World Health Organization, Western Pacific Regional Office
Active TB case finding
in the Western Pacific Regionexperience and policy direction
Nobu Nishikiori
Medical Officer, Stop TB
WHO Western Pacific Regional Office
World Health Organization, Western Pacific Regional Office
Contents
• Importance of ACF for TB control in the Region
• Experience of ACF in the Region
• ACF targeting tool – to guide TB REACH project
formulation
• Suggestions for ACF guidelines
– Risk-by-Risk approach
– Consideration for tailored care and support
World Health Organization, Western Pacific Regional Office
Increasing importance of ACF
• Case detection stagnating in most
of the countries in the Region
• TB concentrates among high risk
populations
• Emerging challenges
– Migrants
– Urban poor
– Emerging risk factors for TB
Aging, tobacco, diabetes
• Low diagnostic sensitivity
• Infectious patients with minor
symptoms may not seek care
0
1000
2000
3000
4000
5000
0
10
20
30
40
50
1998199920002001200220032004200520062007
Nu
mb
er
of
mig
ran
t TB
cas
es
TB C
ase
No
tifi
cati
on
(pe
r 1
00
00
0)
TB among migrants and local residents,Shanghai, 1998 - 2007
Number of TB cases among internal migrants
TB notification rate among local residents
World Health Organization, Western Pacific Regional Office
Migrant TB burden in MalaysiaNumber and % of migrant among all TB cases, by State, 2008
Number of
migrant TB cases
959
Sabah355
Selangor
134
Johor
375
Kuala
Lumpur
Myanmar
Thailand
Cambodia
Viet NamPhilippines
IndonesiaIndonesia
World Health Organization, Western Pacific Regional Office
Experience in ACF (1)
Prisons and confined settings
Entry screening
• e.g. Mongolia
– „double entry screening‟ with fluorography film
– Significant reduction of TB burden
Periodic (or project-based) screening
• e.g. Viet Nam
– X-ray Microscopy + Culture
– Prevalence 1560 (S+) 2537 (C+) per 100 000 (NNS 40)
• e.g. Cambodia
– X-ray Microscopy
– Prevalence 950 (S+) per 100 000 (NNS 105)
„Enhanced‟ case finding
• Philippines
– Peer cough monitoring – cough surveillance
Reduction of TB burden among
prisoners in Mongolia
• Decline in TB
CNR
Prison vs national
– 18 times in 2001
– 10 times in 2005
– 5 times in 2008
• Improvement of
entry TB screening
on detention (461)
and on allocation
(401)
• Decline among
sentenced
prisoners (Red)
Joint Ministerial Order:Screening policy established
•100% entry screening with GF support•Equipment upgraded
Global Fund support
Continuous improvement of prison conditions
World Health Organization, Western Pacific Regional Office
Experience in ACF (2)
TB contact investigation
Routine CI established and reported
– e.g. China, Mongolia, Malaysia and other IBCs
– Yield tends to vary…problem in implementation level ?
Low sensitivity of the procedures?
Other environmental determinants?
Policy established but weak implementation and reporting
– e.g. Many HBCs
– Too labor intensive for over-stretched health systems
CI combined with community-based ACF in Cambodia
– Unique strategy in Cambodia
– Can be very cost-effective
World Health Organization, Western Pacific Regional Office
Community ACF strategies
in Cambodia (2005 – 2010)
• Define target areas with high TB case load
• Identify smear positive index cases from TB register and:
Strategy 1 (Adult contacts):
– House-to-house symptom screening + microscopy sessions
Strategy 2 (Adult contacts):
– House-to-house invitation + X-ray & microscopy sessions
Strategy 3 (childhood contacts):
– House-to-house invitation + PPD sessions
World Health Organization, Western Pacific Regional Office
Community-based ACF in Cambodia:
A step-wise approach
Target
CommunityTB suspects
Step 3: Community
volunteers conduct
house-to-house
visit and invite
contacts and TB
suspects to ACF
sessions
Step 4:
ACF team (stay
1-2 weeks)
screen all TB
suspects with
mobile X-ray
Abnormal
chest X-rayMicroscopy
Step 5:
Three sputum
smear
microscopy for
diagnosis
Step 1:
Geographical
targeting based on
TB case load and
socio-economic
status
Step 2: Local
advocacy meeting
Step 6:
Treatment
follow-up by
local health
workers and
volunteers
World Health Organization, Western Pacific Regional Office
Rationale for
“Retrospective” CI
• Routine contact investigation in
HBCs
– Should be done as much as possible
– But…difficult to implement fully
• Contacts have increased risk of active
TB disease for several years
– One time CI might miss many cases
– Cumulating cases for 1-2 years can
be cost-effective
• Contacts share same environmental
risks with their index
Lee, M. S., et al. 2008. "Early and late tuberculosis risks among
close contacts in Hong Kong." Int J Tuberc Lung Dis 12(3).
Morán-Mendoza, O. et al., 2010. Risk factors for developing
tuberculosis: a 12-year follow-up of contacts of tuberculosis cases.
