Browsing by Author "Ndlangalavu, Gcobisa"

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    Diagnostic accuracy of novel sputum and non-sputum-based tuberculosis diagnostics in HIV-positive patients initiating anti-retroviral therapy
    (Stellenbosch : Stellenbosch University, 2023-12) Ndlangalavu, Gcobisa; Theron, Grant; Reeve, Byron; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: Tuberculosis (TB) is a major health problem killing millions of people worldwide and is the leading cause of death among people living with HIV (PLHIV). PLHIV are at high risk of TB due to their weakened immune systems and 18 times more likely develop TB than people without HIV. Therefore, early detection of TB among PLHIV is fundamental and dependent on good TB diagnostics. The study addressed barriers and limitations of TB screening (triage) and diagnosis, with some limitations being facility-based active case finding, which is challenging, and delayed patient results. To highlight limitations and utility of tests in the pipeline, current and novel TB diagnostics were extensively reviewed (Chapter 2). Additionally, we tested selected PLHIV initiating antiretroviral therapy (ART), in whom TB detection is difficult due to their paucibacillary nature, are negative by the World Health Organization (WHO) recommended four-symptom screen (W4SS), and unable to produce sputum (Chapters 3 to 5). ART initiators were included irrespective of W4SS status, to challenge the existing TB testing algorithm in PLHIV. Formerly, W4SS was exclusively recommended for triage for further TB testing even in PLHIV. Due to W4SS’ suboptimal specificity and poor implementation, alternative triage tools are required, which we investigated. This includes C-reactive protein (CRP) (Chapter 3). CRP (≥10mg/l) had higher specificity than W4SS in ART initiators and reduces unnecessary downstream testing. Since CRP levels varied within groups of the same culture status, Chapter 4 investigated clinical and demographic factors associated with CRP levels, thereby informing which types of patients might be missed or falsely included by CRP-based triage algorithms. Low CD4 cell count, culture-confirmed TB, and increased TBScore II were strongly associated with elevated CRP. Sputum Xpert MTB/RIF Ultra (Ultra) is the frontline rapid pulmonary TB test in South Africa, however, supporting data PLHIV, among whom Ultra may offer sensitivity improvement over Xpert MTB/RIF (Xpert) is limited. Sputum expectoration is challenging in PLHIV, and easily accessible urine can mitigate this. Chapters 3 and 5 investigated the diagnostic accuracy of Ultra using urine versus Determine TB LAM Ag test (LF-LAM). Their performance was similar. We further investigated urine Fujifilm SILVAMP TB-LAM (FujiLAM) diagnostic accuracy versus that of LF-LAM (Chapter 5). FujiLAM had increased sensitivity and comparable specificity versus LF-LAM. However, FujiLAM’s diagnostic accuracy varied between different manufacturer lots. In summary, CRP (>10mg/l) would reduce unnecessary expensive downstream TB testing. CRP increases case detection especially in key and vulnerable populations. CRP data from this study contributed to a meta-analysis that informed the latest screening guidelines for TB, changing decades old triaging approaches. Sputum-Ultra is more sensitive than Xpert and detects ~1/2 W4SS-negative cases. Our sputum-Ultra data contributed to a systematic review evaluating the diagnostic accuracy of Xpert and Ultra, irrespective of W4SS status, and was the only study with Ultra data among PLHIV. TB detection in outpatient PLHIV can be improved with FujiLAM implementation if improved versions of the tests would be available. Non-sputum-based confirmatory tests with improved sensitivity are urgently needed to improve case detection especially in sputum-scarce and W4SS-negative people.
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    The prevalence of Cladosporium species in indoor environments
    (Stellenbosch : Stellenbosch University, 2019-04) Ndlangalavu, Gcobisa; Jacobs, Karin; Stellenbosch University. Faculty of Science. Dept. of Microbiology.
    ENGLISH ABSTRACT: Cladosporium is among the largest and most diverse genera of hyphomycetes, previously reported to include over 772 names. The olive-green to brown or sometimes black colonies are usually the easiest characteristics used to recognise species of this genus. Cladosporium are usually found on both living and dead plant material, and recently in human specimens and indoor environments. Furthermore, Cladosporium are associated with allergenic rhinitis, asthma, subcutaneous infections and other infections in both immunocompetent and immunocompromised individuals. Nevertheless, some Cladosporium species are useful for the production of antibiotics that work against Bacillus subtilis and Candida albicans, while some are efficient biological insecticides targeting insects that are resistant to chemical insecticides. Ambient air pollution has been recognised as the primary source of respiratory illnesses with regards to air pollution. However, in recent years, indoor air has proven to be a potential threat to human health. Indoor environments encompass a lot of gases and microorganisms that may be hazardous to humans. Cladosporium, often referred to as outdoor fungi has been commonly isolated in indoor environments over the last few years. This study investigated the prevalence of a potent allergenic genus, Cladosporium, in South African indoor environments. In an attempt to achieve this, air samples collected from different areas of the Western Cape and Gauteng provinces were studied. Following a polyphasic approach used by several authors, isolates were identified and new species described. Species were represented in all species complexes but mostly resolved in the Cladosporium cladosporioides species complex, the largest complex of the genus. Here, we present 110 isolates from indoor air samples identified as 18 different species of Cladosporium, three of which have been introduced and described as novel. This study has demonstrated that South African indoor environments contain a large diversity of described and undescribed Cladosporium species. Moreover, there is a need for more studies concerning indoor environments with particular regard to this genus.