1. Issues in TB care and financing Gesine Meyer-Rath Health Economics and Epidemiology Research Office (HE 2 RO) University of the Witwatersrand/ Boston University BEMF consolidation meeting 15 July 2011

2. Why TB financing? HIV care and treatment is better planned and funded than ever before in South Africa Lots of cost and epi data is known HIV care has ear-marked, national-level funds (Conditional grant) HIV care has own vertical system including own distribution channels for drugs TB diagnosis and treatment uses outdated tools and drugs and produces shoddy outcomes Very few cost data available, not much epi data TB care is funded at provincial level via Equitable share, like all other provincial programmes TB care is highly localised and integrated into horizontal systems

3. TB issues UninfectedSuspectCase Cured MDR XDR Cured PREVENTIONDIAGNOSIS TB TREATMENT MDR-TB TREATMENT

4. TB prevention UninfectedSuspect PREVENTION

5. TB prevention Early HIV diagnosis and ART initiation –HCT: 11.9 million people tested, but no link to TB diagnosis and treatment, not enough link to ART –ART initiation at >200 CD4 cells/µl <350 for patients with TB since April 2010 Initiation at <500 or irrespective of CD4 cell count? CMX and INH prophylaxis for HIV+ves –IPT: INH prophylaxis for 6 mts irrespective of CD4 cell count after excluding active TB –INH stock-outs as a result of badly planned demand –INH/CMX combination possible but still in development

6. TB diagnosis UninfectedSuspectCase DIAGNOSIS

7. TB diagnosis: Issues 1.Coverage: Case finding –Intensified Case Finding (ICF) campaign: visited 41,000 families and screened 112,000 contacts since Feb 2011 2.Sensitivity of current diagnostics (smear microscopy) 3.Time to result (culture, LPA, DST) 4.Cost of newer diagnostics (Xpert MTB/RIF, line- probe assay, drug-susceptibility testing)

8. TB diagnosis: Current situation Current algorithm starts with smear microscopy Smear microscopy of sputum  technology more than 125 years old Sensitivity of smear microscopy (ability to find TB when it is there) is approximately 70% Sensitivity of smear microscopy in HIV+ population drops to 35-45% Current algorithm depends on culture Culture highly sensitive (considered ‘gold standard’) However, takes 2-6 weeks for results High rates of contamination, missing results

9. Possible solution: Xpert MTB/RIF The Xpert MTB/RIF (Cepheid) test detects TB and rifampicin resistance (indication of MDR-TB) in less than 2 hours The sensitivity of Xpert MTB/RIF has been shown to be 86% in a SA demonstration study HIV status does NOT affect sensitivity of Xpert

10. Xpert roll-out: Planned timing  FAST SCALE-UP scenario: Full coverage by December 2012 (Ministerial mandate)  SLOW SCALE-UP scenario: Full coverage by September 2013 FAST SCALE-UP | June 2011 | Dec 2011 | Sept 2011 | Mar 2011 | Dec 2011 | Dec 2012 SLOW SCALE-UP | June 2011 | Dec 2011 | Sept 2011 | Mar 2012 | Mar 2013 | Sept 2013 PHASES| PILOT | FULL PILOT|HIGH CASE| GF XPERT | CONTROL | DISTRICTS| ALL LABS

11. VISIT 3 VISIT 2 VISIT 1 GeneXpert if negative if positive if unsuccessful RIF resistant/ inconclusive (MTB+/RIF+) Sputum microscopy TB culture + LPA +/- DST TB diagnosis HIV negative Antibiotics if resolved if failed if positive TB diagnosis if positive TB diagnosis Antibiotics Chest X-ray TB culture + LPA +/- DST Chest X-ray TB culture + LPA +/- DST if positive TB diagnosis if negative HIV status HIV positive/ status unknown HIV positive/ status unknown HIV status Antibiotics TB culture + LPA +/- DST if negative if positive TB diagnosis Patients with suspected pulmonaryMTB Xpert algorithm Stop Chest X-ray Repeat GeneXpert Sputum microscopy TB culture + LPA +/- DST if positive TB diagnosis Stop HIV negative HIV positive/ status unknown Antibiotics if positive TB diagnosis if positive TB diagnosis Sputum microscopy Antibiotics Chest X-ray if positive TB diagnosis if negative HIV status TB culture + LPA +/- DST if negative Stop if resolved if failed Stop Patients with TB history Current guidelines Patients without TB history All patients if un- successful HIV negative HIV status Antibiotics TB culture + LPA if negative Chest X-ray Stop TB diagnosis HIV positive if negative if positive TB diagnosis Sputum microscopy if positive Stop if negative Stop if negative

