Browsing by Author "Theron, G."
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- ItemComparison of quantitative techniques including Xpert MTB/RIF to evaluate mycobacterial burden(PLOS, 2011-12) Van Zyl-Smit, Richard N.; Binder, Anke; Meldau, Richard; Mishra, H.; Semple, P. L.; Theron, G.; Peter, J.; Whitelaw, A.; Sharma, S. K.; Warren, Rob; Bateman, E. D.; Dheda, K.Introduction: Accurate quantification of mycobacterial load is important for the evaluation of patient infectiousness, disease severity and monitoring treatment response in human and in-vitro laboratory models of disease. We hypothesized that newer techniques would perform as well as solid media culture to quantify mycobacterial burden in laboratory specimens. Methods: We compared the turn-around-time, detection-threshold, dynamic range, reproducibility, relative discriminative ability, of 4 mycobacterial load determination techniques: automated liquid culture (BACTEC-MGIT-960), [3H]-uracil incorporation assays, luciferase-reporter construct bioluminescence, and quantitative PCR(Xpert -MTB/RIF) using serial dilutions of Mycobacterium bovis and Mycobacterium tuberculosis H37RV. Mycobacterial colony-forming-units(CFU) using 7H10-Middlebrook solid media served as the reference standard. Results: All 4 assays correlated well with the reference standard, however, bioluminescence and uracil assays had a detection threshold $16103 organisms. By contrast, BACTEC-MGIT-960 liquid culture, although only providing results in days, was user-friendly, had the lowest detection threshold (,10 organisms), the greatest discriminative ability (1 vs. 10 organisms; p = 0.02), and the best reproducibility (coefficient of variance of 2% vs. 38% compared to uracil incorporation; p = 0.02). Xpert-MTB/RIF correlated well with mycobacterial load, had a rapid turn-around-time (,2 hours), was user friendly, but had a detection limit of ,100 organisms. Conclusions: Choosing a technique to quantify mycobacterial burden for laboratory or clinical research depends on availability of resources and the question being addressed. Automated liquid culture has good discriminative ability and low detection threshold but results are only obtained in days. Xpert MTB/RIF provides rapid quantification of mycobacterial burden, but has a poorer discrimination and detection threshold.
- ItemINTERGROWTH-21st v. local South African growth standards (Theron-Thompson) for identification of small-for-gestational-age fetuses in stillbirths : a closer look at variation across pregnancy(Health & Medical Publishing Group, 2019) Lavin, T.; Nedkoff, L.; Preen, D.; Theron, G.; Pattinson, R. C.Background. Global growth standards for fetuses were recently developed (INTERGROWTH-21st). It has been advocated that professional bodies should adopt these global standards. Objectives. To compare the ability of INTERGROWTH-21st with local standards (Theron-Thompson) to identify small-for-gestational-age (SGA) fetuses in stillbirths in the South African (SA) setting. Methods. Stillbirths across SA were investigated (>500 g, 28 - 40 weeks) between October 2013 and December 2016 (N=14 776). The study applied the INTERGROWTH-21st standards to classify stillbirths as <10th centile (SGA) compared with Theron-Thompson growth charts, across pregnancy overall and at specific gestational ages. Results. The prevalence of SGA was estimated at 32.2% and 31.1% by INTERGROWTH-21st and Theron-Thompson, respectively. INTERGROWTH-21st captured 13.8% more stillbirths as SGA in the earlier gestations (28 - 30 weeks, p<0.001), but 4.0% (n=315) fewer between 33 and 38 weeks (p<0.001). Observed agreement and the Kappa coefficient were lower at earlier gestations and at 34 - 36 weeks. Conclusions. Our findings demonstrated differences in the proportion of stillbirths considered SGA at each gestational age between the INTERGROWTH-21st and the local SA standard, which have not been considered previously by other studies.
