Browsing by Author "Hughes, J."
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- ItemClinical perspectives on treatment of rifampicin-resistant/multidrug-resistant TB(International Union Against Tuberculosis and Lung Disease, 2020-11) Cox, V.; McKenna, L.; Acquah, R.; Reuter, A.; Wasserman, S.; Vambe, D.; Ustero, P.; Udwadia, Z.; Trivino-Duran, L.; Tommasi, M.; Skrahina, A.; Seddon, J. A.; Rodolfo, R.; Rich, M.; Padanilam, X.; Oyewusi, L.; Ohler, L.; Lungu, P.; Loveday, M.; Khan, U.; Khan, P.; Hughes, J.; Hewison, C.; Guglielmetti, L.; Furin, J.Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second ‘Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
- ItemDecentralised care for child contacts of multidrug-resistant tuberculosis(The Union, 2012-09-21) Seddon, J. A.; Hesseling, A. C.; Dunbar, R.; Cox, H.; Hughes, J.; Fielding, K.; Godfrey-Faussett, P.; Schaaf, H. S.SETTING: Cape Town, South Africa. OBJECTIVE: To determine the number of multidrug-resistant tuberculosis (MDR-TB) child contacts routinely identified by health services, and whether a model of decentralised care improves access. METHODS: All MDR-TB source cases registered in Cape Town from April 2010 to March 2011 were included. All child contacts assessed at hospital and outreach clinics were recorded from May 2010 to June 2011. Electronic probabilistic matching was used to match source cases with potential child contacts; the number of children accessing decentralised (Khayelitsha) and hospital-based care was compared. RESULTS: Of 1221 MDR-TB source cases identified, 189 (15.5%) were registered in Khayelitsha; 31 (16.4%) had at least one child contact assessed. In contrast, 95 (9.2%) of the 1032 source cases diagnosed in the other Cape Town subdistricts (hospital-based care) had at least one child contact assessed (P = 0.003). Children in Khayelitsha were seen at a median of 71 days (interquartile range [IQR] 37–121 days) after source case diagnosis compared to 90 days (IQR 56–132 days) in other subdistricts (P = 0.15). CONCLUSION: Although decentralised care led to an increased number of child contacts being evaluated, both models led to the assessment of a small number of potential child MDR-TB contacts, with considerable delay in assessment.
- ItemHigh heritability of antimycobacterial immunity in an area of hyperendemicity for tuberculosis disease(2010) Cobat, A.; Gallant, C. J.; Simkin, L.; Black, G. F.; Stanley, K.; Hughes, J.; Mark, Doherty T.; Hanekom, W. A.; Eley, B.; Beyers, Nulda; Jais, J.-P.; Van Helden, Paul D.; Abel, L.; Hoal, E. G.; Alcais, A.; Schurr, E.Human antimycobacterial immunity is a critical component of tuberculosis (TB) pathogenesis that is often used to infer the presence of TB infection. We report high heritability (>50%) for in vitro secretion of tumor necrosis factor α and interferon γ (IFN-γ), and the frequency of antigen-specific IFN-γ+CD4+ and IFN- γ+CD8+ cells in the response of whole blood to mycobacterial challenge. In principal component analysis, the first 3 components explain 78% of the overall variance consistent with the effect of pleiotropic regulatory genes of human antimycobacterial immunity. These results directly demonstrate the pivotal role played by host genetics in quantitative measures of antimycobacterial immunity underlying immune diagnosis of TB infection. © 2010 by the Infectious Diseases Society of America. All rights reserved.
- ItemImpact of age and sex on mycobacterial immunity in an area of high tuberculosis incidence(2010) Gallant, C. J.; Cobat, A.; Simkin, L.; Black, G. F.; Stanley, K.; Hughes, J.; Doherty, T. M.; Hanekom, W. A.; Eley, B.; Beyers, Nulda; Jais, J-P.; Van Helden, Paul D.; Abel, L.; Alcais, A.; Hoal, E. G.; Schurr, E.SETTING: The extent of immune reactivity measured by the tuberculin skin test (TST) and interferon-gamma (IFN-γ) T-cell assays is usually not analysed. OBJECTIVE: To determine the impact of age and sex on assay positivity and on the extent of reactivity of both TST and T-cell assays in young persons in an area of South Africa with high TB transmission. RESULTS: Age had a strong impact on assay positivity for all seven immune phenotypes tested (P < 0.0007). Among positive responders, the extent of purified protein derivative (PPD) triggered IFN-γ release (P < 0.003) was sensitive to age. ESAT-6 triggered IFN-γ release (day 7, P = 0.03) and the frequency of PPD-specific IFN-γ+CD4+ (P = 0.03) and IFN-γ+CD8+ cells (P = 0.04) were weakly dependent on age. By contrast, the extent of TST induration was insensitive to age (P > 0.05), and sex had no significant impact on any phenotype measured (P > 0.05). The high proportion of positive responders in the 1-10 year age-group observed with long-term whole blood assays, but not with 3-day assays and TST, suggests that long-term whole blood assays may be confounded by bacille Calmette-Guérin vaccination in this age group. CONCLUSION: There is a significant impact of age, but not sex, on different assays of immune reactivity in this high TB transmission setting. © 2010 The Union.
- ItemImplementing novel regimens for drug-resistant TB in South Africa : what can the world learn?(International Union Against Tuberculosis and Lung Disease, 2020-10) Ndjeka, N.; Hughes, J.; Reuter, A.; Conradie, F.; Enwerem, M.; Ferreira, H.; Ismail, N.; Kock, Y.; Master, I.; Meintjes, G.; Padanilam, X.; Romero, R.; Schaaf, H. S.; te Riele, J.; Maartens, G.Worldwide uptake of new drugs in the treatment of rifampicin-resistant tuberculosis (RR-TB) has been extremely low. In June 2018, ahead of the release of the updated WHO guidelines for the management of RR-TB, South Africa announced that bedaquiline (BDQ) would be provided to virtually all RR-TB patients on shorter or longer regimens. South Africa has been the global leader in accessing BDQ for patients with RR-TB, who now represent 60% of the global BDQ cohort. The use of BDQ within a shorter modified regimen has generated the programmatic data underpinning the most recent change in WHO guidelines endorsing a shorter, injectable-free regimen. Progressive policies on access to new drugs have resulted in improved favourable outcomes and a reduction in mortality among RR-TB patients in South Africa. This supported global policy change. The strategies underpinning these bold actions include close collaboration between the South African National TB Programme and partners, introduction of new TB diagnostic tools in closely monitored conditions and the use of locally generated programmatic evidence to inform country policy changes. In this paper, we summarise a decade´s work that led to the bold decision to use a modified, short, injectable-free regimen with BDQ and linezolid under carefully monitored programmatic conditions.
- 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.