Desmond Tutu TB Centre (Tygerberg)

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Browsing Desmond Tutu TB Centre (Tygerberg) by Subject "Antitubercular agents"

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    Inclusion of key populations in clinical trials of new antituberculosis treatments : current barriers and recommendations for pregnant and lactating women, children, and HIV-infected persons
    (Public Library of Science, 2019) Gupta, Amita; Hughes, Michael D.; Garcia-Prats, Anthony J.; McIntire, Katherine; Hesseling, Anneke C.
    ENGLISH ABSTRACT: Pregnant women, children < 15 years old and, HIV-infected persons contribute approximately 20% of the global tuberculosis (TB) burden, with an estimated 216,000, 1,000,000, and 1,040,000 cases each year, respectively, yet these populations are currently largely excluded from TB clinical trials, leading to suboptimal treatment and poor access to new therapeutics. • Special considerations in these populations include specific TB disease spectrum and severity, lower sensitivity of commonly used TB diagnostic tests, potential differential drug dosing and treatment responses, drug–drug interactions, and challenges in acquiring high-quality data through clinical trials. • To counter the automatic exclusion of pregnant and lactating women that currently pervades the TB trial landscape, early discussions among trialists, pharmaceutical companies, maternal–child clinical experts, ethicists, and regulatory bodies are needed to address risks, benefits, and compelling rationale for inclusion. Reconsenting women when pregnancy occurs on a trial to allow continuation of study drug by informed choice is a practical and valuable approach to expand the currently limited evidence base. • Children tend to have less severe, often paucibacillary TB disease and may respond better to treatment than adults. Consequently, trials of shorter, less intense TB treatment regimens in children are needed; pharmacokinetic and safety studies should be initiated earlier and involve age groups in parallel rather than in an age-de-escalation approach. More rapid development of child-friendly drug formulations is needed. • All HIV-infected populations, including those with advanced disease, who are likely to be the intended population of the TB therapy, should be involved in Phase IIb and/or Phase III trials, as appropriate, to maximize knowledge of treatment, toxicities, drug– drug interactions, and outcomes.
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    Presentation and outcome of culture-confirmed isoniazid-resistant rifampicin-susceptible tuberculosis in children
    (International Union Against Tuberculosis and Lung Disease, 2016) Garcia-Prats, Anthony J.; Du Plessis, L.; Draper, H. R.; Burger, A.; Seddon, J. A.; Zimri, K.; Hesseling, Anneke C.; Schaaf, H. Simon
    Setting: Isoniazid-resistant rifampicin-susceptible (HRRS) tuberculosis (TB) is the most prevalent form of drug-resistant TB globally, and may be a risk factor for poor outcomes. HRRS-TB in children has been poorly described. Objective: To characterize the clinical presentation, treatment, and clinical and microbiological outcomes, and factors associated with poor outcomes among children with culture-confirmed HRRS-TB. Design: Retrospective hospital-based cohort study. Results: Of the 72 children included, median age 50.1 months (IQR 21.5-102.5), 42% were male. Forty-four (51%) had a potential source case; only 13 were confirmed HRRS-TB. Twelve of 66 tested (17%) were HIV-infected, and 36 of 60 (60%) with pulmonary TB had severe disease. Seventy had treatment data; median total duration was 11.3 months (IQR 9-12.3); 25 (36%) initiated treatment with a 3-drug intensive phase; 52 (74%) received a fluoroquinolone. Of 63 with known outcome, 55 (88%) had a favourable outcome; 1 died and 3 had treatment failure. Ten had positive follow-up cultures at ≥2 months after starting treatment (17% of all PTB and 27% of those with follow-up culture data); older age (p=0.008), previous TB treatment (p=0.023) and severe PTB (p=0.018) were associated with failure to culture-convert at ≥2 months. Conclusions: Although overall outcomes were good, prolonged culture positivity and cases of treatment failure emphasize the need for additional attention to clinical management of children with HRRS-TB.