- ItemThe mother-to-child HIV transmission debate(Health & Medical Publishing Group, 1999) Hussey, G.; Fransman, D.; McGillivray, G.; Reynolds, Lindsey; Jacobs, M.; Power, D.; Burgess, J.; Eley, B.; Woods, D.; Coetzee, N.; Coetzee, E.; Anthony, J.; Maartens, G.; Schaaf, S.; Cotton, M.; Theron, G.[No abstract available]
- ItemMother-to-child transmission of hepatitis B virus in sub-Saharan Africa : time to act(Elsevier, 2015-07) Andersson, Monique I.; Rajbhandari, R.; Kew, M. C.; Vento, S.; Preiser, Wolfgang; Hoepelman, A. I.; Theron, G.; Cotton, Mark F.; Cohn, J.; Glebe, D.; Lesi, O.; Thursz, M.; Peters, M.; Chung, R.; Wiysonge, Charles S.; Pathology: Medical VirologyWhat few people thought possible little more than a decade ago is now reality: scientific and operational advances are greatly reducing the number of deaths from HIV. The number of infant infections has decreased by 58% between 2001 and 2013 and mother-to-child transmission (MTCT) of HIV might well be eliminated in the next few years.1 By contrast, the prevention and management of hepatitis B virus (HBV) infection lags well behind, at least in sub-Saharan Africa.
- ItemOvercoming limitations of tuberculosis information systems : researcher and clinician perspectives(International Union Against Tuberculosis and Lung Disease, 2019) Van Der Heijden, Y. F.; Hughes, J.; Dowdy, D. W.; Streicher, E.; Chihota, V.; Jacobson, K. R.; Warren, R.; Theron, G.Setting: Tuberculosis (TB) diagnosis and treatment requires patients to have multiple encounters with health care systems and the different stakeholders who play a role in curing them to coordinate their efforts. To optimize this process, high-quality, readily available data are required. Data systems to facilitate these linkages are a neglected priority which, if weak, fundamentally undermine TB control interventions. Objective: To describe lessons learnt from the use of programmatic data for TB patient care and research. Design: We did a survey of researcher and clinical provider experiences with information systems and developed a tiered approach to addressing frequently reported barriers to high-quality care. Results: Unreliable linkages, incomplete data, lack of a reliable unique patient identifier, and lack of data management expertise were the most important data-related barriers to high-quality patient care and research. We propose the creation of health service delivery environments that facilitate, prioritize, and evaluate high-quality data entry during patient or specimen registration. Conclusion: An integrated approach, focused on high-quality data, and centered on unique patient identification will form the foundation for linkages across health systems that reduce patient management errors, bolster surveillance, and enhance the quality of research based on programmatic data.
- ItemRelationship between chest radiographic characteristics, sputum bacterial load, and treatment outcomes in patients with extensively drug-resistant tuberculosis(Elsevier, 2019) Te Riele, J. B.; Buser, V.; Calligaro, G.; Esmail, A.; Theron, G.; Lesosky, M.; Dheda, K.Background: Data about the relationship between chest radiographs and sputum bacillary load, with treatment outcomes, in patients with extensively drug-resistant tuberculosis (XDR-TB) from HIV/TB endemic settings are limited. Methods: Available chest radiographs from 97 South African XDR-TB patients, at the time of diagnosis, were evaluated by two independent readers using a validated scoring system. Chest radiograph findings were correlated with baseline sputum bacillary load (smear-grade and culture time-to-positive in MGIT), and prospectively ascertained clinical outcomes (culture conversion and all-cause mortality). Results: Radiographic bilateral lung disease was present in 75/97 (77%). In the multivariate analysis only a higher total radiographic score (95% CI) was associated with higher likelihood of death [1.16 (1.05–1.28) p = 0.003], and failure to culture convert [0.85 (0.74–0.97) p = 0.02]. However, when restricting analyses to HIV-infected patients, disease extent, cavitation, and total radiographic scores were not associated with mortality or culture-conversion. Finally, cavitary, disease extent, and total radiographic scores all positively correlated with bacterial load (culture time-to-positive). Conclusions: In endemic settings, XDR-TB radiological disease extent scores are associated with adverse clinical outcomes, including mortality, in HIV uninfected persons. These data may have implications for clinical and programmatic decision-making and for evaluation of new regimens in clinical trials.
