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

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

http://www.123rf.com/photo_9213959_single-cigarette-butt-with-ash-isolated-on-white-background.html

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?