibitors into functionally distinct classes. This study identified druggable pockets in the nsP1 dodecameric structure and provides a basis for rational design, optimization and combination of inhibitors of this unique and promising antiviral drug target.
Læs mere Tjek på PubMedLizza, B. D., Betthauser, K. D., Ritchie, D. J., Micek, S. T., Kollef, M. H.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/β-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intra-abdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of this data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when P. aeruginosa isolates are identified with resistance to other beta-lactams. C/T can also be used empirically at BJH prior to microbiologic detection of an antibiotic-resistant P. aeruginosa isolate in specific clinical situations. These situations include critically ill patients in the ICU setting where there is a high likelihood of infection with multidrug-resistant (MDR) P. aeruginosa including patients failing therapy with a carbapenem, specific patient populations known to be at high risk for infection with MDR P. aeruginosa (e.g., lung transplant and cystic fibrosis patients), and patients know to have previous infection or colonization with MDR P. aeruginosa.
Læs mere Tjek på PubMedDickie, E. A., Ronin, C., Sa, M., Ciesielski, F., Trouche, N., Tavares, J., Santarem, N., Major, L. L., Pemberton, I. K., MacDougall, J., Smith, T. K., Cordeiro-da-Silva, A., Ciapetti, P.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Neglected tropical diseases caused by kinetoplastid parasites (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) place a significant health and economic burden on developing nations worldwide. Current therapies are largely out-dated, inadequate and facing mounting drug resistance from the causative parasites. Thus, there is an urgent need for drug discovery and development. Target-led drug discovery approaches have focused on the identification of parasite enzymes catalysing essential biochemical processes, which significantly differ from equivalent proteins found in humans, thereby providing potentially exploitable therapeutic windows. One such target is ribose 5-phosphate isomerase B (RpiB), an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, which catalyses the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Although protozoan RpiB has been the focus of numerous targeted studies, compounds capable of selectively inhibiting this parasite enzyme have not been identified. Here, we present the results of a fragment library screening against Leishmania infantum RpiB, performed using thermal shift analysis. Hit fragments were shown to be effective inhibitors of LiRpiB in activity assays, and several were capable of selectively inhibiting parasite growth in vitro. These results support the identification of LiRpiB as a validated therapeutic target. The X-ray crystal structure of apo LiRpiB was also solved, permitting docking studies to assess how hit fragments might interact with LiRpiB to inhibit its activity. Overall, this work will guide structure-based development of LiRpiB inhibitors as anti-leishmanial agents.
Læs mere Tjek på PubMedLam, H. N., Lau, T., Lentz, A., Sherry, J., Cabrera-Cortez, A., Hug, K., Lalljie, A., Engel, J., Lokey, R. S., Auerbuch, V.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Antibiotic resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the Yersinia Ysc and Pseudomonas aeruginosa Psc T3SSs, but do not inhibit bacterial growth. Here we describe identification of an isomer, 4EpDN, that is two-fold more potent (IC50 of 4 μM) than its parental compound. Furthermore, 4EpDN inhibited the Yersinia Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells, which requires the T3SS. 4EpDN did not inhibit the unrelated Twin arginine translocation (Tat) system, nor did it impact T3SS gene transcription. Moreover, although the injectisome and flagellar T3SSs are evolutionarily and structurally related, the 4EpDN cyclic peptomer did not inhibit secretion of substrates through the Salmonella flagellar T3SS, indicating that cyclic peptomers broadly but specifically target the injestisome T3SS. 4EpDN reduced the number of T3SS needles detected on the surface of Y. pseudotuberculosis as detected by microscopy. Collectively, these data suggest that cyclic peptomers specifically inhibit the injectisome T3SS from a variety of Gram-negative bacteria, possibly by preventing complete T3SS assembly.
Læs mere Tjek på PubMedRhodes, N. J., Jozefczyk, C. C., Moore, W. J., Yarnold, P. R., Harkabuz, K., Maxwell, R., Sutton, S. H., Silkaitis, C., Qi, C., Wunderink, R. G., Zembower, T. R.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Objective: Hospitalized patients with community-acquired pneumonia (CAP) are at risk of developing Clostridioides difficile infection (CDI). We developed and tested clinical decision-rules for identifying CDI risk in this patient population.
