MDR & XDR TB

PRESENTER:

DR. MANJU PILANIA

JUNIOR RESIDENT

COMMUNITY MEDICINE

PGIMS, ROHTAK

Remembering sir John Crofton (1912–

2009)

• Giant in the history of TB control.

• Initiator of the clinical trials

against TB using combined

regimens in the early 1950s.

• First to study and recognize the

importance of drug resistance in

TB.

FEW DEFINITIONS

MDR TB –SUSPECT

Any TB patient who fails an RNTCP Category I treatment regimen;

Any RNTCP Category II patient who is sputum smear positive at the

end of the fourth month of treatment or later; or

Close contacts of MDR-TB patients who are found to have smear

positive pulmonary TB (PTB) disease.

XDR TB –SUSPECT

Patients on category IV treatment whose 4th month culture is positive

(available after 6th month of treatment )

Category IV patient who has culture converted but is found

subsequently to have 2 consecutive positive cultures,

Source: DOTS Plus Guidelines, 2010

FEW DEFINITIONS

• Confirmed MDR-TB case: An MDR-TB suspect who is sputum

culture positive and whose TB is due to Mycobacterium tuberculosis

that are resistant in-vitro to at least isoniazid and rifampicin (the

culture and DST result being from an RNTCP accredited

laboratory).

• Extensively Drug Resistant TB (XDR–TB) : is a subset of

MDR-TB where the bacilli, in addition to being resistant to R and H,

are also resistant to any fluoroquinolones and any one of the second-

line injectable drugs (namely Kanamycin, Capreomycin, or Amikacin).

FEW DEFINITIONS

• PRIMARY or PRE-TREATMENT RESISTANCE-

When drug resistance is demonstrated in a patient who has never

received anti-TB treatment previously, it is termed primary resistance

• SECONDARY or ACQUIRED RESISTANCE-

Here the bacteria were sensitive to the drug at the start of the treatment

but became resistant to the particular drug during the course of the

treatment with it.

Strains with genetic drug resistance

Wild M.Tuberculosis

Acquired drug resistance

Primary drug resistance

Spontaneous mutation

Selection: inadequate/ improper treatment

Transmission

DEVELOPMENT OF ANTI-TUBERCULOSIS DRUG RESISTANCE

Pablos-Mendez et al. WHO, 1997

HISTORY

• MDR-TB was first seen in the early 90’s.

• The description of XDR-TB was first used earlier in 2006, following a

joint survey by WHO and the US Centres for Disease Control and

Prevention (CDC).

• First case of XDR –TB in India was diagnosed in P. D. Hinduja

National Hospital and Medical Research Centre, Mumbai in 2006.

GLOBAL TB SITUATIONEstimated number

of cases, 2010Estimated number

of deaths, 2010

All forms of TB 8.8 million(8.5–9.2 million)

1.1 million*

(0.9–1.2 million)

Multidrug-resistant TB

~650,000 out of 12 million prevalent TB

cases

150,000

Extensively Drug-

resistant TB

32,500 17,000

HIV-associated TB 1.1 million(1.0–1.2 million)

350,000(320,000–390,000)

Source: WHO Global Tuberculosis Control Report 2011

PROBLEM STATEMENT

MDR- TB • Globally Prevalence of MDR- TB

• 3.4% in new TB patients

• 20% in those previously treated

• In countries like Belarus and parts of the Russian Federation more

than a quarter of new TB cases now have MDR-TB.

• Swaziland reported the highest level of primary MDR –TB ever

reported in Africa in 2009 (7.7%).

Source: TUBERCULOSIS MDR-TB & XDR-TB 2011 PROGRESS REPORT (WHO)

PROPORTION OF MDR AMONG NEW TB CASES LATEST AVAILABLE DATA, 1994-2010

0-<3

3-<6

6-<12

12-<18

>18

No data available

Subnational data only

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border

lines for which there may not yet be full agreement. WHO 2011. All rights reserved

0-<6

6-<12

12-<30

30-<50

>50

No data available

Subnational data only

PROPORTION OF MDR AMONG PREVIOUSLY TREATED TB CASES

LATEST AVAILABLE DATA, 1994-2010

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border

lines for which there may not yet be full agreement. WHO 2011. All rights reserved

• Available data from 74 countries and territories with measurements for

at least two years could not answer the question of whether the

proportion of previously untreated TB cases with MDR was increasing,

decreasing or stable over time at a global or regional level.

