Data from a detailed sub-study of minor adverse effects among 498 Thibela TB enrolees showed that IPT was very well tolerated. Sixty-five percent of participants reported feeling better on IPT, and in 55% of cases, this was attributed by participants to increased appetite. Overall, IPT was well tolerated by the great majority of individuals in this trial.

Data from TB screening at enrolment of almost 26 000 individuals to the Thibela TB intervention showed that 1.4% had definite or probable tuberculosis. Compared with screening by symptoms alone, screening by symptoms plus chest radiography increased the number of definite tuberculosis cases detected by 2.6 fold. The learning from this was that TB screening prior to IPT detects a substantial burden of tuberculosis and contributes to intensified tuberculosis case finding and that in a South African mining setting, chest radiography is a useful addition to a symptom screen. This was particularly interesting because these findings were in the context of an already highly screened population.

This is important because persons with active TB should go onto full TB treatment and not IPT alone.

Among the individuals screened at enrolment into the main Thibela study who were considered not to have active TB and who were therefore dispensed INH, 48 (0.24%) were classified as TB screening failures as they were diagnosed with active TB within three months of enrolment. Being in HIV care, having a lower body mass and alcohol use was associated with increased risk of TB being missed at screening. The learning from this was that the screening protocol missed very few cases, supporting the use of symptom and chest radiographic screening to exclude TB prior to starting IPT.

This finding is particularly important to clinicians who traditionally avoid IPT as a key tool in the fight against TB for fear of INH mono-resistance.

This sub-study of Thibela, with results suggesting no excess of isoniazid resistance among cases occurring after IPT, was published in the journal AIDS.

A major obstacle to wider implementation of IPT was the lack of an evidence-based policy on the most appropriate screening tool to exclude active TB prior to starting IPT. Aurum and its collaborators contributed two datasets to a meta-analysis led by WHO using individual patient data which addressed this question. As a result, a four-symptom screening tool was recommended with high sensitivity and good negative predictive value in most populations. A paper describing this meta-analysis was published by PLoS Medicine.

In January 2010 Thibela investigators participated in a WHO meeting to revise the international body’s guidelines on IPT. The revised guidelines, entitled Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings, recommended:

South Africa was the first country to adopt the new WHO guidelines. In March 2010, Thibela TB investigators participated in a meeting convened by the national Department of Health Thibela TB and CREATE to finalise the South African IPT guidelines. The South African National Strategic Plan on HIV, STIs and TB, 2012-2016 recommends:

As a result of the change in the South African guidelines, researchers reported a dramatic increase in the number of HIV-positive patients in PEPFAR-funded South African clinics who were being prescribed INH, up from 3 309 in January to March 2010 to 49130 in January to March 2011[1].

Disseminating our experience in IPT implementation in a supplement to a high-impact journal Aurum and its collaborators contributed 8 articles to the prestigious CREATE special supplement on IPT implementation published in the journal AIDS in 2010. These articles primarily described lessons learned in wide-scale IPT implementation.

The Thibela experience has been presented at a number of international meetings.

A particular highlight was the WHO/IAS/CREATE-sponsored meeting on TB / HIV research priorities prior to the International AIDS Society meeting in Cape Town, July 2009, which attracted an audience of TB and HIV experts from around the world. A summary of Aurum’s experience in IPT implementation was presented. Clare van Halsema, a Thibela researcher, received an International Aids Society TB/HIV Research Prize for her Thibela paper presented at that conference.

The Thibela study’s work on adverse events was presented at the Union World Conference on Lung Health in Berlin, Germany, in November 2010. Presentations included work on the spectrum of non-tuberculosis mycobacteria identified at microbiological screening for TB at Thibela study sites.

At the CROI conference in Boston, Massachusetts, in February 2011 Dr Alison Grant, a Thibela TB co-investigator, presented on new horizons in latent TB treatment, including new regimens, the duration of IPT, IPT and antiretroviral therapy (ART) and obstacles to implementation of IPT. The CROI conference in Seattle, Washington State, in March 2012 saw a presentation on preliminary data arising out of the Thibela programme, as well the study’s key results.

There was a presentation on Thibela at the annual network meeting of the AIDS Clinical Trials Group meeting in Washington DC in July 2012, which served to inform the HIV/AIDS research world of the relevance of the Thibela study to TB control in HIV-positive individuals. Another important presentation on Thibela at regional level took place at the Southern African Development Community (SADC) ministerial meeting in Luanda, Angola, in April 2012. The meeting brought together ministries of health, finance and labour and industry representatives, to discuss TB in the mining sector. It was expected to culminate in a SADC declaration on the issue of TB and a regional plan of action to inform future TB interventions.

At the third South African TB Conference in Durban in June 2012, a full analysis of the data arising from Thibela was finally presented, to widespread interest and acclaim.

Dr Violet Chihota presented the Thibela findings to a seminal quarterly TB departmental meeting of the South African national Department of Health in August 2012. In November of the same year, she also presented on Thibela to the Union World Conference on Lung Health in Kuala Lumpur, Malaysia, in terms of the contributions of the mining industry to TB care: successes and challenges.

The final papers on Thibela TB are expected to be published in a major international medical journal during 2013.

Gavin Churchyard, Katherine Fielding, Alison Grant, Leonie Coetzee, James Lewis, Violet Chihota, Clare van Halsema, Evans Muchiri, Keith Tomlin, Susan Dorman, Dave Clark, Barun Mathema, Richard White, Emilia Vynnycky, Andy Cox, Tom Sumner, Liz Corbett, Peter Godfrey-Faussett, Dick Chaisson, Richard Hayes.

Trisha Crawford, JJ Govender, N Hattingh, AN Ramphela, D Rossouw, Z Stokwe, H Mabona, A Ward, F Maeko, L Pretorius. Quality Assurance: Lorraine Africa, A Lakhi, I Mantsoe, A Els Laboratory Technologists: Minty van der Meulen, Cynthia Kekana Carletonville: Mariette Luttig, Jeanette Louwies, Smanga Ntshele, Frances de Bruin, Elsie Ngwenya, Petros Molefe, John Mdluli, Philip Herselman, JE Ngwenya, PN Khabeng, C Matlala, MN Khame, MA Khomo, CMK Kitsa, C Lekabe, ME Lonkokile, BD Matlhale, NE Mazini, MM Moagi, PL Morake, S Ntwasa, SA Scwebu, J Mokhetle, TP Ntetha, TTM Mosiro, RZ Maseko, EM Manju, MD Matlanyane, T Balfour, NG Makiba, G Dobo, SP Molefe, AN Mathebula, TM Diko, MS Moraladi, GM Herselman, NM Majikijela, FV Masela, MM Tagane, M Tshitsha, C Vermaak, MM Moleoa, MM Tshangane.

Dorothy Muller, TS Nteleki, Kathy Mngadi, Malebo Moshomane, Ephraim Moseki, Bekiwe Ncwana, Jacob Mongale, Grace Pilane, Nathi Mngadi, Lumkile Tsembei, EK Moseki, CD Mohlomi, FJ Gxaweni, KM Lebone, J Tsotsotso, TB Vilakazi, B Pei, RT Moloisane, C Monnamere, NA Mora, G Soshongane, NR Manyokele, MP Fikizolo, MM Makgale, P Mashupi, AS Senne, VB Malepo, T Booysen, KD Mogoje, MG Polori, A Malachamela, S Kgwefane, G Thwane, NP Motsatse, H Melani, BD Montingoa, MJ Witkoei, G Lebeko, SL Mohammed, L Tlharipe, A Malitjane.