Methods: The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between January 1, 2014 and March 3, 2018. Differences between cases (CDI diagnosed within 180 days following admission) and controls (no test result indicating CDI during the study period) with respect to pre-hospitalization variables were modeled to generate propensity scores. Post-admission variables were used to predict case status on each post-admission day where: a) ≥1 additional case was identified, and b) each model strata contained ≥15 subjects. Models were developed and tested using Optimal Discriminant Analysis and Classification Tree Analysis.
Results: Forty-four cases and 181 controls were included. The median time to diagnosis was 50 days post-admission. After weighting, three models were identified (20-, 117-, and 165-days post-admission). The day 20 model yielded the greatest [weighted (w)] accuracy (wROC area=0.826) and the highest chance-corrected accuracy (wESS=65.3). Having a positive culture (odds 1:4, p=0.001), receipt of ceftriaxone + azithromycin for a defined infection (odds 3:5, p=0.006), and continuation of empiric broad-spectrum antibiotics with activity against P. aeruginosa when no pathogen was identified (odds 1:8, p=0.013) were associated with CDI on day 20.
Conclusion: Three models were identified that accurately predicted CDI in hospitalized patients treated for CAP. Antibiotic use increased the risk of CDI in all models, underscoring the importance of antibiotic stewardship.
Læs mere Tjek på PubMedZarrouk, K., Zhu, X., Pham, V. D., Goyette, N., Piret, J., Shi, R., Boivin, G.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Amino acid substitutions conferring resistance of herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) to foscarnet (PFA) are respectively located in UL30 and UL54 genes encoding the DNA polymerase (pol). In this study, we analyzed the impact of substitutions located in helix K and region II that are involved in the conformational changes of the DNA pol. Theoretical substitutions were identified by sequences alignment of the helix K and region II of human herpesviruses (susceptible to PFA) and bacteriophages (resistant to PFA) and introduced in viral genomes by recombinant phenotyping. We characterized the susceptibility of HSV-1 and HCMV mutants to PFA. In UL30, substitutions I619K (helix K), V715S and A719T (both in region II) increased mean PFA EC50 by 2.5-, 5.6- and 2.0-fold compared to wild type (WT), respectively. In UL54, substitution Q579I (helix K) conferred hypersusceptibility to PFA (0.17-fold change) whereas substitutions Q697P, V715S and A719T (all in region II) increased mean PFA EC50 values by 3.8-, 2.8- and 2.5-fold compared to WT, respectively. These results were confirmed by enzymatic assays using recombinant DNA pol harboring these substitutions. Three-dimensional modeling suggests that substitutions conferring resistance/hypersusceptibility to PFA located in helix K and region II of UL30 and UL54 DNA pol favor an open/closed conformation of these enzymes resulting in a lower/higher drug affinity for the proteins. Thus, this study shows that both regions of UL30 and UL54 DNA pol are involved in the conformational changes of these proteins and can influence the susceptibility of both viruses to PFA.
Læs mere Tjek på PubMedPernaute-Lau, L., Adegnika, A. A., Zhou, Y., Zinsou, J. F., Gil, J. P., Krishna, S., Kremsner, P. G., Lauschke, V. M., Velavan, T. P.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Malaria remains one of the most deadly diseases in Africa, particularly for children. While successful in reducing morbidity and mortality, antimalarial treatments are also a major cause of adverse drug reactions (ADRs). Host genetic variation in genes involved in drug disposition or toxicity constitutes an important determinant of ADR risk and can prime for parasite drug resistance. Importantly however, the genetic diversity in Africa is substantial and thus genetic profiles in one population cannot be reliably extrapolated to other ethnogeographic groups. Gabon is considered a high-transmission country with more than 460,000 malaria cases per year. Yet, the pharmacogenetic landscape of the Gabonese population or its neighboring countries has not been analyzed. Using targeted sequencing, we here profiled 21 pharmacogenes with importance for antimalarial treatment in 48 Gabonese pediatric patients with severe Plasmodium falciparum malaria. Overall, we identified 347 genetic variants of which 18 were novel and each individual was found to carry 87.3±9.2 SD variants across all analyzed genes. Importantly, 16.7% of these variants were population-specific, highlighting the need for high-resolution pharmacogenomic profiling. Between one in three and one in six individuals harbored reduced activity alleles of CYP2A6, CYP2B6, CYP2D6 and CYP2C8 with important implications for artemisinin, chloroquine and amodiaquine therapy. Furthermore, one in three patients harbored at least one G6PD deficient allele, suggesting considerably increased risk of hemolytic anemia upon exposure to aminoquinolines. Combined, our results reveal the unique genetic landscape of the Gabonese population and pinpoint the genetic basis for inter-individual differences in antimalarial drug response and toxicity.