- ItemSlow acceptance of universal antiretroviral therapy (ART) among mothers enrolled in IMPAACT PROMISE studies across the globe(Springer, 2019) Stranix‑Chibanda, L.; Brummel, S.; Pilotto, J.; Mutambanengwe, M.; Chanaiwa, V.; Mhembere, T.; Kamateeka, M.; Aizire, J.; Masheto, G.; Chamanga, R.; Maluwa, M.; Hanley, S.; Joao, E.; Theron, G.; Nevrekar, N.; Nyati, M.; Santos, B.; Aurpibul, L.; Mubiana‑Mbewe, M.; Oliveira, R.; Anekthananon, T.; Mlay, P.; Angelidou, K.; Tierney, C.; Ziemba, L.; Colett, A.; McCarthy, K.; Basar, M.; Chakhtoura, N.; Browning, R.; Currier, J.; Fowler, M. G.; Flynn, P.ENGLISH ABSTRACT: The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the “Treat All” strategy.
- ItemText messages as a learning tool for midwives(Health & Medical Publishing Group, 2012-01-27) Woods, D.; Attwell, A.; Ross, K.; Theron, G.The use of cell phone text messaging to improve access to continuing healthcare education in under-resourced settings is not well documented. We aimed to assess whether this method of education is acceptable to South African midwives in both the public and private sectors. Essential healthcare lessons from the Maternal Care book of the Perinatal Education Programme (PEP) were delivered via text message to more than 2 500 midwives each week for a period of 6 months. Each message concluded with a link to a website, where additional information about each lesson could be accessed. Results of a survey, conducted with 50 of the message recipients, demonstrated that the text messages were well received by the midwives; the information was widely shared with colleagues and was believed to improve learning and patient care. Lack of access to the internet, or failure to utilise this facility to obtain additional information, indicated that limitations still exist in internet-based distance education, especially in the public sector. The use of text messaging promises to provide cost-effective learning opportunities, and improve a wide range of clinical services, such as the management of HIV-infected children and adults.
- ItemTuberculosis research in South Africa over the past 30 years : from bench to bedside(South African Medical Association, 2019-12-05) Warren, R.; Ismail, N. A.; Chegou, N. N.; Theron, G.; Walzl, Gerhard; Malherbe, S. T.; Kinnear, C. J.; van der Spuy, G. D.; Goosen, W.; Miller, M. A.; Diacon, A. H.; van Helden, P. D.ENGLISH ABSTRACT: The South African Medical Research Council Centre for Tuberculosis Research has a rich history of high-impact research that has influenced our understating of this hyper-epidemic which is further exacerbated by the emergence and spread of drug-resistant forms of the disease. This review aims to summarise the past 30 years of research conducted in the Centre which has influenced the way that tuberculosis (TB) is diagnosed and treated. The review includes the development of new technologies for rapid screening of people with probable TB and the repurposing of human diagnostics for wildlife conservation.
- ItemWidespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant tuberculosis diagnosis (MTBDRplus)(Nature Publishing Group, 2018) Derendinger, B.; De Vos, M.; Nathavitharana, R. R.; Dolby, T.; Simpson, J. A.; Van Helden, P. D.; Warren, Robin M.; Theron, G.ENGLISH ABSTRACT: The scale-up of rapid drug resistance testing for TB is a global priority. MTBDRplus is a WHO-endorsed multidrug-resistant (MDR)-TB PCR assay with suboptimal sensitivities and high indeterminate rates on smear-negative specimens. We hypothesised that widespread use of incorrect thermocycler ramp rate (speed of temperature change between cycles) impacts performance. A global sample of 72 laboratories was surveyed. We tested 107 sputa from Xpert MTB/RIF-positive patients and, separately, dilution series of bacilli, both at the manufacturer-recommended ramp rate (2.2 °C/s) and the most frequently reported incorrect ramp rate (4.0 °C/s). Mycobacterium tuberculosis-complex DNA (TUB-band)-detection, indeterminate results, accuracy, and inter-reader variability (dilution series only) were compared. 32 respondents did a median (IQR) of 41 (20–150) assays monthly. 78% used an incorrect ramp rate. On smear-negative sputa, 2.2 °C/s vs. 4.0 °C/s improved TUB-band positivity (42/55 vs. 32/55; p = 0.042) and indeterminate rates (1/42 vs. 5/32; p = 0.039). The actionable results (not TUB-negative or indeterminate; 41/55 vs. 28/55) hence improved by 21% (95% CI: 9–35%). Widespread use of incorrect ramp rate contributes to suboptimal MTBDRplus performance on smear-negative specimens and hence limits clinical utility. The number of diagnoses (and thus the number of smear-negative patients in whom DST is possible) will improve substantially after ramp rate correction.