Photo: Riccardo Venturi
2010-2015: uptake and impact
of Xpert MTB/RIF
Wayne van Gemert
WHO Global TB Programme, Geneva
Joint Partners Forum for Strengthening and Aligning TB Diagnosis and Treatment
27-30 April 2015
GLOBAL TB
PROGRAMME
Xpert MTB/RIF roll-out: global progress
Dec 2010
Q1 2011
99 GeneXperts
(524 modules)
in the public sector
in 23 countries
3,763 GeneXperts
(17,883 modules)
in the public sector
in 116 countries
GLOBAL TB
PROGRAMME
Q4 2014
Data: FIND/Cepheid
Capacity for Xpert MTB/RIF testing today
Numbers of GeneXpert modules procured
under concessional pricing, as of Q4 2014
Top procurers of
modules (GeneXperts) :
4,260 (357) South Africa
3,876 (969) China
780 (204) India
720 (180) Brazil
624 (156) Nigeria
492 (120) Philippines
412 (108) Uganda
388 (98) Ethiopia
388 (88) Zimbabwe
376 (71) Bangladesh
374 (91) Kenya
GLOBAL TB
336
(83) Pakistan
PROGRAMME
Data: FIND/Cepheid
Xpert MTB/RIF cartridges procured under
concessional prices
1,400,000
Xpert MTB/RIF cartridges
1,200,000
1,000,000
800,000
600,000
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Data sources: FIND/Cepheid
Q4
Q1
Q2
Q3
2013
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
Xpert MTB/RIF cartridges
1,200,000
1,000,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
800,000
600,000
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
Xpert MTB/RIF cartridges
1,200,000
1,000,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
800,000
600,000
400,000
56% of all cartridges
have been procured by
South Africa
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
Xpert MTB/RIF cartridges
1,200,000
DFATD Canada (TB REACH/EXPAND-TB)
1,000,000
800,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
600,000
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
India: UNITAID (TBXpert/EXPAND-TB)
Xpert MTB/RIF cartridges
1,200,000
UNITAID (TBXpert/EXPAND-TB)
1,000,000
DFATD Canada (TB REACH/EXPAND-TB)
800,000
600,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
India: UNITAID (TBXpert/EXPAND-TB)
1,200,000
Xpert MTB/RIF cartridges
UNITAID (TBXpert/EXPAND-TB)
1,000,000
DFATD Canada (TB REACH/EXPAND-TB)
800,000
Brazil (MoH)
600,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
India: UNITAID (TBXpert/EXPAND-TB)
Xpert MTB/RIF cartridges
1,200,000
UNITAID (TBXpert/EXPAND-TB)
DFATD Canada (TB REACH/EXPAND-TB)
1,000,000
Brazil (MoH)
800,000
China (Global Fund)
600,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under
concessional prices: Procurers/donors
1,400,000
Others (Global Fund, USAID, PEPFAR, MSF,
etc.)
India: USAID,
others
USAID,IPAQT,
PEPFAR,
IPAQT, others
1,200,000
Xpert MTB/RIF cartridges
India: UNITAID (TBXpert/EXPAND-TB)
UNITAID (TBXpert/EXPAND-TB)
1,000,000
DFATD Canada (TB REACH/EXPAND-TB)
800,000
Brazil (MoH)
China (Global Fund)
600,000
South Africa (MoH, Global Fund, USAID,
PEPFAR, others)
400,000
200,000
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Data sources: FIND/Cepheid (data by country and overall);
WHO (data by donor)
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under concessional prices
1,400,000
1,200,000
1,000,000
800,000
600,000
400,000
200,000
0
GeneXpert modules procured under concessional prices
4,000
3,500
3,000
2,500
2,000
1,500
1,000
500
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under concessional prices
1,400,000
1,200,000
1,000,000
56% of all cartridges
have been procured by
South Africa
800,000
600,000
400,000
200,000
0
GeneXpert modules procured under concessional prices
4,000
3,500
3,000
24% of all modules
have been procured by
South Africa
2,500
2,000
1,500
1,000
500
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Q4
Q1
Q2
Q3
2014
Q4
Xpert MTB/RIF cartridges procured under concessional prices