Læs mere Tjek på PubMedBuehrle, D. J., Wagener, M. M., Clancy, C. J.
Antimicrobial Agents And Chemotherapy, 19.04.2021
Tilføjet 20.04.2021
Background: The impact of United States (US) Food and Drug Administration (FDA) safety warnings on outpatient fluoroquinolone use is unclear.
Methods: Annual changes in outpatient ciprofloxacin, levofloxacin and moxifloxacin prescription fills (IQVIA National Prescription Audit databases) were assessed using a regression model. Monthly fills during baseline (August 2014–April 2016), first (May 2016–June 2018), and second FDA warning periods (July 2018–February 2020) were compared by interrupted time series analysis.
Results: From 2015 through 2019, total fluoroquinolone fills decreased from 35,616,786 (111.1/1000 persons) to 21,100,050 (64.3/1000 persons) annually (10.8% annually (P=0.001)). Ciprofloxacin, levofloxacin, and moxifloxacin fills decreased annually by 10.4% (P=0.001), 11.2% (P<0.001), and 17.7% (P=0.008), respectively. During the baseline period, there was no significant change in monthly fluoroquinolone fills. In May 2016 and during the first warning period, monthly fluoroquinolone fills decreased significantly (P-values<0.001); the trend of decreased fills was significantly greater than that of the baseline period (P=0.02). There was no change in fluoroquinolone fills in July 2018. Monthly fills decreased significantly throughout the second warning period (P<0.001), but the trend did not differ from that of the first warning period. Trends for ciprofloxacin, the most commonly prescribed fluoroquinolone, were similar to those for the class. Fills of prescriptions by infectious diseases specialists (P<0.005) and nurse practitioners (P=0.04) significantly increased during the study.
Conclusions: US outpatient fluoroquinolone prescription fills significantly decreased from August 2014-February 2020, most strongly in association with May 2016 FDA warnings. FDA safety warnings are useful tools for leveraging outpatient antimicrobial stewardship.
Læs mere Tjek på PubMedSarah C Gilbert, Teresa Lambe
Lancet Infectious Diseases, 20.04.2021
Tilføjet 20.04.2021
The development of vaccines against SARS-CoV-2 has proceeded at an unprecedented pace, resulting in emergency use approvals and accelerated deployment of multiple vaccines. This development and deployment has occurred within a year of the Public Health Emergency of International Concern declaration by WHO. However, some attempts to develop vaccines have run into difficulties in early clinical development.
Læs mere Tjek på PubMedStephen Obaro
Lancet Infectious Diseases, 20.04.2021
Tilføjet 20.04.2021
The scourge of COVID-19 has been global, but the most affected subgroups in the population have largely been older people and individuals with comorbid conditions that predispose them to increasingly severe disease and poor outcomes. Overall, the disease burden in children has been reasonably mild, even in those with comorbidities, such as oncological conditions. Protection from severe disease in children might be related to a lower expression of host factors required for viral replication, and to differences in the magnitude and timing of innate or adaptive immune responses.
Læs mere Tjek på PubMedKeith J Chappell, Francesca L Mordant, Zheyi Li, Danushka K Wijesundara, Paula Ellenberg, Julia A Lackenby, Stacey T M Cheung, Naphak Modhiran, Michael S Avumegah, Christina L Henderson, Kym Hoger, Paul Griffin, Jillian Bennet, Luca Hensen, Wuji Zhang, Thi H O Nguyen, Sara Marrero-Hernandez, Kevin J Selva, Amy W Chung, Mai H Tran, Peter Tapley, James Barnes, Patrick C Reading, Suellen Nicholson, Stavroula Corby, Thomas Holgate, Bruce D Wines, P Mark Hogarth, Katherine Kedzierska, Damian F J Purcell, Charani Ranasinghe, Kanta Subbarao, Daniel Watterson, Paul R Young, Trent P Munro
Lancet Infectious Diseases, 20.04.2021
Tilføjet 20.04.2021
This first-in-human trial shows that a subunit vaccine comprising mammalian cell culture-derived, MF59-adjuvanted, molecular clamp-stabilised recombinant spike protein elicits strong immune responses with a promising safety profile. However, the glycoprotein 41 peptide present in the clamp created HIV diagnostic assay interference, a possible barrier to widespread use highlighting the criticality of potential non-spike directed immunogenicity during vaccine development. Studies are ongoing with alternative molecular clamp trimerisation domains to ameliorate this response.
