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

Taking the first steps Xpert MTB/RIF Implementation in

public sector in South Africa: Lessons Learned

Wendy StevensMolecular Medicine and HaematologyUniversity of the Witwatersrand & NHLS

1

Acknowledgments to:

Health Economics and Epidemiology Research Office

Wits Health Consortium University of the Witwatersrand

HERO2

GeneXpert Technology (Cepheid)

16 64 255 throughput/ 8hr day

GX4

GX16

FiND , 2010

GX48 (Infinity)

• 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

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)

4

NHLS TB Laboratory Facilities: 2010/2011

5

• 4.7 million smears

• 1 million cultures

• 90 000 LPA

N=244

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)

Where should Xpert be placed within TB diagnostic algorithm?

7

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)8

54 NHLS staff members trained prior to world TB day

National Xpert MTB Results (cumulative March to June)

ICF MTB detected

MTB notdetected

Test failure Total %

Positive

ICF 2218 12 762 744 15 724 14.11%

Non-ICF 6373 26 725 1271 34 369 18.54%

Total 8591 39 487 2015 50 093 17.15%

% Total 17.15% 78.83% 4.02% 100%

10

N = 50 093

National Xpert RIF results: March-June 2011

ICF Status

Indeterminate No result Resistant Sensitive Total %

ICF 15 78 195 1930 2218 8.79

Non-ICF 57 57 435 5824 6373 6.83

Total 72 135 630 7754 8591 7.33

% 0.84 1.57 7.33% 90.26% 100% 7.3311

N = 8591 (MTB detected); 630 RIF Resistance

Geographical VariationProvince MTB

DetectedMTB Not Detected Test Failure Total % MTB

Positive % RIF

Eastern Cape632 3141 148 3921

16.12 7.12

Free State523 2701 1 3225

16.22 5.93

Gauteng 683 3528 94 4305

15.87 7.32

Kwazulu-Natal

3941 14490 788 19219

20.51 7.13

Limpopo515 4142 62 4719

10.91 8.16

Mpumalanga 879 4515 557 5951

14.77 8.08

North West527 2867 72 3466

15.20 9.30

Northern Cape

868 4049 292 5209

16.66 7.03

Western Cape23 54 1 78

29.49*

-

Total8591 39487 2015 50093

17.15 % 7.33 %

TB GeneXpert Positivity: eThekwini District in KZN

YEAR MONTH MTB Detected MTB Not Detected Test Unsuccessful Total % MTB Detected3 470 1455 214 2 139 21.97 4 1568 5647 646 7 861 19.95 5 847 3179 490 4 516 18.76 6 232 1013 55 1 300 17.85

3 117 11 294 1 405 15 816 19.71 19.71 71.41 8.88 100

eThekwini GeneXpert Positivity DataDate period: March 2011 to 9 June 2011

2011

Grand Total% of Total

Average smear positive rates for same period 2010 and 2011: 8%-9%

Challenges and Lessons learnedChallenges Lessons LearnedAlgorithm development Time to get consensus, ideally before implementation

Need to build in flexibilityChanges: TB guidelines, request forms, training etc, resistance reporting

Training Site needs assessmentAt least 2 days, several individuals at each siteBetter on site, Include GLP, safety, computer literacyFocus on sample preparationClinician training criticalWorkflow issues problematic on large instrumentsRegulatory issues

Costing implementation & modelling future costs

Numerous sources for inputNeed to model futureOpportunity for costing and reviewing current TB service

Error rates 3-4%: error codes: 5011 (73%), 5006/7 (16%)(insufficient vol), 2008 (10%)

EQA program Verification program : DCSFrequency? Per module?Need for negative controls for larger analysers?

Electricity, temperature, waste disposal, cartridge storage

UPS, A/C (if>30C)Cartridges fairly bulky (2-28C)

Safety Biohazard hood for infinity and GX16

National Phased Implementation

FAST SCALE-UP scenario: Full coverage by December 2012 (Ministerial mandate) SLOW SCALE-UP scenario: Full coverage by September 2013

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

PHASES| PILOT | FULL PILOT|HIGH CASE| GF XPERT | CONTROL | DISTRICTS| ALL LABS

Model for instrument placement(Fast scale-up, 10% growth in suspects)

2011/12 2012/13 2013/14 Tests/ day at full capacity

ProvinceGX4 GX16 GX48 GX4 GX16 GX48 GX4 GX16 GX48

EC 4 12 10 14 2 2,720

FS 1 5 3 496

GP 3 13 14 1,552 KN 6 11 1 18 36 2,944 LP 3 4 7 20 1,056

MP 2 5 3 7 544

NC 2 2 1 192

NW 3 1 11 656

WC 1 1 1 4 7 1,088 TOTAL 65 GX4, 169 GX16, 4GX48 11,248

Initiated at current microscopy centres, volumes based on adjusted smear per patient , throughput of analysers. CAPITAL : $21 M

Recurrent costCost per MTB/RIF test (including hidden costs)Cost item Cost % of totalCartridge R 161.45 70%Calibration R 4.47 2%Staff R 18.77 8%Consumables R 5.02 2%Waste disposal R 1.92 1%Transport and logistics R 15.33 7%Training and QA R 3.83 2%Overheads R 19.17 8%Total R 229.96 100%

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

Cost will vary: dependent on implementation rate, exchange global volumes, negotiation, freight

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)

Programme cost:Total and per case cost in 2013 [2011 USD]

(Fast scale-up, 10% growth , SA at 50% of global volume, purchase)

Scenario Annual cost Cost per suspect

Cost per case

1) Cost of diagnosis onlyBaseline $ 105 M $ 45 $ 312Xpert scenario $ 160 M $ 69 $ 367Difference to Baseline $ 55 M $ 24 $ 54

% change +53% +53% +17%2) Cost of diagnosis and outpatient treatmentBaseline $ 280 M $ 121 $ 835Xpert scenario $ 399 M $ 172 $ 912Difference to Baseline $ 118 M

$ 51 $ 77

% change +42% 42% 9%

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

Infinity Installation in Prince Msheyni in KZN: truly a team

effort

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