Revised National Tuberculosis Control Programme

Tuberculosis

• TB is an infectious disease caused predominately by Mycobacterium tuberculosis

• Commonly transmitted when a person with untreated TB coughs or sneezes.

• Usually affects the lungs. But can affect any part of the body.

• (LN’s, pleura, bones and joints, genito-urinary tract, nervous system, abdominal TB, skin, etc.

Burden Of TB

In India everyday• More than 6000 people develop TB diseases• More than 600 people die of TB(i.e.2 deaths in every 5mins)

India accounts for one fourth of the global TB burden.More than 40% of the population is infected. Highest burden of TB and MDR-TB. And 2nd highest of HIV associated TB Globally(2015).

• Estimated Multi-drug resistant TB– ~3% in new cases– 12-17% in re-treatment cases

• TB-HIV– ~2.31 million people living with HIV (PLWHA)– 10-15% annual risk (60% lifetime risk) of developing active

TB disease in PLWHA– Estimated ~ 5% of TB patients are HIV infected

Burden Of TB

Evolution of TB Control in India 1950s-60s Important TB research at TRC and NTI 1962 National TB Programme (NTP) 1992 Programme Review

only 30% of patients diagnosed; of these, only 30% treated successfully

1993 RNTCP pilot began 1998 RNTCP scale-up 2001 450 million population covered 2004 >80% of country covered 2006 Entire country covered by RNTCP

National Tuberculosis Programme(NTP)

Operational since 1962. Unacceptably low success rate. Spread of multidrug resistant TB. Managerial weakness Inadequate funding. Over-reliance of X-ray for diagnosis. Frequent interrupted supplies of drugs. Low rate of treatment completion.

Revised national tuberculosis control programme (RNTCP)

• Launched in 1997 based on WHO DOTS Strategy– Entire country covered in March’06 through an unprecedented rapid

expansion of DOTS

• Implemented as 100% centrally sponsored program– Govt. of India is committed to continue the support till TB ceases to be

a public health problem in the country

• All components of the STOP TB Strategy-2006 are being implemented

Stop TB Strategy

• Pursuing High quality DOTS expansion and enhancement

• Addressing TB-HIV,MDR-TB and other challenges

• Contributing to health system strengthening• Engaging all care providers• Empowering patients and communities• Enabling and promoting research

Objectives of RNTCP

Achievement of at least 85% cure rate of infectious cases; through DOTS involving peripheral health functionaries.

Augmentation of case finding activities through quality sputum microscopy to detect at least 70% of estimated cases.

The 5 components of DOTS

5Political & administrative

commitmentDiagnosis by good quality sputum

microscopyAdequate supply of good quality

drugsDirectly observed treatmentSystematic monitoring &

Accountability

Organisation

Organisation

RNTCP Laboratory Network

National Reference Laboratory (NRL)

NRL conducts annual On-site evaluation/supervisory visits to laboratories for assessing quality of microscopy, Culture and DST, and for improvement of overall laboratory quality .

The programme has provided HR support by way of three microbiologists and four senior laboratory technicians to each NRL for these activities under the head of NRL strengthening.

The functions of the NRLs include conduct of Culture and DST trainings to the IRLs, develop SOPs for the technical procedures, equipment maintenance, infection control, and recording and reporting.

Intermediate Reference Laboratory (IRL)

There is at least one IRL per state. Its functions is to provide culture and DST for the

category IV services in the State . The IRL conducts on-site evaluation visits to districts

for sputum microscopy at least once a year. The IRL undertakes panel testing of STLS at each DTC. The IRL ensures the proficiency of staff performing

RNTCP smear microscopy activities by providing training to laboratory technicians and STLS.

Designated Microscopy Centre (DMC)

The most peripheral laboratory under the RNTCP network is the designated microscopy centre (DMC) which serves a population of around 100,000 (50,000 in tribal and hilly areas).

RNTCP has provided financial assistance for upgrading existing health facilities, supplied a binocular microscope for each DMC and ensured adequate supply of staining reagent and consumables at the DMCs.

DMCs are manned by a trained laboratory technician (LT) of the state health system.

