Brian Williams with acknowledgements to Philippe Glaziou · ARTI in South Korea South Korea Halving...
Transcript of Brian Williams with acknowledgements to Philippe Glaziou · ARTI in South Korea South Korea Halving...
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Late night thoughts on tuberculin surveys
Brian Williams with acknowledgements to
Philippe Glaziou
Cairo, October 2009
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Karel Styblo: 1985
If the annual risk of TB infection
is 1% the annual incidence of
TB disease is 50/100k/yr.
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If the prevalence of TB in
children aged A is P then the
annual risk of TB infection is
ARI = 1-(1-P)1/A
We can use the prevalence in
children to estimate the
incidence in adults
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First the good news…
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Frequency distribution of induration sizes in Cape Town
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1955 1965 1975 1985 1995
AR
TI in
So
uth
Ko
rea
South Korea
Halving every
ln(2)/0.08 ≈ 10 years
Rate of decline = 7.8%/yr
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1960 1965 1970 1975 1980 1985 1990 1995
Pre
va
len
ce
SS
+ T
B/1
00
kSouth Korea
Rate of decline = 8.0%/yr
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1960 1970 1980 1990
SS
+ T
B in
cid
en
ce
/10
0k
ARTI×50
Civil servants
South Korea
Rate of decline = 8%/yr
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Now the bad news…
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South Korea Survey of
Incidence among Civil Servants
1998: Baseline
920,000 had chest radiography
1990: Follow up
790,000 available for CXR
2,500 with suspicious X-rays
2000 had sputa taken
300 culture positive
200 smear positive
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Styblo’s argument assumptions (before chemotherapy)
Each prevalent SS+ case infects 10 people per year
Disease duration is 2 years
Each incident SS+ case infects 20 other people
ARI = 20××××Incidence
Incidence = ARI/20
Incidence××××100k = (ARI××××100)/100××××100k/20
= (ARI/100)××××50
1% ARI corresponds to and incidence of 50/100k
ARI is independent of age. Average over last ten years
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Low prevalence
As the incidence declines, the
prevalence of infection declines and it
gets much harder to measure it.
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Changes in distribution patterns of
induration size in Korea
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Environmental mycobacteria
Prevalence of environmental
mycobacteria seems to be very high
around the equator and declines at very
high and very low latitudes
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Frequency distribution of induration sizes in Somalia.
Red: fitted; black: environmental; green: TB
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Dependence on testing day
(Somalia 2006)
Proportion positive when the induration was read on
three of four days after the challenge
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Dependence on BCG
(Somalia 2006)
Proportion positive with and without a BCG scar
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The way forward?
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Tuberculin skin test responses in
houehold contacts of active TB cases979 children, median age 7yr, Istanbul
0
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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
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Thank you
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0 5 10 15 20 25
Induration size (mm.)
Fre
qu
en
cy (
%)
10
8
6
4
2
0
Annual risk of tuberclous infection in the northern zone of India
Chadha, V.K. et al. Bull. WHO (2003)
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Styblo assumptions (cont)
• An infected case develops TB with probably 0.1 over his lifetime
• The probability for TB to be smear positive is 0.5
• Therefore, 1 smear positive generates: 10 x 2 x 0.1 x 0.5 = 1 new smear positive case over 1 transmission cycle and TB is stably endemic
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Origin of Styblo’s ruleBull IUAT vol 60, 1985
Ratio basedon
Risk of infection(%)
Ratio ofrisk:incidence
Netherlands 1921-38 Mortality 2.7 – 6.0 38
Netherlands 1951-76 Incidence 0.038 – 0.4 37
Developingcountries
1956-61 Prevalence 2.0 – 8.0 40-60
Alaskaeskimos
1948-51 Mortality 25 52
Indialongitudinalstudy
1961-68 Prevalence 1.5 53
Indiapreventiontrial
1969-71 Prevalence 4.1 51
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Changes in Styblo ratio in Chennai, S. India
0
50
100
K P E Th Ti TiT All
Blocks in Chingelput district
Inc
ide
nc
e S
+C
+/A
RT
I
1968-71
1973-78
Source: IJTLD 5, 142 (2001)
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Assumptions (cont)
• 2 year duration of infectiousness: not necessarily true, duration may decrease with increasing programme performance
• 10 cases infected per year: depends on living conditions, number of household members, etc, and may decline over time
• TB is in a steady state: untrue in most countries
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High sensitivity to assumptions on
distributions in Somalia
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Inconsistent patterns
(Somalia 2006)
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In summary
• Interpretation of data can be problematic
• Diagnostic value of PPD test difficult to predict
• Uncertainty about the relationship between prevalence of infection and incidence
• Uncertainty about time changes in the distribution of determinants of induration size
• Difficult to interpret time-changes in ARI
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Diverging time-changes between
SS(+) prevalence and ARI in China
Source: Bulletin of the World Health Organization 2008;86:20–26.
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Diverging time-changes between SS(+)
prevalence and ARI in the Philippines
Source: Bulletin of the World Health Organization 2008;86:20–26.
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Ethical considerations
• No (or little) benefit to surveyed individuals
• Most often done in children
• Ethical requirements:
– Clearance from ethical committee
– Informed consent from parents
– Informed consent from children
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Sampling
Typically multistage with clusters defined as schools or classes within schools→ need to account for sampling design when computing age-specific prevalence of infection→ is the sample self-weighed (each selected child should represent the same number of children)?→ missing values (e.g. Malawi, 21%)
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Induration (mm.)
Nu
mb
er/
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.Can tuberculin surveys measure risk of infection?
Data from Somalia 2006