تم القاء هذه المحاضرة خلال مؤتمر طب الازهر (بنات) بفندق كونراد القاهرة - الخميس 27 نوفمبر 2014

2. MDR / XDR Tuberculosis
Dr. Wagdy Amin
Training Coordinator
NTP Egypt
drwagdy@yahoo.com

4. Global TB Situation
Tuberculosis (TB) remains one of the world’s deadliest communicable diseases.
In 2013, an estimated :
9.0 million people developed TB
1.5 million died from the disease,
360 000 of whom were HIV-positive.

5. Of the estimated 9 million people who developed TB,
more than half (56%) were in the South-East Asia and Western Pacific Regions.
A further one quarter were in the African Region, which also had the highest rates of cases and deaths relative to population.
India and China alone accounted for 24% and 11% of total cases, respectively.

6. An estimated 1.1 million (13%) of the 9 million people who developed TB in 2013 were HIV- positive.
The African Region accounts for about four out of every fiveHIV-positive TB cases and TB deaths among people who were HIV positive.

7. TB detection and treatment outcomes 2013,
6.1 million TB cases were reported to WHO.
Of these, 5.7 million were people newly diagnosed and another 0.4 million were already on treatment.
the treatment success rate continued to be high at 86% among all new TB cases.

8. MDR-TB detection and treatment outcomes
Globally, 3.5% of new and 20.5% of previously treated TB cases were estimated to have had MDR- TB
This translates into an estimated 480 000 people having developed MDR-TB.
On average, an estimated 9% of patients with MDRTB had extensively drug resistant TB (XDR-TB).

9. IfallnotifiedTBpatients(6.1million,newandpreviouslytreated)hadbeentestedfordrugresistance,anestimated300000casesofMDR-TBwouldhavebeendetected,morethanhalfoftheseinthreecountriesalone:India,ChinaandtheRussianFederation
TheproportionofMDR-TBcaseswithXDR-TBwashighestinGeorgia(20.0%),Kazakhstan(22.7%), Latvia(21.7%),Lithuania(24.8%)andTajikistan.
Bytheendof2013,100countrieshadnotifiedatleastonecaseofXDR-TB.

10. 136 000 of the estimated 300 000 MDR-TB patients who could have been detected were diagnosed and notified.
A total of 97 000 patients were started on MDR-TB treatment in 2013, a three-fold increase compared with 2009.

11. 9 Million 7 Billion
6.1million notified 64%
Deaths
1.5 million1.1 millionTB/HIVEstimated MDR 480 000 / 9 M300 000 /6.1M
97 000 enrolled

12. Estimates of burden
Number (thousands)
Rate (per 100 000 pop)
Mortality (excludes HIV+TB)
0.55
(0.49–0.62)
0.67
(0.6–0.75)
Prevalence (includes HIV+TB)
22
(12–36)
27
(14–44)
Incidence (includes HIV+TB)
13
(12–15)
16
(15 -18)
Case detection, TB all forms
59%
(53% –65%)

13. Millennium Development Goals (MDGs)
Egypt had achieved Millennium Development Goals (MDGs) However, the case detection rate is still at 59%.
Prevalencehas declined from 85 cases/ 100 000 population in 1990 to 27 cases / 100 000 population in 2013
Incidenceof TB has declined from 34 cases / 100 000 population to 16 cases / 100 000 population in 2013
Mortalitycases has declined from 4 cases / 100 000 population to 0.6 cases / 100 000 population

14. 85
60
42
34
3029
2927
34
3226
2118
17
17160
10
20
30
40
50
60
70
80
90
1990
1995
2000
2005
2010
20112012
2013
Prevelance rate /100000
incidence rate /100000

15. Trend of mortality Rate

16. Burden of MDR in Egypt
3.4% (1.9%-4.9%) in new
32.1% (24.3%-39.9%) in retreated cases
(Drug resistance survey 2011).

17. MDR-TB management in Egypt
Egypt appliedto the green light committee, GLC, in 2003.
We received a review mission in January 2004.
The program was approvedand the first team was trained in Latvia.
The first MDR-TB center was established in Abbassiachest hospital and patient enrolled in June 2006.
Later on, another two centers were established, one in Maamoura chest hospital in 2008 and a third one in Mansoura chest hospital in 2012
A fourth center is being prepared now in Asuitchest hospital.

18. Second line drugs used in management of theses cases are funded from global fund grant.
The average treatment course costs around 4000 US$ and lasts up to two years compared to 6 months for susceptible tuberculosis and less than a 1000 EP.
From 2006 to 2013 ( 461patients enrolled in the treatment) with success treatment 68% MDR-TB management in Egypt, cont.

