Program Management Of DR-TB (PMDT) “Diagnose, Treat and Cure All Missing TB Cases” Dr Mohan K Prasai Consultant Chest Physician NTC

Global Burden Of MDR-TB: 2012 Global Estimation 310,000 Diagnosed cases 86,000

Types of Drug Resistance Mono-resistance : resistance to single first line drug Poly-resistance: resistance to more than one drug other than HR together Multi- Drug resistance (MDR): resistance to at-least Rifampicin & Isoniazide or RIF Resistance confirmed by GeneXpert. Pre-XDR: MDR with resistance to one of injectable or floroquinolone. Extensive Drug resistance (XDR): resistance to floroquinolone and injectable second line in addition with MDR TB. XXDR: Resistance to almost all ATT.

Types of Resistance (By Treatment history) Initial resistance ( New cases - never have prior ATT or less than one month) Acquired resistance (Re-treatment or new case with more than one month of ATT)

Multi Drug resistant Tuberculosis MDR TB is an increasing health problem. A serious challenge to TB control programm. It is regarded as a result of failure of effective implementation of Tuberculosis control program. Minimize the transmission of DR-TB by Infection control measures. GeneXpert is a gold standard diagnosis tool for early and confirmatory diagnosis of MDR-TB.

How is it caused ? It is the result of inadequate or poorly administered treatment regimen. Causes of inadequate treatment: 1. Health care providers- inadequate regimens 2. Drugs -inadequate supply or quality 3. Patients -inadequate drugs intake

When to Suspect of MDR TB ? Failure of Re-treatment Regimen Persistent positive sputum Fall and Rise Phenomenon Clinical and radiological Deterioration

DR-TB(M/XDR) Management sites 50% Treatment Centers and 25% Sub Treatment Centers in private sector Rx Centres: 13 Rx Sub-centres: 71

Key Policies of PMDT GeneXpert test is gold standard test Provision of free quality assured second line drugs Fully supervised treatment Prepare the patient for treatment Clinical monitoring, treatment and documentation of side effects Regular sputum microscopy and culture monitoring Standardized recording and reporting system Monitoring of treatment outcome and evaluation of program progress through cohort analysis

Candidates for Second line DST(SLDST) Any patient who has had a past history of previous second line drugs Any patient who remains culture positive on or after four months of the standard regimen used for MDR TB Contacts of an individual documented with XDR TB.

Where To Refer ? Near by GeneXpert centre Line Probe Assay (LPA) Near by GeneXpert centre National Reference Lab, GENETUP, Kalimati National Tuberculosis Center, Thimi

Nepal Report In % (MDR-TB)

Nepal Report In % (XDR-TB)

DR TB Program Milestones 2005 - DOTS PLUS Pilot Program started with 350 pts for 2 yrs(Treatment Centers- 5, Sub Centers – 11) 2007 - GLC review and permission for expansion (300/year) 2010 - XDR-TB Treatment started 2011 - Treatment Centre - 12, Sub-Centre - 62 (8 DRTB Hostels established in 5 regions (EDR-1, CDR-3, WDR-1, MWDR-2, FWR-1) 2012 - 2 hostels planned 2013 - Treatment centre 13,sub-centre-71, DR Home in Bandipur

List of DR-TB centers National TB centre,Thimi (G) National Medical College,Birgunj (NG) Lalgadh Hospital (G) NATA Morang (NG) BPKIHS Dharan(NG) Regional TB centre, Kaski(G) Bhim Hospital,Bhairawa(G) Lumbini Zonal Hospital, Butwal(G) NATA,Banke (NG) Mahakali Zonal Hospital, Mahendra Nagar (G) Seti Zonal Hospital,Dhangadhi(NG) TEAM Hospital- Dadeldhura(NG) NATA/GENETUP-Kathmandu(NG)

Differences between DR Centre and Sub centre Treatment centre Sub centre Facility of Medicines Facility of Sputum examination Facility of Baseline investigations Responsible for filling all the documents required for enrollment and follow-up Responsible to transport the sputum samples to NRL for C/S Facility of management of severe side effects Responsible to Quarterly reporting to Regional monitoring & evaluation WS Facility of medicines Facility of management of minor side effects Responsibility of referring the patient to DR Centre for each monitoring investigations Responsible to Quarterly reporting to Treatment centre (DR-TB management WS)

