- ItemRelationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection(American Society for Clinical Investigation, 2021-05) Riou, Catherine; Du Bruyn, Elsa; Stek, Cari; Daroowala, Remy; Goliath, Rene T.; Abrahams, Fatima; Said-Hartley, QonitaT cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARSCoV- 2–specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARSCoV- 2–specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.
- ItemPost-tuberculosis lung health : perspectives from the First International Symposium(International Union Against Tuberculosis and Lung Disease, 2020-08-01) Allwood, B. W.; van der Zalm, M. M.; Amaral, A. F. S.; Byrne, A.; Datta, S.; Egere, U.; Evans, C. A.; Evans, D.; Gray, D. M.; Hoddinott, G.; Ivanova, O.; Jones, R.; Makanda, G.; Marx, F. M.; Meghji, J.; Mpagama, S.; Pasipanodya, J. G.; Rachow, A.; Schoeman, I.; Shaw, J.; Stek, C.; van Kampen, S.; von Delft, D.; Walker, N. F.; Wallis, R. S.; Mortimer, K.ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.
- ItemTransition from restrictive to obstructive lung function impairment during treatment and follow-up of active tuberculosis(Dove Press, 2020-05) Allwood, Brian W.; Maasdorp, Elizna; Kim, Grace J.; Cooper, Christopher B.; Goldin, Jonathan; van Zyl-Smit, Richard N.; Bateman, Eric D.; Dawson, RodneyBackground: Pulmonary tuberculosis (PTB) is associated with many forms of chronic lung disease including the development of chronic airflow obstruction (AFO). However, the nature, evolution and mechanisms responsible for the AFO after PTB are poorly understood. The aim of this study was to examine the progression of changes in lung physiology in patients treated for PTB. Methods: Immunocompetent, previously healthy, adult patients receiving ambulatory treatment for a first episode of tuberculosis were prospectively followed up with serial lung physiology and quantitative computed tomography (CT) lung scans performed at diagnosis of tuberculosis, 2, 6, 12 and 18 months during and after the completion of treatment. Results: Forty-nine patients (median age 26 years; 37.2% males) were included, and 43 were studied. During treatment, lung volumes improved and CT fibrosis scores decreased, but features of AFO and gas trapping emerged, while reduced diffusing capacity (DLco) seen in a majority of patients persisted. Significant increases in total lung capacity (TLC) by plethysmography were seen in the year following treatment completion (median change 5.9% pred., P<0.01) and were driven by large increases in residual volume (RV) (median change +19%pred., P<0.01) but not inspiratory capacity (IC; P=0.41). The change in RV/TLC correlated with significant progression of radiological gas trapping after treatment (P=0.04) but not with emphysema scores. One year after completing treatment, 18.6% of patients had residual restriction (total lung capacity, TLC <80%pred), 16.3% had AFO, 32.6% had gas trapping (RV/TLC>45%), and 78.6% had reduced DLco. Conclusion: Simple spirometry alone does not fully reveal the residual respiratory impairments resulting after a first episode of PTB. Changes in physiology evolve after treatment completion, and these findings when taken together, suggest emergence of gas trapping after treatment likely caused by progression of small airway pathology during the healing process. Keywords: airflow obstruction; chronic obstructive pulmonary disease; computed tomography; lung function; post-tuberculosis; tuberculosis.
- ItemFourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis(2020-01) Diacon, Andreas; De Jager, Veronique R; Dawson, RodneyBackground: Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown. Methods: Between November 2014 and November 2016, we randomised 114 drug-sensitive treatment-naïve pulmonary tuberculosis patients from Cape Town, South Africa, to one of six 14-day treatment arms containing linezolid 300 mg once daily (qd), 300 mg twice daily (bd), 600 mg qd, 600 mg bd, 1200 mg qd, 1200 mg three times per week (tiw) or a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Sixteen-hour sputum samples were collected overnight, and bactericidal activity characterized by the daily percentage change in time to positivity (TTP) and colony forming units (CFU). We also assessed the safety and pharmacokinetics of the study treatments. Results: Bactericidal activity increased with increasing doses of linezolid. Based on the daily percentage change in TTP, activity was highest for 1200 mg qd (4.5; 95% Bayesian confidence interval [BCI]: 3.3-5.6), followed by 600 mg bd (4.1; BCI: 2.5-5.7), 600 mg qd (4.1; BCI: 2.9-5.3), 300 mg bd (3.3; BCI: 1.9-4.7), 300 mg qd (2.3; BCI: 1.1-3.5) and 1200 mg tiw (2.2; BCI: 1.1-3.3). Similar results were seen with bactericidal activity characterized by the daily rate of change in CFU count. Antimycobacterial activity correlated positively with plasma drug exposure and percentage time over minimum inhibitory concentration. There were no unexpected adverse events. Conclusion: All linezolid doses showed bactericidal activity. For the same total daily dose, once daily dosing proved to be at least as effective as a divided twice daily dose. An intermittent dosing regimen, with 1200 mg given three times weekly, showed the least activity.
- ItemThe utility of hand-held mobile spirometer technology in a resource-constrained setting(Health & Medical Publishing Group, 2019) Du Plessis, E.; Swart, F.; Maree, D.; Heydenreich, J.; Van Heerden, J.; Esterhuizen, T. M.; Irusen, E. M.; Koegelenberg, C. F. N.Background. Mobile phone-linked spirometry technology has been designed specifically for evaluating lung function at primary care level. The Air-Smart Spirometer is the first mobile spirometer accepted in Europe for the screening of patients with chronic respiratory diseases. Objectives. To prospectively assess the accuracy of the device in measuring forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in a South African population, and to investigate the ability of the device to detect obstructive ventilatory impairment. Methods. A total of 200 participants were randomly assigned to perform spirometry with either the mobile spirometer connected to a smartphone or the desktop spirometer first, followed by the other. The FEV1/FVC ratio as well as the absolute FEV1 and FVC measurements were compared, using each participant as their own control. A Pearson correlation and Bland-Altman analysis were performed to measure the agreement between the two devices. We defined obstructive ventilatory impairment as FEV1/FVC <0.7 measured by desktop spirometry in order to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Air-Smart Spirometer. Results. There was a strong correlation between the absolute FEV1 and FVC values and FEV1/FVC ratio measured with the mobile Air-Smart Spirometer and more conventional pulmonary function testing, with r=0.951, r=0.955 and r=0.898, respectively. The Air-Smart Spirometer had a sensitivity of 97.6%, specificity of 74.4%, PPV of 73.0% and NPV of 97.8% for obstructive ventilatory impairment. Conclusions. The mobile Air-Smart Spirometer compared well with conventional spirometry, making it an attractive and potentially affordable tool for screening purposes in a primary care setting. Moreover, it had a high sensitivity and NPV for obstructive ventilatory impairment.