Publications by authors named "Christopher T Williams"

Objectives: Evaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert® Mpox (Cepheid, Inc., USA) and STANDARD™ M10 MPX/OPX (SD Biosensor, Inc., Korea).

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The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs.

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Objectives: Neonatal sepsis, a major cause of death amongst infants in sub-Saharan Africa, is often gut derived. Gut colonisation by Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) or carbapenemase enzymes can lead to antimicrobial-resistant (AMR) or untreatable infections. We sought to explore the rates of colonisation by ESBL or carbapenemase producers in two neonatal units (NNUs) in West and East Africa.

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Article Synopsis
  • The study focuses on developing a low-cost method for extracting antimicrobial resistance genes (ARGs) from river water, as current environmental monitoring techniques are inconsistent.
  • A new magnetic bead-based method, called MagnaExtract, is introduced and tested against commercial kits and traditional methods, showing comparable or superior results for isolating ARGs.
  • The MagnaExtract technique is significant for enhancing environmental surveillance in East Africa, offering a simple and effective option for monitoring ARGs in water samples.
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Long-lasting insecticide-treated nets (LLINs) play a crucial role in preventing malaria transmission. LLINs should remain effective for at least three years, even after repeated washings. Currently, monitoring insecticides in LLINs is cumbersome, costly, and requires specialized equipment and hazardous solvents.

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Background: The emergence of variants of concern (VOCs) requires an ongoing assessment of the performance of antigen lateral flow tests (Ag-RDTs). The limit of detection (LOD) of 32 Ag-RDTs was evaluated using the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant.

Methods: Ag-RDTs were performed according to the manufacturer's instructions with a clinical isolate of the Gamma variant.

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Article Synopsis
  • * Found that the TZP-R/3GC-S phenotype appeared across various genetic sequences and had a diverse set of plasmids, suggesting multiple origins for the resistance rather than just one.
  • * Identified multiple mechanisms contributing to resistance, including increased production of specific enzymes and new mutations; emphasized the importance of ongoing monitoring to detect and predict these complex resistance patterns.
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Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells.

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Article Synopsis
  • - Recent research suggests that while pneumococci might increase COVID-19 risk, reports of co-infection in hospitalized patients are rare, possibly due to how these pathogens interact in the upper airway, affecting immune protection against SARS-CoV-2.
  • - The study examined health care workers and hospitalized patients to explore how the presence of Streptococcus pneumoniae impacts immune responses to SARS-CoV-2, particularly focusing on antiviral antibodies and cellular responses.
  • - Results indicated that pneumococcal colonization weakens immune defenses against SARS-CoV-2, particularly reducing levels of mucosal IgA in mild cases and affecting memory immune responses in more severe infections, raising concerns about potential immune evasion by other respiratory viruses as well
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Background: There are an abundance of commercially available lateral flow assays (LFAs) that detect antibodies to SARS-CoV-2. Whilst these are usually evaluated by the manufacturer, externally performed diagnostic accuracy studies to assess performance are essential. Herein we present an evaluation of 12 LFAs.

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Article Synopsis
  • The COVID-19 pandemic has led to increased use of antigen-detection rapid diagnostic tests (Ag-RDT), but their performance varies widely among manufacturers, highlighting the need for evaluation of their limits of detection (LOD).
  • This study evaluated the LOD of 19 Ag-RDTs using live SARS-CoV-2 samples in different conditions, including culture media and swabs stored at -80°C.
  • Fourteen Ag-RDTs met World Health Organization criteria for acceptable LOD, while six were incompatible with certain media and many showed reduced sensitivity after storage, providing important data for future test selection and evaluations.
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Objectives: This study aimed to develop and evaluate a novel air-dried high-resolution melt (HRM) assay to detect eight major extended-spectrum β-lactamase (ESBL) (bla and bla groups 1 and 9) and carbapenemase (bla, bla, bla, bla and bla) genes that confer resistance to cephalosporins and carbapenems.

Methods: The assay was evaluated using 439 DNA samples extracted from bacterial isolates from Nepal, Malawi and the UK and 390 clinical isolates from Nepal with known antimicrobial susceptibility. Assay reproducibility was evaluated across five different real-time quantitative PCR (qPCR) instruments [Rotor-Gene® Q, QuantStudio 5, CFX96, LightCycler® 480 and Magnetic Induction Cycler (Mic)].