Læs mere Tjek på PubMedPaul A Goepfert, Bo Fu, Anne-Laure Chabanon, Matthew I Bonaparte, Matthew G Davis, Brandon J Essink, Ian Frank, Owen Haney, Helene Janosczyk, Michael C Keefer, Marguerite Koutsoukos, Murray A Kimmel, Roger Masotti, Stephen J Savarino, Lode Schuerman, Howard Schwartz, Lawrence D Sher, Jon Smith, Fernanda Tavares-Da-Silva, Sanjay Gurunathan, Carlos A DiazGranados, Guy de Bruyn
Lancet Infectious Diseases, 20.04.2021
Tilføjet 20.04.2021
The lower than expected immune responses, especially in the older age groups, and the high reactogenicity after dose two were probably due to higher than anticipated host-cell protein content and lower than planned antigen doses in the formulations tested, which was discovered during characterisation studies on the final bulk drug substance. Further development of the AS03-adjuvanted candidate vaccine will focus on identifying the optimal antigen formulation and dose.
Læs mere Tjek på PubMedDavid L. Hahn
PLoS One Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
by David L. Hahn
Background Chlamydia pneumoniae (Cp) is an obligate intracellular human respiratory pathogen producing persisting lung infection with a plausible link to asthma pathogenesis. The population attributable risk of potentially treatable Cp infection in asthma has not been reported.
Methods The author searched from 2000 to 2020 inclusive for previously un-reviewed and new cross sectional and prospective controlled studies of Cp biomarkers and chronic asthma in both children and adults. Qualitative descriptive results and quantitative estimates of population attributable risk for selected biomarkers (specific IgG, IgA and IgE) are presented.
Findings No large, long-term prospective population-based studies of Cp infection and asthma were identified. About half of case-control studies reported one or more significant associations of Cp biomarkers and chronic asthma. Heterogeneity of results by age group (pediatric v adult asthma), severity category (severe/uncontrolled, moderate/partly controlled, mild/controlled) and antibody isotype (specific IgG, IgA, IgE) were suggested by the qualitative results and confirmed by meta-analyses. The population attributable risks for Cp-specific IgG and IgA were nul in children and were 6% (95% confidence interval 2%-10%, p = 0.002) and 13% (9%-18%, p<0.00001) respectively in adults. In contrast to the nul or small population attributable risks for Cp-specific IgG and IgA, the population attributable risk for C. pneumoniae-specific IgE (children and adults combined) was 47% (39%-55%, p<0.00001). In the subset of studies that reported on asthma severity categories, Cp biomarkers were positively and significantly (p<0.00001) associated with asthma severity.
Interpretation C. pneumoniae-specific IgE is strongly associated with asthma and asthma severity, suggesting a possible mechanism linking chronic Cp infection with asthma in a subset of individuals with asthma. Infection biomarkers should be included in future macrolide treatment trials for severe and uncontrolled asthma.
Læs mere Tjek på PubMedUgochinyere Ijeoma Nwagbara, Emmanuella Chinonso Osual, Rumbidzai Chireshe, Obasanjo Afolabi Bolarinwa, Balsam Qubais Saeed, Nelisiwe Khuzwayo, Khumbulani W. Hlongwana
PLoS One Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
by Ugochinyere Ijeoma Nwagbara, Emmanuella Chinonso Osual, Rumbidzai Chireshe, Obasanjo Afolabi Bolarinwa, Balsam Qubais Saeed, Nelisiwe Khuzwayo, Khumbulani W. Hlongwana
Background Knowledge, attitudes, perception, and preventative practices regarding coronavirus- 2019 (COVID-19) are crucial in its prevention and control. Several studies have noted that the majority of people in sub-Saharan African are noncompliant with proposed health and safety measures recommended by the World Health Organization (WHO) and respective country health departments. In most sub-Saharan African countries, noncompliance is attributable to ignorance and misinformation, thereby raising questions about people™s knowledge, attitudes, perception, and practices towards COVID-19 in these settings. This situation is particularly of concern for governments and public health experts. Thus, this scoping review is aimed at mapping evidence on the knowledge, attitudes, perceptions, and preventive practices (KAP) towards COVID-19 in sub-Saharan Africa (SSA).