1,400,000
1,200,000
1,000,000
56% of all cartridges
have been procured by
South Africa
800,000
600,000
400,000
200,000
0
GeneXpert modules procured under concessional prices
4,000
3,500
GeneXperts being
underutilized…
3,000
24% of all modules
have been procured by
South Africa
2,500
2,000
1,500
1,000
500
0
Q4
Q1
2010
GLOBAL TB
PROGRAMME
Q2
Q3
2011
Q4
Q1
Q2
Q3
2012
Q4
Q1
Q2
Q3
2013
Q4
Q1
Q2
Q3
2014
Q4
TBXpert Project
• $25.9 million UNITAID-funded project for procurement and use of
237 GeneXperts and 1.4 million Xpert MTB/RIF cartridges in 21
countries (2013-2015)
• Managed by the WHO Global TB Programme with the
Stop TB Partnership
• Implementation funding for selected sites by TB REACH
• Innovative social business models
designed by IRD in Bangladesh,
Indonesia and Pakistan
• Technical assistance provision
coordinated by African Society for
Project
Laboratory Medicine (ASLM) in
countries
5 African countries
GLOBAL TB
PROGRAMME
TBXpert Project: Interim progress
Xpert MTB/RIF tests procured and performed
Rifampicin-resistant TB cases detected
Target
procured
607,240 procured
394,240 performed
2013
2014
2015
2013-2014 cumulative:
• 607,240 tests procured
(1.4 million target by 2015)
• 394,240 Xpert MTB/RIF tests
performed
GLOBAL TB
PROGRAMME
2013-2014 cumulative:
• 17,017 rifampicin-resistant TB
cases detected
• Significant numbers of incident
TB and HIV-associated TB also
detected
Uptake of WHO policy recommendations:
national policies on Xpert MTB/RIF
Initial diagnostic
for people at risk
of DR-TB (2013)*
22 high TB burden 86%
countries
27 high MDR-TB
89%
burden countries
All countries
61%
Initial diagnostic
for PLHIV
(2013)*
82%
For diagnosing
TB in children
(2014)ǂ
59%
For diagnosing
extrapulmonary
TB (2014)ǂ
18%
89%
56%
– Countries using Xpert as the initial diagnostic test for all people suspected of having
TB: South Africa, Swaziland, Brazil, Moldova
– Moving beyond risk groups (though not for all people suspected of having TB):
• Testing of all smear-negative with chest X-ray abnormalities (e.g., Philippines)
• Testing of all people suspected of having TB, at sites with a GeneXpert;
specimens from risk groups referred from sites without GeneXpert (e.g., Tanzania)
GLOBAL TB
PROGRAMME
* WHO Global Tuberculosis Report 2014
ǂ Z.Z. Qin et al. Eur Respir J. Feb 2015; 45(2): 549-54.
Impact of Xpert MTB/RIF
Impact measures under assessment:
1.
2.
3.
4.
5.
Increase in TB cases detected
Increase in rifampicin-resistant TB cases detected
Reduction in diagnostic delay and time to treatment initiation
Reduction in morbidity and mortality
Cost-effectiveness and patient costs
GLOBAL TB
PROGRAMME
Impact of Xpert MTB/RIF
Impact measures under assessment:
1.
2.
3.
4.
5.
Increase in TB cases detected
Increase in rifampicin-resistant cases detected
Reduction in diagnostic delay and time to treatment initiation
Reduction in morbidity and mortality
Cost-effectiveness and patient costs
GLOBAL TB
PROGRAMME
Impact of Xpert MTB/RIF
Impact measures under assessment:
1. Increase in TB cases detected
- Given higher sensitivity of Xpert MTB/RIF compared to microscopy,
increases in numbers of bacteriologically positive cases have been
widely reported
- However, several studies from southern African countries1-2, Brazil3
and Nepal4 have not found a significant increase in overall case
notifications
 In these settings, patients are often started on treatment empirically,
even when Xpert does not detect TB
- An increase in bacteriologically positive cases may indicate that the
frequency of misdiagnosis and unnecessary treatment has been
reduced
GLOBAL TB
PROGRAMME
1 Theron
G et al. Lancet. 2014 Feb 1; 2 XTEND study; 3 Durovni B et al.