• For some countries (e.g. Latvia, USA) and regions (e.g. Orel and

Tomsk in the Russian Federation) time trends based on observations

over several years indicate a decrease in MDR-TB frequency, while in

others (e.g. Botswana and Swaziland) there appears to be an

increase.

TIME TRENDS IN MDR-TB

WHO Region 2010

Estimated Reported Ratio

African 32,000 9,504 30%

American 6,200 2,158 35%

East Med. 14,000 829 6%

European 53,000 32,616 62%

S-E Asian 88,000 3,779 4%

West Pacific 77,000 4,222 5%

Global 290,000 53,108 18%

MDR-TB notification and enrolment (3)MDR cases reported vs estimated among notified TB, 2010

MDR- TB INDIA

• Estimated no of MDR-TB cases - 110,132

• A large scale population based DRS in the state of Gujarat and

Maharashtra has indicated multi drug resistance levels of 3% among

new TB cases and 12-17% among previously treated TB patients.

• MDR TB is a manmade

problem…..It is costly, deadly,

debilitating, and the biggest threat to

our current TB control strategies.

PROBLEM STATEMENT

XDR-TB

• By October 2011, 77 countries had reported at least one case of XDR.

• Coverage is low particularly in the African continent as a result of low

capacity for testing for second-line medicines.

• WHO estimate that some 5% of people with multi drug resistant TB may

actually have extensively drug resistant TB.

COUNTRIES THAT HAD REPORTED AT LEAST ONE

XDR-TB CASE BY OCT 2011

HIGH MDR-TB AND XDR-TB BURDEN COUNTRIES

PROBLEM STATMENT

INDIA

• XDR-TB has been reported in India by isolated studies with non-representative and highly selected clinical samples.

• The magnitude of the problem remains to be determined due to the absence of laboratories capable of conducting quality assured second line DST.

• Preliminary results of second-line DST for MDR-TB patients from DOTS Plus sites and also isolates collected from Gujarat and Maharashtra drug resistance surveys show that there is not yet any XDR-TB amongst new cases and ~0.5% amongst re-treatment cases.

MECHANISM OF RESISTANCE

ANTIMICROBIAL

AGENT

MECHANISM OF ACTION MECHANISM OF RESISTANCE

ISONIAZID Inhibition of mycolic acid biosynthesis -Mutations in katG

-overexpression of inhA

-ahpC mutation

RIFAMPICIN Inhibition of transcription Mutation of rpoB prevent interaction

with rifampicin

STREPTOMYCIN Inhibition of protein synthesis Mutation prevent interaction with

streptomycin resistance .

MECHANISM OF RESISTANCE

ANTIMICROBIAL

AGENT

MECHANISM OF ACTION MECHANISM OF RESISTANCE

ETHAMBUTOL Inhibition of arabinogalactan and

lipoarabinomannan biosynthesis

Overexpression or mutation of Emb B

allow continuation of arabinan

biosynthesis

PYRAZINAMIDE Unknown

???

FLUORO-

QUINOLONE

Inhibition of the DNA gyrase Mutation in gyr A prevent interaction

with fluoro-quinolones

CAUSES OF DRUG RESISTANCE

• Microbial:

• As a result of genetic mutation.

• Caused by random chromosomal mutations at predictable

frequencies.

• Clinical

• Due to inadequate treatment

CAUSES OF INADEQUATE

TREATMENT

Causes of emergence and potential

threat of XDR-TB • Like all forms of drug-resistant tuberculosis, XDR-TB is human-made.

• MDR-TB can be amplified into XDR-TB by:

Inadequate/interrupted treatment with second line anti-TB drugs.

Indiscriminate use of second-line drugs.

Non-adherence to national and/or international guidelines.

• Wide-spread availability of SLDs.

