Wendy Stevens Molecular Medicine and Haematology University of the Witwatersrand & NHLS

1. Taking the first steps Xpert MTB/RIF Implementation in public sector in South Africa: Lessons Learned Wendy Stevens Molecular Medicine and Haematology University of the Witwatersrand & NHLS Acknowledgments to:

2. GeneXpert Technology (Cepheid) GX48 (Infinity) GX16 GX4 16 64 255 throughput/ 8hr day FiND , 2010

3. Automated • Real-time PCR • Rapid (2 hours) • Cartridge based • Result • Positive/negative TB • Resistance yes/no to Rifampicin • Low contamination risk Boehme,C et al NEJM 2010

4. Disease Burden in South Africa • 20% worlds reported HIV‐associated TB cases and 2nd largest reported numbers of MDR • 70%-80% TB suspects infected with HIV • Overall TB rates 980/100,000 • Mining populations 2500/100,000 • Correctional Services 4500/100,0000 • Increasingly smear negative (8-10% positivity) and extra-pulmonary TB(16%) • WHO Strong Recommendation: “The new automated DNA test for TB should be used as the initial diagnostic test in individuals suspected of MDR-TB or HIV/TB” (i.e. all SA TB suspects)

5. NHLS TB Laboratory Facilities: 2010/2011 N=244 • 4.7 million smears • 1 million cultures • 90 000 LPA

6. Phase 1 rollout High burden, TB Intensified Case Finding campaign districts • Limited Pilot in all 9 provinces • Selection: volumes, district selected • 25 sites, 30 instruments • 20 GX4, 9 GX16, 1 GX48 • Placement by world TB day: March 24th • 11% national coverage based on 2010 smears/2.0 2 smears at diagnosis to be replaced by one Xpert MTB/RIF (Phased approach) (microscopy centre based)

7. Where should Xpert be placed within TB diagnostic algorithm?

8. Methodology: March-June 2011 • Site needs assessment: 25 sites • Hoods, space, network points, power, A/C, HR, checklist developed • Training • 80 laboratory technologists : intensive 2 day centralised training • -microscopists currently first cadre • SOP driven • LIMS interfacing (pilot) • A Lab-Track LIS interface was developed to automatically report: Lab number, cartridge number, TB detected/not, RIF detected/not. • A verification program (“fit for purpose”) for placement and calibration of each module • [MOPE147] • Development of implementation plan, budget and National TB Costing Model (NTCM)

9. 54 NHLS staff members trained prior to world TB day

10. National Xpert MTB Results (cumulative March to June) N = 50 093

11. National Xpert RIF results: March-June 2011 N = 8591 (MTB detected); 630 RIF Resistance

12. Geographical Variation

13. TB GeneXpert Positivity: eThekwini District in KZN Average smear positive rates for same period 2010 and 2011: 8%-9%

14. Challenges and Lessons learned

15. National Phased Implementation PHASES| PILOT | FULL PILOT|HIGH CASE| GF XPERT | CONTROL| DISTRICTS| ALL LABS FAST SCALE-UP | July 2011 | Dec 2011 | Sept 2011 | Mar 2011 | Dec 2011 | Dec 2012 SLOW SCALE-UP | July 2011 | Dec 2011 | Sept 2011 | Mar 2012 | Mar 2013 | Sept 2013 • FAST SCALE-UP scenario: Full coverage by December 2012 (Ministerial mandate) • SLOW SCALE-UP scenario: Full coverage by September 2013

16. Model for instrument placement(Fast scale-up, 10% growth in suspects) Initiated at current microscopy centres, volumes based on adjusted smear per patient , throughput of analysers. CAPITAL : $21 M

17. Recurrent costCost per MTB/RIF test (including hidden costs) Cost will vary: dependent on implementation rate, exchange global volumes, negotiation, freight • Modelled Average per test cost across all scenarios • 2011/12 to 2013/14: R 216.30 $ 26-36 • 2014/15 to 2016/17: R 189.85

18. National TB Cost Model • To estimate implementation costs for NHLS lab network • To inform national-level budget requirements (2011-2017) • To estimate the incremental national health service cost of replacing the existing pulmonary TB diagnostic algorithm with a new algorithm incorporating Xpert MTB/RIF molecular technology, under routine care conditions and at costs incurred by the government (Excel-based population level decision model) (HER0) • Built into Rollout BMGF study: cluster randomised trial design (phase 3a and b) : to verify modelling and assess impact ( Aurum Institute)

19. Programme cost:Total and per case cost in 2013 [2011 USD] (Fast scale-up, 10% growth , SA at 50% of global volume, purchase)

20. Conclusions I • Pilot demonstrated feasibility of implementation • Significantly increased early detection of MTB • Significantly increased screening for potential MDR cases • Significant changes to National TB program envisaged • Facilitating HIV/TB integration at laboratory, clinic and programmatic level • Expensive algorithm which may well have to be modified as confidence in technology and data emerges

21. Infinity Installation in Prince Msheyni in KZN: truly a team effort

22. Acknowledgements • NHLS NPP program • NDoH: Drs Mametje, Pillay, Mvusi, Barron • NTBRL: Drs Erasmus and Coetzee • CHAI SA • HERO team, G. Meyer –Rath, K. Bistline • Right to care: Ian Sanne • MM&H: Prof Scott, N. Gous, B. Cunningham • USAID South Africa • CDC for funding and support • FIND • Aurum Institute