Xpert in the diagnostic algorithm
of pulmonary TB in adult patients
who are neither high risk for HIV,
nor high risk for MDR-TB
Preparations for the global consultation
DEWG core team meeting, Berlin 10 Nov 2010
Jacob Creswell, Knut Lönnroth, Ikushi Onozaki, Salah
Ottmani, Suvanand Sahu, Mukund Uplekar
Group work in the consultation
• Operationalize STAG recommendations – develop implementation
road map:
1.
2.
3.
HIV (high HIV prevalence settings / people suspected of HIV)
MDR-TB (high MDR-TB prevalence settings / MDR risk groups)
DOTS expansion and enhancement (settings and individuals
where HIV and MDR-TB are of lesser concern).
• Three topics for discussion
1.
2.
3.
Proposed algorithm(s)
Implementation issues
Operational research
• Preparations for group 3:
1.
2.
3.
Small ad hoc group in Secretariat have done preliminary work
Discussion in DEWG core team 10 Nov
Mini task force to finalise draft for the consultation
STAG-TB supports Expert Group
guidance that:
1. Xpert MTB/RIF should be used as the initial
diagnostic test in individuals suspected of MDR-TB or
HIV-associated TB (strong recommendation);
2. Xpert MTB/RIF may be used as a follow-on test to
microscopy in settings where MDR and/or HIV is of
lesser concern, especially in smear-negative
specimens (conditional recommendation, recognising
major resource implications).
Group 3 algorithms - assumptions
1. The issue is not only to find the appropriate place of Xpert in the
current algorithm, but also to re-consider the whole algorithm,
including potentially changed role of microscopy and X-ray for
screening, diagnosis and case categorization.
2. The priority is algorithms for "passive" case finding. Additional
algorithms may have to be developed for "active" case findings in
TB risk groups other than people with HIV.
3. The algorithms need to be linked to / integrated with / consistent with
algorithms for people at high risk of MDR-TB and people with HIV,
which have not yet been finalized.
4. The recommendation to use Xpert "as the initial diagnostic test" for
people at high risk of HIV or MDR-TB, does not necessarily mean
first screening test
5.
Different algorithms are required for at least two
different levels of the health system:
a. Facilities with smear microscopy but no X-ray
b. Facilities with X-ray
6.
The algorithms should work in both high and low MDR
prevalance / HIV prevalance settings
7.
The first step is to identify the most effective and costeffective approach. Affordability and feasibility issues
are considered under implementation challenges.
•
Not HIV
clinic
Legend/Guide
•
Not TB
cases failing
treatment
Start
•
Not contact
investigation
•
Not active
case findings
Process/Action
TB
SUSPECT
Is HIV+?
Option 1: Diagnostic
algorithm for passive case
finding in a facility with
microscopy and no CXR
HIV- or
Unknown
Result
Microscopy
HIV+
Decision
Follow
HIV
Algorithm
Referral
for CXR
SS-
Endpoint
Result
CXR
Abnormal
SS+
CXR
Normal
YES
XPERT
TB+
No Res
MDR Risk Factors?
Result
NO
No TB
TB+
Rif Res
Further
FLD
SLD
Clinical
Management
FLD
Legend/Guide
TB
SUSPECT
Start
Process/Action
Option 2a: Diagnostic
algorithm for passive case
finding in facilities with CXR
CXR
Result
CXR
Abnormal
Decision
CXR
Normal
XPERT
Endpoint
Result
**Note - Use of
culture and DST will
be necessary in
parallel with
GeneXpert use
TB+
No Res
No TB
TB+
Rif Res
Further
FLD
SLD
Clinical
Management
Legend/Guide
TB
SUSPECT
Start
Process/Action
Option 2b: Diagnostic
algorithm for passive case
finding in facilities with CXR
CXR
Result
CXR
Abnormal
Decision
XPERT
Endpoint
ss-
Smear?
?
ss+
Result
**Note - Use of
culture and DST will
be necessary in
parallel with
GeneXpert use
TB+
No Res
No TB
TB+
Rif Res
Further
FLD
SLD
Clinical
Management
CXR
Normal
Absolute Increases in bacteriologically identified Case Detection Asuming
12% C+ in Population of 10,000 TB Suspects
1400
1276
1200
1104
1250
1146
1093
1164
1121
1070
1058
1055
1000
800
720 720
Absolute TB Cases
TB Cases
Absolute True Positives
600
400
200
0
Standard
Xpert
CXR, Xpert CXR, Smear
Xpert
Algorithm
SS Xpert
SS CXR
Xpert
90%
80%
Percentage Increase in bacteriologically identified Case Detection
from Current Algorithm
% increase in CD compared to
standard
77%
% increase in true CD
74%
70%
62%
59%
60%
53%
56%
52%
49%
50%
50%
47%
%
40%
30%
20%
10%
0%
Xpert
CXR, Xpert
CXR, Smear Xpert
Algorithm
SS Xpert
SS CXR Xpert
Costs per Case of TB Diagnosis
Equipment cost
only for Xpert!
180
200
$/case (tests)
173
$/case with digital CXR
(tests)
160
163
144
133
140
120
114
120
USD 100
80
60
74
68
56
40
20
0
Standard
Screening
Xpert
CXR, Xpert
CXR, Smear
Xpert
Algorithm
SS Xpert
SS CXR Xpert
Algorithm- Issues to discuss during
consultation
• Detailed technical discussion on proposed algorithms
• Can we use the same algorithm in both low- and high MDR-TB / HIV
settings?
• How to link with algorithms for people at risk of HIV and MDR-TB?
• Can we use the same algorithm in high and low TB prevalance
settings?
• Do we need to change the definition of a TB case and method for
monitoring treatment outcomes (if sputum smear microscopy is no
longer essential for diagnosis)?
Implementation
• Considerations for NTPs, partners, and
donors:
– Should we develop an interim algorithm for settings
that are already planning to purchase Xpert, or
discourage general use until results from further
research findings?
– If interim algorithm, should we prepare an operational
research protocol that should be used in all sites?
– Where is the appropriate place of Xpert in the health
system?
– What are the capacity strengthening needs for Xpert,
X-ray, R&R, etc?
– What are the health systems pros and cons of
different algorithms (e.g. improving X-ray capacity is
beneficial for diagnosis of many other conditions)
Strategy for Xpert use in the
private sector
– Should private providers engaged in PPM schemes
have access to Xpert at reduced cost?
– Should the be an agreement with Sepheid to only sell
Xpert to private providers on condition of report to
NTP where Xpert has been purchased as well as
mandatory reporting/notification of diagnosed cases?
– Accreditation / certification?
– Need to update ISTC?
– Should NTPs accept cases diagnosed with Xpert in
the private sector (need to change case definition)?
Research needs
• What recommendations for the evaluation of Xpert in the FIND sites,
concerning cases that are neither HIV-positive, nor high risk for
MDR?
– Use sputum smear microscopy, Xpert, X-ray, and culture for all suspects
in order to fully assess sensitivity and specificity of all permutations?
– Full assessment of risk factor profile for MDR and TB (HIV, smoking,
diabetes, etc) among all suspects in order to assess differences in yield
and precision across risk groups
• Operational research questions and protocol; which operational
question?