PaperPlayer medrxiv infectious diseases PaperPlayer

Link to bioRxiv paper:
http://medrxiv.org/cgi/content/short/2023.07.29.23293322v1?rss=1

Authors: Rogier, E., Battle, N., Bakari, C., Seth, M. D., Nace, D., Herman, C., Madebe, R. A., Mandara, C. I., Lyimo, B. M., Giesbrecht, D. J., Popkin-Hall, Z. R., Francis, F., Mbwambo, D., Garimo, I., Aaron, S., Lusasi, A., Molteni, F., Njau, R., Cunningham, J. A., Lazaro, S., Mohamed, A., Juliano, J. J., Bailey, J. A., Udhayakumar, V., Ishengoma, D. S.

Abstract:
Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes greater than or equal to 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7,863 persons of all ages enrolled and providing RDT result and blood sample, 3,777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7,847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n=9) or only pfhrp3 (n=6). No dual pfhrp2/3 deleted parasites were observed. This survey estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC

Link to bioRxiv paper:
http://medrxiv.org/cgi/content/short/2023.07.28.23293338v1?rss=1

Authors: Mushebenge, A. G.-A., Ugbaja, S. C., Mbatha, N. A., Riziki, M. G., Muzumbukilwa, T. W., Kadima, M. G., Kumalo, H. M.

Abstract:
COVID-19 is a rapidly spreading infectious disease caused by the SARS-CoV-2 virus. Although several therapeutic interventions have been developed, the mortality rate of the disease remains high, and effective treatment options are urgently needed. Host-directed therapies targeting enzymes involved in the immune response represent a promising strategy for the development of novel therapeutics against COVID-19. This study aims to conduct a systematic review and meta-analysis of the literature to evaluate the potential of drug candidates targeting host enzymes involved in the immune response for the treatment of COVID-19. We will conduct a systematic search of electronic databases including PubMed, Embase, and Cochrane Library, as well as preprint servers and clinical trial registries for relevant studies. We will include randomized controlled trials, observational studies, and preclinical studies evaluating the efficacy of drug candidates targeting host enzymes involved in the immune response in COVID-19. Two reviewers will independently screen articles, extract data, and assess study quality. The primary outcome will be the effect of drug candidates on mortality, while secondary outcomes will include time to recovery, adverse events, and changes in immune markers. A meta-analysis will be performed to estimate pooled effect sizes of the interventions, and a narrative synthesis will be conducted for studies that are not amenable to quantitative analysis. This study will provide a comprehensive evaluation of the potential of host-directed therapies targeting enzymes involved in the immune response for the treatment of COVID-19. The results of this study may guide the development of novel therapeutics against COVID-19 and inform clinical practice.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC

Link to bioRxiv paper:
http://medrxiv.org/cgi/content/short/2023.07.28.23293335v1?rss=1

Authors: Yang, J., Andersen, K. M., Rai, K. K., Tritton, T., Mugwagwa, T., Tsang, C., Reimbaeva, M., McGrath, L., Payne, P., Backhouse, B. E., Mendes, D., Butfield, R., Wood, R., Nguyen, J. L.

Abstract:
Background Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial healthcare resource burden. This study aimed to describe healthcare resource utilization (HCRU) and costs associated with COVID-19 in pediatrics aged 1-17 years in England. Methods A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care (HES APC) secondary care data. HCRU and associated costs to the National Health Service (NHS) were stratified by age, risk of severe COVID-19, and immunocompromized status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). Results This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those aged 1-4 years (face-to-face: 4.3%; telephone: 6.0%) compared to those aged 5-11 (2.0%; 2.1%) and 12-17 years (2.2%; 2.5%). In the hospitalized cohort, mean [SD] length of stay was longer (5.0 [5.8] days) among those aged 12-17 years (n=24) than those aged 1-4 (n=15; 1.8 [0.9] days) and 5-11 years (n=21; 2.8 [2.1] days). Conclusions Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those aged 12-17 years. Our results may help optimize the management and resource allocation of COVID-19 in this population.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC

Link to bioRxiv paper:
http://medrxiv.org/cgi/content/short/2023.07.31.23293337v1?rss=1

Authors: Hurst, J. H., Mohan, A., Dalapati, T., George, I. A., Aquino, J. N., Lugo, D. J., Pfeiffer, T. S., Rodriguez, J., Rotta, A. T., Turner, N. A., Burke, T. W., McClain, M. T., Henao, R., DeMarco, C. T., Louzao, R., Denny, T. N., Walsh, K. M., Xu, Z., Mejias, A., Ramilo, O., Woods, C. W., Kelly, M. S.

