1. Models of Care for People with Drug-Resistant TB: Advancements in South Africa
Dr. Norbert Ndjeka MD, DHSM (Wits), Dip HIV Man (SA), MMed (Fam Med) (MED) Director, Drug-Resistant TB, TB & HIV
National TB Prevalence Survey

2. OUTLINE Background and TB burden in South Africa Models of care
The use of bedaquiline in South Africa
Concluding remarks

3. BACKGROUND

4. HEALTH SERVICES IN SOUTH AFRICA
Population: 50,
Provinces – 9
Districts - 53
Sub districts - 253
Health facilities – 4790
MDR-TB beds: 2,500
DR-TB treatment sites: 298
GP 22.4%
LP 11%
NW 6.4%
MP 7.2%
FS 5.5%
KZN 21.4%
NC 2.2%
EC 13.5%
WC 10.5%
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Dr. Norbert Ndjeka

5. GXP sites Culture / LPA sites NTBRL

6. TB Burden in RSA
TB patients initiated on treatment decreasing: 406,082 to 332,170 (2009 and 2013)
Treatment success rate: 80,9 % for 2012 cohort
MDR-TB numbers initiated on treatment doubled between 2010 and 2013 (5,313 to 10,719)
MDR-TB treatment success rate of 49 % (2012 cohort > 8,000)
XDR-TB treatment success rate is 20 %

7. Challenges Waiting time before admission : 1 - 3 month (s)
Long distance of transportation for admission and follow up
Negative impact on social and economic status
Risk of transmission in hospital
Poor outcome of DR-TB cases
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Dr. Norbert Ndjeka

8. Benefits of Decentralization
Reduce transmission of DR-TB by initiating treatment sooner
Make more beds available
Improved adherence to medication
Improved cost effectiveness
Accommodate patient roles and responsibilities
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Dr. Norbert Ndjeka

9. Historical background
July ‘09
First workshop on community-based MDR-TB at Kopanong Hotel, Johannesburg, facilitators Drs. Jaramillo & Nkhoma
Oct ‘09
Workshop on best practices and community MDR-TB. Facilitators: Drs. Bayona & Alcantra
May ‘10
Discussion and adoption of the decentralised MDR-TB approach by TB Managers during quarterly meeting
Jun ‘10
Circulated draft policy framework on decentralized management of MDR-TB
Nov ‘10
National MDR-TB workshop to plan implementation
May ’11
Final draft discussed by Technical Committee at National Health Council meeting
26 Aug ’11
Approval
Oct ‘11
Printing
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Dr. Norbert Ndjeka

10. Levels for the Decentralized Management of DR-TB
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Dr. Norbert Ndjeka

11. Essential elements for Decentralization
Decentralized site
Access to lab services
Access to DR TB Drugs
Access to Audiometry
Health care professional initiating DR TB mx

12. MODELS OF CARE

13. Provinces requested to
Call meetings of all stakeholders to introduce the policy framework
Identify health facilities for scale up of MDR-TB services (plan, decentralized units, satellite units, PHC and injection teams)
Conduct facility readiness assessment of all proposed/identified facilities
Train all potential Care providers
Monitor & Evaluate decentralization of MDR-TB activities
11/26/2018
Dr. Norbert Ndjeka

15. Criteria for models of care
In patient care
Patient is not clinically well
Co-morbidities that presents with secondary complications
Serious adverse reactions
Outreach Model
A clinician based at another unit provides outreach services to areas where there are no initiators
The clinician will travel to the various facilities to initiate patients and also provide follow up
The above can be done as an ambulatory service or admission to a satellite facility
Ambulatory Model
Patients are initiated at Primary health care level
No admission is required
The patient managed according to this model is clinically stable

17. MDR-TB Treatment Strategies

18. Initiatives to support Decentralization

19. Initiatives to support Decentralization
Park homes are being utilized to bridge the infrastructure challenges.
They are utilized as the OPD facilities for DR TB patients.
It is also an option for admission and serving as a ward where infrastructure is inadequate

20. Summary of Decentralization: before 2011
Province
Central site
Decentralized site(Initiating)
Satellite
Injection teams
NIMDR SITES
Eastern Cape 1
Free State
Gauteng
KZN 4 -
Limpopo
Mpumalanga
Northern Cape
North West
Western Cape 2
South Africa 9 8

