MDR TB. Jaime C. Montoya MD, MSc

Transcription

1 MDR TB Jaime C. Montoya MD, MSc

2 Definitions of MDRTB and XDRTB Historical background of the problem Global and Philippine Data on MDRTB Risk Factors Diagnosis Treatment Research Gaps

3 Guidelines for the programmatic management of drug-resistant tuberculosis, WHO, 2006, 2008, 2011 update Towards universal access to diagnosis and treatment of multidrug-resistant and extensively drug-resistant tuberculosis by 2015, WHO Progress Report 2011 Management of MDRTB: A Field Guide, WHO and Partners in Health, 2009 Multidrug-resistant tuberculosis (MDRTB) indicators, WHO, 2010

4 Discussions and recommendations apply only to MDR-TB Findings may not be generalizeable to all populations in settings with high or low prevalences of drug resistance or different levels of resources Problems, however, in resource poor settings considered Results represent best available evidence to date for recommendations

5 Multidrug resistant tuberculosis (MDRTB) - TB caused by strains of Mycobacterium tuberculosis that are resistant to at least isoniazid and rifampicin Extensively drug resistant tuberculosis (XDRTB) - MDRTB plus resistance to a fluoroquinolone and at least one second line injectable agent: amikacin, kanamycin and/or capreomycin

6 In 2006, first reports of XDR-TB (Extensively Drug Resistant TB) Within the same year, cases of TB resistant to all first line and second line drugs reported in Italy (Extremely Drug Resistant TB or XXDRTB?) In 2009, cohort of 15 patients in Iran resistant to all anti-tb drugs reported (Totally Drug Resistant TB or TDRTB?)

7 In 2009, the Beijing Call for Action and the passage of World Health Assembly Resolution signaled a major step forward in coordinated planning for the treatment and control of MDRTB and commitment to achieve universal access to diagnosis and treatment by 2015

8 In the Philippines Mainstream PMDT to NTP With implementing guidelines for PMDT implementation DOH AO Guidelines for the Implementation of PMDT With the development of Philippine Plan of Action to Control TB (PhilPACT) The vision is a TB-free Philippines. - # 5 strategy:address MDR-5. TB, TB/HIV, and needs of vulnerable populations Training for different health staff involved in the management of DR/MDR cases (TOT, TC/STC/ TS, Volunteers)

9 Stop TB department of WHO convened technical consultation in Geneva March 2012 back to back with expert group meeting Objectives included overview of current information on XDRTB with additional drug resistance and feasibility and implications of new definitions

10 A new definition or category beyond XDRTB not recommended given technical difficulties of DST Insufficient evidence for linking DST results to treatment outcomes of patients Lack of standardised DST methods for several anti-tb drugs including investigational drugs DST for drugs used to define MDR and XDRTB are standardised, accurate and reproducible

11 All injectables and fluoroquinolones should routinely be tested in specimens from confirmed MDRTB to screen for XDRTB DST for all other drugs remains problematic for technical reasons Countries not advised to invest resources for developing capacity for DST of new drugs Need for research to develop standardized DST methods

12

13

14 Estimated % of New TB cases with MDR TB Estimated % of Retreatment TB cases with MDR TB Global Western Pacific Region (WPR) High MDR TB Burden Countries Estimated Proportion of TB Cases that Have MDR - TB Philippines Global tuberculosis control: WHO report 2011

15 As of January 2012, a total of: 12 regions are engaged in PMDT 18 PMDT treatment centers (12 public and 6 private facilities) 13 PMDT Satellite treatment centers (12 public facilities and 1 private facility) Total of 2, 303 patients currently ongoing Category IV Treatment

16 ) CAR NCR Reg. 7 Reg. 10 CAR CARAGA Reg. 11 Reg. 6 Reg. 1 Reg. 9 Reg. 5 Reg. 12 Reg. 4A 5) Reg. 1 1) NCR 7) Reg. 4A 6) Reg. 5 Regions to be engaged in : Reg. 2 Reg. 3 Reg. 4B Reg. 8 ARMM 9) Reg. 6 2) Reg. 7 3) Reg ) Reg. 9 15) CARAGA 11) Reg. 12 4) Reg. 11

17 Region Treatment Center Satellite Treatment Center NCR KASAKA QI LCP PHDU DJNRMH PTSI Tayuman San Lazaro Hospital Lagrosa HC Gat Andres MMH Tondo foreshore Moonwalk Super Batasan Grace Park Lacson HC 7 Eversley Child s Vicente Sotto MC 1 ITRMC Region 1 MC 4A DLSHSI and Batangas Reg. Hosp Cainta PPMD, Gumaca and Laguna 5 SMMGHHSC BMC 10 German Doctors ISI PPMD 11 SPMC DRH 6 WVMC and DPOTMH Roxas CHO 9 ZCMC Dr. Jose Rizal Mem Hosp 12 Koronadal CHO CAR BGHMC CARAGA CARAGA Reg. Hosp. OVERALL 18 TCs 13 (4 incomingstc)

