TB, Silicosis and HIVArchitectural and Engineering Approaches

to Airborne Infection ControlWinter Course 6 July 2015

Brian WilliamsSouth African Centre for Epidemiological Modelling and Analysis

Wits HIV Reproductive Health Institute

Silicosis: An inflammatory condition: particles of silica dust are inhaled, macrophages ingest the dust particles and set off an inflammation response which leads to fibrosis or progressive scarring of the lungs.

Tuberculosis: A bacterial infectious disease transmitted though coughing.

HIV: a viral, mainly sexually transmitted, disease.

Silicosis increases the risk of TB by about 3 times.HIV increases the risk of TB by 5 to 10 times.

Before Europeans colonized southern Africa

• There were no hard-rock mines so no silicosis

• There was no tuberculosis

• HIV did not exist.

All diseases of colonization and industrialization in the 19th and 20th century

Countries of the world ordered by TB incidence

TB in

cide

nce/

100k

/yea

r

0

200

400

600

800

1000

1200

0 50 100 150 200 250

SwazilandSouth Africa

NamibiaZimbabwe

Sierra LeoneLesothoDjibouti

BotswanaMozambique

Swaziland

South Africa

NamibiaSierra Leone

DjiboutiMozambique

ZimbabweLesotho

Botswana

TB in the world

0

5

10

15

20

25

30

0 50 100 150 200

SwazilandBotswana

LesothoSouth Africa

ZimbabweZambia

NamibiaMozambique

MalawiUganda

KenyaTanzania

Countries of the world ordered by HIV prevalence

HIV

pre

vale

nce

in a

dults

(%)

Swaziland

South Africa

NamibiaMozambique

Zimbabwe

BotswanaLesotho

ZambiaMalawi

UgandaKenyaTanzania

HIV in the world

Where did it all begin?

William Gorgas, Surgeon General, US Army

1910: Controlled yellow fever and malaria in Panama by draining swamps, fumigation, mosquito netting and clean water.

1913: Report for the Transvaal Chamber of Mines“The crowded and unsanitary living conditionscombined with the stressful working conditions lead to very high rates not only of silicosis and tuberculosis but also of pneumonia.”

Tuberculosis on the mines in the 1920s

Annual incidence of TB ~1,800 per 100,000 miners

Approximately 1,000 miners with TB disease were being repatriated every year to rural areas of southern Africa.

Leon Commission of Enquiry into Health and Safety on the Mines: 1996

Men working underground for 20 years have a 20% to 30% chance of developing silicosis.

“There is no evidence to indicate a decline in the prevalence or severity of any occupational disease in the mining industry during the past twenty years ... radical steps are required to deal with the seriousoccupational health problems described in the evidence presented to the Commission.”

Start with HIV

1985 1990 1995 2000 1985 1990 1995 2000

Impact of ART on HIV and TBin Brazil

Mortality TB incidence MonoDualTriple

www.aids.gov.br/boletim/bol_htm/boletim.htm March 2001

ART reduced mortality in AIDS cases by 96% and TB incidence by 88%

2000

Viral load suppression

Weeks Months Years

Palmer 2008 Proceedings of the National Academy of Science

Good news: 10,000x reduction after 1 year Bad news: No elimination of the virus

Vira

l loa

d/m

L2008

Viral load & transmission

Reducing viral load to 100/mL reduces transmission by 99%

Attia 2009 AIDS

Viral load/mL

Tran

smis

sion

s/yr

0.00001

0.00010

0.00100

0.01000

0.10000

1.0000010 100 1000 10000 100000 1000010 100 1,000 10,000 100,000 1,000,000

1.00000

0.10000

0.01000

0.00100

0.00010

0.00001

2009

20080.02

0.01

0.001980 2000 2020 2040

0.15

0.10

0.05

0.001980 2000 2020 2040

Pre

vale

nce

I

ncid

ence No intervention

ART CD4 < 350/μLImmediate ART

Stopping the epidemic with ART

0.001

0.005

0.0001980 2000 2020 2040

Mor

talit

y

Drug resistance: Vancouver

Inci

denc

e/yr

Acquired resistance

Vira

l loa

d<

50/m

L (%

)

Plasma viral load

Gill 2010 Clinical Infectious Diseases

0.01

0.10

0.20

0.02

0.04

1995 2000 20050.01

0.10

0.20

0.02

0.04

1995 2000 200501

90

80

70

600101

90

80

70

60

Reducing community viral load drives acquired resistance down

0.20

0.10

0.04

0.020.01

90

80

70

601995 2000 2005 1995 2000 2005

2010

Cos

t of u

nive

rsal

AR

T as

a p

erce

ntag

e of

GD

P

Cum

ulat

ive

cost

of u

nive

rsal

AR

T

What does this do to TB?

HIV drives TBNunn et al. Nature Reviews of Immunology. 2005; 5: 819-26.

Delay ~ 5 years

IRR ~ 15

Kisumu, Kenya

9.4

1.11.11.0

5.9

2.2

0

2

4

6

8

10

1991 1994 1995 1997 1998 1999

Ann

ual i

ncid

ence

(%)

. HIV- HIV+HIV- HIV+

1.02.2

1.1

5.9

1.1

9.4

1991-1994 1995-1997 1998-1999

10

8

6

4

2

0

Inci

denc

e (%

p.a

.)9.4

1.11.11.0

5.9

2.2

0

2

4

6

8

10

1991 1994 1995 1997 1998 1999

Ann

ual i

ncid

ence

(%)

. HIV- HIV+HIV- HIV+

1.02.2

1.1

5.9

1.1

9.4

1991-1994 1995-1997 1998-1999

10

8

6

4

2

0

Inci

denc

e (%

p.a

.) IRR ~ 10

IRR ~ 2

Gold Miners in South Africa

Corbett et al. Journal of Infectious Diseases 2003; 188: 1156-63

TB in HIV positive people does not affect HIV-negative people

Prevalence = Incidence x Duration

HIV-positive people with TB progress about 10 times faster

than HIV negative people.

