Robin Wood Desmond Tutu HIV Centre

University of Cape Town

HIV/TB Transmission

1000 BC. Adult Male Mummy, Pre-Columbian Atacama Desert

Tuberculosis case isolation Sanatorium movement

History of Tuberculosis Control

Death rates for tuberculosis England and Wales

2012: HIV and TB

Latent TB

TB disease Susceptible

Time from infection HIV-CD4 ART IPT

Chemotherapy Case finding

1o infection

2ary infection

Latent TB

TB disease Susceptible

Time from infection HIV-CD4 ART IPT

Chemotherapy Case finding

1o infection

2ary infection TUBERCULOSIS TRANSMISSION

Masiphumelele Township

Middelkoop et al. BMC Infect Dis. 2011

Force of TB Infection

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

10.00

6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Forc

e of

Infe

ctio

n (%

)

Force of Infection: Female Force of Infection: Male

• Calculated at specific ages: annual change in prevalence/(1-prevalence)

0

10

20

30

40

50

60

70

80

90

100

5 10 15 20 25 30 35 40

Age

Popu

latio

n pe

rcen

tage

Total TB burden; TST positive prevalence and cumulative TB disease ages 5 to 40 years

School entry 20%

Sexual debut 55%

Peak HIV Prevalence

88%

Wood R, et al. Changing prevalence of TB infection with increasing age in high TB burden townships in South Africa. Int J Tuberc Lung Dis. 2010; 14(4): 406-412.

Proportion infected at force of TB infection of 1% and 7% per annum

Number of Potential TB Exposures is Dependent on the Prevailing Force of Infection

A FOI=1% B FOI=7%

KM 1(100%)

I, PGG1

III, PGG2

BW90 BW900 CH34 NG22 NG24 NG27 NG29 NG30 001

32 (59%)

BW16 BW369 BW393 BW408 BW443 BW444 BW526 BW528 BW558 BW607

GD112 BE GD343 MB7 GD422 001 7 (78%)

IIA, PGG1,2

AF140 AF24 AF151 AF27 AF152 AF86 AF154 AF159 14 (57%)

VIII, PGG3

VII, PGG3

BF107 BF108 BF115 BF71 BJ114 BJ117 BJ119 BJ12 BJ150 BJ156 DF3 EH13 EH7 EH9

GY15 GY18 GY9 HM27 JG JG1 LE14 LU13 LU8 M101 M106 M107 M48 M54

M98 001 45 (71%)

V, PGG2

AH AH5 AH10 AH51 AH13 AH53 AH26 AH55 AH30 55 (18%)

667 patients 676 isolates Clustered isolates: 465 (69%)

II, PGG1

W1033 W1151 W1153 W1178 W1195 W1263 W1264 W1265 W1266 W1275 W1276 W1350 W145 W181 W320

W321 W330 W451 W570 W577 W616 W636 W655 W656 W657 W706 W713 W724 W725 W726

W757 W777 W778 W799 W898 W942 W943 W944 W945 W967 W968 W969 W970 W971 001

195 (23%

)

BE13 H28 BE3 H36 C2 L1 H 15(47%)

IV, PGG2

Total number of Isolates in SNP cluster (% diversity)

VI, PGG2

AI109 AI134 AI214 AI225 AI230 AI237 AI244 AI265 AI266 AI274 AI280 BA BA130 BA55 BH25 BH26 BH28 BH35 BH42 BH44 BH54 BH57 BM10 BM15 BM16 BM17

BM18 BM2 BM20 BM23 BM29 BM30 BM32 BM33 BM38 BM39 BM46 BM47 BM48 BM49 BM52 BM57 BM67 BM81 BM82 BM83 BM96 BM98 CC100 CC102 CC107 CC112

CC113 CC118 CC12 CC121 CC122 CC123 CC124 CC125 CC126 CC127 CC128 CC129 CC13 CC130 CC131 CC136 CC156 CC159 CC172 CC179 CC187 CC202 CC203 CC208 CC222 CC223

CC224 CC225 CC226 CC227 CC230 CC25 CC251 CC252 CC253 CC259 CC26 CC27 CC28 CC281 CC282 CC283 CC284 CC285 CC302 CC306 CC316 CC317 CC33 CC34 CC44 CC53

