Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2016

Open Access 01-12-2016 | Research article

The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study

Authors: Sabine M. Hermans, Alison D. Grant, Violet Chihota, James J. Lewis, Emilia Vynnycky, Gavin J. Churchyard, Katherine L. Fielding

Published in: BMC Medicine | Issue 1/2016

Login to get access

Abstract

Background

The durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection.

Methods

In a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9 months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT.

Results

Among 18,520 participants (96 % male, mean age 41 years, median follow-up 2.1 years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95 % confidence interval (CI), 1.0–1.6) and afterwards 2.3/100 pyrs (95 % CI, 1.9–2.7). TB incidence increased within 6 months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95 % CI, 1.8–2.7).

Conclusions

The durability of protection by IPT was lost within 6–12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010;1:CD000171.PubMed
4.
Rangaka M, Wilkinson RJ, Boulle A, Glynn JR, Fielding K, Van Cutsem G, et al. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial. Lancet. 2014;384(9944):682–90.CrossRefPubMedPubMedCentral
5.
Kirenga BJ, Worodria W, Massinga-Loembe M, Nalwoga T, Manabe YC, Kestens L, et al. Tuberculin skin test conversion among HIV patients on antiretroviral therapy in Uganda. Int J Tuberc Lung Dis. 2013;17(3):336–41.CrossRefPubMed
6.
Churchyard GJ, Fielding KL, Lewis JJ, Coetzee L, Corbett EL, Godfrey-Faussett P, et al. A trial of mass isoniazid preventive therapy for tuberculosis control. N Engl J Med. 2014;370(4):301–10.CrossRefPubMed
7.
Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T, Shang N, et al. 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377(9777):1588–98.CrossRefPubMed
8.
Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011;365(1):11–20.CrossRefPubMedPubMedCentral
9.
Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T, Mosimaneotsile B, et al. Tuberculosis incidence after 36 months' isoniazid prophylaxis in HIV-infected adults in Botswana: a posttrial observational analysis. AIDS. 2015;29(3):351–9.CrossRefPubMed
10.
Enarson DA, Grzybowski S. Incidence of active tuberculosis in the native population of Canada. Can Med Assoc J. 1986;134(10):1149–52.
11.
Comstock GW, Baum C, Snider Jr DE. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am Rev Respir Dis. 1979;119(5):827–30.PubMed
12.
Fielding KL, Grant AD, Hayes RJ, Chaisson RE, Corbett EL, Churchyard GJ. Thibela TB: design and methods of a cluster randomised trial of the effect of community-wide isoniazid preventive therapy on tuberculosis amongst gold miners in South Africa. Contemp Clin Trials. 2011;32(3):382–92.CrossRefPubMed
13.
Grant AD, Coetzee L, Fielding KL, Lewis JJ, Ntshele S, Luttig MM, et al. ‘Team up against TB’: promoting involvement in Thibela TB, a trial of community-wide tuberculosis preventive therapy. AIDS. 2010;24 Suppl 5:S37–44.CrossRefPubMed
14.
Hanifa Y, Grant AD, Lewis J, Corbett EL, Fielding K, Churchyard G. Prevalence of latent tuberculosis infection among gold miners in South Africa. Int J Tuberc Lung Dis. 2009;13(1):39–46.PubMed
15.
Lewis JJ, Fielding KL, Grant AD, Chihota VN, Popane F, Luttig M, et al. Eligibility for isoniazid preventive therapy in South African gold mines. PLoS One. 2013;8(11):e81376.CrossRefPubMedPubMedCentral
16.
Lewis JJ, Charalambous S, Day JH, Fielding KL, Grant AD, Hayes RJ, et al. HIV infection does not affect active case finding of tuberculosis in South African gold miners. Am J Respir Crit Care Med. 2009;180(12):1271–8.CrossRefPubMedPubMedCentral
17.
Smieja MJ, Marchetti CA, Cook DJ, Smaill FM. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev. 2000;2:CD001363.PubMed
18.
Verver S, Warren RM, Beyers N, Richardson M, van der Spuy GD, Borgdorff MW, et al. Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med. 2005;171(12):1430–5.CrossRefPubMed
19.
Lahey T, Mackenzie T, Arbeit RD, Bakari M, Mtei L, Matee M, et al. Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior active tuberculosis. Clin Infect Dis. 2013;56(1):151–8.CrossRefPubMedPubMedCentral
20.