RNTCP External Quality Assessment

o Panel testing

o On site evaluation‐o Random blinded rechecking of routine slides

Case Definitions

• Presumptive PTB: any of the symptoms and signs suggestive of TB including cough >2 weeks, significant weight loss, haemoptysis, any abnormality in CXR.

• Presumptive EPTB: presence of organ specific signs and symptoms like swelling of LN, pain and swelling of joints, neck stiffness, disorientation, etc and/or constitutional symptoms like significant weight loss, persistent fever ≥2weeks, night sweats.

• Presumptive paediatric TB: children with persistent fever and/or cough for >2weeks, loss of weight/no weight gain and/or history of contact with infectious TB cases.

• Presumptive DR TB: TB pts who have failed treatment with first line drugs, paedritic TB non responders, TB pts who are contacts od DR TB, pts found +ve on any follow up sputum smear examination during treatment with first line drugs, previously treated cases, HIV co-infection.

Case Definitions

Diagnostic Tools

1. Smear Microscopy (for AFB)

• – Sputum smear stained with Zeil-Nelson Staining or

• – Fluorescence stains and examined under direct or indirect microscopy with or without LED.

Sputum AFB GradingNo of fields to examine

Grading Result

No AFB in 100 fields 100 0 Neg

1-9 AFB per 100 fields 100 Scanty Pos

10-99 AFB per 100 fields

100 1+ Pos

1-10 AFB per field 50 2+ Pos

>10 AFB per field 20 3+ Pos

2. Culture• – Solid (Lowenstein Jansen) media or Liquid

media (Middle Brook) using manual, semiautomatic or automatic machines e.g. Bactec , MGIT etc.

• Drug sensitivity testing

3. Rapid diagnostic molecular test• – Conventional PCR

based Line Probe Assay for MTB complex or Real-time PCR based Nucleic Acid Amplification Test (NAAT) for MTB complex e.g. GeneXpert

CBNAAT (Cartridge Based Nucleic Acid Amplification Test)

CBNAAT is an automated Cartridge Based Nucleic Acid Amplification Test that has demonstrated its potential to detect tuberculosis and Rifampicin resistance with high accuracy.

It is also called Gene Xpert MTB/RIF (Cepheid Inc, USA) test, a highly sensitive and specific tool with a quick turn-around time (TAT), offers early diagnosis of TB and DR-TB) in the programmatic settings amongst adult and children as well.

X-ray is an Important Complementary Tool

• Highly sensitive; with low specificity• Plays a useful supportive role:• May lead to over-diagnosis

– May miss the diagnosis of other diseases (e.g. malignancies)

• NOT a good tool for follow-up of patients on ATT

• Note: Diagnosis of TB based on radiology (e.g. X-ray) will be termed as clinical TB.

Others:Tuberculin skin test- may be used as a complimentary test in children.

Serological tests: unreliable and banned.

Multi Drug Resistance Tuberculosis (MDR-TB)/ Rifampicin Resistance

• Patient with a drug susceptibility test result from a RNTCP-certified laboratory or WRD (WHO-endorsed Rapid Diagnostics) drug susceptibility test report showing resistance to rifampicin.

• Rapid Molecular Test ( LPA/ CB-NAAT)• Liquid Culture & DST• Solid Culture & DST

Diagnostic Algorithm for PTB

2016 Guidelines

Diagnostic Algorithm for Paedatric TB

2016 Guidelines

MDR TB

Cases

Microbiologically confirmed TB Case

Clinically diagnosed TB case

Anatomical site TB Rx History Drug resistance

Pulmonary TB

Extra Pulmonary TB

New case

Previously treated

Transferred in

MR

PDR

MDR

XDR

RR

Recurrent Rx after Failure

Rx after loss to follow up

Others

Miliary TB

Cure: initially sputum smear positive who has completed treatment and has negative sputum smear on two occasions, one od which is at the end of treatment.

Treatment completed: A patient who has completed treatment according to guidelines but does not meet the definition for cure or treatment failure due to lack of bacteriological results.

Treatment failure: if still positive at the end of 5 mths or more after initiation of treatment and not put on MDR TB

Treatment default: A patient whose treatment was interrupted for 2 or >2 consecutive months for any reasons.