Int J Tuberc Lung Dis, 14(9),
3mon Y1 Y2 Y3 Y4 Y5
World Health Organization, Western Pacific Regional Office
Results (2005-2010)
How much yield we can get?
TB cases diagnosed:
(among all participants
attended ACF sessions)
All TB: 6% to 12%
NNS: 8 ~ 17
Smear +ve: 2% to 3.5%
NNS: 28 ~ 50
* A systematic review (Morrison
et al, 2008) reported pooled yields
of 4.5% and 2.3% for all and
confirmed TB respectively.
World Health Organization, Western Pacific Regional Office
Was it cost-effective?
• Cost data was available for the
sessions in 2010
• The strategy is highly cost
effective
– Cost per case identified
Diagnostic cost: $21 per case
Overall cost: $113 per case
(logistics and operations cost)
(c.f. TB REACH criteria $350 per
case diagnosed and successfully
treated)
Cost per case identified
Diagnostic cost 18$ 18$ 16$ 25$ 41$ 21$
Overall cost 91$ 86$ 86$ 129$ 223$ 113$
Proportion of TB cases identified among all TB suspects
attended in outreach active case finding sessions, 2010.
World Health Organization, Western Pacific Regional Office
The upgraded strategy for TB REACH
Project 2011
• Better area targeting using:
– Socio-economic indicators
(poverty, health access, etc)
– TB case load
• Further increase the yield
– Screening: Symptom + X-ray
for all contacts
– Diagnostic: Xpert MTB/RIF
– Target adult and childhood
contacts together
(Poor) Poverty/access index (Better-off)
TB
no
tifica
tio
n r
ate
(p
er
10
0 0
00
)
Targeted districts
○ Non-targeted districts
World Health Organization, Western Pacific Regional Office
A tool for ACF targeting and strategy selection
Guidance was needed to support formulating ACF projects (for TB REACH)
An electric tool for ACF targeting developed
What factors determine the yield and cost-effectiveness of ACF?
1. TB prevalence among the target• Higher prevalence higher yield
2. Diagnostic algorithms• More comprehensive screening higher cost & yield
3. Targeting approaches (not yet included)• Scattered target higher „opportunity‟ cost
Increased TB case detection
Prisoners
TB contacts
Mal-nourished
Diabetics
World Health Organization, Western Pacific Regional Office
1. TB Prevalence among the target
• Number needed to screen (NNS) shoot
up as TB prevalence goes down
• Roughly, ACF is not feasible for a
target < 0.5% prevalence (if X-ray for
all)
• However, NNS alone cannot guide
whether we should target or not
– Diagnostic cost significantly varies
between dx algorithms
– Operational and logistics cost also
different for each target/context
• How to find populations with >
0.5% prevalence?
Tentative cost effective zone
World Health Organization, Western Pacific Regional Office
2. Diagnostic algorithms and yields
Model algorithms
1. Symptom screening microscopy
(routine programme model)
low cost & low yield
2. Symptom microscopy + x-ray
3. X-ray + symptom microscopy
4. X-ray + symptom microscopy + culture
(prevalence survey model)
high-cost & high-yield
5. X-ray + symptom Xpert MTB/RIF
(prevalence survey model with Xpert)
high cost model with Xpert
6. Symptom X-ray Xpert MTB/RIF
low cost model with Xpert
Estimating yields
• How many TB cases detected for
each algorithm roughly defined by
suspect/yield profile as below
example
• Important to note that:
– Initial symptom screening substantially
decrease a yield
– Low sensitivity of microscopy
Suspects (additionally) identified by X-ray
Smear- positive TB11%
Culture-positive Smear-negative TB
49%
Suspects identified by symptom screening
Smear- positive TB19%
Culture-positive Smear-negative TB
21%
Fig. An example of yield profile based on the
prevalence survey, Cambodia 2002.
World Health Organization, Western Pacific Regional Office
An example of the tool outputs:
Diagnostic cost per case detected
Prevalence > 2%
• Cost effective for all strategies
including prevalence survey
models (culture or Xpert)
Prevalence 1-2%
• X-ray screening (strategy 3)
may be still cost-effective
• Culture probably feasible but
requires careful planning
Prevalence <1.0%
• Up to strategy 1 &2 acceptable
(i.e. routine procedure)
* Cut-off of USD 200 are arbitrary. TB REACH
criteria employ USD 350 per case detected and
successfully treated.