Responsibilities of DR TB centre Counseling to the patient Registration of the patients Baseline and follow-up investigations Collection & transportation of the samples to NRL Provide DOT Management of the side effects Supervision of DR Sub centers Participation in the National monitoring and evaluation workshop

Responsibilities of DR TB Sub-centre 1. Counseling to the patient 2. Provide DOT 3. Refer the patients to DR centre for regular investigations 4. Management of minor side effects

Standard MDR-TB Treatment Regimens First Phase 8 – 12 months (intensive phase) Kanamycin (KM) Pyrazinamide(Z) Levofloxacin (Lfx) Ethionamide (Eto) Cycloserine (Cs) Second Phase 12 – 14 months (continuation phase) All the drugs except the injectables.

Extensively Drug Resistance (XDR )TB XDR-TB is a form of TB which is resistant to at least four of the core anti-TB drugs. XDR-TB involves resistance to the two most potential anti TB drugs, that is Isonized & Rifampicin, also known as MDR-TB in addition to resistance to any of the floroquinolone (ofloxacin,Moxifloxacin) and any injectable aminoglycosides (Capreomycin, Kanamycin). Take substantially longer to treat than ordinary(drug susceptible). Require the use of second line anti TB drugs ,which are more expensive and have more side effects.

Management of XDR TB cases Started since Feb 2010 Much more difficult to treat than MDR TB cases Standard regimen (but individualization is implemented in the substitution of drugs for severe side effects) Intensive phase for 12 months and continuation for another 12 months. (Injectable first 8 months six days a week ,and then 4 months thrice a week)

Standard XDR –TB Treatment Regimens First Phase 12 – 16 months (intensive phase) Capreomycin(CM) Pyrazinamide(Z) Moxifloxacin(Mfx) Amoxycillin/clavunate(Amoxy/clav) Cycloserine (Cs) Paraaminosalicylic Acid (PAS) Clofazamine(cfz) Second Phase 12 – 14 months (continuation phase) All the drugs except Injectables one.

Drug Resistance Survey Report Year Initial Any Resistance Initial MDR Acquired Any Resistance Acquired MDR 1999 13.32% 3.74% 28.20% 11.96% 2002 10.99% 1.32% 40.93% 20.46% 2007 14.71% 2.86% 25.3% 11.72% 2011 9.6% 2.2% 25.4% 15.4%

Estimation Of MDR/XDR TB In Nepal    DRS- 2011 2013-14 2014-15 2015-16 Estimated MDR-TB cases among new cases 2.2% 553 557 561 Estimated MDR-TB cases among retreatment cases 15.4% 455 464 467 Total estimated MDR-TB among notified cases 1008 1021 1027 XDR-TB cases targeted for enrolment 35 40 45 Pre-XDR 63 95 120

MDR-TB patients enrolled in DR program of Nepal

Treatment : Comparisons

Facility/Support To Health Care Providers: To the patients Health Hazard (Nrs.1000 per month) Supply of PPE (N-95 mask and gloves). To the patients Nutritional support (Nrs.1500 per month) throughout the treatment period. Supply of surgical mask

Prevention of MDR TB ????? Rapid diagnosis and adequate treatment of TB with qualitative drugs Sound implementation of DOTS program Identify contacts who could have contracted TB, i.e family members, people in close contact etc. Patients with HIV/AIDS should be identified and diagnosed ASAP. Contact tracing for MDR -TB cases in place Early diagnosis of DR-TB cases referring suspected cases for GeneXpert Infection control measures taken where all DR- TB patients will be treated Indoor Facilities ( Isolation) during Ss positive

What Improves Outcomes: Early identification (and treatment) of MDR-TB Use of an “effective” regimen Adequate patient support DOT Prompt management of side-effects Social economic support

“ STOP TB IN MY LIFETIME” REQUEST Drug resistant tuberculosis is entirely the end results of a number of different Failures, which is possible to Avoid by providing qualitative service . LET us work all together for the sake of future generation. Be sincere towards to own responsibilities “ STOP TB IN MY LIFETIME”

Challenges !!! Ignorance/Poverty Low MDR-TB case finding Limitation of sample currier system Limitation of Diagnostic centers Insufficient socio-economic support to patients High prevalence of Floroquinolone Resistance Infection control measures are not in place Limitation of qualified health personnel in DR centres Social stigma

I am Stopping TB We Must Stop TB

Thank you for your kind Attention