• Increasing use of fluoro-quinolones in combination with standard first-line drugs esp. in new cases outside RNTCP.

• Weak systems to ensure standardized regimens and treatment adherence for MDR-TB outside RNTCP.

Many failures are due to

“failure to take the treatment”

and not

“failure of the treatment”

IMPACT OF DRUG RESISTANCE

• Prolonged illness

• Increased mortality

• Prolonged periods of infectiousness with increased risk of transmission of resistant pathogens to others

• Indirect costs (prolonged absence from work, etc)

• Increased direct cost (longer hospital stay, use of more expensive 2nd or 3rd line drugs)

Huge individual as well as public health consequences in terms of

LABORATORY ASPECT

• Sputum should be good and

satisfactory.

• Specimen should be

transported as soon as

possible.

• If delay Refrigeration

Preservation -1% Cetyl

Pyridinium Chloride (CPC) +

2% NaCl.

RNTCP DOTS-Plus Guidelines,2008

LABORATORY ASPECT

• Sputum container labelled as BIO- HAZARD.

• N 95 mask protects from Biohazard

METHODS OF DRUG SUSCEPTIBILITY

• Absolute concentration method

• Resistance Ratio Method

• Proportion Method

METHOD OF CHOICE RECOMMENDED BY DOTS-PLUS

CRITERIA OF RESISTANCE

• Any strain with 1% (the critical proportion) of bacilli resistant to any of the four

drugs.

MOLECULAR METHODS

DNA sequencing

• Most accurate and reliable method

• Detect both previously recognized and unrecognized mutations

• For rifampicin only

The Line Probe assay (LiPA)

• Detect rpoB mutations of rifampicin

• Result in less than 48 hours

Xpert MTB/RIF

• The Xpert MTB/RIF is based on the GeneXpert platform, a highly

sensitive, rapid and simple-to-use nucleic acid amplification

test (NAAT).

• The Xpert® MTB/RIF purifies, concentrates, amplifies (by real-time

PCR) and identifies targeted nucleic acid sequences in the TB

genome, and provides results from unprocessed sputum samples in

90 minutes, with minimal biohazard and very little technical training

required to operate

LABORATORY NETWORK

• SUPRA NATIONAL

LABRORATORY• The Supranational Reference

Laboratory Network expanded to

include three additional laboratories

in 2007–2009 and now comprises 28

laboratories worldwide.

• This network acts as a global

mechanism to ensure the quality of

laboratory data through a system of

proficiency testing.

LABORATORY NETWORK

LABORATORY NETWORK

• NATIONAL REFERENCE LABORATORY

• The four NRLs under the programme are

• Tuberculosis Research Centre [TRC], Chennai,

• National Tuberculosis Institute [NTI], Bangalore,

• Lala Ram Swarup Institute of Tuberculosis and Respiratory diseases

[LRS], Delhi

• and JALMA Institute, Agra.

LABORATORY NETWORK

• Intermediate Reference

Laboratory (IRL)• March 2011, 27 C‐DST Labs are

accredited for Solid C‐DST that includes

19 Govt Labs (4 NRLs +15 IRLs) and 8

other sector laboratories.

• Moreover, 4 C‐DST labs are currently

providing diagnostic services for MDR TB

suspects using Line Probe Assay (LPA).

• At the end of 1st quarter 2011, 15 States

are implementing DOTS Plus service.

MDR TB Suspect identified

and referred by MO-PHI to

DTO

DTO confirms suspect and sends

Patient/sputum to IRL for culture

and DST

Results of culture and DST

communicated to DTO by IRL

Patient returns to continue

Cat-II treatment

Not an MDR

(continue

Cat-II)

MDR

Patient referred by the DTO to DOTS PLUS

Site for evaluation and initiation of

treatment

Patient flow ….Diagnosis

It should be ensured that the MDR suspects are identified and

referred to the DTO for confirmation at the earliest i.e.within 2 weeks of failing a Category I regimen, and

in case of Category II patients (who have taken at least 4 months of

treatment) and close contacts of MDR-TB cases as soon as the sputum

results are available.