PLoS Med. 2014 Dec 9, 4 Creswell J et al. Int J Tuberc Lung Dis. 2015 May
Impact of Xpert MTB/RIF
Impact measures under assessment:
1. Increase in TB cases detected
2. Increase in rifampicin-resistant cases detected
- Countries are now able to detect rifampicin-resistant cases at
decentralized levels (e.g., 15 times more in India TBXpert Project sites)
- Quantification at global-level is challenging: countries report
numbers of rifampicin-resistant cases to WHO, but cases that are
detected with isoniazid resistance are classified as MDR-TB
- Scale-up of other DST technologies (LPA, MGIT) has been in parallel
GLOBAL TB
PROGRAMME
Impact of Xpert MTB/RIF
Impact measures under assessment:
1. Increase in TB cases detected
2. Increase in rifampicin-resistant cases detected
3. Reduction in diagnostic delay and time to treatment initiation
- Reduced time to TB treatment initiation in Brazil (11.4 to 8.1 days)1,
remote Canada (7.7 to 1.8 days)2, and in several southern African
settings3-5 with high HIV burden (2 to 1 day; 8 to 4 days; 11.5 to 1 day)
- South Africa EXIT-RIF study6 focusing on RR-TB: increase in enrolment
and reduced time to MDR treatment initiation (43 to 11 days)
- Health system conditions often prevent rapid turnaround time, return
of results and start to treatment (e.g., no TBXpert Project sites are able
to test, return results and initiate treatment on the same day)
1 Durovni
B et al. PLoS Med. 2014 Dec 9; 2 Alvarez GG et al. Chest 2015
May; 3 Theron G et al. Lancet. 2014 Feb 1; 4 Cox H et al. PLoS Med Nov.
GLOBAL TB 2014; 5 Van Den Handel, T et al. IJTLD 2015 April; 6 Van Rie A et al.
PROGRAMME Union conference 2014 abstract
Impact of Xpert MTB/RIF
Impact measures under assessment:
1.
2.
3.
4.
Increase in TB cases detected
Increase in rifampicin-resistant cases detected
Reduction in diagnostic delay and time to treatment initiation
Reduction in morbidity and mortality
- Studies in southern African settings1,2 have not found a significant
reduction in mortality or morbidity among drug-sensitive cases
- EXIT-RIF study3 in South Africa found a significant reduction
(10-fold) in mortality among rifampicin-resistant patients who
were HIV-negative; no significant difference among HIV-positive
patients
GLOBAL TB
PROGRAMME
1 Theron
G et al. Lancet. 2014 Feb 1; 2 XTEND study; 3 Van Rie A et al.
Union conference 2014 abstract
Impact of Xpert MTB/RIF
Impact measures under assessment:
1.
2.
3.
4.
5.
Increase in TB cases detected
Increase in rifampicin-resistant cases detected
Reduction in diagnostic delay and time to treatment initiation
Reduction in morbidity and mortality
Cost-effectiveness and patient costs
- Modeling studies1-5 have shown Xpert as a replacement or in
addition to microscopy is cost-effective for TB and DR-TB in high
burden settings
- One study6 in Brazil: Xpert can reduce patient costs by
approximately 30% vs microscopy
1 Theron
G et al. ERJ 2012; 2 Pantoja A et al. ERJ 2013; 3 Vassal A et al.
GLOBAL TB PLoS Med 2011; 4 Menzies N et al PLoS Med 2012; 5 Langley I et al.
PROGRAMME Lancet Global Health 2014; 6 da Silva Antunes R. et al. IJTLD 2014
Impact assessment: what more is needed
• Given impact is setting-specific, what is the impact of Xpert (on
TB/RR-TB case detection, mortality, time to treatment initiation, etc.)
in other settings with differing epidemiologies and health systems?
• What is the impact of Xpert on detection of paediatric TB and
extrapulmonary TB, and subsequent treatment outcomes?
• What is the impact of Xpert on reducing false-positive TB diagnosis,
and related adverse effects and costs?
• What is the impact of Xpert on reducing transmission of TB and drugresistant TB, and reduction of population-level TB burden?
GLOBAL TB
PROGRAMME
Acknowledgements
Laboratories, Diagnostics and Drug Resistance Unit, WHO Global TB Programme:
Fuad Mirzayev, Chris Gilpin, Jean Iragena, Alexei Korobitsyn, Henriikka Weiss,
Fraser Wares, Ernesto Jaramillo, Dennis Falzon, Linh Nhat Nguyen, Medea Gegia,
Lynne Harrop, Karin Weyer
Thank you
Wayne van Gemert
[email protected]
GLOBAL TB
PROGRAMME