Update on MDR TB services under RNTCP

Dr D BeheraDirector

LRS Institute of Tuberculosis and Respiratory DiseasesNew Delhi

contents

• Burden of MDR-TB in India

• RNTCP response to the challenge of MDR-TB

• Status, vision and challenges

• Recent Key policy changes

• India is highest TB burden country with an

annual 1.98 million incident cases

• Estimated prevalence of 2.29 million cases

• Annual deaths due to TB 2,76,000

• TB/HIV Prevalence

– 2.31 million population living with HIV;

– ~ 0.9 million co-infected

– ~5% of TB patients estimated to be HIV +

Indonesia6%

Nigeria5%

Other countries20%

Other 13 HBCs16% China

14%

South Africa5%

Bangladesh4%

Ethiopia3%

Pakistan3%

Phillipines3%

India21%

Source: WHO Geneva; WHO Global Report 2009 & Short update to 2009 report

1.3 million

1.9 million

4.2 million

7.3million

0%

20%

40%

60%

80%

100%

Estimated Incidence of TB Cases Notified

India Rest of world

24%21%

Challenges to TB Control

• Wide variations in capacity of Health Systems across the country

• Burden due to TB-HIV Co-infection• Ensuring adherence of treatment for

migratory population• Large and unregulated Private Sector • Limited availability of new rapid diagnostic

tools, drugs and vaccine• Drug Resistance

Global Burden of MDR-TB*

79%

1. China – 100,0002. India- 99,0003. Russian Fed. – 38,0004. Pakistan- 15,0005. Phillipines-13,0006. South Africa- 13,000

0.44 million “incident” cases

27 HBC which account for 85% of

all cases

* WHO 2010 M/XDR-TB Global Report on Surveillance and Response

Drug resistant TB in India

• MDR-TB

– India has 2nd highest MDR-TB burden in the world after China

– As per DRS surveys done in 2005-06 in the states of Gujarat and

Maharashtra prevalence of MDR-TB is:

• <3% in new cases and 14-17% in previously treated cases

• As per WHO estimates 99,000 MDR cases emerged in India in 2008

• Mono and Poly resistance (Non MDR) TB

– Relatively high levels of non MDR resistance to H & S seen both in new

and previously treated cases, either as mono-resistance or PDR

Drug resistance in cases detected in Drug resistance in cases detected in prevalence surveys 1968-2003prevalence surveys 1968-2003

0

5

10

15

20

25

1968-70 1971-73 1973-75 1976-78 1979-81 1981-83 1984-86 1991-92 1994-96 1999-01 2001-03

Year

Percentage

H

S

HRSH

Source: TRC Chennai

Drug resistant TB in India

• Extensively Drug Resistant TB (XDR-TB)

– Reported in India though the data is limited and non-

representative

– Gujarat DRS survey shows

• No XDR-TB amongst new cases

• 4% amongst those previously treated cases found to be

MDR

• High levels of non-XDR resistance seen to Ofx and Eto in

both new and previously treated cases

57 countries

XDR –TB in the world as of March 2010

XDR-TB in IndiaStudy Setting No. of MDR

casesNo. Of HIV +ve

Prevalence of XDR-TB (%)

Reference

Mondal and Jain, 2007

Tertiary care centre, Lucknow

68 Not Reported 5(7.4) Emerg Infect Dis, 2007

Jain et al, 2007 Teritiary care centre, Mumbai

326 Not reported 36 (11) ATS, abstract, 2007

Singh et al, 2007

Tertiary care center, New Delhi

12 All HIV –infected

4 (33,3) AIDS, 2007

Thomas et al, 2007

Field trial, Chennai

66 Not reported 1(1.5) IJT, 2007

Sharma et al, 2009

AIIMS, New Delhi, tertiary care hospital

211 All HIV-negative

5(2.4) IJMR, 2009

Ramchandran et al, 2009

Gujrat, Field study

216 Not reported 7(3.1)All previously treated cases

IJTLD,2009

Causes of drug resistance • Essentially a man made phenomenon• Inadequate Regimens

– Irrational use – Inappropriate combinations– Sub-optimal doses and duration

• Inadequate supply or poor quality of drugs• Inadequate drug intake

DOTS Strategy adopted by RNTCP addresses all these

issues

RNTCP Response to Drug resistance TB

Multi-faceted approach …..