PRE-TREATMENT EVALUATION

• Since the drugs used for the treatment of MDR-TB are known to

produce adverse effects, a proper pre-treatment evaluation is

essential to identify patients who are at increased risk of developing

such adverse effects. The pre-treatment evaluation will include the

following:

• Detailed history (including screening for mental illness, drug/alcohol

abuse etc.)

• Weight

• Height

• Complete Blood Count

• Blood sugar to screen for Diabetes Mellitus

PRE-TREATMENT EVALUATION

• Liver Function Tests

• Blood Urea and S. Creatinine to assess the Kidney function

• TSH levels to assess the thyroid function

• Urine examination – Routine and Microscopic

• Pregnancy test (for all women in the child bearing age group)

• Chest X-Ray.

ANTI-TUBERCULOSIS DRUGS BY

GROUP

STANDARDISED TREATMENT REGIMEN

For the treatment of MDR-TB cases

6 drugs

- kanamycin - ofloxacin

- ethionamide - pyrazinamide

- ethambutol - cycloserine

for 6-9 months of the Intensive Phase

44

TREATMENT

• CONTINUATION PHASE-

4 drugs

ofloxacin,

ethionamide

ethambutol

Cycloserine

for 18 months.

TREATMENT

TREATMENT

• All drugs should be given in a single daily dosage under directly observed treatment (DOT) by a DOT Provider.

• On the 7th day (Sunday) the oral drugs will be administered unsupervised whereas injection kanamycin will be omitted.

• If intolerance occurs to the drugs, ethionamide, cycloserine and PAS may be split into two dosages.

• Pyridoxine at a dose of 100mg should be administered to all patients on

an RNTCP Category IV regimen.

• Local arrangements will need to be made for daily injections during the

intensive phase.

• Patients which are not MDR but have any Rifampicin resistance will

also be treated with Cat IV regimen.

DOTS Plus Site

MDR TB Case admitted for evaluation and treatment

initiation

Patient discharged to the home

district with information to DTO

Daily DOT continued by a

trained DOT Provider

Follow up ProtocolSmear and Culture monthly during IP and Quarterly during CP

Physical evaluation monthly during IP and Quarterly during CP by the DTO

KFT and other investigations at regular intervals

Patient flow …. Treatment and follow up

Follow up smear and culture schedule

during treatment

Two specimens for AFB (one early

morning and one supervised spot) will

be collected and examined at the

respective DMC/DTC (at the end of the

months 3, 4, 5, 6, 7, 9, 12, 15, 18, 21

and 24).

Two specimens for culture (one early

morning and one supervised spot) will

be collected and transported in CPC

bottles from the respective DTC to the

RNTCP accredited laboratory (at the

end of the months 3, 4, 5, 6, 7, 9, 12,

15, 18, 21 and 24).

If any of the cultures in the last three quarters becomes positive, it will

be followed up by monthly cultures in the following 3 months

Contd.

After 6 months of

treatment (Intensive

phase)

Patient will be reviewed

and the treatment

changed to CP if the 4th

month culture result is

negative

If the result of the 4th

month culture is still

awaited after 6 months of

treatment, the IP is

extended until the result

is available.

IP can be extended up

to a maximum of 3

months after which the

patient will be initiated on

the CP irrespective of the

culture result

TREATMENT INTERRUPTION AND

DEFAULT• Cat IV patients in IP/CP who miss doses:

• All the missed doses during IP must be completed prior to switching the patient to CP.

• Similarly all missed doses during CP must be administered prior to ending treatment.

• Cat IV patients who interrupt treatment for less than 2 months during IP:

• When the patient returns to resume treatment the IP will be continued, however the duration of treatment will be extended to complete IP.

• The follow up cultures will be done as per the revised schedule.

TREATMENT INTERRUPTION AND

DEFAULT

• Cat IV patients who interrupt treatment for less than 2 months

during CP:

• When the patient returns to resume treatment, the CP will be

continued, however the duration of treatment will be extended to

complete the CP.

• The follow up cultures will be done as per the revised schedule.

• Cat IV patients who default (interrupt treatment for 2 or more

months) and return back for treatment:

• Such patients will be given an outcome of “default” and then will be

re-registered for further treatment which is based on the duration of

default.

