TB in South African mines

ILO/ WHO Consultation to promote the

engagement of workplaces

12th October 2009

Dr Salome Charalambous

The Aurum InstituteThe Aurum InstituteThe Aurum InstituteThe Aurum Institute

� Independent public benefit organisation that

originated in the South African gold mining industry

� Mission: “An internationally respected African institution that transforms health in the community.”

� TB and HIV prevention and treatment

� Medical research and health systems management

OverviewOverviewOverviewOverview

� Epidemiology of TB in miners

� TB control amongst miners:

� INH preventive therapy

� Active case finding

� TB risk reduction in HIV-infected miners:

� INH preventive therapy

� Active case finding

� Antiretroviral therapy

Epidemiology HIV and TBEpidemiology HIV and TBEpidemiology HIV and TBEpidemiology HIV and TB

TB in South African minersTB in South African minersTB in South African minersTB in South African miners

incidence per 100 000 pop p.a.

Risk factors for TB incidenceRisk factors for TB incidenceRisk factors for TB incidenceRisk factors for TB incidence

2.2

4.4

1.7

4.1

Age

HIV

Silicosis

<40

>40

-ve

+ve*

No

Early

Advanced*

* remained significant in multivariate analysis

p trend <0.001

(Corbett. Am J Resp Crit Care Med 2004:170:673-9)

TB risk with HIV & silicosisTB risk with HIV & silicosisTB risk with HIV & silicosisTB risk with HIV & silicosis

None Possible Probable Early

Silicosis

0

2

4

6

8

10

12

14

16

Per

100 p

ers

on y

ears

HIV-positive HIV-negative

(Corbett EL, AIDS 2000;14:2759-68 )

Silicosis & TB case fatalitySilicosis & TB case fatalitySilicosis & TB case fatalitySilicosis & TB case fatality

(Churchyard GJ, Int J Tuberc Lung Dis, 2000;4;705-712)

Duration of infectiousnessDuration of infectiousnessDuration of infectiousnessDuration of infectiousness

(Corbett L. Am J Resp Crit Care Med 2004:170:673-9)

Smear +ve TBHIV+veHIV-ve

All forms of TB

HIV+veHIV-ve

0.17

1.15

0.8

2.39

0 1 2 3

Mean duration (years)

TB recurrenceTB recurrenceTB recurrenceTB recurrence0.0

00.2

50.5

00.7

51.0

0

0 1 2 3analysis time

hiv3 = HIV negative hiv3 = HIV positive

Kaplan Meyer graph by HIV status

3.5 / 100 py

8.7 / 100 py

• Re-infection accounted for 68% of recurrence

(N=609, FU = 1.02 years)

(Charalambous S et al. Int J Tuberc Lung Dis 2008;12(8):942–948)

Strategies to reduce TB incidenceStrategies to reduce TB incidenceStrategies to reduce TB incidenceStrategies to reduce TB incidence

Reduced burden of

disease, health care

and compensation

costs

HIV prevention

Reduce HIV

incidence/prevalenceReduce silicosis

prevalence

Better dust control

Reduce latent

TB prevalence

Preventive therapy

Reduce active

TB prevalence

Increase active case finding

Reduce institutional TB

transmission

Reduce TB

transmissionReduce rate of

TB in HIV +ves

Diagnose HIV & treat

with ART

(Churchyard GJ, Corbett EL. Handbook of Occupational Health. SIMRAC, 2001)

Strategic framework for TB controlStrategic framework for TB controlStrategic framework for TB controlStrategic framework for TB control

morbidity

infectiousness

asymptomatic

symptomatic, does

not seek care

symptomatic, seeks

care

smear neg, culture neg

smear neg, culture pos

smear pos, culture pos

Passive TB case findingPassive TB case findingPassive TB case findingPassive TB case finding

morbidity

infectiousness

asymptomatic

symptomatic, does

not seek care

symptomatic, seeks

care

smear neg, culture neg

smear neg, culture pos

smear pos, culture pos

Active TB case finding

Active case findingActive case findingActive case findingActive case finding

(Lewis, Am J Resp Crit Care Med in press; Day J, Int J Tuberc Lung Dis 2006;10(5):523-9)

Miners (general) HIV-infected miners

N 1960 899

TB Prevalence 54 (2.7%) 44 (4.9%)

Sensitivity Specificity Sensitivity Specificity

% % % %

Symptoms* 29.4 90.3 59.1 75.6

Symptoms & CXR 49.0 89.4 90.9 59.2

*Symptoms: Night sweats, cough or reported weight loss

Community INH preventive therapy Community INH preventive therapy Community INH preventive therapy Community INH preventive therapy

(IPT): Thibela TB (IPT): Thibela TB (IPT): Thibela TB (IPT): Thibela TB

Standard TB control plus

Community wide IPT

Standard TB control

1954 1957 1960 1963 1966 1969 1972

500

1,000

1,500

2,000

2,500

3,000Passive CFT

INH RCT: 42% pop INH 12mos

INH all residents

TB

incid

ence r

ate

per

100,0

00 p

op p

a

Year

CommunityCommunityCommunityCommunity----wide IPTwide IPTwide IPTwide IPT

(Bethel(Bethel(Bethel(Bethel district, Alaska)district, Alaska)district, Alaska)district, Alaska)