Key focus is on prevention

Sustained high-quality DOTS implementation

Promote rational use of anti-TB drugs

Improve laboratory capacity: Diagnosing MDR-TB

Effective treatment of MDR-TB patients

Initiation and rapid scale up of MDR-TB services

Evaluate the extent of the threat of second-line anti-TB drug

resistance and management of XDR-TB

Strategies….. • Prevention of drug resistance through sustained

high-quality DOTS implementation

• Improve laboratory capacity

• Effective treatment of MDR-TB patients

– RNTCP DOTS Plus (Category IV services)

Promote rational use of anti-TB drugs in the

country

• Implement infection control measures

MDR-TB services under rntcp

DOTS PLUS – model of care

DOTS PLUS SITE(IN-PATIENT FACILITY)CULTURE AND DST LAB

DISTRICT

HEALTH FACILITY (PHI)

MDR SUSPECT•Cat I/III failure•Cat II sm+ at 4 months of Rx •Contacts of MDR cases

SPUTUM SAMPLE MDR CASE

MDR CASE

RESULT

Initial hospitalization followed by

ambulatory care

Follow up protocol•Physical exam•Culture •Kidney function

Treatment Delivery

• Standardized regimen- Cat IV– Intensive phase (6-9 months)

• Kanamycin, levofloxacin (ofloxacin), Cycloseine, Ethionamide, Z, E

– Continuation phase (18 months)• Levofloxacin (Ofloxacin), Cycloseine, Ethionamide , E

– PAS is used as a substitute drug – Three weight bands –

• 16-25 Kg ; 26-45 Kg and >45 Kg

– Daily DOT (Kanamycin is given 6/7 days)

– Follow up• Smear and Culture monthly during IP and quarterly during CP• S Creatinine monthly till Kanamycin is administered

– Patients who remain culture + after 6 months of Rx are subjected to SLDST (Km and Ofx)

• If found to be XDR will be started on Cat V regimen

DOTS Plus Site – Gujarat

DOTS-Plus In-patient site •Tertiary level centre @1 per 10 million population•Dedicated in-patient facility with infection control measures in place •Trained staff available•Facilities for pre-Rx assessment & management of adverse reactions

Drug logistics

• Quality assured drugs procured nationally

– GLC

– GoI procurement

• Supply line

– Loose drugs supplied to State drug stores

– Repackaged into 3 monthly IP and CP boxes

– Supplied to the districts and downwards

– Loose drugs provided at DOTS Plus sites

• Logistics and reporting on consumption

integrated with first line drugs

3 monthly drug box

Recording and reporting

• Standardized records and reports

– Treatment card

– DOTS Plus TB register

– C & DST lab register

– DTC Referrral register

• Quarterly reporting

– Case finding report

– Interim culture conversion reports

– Final outcome report

• Plan to establish a dedicated web based

DOTS Plus information management

system shortly

Status of rntcp dots plus services

History…….• 2005

– Plan to initiate DOTS Plus services under RNTCP II project (2006-2011)• 24 IRLs to be established and enroll 5000 patients on treatment annually

– Constitution of National DOTS Plus committee • 2006

– National DOTS Plus guidelines developed • 2007

– Gujarat and Maharashtra initiate MDR services • 62 patients enrolled on Rx

• 2008– Services available in 8 States- AP, WB, Haryana, Kerala and Delhi

• 252 patients enroled on Rx

• 2009– Services available in 10 States-Rajasthan and Orissa

• 1415 patients enroled on Rx

Implementing DOTS Plus

Implement shortly

Under preparation

Present status

• 10 States implementing DOTS Plus services

– 127/632 districts covered

• Another 5 States to initiate services shortly

• More than 2300 patients on treatment

10 States implementing MDR services

~2300 patients on Rx

Status of c & dst labs 2Q10

• 14 C & DST labs accredited– 10 IRLs

• Gujarat, Maharashtra, AP, Kerala, Delhi, West Bengal, Tamil Nadu, Rajasthan, Orissa and Jharkhand

– 4 other sector labs• Medical Colleges- CMC, Vellore; SMS Jaipur• NGO Lab- BPRC, Hyderabad• Private sector – Hinduja Hospital, Mumbai