• Re-registration of patients will be done by the DOTS Plus site.

Standardised treatment outcome

definitions

• Cure: An MDR-TB patient who has completed treatment and has

been consistently culture negative (with at least 5 consecutive

negative results in the last 12 to 15 months). If one follow-up positive

culture is reported during the last three quarters, patient will still be

considered cured provided this positive culture is followed by at least

3 consecutive negative cultures, taken at least 30 days apart,

provided that there is clinical evidence of improvement.

• Treatment completed: An MDR-TB 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.

Standardised treatment outcome

definitions

• Death: An MDR-TB patient who dies for any reason during the

course of MDR-TB treatment.

• Treatment failure: Treatment will be considered to have

failed if two or more of the five cultures recorded in the final 12-15

months are positive, or if any of the final three cultures are positive.

• Treatment default: An MDR-TB patient whose MDR-TB

treatment was interrupted for two or more consecutive months for

any reasons.

Management Guidelines for

Patients with XDR-TB• Use any Group 1 agents that may be effective.

• Use an injectable agent to which the strain is susceptible and

consider an extended duration of use (12 months or possibly the

whole treatment). If resistant to all injectable agents, it is

recommended to use one the patient has never used before.

• Use a later-generation fluoroquinolone such as moxifloxacin.

• Use all Group 4 agents that have not been used extensively in a

previous regimen or any that are likely to be effective.

Management Guidelines for

Patients with XDR-TB• Use two or more agents from Group 5.

• Consider high-dose isoniazid treatment if low-level resistance is

documented.

• Consider adjuvant surgery if there is localized disease.

• Ensure strong infection control measures.

• Treat HIV

• Provide comprehensive monitoring

ROLE OF SURGERY

• In MDR-TB patients with localized disease, surgery, as an adjunct to chemotherapy, can improve outcomes provided skilled thoracic surgeons and excellent post-operative care are available.

• When unilateral resectable disease is present, surgery should be considered for the following cases:

• Absence of clinical or bacteriological response to chemotherapy despite six to nine months of treatment with effective anti-tuberculosis drugs;

• High risk of failure or relapse due to high degree of resistance or extensive parenchymal involvement;

ROLE OF SURGERY

• Morbid complications of parenchymal disease e.g. haemoptysis,

bronchiectasis, broncho-pleural fistula, or empyema;

• Recurrence of positive culture status during course of treatment

• Relapse after completion of anti-tuberculosis treatment.

• If surgical option is under consideration at least six to nine

months of chemotherapy is recommended prior to surgery.

MDR- TB AND HIV

• Outbreaks of drug-resistant TB among people living with HIV have

been widely documented in nosocomial and other settings.

• But limited information has been available about the association of

HIV and drug-resistant TB at a population level.

• This may be a result of lack of testing of patients or of incomplete

reporting of results.

MDR- TB is more common in HIV positive patients because

• People living with HIV

– have weakened immune systems which left them vulnerable to

TB.

– socially vulnerable populations, including injecting drug users

– Socio-behavioural problems and/or lack of access to proper care

may make these populations, as TB patients,

– vulnerable to developing drug resistance as a result of poor

adherence to treatment or suboptimal treatment.

MDR- TB AND HIV

– More likely to be exposed to MDR-TB patients, due either to

increased hospitalizations in settings with poor infection control or

association with peers who may have MDR-TB.

– In addition, acquisition of rifampicin resistance may also be the

result of anti-TB drug malabsorption.

MDR- TB AND HIV

MDR- TB AND HIV

The epidemiological impact of HIV infection on the transmission of

MDR-TB :

• HIV positive TB cases are more likely to be sputum smear negative,

and therefore less likely to transmit TB.

• Delayed diagnosis of drug resistance have led to high death rates in

people living with HIV, which may also result in a lower rate of TB

transmission.

