Florian M Marx1, Rory Dunbar2, Donald A Enarson3, Brian G Williams4, Robin M Warren5, Gian D van der Spuy5, Paul D van Helden5, Nulda Beyers2. 1. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University Department for Pediatric Pneumology and Immunology, Charité-Universitätsmedizin, Berlin, Germany. 2. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University. 3. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University International Union Against Tuberculosis and Lung Disease, Paris, France. 4. DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa. 5. DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, US/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg Campus, Cape Town.
Abstract
BACKGROUND: There is increasing evidence from tuberculosis high-burden settings that exogenous reinfection contributes considerably to recurrent disease. However, large longitudinal studies of endogenous reactivation (relapse) and reinfection tuberculosis are lacking. We hypothesize a relationship between relapse vs reinfection and the time between treatment completion and recurrent disease. METHODS: Population-based retrospective cohort study on all smear-positive tuberculosis cases successfully treated between 1996 and 2008 in a suburban setting in Cape Town, South Africa. Inverse gaussian distributions were fitted to observed annual rates of relapse and reinfection, distinguished by DNA fingerprinting of Mycobacterium tuberculosis strains recultured from diagnostic samples. RESULTS: Paired DNA fingerprint data were available for 130 (64%) of 203 recurrent smear-positive tuberculosis cases in the 13-year study period. Reinfection accounted for 66 (51%) of 130 recurrent cases overall, 9 (20%) of 44 recurrent cases within the first year, and 57 (66%) of 86 thereafter (P < .001). The relapse rate peaked at 3.93% (95% confidence interval [CI], 2.35%-5.96%) per annum 0.35 (95% CI, .15-.45) years after treatment completion. The reinfection tuberculosis rate peaked at 1.58% (95% CI, .94%-2.46%) per annum 1.20 (95% CI, .55-1.70) years after completion. CONCLUSIONS: To our knowledge, this is the first study of sufficient size and duration using DNA fingerprinting to investigate tuberculosis relapse and reinfection over a lengthy period. Relapse occurred early after treatment completion, whereas reinfection dominated after 1 year and accounted for at least half of recurrent disease. This temporal relationship may explain the high variability in reinfection observed across smaller studies. We speculate that follow-up time in antituberculosis drug trials should take reinfection into account.
BACKGROUND: There is increasing evidence from tuberculosis high-burden settings that exogenous reinfection contributes considerably to recurrent disease. However, large longitudinal studies of endogenous reactivation (relapse) and reinfection tuberculosis are lacking. We hypothesize a relationship between relapse vs reinfection and the time between treatment completion and recurrent disease. METHODS: Population-based retrospective cohort study on all smear-positive tuberculosis cases successfully treated between 1996 and 2008 in a suburban setting in Cape Town, South Africa. Inverse gaussian distributions were fitted to observed annual rates of relapse and reinfection, distinguished by DNA fingerprinting of Mycobacterium tuberculosis strains recultured from diagnostic samples. RESULTS: Paired DNA fingerprint data were available for 130 (64%) of 203 recurrent smear-positive tuberculosis cases in the 13-year study period. Reinfection accounted for 66 (51%) of 130 recurrent cases overall, 9 (20%) of 44 recurrent cases within the first year, and 57 (66%) of 86 thereafter (P < .001). The relapse rate peaked at 3.93% (95% confidence interval [CI], 2.35%-5.96%) per annum 0.35 (95% CI, .15-.45) years after treatment completion. The reinfection tuberculosis rate peaked at 1.58% (95% CI, .94%-2.46%) per annum 1.20 (95% CI, .55-1.70) years after completion. CONCLUSIONS: To our knowledge, this is the first study of sufficient size and duration using DNA fingerprinting to investigate tuberculosis relapse and reinfection over a lengthy period. Relapse occurred early after treatment completion, whereas reinfection dominated after 1 year and accounted for at least half of recurrent disease. This temporal relationship may explain the high variability in reinfection observed across smaller studies. We speculate that follow-up time in antituberculosis drug trials should take reinfection into account.
Authors: Florian M Marx; Ted Cohen; Nicolas A Menzies; Joshua A Salomon; Grant Theron; Reza Yaesoubi Journal: Lancet Glob Health Date: 2020-09 Impact factor: 26.763
Authors: Julian S Peters; Jason R Andrews; Mark Hatherill; Sabine Hermans; Leonardo Martinez; Erwin Schurr; Yuri van der Heijden; Robin Wood; Roxana Rustomjee; Bavesh D Kana Journal: Lancet Infect Dis Date: 2018-12-13 Impact factor: 25.071
Authors: Krishna P Reddy; C Robert Horsburgh; Robin Wood; Naomi F Fields; Michael P Girouard; Sydney Costantini; Taige Hou; Kenneth A Freedberg; Rochelle P Walensky Journal: Ann Am Thorac Soc Date: 2020-02
Authors: Y F van der Heijden; F Karim; T Chinappa; G Mufamadi; L Zako; B E Shepherd; F Maruri; M-Y S Moosa; T R Sterling; A S Pym Journal: Int J Tuberc Lung Dis Date: 2018-08-01 Impact factor: 2.373