Hayes RJ, Moulton LH. Cluster randomised trials. Interdisciplinary Statistics Series. London: Chapman & Hall/CRC Press; 2009.CrossRef
21.
Marx FM, Dunbar R, Enarson DA, Williams BG, Warren RM, van der Spuy GD, et al. The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study. Clin Infect Dis. 2014;58(12):1676–83.CrossRefPubMed
22.
Vynnycky E, Sumner T, Fielding KL, Lewis JJ, Cox AP, Hayes RJ, et al. Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy. Am J Epidemiol. 2015;181(8):619–32.CrossRefPubMedPubMedCentral
23.
Kleinschmidt I, Churchyard G. Variation in incidences of tuberculosis in subgroups of South African gold miners. Occup Environ Med. 1997;54(9):636–41.CrossRefPubMedPubMedCentral
24.
Quigley MA, Mwinga A, Hosp M, Lisse I, Fuchs D, Porter JDH, et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults. AIDS. 2001;15(2):215–22.CrossRefPubMed
25.
Johnson JL, Okwera A, Hom DL, Mayanja H, Mutuluuza Kityo C, Nsubuga P, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS. 2001;15(16):2137–47.CrossRefPubMed
26.
Golub JE, Saraceni V, Cavalcante SC, Cohn S, Pacheco AG, Lau B, et al. Durability of isoniazid preventive therapy in HIV-positive patients in a medium burden TB setting. Atlanta, GA: 20th Conference on Retroviruses and Opportunistic Infections; 2012. Poster 190 LB.
27.
Golub JE, Cohn S, Saraceni V, Cavalcante SC, Pacheco AG, Moulton LH, et al. Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: The TB/HIV in Rio (THRio) Study. Clin Infect Dis. 2015;60(4):639–45.CrossRefPubMedPubMedCentral
28.
Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2013;41(1):140–56.CrossRefPubMedPubMedCentral
29.
Houben RM, Sumner T, Grant AD, White RG. Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings. Proc Natl Acad Sci U S A. 2014;111(14):5325–30.CrossRefPubMedPubMedCentral
30.
van Rie A, Warren R, Richardson M, Victor TC, Gie RP, Enarson DA, et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med. 1999;341(16):1174–9.CrossRefPubMed
31.
Charalambous S, Grant AD, Moloi V, Warren R, Day JH, van Helden P, et al. Contribution of reinfection to recurrent tuberculosis in South African gold miners. Int J Tuberc Lung Dis. 2008;12(8):942–8.PubMed
32.
Crampin AC, Mwaungulu JN, Mwaungulu FD, Mwafulirwa DT, Munthali K, Floyd S, et al. Recurrent TB: relapse or reinfection? The effect of HIV in a general population cohort in Malawi. AIDS. 2010;24(3):417–26.CrossRefPubMedPubMedCentral
33.
Andrews JR, Noubary F, Walensky RP, Cerda R, Losina E, Horsburgh CR. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin Infect Dis. 2012;54(6):784–91.CrossRefPubMedPubMedCentral
34.
Sharma SK, Sharma A, Kadhiravan T, Tharyan P. Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB. Cochrane Database Syst Rev. 2013;7:CD007545.PubMed
35.
Stagg HR, Zenner D, Harris RJ, Munoz L, Lipman MC, Abubakar I. Treatment of latent tuberculosis infection: a network meta-analysis. Ann Intern Med. 2014;161(6):419–28.CrossRefPubMed
36.
Corbett EL, Churchyard GJ, Clayton TC, Williams BG, Mulder D, Hayes RJ, et al. HIV infection and silicosis: the impact of two potent risk factors on the incidence of mycobacterial disease in South African miners. AIDS. 2000;14(17):2759–68.CrossRefPubMed
37.
38.
Suthar AB, Lawn SD, del Amo J, Getahun H, Dye C, Sculier D, et al. Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis. PLoS Med. 2012;9(7):e1001270.CrossRefPubMedPubMedCentral
Metadata
Title
The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study
Authors
Sabine M. Hermans
Alison D. Grant
Violet Chihota
James J. Lewis
Emilia Vynnycky
Gavin J. Churchyard
Katherine L. Fielding
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2016
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-016-0589-3

Other articles of this Issue 1/2016

BMC Medicine 1/2016 Go to the issue

Commentary

Empowered citizen ‘health hackers’ who are not waiting

Research article

Predictive validity of the UKCAT for medical school undergraduate performance: a national prospective cohort study

Review

Diagnostic ‘omics’ for active tuberculosis

Guideline

Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression

Research article

Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature

Research article

What works for whom in pharmacist-led smoking cessation support: realist review