School of Pathology (Journal Articles)

Permanent URI for this collectionhttps://hdl.handle.net/10539/37877

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Start date: 2020

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Now showing 1 - 4 of 4
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    Opportunistic bacterial pathogens in bioaerosols emitted at municipal wastewater treatment plants, South Africa
    (Nature Research, 2025-03) Poopedi, Evida; Pierneef, Rian; Singh, Tanusha; Gomba, Annancietar
    Aeration tanks at wastewater treatment plants (WWTPs) emit significant amounts of bioaerosols containing potentially hazardous infectious material. Occupational exposure to airborne pathogens can pose health risks to WWTP workers. Bioaerosol samples collected at aeration tanks of two typical municipal WWTPs that use different aeration modes were analysed to investigate the composition and diversity of airborne bacteria in wastewater environments, using the Illumina MiSeq platform. Thirty-six potential airborne bacterial pathogens were identified in the air samples, and these were dominated by Bacillus, Enterococcus, Clostridium, Streptococcus, Acinetobacter, Enterobacter, Pseudomonas, Bacteroides fragilis, Acinetobacter baumannii, and Escherichia/Shigella. Bioaerosols from mechanical aeration tanks (72%, 26/36) had a relatively higher richness and diversity of airborne bacterial pathogens than diffused aeration tanks (17%, 6/36). Furthermore, most of the identified airborne bacterial pathogens (78%, 28/36) were classified as Risk Group 2 according to the revised South African Regulation for Hazardous Biological Agents, 2022, and up to 70% of these were gram-negative bacteria. The presence of potentially pathogenic bacteria in the ambient air at WWTPs suggests an elevated risk of bioaerosol exposure for workers. Therefore, further research and site-specific risk assessments are recommended to guide the implementation of effective bioaerosol strategies to protect workers’ health, with special attention paid to WWTPs that use mechanical aerators.
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    Long-term inhibition of Hepatitis B virus gene expression by a primary microrna expressing ancestral adeno-associated viral vector
    (BioMed Central, 2025-02) Mnyandu, Njabulo Ziphezinhle; Limani, Shonisani Wendy; Ely, Abdullah; Arbuthnot, Patrick; Maepa, Mohube Betty; Wadee, Reubina
    Current treatments for chronic infection with the hepatitis B virus (HBV) rarely cure carriers from the disease. Previously reported use of serotype 8 adeno-associated viral (AAV8) vectors to deliver expression cassettes encoding anti-HBV artificial primary microRNAs (apri-miRs) has shown promise in preclinical studies. A recently designed synthetic ancestral AAV (Anc80L65) with high liver transduction efficiency is a promising new addition to the anti-HBV vector toolbox. This study engineered Anc80L65 to express HBx-targeting apri-miRs. Single dose administration of the vectors to cultured cells and HBV transgenic mice effected reductions of secreted HBV surface antigen (HBsAg). Circulating HBV particles and HBV core antigen (HBcAg) were also significantly diminished in mice receiving the anti-HBV apri-miR-expressing ancestral AAVs. Downregulation of HBV biomarkers occurred over a period of 12 months. Absence of inflammatory responses or liver toxicity indicated that the vectors had a good safety profile. These data suggest that a single dose of apri-miR-expressing Anc80L65 is safe and capable of mediating durable suppression of HBV gene expression. Targeting HBx, which is required for transcriptional activity of covalently closed circular DNA of HBV, makes this Anc80L65-derived vector a promising candidate for functional cure from chronic HBV infection.
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    A histopathological snapshot of bladder cancer: a Johannesburg experience of 1480 histopathology reports
    (Springer, 2025-03) Jonosky, Jaclyn; Adam, Ahmed
    Purpose: To evaluate the histopathological characteristics of bladder cancer in patients presenting to Johannesburg hospitals over a13-year period (2010–2023). Methods: Following ethical clearance, a retrospective observational, descriptive review of histopathological reports over 13 years was conducted in Johannesburg. Inclusion criteria was bladder biopsies, TURBT specimens, and radical cystectomy (RC) specimens positive for bladder cancer. Exclusion criteria was non-primary bladder cancers (prostate, cervical, colon) and urothelial carcinoma of upper tract origin (N=970). Of the initial specimens N=2450), 1480 met the inclusion criteria, representing 858 patients, owing to multiple transurethral resections of bladder tumours (TURBT). Categorical variables were summarised as counts and percentages, while numerical variables were reported as means with standard deviations or medians with interquartile ranges, depending on data distribution and tested via the Shapiro‒Wilk test. Statistical comparisons were performed using Fisher’s exact test (sex), one-way ANOVA, or the Kruskal‒Wallis test (age). Statistical signifi cance was set at p<0.05. Results: Urothelial carcinoma accounted for 88.8% of bladder cancer, squamous cell carcinoma (7.7%), adenocarcinoma (1.5%), and other malignancies (2%). High-grade urothelial carcinoma was predominant at 75%. Non-muscle invasive disease accounted for 72% of these cases, while 28% were muscle invasive. Data from radical cystectomies showed a high proportion of aggressive and advanced disease. Conclusions: The study highlights the predominance of high-grade non-muscle invasive bladder cancer in Johannesburg, consistent with global trends. The findings suggest a shift in bladder cancer trends in Johannesburg away from assumed squamous cell carcinoma towards urothelial carcinoma.
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    Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance
    (Elsevier, 2025-02) Cohen, Paula; Lambson, Bronwen E.; Mkhize, Nonhlanhla N.; Morris, Lynn; Moore, Penny L.; Moodley, Chivonne; Yssel, Anna E. J.; Moyo-Gwete, Thandeka; York, Talita; Gwashu-Nyangiwe, Asanda; Ndabambi, Nonkululeko; Thebus, Ruwayhida; Williamson, Carolyn
    The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC50 < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity. In four pairs, a single mutation restored partial or full sensitiv ity to VRC01, whereas in the fifth participant, transfer of the entire β23-V5 loop was required. No VRC01 resistance mutations could be identified in the sixth participant, with the discordant clones differing by >100 amino acids. Mutations responsible for the differential neutralization phenotypes occurred at distinct sites across Env, including residues in loop D, the CD4-binding loop, and between the β23 and V5 loops. Analysis of deep sequencing env data showed that VRC01 resistance was likely the property of the acquired virus, rather than occurring through post-acquisition evolution. Although VRC01-resistant parental clones generally retained sensitivity to other CD4-binding site bNAbs, they were less potently neutralized than the VRC01-sensitive clones. In conclu sion, VRC01 resistance mutations occurred through multiple mutational pathways, but sensitivity to second-generation CD4bs bNAbs was retained even in VRC01-resistant transmitted viruses, confirming the potential of these bNAbs for HIV-1 prevention studies.