Global Tuberculosis Control Strategies

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Global Tuberculosis Control Strategies

• Richard Laing
• Kayla Laserson

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Tuberculosis A Global Emergency

• One third of the worlds population is infected
• TB kills 5,000 people a day 2 to 3 million/yr
• More than 100,000 children will die this year
• Hundreds of thousands of children will become TB
  orphans this year
• HIV and TB co-infection are producing explosive
  epidemics
• MDR is seriously threatening global TB control

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TB is the Leading Infectious Cause of Death among
Persons gt5 years old
Number of deaths (millions)
Source WHO World Report 2000
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Tuberculosis the Disease (1)

• Caused by mycobacterium, slow growing slow
  healing
• Infection is initially latent, only skin test
  positive with no symptoms
• A proportion of infected individuals progress to
  active disease usually affecting lungs
  (infectious) but any organ can be a site of
  disease (non-infectious)

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Tuberculosis the Disease (2)

• Normal progression of disease
• 50 die, 25 spontaneous cure, and 25 chronic
  excretors
• Treatment requires multiple drugs for prolonged
  periods. Good results possible
• Treatment interruptions or monotherapy lead to
  drug resistance
• Drug resistance can be transmitted (primary) or
  developed (secondary)

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Tuberculosis the Disease (3)

• TB is primarily a disease of poverty aggravated
  by overcrowding, poor ventilation and
  undernutrition
• Prior to drug treatment, incidence fell with
  improvements in environment and living standards
  in developed countries
• Recently TB has dramatically increased due to HIV
  and collapse of economic and health systems

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Treatment of TB

• TB is treated with multiple drugs to avoid drug
  resistance and treatment failures
• Intensive phase 4 drugs Rifampicin, Isoniazid,
  Pyrazinamide, and Ethambutol or Streptomycin
• Continution phase 2 drugs INH Rif or Eth
• If drugs are counterfeit or substandard, may
  cause treatment failures and lead to the
  development of Multidrug-Resistant TB (MDRTB)

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Risk Factors for TB

• Poverty and unemployment
• Homelessness
• Congregate settings (prisons)
• Alcoholism and drug abuse
• HIV

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World TB Situation Estimated incidence of TB 1999

• Country Cases (000S) Rate /100K
• 1 India 1,847 185
• 2 China 1,300 103
• 3 Indonesia 590 282
• 4 Nigeria 327 301
• 9 South Africa 197 495
• 13 Kenya 123 417
• 19 Uganda 72 343
• 21 Zimbabwe 65 562

Source Global Tuberculosis Control WHO Report
2001
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Geographical Distribution of Notified Cases of
TB, 1999
Africa
Western Pacific
17
22
Americas
6
4
Middle East
10
41
Southeast Asia
Europe
Source Global Tuberculosis Control WHO Report
2001
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Source Global Tuberculosis Control WHO Report
2000
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Global TB Control

• Global control of TB is a leading health priority
• Directly observed treatment, short-course
• DOTS
• WHO global strategy
• National case management of populations
• March 1997, declared to represent the most
  important public health breakthrough of the
  decade, in terms of the lives which will be
  saved

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Components of DOTS

• Government commitment to TB control
• Passive diagnosis by smear microscopy
• Observed administration of free, standard,
  short-course chemotherapy (SCC)
• Continuous and reliable drug supply
• Efficient recording and reporting system

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Government Commitment to TB Control

• Creation of a national TB program
• Political and financial support
• Integrated with the primary health care system
• Commitment to provision of
• Technical leadership
• Drugs free of charge
• Diagnostic materials
• Regulation of TB drugs

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Obstacles toGovernment Commitment

• Magnitude of the problem underestimated by
  policymakers
• Disease of poor people
• Historical stigma of TB
• Lack of donor support
• Strong vertical components of a traditional DOTS
  program conflict with trend towards
  decentralization

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Passive Diagnosis by Smear Microscopy

• Case-finding
• Focus on patients attending general health
  facilities
• Avoid active case-finding in the community
• Diagnosis
• Bacteriologic confirmation based primarily on
  microscopy (culture when available) rather than
  x-ray
• Sputum microscopy highly specific
• Smear correlates with severity of disease and
  infectiousness
• Inexpensive

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Obstacles to Passive Diagnosis by Smear
Microscopy

• Training needed
• More and better microscopes needed
• Diagnostic materials needed
• Quality control systems not in place
• Historic reliance on chest x-ray examination
• Historic tendency to perform active surveillance

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SCC with Directly Observed Treatment

• Abbreviated DOT, not DOTS
• Use of a standard regimen for 6 months
• 4 drugs for 2 months, 2 drugs for 4 months
• Efficacy of short-course regimen demonstrated in
  controlled clinical trials
• Standardized regimens are safe and effective
• DOT for at least first 2 months, preferably all 6

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Directly Observed Treatment

• One of the most difficult and controversial
  aspects of the DOTS strategy
• An observer watches patient swallow pills
• DOT ensures adequate treatment
• With the right drugs
• In the right doses
• At the right intervals

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Directly Observed Treatment

• Treatment observer must be accessible and
  acceptable to the patient and accountable to the
  health system
• Observation is a service to patients and
  providers
• Studies have demonstrated that 30 of patients
  do not take medicines regularly
• Impossible to predict which patient will take
  medicine

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Observation Models

• General health care service delivery
• Community volunteerism
• Religious community
• Community health care delivery such as child
  survival workers and lay midwives
• Non-governmental organizations

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Obstacles to Standard SCC with DOT

• Patient adherence
• DOT delivery in rural areas difficult
• System burdened by DOT
• Need for enablers and incentives
• Government financial burden of providing TB
  medicines free of charge
• Creation of drug resistance makes standard
  regimens less effective