18 PMDT Indicators TOTAL No. of lab confirmed MDR-TB cases detected No. of MDR- TB cases enrolled for treatment among those detected Interim Outcome Target Actual Target , Actual * 3620 (83.4%) Target 70% 70% 70% 70% Actual 73% 74%

19 Patient enrolment under Category IV treatment from 1999 to 2011 New patients Cumulative Start of RCC New patients Cumulative An additional 6,981 MDR TB cases is targeted to be treated under Category IV teatment from 2012 to 2014 A total of about 15,000 MDR TB cases is targeted to be treated by 2016 (PhilPACT)

20

21 Cure rate = 48.5% Success rate = 64%

22 Cure rate = 38.31% Success rate = 53.64%

23 Medium Risk Migrant worker Health worker with new TB Treatment after relapse or default High Risk Household contact of known MDRTB patient with new TB Probable treatment failure History of treatment with second-line drugs

24 Mediated exclusively by chromosomal mutations Affect either the drug itself or bacterial enzymes that activate prodrugs Well identified in INH and Rifampicin Local studies being done using spoligotyping and VNTR to identify the common mutations in Philippine isolates

25

26

27 Rapid diagnostic tests - tests providing diagnosis within two days of specimen testing - include test using molecular techniques (line probe assay and Xpert MDR/RIF)

28 Rapid DST of isoniazid and rifampicin or rifampicin alone is recommended over conventional testing or no testing at the time of diagnosis of TB subject (very low quality of evidence) Best strategy for averting deaths and preventing acquired MDR-TB Most cost-effective strategy for any patient group or setting, even at very low levels of resistance among TB patients

29 For previously untreated patients, DST at start of treatment was a better strategy than waiting to test only those patients who remained sputum smear-positive later in the course of their first line treatment High value placed on prevention of death, transmission of MDR-TB as a result of delayed diagnosis and lowered costs to TB control program

30 Sputum smear microscopy and culture rather than sputum smear microscopy alone recommended for the monitoring of patients with MDR-TB during treatment (very low quality of evidence) Limit of detection: smear 10,000 bacilli/ml culture bacilli/ml

31 Concomitant use of sputum smear and culture helps identify patients whose bacteriology remains positive or reverts to positive following initial conversion to negative fall and rise phenomenon

32

33

34 In the treatment of patients with MDR-TB: A fluoroquinolone (FQ) should be used (SR) A later gen FQ rather than earlier gen FQ should be used (SR) Ethionamide (or prothionamide) should be used (SR)

35 In the treatment of patients with MDR-TB: Four second-line anti-tb drugs likely to be effective (including a parenteral agent) as well as PZA should be included in the intensive phase (CR) Should include at least PZA, a FQ, a parenteral agent, ethionamide (or prothionamide) and either cycloserine or PAS if cycloserine cannot be used (CR)

36

37 Recommendations based on three major systematic reviews Meta-analysis included 32 studies with more than 900 treatment episodes No superior second line parenteral agent However, due to lower cost, kanamycin preferred Use of streptomycin not recommended Ciprofloxacin, even if with some anti-tb activity should not be used

38 Cure rates among bacteriostatic drugs: Ethionamide>cycloserine>PAS For Group 5 drugs, no significant association with cure due to confounders so not included in recommended standard MDR-TB regimen

39

40 In the treatment of patients with MDR-TB: Intensive phase of at least 8 months duration is recommended (CR) A total treatment duration of at least 20 months is recommended in patients without any previous MDR-TB treatment (CR)

41 In the treatment of patients with MDR-TB: Intensive phase of at least 8 months duration is recommended (CR) A total treatment duration of at least 20 months is recommended in patients without any previous MDR-TB treatment (CR)

42

43 Patients with MDR-TB should be treated using mainly ambulatory care rather than models of care based principally on hospitalization (CR) Benefit of reduced transmission can only be expected if proper infection control measures are in place

44 Persistent or new weight loss Persistent or new TB symptoms (fever, cough) Persistently positive sputum smears or culture Smear or culture positive after being negative for sometime

45 Lack of high quality evidence from RCT for optimizing treatment regimens in patients with MDR-TB including the best combination of drugs and treatment duration Lack of evidence for the best drug regimens for treating patients with MDRTB, with XDR-TB and others Very limited information about treatment of pediatric MDR-TB

46 Identification of most effective chemoprophylaxis for contacts of MDR-TB cases Therapy for symptomatic relief from adverse reactions linked to second-line anti-tb drugs

47 Dr. Rosalyn Vianzon, NTP, DOH Dr. Celine Garfin, NTP, DOH Dr. Vivian Lofranco, Lung Center and NTP, DOH Dr. Charles Yu, DLSU Dr. Toro Mori, Research Institute of TB, Japan Dr. Yoshiro Murase, Research Institute of TB, Japan Dr. Akihiro Ohkado, Research Institute of TB, Japan

48 So here we are quite frankly and free So tell Pasteur and Koch and whoever they may be That they have not seen the last of my comrades and me

49