Abstract:
Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC

Link to bioRxiv paper:
http://medrxiv.org/cgi/content/short/2023.07.29.23293373v1?rss=1

Authors: Kanki, P. J., Hamel, D. J., Riedel, S., Dutta, S., Cheng, A., Chang, C. A., Arnaout, R., Kirby, J. E.

Abstract:
The COVID-19 pandemic has presented unique diagnostic challenges including the need to store and test large number of samples for clinical and research studies. While SARS CoV-2 diagnosis relies on RT-qPCR and antigen testing, live virus culture remains an important surrogate for viral 'infectiousness', as we previously described in 'SARS-CoV-2 Antigen Tests Predict Infectivity Based on Viral Culture: Comparison of Antigen, PCR Viral Load and Viral Culture Testing on a Large Sample Cohort' (Clin Microbiol Infect, 2022, PMC9293398). Live virus isolation and characterization has also been important to the SARS CoV-2 research community, to assess viral fitness, cellular tropism, and live virus neutralization, particularly with the emergence of new variants. Many clinical and research studies make use of samples that are frozen in transport media and investigated at later dates. The effect of freezing on RT-qPCR results is well established. However, the effect of freeze-thaw on viral viability has not been. Here, we therefore examined the effect of freeze-thaw on viral culture isolation from a large number of clinical samples that were split, and then cultured either fresh or after being frozen for 7 or 17-18 days. Samples represented the range of viral loads (genome copies/mL) observed in our patient population. We found that freeze-thaw did not significantly affect viral culture isolation. Therefore, the ability to assess infectiousness of samples previously frozen in transport medium appears to be maintained.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC

Link to bioRxiv paper:
http://medrxiv.org/cgi/content/short/2023.08.02.23293478v1?rss=1

Authors: Macesic, N., Dennis, A., Hawkey, J., Vezina, B., Wisniewski, J. A., Cottingham, H., Blakeway, L. V., Harshegyi, T., Pragastis, K., Badoordeen, G. Z., Bass, P., Stewardson, A. J., Dennison, A., Spelman, D. W., Jenney, A. W. J., Peleg, A. Y.

Abstract:
Objectives: New Delhi metallo-beta-lactamases (NDMs) are major contributors to the spread of carbapenem resistance globally. In Australia, NDMs were previously associated with international travel but from 2019 we noted increasing NDM episodes. We conducted an investigation to determine the clinical and genomic epidemiology of NDM-carriage at a tertiary Australian hospital from 2016-2021. Methods: We identified 49 patients with 84 NDM-carrying isolates in an institutional database and collected clinical data from electronic medical records. Short- and long-read whole genome sequencing was performed on all isolates. Completed genome assemblies were used to assess the genetic setting of blaNDM genes and compare NDM plasmids. Results: Of 49 patients, 38 (78%) were identified in 2019-2021 and only 11/38 (29%) reported prior travel compared with 9/11 (82%) in 2016-2018 (P=0.037). In patients with NDM infection, crude 7-day mortality was 0% and 30-day mortality was 14% (2/14 patients). NDMs were noted in 41 bacterial strains (i.e. species/sequence type combinations). Four NDM variants (blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7) were detected across 13 plasmid groups. We noted a change from a diverse NDM plasmid repertoire in 2016-2018 to the emergence of conserved blaNDM-1 IncN and blaNDM-7 IncX3 epidemic plasmids with inter-strain spread in 2019-2021. These plasmids were noted in 19/38 (50%) patients and 35/68 (51%) genomes in 2019-2021. Conclusions: Increased NDM case numbers were due to local circulation of two epidemic plasmids with extensive inter-strain transfer. Our study underscores the challenges of outbreak detection when horizontal transmission of plasmids is the primary mode of spread.

Copy rights belong to original authors. Visit the link for more info

Podcast created by Paper Player, LLC