200
0
200
400
600
Strategy 1 Strategy 2 Strategy 3 Strategy 4 Strategy 5 Strategy 6
Dia
gn
osti
c c
ost
per
case d
ete
cte
d (
US
D)
Cost-effectiveness of TB screening by diagnostic algorithm, Cambodia
RR = 1.0 (0.69% -baseline)
RR = 1.5 (1.04%)
RR = 2.0 (1.39%)
RR = 3.0 (2.08%)
RR = 5.8 (4.00%)
RR = 8.7 (6.00%)
Cost-effectiveness target (200)
Symptom
microscopy
Symptom
microscopy
+ X-ray
Symptom
+ X-ray
microscopy
Symptom
+ X-ray
microscopy
+ culture
Symptom
+ X-ray
Xpert
Symptom
X-ray
Xpert
General
population
Urban
slum
Smokers
Diabetics
Contacts
Prisoners
Contacts Prisoners
General
population
Urban
slum
Smokers Diabetics
World Health Organization, Western Pacific Regional Office
General observations from the tool outputs
• Conservative algorithm can be acceptable even NNS is high
• The higher the prevalence
the more extensive approach high yield
However, we have a dilemma…
– Very high risk groups tend to be small
– Lower risk groups larger size and difficult to target
So the key is to find a high risk target with a good pop size
Risk-by-Risk – combining multiple risks – might be a way to manipulate a risk
profile and a target size
e.g. Geographical targeting x TB contacts (Cambodian Retro CI),
Deported migrants x detention history (another TB REACH project in
Cambodia)
World Health Organization, Western Pacific Regional Office
Narrowing down the target: Risk x Risk approach
(Elderly x diabetics) (Elderly x smokers)
Current smoker:
annual incidence
735 per 100 000
Ex-smoker:
annual incidence
427 per 100 000
Never smoked:
annual incidence
174 per 100 000
Cumulative hazards for active TB by smoking status,
among a cohort of clients (>65yrs) registered with an
elderly health service in Hong Kong
Leung, et al. 2004. "Smoking and tuberculosis among the elderly in
Hong Kong." Am J Respir Crit Care Med 170(9): 1027-1033.
Cumulative hazards for active TB by diabetic status,
among a cohort of clients (>65yrs) registered with an
elderly health service in Hong Kong
Leung, et al. 2008. "Diabetic control and risk of tuberculosis: a cohort
study." Am J Epidemiol 167(12): 1486-1494.
HbA1c >= 7%:
annual incidence
422 per 100 000
No diabetes:
annual incidence
214 per 100 000
World Health Organization, Western Pacific Regional Office
Neighborhood factor
analysis for geo-targeting
• Neighourhood factor analyses using
socio-economic characteristics have a
potential to guide geo-targeting
• Risk micro-stratification to identify
target area/population
• Risk x Risk approach
e.g. poor neighborhood x malnourished
e.g. densely populated area x contact
investigation
Quezon City
Manila
Taguig
Paranaque
Valenzuela
Las Pinas
Muntinlupa
Pasig City
Makati City
Kalookan City
Marikina
Malabon
Pasay City
Navotas
Mandaluyong
San Juan
Pateros
Obando
Barangay-wise population density, Metro Manila
Barangay
Population density
0.000000 - 199438000.000000
199438000.000001 - 392535008.000000
392535008.000001 - 651995008.000000
651995008.000001 - 1044950016.000000
1044950016.000000 - 16246800384.000000
±
World Health Organization, Western Pacific Regional Office
Entire
gro
up
HIV
Sm
okers
Maln
ourished
TB
conta
ct
his
tory
Alc
oholic
s
Dia
bete
s
Eld
erly
Pre
vio
us T
B
Slum dwellers x x x x x x x x
HIV x
Smokers
Prisoners x
Migrants x x x x
Malnourished x
TB contacts x x x x x x x
Alcoholics
Miners x
Diabetes x x x x x x
Elderly x x x x x x
previous TB
Target population (venue)
Risk factors (to be included in suspect definition)
Risk-by-Risk Table
World Health Organization, Western Pacific Regional Office
Targeted case finding approaches require
specific measures to provide care
• High risk populations requires a
tailored service delivery mechanism
– e.g. Migrants / urban poor
• highly mobile / high default and transfer
• Social and financial insecurity
– e.g. Prisons
• High co-morbidity including HIV (what if
ARV is not available?)
• Transfer and referral system (release
screening?)
• For guidelines:
– Cases successfully treated is important
outcome (not only case finding)
– Is there any group for which ACF should not
be conducted unless the specific support
mechanism is not ensured (other than routine
DOTS)?
91%
37%
13%
11%
39%
0%
20%
40%
60%
80%
100%
Permanent Residents (N=5915)
Migrants(N=2423)
Treatment outcome of new smear positive TB by residence status, Beijing, 1997-2002
Transferred
Defaulted
Died
Failed
Completed
Cured
Cases among
migrants
(Up to 35%)
Zhang, L.X. et al., 2006.
Int J Tuberc Lung Dis,
10(9).
World Health Organization, Western Pacific Regional Office
Summary
• ACF is potentially a very important TB control strategy in the Region
• Experience shows some positive outcomes in the Region (though limited)
• An interactive tool can facilitate country level targeting, strategy selection
and planning
• Risk-by-risk approach can help increase the TB risk and narrowing down
the size of the target population (concentration and selection)
– “Does combining more than two risk factors to identify the target population increase the
yield and cost-effectiveness of TB screening?”
• Targeted ACF requires extensive consideration for treatment and care
delivery strategies
– “Does a tailored care mechanism for a specific high risk group (migrant, prisoners, etc)
improve TB treatment outcome compare to the routine DOTS programme”
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