21. Summary of Decentralization: progress
Province
Central site
Decentralized site(Initiating)
Satellite
Injection teams
NIMDR SITES
Reporting units
Districts without decentralized units
Eastern Cape 1 14 10 4
Free State 15 5 3
Gauteng 46 2
KZN 11 80 8
Limpopo 9 19
Mpumalanga
Northern Cape 13
John Toale Ambulatory care
North West
Western Cape
185
261
2 Districts have an outreach Model
South Africa
298
272
150 37

22. MDR-TB treatment outcomes (2012 cohort KZN)
All Cases
HIV Positive
On ART
Cured
1277
949
847
Treatment Completed
477
348
302
Failed 98 75 72
Defaulted
566
406
326
Died
440
362
327
Transferred Out 46 32 23
Not evaluated 83 60 50
Still on treatment 21 19
Total
3010
2253
1966
Treatment Success Rate
58 %

23. XDR-TB treatment outcomes (2012 cohort KZN)
All Cases
HIV Positive
On ART
Cured 32 25
Treatment Completed 20 17 14
Failed 22 15
Defaulted 30 23 21
Died 40 28 26
Transferred Out
Not evaluated 5 4
Still on treatment
Total
154
117
108
Treatment Success Rate
34 %
36 %

24. National TB Prevalence Survey

26. THE USE OF BEDAQUILINE IN SOUTH AFRICA

28. Methods
Pre-XDR and XDR TB patients at five approved sites across South Africa were selected by pre-defined criteria

29. Provides energy (ATP) from a trans-membrane proton gradient
Mechanism of Action
In strains resistant to bedaquiline, mutations were identified in the gene coding for ATP synthase
Provides energy (ATP) from a trans-membrane proton gradient
Adapted from Science 2005, 307, 214

30. Culture negative at start n=15 Culture negative at start n=6
Enrolled, started on BDQ and included in the analysis n=91 33 XDR-TB 41 pre XDR (FLQ) 17 pre XDR (injectable)
>24 weeks since treatment start n=60
Completed 24 weeks BDQ n=58
Died n=2
Transferred out n=1
Defaulted n=1
On continuation treatment n=54
Culture negative at start n=15
Culture converted n=33
Still culture positive n=6
Did not complete BDQ n=2
Died n=1
<25 weeks since treatment start n=31
Still on treatment n=31
Culture negative at start n=6
Culture converted n=10
Culture pending n=15
Figure 1. Interim outcomes for XDR and pre XDR TB patients enrolled in National Bedaquiline Clinical Access Programme in South Africa
60 patients started BDQ over 6 months ago and 58 patients completed 6 months of treatment (one died and one defaulted)
52 were culture negative at 6 months giving a culture negative rate at 6 months of 86.6%
31 have had less than 6 months of treatment of those 16 have had at least two negative cultures separated by 30 days.
BDQ: bedaquiline; XDR TB: extensively drug resistant TB; FLQ: fluoroquinolone
National TB Prevalence Survey

31. Culture conversion by resistance pattern
Although the numbers are small, the rate of culture conversion is not affected by resistance patterns.
National TB Prevalence Survey

32. Culture conversion by HIV status status
All patients who were HIV infected were on ART at the time of starting BDQ. There is not difference in the culture conversion rate by HIV status.
National TB Prevalence Survey

33. Results – median QTcF

34. Results – QTcF by ART regimen
Although there are small numbers, there increase in QTcF does not appear to be greater in patients who are given LPV/ vs NVP. Also of note that that patient with a QTcF at two and three months was no NVP and not LPV/r
National TB Prevalence Survey

35. Results – QTcF by clofazimine exposure
National TB Prevalence Survey

38. CONCLUDING REMARKS

39. Conclusion
The programme has allowed access to better treatment hence the good interim outcomes for (pre-)XDR patients with otherwise limited options and poor prognosis
Bedaquiline is now registered in South Africa and will be used next year within the TB programme under strict control

40. Conclusion (2)
Decentralized management of MDR-TB increases access to care + NIMDR
It reduces time to MDR-TB treatment initiation which may reduce community transmission of MDR-TB
Decentralized management of MDR-TB produces outcomes similar to hospitalization generally; and sometimes even better outcome than hospitalization
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Dr. Norbert Ndjeka

41. Thank you
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Dr. Norbert Ndjeka