Challenges in the treatment of MDR- TB with HIV

• Diagnosis of TB is more difficult in HIV positive people

– Smear negative; Extra-pulmonary

• Treatment is challenging

– Drug interactions

– Intolerance and non-adherence

• Protecting health care workers (HCWs) is important

– Special risk for HIV+ MDR - TB

MDR- TB AND HIV

• Increased burden on health care system

– Need for hospitalization, heavier workload, stricter infection control

• Fear and stigma

– Alarmist messages increase stigma

– Negative impact on health seeking behaviour

MDR- TB AND HIV

• In 2010, the Stop TB Partnership launched its Global Plan to Stop TB, 2011-2015 having, as an ultimate focus, the elimination of TB in the world by 2050.

• The plan has important implications for the funding of MDR-TB activities in detecting patients, notifying and enrolling them on treatment.

• The plan includes 6 objectives aimed at reducing the global burden of drug-resistant TB with intermediate targets to be reached by 2015.

THE GLOBAL PLAN TO STOP TB, 2011-2015

THE GLOBAL PLAN TO STOP TB, 2011-2015

THE GLOBAL PLAN TO STOP TB, 2011-2015

DOTS PLUS

• DOTS-Plus refers to DOTS programmes that add components for MDR-TB diagnosis, management and treatment.

• The first WHO endorsed DOTS-Plus programmes began in 2000.

• At that time, the Green Light Committee (GLC) was established to promote access to high quality second-line drugs for appropriate use in TB control programmes.

• Gujarat has been the first state to initiate DOTS Plus services in August 2007.

• Haryana – December 2008

DOTS PLUS

RNTCP DOTS PLUS VISION

• By 2012, it is aimed to extend these services to all smear positive

retreatment cases and new cases who have failed an initial first line

drug treatment.

• And by 2015, these services will be made available to all smear

positive pulmonary TB cases registered under the programme.

• DOTS PLUS SITES –• These sites will be in highly specialized centres (e.g. Medical

College hospitals, Chest and respiratory disease institutes etc.)

which

– will have ready access to an RNTCP accredited culture and DST laboratory,

– with qualified staff available to manage patients using standardized second-

line drug regimens given under daily DOT and standardized follow-up

protocols,

– have systems in place for an initial short period of in-patient care to stabilise

the patient on the second-line drug regimen followed by ambulatory DOT

– with a logistics system and standardized information system in place.

• Each DOTS Plus site will cater to approximately 10 million

population.

DOTS PLUS

DOTS PLUS

The core components are as follows:

• Sustained political and administrative commitment.–

– A well-functioning DOTS program.

– Long-term investment of staff and resources.

– Coordination efforts between the community, local governments, and

international agencies.

– Addressing the factors leading to the emergence of MDR-TB

DOTS PLUS

• Diagnosis of MDR TB through quality-assured culture and drug

susceptibility testing.– Proper triage of patients into DST testing and the DOTS-Plus program.

– Co-ordination with National and Supra-National Reference Laboratories

• Appropriate treatment strategies that utilize second-line drugs under

proper management conditions.– Rational treatment design (evidence-based.)

– Directly observed therapy (DOT) ensuring long-term adherence.

– Monitoring and management of adverse drug reactions.

– Adequate human resources

DOTS PLUS

• Uninterrupted supply of quality-assured anti-TB drugs.

• Recording and reporting system designed for the DOTS Plus

programs that enable performance monitoring and evaluation of

treatment outcome.

.

CURRENT DOTS PLUS STATUS

INDIA HARYANA

No of district implementig DOTS

plus

141 7

Percentage of population with

access to MDR-TB services under

RNTCP in 2010

24% 38%

No of DOTS Plus sites functional 20 1

Source :TB INDIA 2011 Revised National TB Control Programme: Annual Status Report

CURRENT DOTS PLUS STATUS

• No of MDR-TB cases detected in 2010= 2967

• No of MDR-TB cases detected that registered and initiated on category IV treatment in 2010= 2178

Outcome of treatment of category IV in India• Success rate – 43%

• Death rate - 20%

• Defaulted - 21%

• Failed treatment - 15%

Source :TB INDIA 2011 Revised National TB Control Programme: Annual Status Report

TOTALLY DRUG RESISTANT TB

• TB that is resistant to all first-line and second-line drugs tested.

