Browsing by Author "Goliath, Rene"

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    Complications of antiretroviral therapy initiation in hospitalised patients with HIV-associated tuberculosis
    (Public Library of Science, 2013) van der Plas, Helen; Meintjes, Graeme; Schutz, Charlotte; Goliath, Rene; Myer, Landon; Baatjie, Dorothea; Wilkinson, Robert J; Maartens, Gary; Mendelson, Marc
    BACKGROUND: HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. METHODS: Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. RESULTS: Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm 3 (IQR 31-106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. CONCLUSIONS: High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1 st three months following ART initiation.
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    Detailed investigation of the unstable (CAG) repeat and the immediate surrounding region of the IT15 gene in some South African families with Huntington disease
    (2005) Scholefield, Janine; Greenberg, Jacquie; Goliath, Rene
    The primary aim of this study was to investigate the origins of the HD mutation in South Africa (SA) by constructing a single nucleotide polymorphism (SNP) haplotype around the IT15 gene and to determine how many haplotypes there are in SA. Haplotypes were created by genotyping 6 SNPs in a total of 15 HD families. These families were comprised of seven Caucasian, 6 Mixed Ancestry and two Black African families.
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    Duchenne muscular dystrophy : mutation profiling in view of the emerging gene-based therapies
    (2010) Esterhuizen, Alina; Goliath, Rene
    Duchenne Muscular Dystrophy (DMD) is a lethal, X-linked, recessive muscle-wasting disorder affecting 1 in 3 500 live male births worldwide, for which only palliative care is available to date. Large exonic deletions or duplications are found in approximately 70% of DMD patients, for which diagnostic testing is available. The remaining 30% carry point mutations, which go largely undetected, as no testing is currently offered due to the great size of the DMD gene and the logistical challenges involved.
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    Exploration of the impact of genetic counselling and patient support group involvement on retinal degenerative disorders (RDD) patients: a qualitative study
    (2018) Goliath, Rene; Wessels, Tina-Marié; Greenberg, Jacquie
    This study explored the experiences of individuals within the clinical genetic service in South Africa, with inherited retinal disease. Methods: This qualitative research was based on a grounded theory approach. Semi-structured interviews were carried out after obtaining approval from the University of Cape Town Research and Ethics committees as well as from study participants themselves. Ten willing individuals were interviewed using an open-ended question guide to extract information about their experiences with vision loss including but not exclusively, concerning participants knowledge about their condition, ability to make decisions and their adaptation experiences. Interviews were audio recorded, transcribed verbatim and a reiterative thematic analysis performed on the raw data. Results: A range of themes and sub-themes emerged from the data that marked participants' experiences from the time of onset of vision loss. The main broad themes include "a roller coaster journey," "learning how to survive," "a genetic condition affecting the back of the eye, and "paving the way forward." Conclusions: The four themes presented in an almost linear fashion, marking a journey patients experienced from the onset of symptoms to the time of the interview. The initial stage of their journey was marked by difficulties and challenges exacerbated by the psychopathological responses reported in this dissertation. This stage was perceived to be prolonged and often extended into adulthood. The messages from the data support a view that the diverse and extended nature of this initial period was due to the limited support this group of participants received from the low vision specialists they consulted with. A significant impression of frustration and disillusionment was experienced by participants on not receiving information and guidance from these health care providers. Various mechanisms of support and control positively influenced patients' learning how to cope and survive their journey with visual impairment. Coping, learning what their condition is, what the causes are and the risks involved for future generations, empowered the participants in this study to obtain a view of a future for themselves and to make relevant decisions and choices necessary to realise the way ahead. Taken together though, continued education was deemed worthwhile.
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    Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors
    (BioMed Central, 2016-09-27) Bana, Tasnim M; Lesosky, Maia; Pepper, Dominique J; van der Plas, Helen; Schutz, Charlotte; Goliath, Rene; Morroni, Chelsea; Mendelson, Marc; Maartens, Gary; Wilkinson, Robert J; Meintjes, Graeme
    Background: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher’s exact test, multivariate logistic regression and Cox proportional hazards models. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0–113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13–4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97–12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients. Conclusions: Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS. Trial registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005.
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    QuantiFERON conversion following tuberculin administration is common in HIV infection and relates to baseline response
    (BioMed Central, 2016-10-07) Esmail, Hanif; Thienemann, Friedrich; Oni, Tolu; Goliath, Rene; Wilkinson, Katalin A; Wilkinson, Robert J
    Background: HIV-1 infection impairs tuberculosis (TB) specific immune responses affecting the diagnosis of latent TB. We aimed to (1) determine the proportion of HIV-1-infected adults with a negative QuantiFERON®-TB Gold in-tube (QFT-GIT) and Tuberculin skin testing (TST) that convert to QFT-GIT positive following TST, and (2) evaluate the relationship between conversion and baseline QFT-GIT results. Methods: HIV-1 infected adults being screened for a TB vaccine study in South Africa underwent QFT-GIT followed by TST. As per protocol, QFT-GIT was repeated if randomization was delayed allowing for evaluation of TST boosting in a proportion of participants. Results: Of the 22 HIV-1 infected, TST and QFT-GIT negative adults (median CD4 477/mm3 IQR 439–621) who had QFT-GIT repeated after median 62 days (IQR 49–70), 40.9 % (95 % CI 18.6–63.2 %) converted. Converters had a significantly greater increase in the background subtracted TB antigen response (TBAg-Nil – all units IU/mL) following TST, 0.82 (IQR 0.39–1.28) vs 0.03 (IQR −0.05–0.06), p = 0.0001. Those who converted also had a significantly higher baseline TBAg-Nil 0.21(IQR 0.17–0.26) vs 0.02(IQR 0.01–0.07), p = 0.002. Converters did not differ with regard to CD4 count or ART status. ROC analysis showed a baseline cut off of 0.15 correctly classified 86.4 % of converters with 88.9 % sensitivity. Conclusions: Our findings support the possibility that there are 2 distinct groups in an HIV-1 infected population with negative QFT-GIT and TST; a true negative group and a group showing evidence of a weak Mtb specific immune response that boosts significantly following TST resulting in conversion of the test result that may represent false negatives. Further evaluation of whether a lower cut off may improve sensitivity of QFT-GIT in this population is warranted.