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Targets for global TB controlMILLENNIUM DEVELOPMENT GOALS"to have halted and begun to reverse
incidence.."
Implementation (DOTS) Target yearCase detection 70% 2005Treatment success 85% 2004/5
ImpactPrevalence 50% of ≈ 300/100K 2015Deaths 50% of ≈ 30/100K (<1m) 2015Incidence <1 per million 2050
1.Measuring and estimating
TB incidence
Direct measures of TB burdenincidence and prevalence
Korean civil servantsTubercle and Lung Disease 76, 534 (1995)
• Prevalence PTB 1990 241/100K • Incidence PTB 1989-90 84/100K/yr
• Estimated duration = 241/84 = 2.9 years (bigger ratio for older age groups)
02468
101214161820
1980 1985 1990 1995 2000 2005
Rep
orte
d TB
cas
es/1
00,0
00/y
r USANetherlandsUKNorway
Where case notifcations = true incidence
Four indirect measures of TB incidence
durationprevalenceTB incidence 2. =
detected proportiononsnotificatiTB incidence 1. =
ratio Styblo infection incidenceTB incidence 3. ×=
rate)fatality (case dying cases proportion
deaths TB incidence 4. =
Incidence, prevalence, deaths derived by rearranging 4 equations
4 steps to check accuracy and completeness of surveillance data
1. Inventory of, and cross-check, data from all possible sources, removing duplications
2. Capture-recapture techniques to estimate case detection from lists of patients that have been "captured" in different ways
3a. Consistency of case reports: spatial and temporal variation, to check for inconsistencies
3b. Consistency of case reports: norms of TB epidemiology and natural history
Completeness of case registrations
TB cases notified by compulsory (CSS) and Varese surveillance systems (VSS)
VSS CSSTotal cases notified 143 89Duplicates 8 13Not TB 14 0True cases 121 76
(-37%)Source: Migliori ERJ 8, 1252 (1995)
Capture-recapture methodPetersen 1896, Lincoln 1930 (ducks)
Take 2 independent samples from an unknown population of N (TB patients):
Method 1 e.g. lab registerPresent Absent Total
Method 2 Present 20 5 25e.g. hospital register Absent 30 c b
Total 50 a N
N = 50×25/20 = 62.5a = 62.5 - 50 = 12.5 CDR lab = 50/62.5 = 0.8b = 62.5 - 25 = 37.5 CDR hosp = 25/62.5 = 0.4 c = 62.5 - 55 = 7.5
Indonesia: why does the fraction of TB cases among suspects vary between provinces?
0.00
0.10
0.20
0.30
0.40
0.50
MALUKU U
TARABANTENMALU
KUJA
BARKALTENG
JAWA TENGAH
PAPUARIA
U
DKI JAKARTAKALSEL
LAMPUNGKALBARSULS
ELD.I.
ACEH N
T T BALI
JAWA TIM
URSUMUTSULT
RASUMSEL
NTB
KALTIMSULU
TSUMBARSULT
ENGBABELD. I
. Y.
GORONTALOJA
MBI
BENGKULUTB
cas
es/s
uspe
cts
Morocco: consistent 40-60% smear+ across 16 regions
0.0
0.2
0.4
0.6
0.8
Oued Ed
Laâyo
une Guelm
imSou
ssGharb
Chaouia
Marrak
ech
Oriental
Casab
lanca
Rabat
Douka
laTad
laMek
nès FèsTaz
aTan
gerPr
opor
tion
smea
r-pos
itive
1b. Assessing trends in TB
incidence, and the impact of control
Cambodia: higher case rates among older people imply long-term epidemic decline
0
200
400
600
800
1000
1200
0–14 15–24 25–34 35–44 45–54 55–64 65+
Age group (yrs)
Rep
orte
d TB
cas
es/1
00k
in 2
006 Male
Female
0
5
10
15
20
25
30
-10 -8 -6 -4 -2 0 2 4 6 8 10 >10
Annual change incidence (up to % marked)
Num
ber c
ount
ries
High incomeSE Asia & W PacificLatin AmericaE MediterraneanC&E EuropeSub-Saharan Africa
TB incidence is falling slowly in 95 of 135 countries, 1996-2005
Morocco:PTB incidence projected to 2015
0
10
20
30
40
50
60
70
1980 1985 1990 1995 2000 2005 2010 2015
Inci
denc
e ra
te/1
00K
on 1994 age-structure
on aging population
31
32
33
34
35
1980 1985 1990 1995 2000
Mea