• Total drug resistant TB is a relative notion and depends on the local

drugs available and tested on. This term/expression should either be

avoided or should be defined worldwide.

• The term “totally drug resistant” tuberculosis is neither recognized by

the WHO nor by Revised National Tuberculosis Control Programme

(RNTCP). .

• Totally drug resistant TB / Extremely drug resistant TB was first

reported in Iran in 2009 in a cohort of 15 patients by Velayati et al.

TOTALLY DRUG RESISTANT TB

• Udwadia F. et al. reported (Clinical Infectious Diseases on 21 Dec.

2011) four cases of total drug resistant tuberculosis (TB).

• Since the first cases of XDR tuberculosis in India were reported from

the P. D. Hinduja National Hospital and Medical Research Centre,

physicians here have grappled with increasingly resistant strains of

tuberculosis.

• According to the article, these patients have shown resistance to all

the first line TB drugs (isoniazid, rifampicin, ethambutol,

pyrazinamide, streptomycin) and to seven second line anti-TB drugs

(ofloxacin, moxifloxacin, kanamycin, amikacin, capreomycin, para-

aminosalcyclic acid and ethionamide).

TOTALLY DRUG RESISTANT TB

• All DSTs were performed by Mycobacterial Growth Indicator Tube

960 at critical concentrations for first-line and second-line drugs

recommended by the World Health Organization (WHO).

• Drug susceptibility testing (DST) was performed at the Hinduja

Hospital.

• However, this Hospital Laboratory is not accredited by the Revised

National Tuberculosis Control Programme, GOI for culture and

sensitivity for second line drugs to diagnose Extensively Drug-

Resistant (XDR) / Totally Drug Resistant (TDR) cases and is only

accredited for conducting Drug Susceptibility Testing (DST) by liquid

culture and sensitivity for first line drug only.

TOTALLY DRUG RESISTANT TB

• These patients received erratic, unsupervised second-line drugs,

added individually and often in incorrect doses, from multiple private

practitioners.

• Although India's RNTCP has been a tremendous success, patients

with MDR tuberculosis currently are not covered, with only 24%

having access to Directly Observed Treatment, Short-course

(DOTS)–Plus initiatives.

• The vast majority of these unfortunate patients seek care from

private physicians in a desperate attempt to find a cure for their

tuberculosis.

• This sector of private-sector physicians in India is among the largest

in the world and these physicians are unregulated both in terms of

prescribing practice and qualifications.

TOTALLY DRUG RESISTANT TB

• A study conducted in Mumbai also showed that only 5 of 106 private

practitioners practicing in a crowded area called Dharavi could

prescribe a correct prescription for a hypothetical patient with MDR

tuberculosis.

• The majority of prescriptions were inappropriate and would only have

served to further amplify resistance, converting MDR tuberculosis to

XDR tuberculosis and TDR tuberculosis.

FUNDING FOR MDR

• According to the 2011 WHO Global TB report, funding for MDR-TB in

2011 was US$0.7 billion, US$ 0.2 billion less than the need

estimated in the Global Plan to Stop TB.

• The funding required for MDR-TB to reach the 2015 target of

universal access to care rises from US$ 0.9 billion in 2011 to US$ 2

billion in 2015; most of this funding is needed in middle-income

countries.

• Thus, much more funding needs to be mobilized in high MDR-TB

burden countries to ensure proper diagnosis and treatment.

Bill Gates' donates millions to battle

TB

• Many more

powerful hands

needed to

Control

Tuberculosis

PGIMS DOTS PLUS REPORT 2011

• Suspected MDR-TB patients tested at IRL – 380

• MDR-TB cases detected – 120

• MDR-TB cases registered and started on category IV treatment – 82

• XDR-TB case - 1

Contribute your Knowledge, Wisdom, to

prevent spread and control of Tuberculosis

• Haryana 250.2 21 7 94.5 38% 1 2857 303 11% 77

54

World Tuberculosis Day (March 24)

HIV

• About 13% of TB cases occur among people living with HIV.

• 0.35 million (range, 0.32–0.39 million) deaths from HIV-associated

TB.