Anti TB Drugs

New Anti TB drugs

• Bedaquiline• Delamanid• Pretomanid• NC-002, NC-003• Sutezolid• SQ 109• Benzothiazinones

Repurposed Anti TB drugs

• Linezolid• Clofazamine• Imipenem/ Meropenem• Amoxicillin – Clavulanate• Thioacetazone• Clarithromycin

Bedaquiline (BDQ)

• New class of drug - Diarylquinone.• Specifically targets Mycobacterial ATP Synthase.• Strong Bactericidal and sterilizing activity.• June 2013 – WHO published Interim policy guidance

for use of BDQ in conjunction with WHO recommended MDR-TB STRs.

• 2016 – RNTCP is introducing BDQ through conditional access programme at 6 sites in India.

Has extended half life. Will be present in plasma upto 5.5 months after stopping BDQ

Criteria to receive BDQ (Apex Committee):• Adults >18y with Pulmonary MDR-TB• Non pregnant females using non-hormonal birth

control methods.• Absence of arrhythmias or Controlled stable

arrhythmias.

Rx of Drug sensitive TB:Till 2015 2016

Thrice weekly regimen Once daily for all Paediatric & PLHIV cases – 104 districts

Individual drug doses based on 3 weight bands for MDR TB Rx

FDCs based on weight bands (4 in adult, & in child) for TB Rx

Continuation of IP for 1 month if sputum positive

IP need not be continued

CP is with HR CP includes Ethambutol (HRE)

For EP Tb cases, CP is for 7 mo For EP TB cases, CP is extended for 12-24 wks (3-6mo)

For TBM cases Inj SM added in IP

No change in IP

Follow Up sputum tests:At the end of Intensive PhaseTwo months into Continuation PhaseAt the end of Continuation Phase

Drug Resistance

• Drug Resistant case: A patient whose TB is due to tubercle bacilli that are resistant in vitro to at least to one Anti TB drug according to accredited laboratory methods in an RNTCP accredited laboratory

• MONO RESISTANCE: A patient whose TB is due to tubercle bacilli that are resistant in vitro to exactly to one anti TB drug in an RNTCP accredited laboratory

• POLY RESISTANCE: A patient whose TB is due to tubercle bacilli that are resistant in vitro to more than one anti TB drug, except not due to INH and Rifampicin in an RNTCP accredited laboratory

Drug Resistance

Multi Drug Resistant TB (MDR-TB)

• DEFINITION: An isolate of M. Tuberculosis resistant to at least INH and Rifampicin with or without other antitubercular drugs based on DST result from an RNTCP accredited culture and DST laboratory.

How does drug resistance happen?

• When these drugs are misused or mismanaged. – When patients do not complete their full course of

treatment; – When health-care providers prescribe the wrong

treatment, the wrong dose, or length of time for taking the drugs;

– When the supply of drugs is not always available; – When the drugs are of poor quality.

Who is at risk for getting MDR TB?

People who– Are irregular in taking medicines– Do not take all of their TB medicine as told by

their doctor or nurse – Relapse– Come from areas of the world where drug-

resistant TB is common – Have been exposed to DR TB

Extensively drug resistant TB-XDRTB

• DEFINITION: TB showing resistance to INH, Rifampicin, and any fluroquinoline, and at least one of the three injectable drugs used in Anti TB treatment: Capriomycin, Kanamycin and Amikacin

Programmatic management of drug resistant TB (PMDT) services

The term “Programmatic Management of Drug Resistant TB” (PMDT) (erstwhile DOTS Plus), refers to programme based MDR TB diagnosis, management and treatment.

RNTCP introduced the PMDT services since 2007 to address the MDR TB issue in the country.

MDR TB suspect criteria as per current programme ‑guidelines.

Criteria A: All failures of new TB cases, Smear +ve previously treated cases who remain smear +ve at 4th month onwards, All pulmonary TB cases who are contacts with known MDR TB case

Criteria B – in addition to Criteria A, All smear +ve previously treated pulmonary TB cases at diagnosis, Any smear +ve follow up result in new or previously treated cases

Criteria C – in addition to Criteria B, All smear −ve previously treated pulmonary TB cases at diagnosis HIV TB co infected ‑cases at diagnosis

Policy changes related to the DOTS plus

• The definition of the MDR suspects has been revised to include ‘contacts of MDR cases who are found to be smear positive; besides Category I failures and Category II patients who are smear positive at 4 months or later.