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy in humans, is prevalent in tropical and subtropical areas where malaria is endemic. Anti-malarial drugs, such as primaquine and tafenoquine, can cause haemolysis in G6PD-deficient individuals. Hence, G6PD testing is recommended before radical treatment against vivax malaria.

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Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture, and the limited sensitivity of lateral flow tests. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative.

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The Food and Drug Administration (FDA) classifies herbal preparations as food supplements. New herbal supplements and products are not governed by the strict FDA drug approval process and there is no premarket approval required. The FDA prohibits manufacturers and distributors from marketing adulterated or misbranded products but does not rigorously define safe practices.

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Article Synopsis
  • - The study analyzed antibody responses (IgG) in 177 individuals with SARS-CoV-2 infection in London from March to May 2020, linking antibody levels to patient demographics and outcomes.
  • - Findings revealed that 2.0%-8.5% of participants did not develop antibodies after 3-6 weeks, and those who did were generally older, had more health issues, and higher inflammatory markers.
  • - Additionally, non-White participants had stronger antibody responses that persisted over time, suggesting that serologic assays could help monitor immune responses and inform public health strategies.
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PCR of upper respiratory specimens is the diagnostic standard for severe acute respiratory syndrome coronavirus 2 infection. However, saliva sampling is an easy alternative to nasal and throat swabbing. We found similar viral loads in saliva samples and in nasal and throat swab samples from 110 patients with coronavirus disease.

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Background: Plasmodium falciparum and Plasmodium vivax infections are important causes of adverse pregnancy outcomes in the Asia-Pacific region. We hypothesised that monthly intermittent preventive treatment (IPT) or intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine is more effective in reducing malaria in pregnancy than the existing single screening and treatment (SST) strategy, which is used to screen women for malaria infections at the first antenatal visit followed by passive case detection, with management of febrile cases.

Methods: We did an open-label, three-arm, cluster-randomised, superiority trial in Sumba (low malaria transmission site) and Papua (moderate malaria transmission site), Indonesia.

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Objectives: Chloramphenicol is a broad-spectrum antimicrobial widely available in sub-Saharan Africa. With susceptibility re-emerging among Enterobacteriaceae in Blantyre, Malawi, we designed and evaluated a new high-resolution melt (HRM) RT-PCR assay, ChloS-HRM, to identify chloramphenicol-susceptible infections in a hospital setting.

Methods: Seventy-two previously whole-genome sequenced isolates of Escherichia coli and Klebsiella pneumoniae from the Queen Elizabeth Central Hospital, Malawi, were subjected to determination of chloramphenicol MICs.

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An atomic- and molecular-level understanding of heterogeneous catalysis is required to characterize the nature of active sites and improve the rational design of catalysts. Achieving this level of characterization requires techniques that can correlate catalytic performances to specific surface structures, so as to avoid averaging effects. Tip-enhanced Raman spectroscopy combines scanning probe microscopy with plasmon-enhanced Raman scattering and provides simultaneous topographical and chemical information at the nano/atomic scale from ambient to ultrahigh-vacuum and electrochemical environments.

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Platinum catalysts are extensively used in the chemical industry and as electrocatalysts in fuel cells. Pt is notorious for its sensitivity to poisoning by strong CO adsorption. Here we demonstrate that the single-atom alloy (SAA) strategy applied to Pt reduces the binding strength of CO while maintaining catalytic performance.

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In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively.

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The precise control over the locations of hot spots in a nanostructured ensemble is of great importance in plasmon-enhanced spectroscopy, chemical sensing, and super-resolution optical imaging. However, for multiparticle configurations over metal films that involve localized and propagating surface plasmon modes, the locations of hot spots are difficult to predict due to complex plasmon competition and synergistic effects. In this work, theoretical simulations based on multiparticle-film configurations predict that the locations of hot spots can be efficiently controlled in the particle-particle gaps, the particle-film junctions, or in both, by suppressing or promoting specific plasmonic coupling effects in specific wavelength ranges.

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Taking advantage of the unique capacity of surface plasmon resonance, plasmon-enhanced heterogeneous catalysis has recently come into focus as a promising technique for high performance light-energy conversion. This work performs a theoretical study on the reaction mechanism for conversions of p-aminothiophenol (PATP) and p-nitrothiophenol (PNTP) to aromatic azo species, p,p'-dimercaptoazobenzene (DMAB). In the absence of O2 or H2, the plasmon-driven photocatalysis mechanism (hot electron-hole reactions) is the major reaction channel.

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