Methods Systematic searches of relevant articles were performed using databases such as the EBSCOhost, PubMed, Science Direct, Google Scholar, the WHO library and grey literature. Arksey and O™Malley™s framework guided the study. The risk of bias for included primary studies was assessed using the Mixed Method Appraisal Tool (MMAT). NVIVO version 10 was used to analyse the data and a thematic content analysis was used to present the review™s narrative account.
Results A total of 3037 eligible studies were identified after the database search. Only 28 studies met the inclusion criteria after full article screening and were included for data extraction. Studies included populations from the following SSA countries: Ethiopia, Nigeria, Cameroon, Uganda, Rwanda, Ghana, Democratic Republic of Congo, Sudan, and Sierra Leone. All the included studies showed evidence of knowledge related to COVID-19. Eleven studies showed that participants had a positive attitude towards COVID-19, and fifteen studies showed that participants had good practices towards COVID-19.
Conclusions Most of the participants had adequate knowledge related to COVID-19. Despite adequate knowledge, the attitude was not always positive, thereby necessitating further education to convey the importance of forming a positive attitude and continuous preventive practice towards reducing contraction and transmission of COVID19.
Læs mere Tjek på PubMedAdam Palayew, Alexandra M. Schmidt, Sahar Saeed, Curtis L. Cooper, Alexander Wong, Valérie Martel-Laferrière, Sharon Walmsley, Joseph Cox, Marina B. Klein, for the Canadian Coinfection Cohort Study Investigators
PLoS One Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
by Adam Palayew, Alexandra M. Schmidt, Sahar Saeed, Curtis L. Cooper, Alexander Wong, Valérie Martel-Laferrière, Sharon Walmsley, Joseph Cox, Marina B. Klein, for the Canadian Coinfection Cohort Study Investigators
Background HIV-HCV coinfected individuals are often more deprived than the general population. However, deprivation is difficult to measure, often relying on aggregate data which does not capture individual heterogeneity. We developed an individual-level deprivation index for HIV-HCV co-infected persons that encapsulated social, material, and lifestyle factors.
Methods We estimated an individual-level deprivation index with data from the Canadian Coinfection Cohort, a national prospective cohort study. We used a predetermined process to select 9 out of 19 dichotomous variables at baseline visit to include in the deprivation model: income >$1500/month; education >high school; employment; identifying as gay or bisexual; Indigenous status; injection drug use in last 6 months; injection drug use ever; past incarceration, and past psychiatric hospitalization. We fitted an item response theory model with: severity parameters (how likely an item was reported), discriminatory parameters, (how well a variable distinguished index levels), and an individual parameter (the index). We considered two models: a simple one with no provincial variation and a hierarchical model by province. The Widely Applicable Information Criterion (WAIC) was used to compare the fitted models. To showcase a potential utility of the proposed index, we evaluated with logistic regression the association of the index with non-attendance to a second clinic visit (as a proxy for disengagement) and using WAIC compared it to a model containing all the individual parameters that compose the index as covariates.
Results We analyzed 1547 complete cases of 1842 enrolled participants. According to the WAIC the hierarchical model provided a better fit when compared to the model that does not consider the individual™s province. Values of the index were similarly distributed across the provinces. Overall, past incarceration, education, and unemployment had the highest discriminatory parameters. However, in each province different components of the index were associated with being deprived reflecting local epidemiology. For example, Saskatchewan had the highest severity parameter for Indigenous status while Quebec the lowest. For the secondary analysis, 457 (30%) failed to attend a second visit. A one-unit increase in the index was associated with 17% increased odds (95% credible interval, 2% to 34%) of not attending a second visit. The model with just the index performed better than the model with all the components as covariates in terms of WAIC.
Conclusion We estimated an individual-level deprivation index in the Canadian Coinfection cohort. The index identified deprivation profiles across different provinces. This index and the methodology used may be useful in studying health and treatment outcomes that are influenced by social disparities in co-infected Canadians. The methodological approach described can be used in other studies with similar characteristics.