CC61 CC62 CC71 CC73 CC76 CC77 CC80 CC82 CC83 CC84 CC86 CC91 CC95 CC96 CC97 CC98 CC99 CP3 CP4 CP6 CP8 DB21 ED26 ED30 FA3 FO

FO8 GB11 GG GO17 GO33 GO41 GO8 HP17 HP27 HP71 HP73 HP78 HP95 IH2 IL2 IL34 IL66 IL69 LX27 LX29 MH OJ P27 Q35 Y5 001

303 (52%)

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

2002 2003 2004 2005 2006 2007 2008

Year

TB n

otifi

catio

n ra

tes/

100,

000

HIV-infected TBrates

HIV-uninfectedTBrates

All patients of unknown status assumed HIV-infected

All patients of unknown status assumed HIV-uninfected

Changes in TB incidence with “ART Roll Out”

Middelkoop K, et al. Am J of Resp Crit Care Med. 2010; 182: 1080-5.

Know your Epidemic. Know your Response. Know where Infections are Occurring

Wells Riley Equation predicts TB Cases among Susceptibles exposed to TB Infection within Closed Spaces

TB infections = S(1-e-Itpq/Q)

Infective sources = I Infective quanta = q

Susceptible = S Respiratory rate = p

Time at risk = t Ventilation = Q

Social Mixing Patterns in a South African Township

Johnstone-Robertson SP, et al. Am J Epidemiol

Community Buildings

Creche/School

Health Clinics

Other Locations

Other Households

Shebeens Shops

Sports Activities

Transport Work

Own Household

1

10

100

1000

10000

1 10 100 1000 10000

Tim

e Sp

ent a

t Loc

atio

n (h

ours

)

Number of Indoor Contacts at Location

Where are Indoor Contacts Made?

• Low contact number • Prolonged period • Intergenerational mixing

• Childhood TB disease and infection associated with adult TB cases on residential plot

Childhood Household Transmission

Middelkoop et al. SAMJ 2009

TB cases TB infections

Adult Household Transmission

Middelkoop et al. JID 2009

0

10

20

30

40

50

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >450

10

20

30

40

50

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >45

0

10

20

30

40

50

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >450

10

20

30

40

50

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 >45

Age strata

Mea

n nu

mbe

r of c

onta

cts/

part

icip

ant/

day

Households Transport

School/Creche Work

Number of Indoor Contacts by Location and Age

CO2, RH & Temperature Sensor (CoZIR)

Power Supply

Thermal cut out

USB interface

GPS

Figure 1. Average C02 concentrations (solid lines) and 95% confidence intervals (shaded regions) over time in single trips on taxis, trains, and buses. The horizontal dashed line indicates the average outdoor CO2 concentration (410 ppm).

Andrews, Morrow, Wood. Modeling the role of public transportation in sustaining tuberculosis transmission in South Africa

Figure 2. Annual risk of tuberculosis infection (ARI) according to number of trips taken in a year, stratified by mode of transit (not including combinations of modes).

Andrews, Morrow, Wood. Modeling the role of public transportation in sustaining tuberculosis transmission in South Africa

Work / school Transport Own Home Other Home Other Place

0

0.05

0.1

0.15

0.2

0.25

17:00 19:00 21:00 23:00 1:00 3:00 5:00 7:00 9:00 11:00 13:00 15:00 17:00

Time of Day

Rebre

athed

litres

per m

inute

0

1

2

3

4

5

6a

0

0.05

0.1

0.15

0.2

0.25

17:00 19:00 21:00 23:00 1:00 3:00 5:00 7:00 9:00 11:00 13:00 15:00 17:00

Time of Day

Rebre

athed

litres

per m

inute

0

1

2

3

4

5

6b

0

0.05

0.1

0.15

0.2

0.25

17:00 19:00 21:00 23:00 1:00 3:00 5:00 7:00 9:00 11:00 13:00 15:00 17:00

Time of Day

Rebre

athed

litres

per m

inute

0

1

2

3

4

5

6c

Liters of Rebreathed Air (a=15, b=77, c=150 Lts/day)

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

8:00 8:30 9:00 9:30 10:00 10:30 11:00 11:30 12:00 12:30 13:00 13:30 14:00 14:30 15:00

Time of Day

Reb

reat

hed

litr

es p

er m

inu

te

Acknowledgements • Carl Morrow • Samuel Ginsberg

• Jason Andrews • Kimberley Racow