19. Different resistance patterns

20. Mono-resistance
colonies are resistant to only one of the first-line anti- TB drugs.
Poly-resistance Coloniesareresistanttomorethanoneofthefirstlineanti-TBdrugsbutdonotcombineresistancetobothIsoniazidandRifampicin. Examplesofpoly-resistancemayincludeStreptomycin,IsoniazidandEthambutolorStreptomycin,RifampicinandEthambutol.

21. Multiple drug resistant
colonies combine resistance to at least Isoniazidand Rifampicin.
Extensively Drug Resistant TB (XDR-TB): Colonies are resistant to:
1.1stLine drugs , at least Rifampicinand Isoniazid, (MDR- TB)
2.A fluoroquinolone
3.One or more of the following injectabledrugs: kanamycinAmikacinCapreomycin

22. Totally Drug–Resistant Tuberculosis (TDR-TB)
“for TB strains that showed in-vitroresistance to all first and second line drugs tested
Rifampicinresistance
resistancetorifampicindetectedusingphenotypicorgenotypicmethods,withorwithoutresistancetootheranti-TBdrugs.
Itincludesanyresistancetorifampicin,whethermono- resistance,multidrugresistance,polydrugresistanceorextensivedrugresistance.
AnyPatientfoundtohaveanRR-TBstrainatanypointintimeshouldbestartedonanadequatesecond-linedrugregimen.

23. Primary resistance and acquired resistance
“Primaryresistance”meansthatthepatientwasinfectedwithalreadyresistantbacilli.
“Acquiredresistance”meansthatpatientwasinitiallyinfectedwithsensitivebacillibutdevelopedresistanceofanypatternduringthecourseoftreatment

25. Compositionofsecond-lineanti-tuberculosisregimens
Fluoroquinolonesshouldbeusedtoallpatients.
Later-generationFluoroquinolonesratherthananearlier- generation
Fluoroquinolonesshouldbeused(levofloxacin- Moxifloxacin).
Ciprofloxaciniscontraindicatedasanti-TBdrugsbecauseofrapidemergingofresistantstrain.
Ofloxacinisnotrecommendedbecauseofweakefficacy

26. Ethionamide(orProtiomamide)shouldbeused.
Foursecond-lineanti-tuberculosisdrugslikelytobeeffective(includingaparenteralagent),aswellasPyrazinamide(regardlessthesusceptibility),shouldbeincludedintheintensivephase.
Pyrazinamidemaybeusedduringthewholetreatmentcourseifthepatientcantolerate.

27. MDR-TB,regimensshouldincludeatleast:
1)pyrazinamide,
2)aFluoroquinolones,
3)aparenteralagent,
4)Ethionamide(orProtiomamide),
5)andeitherCycloserineorPAS(p-amino-salicylicacid) ifCycloserinecannotbeused.

28. Intensivephaseofatleast8months’duration
totaltreatmentdurationofatleast20monthsisrecommendedinpatientswithoutanypreviousMDR-TBtreatment.

29. MDR-TB/HIV co-infection
AntiretroviraltherapyisrecommendedforallpatientswithHIVanddrug-resistantTBrequiringsecond-lineanti- tuberculosisdrugs,irrespectiveofCD4cell-count,asearlyaspossible(withinthefirst8weeks)followinginitiationofanti-tuberculosistreatment.

31. New treatment approach is highly needed in Egypt to overcome the challenge of patients’ adherence to treatment.
Community based ambulatory care rather than facility based treatment is the needed one where:
DR-TB patients receive their treatment at their homes
This help addressing serious barriers to adherence and DOT
Can be more cost-effective than hospital care (need to be investigated)
Compatible with hospital care and does not exclude it
Increases community awareness about DR-TB.
This needs developing a mass of trained treatment supporters to implement to ensure
Quality clinical care
Socioeconomic support
Psycho-emotional support
In addition, this needs incentives for the network personnel responsible for community based treatment of MDR-TB.

32. New rapid diagnostics are urgently needed in Egypt to enhance case detection and patients’ enrollment on treatment
TheGene-XpertMTB/RIFsystemisarecentlydevelopedTB-specificapplication,designedfortheGene-Xpertplatform,todetectM.tuberculosisaswellasrifampicinresistancedirectlyfromsputum.
OtherrapidmoleculartestingtechniquedetectingresistanceagainstbothIsoniazidandRifampicinaremorepreferableinEgyptbecausetherelativelyhighprevalenceofRifampicinmono-resistanceamongnewlydiagnosedTBcaseswhichisaround9%whiletheMDR-TBprevalenceisonly3.4%.
IncreasingnumberoflabsdoingDST(currentlyonly2)

33. New Medicine
BedaquilineanddelamanidaretwonewdrugsforuseinthetreatmentofMDR-TBwhichhaveemergedover2013–14,andWHOhasdevelopedinterimguidanceontheiruse.