Læs mere Tjek på PubMedGeorge Edwards, Louise Newbould, Charlotte Nesbitt, Miranda Rogers, Rebecca L. Morris, Alastair D. Hay, Stephen M. Campbell, Gail Hayward
PLoS One Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
by George Edwards, Louise Newbould, Charlotte Nesbitt, Miranda Rogers, Rebecca L. Morris, Alastair D. Hay, Stephen M. Campbell, Gail Hayward
Background Demand for NHS services is high and rising. In children respiratory tract infections (RTI) are the most common reason for consultation with primary care. Understanding which features are associated with good and poor prognosis with RTI will help develop interventions to support parents manage illness.
Aim To identify symptoms, signs, and investigation results associated with good and poor prognosis, and clinical decision making in children aged 1-12 years with RTI symptoms, at home and presenting to ambulatory care.
Design and setting Systematic literature review.
Methods We searched MEDLINE, EMBASE, Cinahl, Web of Science and the Cochrane database of systematic reviews for studies of children aged 1 to 12 years with a RTI or related condition reporting symptoms, signs and investigation results associated with prognostic outcomes. Quality was assessed using the QUIPS tool.
Results We included 27 studies which included 34802 children and measured 192 factors. Nine studies explored future outcomes and the remainder explored clinical management from the initial consultation with the health services. None were conducted in a home setting. Respiratory signs, vomiting, fever, dehydration and tachycardia at the initial contact were associated with future hospitalisation. Little evidence was available for other outcomes.
Conclusion Some evidence is available to clinicians to stratify risk of, future hospitalisation, but not of other prognostic outcomes. There is little evidence available to parents to identify children at risk of poor prognosis. Research is needed into whether poor prognosis can be predicted by parents in the home.
Læs mere Tjek på PubMedCalderaro, A., Buttrini, M., Martinelli, M., Montecchini, S., Covan, S., Ruggeri, A., Rodighiero, I., Di Maio, A., Galullo, M., Larini, S., Arcangeletti, M. C., Chezzi, C., De Conto, F.
BMJ Open, 19.04.2021
Tilføjet 19.04.2021
Objectives
The distribution of carbapenemase-producing Klebsiella pneumoniae (CPKP) phenotypes and genotypes in samples collected during 2011–2018 was evaluated. The association between patients with CPKP-positive rectal swab and those with CPKP infection, as well as the overall analysis of CPKP-infected patients, was performed.
Setting
The study was performed in a tertiary-care hospital located in Northern Italy.
Participants
Two groups were considered: 22 939 ‘at-risk’ patients submitted to active surveillance for CPKP detection in rectal swabs/stools and 1094 CPKP-infected patients in which CPKP was detected in samples other than rectal swabs.
Results
CPKP-positive rectal swabs were detected in 5% (1150/22 939). A CPKP infection was revealed in 3.1% (719/22 939) of patients: 582 with CPKP-positive rectal swab (50.6% of the 1150 CPKP-positive rectal swabs) and 137 with CPKP-negative rectal swab. The 49.4% (568/1150) of the patients with CPKP-positive rectal swab were carriers. The overall frequency of CPKP-positive patients (carriers and infected) was almost constant from 2012 to 2016 (excluding the 2015 peak) and then increased in 2017–2018. blaKPC was predominant followed by blaVIM. No difference was observed in the frequency of CPKP-positive rectal swab patients among the different material groups. Among the targeted carbapenemase genes, blaVIM was more significantly detected from urine than from other samples.
Conclusions
The high prevalence of carriers without evidence of infection, representing a potential reservoir of CPKP, suggests to maintain the guard about this problem, emphasising the importance of active surveillance for timely detection and separation of carriers, activation of contact precautions and antibiotic treatment guidance on suspicion of infection.
Læs mere Tjek på PubMedOliveira, C. R., Ortiz, A. M., Sheth, S. S., Shapiro, E. D., Niccolai, L. M.
