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Tuberculosis in the Mining Industry: Clinical and Epidemiological Issues
David Rees
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
IPT INH-resistant TB?
Systematic review 1950s to 2003 Balcells et al 2006
13 studies18 095 persons on INH 31 resistant cases17 985 controls 24-28 in controls
Summary RR = 1.45 (0.85-2.47)
HIV + = HIV negative
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.”
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.
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 ++++)
Adverse events
• Hepatitis
• Hypersensitivity (skin)
• Peripheral neuropathy
• CNS toxicity
Hepatitis is rare
Uganda 2018 Haiti 784 subjects No 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
Thibela (Grant et al. AIDS 2010) Adverse events n Percentage of 24 221 participants
Total 132 (130 people) 0.54%Hypersensitivity rash
61 0.25%
Peripheral neuropathy
50 0.21%
Clinical hepatotoxicity
17 0.07%
Convulsions 4 0.02%Serious adverse events (2 hapatotoxicity + 2 convulsions)
4 0.02%
Guidelines for IPT in people with silicosis (1/1 ILO)
Category Duration of IPTHIV + Follow DoH
GuidelinesNDoH The South African Antiretroviral Treatment Guidelines 2013
HIV - TST not done IPT for 6 monthsTST negative No IPT indicatedTST positive IPT for at least 36
months
?
IPT in currently employed
Silicosis
UVGI
National UVGI Technical Task TeamNIOH, 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?
UVGI
Works √
Design (closed, open)Installation (e.g. air movement, energise bugs)Maintenance (8000 hours)
UVGI
National .....
Regulation at the Department of Health
Two SABS standards: (1) Design; (2)Due end of 2014
Tuberculosis and silica exposure
In vitro Strong
Animal Very few (convincing)
Human Not many
Human One(definitely no silicosis)
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)
LowMedium
Medium highHigh
1.0 1.6 (0.6-4.0)2.4 (.97-5.9)3.8 (1.6-9.4)
Hnizdo E and Murray JOccup Environ Med 1998
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)
LowMedium
Medium highHigh
1.0 1.11 (0.3-4.0)1.42 (0.4-4.7)1.38 (0.3-5.6)
Hnizdo E and Murray JOccup Environ Med 1998
Tuberculosis and silica exposure (teWaterNaude et al. 2006)
Tuberculosis and silica exposure (teWaterNaude et al. 2006)
POR 95% CI
Cumulative respirable quartz
1.86 1.08-3.22
How much silica to increase risk of PTB?When does risk start?
PTB at autopsy in gold and platinum miners,1975 - 2012
Data source: PATHAUT database, 28 August 2014Pathology Division, National Institute for Occupational Health, JohannesburgA gold or platinum miner is defined as any miner who worked mostly in the gold or platinum mining industries
19751978
19811984
19871990
19931996
19992002
20052008
20110.00
0.10
0.20
0.30
0.40
0.50
TB gold TB plat TB plat no gold
Year
Prop
ortio
n w
ith P
TB
PATHAUT
HIV
Social conditions
Gold miners (increased infector pool)
Silica in platinum mines (even at low levels)??
Return to work
Silica exposure platinum minesAuthors Number of mines Silica % or concentrations
Biffi and Belle 2 0.45% stope rock samples
Respirable dust < 0.2%
Decker et al 1 Respirable dust 0.018 – 0.035 mg/m3
Breedt et al 1 (48 measurements)
Respirable dust 8% and 16% rest < 5% respirable dust 0 – 0.032 mg/m3
TLV TWA = 0.025mg/m3
Platinum mining and silicosisNo. of autopsies: employed > 1 year + preliminary information only platinum mining
No. with silica related conditions
No. with silicosis and “confirmed” no gold mining
3 863 490 lymph nodes 25 lymph 3 863 85 silicosis 5 silicosis
Nelson G, Murray J. Occupational Medicine 2013
Platinum mining probably causes silicosisRareRadiologically apparent?Hesitant
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]
Does TB increase the risk of silicosis?
No evidence
May do so on theoretical grounds
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]
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?
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