Corbett et al. Am J Respir Crit Care Med. 2004; 170: 673-9; Wood et al. Am J Respir CritCare Med. 2007; 175: 87-93; Williams et al. Am J Respir Crit Care Med. 2007; 175: 6-8.

If CD4 falls by 100/μLTB increases by 38% (25%− 53%)

CD4 cells/μL

Ann

ul in

cide

nce

of T

B

Antonucci et al. JAMA. 1995; 274: 143-8; Badri et al. Lancet. 2002; 359: 2059-64.

I ∝ e-0.0038C

During the acute phase of HIV:

CD4 cell counts drop by 25% (9%−41%)1

TB incidence rises 3.8 (1.6−15.2) times.2

1. Williams et al. J Infect Dis. 2006; 194: 1450-8; Williams et al. Proc Nat Acad Sc USA. 2010; 107: 17853-4; 2. Antonucci et al. JAMA. 1995; 274: 143-8; Badri et al. Lancet. 2002; 359: 2059-64.

Explains the early impact on gold mines

0

100

200

300

400

500

600

700

1980 1985 1990 1995 2000 2005 2010

TB in

cide

nce/

100k

/yr

TB in

cide

nce/

100k

/yr

0

100

200

300

400

500

600

700

1980 1985 1990 1995 2000 2005 2010

TB in

cide

nce/

100k

/yr

TB in

cide

nce/

100k

/yr

0.00

0.05

0.10

0.15

0.20

0.25

0.30

1980 1985 1990 1995 2000 2005 2010

HIV

pre

vale

nce

0

100

200

300

400

500

1980 1985 1990 1995 2000 2005 2010

TB in

cide

nce/

100k

/yr

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

1980 1985 1990 1995 2000 2005 2010

HIV

pre

vale

nce

IRR ~ 34 IRR ~ 7.4

11x 2.7x

Zimbabwe Botswana

Williams et al. Proc Nat Acad Sc USA. 2010; 107: 17853-4.

Tube

rcul

osis

HIV

Impact depends on the setting

0

100

200

300

400

500

600

700

1980 1985 1990 1995 2000 2005 2010

TB in

cide

nce/

100k

/yr

TB in

cide

nce/

100k

/yr

0

100

200

300

400

500

1980 1985 1990 1995 2000 2005 2010

TB in

cide

nce/

100k

/yr

IRR ~ 34 IRR ~ 7.4

Zimbabwe Botswana

Williams et al. Proc Nat Acad Sc USA. 2010; 107: 17853-4.

Tube

rcul

osis

Impact depends on the setting

0

200

400

600

800

0 2 4 6 8 10 120

200

400

600

800

0 2 4 6 8 10 12

CD

4/μL

CD

4

CD

4/μL

High CD4: Low TBFast decline: big increase

Low CD4: High TBSlow decline: small increase

Emergence of XDR-TB in Tugela Ferry

Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South AfricaGandhi NR, Moll A, Sturm AW, et al. Lancet 2006; 368: 1575-80.

In 2005 there was an outbreak of XDR TB at COSH. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis.

Year 2004 2005 2006 2007Cases 5 140 97 133

0.0

0.1

0.2

0.3

0.4

0.5

0.6

eThe

kwini

Ugu

uMgu

ngun

dlovu

uT

huke

la uM

zinya

thi

Amajuba

Zu

lulan

d

uMkh

anya

kude

uT

hung

ulu

iLembe

Siso

nke

XD

R /

MD

R

XDR TB in Districts of KwaZulu-Natal 2006

XDR TB in hospitals in uMzinyathi 2006

The outbreak in Tugela Ferry was a failure of

infection control

TB cure rates

WHO says that at least 85% of all TB patients should be cured. Out of 40 countries in sub-Saharan Africa our cure rate of 79% puts us in 25th place. A good place to start would be to make sure that we can cure the patients that we already have.

What about silicosis?

Prevalence of Silicosis in ex-Mine Workers

White in Botswana 30%Trapido in Libode 28%Churchyard in Free State 21%

The mining industry owes ex-miners living in rural areas approximately R3 billion in unpaid compensation

The Occupational Disease in Mines and Works Act

Any person who works or who has worked at a mine or works, or any other person acting on behalf of such a person, may at any time apply to the Director for a medical examination of such a person for the purpose of determining whether such a person is suffering from a compensatable disease....The Director of the Medical Bureau for Occupational Disease is obliged to cause such a person to be medically examined as soon as possible.... ex-mineworkers are entitled to a bi-annual benefit examination and to transport costs on an annual basis.

The way forward: HIV

• People at risk of HIV must be tested at least once a year and started on ART as soon as they become infected.

• Mobilize community support to ensure high rates of uptake and compliance.

• Find a way to provide drugs and support to a very mobile population especially migrant workers.

• Smart cards for providing drugs and monitoring patients? Regional network of clinics?

The way forward: TB

• Universal access to ART will take care of about half of the TB problem.

• Cure the patients we already have.• Life-time follow up of all TB patients.• Good infection control. Ventilation? UV lights?• Smart cards for providing drugs and monitoring

patients?

The way forward: silicosis

• Ensure that all ex-miners receive the compensation to which they are entitled under law.

• Find ways to limit exposure to silica dust.• If necessary plan a future which does not depend

on gold.