TB and Pharmaceuticals

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TB and Pharmaceuticals

• Richard Laing
• BUSPH
• DPI 2001

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TB and Development
450-1000
22,000-31,100
GNP per capita (1995)
Source J. Sachs (Harvard)
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Source Global Tuberculosis Control WHO Report
2000
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Source Global Tuberculosis Control WHO Report
2000
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Source Global Tuberculosis Control WHO Report
2000
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Case notifications 23 high-burden countries,
ranked by total number of cases
1 India 2 China 3 Indonesia 4 Nigeria 5
Bangladesh 6 Pakistan 7 Philippines 8 Ethiopia
9 South Africa 10 Russia 11 DR
Congo 12 Viet Nam 13 Kenya 14 Brazil 15 UR
Tanzania 16 Thailand 17 Mozambique 18 Myanmar
19 Uganda 20 Afghanistan 21 Zimbabwe 22
Cambodia 23 Peru Global total high-burden
countries 1 679 086 All Cases
under DOTS 2 010 736 All Cases not under
DOTS
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Countries Ranked by Incidence Rate per 100,000

• 1. Zimbabwe 562 13. Indonesia 282
• 2. Cambodia 560 14. Bangladesh 241
• 3. South Africa 495 15. Peru 228
• 4. Kenya 417 16. Vietnam 189
• 5. Mozambique 407 17. India 185
• 6. Ethiopia 373 18. Pakistan 177
• 7. Uganda 343 19. Myanmar 169
• 8. Tanzania 340 20. Thailand 141
• 9. Afghanistan 325 21. Russia 123
• 10. Philippines 314 22. China 105
• 11. DR Congo 301 23. Brazil 70
• 11. Nigeria 301 Average of 23 high burden
  countries
• 141 per 100,000

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Incidence Rates by Age and Sex sub-Saharan
Africa, 1998
300
4
250
3
200
ratio of incidence rates malefemale
incidence rate (per 100 000)
150
2
100
1
50
0
0
0-14
15-24
25-34
35-44
45-54
55-64
65
age (years)
ratio of incidence rates,malefemale
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Incidence Rates by Age and Sex Eastern
Mediterranean Region, 1998
40
2.5
2.0
30
1.5
ratio of incidence rates malefemale
incidence rate (per 100 000)
20
1.0
10
0.5
0
0.0
0-14
15-24
25-34
35-44
45-54
55-64
65
age (years)
ratio of incidence rates,malefemale
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Poverty TB

• Poor 2.6 times as likely to get TB than non-poor
• Poor less likely to seek and receive care, more
  likely to self medicate
• Non-treatment costs higher than treatment costs
• Largest indirect cost loss of work, 3-4 months
  per patient (20-30 annual household income)
• Premature death means loss of about 15 years
  income

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MDR-TB

• M. tuberculosis resistant to INH and RIF
• Naturally occurring mutants, 1 in 106 organisms
• Further selection precipitated by inadequate
  therapy (acquired resistance)
• Primary resistance occurs through transmission
• Requires longer, more expensive treatment with
  less effective and more toxic drugs
• Requires access to culture and Drug Sensitivity
  Testing (DST)

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Prevalence Estimates Vary

• 50 million infected with drug-resistant strains
• 1997 estimate 100,000 cases of MDR-TB
• 1997 WHO/IUATLD antituberculosis resistance
  report (35 sites)
• prevalence believed to be an underestimate
• median, any resistance 7.5 (0.9-35.1)
• median, MDR-TB 2.2 (0-22.1)
• hot spots Dominican Republic, Argentina,
  Ivanovo, Latvia, Estonia, Ivory Coast

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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 and
  HIV
• About 8 of TB cases were associated with HIV
  infection in 1997
• Increased TB case fatality rates (23 on average)

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TB incidence and HIV seroprevalence in AFRO
Source WHO/CDS
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Global Prison Population Rates per 100,000

• Rwanda 1623 (Total 125,000)
• USA 690 (Total gt2 mln)
• Russia 687 (Total 1,009,863)
• Kazakhstan 452 (Total 77,750)
• South Africa 416 (Total 172,271)

Epidemiological pump - Reservoir of TB that
threatens prisoners, staff, visitors, society.
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Prison in Russia
source www.soros.org/tb
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• Government commitment
• Passive case finding
• Diagnosis by sputum microscopy
• Directly observed Rx, short-course
• Standardized regimens
• Continuous supply of effective drugs
• Cohort analysis of outcome

DOTS
S
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Diagnosis

• Primary method of diagnosis is smear microscopy
  Specific though not sensitiveMultiple smears
  used but become less cost effective
• Culture very specific and more sensitive but slow
  and relatively expensive
• X-rays less specific, fairly specific, dangers of
  false positives especially with HIV

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Treatment Overview

• Intensive Phase 4 drugs for 2 months
• Continuation phase 2 drugs for 4 to 6 months
• Problem of compliance addressed with DOT
• Treatment failures add 5th drug and repeat
• Complete treatment failure MDRTB This pm

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TB Drug Prices

• DOTS course of therapy 8-12 through GDF
• MDRTB prices come down to about 450 through
  Green Light Committee drugs will be available
  through IDA at reduced prices

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Global TB Drug Facility

• STOP TB activity based at WHO to assist countries
  expand DOTS coverage
• During 2001, drugs procured and being distributed
  to 15 countries
• Decisions about which drugs and which suppliers
  difficult
• If Global Health fund provides resources more
  countries will be supplied next year

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Global Progress with DOTS
Total number of countries
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Conclusion

• TB is a serious disease that will be with us for
  the foreseeable future
• Likely to get worse in poor and HIV affected
  countries
• Management is possible but requires substantial
  program management skills and resources
• In some countries MDRTB a serious problem