• The existing exclusion criteria for MDR suspects i.e. Age < 15 years and history of intake of second line drugs for more than 1 month in the past has been withdrawn. A new weight band (16-25 Kgs) has been added for the treatment of the paediatric MDR patients.

• In order to make Category IV regimen more effective it has been decided to replace Ofloxacin with Levofloxacin.

• Guidelines for the management of MDR patients with pregnancy have been finalized.

• Guidelines for the management of Extensively Drug Resistant TB (XDR TB) patients with Category V regimen have been formulated.

RR/MDR TB MxDrugs given are -• Kanamycin• Levofloxacin• Ethionamide

• Pyrazinamide• Ethambutol• Cycloserine

For MDR TB cases, IP can be extended for 3mo maximumFor all MDR TB cases with additional resistance, IP can be extended for maximum 6mo.

XDR TB MxDrugs given are – • Capreomycin• Moxifloxacin• Linezolid• PAS• Clofazamine• Amoxi/Clav• High Dose INH

Weight Bands

• Recommendation of drug doses according to weight have been made since 2010 itself.

• New (2016) guidelines by Govt of India Central TB Division provides number of FDCs according to weight bands.

• 4 weight bands for Adults, 7 for children.• This is to prevent further drug resistance and assured

bioavailability by increasing drug compliance.

Adults

Paediatric

Paediatric

• STRs to drug sensitive and MDR TB for paediatric age group are similar to adult, with dose changes.

• INH Preventive therapy for <6y age children who are – Close contacts of TB– Excluded to have active TB

• Irrespective of BCG and nutritional status.• INH 10mg/kg for 6mo given.

Link between TB and HIV

• HIV co-infection strongest known risk factor for the progression of latent TB infection

• Conversely, TB is amongst the most common causes of morbidity and mortality in people living with HIV/AIDS

• Immune response to TB bacilli increases HIV replication leading to a rapid progression of HIV disease

• Optimal access to DOTS will significantly reduce morbidity and mortality in PLWHA

• PLHA’s should be screened for TB and vise versa.

Treatment of TB in HIV• TB can be successfully treated even in HIV-infected patients• But, cannot alone prevent people from dying of AIDS

– In addition to TB treatment, ART and CPT needed for those eligible• Daily DOTS is the treatment of choice.• Supply of ATT drugs at ART center itself.• If ART is not started:• Start pt on ATT. Once pt tolerates the treatment(2-wks-2mth)

then start ART.• New pts TLE is preferred.• Drug interactions between Rifampicin and ARVs

– National policy is to start ART after completing anti-TB treatment, or modify ART by replacing Nevirapine with Efavirenz for the duration of TB treatment

Surveillance

Case-based web-based reporting system (NIKSHAY)

• The database of RNTCP was conventionally on Epiinfo based software for reporting with electronic data transmission from district level upwards.

• CTD in collaboration with National Informatics Centre (NIC) developed a case based web-based online (Cloud) application - ‘Nikshay’, launched in May 2012, which has been now scaled up nationally.

NIKSHAY• It has following components –• • Master management• • User details• • TB patient registration &

detail of diagnosis, DOT provider, HIV status, follow up, contact tracing, outcome

• • Details of Solid and liquid culture & Drug Sensitivity Testing (DST), Luciferin Probe Assay (LPA), CBNAAT

• • DRTB patient registration with details

• • Referral & transfer of patients• • Private health facility

registration and notification• • Mobile application for TB

notification• • SMS alert to patients on

registration and to programme• officer• • Automated periodic report

(case finding, sputum conversion and outcome).

Pill Adherence:

Newer methods to check adherence in daily DOTS.Mobile based missed call registrations.Some tablets have a number on the underside. Pts have to a give a missed call on that number from their phone which records adherence.

End TB Strategy

• WHO’s End TB Strategy

The strategy aims to end the global TB epidemic, with targets to reduce TB deaths by 95% and to cut new cases by 90% between 2015 and 2035, and to ensure that no family 100% is burdened with catastrophic expenses due to TB.