n ag
e of
adu
lt pa
tient
s (y
r)TB patients in Morocco
Women: 0.15 ± 0.02
Men: 0.14 ± 0.01
Year
0
1
2
3
4
5
6
Men Women Men Women
All forms Smear+
Dec
line
repo
rted
cas
es (%
/per
son/
yr)
UrbanRural
Morocco: TB falling slowly in women, very slowly in men
Trends in case notificationrates in Viet Nam, 1997-2004
-8
-4
0
4
8
15-24 25-34 35-44 45-54 55-64 65+ total
Ann
ual p
erce
ntag
e ch
ange
Men Women Total
020406080
100120140
1990 1995 2000 2005Rep
orte
d TB
cas
es/1
00K
/yr
Average age of men 15-54 yrs with TB is falling in some countries
37
38
39
40
41
42
1996 1998 2000 2002 2004
Ave
rage
age
(yr)
Viet Nam
Sri Lanka
Myanmar
China
TB trends: New Caledonia
All TB 9.4%/yr
Smear+ 8.2%/yr
0
10
20
30
40
50
60
70
80
90
1990 1995 2000 2005
Not
ifica
tion
rate
(per
100
000
) Notifications(new &relapse)
Notificationsnew smear-positive
0
50
100
150
200
250
1980 1985 1990 1995 2000 20050
500
1000
1500
2000
2500
Pul
mon
ary
TB c
ases
/100
k/ye
ar
Slid
es e
xam
ined
(k/y
r)
Suarez, P. G. et al. The dynamics of tuberculosis in response to 10 years of intensive control effort in Peru. J Inf. Dis 184, 473-8 (2001)
DOTS
Increasingdiagnostic effort
Decliningnotification rate
Impact of DOTS in Peru
2. Measuring and estimating
TB prevalence
When to do a prevalence survey
• High burden (e.g. among 22 HBC)• Uncertain burden, in part because surveillance
is weak • Potential for collecting other data e.g. about
where patients are diagnosed and treated • Logistically feasible - terrain, population
density, staff security, mobile X-ray, culture etc
• Potential source of funds: $100,000 - $1m• Potential for doing 2 or more surveys (to
measure change)• Participatory population
Country Design Number examined
Number active pulmonary cases (prevalence ±
95%CL, per 100,00)
Number culture-positive cases
(prevalence ±95%CL, per
100,000)
Number smear-
positive cases (prevalence ± 95%CL, per 100,000)
Republic of Korea 1995 28
Stratified, cluster randomized; Age ≥ 5 years;
X-ray (miniature) screen
64 713 668 (1032 ± 80)[1] 142 (219 ± 37)[2]
(culture+ and/or smear+)
60 (93 ± 24)
Philippines 1997 31
Stratified, cluster randomized; Age ≥ 10 years;
X-ray screen
21 960 537 (4200 ± 330)[3] 124 (810 ± 88) 47 (310 ± 99)
China 2000 29 Stratified, cluster randomized;Age ≥ 3 months;
Tuberculin/symptom/fluoroscopy screen
365 097 1340 (367 ± 28) 584 (160 ± 16) 447 (122 ±14)
Cambodia 2002 50
Stratified, cluster randomized; Age ≥ 10 years;
X-ray/symptom screen
22 160 580 (1916 ± 300) 271 (899 ± 165)(culture+ and/or
smear+)
81 (269 ± 66)
Indonesia 2004 30
Stratified, cluster randomized; Age ≥ 15 years; Symptom screen
50 154 N/A 48 (186 ± 49)[4] 80 (104 ± 38)
Eritrea 2004 120
Stratified, cluster randomized; Age ≥ 15 years;
No screen
18 152 N/A N/A 15 (50 ± 30)
The 6 national TB prevalence surveys carried out since 1995
DOTS reduces prevalence of TB by 37% in less than a decade in China
0
50
100
150
200
250
1990 2000
Prev
alen
ce c
ultu
re+
TB/1
00,0
00
DOTSOther
Progress towards MDGs in Indonesia prevalence rate fell 4%/yr 1980-2004?
61%
45%
74%
53%
0
100
200
300
400
500
600
Sumatera Java-Bali KTI (East) National
Smea
r+ p
reva
lenc
e/10
0K
1980 regional surveys
2004 national survey
% fall 1990-2004
"Model DOTS Project" reduces TB prevalence in south India
source: TRC Chennai
0
1000
2000
68-70
71-73
73-75
76-78
79-81
81-83
84-86
99-01
01-03
Year
Pre
vale
nce/
100K
Male C+Male S+Female C+Female S+
fall ~10%/yr in MDP
Incidence cannot reliably be estimated from prevalence e.g. Cambodia?
