20/03/2012 1 Global value chain in action: Xpert MTB/RIF Mark Nicol Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town and National Health Laboratory Service [email protected]Disclosure The University of Cape Town (PI Mark Nicol) has received funding from FIND to support evaluation and demonstration studies for GeneXpert. I have no other conflicts of interest to declare. Acknowledgement I gratefully acknowledge Prof. Wendy Stevens, NHLS Priority Programmes and University of the Witwatersrand for information and slides on the national roll‐out of Xpert MTB/RIF
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Global value chain in action: Xpert MTB/RIF
Mark NicolDivision of Medical Microbiology and
Institute for Infectious Diseases and Molecular Medicine,
University of Cape Town and National Health Laboratory Service
The University of Cape Town (PI Mark Nicol) has received funding from FIND to support evaluation and demonstration studies for GeneXpert.
I have no other conflicts of interest to declare.
Acknowledgement
I gratefully acknowledge Prof. Wendy Stevens, NHLS Priority Programmesand University of the Witwatersrand for information and slides on the national roll‐out of Xpert MTB/RIF
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Xpert MTB/RIF for the diagnosis of TB
Lawn, Nicol. Future Microbiol 2001; 6(9): 1067‐82
Lawn, Nicol. Future Microbiol 2001; 6(9): 1067‐82
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Sensitivity of Xpert for diagnosis of TB in adults
Lawn, Nicol. Future Microbiol 2001; 6(9): 1067‐82
TB diagnostic services in SA: before Xpert
Microscopy Sites and Smear volumes (2010)4.7 million smears
1 million cultures (22% positive)
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WHO recommendation process
• WHO Expert group meeting (September 2010)
– Reviewed 4 published papers and unpublished data (GRADE)
– Confirmed solid evidence base to support widespread use
• STAG‐TB endorsed Expert group recommendations
– Advised implementation within the context of national strategic plans
– Recommendations:
• Xpert should be used as the initial diagnostic test in individuals suspected of having MDR‐TB or HIV‐associated TB. (Strong recommendation)
• Xpert MTB/RIF may be considered as a follow‐on test to microscopy in settings where MDR‐TB or HIV is of lesser concern, especially in further testing of smear‐negative specimens. (Conditional recommendation acknowledging major resource implications)
WHO recommendation process
• Global consultation called by WHO (December 2010)– Discuss implementation considerations
– Interim diagnostic algorithms and case definitions
– Positioning of Xpert• District and sub‐district level
• Prioritize high MDR‐TB and HIV‐TB sites
• Sufficient workload
• Adequate infrastructure
• Dedicated personnel
• Capacity for treatment
– Implementation considerations to optimize use and benefits
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The decision to roll out Xpert in SA
• December 2010: WHO recommendation
• Early 2011: Minister of Health requests implementation
• NDoH proposed pilot study (while feasibility being assessed)
– >1 instrument per province in high burden districts (selected by TB cluster)
– 25 sites selected and 30 instruments placed (funded by NDoH, FIND, PEPFAR)
– All instruments placed by world TB day (March 24th)
Phase I placements
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Phase I results
• By October 2011:
– 135,601 specimens tested
– 16% positive
– Average rifampicin resistance 7%
– Error rate <3% (except May – 5% due to batch issue)
– Invalid rate <1%
Phase I sites
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Instrument utilization rates
Phased roll out of Xpert in SA
• Phase I: completed • Phase IIa: full capacitation of existing labs (17 additional
instruments, completed October 2011) • Phase IIb: full capacitation of high burden districts
(Global Fund, roll‐out in April 2012) • Phase IIIa and b: BMGF funded study (Gauteng, EC and
Free State) • Phase IIIc: ensuring all districts have a minimum of 1
instrument per district • Phase IIId: completion of all current microscopy and
clinic sites
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Phase I and IIa results
• By January 5, 2012:
– 209,099 specimens tested
– 17% positive (35,737 new cases)
– Average rifampicin resistance 7%
– Error rate <3% (except May – 5% due to batch issue)
2 and 6 months follow upIn all TB treated and TB test positive patients
Speciation and DST for C+
Sputum 2 Sputum 1
Smear(local lab)
Sputum 2
SmearMGIT
(regional lab)
Impact assessment: Cape Town Demo Study
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Khayelitsha (1 clinic)
768 TB suspects
2 smear sensitivity: 46%
TB suspect / MDR suspectTwo sites
Paarl (6 clinics)
1399 TB suspects
Xpert 373
Xpert sensitivity: 88%
Control 395 Xpert 614 Control 785
2 smear sensitivity: 48%Xpert sensitivity: 88%
Cape Town Demo Study: Summary
MGIT pos 37%
Ref smear pos: 15%
MGIT pos 35%
Ref smear pos: 14%
MGIT pos 18%
Ref smear pos: 5%
MGIT pos 21%
Ref smear pos: 7%
Additional yield 42% Additional yield 40%
• Sensitivity of Xpert:
– HIV‐negative patients• All HIV neg: 95%
• Smear pos: 100%
• Smear neg: 92%
– HIV‐infected patients• All HIV pos: 85%
• Smear pos: 100%
• Smear neg: 79%
Impact of HIV on performance of smear microscopy and Xpert
S‐ X‐
S‐ X‐
S+ X+
S‐ X+S+ X+
S‐ X+
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Both laboratory sites:– Fluorescent AFB microscopy– NHLS QA programme
KY clinic laboratory – started operation 1 month prior to study– Single experienced technician– 40‐50 smears per day
vs.
Paarl laboratory– Established district laboratory– 2 staff members performing/reading AFB smears– 200 smears per day (multiple clinics)
What is in a smear?
Variable performance of smear microscopy
Both smears +
Local smear +
Reference smear +
38
53
9
Both smears +
Local smear +
Reference smear +
30
60
10
Khayelitsha Paarl
Xpert sensitivity: 88.3% Xpert sensitivity: 87.5%
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Time to treatment
6
38
4
4
9
7
938
6
38
44
938
9
7
Time to treatment
P<0.001P<0.001
82737165
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Further impact assessment
• Phase II of Demo study
• XTEND study
– to evaluate the effectiveness and cost effectiveness of Xpert MTB/RIF in the investigation of TB and TB drug resistance, and its impact on patient and programmeoutcomes and transmission at a population level
– cluster randomised pragmatic trial (CRT) with the unit of randomisation as the laboratory
Acknowledgements
• FIND– Catharina Boehme– Pamela Nabeta– Christen Gray