• Labs to be accredited shortly– IRL- Haryana; – KGMU, Lucknow

• Labs under accreditation process– IRL-Chattisgarh, Uttarakhand – PGI, Chandigarh; AIIMS, New Delhi, – Quest diagnostics; Ranbaxy Mumbai, Metropolis , Mumbai

TRC

HARYANANDTC

AIIMS

RNTCP Culture & DST Labs(15 August 2010)

LRS

NTI

Med Col / NGO / Private Labs (Accredited)

IRL (Accredited)

IRL (Under Accreditation)

Med Col / NGO / Private Labs (Under Accreditation)

IRL (Equipments being supplied)

Med Col / NGO / Private Labs (Preparatory)

National Reference Labs

10 Govt and 4 other

sector labs accredited

Gurgaon

Final Treatment outcomes

• First cohort of patients (2007)

– Most of them were chronic cases with h/o multiple Cat II treatments

– High level of second line drug resistance

Patients registered

Cured Rx completed

Failure Death Default

62 32(52%) 1 (1%) 5 (7%) 12 (20%) 12 (20%)

Dots plus vision….road ahead

DOTS Plus Vision……

• By 2010, RNTCP Category IV services will be introduced in all states with

complete geographical coverage by 2012

• By 2012, access to laboratory based quality assured MDR-TB diagnosis

and treatment for

– all smear positive re-treatment TB cases and

– new cases who have failed an initial first-line drug treatment

• By 2015, access to MDR-TB diagnosis and treatment for all smear

positive TB (new and re-treatment) cases registered under RNTCP

• RNTCP plans to initiate at least 30,000 MDR cases on treatment annually

by 2013

35000

80000

144000

160000160000

8000

1500

8000

15000

2500030000 32000

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2009 2010 2011 2012 2013 2014

% S

+ re

trea

tmen

t pat

ient

s fo

r D

ST

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

Patients tested for MDR-TB MDR-TB detected

Multi-year plan…..

*Based on RNTCP 2012 goal of MDR diagnosis for all S+ retreatment patients,

Strategies for achieving the vision

• Enhancing the laboratory capacity

– National Laboratory scale up plan

– Additional support from private and NGO laboratories

• Scaling up treatment services

• Mobilization of Resources

Lab scale up plan

• ~43 laboratory units to be established– Enhanced sputum processing capacity

– Solid culture and DST in all lab units

– Line Probe Assay (LPA) in all lab units

– Liquid culture in 33 lab units

Lab unit 2010-11 2011-12 2012-13 Total

Enhanced capacity for solid culture and sputum processing

12 13 18 43

Establish Molecular unit-LPA 12 13 18 43

Establish liquid culture systems 13 9 11 33

Expected annual DST capacity 35000 80000 144000 220000

Scaling up treatment services• DOTS Plus sites

– 120 DOTS Plus sites across the country (1/10 m population)

– Tertiary care centres with in patient facilities

– Upgraded to incorporate infection control measures

– Function

• Pre-treatment evaluation and treatment initiation

• Follow up of progress of patient

• Management of adverse reactions

• Recording and Reporting

• Uninterrupted supply of adequate quality assured second line drugs

• Provision for daily DOT

– Includes 6-9 months of injectables

Resource mobilization• Lab scale up to be undertaken with support from

– UNITAID Expand TB– Global Fund –RCC and Rd 9– World Bank – USAID through WHO

• Second line drugs Source 2010-11 2011-12 2012-13 2013-14 2014-15

Global Fund –RCC

800 1200 2450 3500 4250

World Bank

2350 3450 4550 9000 13250

UNITAID 4850 5000 - - -

Global Fund Rd 9

- 5350 18000 17500 14500

Total 8000 15000 25000 30000 32000

Recent Key policy changes

Recent Key policy changes….• Revision of MDR-TB suspect definition

– Cat I and III failures– Cat II patients who remain smear positive after 4 months of treatment

or later– Contacts of MDR-TB cases found to have smear positive TB

• Replacement of Ofloxacin by Levofloxacin in Cat IV regimen

– Regimen will now be

• IP: Km, Lvx, Cs, Eto, Z, E (6-9 months)

• CP: , Lvx, Cs, Eto, E (18 months)