prevalence ss+ (survey) 269/100K in 2002
weighted duration DOTS 0.65 @1.0 yearnon DOTS 0.10 @1.5 yearsuntreated 0.25 @2.0 years
= 1.3 years
Therefore: incidence ss+ = 269/1.3 = 207/100K/yearNB: usually wide range on estimates
duration weighted incidence ss prevalence ×=+
3. Measuring and estimating
TB mortality
Measuring and estimating TB deaths
Three approaches1. Incidence × case fatality (method 4)2. Verbal autopsy (in sample vital
registration)3. Vital (death) registration
rate)fatality (case dying cases proportion
deaths TB incidence :4 Method =
Comparing unknownsCause of death from vital statistics (VSD) and verbal autopsy (VA) of 48 000 adult (> 25) deaths in Chennai, India: 1995-97
Cause of death in VSD
Cause of death based on VA
Other Respiratory 1088 ( 4) 596 ( 3) 1597 ( 6) 855 ( 4)
Cause ofdeath
M (%) F(%) M (%) F(%)
Vascular disease 8319 (30) 5168 (25) 11056 (41) 7435 (37)
1999 (10)
618 ( 3)
5889 (29)
2804 (14)
Nil
20175
Tuberculosis (TB) 1399 ( 5) 372 ( 2) 2231 ( 8) 575 ( 3)
Neoplasm 1163 ( 4) 1002 ( 5) 2344 ( 9)
Infectious (ex Resp/TB) 584 ( 2) 303 ( 2) 1034 ( 4)
Unspec med. 12291 (44) 11511 (56) 4367 (16)
Other spec med. 1899 ( 7) 1045 ( 5) 4414 (16)
Cause NA 983 ( 4) 634 ( 3) Nil
Total deaths - med 27726 20631 27043
Source: Jha, Gajalakshmi et al
Regional trends in TB death registrationsfew data from Asia & Africa, long reporting delays
0
5
10
15
Geo
met
ric m
ean
TB m
orta
lity
(per
100
K)
20
1985 1990 1995 2000 20050
10
20
30
40
TB m
orta
lity
Phili
ppin
es
50
(per
100
K)
ex Soviet UnionCentral EuropeIndustrializedLatin AmericaRep. KoreaPhilippines
4. Measuring and estimating risk of
TB infection
0
5
10
15
20
25
5 10 15 20 25 30Tuberculin reaction (mm)
Num
ber o
f chi
ldre
n
Curve fitting
Chadha, V. K. et al. Annual risk of tuberculous infection in the northern zone of India. Bull World Health Organ 81, 573-80 (2003).
Cut-off
Mirror
0 to 9 years19651995
0 10 20 30 0 10 20 30 Size of induration (mm) Size of induration (mm)
Freq
uenc
y (%
) 10
5
0 Freq
uenc
y (%
) 10
5
0
0 to 20 years19651995
a b
c d
BCG
No BCG
BCG
0 10 20 30 0 10 20 30Size of induration (mm) Size of induration (mm)
Freq
uenc
y (%
)
Freq
uenc
y (%
)4
2
0
15
10
5
0
Tanzania 1983 to 1988 Egypt 1995 to 1997
No BCG
Korea
Styblo's 1:50 rule and endemic (untreated) TB
Prevalence infectious TB
~ sputum smear+, 2yr
Infected with M tuberculosis
Prevalence non-infectious TB ~ sputum smear-
0.5 0.5
10 × p
MTB infection
0.1 0.1
TB incidence
Styblo (incidence × 105)/(risk infection × 102) = 1000/(10 × 2) = 50
Endemic TB 1 smear+ cases gives 10 × 2 × 0.1 × 0.5 = 1 smear+ case
0
5
10
15
20
25
30
ALDEWANIA
AL-NAJA
FKARBALA
AL-MUTH
ANNAWASIT
AL-BASRAHMESAN
BAGHDADBABIL
KURKOKTHE-Q
AR
SALAH ADDEN
NINAWA
DIYALAAL-A
NBAR
Smea
r+ n
otifi
catio
ns/1
00K
20052004
IRAQ Notification rate varies 5-fold among governerates
0.51% infection1.43% infection
Tuberculin skin test responses in houehold contacts of active TB cases
979 children, median age 7yr, Istanbul
01020304050607080
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31
ELISpot -veELISpot +ve
Source: Bakir et al 2006
5. Summary
Measuring TB burden and the impact of control
• Routine surveillance the ultimate tool for evaluating TB epidemiology and control; completeness of reporting to be formally examined in all countries
• Disease prevalence surveys best for measuring prevalence (and change), not incidence
• Tuberculin surveys feasible where ARI high and BCG coverage low; better for comparisons (trends); Styblo'srule defunct
• TB death registrations need to be improved in all countries with high TB burden, and compared with data from NTPs; verbal autopsy needs validation
Measuring tuberculosis burden, trends and the impact of control
programmesLancet Infectious Diseases 2008
"By 2015, every country should be able to assess progress in control by evaluating the time trend in incidence, and the magnitude of reductions in either TB prevalence or deaths."
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