Preliminary results: EnrollmentPreliminary results: EnrollmentPreliminary results: EnrollmentPreliminary results: Enrollment

0%

20%

40%

60%

80%

100%

1 3 5 7 9 11 13 15 17 19 21 23 25 27

recruitment month

% c

onsenting o

f clu

ste

r

1st and 2nd clusters

3rd and 4th clusters

5th, 6th and 7th clusters

8th cluster

N ~27,500

Reasonable retention is achievableReasonable retention is achievableReasonable retention is achievableReasonable retention is achievable0.0

00.2

50.5

00.7

51.0

0pro

portio

n s

till

in the s

tudy

0 30 60 90 120 150 180 210 240 270 300days since first dispensed INH

I1 I2 I3 I4 I5 I6 I8

Clusters

1st & 2nd

3rd & 4th

5th - 7th

INH is safeINH is safeINH is safeINH is safe

� 23,585 pts started INH between July 06 – 31Mar 09

� 126 adverse events recorded� 60 hypersensitivity� 49 peripheral neuropathy� 14 hepatitis� 3 convulsions

� 4 SAEs� 3 hepatitis; 1 definitely related� 1 convulsion; possibly related

� 33 deaths� 31 not related � 1 possibly related� 1 relationship to INH not coded

Control s : Lab subControl s : Lab subControl s : Lab subControl s : Lab sub----studystudystudystudy

First First First First

episodesepisodesepisodesepisodes

Retreatment Retreatment Retreatment Retreatment

episodesepisodesepisodesepisodes

Mean (95% CI)

INH resistance INH resistance INH resistance INH resistance

Controls : Routine dataControls : Routine dataControls : Routine dataControls : Routine data

(Van Halsema, IAS Cape Town 2009)

Strategies to reduce the risk of TB Strategies to reduce the risk of TB Strategies to reduce the risk of TB Strategies to reduce the risk of TB

among HIV positive minersamong HIV positive minersamong HIV positive minersamong HIV positive miners

pre-clinic phase

post-clinic phase

Effectiveness of IPT preEffectiveness of IPT preEffectiveness of IPT preEffectiveness of IPT pre----ARTARTARTART

(Grant AD, JAMA, 2005; 293:2719-2725)

0

500

1000

1500

2000

0 6 12 18 24

time (months)

no

. p

art

icip

an

ts

pre-clinic phase

post-clinic phase

Effectiveness of IPT preEffectiveness of IPT preEffectiveness of IPT preEffectiveness of IPT pre----ART ART ART ART

(Grant AD, JAMA, 2005; 293:2719-2725)

Adjusted IRR 0.54 (0.35-0.83)

IR: 10.9/100PYO

IR: 8.4/100PYO

Antiretroviral therapyAntiretroviral therapyAntiretroviral therapyAntiretroviral therapy

0

5

10

15

20

25

30

35

40

45

<90days 91-180days 181-365days 365-545days 546-720days 721 -900 days

TB

cases/1

00p

yrs

Days since ART initiation

TB incidence (first episode) following ART initiation

>900days

INH preventive therapy on ARTINH preventive therapy on ARTINH preventive therapy on ARTINH preventive therapy on ART0.0

00.2

50.5

00.7

51.0

0

0 5 10 15analysis time in months

inhstart = 0 inhstart = 1

Kaplan-Meier survival estimates

Unadjusted analysis

3.5/100pyrs vs 9.8/100pyrs

Hazard ratio: 0.37 (95%CI 0.25-0.54)

Adjusted analysis

Hazard ratio: 0.57 (95%CI 0.38-0.88)

Conclusions

� Miners high burden of disease due to dual risk factors: silicosis and HIV infection

� Additional strategies are required to control TB:� Active case finding

� INH preventive therapy may be an additional mechanism

� HIV infected individuals� ART

� INH preventive therapy

Aurum Institute for Health Research

Prof. G J Churchyard

Dr D Clark

Dr F Randera

Dr L Coetzee

V. Chihota

Dr C. Van Halsema

Dr J. Day

M. Luttig

T. Crawford

K. Mngadi

London School of Hygiene and Tropical Medicine

Dr K Fielding

Dr A Grant

Dr L Corbett

Dr J Lewis

Dr Y Hanifa

Acknowledgments

INH preventive therapy: Thibela TB INH preventive therapy: Thibela TB INH preventive therapy: Thibela TB INH preventive therapy: Thibela TB

Standard TB control

plus

Community wide IPT

Standard TB control

ResourcesResourcesResourcesResources• TB/HIV tool kit for South African businesses. Global

Health Initiative 2008

• Good Practice Guidance on HIV/AIDS, Tuberculosis and Malaria. International Chamber of Mines and Minerals 2007

• Isoniazid preventive therapy for patients with silicosis 2007. www.wahsa.net.

• Medical surveillance of silicosis and silica-related diseases. Expert Group Meeting. 2008