BMJ Open, 19.04.2021
Tilføjet 19.04.2021
Introduction
In 2006, the first human papillomavirus (HPV) vaccine was approved by the Food and Drug Administration in the USA based on pre-licensure clinical trials that found it to be highly efficacious at preventing persistent infection and precancerous, high-grade cervical lesions (HGCLs) caused by viral types the vaccine protects against. However, the real-world effectiveness of HPV vaccines as used in clinical practice may be quite different from the efficacy found in pre-licensure clinical trials. More than 10 years have passed since the introduction of the vaccine programme. It is critical to determine if the full benefits of HPV are being realised in real-world settings.
Methods and analysis
The objectives of this study were to estimate the effectiveness of HPV vaccines as used in real-world clinical settings and to determine the degree to which the vaccine’s effectiveness varies based on age at the time of immunisation and the number of doses received. The study will be a population-based, matched case–control study. Cases will be women with newly diagnosed HGCL associated with HPV types 16 and 18. Matched controls will be women with a normal Pap test result, matched individually to cases in a 2:1 ratio by age, a practice and date of testing. Medical records will be reviewed to determine dates of receipt of the HPV vaccine for all participants. We will use multivariate conditional logistic regression to control for potential confounders.
Ethics and dissemination
This protocol presents minimal risk to the subjects. This protocol has received approval from the Institutional Review Board of Yale University (HIC: 1502015308), and a Health Insurance Portability and Accountability Act (HIPAA) Waiver of Authorisation has been granted to allow investigators to recruit subjects for the study. Findings will be disseminated through peer-reviewed, open-access scientific journals and conference presentations.
Læs mere Tjek på PubMedDayem Ullah, A. Z. M., Sivapalan, L., Kocher, H. M., Chelala, C.
BMJ Open, 19.04.2021
Tilføjet 19.04.2021
Objective
To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato–pancreato–biliary (HPB) conditions.
Design
Cross-sectional study.
Setting
East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.
Participants
EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.
Main outcome measure
COVID-19 incidence and mortality.
Results
Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).
Conclusions
In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.
Læs mere Tjek på PubMedAlison Farrell
Nature, 19.04.2021
Tilføjet 19.04.2021
Nature Medicine, Published online: 19 April 2021; doi:10.1038/d41591-021-00020-w
Feeding the gut microbiota aids growth in undernourished children.
Læs mere Tjek på PubMedMonette Zard, Ling San Lau, Diana M. Bowser, Fouad M. Fouad, Diego I. LucumÃ, Goleen Samari, Arturo Harker, Donald S. Shepard, Wu Zeng, Rachel T. Moresky, Mhd Nour Audi, Claire M. Greene, S. Patrick Kachur
Nature, 19.04.2021
Tilføjet 19.04.2021
Nature Medicine, Published online: 19 April 2021; doi:10.1038/s41591-021-01328-3
Ensuring access to vaccines against COVID-19 for refugee and displaced populations and addressing health inequities are vital for an effective pandemic response.
Læs mere Tjek på PubMedEmerging Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
BMC Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
Abstract
Background
Since the outbreak of COVID-19 pandemic, clinical data from various parts of the world have been reported. Up till now, there has been no clinical data with regards to COVID-19 from Bosnia and Herzegovina (B&H). The aim was to report on the first cohort of patients from B&H and to analyze factors that influence COVID-19 patient™s length of hospitalization (LOH).
Methods
This retrospective cohort study was conducted at Tuzla University Clinical Center (UKC), B&H. It involved 25 COVID-19 positive patients that needed hospitalisation between March 28th and April 27th 2020. The LOH was measured from the time of admission to discharge. Factors analyzed induced age, BMI, presence of known comorbidities, serum creatinine and O2 saturation upon admission.
Results
The mean age was 52.92‰±‰19.15‰years and BMI 28.80‰±‰4.22. LOH for patients with BMI <‰25 was 9‰±‰SE2.646‰days (CI 95% 3.814-14.816) vs 14.182‰±‰SE .937 (CI 95% 12.346-16.018 p <‰0.05; HR 5.148 CI95% 1.217 to 21.772 p =‰0.026) for ≥25 BMI. The mean LOH of patients with normal levels of O2 ≥‰95% was 11.667‰±‰SE1.202 (CI95% 8.261 to 13.739; p =‰0.046), while LOH for patients with <‰95% was 14.625‰±‰SE 1.231 CI95% 12.184 to 16.757 p =‰0.042; HR 3.732 CI95%1.137-12.251 p =‰0.03). Patients without known comorbidities had a mean LOH of 11.700‰±‰SE1.075 (CI 95% 9.592-13.808), while those with comorbidities had a mean of 14.8‰±‰1.303 (CI 95% 12.247-17.353; p =‰0.029) with HR2.552.
