TB control in risk groups DOTS-plus

Lucica Ditiu, Antalya, April 2005

Risk of being exposed: no. of cases capable of transmitting M.tb, duration of infectiousness, no. and duration of encounters between a source and susceptible persons

Risk of becoming infected: no. of droplets produced by an infectious case, the volume of air, the “inhaling period “

Risk of becoming sick after infected

Risk groups

Close contacts of persons known or suspected to have TB, infants and children esp. Persons infected with HIV Persons with medical factors known to increase the risk of progression from

infection to disease: silicosis, gastroectomy, diabetes mellitus, chronic renal failure, jejunoileal by-pass, some hematological disorders (leukemia, lymphomas), other malignancies, treatment with high dose corticosteroid therapy and other immunosuppressive, weight 10% or more below ideal body.

Alcoholics and iv drug users Residents of facilities such as: correctional institutions, prisons, mental institutions,

nursing homes, long term facilities for elderly Foreign born persons from countries with high TB prevalence, recently enterred a

country Health and other category of workers – in hospitals and other health care facilities,

especially serving the high risk groups

These groups are now high priority, may decline in risk over time!!!

Responsibility of national public health officials to identify the risk groups using the national data

Risk of being exposed: no. of cases capable of transmitting M.tb, duration of infectiousness, no. and duration of encounters between a source and susceptible persons

Risk of becoming infected: no. of droplets produced by an infectious case, the volume of air, the “inhaling period “

IDENTIFY THE TB CASES AS QUICK AS POSSIBLE WHEN THEY PRESENT TO THE HEALTH CARE FACILITIES

PLACE THE CASES ON EFFECTIVE TREATMENT, WITH THE REQUIRED FREQUENCY AND DURATION

IMPROVE/INTRODUCE INFECTION CONTROL MEASURES IN SPECIAL SETTINGS – PRISONS, HOSPITALS, LABORATORIES

… will not prevent the new TB cases to appear from

individuals

infected long time ago!

Latent TB Infection (LTBI) Identify LTBI – skin test (only for infection!) Rule out active TB – clinical history, physical

examination, chest X-ray, bacteriological exam. Think about treatment of LTBI: can potentially

reduce the risk of developing active TB versus hepatotoxicity, non-adherence, drug resistance (inefficient/creating), operational problems, cost.

Children under 5 years old – contacts with positive TB case (household)

INH 5 mg/kg for 6-12 mos

Persons infected with HIV and M.tb (annual risk of developing TB among HIV + is 6-16% in comparison with a lifetime risk of 10% for HIV-)

INH daily 9 mos RMP + PZM daily 2 mos

TB and HIV HIV is the most powerful factor known to

increase the risk of TB HIV increases susceptibility to M.tb and the

risk of progression from infection to disease Between 1% and 70% (sub-Saharan African

countries) of TB patients are HIV +

75-85% of all HIV cases in Europe are male 30-70% of all HIV cases are among younger than

25 years Groups vulnerable to HIV: IDU, immigrants, ethnic

minorities, prisoners, sex workers Mainly IDU-related HIV transmission in Eastern

Europe Up to 30% of HIV infected females are IDU and

50% are partners of IDU Similarities with the TB pattern: mostly males,

younger in the East, older in the West, prisoners, immigrants

HIV epidemic features in EUR

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Russia 11th of the 22 TB high-burden countries

New TB cases notified by area; EUR, 1980-02

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1995 1996 1997 1998 1999 2000 2001 2002 2003

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1995 1996 1997 1998 1999 2000 2001 2002 2003

New HIV cases notified by area; EUR, 1995-03

Diagnosis and treatment: Immunity only partial compromised – features are typical for

TB Clinical: less cough, less haemoptysis Bacteriology: proportion of smear negative is greater; fewr

organisms in sputum Chest X-ray: normal – typical – atypical TB drugs: Short course chemotherapy with RMP, given under

DOT No thioacetazone Attention to SM!

ARVs: can determine development of active TB in a HIV+ LTBI or worsening the symptoms

Protease inhibitors and Non Nucleoside Reverse Transcriptase / RMP.

DRUG RESISTANT TUBERCULOSIS IS

A MAN MADE PROBLEM! RESISTANCE TO ANTI-TB DRUGS IS THE

RESULT OF A CHROMOSOMAL MUTATION

DEVELOPMENT OF DRUG RESISTANCE IS THE RESULT OF INADEQUATE THERAPY – PHYSICIAN ERROR, LACK OF DRUGS, LACK OF ADHERENCE – (ADHERENCE

TO SELF ADMINISTERED MEDICATION IS UNPREDICTABLE)

Drug Resistance Surveys

3 Global Projects on DR (1997/35, 2001/58 and 2004/77 settings)

New cases 55.779 patients surveyed/75 settings Prevalence of any resistance – 0-57% in Kazakhstan Prevalence of MDR TB – 0–14.25% in Kazakhstan Increasing trends in MDR TB : Tomsk Region and Poland Increase due to: poor/worsening TB Control, immigration of patients from areas of high resistance,

outbreaks of DR and variations in surveillance methodologies.