• Earlier exclusion criteria (pregnancy, paediatric age group,

intake of SLD >1 mth) removed

Key policy changes ….2• Guidelines on the management of XDR-TB patients under RNTCP

finalized

– XDR-TB to be suspected in Category IV patients who remain culture positive after 6 months of treatment, SLDST to be done

– Such patients are to be treated with the Category IV regimen

• Guidelines on management of patients who default from Category IV treatment for more than 2 months and subsequently report back to RNTCP developed

• Management of DR-TB patients other than MDR-TB

– Patients with any rifampicin resistance will be treated with the MDR TB regimen, in addition to those with MDR-TB.

– Need to generate more evidence on treatment of other forms of mono and poly (non MDR) drug resistant TB

Challenges in achieving the vision

Challenges in diagnosis of MDR TB…

• Delay in establishment of accredited state level laboratories due to a host of reasons

• Sub-optimal functioning of the accredited labs

– Non-availability of trained manpower

• Dedicated regular staff in addition to the contractual posts

– Uninterrupted power supply

• Diagnostic delay with conventional method (3-4 months turn around time)

• Special requirements for introduction of newer rapid diagnostics- laboratory infrastructure and training

Treatment Challenges…….

• Long duration, toxic, expensive treatment – ~2,100 $ per patient course

• Daily ambulatory DOT – 6-9 months of injectables

• Availability of DOTS-Plus in-patient sites (1 per 10 million population)

• Extensive training, supervision and monitoring needed at all levels • Ensuring treatment adherence and timely follow up• Uninterrupted supply of second line drugs

•

Rational use of anti-TB drugs

• Problem – In 2006, substantial quantity of FLDs and almost 100% of SLDs were sold and used outside of RNTCP

– Well documented that management of TB patients outside of RNTCP is often poor leading to risk of failure of treatment and development of drug resistance

– Large unregulated private sector

– Conflict of Interest

– Easy availability of anti TB drugs

• Steps to promote rational use of anti TB drugs – “Chennai Consensus Statement” developed and disseminated

– IMA on behalf of RNTCP interacting with MCI for guidelines to all healthcare providers on rational use of anti TB drugs

– Interactions with office of DCGI to draft guidelines for the regulation of anti-TB drugs, especially SLDs,

– Encouragement of additional pre-qualified drug manufacturers

•

Infection Control……. • Problem

– Infection control considered synonymous with waste management

– Lack of National guidelines on Airborne Infection control in context of TB

– Overcrowding/lack of space at health facilities

– Lack of awareness and commitment of hospital administrators

• Steps taken – National Airborne Infection Control Committee constituted – “National guidelines for airborne infection control” for all healthcare facilities developed and pilot

tested – Provision of support to upgrade IC measures at

• DOTS-Plus site indoor facilities• Intermediate Reference laboratories

– Collaboration with AIDS control programme to ensure IC measures at ICTCs and ART centres– Encouraging Medical Colleges (through NTF, ZTF and STF mechanism) to develop and implement

infection control measures

•

Role of medical colleges in supporting scale up of dots plus services under rntcp

strengthening lab capacity• Medical colleges (public and private) with functional Mycobacteriology

laboratories encouraged to apply for accreditation

• Steps for accreditation-

– Download the application format for accreditation from www.tbcindia.org

– Submit the format to the State TB Officer with a copy to CTD

– Pre-accreditation visit

– Proficiency testing

– Accreditation

• Once accredited the lab can provide diagnostic and follow up services under RNTCP

• RNTCP will provide financial/commodity assistance for services provided

Treatment services • RNTCP can benefit from the rich experience of the Medical Colleges in

treating MDR TB • Medical Colleges (Public and Private) can serve as DOTS Plus sites

– Dedicated in patient facility (ward) • Separate space/ward for Male and Female patients • Adequate number of beds

– Facilities for pre-treatment evaluation– Constitution of DOTS Plus site Committee– Upgradation to incorporte infection control measures

• Responsibilities– Treatment initiation and follow up of MDR patients – Management of adverse reactions – Recording and Reporting

• RNTCP support– Funds upto 10 lakhs for upgradation – Human Resource- 1 Medical Officer; 1 Statistical Assistant – Computer with Internet facility

Thought for the day