12. Xpert roll-out: Cost input Cost itemCost in 2011 ZAR TB diagnostics Xpert MTB/RIF testR190-220 Sputum microscopy (fluorescent microscopy)R26 TB culture (liquid medium, growth)R114 TB culture (liquid medium, no growth)R87 Line probe assay (LPA) for all positive culturesR189 Drug susceptibility test (DST) (first-line drugs only)R519 Chest x-rayR110 Antibiotic trialR19 Clinic visit: NurseR71 Clinic visit: PhysicianR130 TB treatment - First-line treatment (non- resistant)R3,441 - Second-line treatment (non-resistant)R6,806 - RIF monoresistanceR29,677 - INH monoresistanceR6,275 - Multi-drug resistance (outpatient care only)R29,677

13. Xpert roll-out: Results of National TB Cost Model  Xpert leads to an increase of 30% in TB cases diagnosed 76% in MDR cases identified 39% in number of patients treated 55% in the cost of the TB diagnostic programme 32% in the outpatient cost of the TB treatment programme if scaled-up fast  Under the Xpert scenario, 87% of diagnosed patients are diagnosed by Xpert 83% are diagnosed after the first visit

14. TB treatment UninfectedSuspectCase Cured MDR TB TREATMENT

15. Patients with diagnosed pulmonaryMTB Regimen 1 (RHZE for 2 months, RH for 4 months) Patients without TB history (New cases) Regimen 2 (RHZES for 2 months, RHZE for 1 month, RHE for 4 months) Patients with TB history (Retreatment cases, old guidelines only) RHZE for 2 months, RH for 4 months + OFL for 6 months Patients with INH mono-resistance KNM, ETH, PZA, OFL+ TZ for 6 months + ETH, OFL+ TZ for 18 months Patients with RIF mono-resistance Patients with multi-drug resistant TB (MDR-TB) KNM, ETH, PZA, OFL + TZ for 6 months + ETH, OFL + TZ for 18 months + Inpatient care until culture -

16. TB treatment: Non-resistant TB Community-based treatment Good coverage, but low quality: –Low completion rate –Low cure rate –High MDR and XDR rate 2008 NHLS data: 6,219 MDR cases and 576 XDR cases Community-based system needs re- strengthening –PHC revitalisation –Community health-worker framework –Intensified case-finding (ICF) campaign

17. MDR/ XDR-TB treament UninfectedSuspectCase Cured MDR XDR Cured MDR-TB TREATMENT

18. MDR-TB treatment: Issues 1.Cost of drugs and monitoring of side effects 2.Centralised vs. decentralised care; inpatient vs. community care –Infection control –Patient autonomy –Operational challenges Drug supply chains Administration of daily injectibles for 6 months 3.Improving outcomes –Cure rates between 33% and 45% –Default rates up to 70% –Death rate at Tugela Ferry after 1 year 75% (2005-2007)

19. MDR-TB treatment: Current situation MDR-TB care differs vastly by province –KZN: mostly community care; GP: exclusively centralised care Current guidelines prescribe inpatient care until culture negative (2 cultures taken 30 days apart) –currently at specialised MDR/ XDR hospitals (9 specialised, 11 decrentralised units) –73% of known MDR/ XDR cases in 2008 were hospitalised –on average 4 months –not enough capacity (1,854 beds in Feb 2010), waiting list –at average cost per patient-day equivalent (R 1,069) 4 months cost R163,000

20. MDR-TB treatment: Decentralised care Decentralisation plan for MDR care approved by National Health Council Rationale: –Low capacity and infection risk while waiting –Nosocomial transmission of MDR/XDR-TB –Patients abscond due to lack of recreational facilities, family responsibilities and lack of income –Even if ambulant, monthly trips to centralised hospitals are difficult –Decentralised care is uncoordinated and chaotic

21. Planned guidelines: –MDR-TB treatment at MDR units in TB hospitals (district and sub-district level) and at PHC clinics –Inpatient treatment for 8 weeks or until 2 consecutive sputum smears negative –Follow-up at community level by PHC staff or mobile units and DOTS plus supporters MDR-TB treatment: Decentralised care

22. Summary: Cost issues I Very few data available –Cost of diagnosis modelled –Cost of treatment: 1 study of community-based treatment (Sinanovic et al Int J TB Lung Dis 2003) 1 study on cost of care for HIV-co-infected patients (Cleary et al Cost Effect Resource Alloc 2006) –No data on cost of MDR care Studies on real cost of Xpert roll-out and on cost of MDR-TB inpatient care planned

23. Summary: Cost issues II ICF: more suspects (target: 10% growth every year) Xpert: 30% more cases, 76% more MDR cases, 39% more patients on treatment  Higher cost ICF: lower smear sensitivity in suspects Xpert: more cases treated, lower transmission, less new cases (including of MDR-TB) MDR/XDR-TB treatment decentralised with less inpatient care  Lower cost