1. Tuberculosis in the Mining Industry: Clinical and Epidemiological Issues David Rees

2. IPT silicosis Clinical guidelines on IPT for patients with silicosis in South Africa de Jager et al. Occupational Health Southern Africa, 2014 TST testing recommended Increase in INH treatment to 36 months in some

3. IPT INH-resistant TB? Systematic review 1950s to 2003 Balcells et al 2006 13 studies 18 095 persons on INH 31 resistant cases 17 985 controls 24-28 in controls Summary RR = 1.45 (0.85-2.47) HIV + = HIV negative

5. Systematic review conclusions “The findings do not exclude an increased risk for INH-resistant TB after IPT.” “IPT substantially reduces the risk for active TB disease…and we support the expansion of its use.”

6. Thibela ( van Halsema et al. AIDS 2010) TB after recent IPT has prevalence of drug resistance similar to background and treatment outcomes typical of this setting. These data support wider implementation of IPT.

7. Silicosis excluding active TB Message: exclude from IPT programmes persons with active TB Symptom screen + CXR (Night sweats, fever, weight loss or cough > 24 hours) HIV positive add sputum culture/XPERT (HIV positive + silicosis = PTB ++++)

8. Adverse events Hepatitis Hypersensitivity (skin) Peripheral neuropathy CNS toxicity

9. Hepatitis is rare Uganda 2018 Haiti 784 subjectsNo severe or fatal hepatitis Significant ALT elevation generally in < 1% Case fatality rate of 0.07/1000 persons completing therapy HIV + = HIV negative ATS Hepatotoxicity of anti-TB drugs 2006

10. Thibela (Grant et al. AIDS 2010) Adverse events nPercentage of 24 221 participants Total132 (130 people)0.54% Hypersensitivity rash 610.25% Peripheral neuropathy 500.21% Clinical hepatotoxicity 170.07% Convulsions40.02% Serious adverse events (2 hapatotoxicity + 2 convulsions) 40.02%

11. Guidelines for IPT in people with silicosis (1/1 ILO) CategoryDuration of IPT HIV + Follow DoH Guidelines NDoH The South African Antiretroviral Treatment Guidelines 2013 HIV - TST not doneIPT for 6 months TST negativeNo IPT indicated TST positiveIPT for at least 36 months

12. ? IPT in currently employed

13. Silicosis

14. UVGI National UVGI Technical Task Team NIOH, UP, UCT, CSIR (Harvard, CDC/NIOSH) Proposal for regulating devices at the DoH Two new SABS Standards proposed: (1) Design; (2) Installation and Maintenance Late 2014?

15. UVGI

16. Works √ Design (closed, open) Installation (e.g. air movement, energise bugs) Maintenance (8000 hours)

17. UVGI National..... Regulation at the Department of Health Two SABS standards: (1) Design; (2) Due end of 2014

18. Tuberculosis and silica exposure In vitroStrong AnimalVery few (convincing) HumanNot many HumanOne (definitely no silicosis)

19. Smoking adjusted rate ratio (RR) for tuberculosis for 2 255 gold miners Presence of silicosis Cumulative dust quartile RR (95% Confidence interval) Absent on necropsy OR radiology (1 388, PTB = 40) Low Medium Medium high High 1.0 1.6 (0.6-4.0) 2.4 (.97-5.9) 3.8 (1.6-9.4) Hnizdo E and Murray J Occup Environ Med 1998

20. Smoking adjusted rate ratio (RR) for tuberculosis for 2 255 gold miners Presence of silicosis Cumulative dust quartile RR (95% Confidence interval) Absent on necropsy (577, PTB = 18) Low Medium Medium high High 1.0 1.11 (0.3-4.0) 1.42 (0.4-4.7) 1.38 (0.3-5.6) Hnizdo E and Murray J Occup Environ Med 1998

21. Tuberculosis and silica exposure (teWaterNaude et al. 2006)

22. POR95% CI Cumulative respirable quartz 1.861.08-3.22 How much silica to increase risk of PTB? When does risk start?

23. PTB at autopsy in gold and platinum miners,1975 - 2012 Data source: PATHAUT database, 28 August 2014 Pathology Division, National Institute for Occupational Health, Johannesburg A gold or platinum miner is defined as any miner who worked mostly in the gold or platinum mining industries

24. PATHAUT HIV Social conditions Gold miners (increased infector pool) Silica in platinum mines (even at low levels)?? Return to work

25. Silica exposure platinum mines AuthorsNumber of minesSilica % or concentrations Biffi and Belle20.45% stope rock samples Respirable dust < 0.2% Decker et al1Respirable dust 0.018 – 0.035 mg/m 3 Breedt et al1 (48 measurements) Respirable dust 8% and 16% rest < 5% respirable dust 0 – 0.032 mg/m 3 TLV TWA = 0.025mg/m 3

26. Platinum mining and silicosis No. of autopsies: employed > 1 year + preliminary information only platinum mining No. with silica related conditions No. with silicosis and “confirmed” no gold mining 3 863490 lymph nodes25 lymph 3 86385 silicosis5 silicosis Nelson G, Murray J. Occupational Medicine 2013 Platinum mining probably causes silicosis Rare Radiologically apparent? Hesitant

28. Smoking Current smoking increases the risk of TB (10% reduction in TB cases if no one smoked) In people with silicosis smoking cessation may reduce 32.4% of the risk of getting TB [Leung, 2007] Current smoking may double the risk of recurrence of TB [Yen, 2014]

29. Does TB increase the risk of silicosis? No evidence May do so on theoretical grounds

30. Does continued silica exposure increase risk of recurrence of TB? Unclear No? In silicotics, prior TB treatment protective (4 x less chance of TB) [Chang, 2001] Treatment conferred slight protection South African gold miners for 5 years [Corbett, 2000]. Then risk increased. South African gold miners: no increased risk of recurrence with continued exposure [Cowie, 1989]

31. Does continued silica exposure increase risk of recurrence of TB? Yes? HIV negative South African gold miners: past TB increased risk of TB by 2.2 times; surface work reduced risk of TB by 70% compared to underground. [Corbett, 2003] South African gold miners: recurrence in 20% of treated TB [Sonnenberg, 2001] Recurrence without silica exposure?