Are tuberculin surveys in

children useful to assess TB

incidence?

Babis Sismanidis with acknowledgements

to Brian Williams & Philippe Glaziou

Ho Chi Minh City, 3 June 2010

If the prevalence of tuberculous infection in

children aged A is P then the annual risk of

TB infection is (Styblo rule):

ARI = 1-(1-P)1/A

We use infection prevalence in children to

estimate disease incidence in adults

(assuming infection constant over time)

First the good news…

Frequency distribution of induration sizes in Cape Town

0.00

0.01

0.02

0.03

0.04

0.05

0.06

0.07

1955 1965 1975 1985 1995

AR

TI in

So

uth

Ko

rea

Repeat surveys in South Korea

Halving every ln(2)/0.08

≈ 10 years

Rate of decline = 7.8%/yr

Now the bad news…

0 5 10 15 20 25

Induration size (mm.)

Fre

qu

en

cy (

%)

10

8

6

4

2

0

Annual risk of tuberculous infection in the northern zone of India

Chadha, V.K. et al. Bull. WHO (2003)

A lot of 'noise'!

False test reactions due to

environmental mycobacteria

and (possibly) BCG

Prevalence of environmental mycobacteria seems

to be very high around the equator, declining at

very high and very low latitudes

Frequency distribution of induration sizes in Somalia. Red:

fitted; black: environmental; green: TB

Dependence on BCG

(Somalia 2006)

Proportion positive with and without a BCG scar

Scar No scar Unknown

Lack of clear method for

establishing prevalence of infection

and hence ARTI

Cut-off methods, mirror methods, model-

based mixture methods, latent class analysis

ARTI calculated based on different methods;

Snanaube, PLoS ONE, 4;11:7749

Wide uncertainty of the process

Measurement error, time dependency with

reading time,

Clear digit

preference

Dependence on testing day

(Somalia 2006)

Proportion positive when the induration was read on three

of four days after the challenge

Low infection prevalence

As the incidence declines, the prevalence

of infection declines and it gets much

harder to measure it

Changes in distribution patterns of

induration size in Korea

Ethical considerations

• No (or little) benefit to surveyed individuals

• Most often done in children

• Ethical requirements:

– Clearance from ethical committee

– Informed consent from parents/guardians

– Ascent from children

The way forward?

New generation of diagnostic tools;

Interferon Gamma Release Assays

Tuberculin skin test responses in

houehold contacts of active TB cases979 children, median age 7yr, Istanbul

0

10

20

30

40

50

60

70

80

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31

ELISpot -ve

ELISpot +ve

Source: Bakir et al 2006

In summary

• Interpretation of data can be problematic

• Diagnostic value of test difficult to predict

• Uncertainty about the relationship between prevalence of infection and disease incidence

• Uncertainty about time changes in the distribution of determinants of induration size

• Difficult to interpret time-changes in ARI

Use of tuberculin surveys among children to estimate

disease incidence is not recommended