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

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dc.contributor.authorHermans, Sabine M
dc.contributor.authorGrant, Alison D
dc.contributor.authorChihota, Violet
dc.contributor.authorLewis, James J
dc.contributor.authorVynnycky, Emilia
dc.contributor.authorChurchyard, Gavin J
dc.contributor.authorFielding, Katherine L
dc.date.accessioned2021-10-08T06:54:43Z
dc.date.available2021-10-08T06:54:43Z
dc.date.issued2016
dc.description.abstractBackgroundThe 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.MethodsIn 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 9months 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.ResultsAmong 18,520 participants (96% male, mean age 41years, median follow-up 2.1years), 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 6months 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0589-3) contains supplementary material, which is available to authorized users.
dc.identifier.apacitationHermans, S. M., Grant, A. D., Chihota, V., Lewis, J. J., Vynnycky, E., Churchyard, G. J., & Fielding, K. L. (2016). The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study. <i>BMC Medicine</i>, 14(1), 174 - 177. http://hdl.handle.net/11427/34320en_ZA
dc.identifier.chicagocitationHermans, Sabine M, Alison D Grant, Violet Chihota, James J Lewis, Emilia Vynnycky, Gavin J Churchyard, and Katherine L Fielding "The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study." <i>BMC Medicine</i> 14, 1. (2016): 174 - 177. http://hdl.handle.net/11427/34320en_ZA
dc.identifier.citationHermans, S.M., Grant, A.D., Chihota, V., Lewis, J.J., Vynnycky, E., Churchyard, G.J. & Fielding, K.L. 2016. The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study. <i>BMC Medicine.</i> 14(1):174 - 177. http://hdl.handle.net/11427/34320en_ZA
dc.identifier.issn1741-7015
dc.identifier.ris TY - Journal Article AU - Hermans, Sabine M AU - Grant, Alison D AU - Chihota, Violet AU - Lewis, James J AU - Vynnycky, Emilia AU - Churchyard, Gavin J AU - Fielding, Katherine L AB - BackgroundThe 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.MethodsIn 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 9months 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.ResultsAmong 18,520 participants (96% male, mean age 41years, median follow-up 2.1years), 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 6months 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0589-3) contains supplementary material, which is available to authorized users. DA - 2016 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Medicine LK - https://open.uct.ac.za PY - 2016 SM - 1741-7015 T1 - The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study TI - The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study UR - http://hdl.handle.net/11427/34320 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34320
dc.identifier.vancouvercitationHermans SM, Grant AD, Chihota V, Lewis JJ, Vynnycky E, Churchyard GJ, et al. The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study. BMC Medicine. 2016;14(1):174 - 177. http://hdl.handle.net/11427/34320.en_ZA
dc.language.isoeng
dc.publisher.departmentDivision of Infectious Disease and HIV Med
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Medicine
dc.source.journalissue1
dc.source.journalvolume14
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12916-016-0589-3
dc.subject.otherIsoniazid preventive therapy
dc.subject.otherLatent infection
dc.subject.otherReactivation
dc.subject.otherReinfection
dc.subject.otherTuberculosis
dc.subject.otherAdult
dc.subject.otherAntitubercular Agents
dc.subject.otherCohort Studies
dc.subject.otherDisease-Free Survival
dc.subject.otherDrug Resistance, Bacterial
dc.subject.otherFemale
dc.subject.otherGold
dc.subject.otherHumans
dc.subject.otherIncidence
dc.subject.otherIsoniazid
dc.subject.otherMale
dc.subject.otherMiddle Aged
dc.subject.otherMiners
dc.subject.otherMycobacterium tuberculosis
dc.subject.otherPrevalence
dc.subject.otherProspective Studies
dc.subject.otherRisk Factors
dc.subject.otherSouth Africa
dc.subject.otherTuberculosis
dc.subject.otherAntitubercular Agents
dc.titleThe timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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