Conclusion
LOH varied among COVID-19 patients and was prolonged when analyzed for BMI ≥25, comorbidities, elevated creatinine, and O2 saturation‰<‰95%. Furthermore, risk factors for COVID-19 patients in B&H do not deviate from those reported in other countries.
Læs mere Tjek på PubMedVictoria Birlutiu, Alin Iulian Feiereisz, George Oprinca, Simona Dobritoiu, Maria Rotaru, Rares Mircea Birlutiu, Gabriela Mariana Iancu
International Journal of Infectious Diseases, 19.04.2021
Tilføjet 19.04.2021
The expression levels of the ACE2 receptors in various human tissues may be responsible for the pathogenesis of SARS-CoV-2 infection. The presence of ACE2 receptors in the respiratory system, cardiovascular system, digestive tract (esophageal mucosa, ileum), kidneys and uroepithelium explains their involvement in the context of SARS-CoV-2 infection. Skin involvement in the severe acute respiratory syndrome coronavirus 2 infection has been clinically and histopathological incompletely studied. The Academic Emergency Hospital Sibiu, Romania, was involved from the beginning in the treatment of SARS-CoV-2 infected patients.
Læs mere Tjek på PubMedM. Isabel GarcÃaLaorden, Arie J. Hoogendijk, Maryse A. Wiewel, Lonneke A. van Vught, Marcus J. Schultz, Niels Bovenschen, Alex F. de Vos, Tom van der Poll
Clinical & Experimental Immunology, 18.04.2021
Tilføjet 19.04.2021
Manuel Othoniel LópezTorres, Brenda MarquinaCastillo, Octavio RamosEspinosa, Dulce MataEspinosa, Jorge A. BarriosPayan, Guillermina BaayGuzman, Sara Huerta Yepez, Estela Bini, Ivan TorreVillalvazo, Nimbe Torres, Armando Tovar, William Chamberlin, Yu Ge, Andrea Carranza, Rogelio HernándezPando
Clinical & Experimental Immunology, 18.04.2021
Tilføjet 19.04.2021
Emily Treleaven, Caroline Whidden, Faith Cole, Kassoum Kayentao, Mohamed Bana Traoré, Djoumé Diakité, Seydou Sidibé, Tracy Kuo Lin, David Boettiger, Souleymane Cissouma, Vincent Sanogo, Nancy Padian, Ari Johnson, Jenny Liu
Tropical Medicine & International Health, 18.04.2021
Tilføjet 19.04.2021
Hagai Rossman, Smadar Shilo, Tomer Meir, Malka Gorfine, Uri Shalit, Eran Segal
Nature, 19.04.2021
Tilføjet 19.04.2021
Nature Medicine, Published online: 19 April 2021; doi:10.1038/s41591-021-01337-2
A retrospective analysis of data from the Israeli Ministry of Health collected between 28 August 2020 and 24 February 2021 documents the real-life effect of a national vaccination campaign on the pandemic dynamics.
Læs mere Tjek på PubMedPere Domingo, Virgina Pomar, Isabel Mur, Ivan CastellvÃ, Héctor Corominas, Natividad de Benito
Clinical Microbiology and Infection, 18.04.2021
Tilføjet 19.04.2021
We aimed to assess differences in patients™ profiles in the first two surges of the SARS-CoV-2 pandemic in Barcelona, Spain.
Læs mere Tjek på PubMedGabriela Abelenda-Alonso, Alexander Rombauts, Núria Burguillos, Jordi CarratalÃ
Clinical Microbiology and Infection, 18.04.2021
Tilføjet 19.04.2021
Air pollution and antimicrobial resistance are two of the most important public health problems facing the world today. Although the harmful effects of air pollution have been known at least since the beginning of the twentieth century, governments and economic leaders around the world remain reluctant to comply with international agreements drawn up to reduce the emission of air pollutants and greenhouse gases. A statistic that arouses particular concern is the fact that, in 2019 according to the 2020 State of Global Air report, air pollution moved up from the fifth to the fourth leading risk factor for mortality worldwide, with 6.67 million attributable deaths.
Læs mere Tjek på PubMed