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Regular, Uninterrupted Supply of Drugs

• Each patient must be ensured the entire course of
  prescribed treatment, without interruption
• Drugs must be of good quality, with adequate
  bioavailability

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Obstacles to Regular, Uninterrupted Supply of
Drugs

• TB drugs too expensive for some countries but
  getting cheaper lt10 per course
• Issues of sustainability limit donor purchase of
  TB drugs
• Procurement and drug delivery difficult
• Drugs not systematically tested for quality
• Purchase of poor quality drugs

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Efficient Recording and Reporting System

• Laboratory Register records every sputum from
  every patient
• TB Register records the case management and
  treatment outcomes of every TB case
• Maintained system of quarterly reporting and
  analysis of cohorts of patients
• Facilitates operational research to improve
  program effectiveness

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Obstacles to Efficient Recording and Reporting
System

• Trained supervisory staff needed
• Maintenance of system is labor intensive
• Data are often not used at the local level
• Non-DOTS registries are often used

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DOTS Indicators WHO-IUATLD

• Measures of government commitment
• Organizational and budgetary decisions
• Proportion of population with access to DOTS
• Smear-positive cases should be 45 of all
  notified cases and 65 of all pulmonary cases
• 2- or 3-month sputum smear conversion rate
• Case notification rate gt 70
• Cure of new smear-positive patients gt 85

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DOTS is Effective

• In Malawi, Mozambique, and Tanzania, DOTS led to
  cure rates between 86 to 90
• In Beijing, China, DOTS led to a decrease of
  smear-positive TB from 127/100,000 to 16/100,00
  in 11 years with cure rates gt 90
• In Bangladesh, DOTS led to cure rates gt 80
• In India, DOTS led to cure rates of 75 to 80

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Treatment Outcomes for Smear Cases 1998 Cohort
DOTS/ Non-DOTS Strategy
Country Cured CpltRX Died Failed Default Tfrd
Success 1 India 83 1.2 4.4 2.7
7.5 1.0 84 1.9 22 0.1
0.1 2 0.2 24 2 China 97 0
1.2 0.8 0.6 0.3 97
85 0 1.8 6.5 4.5
1.7 85 9 S. Africa 68 6.6 5.6 1.7
6.8 12 74 30 17 5.1 0.9
13 34 47 11 DRC 58 12 5.3
1 9.4 8.4 70 21 Zimbabwe 50
19 10 0.3 8.3 12
70
Source Global Tuberculosis Control WHO Report
2001
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Treatment Success 1995-96WHO Target 85
100
overall
DOTS
non-DOTS
80
60
Treatment Success
( of registered cases)
40
20
0
1995 1996
1995 1996
1995 1996
WHO/CDS 1999
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TB and HIV

• Profound impact on TB epidemic in sub-Saharan
  Africa and parts of South East Asia
• Nearly 11 million people co-infected with TB- HIV
• About 8 of TB cases were associated with HIV
  infection in 1997
• Increased TB case fatality rates (23 on average)
  
• TB/HIV cases can be effectively treated with
  existing drugs

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TB Incidence and HIV Seroprevalence in AFRO
Source WHO/CDS
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Effect of HIV on TB in Botswana
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Multidrug-Resistant TB

• Primary resistance is when a person is infected
  with a resistant organism
• Secondary resistance is when a person is treated
  inadequately either because of drug shortages,
  system breakdown, compliance failure OR possibly
  poor DRUG QUALITY
• Cost of treatment very high --gt 2 years of 4-5
  other drugs, with high cost SE

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Prevalence Estimates Vary

• 2000 Resistance Report (72 sites)
• Median, any resistance 11.1 (0-52)
• Median, MDR-TB 1.7 (0-22.1)
• gt3 prevalence MDR Estonia, Henan Zhejiang
  provinces, Latvia, Ivanovo Tomsk oblasts, Iran,
  Mozambique, Tamil Nadu, Peru

WHO. Anti-tuberculosis Drug Resistance in the
World. Report 2 Prevalence and Trends The
WHO/IUATLD Global Project on Anti-Tuberculosis
Drug Resistance Surveillance, 2000
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Distribution of MDR TB in the World
FORMER USSR high MDR
INDUSTRIALIZED WORLD low MDR
MIDDLE EAST MDR?
ASIA high MDR
AFRICA low MDR?
LATIN AMERICA medium MDR
WHO Global TB Programme
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MDR Prevalence in Selected African Countries,
1996-1999 WHO/ IUATLD Survey
Percent
Country
Source WHO. Anti-tuberculosis Drug Resistance in
the World. Report 2 Prevalence and Trends The
WHO/IUATLD Global Project on Anti-Tuberculosis
Drug Resistance Surveillance, 2000
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Policy Response to MDR-TB - DOTS

• Government commitment
• Bacteriologically confirmed diagnosis
• Standardized, short-course, directly observed
  multidrug regimen for treatment of TB (SSCC)
• Regular, uninterrupted supply of quality drugs
  and diagnostic materials
• Systematic monitoring and evaluation of program
  activities

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Newer Policy Response to MDR-TB - DOTS-Plus

• Government commitment
• Bacteriologically confirmed diagnosis (generally
  includes culture and drug susceptibility testing)
• Observed standardized and/or individualized
  multidrug regimens
• Regular, uninterrupted supply of quality
  second-line drugs and diagnostic materials
• Systematic monitoring and evaluation of program
  activities

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Future of TB in World Finely Balanced

• If all existing sensitive cases are treated
  effectively with DOTS effective drugs, rates
  will decline
• But if this does not occur, cases will increase,
  MDRTB will spread, and TB may return to be a
  major global threat
• Ensuring drug quality is an essential component
  of any National TB Program but is often neglected