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
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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)
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NHLS TB Laboratory Facilities: 2010/2011
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• 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?
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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%
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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