Drug Resistance Surveys

Previously treated cases 8,405 patients surveyed/66 settings Highest prevalence of any resistance – 82.1% in

Kazakhstan Highest prevalence of MDR TB – 58.3% in Oman Increasing trends for MDR TB : Estonia,

Lithuania and Tomsk region.

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Prevalence of MDR by treatment status, ranked by new cases

Settings with MDR prevalence above 30% in previously treated cases

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5 components of DOTS - Plus1. Sustained political commitment

2. Diagnosis of MDR-TB through quality-assured culture and drug susceptibility testing (DST).

3. Appropriate treatment strategies that utilize second line drugs under proper management conditions.

4. Uninterrupted supply of quality assured reserve antituberculosis drugs.

5. Recording and reporting system designed for DOTS-Plus programs.

Sustained political commitment

Long term investment in human and financial resources

Coordination efforts between community, local governments and international agencies

A well functioning DOTS program Addressing the factors leading to the

emergence of MDR-TB

Proper triage of patients for DST and DOTS-Plus Most programmes cannot do DST on all patient. Only

patients with an increased risk for resistance are tested. Some programmes will use strategies that target

MDR-TB risk groups (failures, chronics). In some settings with high prevalence of MDR-TB, DST

may be done on all patients.

Relationship with SNRL

Diagnosis of MDR-TB through quality-assured culture and DST

Appropriate treatment strategies that utilize second-line drugs under proper management conditions

Rational treatment design Directly observed treatment Monitoring and management of

side effects Human resources

Uninterrupted supply of quality assured second-line drugs

Many challenges for drug procurement Regimens are frequently adjusted

(side-effects, DST results, lack of treatment response)

Short shelf life (18 – 36 months) Limited global production of quality-assured

drugs Drug registration may be a lengthy and costly

Recording and reporting system

Enables patient registration monitoring (including culture, DST, laboratory

tests…etc) interim indicators final outcome analysis comparison of different cohorts

DOTS-Plus is far more complicated than DOTS

Laboratory capacity: diagnosis and monitoring (culture, DST)

Treatment design DOT during 18-24 months Management of (frequent) side-effects Often difficult patient categories Drug procurement and management DOTS-Plus recording & reporting system

GLC-approved projects by March 2005

Applications under review by the GLCApplications under review by the GLC

GLC-approved DOTS-Plus projectsGLC-approved DOTS-Plus projects

Countries preparing applicationCountries preparing application

33 projects

11,000 patients

33 projects

11,000 patients

GLC-approved projects in EURO Georgia –

Abkhazia Latvia Kyrgyzstan Moldova Georgia Estonia

Karakalpakstan, Uzbekistan

Romania Russian Federation

Arkhangelsk Orel Ivanovo Tomsk

Preliminary results of DOTS-Plus projects

More than 3000 patients have been enrolled and 1100 have completed treatment

MDR-TB among new cases in projects assessed range from 1.5-17.1%

57% of the MDR-TB cases treated are resistant to all first line-drugs and also to second-line anti-TB drugs

All 5 first DOTS-Plus pilot projects assessed use individualised treatment regimens; average number of drugs used is 5

Treatment success rates range from 61-82% Only 2% of patients have stopped treatment due to adverse

events

Preliminary resultsTreatment outcomes in some DOTS-Plus sites

0%

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100%

Latv

ia c

ivili

an

Tom

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Peru

Transferred

Died

Failed

Default

Treatment success

Recent developments

From pilot phase to expansion phase

Mainstreaming DOTS-Plus (including DRS) into DOTS

DOTS-Plus not longer limited to so-called "hot spots"

Cat 4 regimens recognised as the standard of care for MDR-TB

Politics: EB resolution 114.R1, GFATM

DOTS-Plus guidelines are under revision

SLD are used almost everywhere!

Conclusion

DOTS is priority to stop MDR-TB creation

DOTS-Plus should be built upon and fully integrated with DOTS – new vision of TB control

The GLC provides access to reduced-cost quality-assured second-line drugs and technical assistance

All GFATM financial support for MDR-TB must go through the GLC

• DOTS-Plus is feasible under routine programme conditions

• Country-specific: Frame-work approach!

• Cost-effective intervention

• Acceptable-good results, even in difficult patient categories

• Mainstreaming DOTS and DOTS Plus is crucial in Eastern Europe

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