Transcript TB and DOTS - SOTA-Technical Meeting Web Site

TB: A Global Emergency
• 1/3 of the world (2 billion people) infected
• 1 person infected/second resulting in >30
million new infections, 8 million new cases
• Left untreated 1/3 die, 1/3 self-cure, 1/3
remain infectious
• TB kills 1 person every 10 seconds =
5000/day = 2-3 million each year
22 High Burden Countries
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India
China
Indonesia
Bangladesh
Pakistan
Nigeria
Philippines
South Africa
Ethiopia
Vietnam
Russian Federation
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Congo
Brazil
Tanzania
Kenya
Thailand
Myanmar
Afghanistan
Uganda
Peru
Zimbabwe
Cambodia
TB: Clinical Features
• TB is caused by Mycobacterium tuberculosis
• TB can affect any organ system: bone, kidney, CNS;
80% are pulmonary
• Classic pulmonary systems of active disease: cough
> 3 weeks duration, chest pain, bloody sputum
• Classic systemic symptoms: fever, night sweats,
weight loss, malaise
• Treated for many years with long hospitalization,
surgery, myriad of drugs leading to belief that TB is
not treatable or treatment worse than disease.
TB Infection vs TB Disease
• TB infection – organism is present, but
dormant, cannot infect others
• TB disease – person is sick and can
transmit disease to others if in lungs
• 10% of individuals with TB infection will
develop TB disease
• Each individual with active TB can infect
10-15 people/year
When does TB infection
become disease?
• Most likely to occur in first two years
after infection
• If person becomes immunocompromised
– HIV
– Cancer
– Chemotherapy
– Poorly controlled diabetes
– malnutrition
The 5 Essential Components of
the DOTS Strategy
• Government commitment to a National TB
Program
• Priority to detect infectious cases by sputum
smear microscopy
• Standardized regimens of short-course
chemotherapy, given under direct observation for ,
at least, the intensive phase
• Regular, uninterrupted supply of anti-TB meds
• Monitoring system for program supervision and
evaluation
1. Political/Administrative
Commitment
• Perception of TB as a priority problem
with real solution
• Government acknowledges importance
of disease
• Public commitment to National TB
Program (NTP)
• Support for personnel, training,
transportation, drugs
2. Accurate Diagnosis=Sputum
Microscopy
• Identification/cure of infectious cases
(smear+) is highest priority of TB control
– Smear+s 4-20 times more infectious; may infect
10-15/year; more likely to die if untreated
• Timely results to reduce potential for
transmission
• Quality assurance/training--national
reference lab is key
Diagnosis of pulmonary TB
Cough 3 weeks
If 1 positive,
X-ray and
evaluation
AFB X 3
If 2/3 positive:
Anti-TB Rx
If negative:
Broad-spectrum antibiotic 10-14 days
If symptoms persist, repeat AFB smears, X-ray
If consistent with TB
Anti-TB Treatment
Chest X-ray (CXR) as
Diagnostic Tool
• No CXR pattern is typical
– Many TB cases are missed (10-15% culture+s)
– Many non-TB cases misdiagnosed (40%
diagnosed by CXR alone do not have active TB
• Previous MD training emphasized CXR as
best diagnostic tool
• Often reaction to poor, inaccurate, or
unavailable lab services
X-ray-based evaluation
causes over-diagnosis of TB
100
Overdiagnosis
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60
40
20
0
Diagnosed by Xray alone
NTI, Ind J Tuberc, 1974
Actual cases
Microscopy is a more specific
test than X-ray for TB diagnosis
100
98%
Specificity
80
60
50%
40
20
0
AFB Microscopy
X-ray
3. Adequate Supply of Drugs
• Treatment requires regular doses of
combination regimens for >6 months
• Identification of an adequate supply of
appropriate drugs for patients prior to
initiation of treatment essential
• If regimens incomplete, real chance of
development of drug-resistant strains which
are hard or impossible to cure
• Requires continuum of drug management
services: selection, procurement, distribution,
use.
4. Directly Observed Treatment
• Why? Many patients don’t take medicines regularly,
even if excellent health education provided
• Who? All patients... impossible to predict which
patient will take medicine (1/3 not adherent)
• What? Observer watches and helps patient swallow
tablets
• Where? Anywhere! (home, clinic, work, school,
etc)
• Who does it? HCW, community liaisons, teachers,
Direct observation ensures treatment for entire course
with the right drugs, in the right doses, at the right
intervals
DOT is necessary even when
drug supply ensured
100%
88%
Treatment Success
80%
61%
60%
40%
20%
0%
DOT
Chaulk CP. JAMA 1998;279:943-8
No DOT
DOT prolongs survival of
HIV-infected TB patients
Survived
56.7%
Survived
85.4%
Died
43.3%
SCC without DOT
SCC with DOT
Died
14.6%
5. Systematic
Monitoring/Accountability
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TB Register
Recording system is simple to use, essential,
integrated component of DOTS enabling
– Monitoring of patient outcomes
– Evaluation of program performance
– Analysis of epidemiologic data
– Identification of areas for OR
Every level of health system accountable for
patient diagnosis and cure; “report card”
TB and HIV/AIDS
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HIV negatively impacts TB and TB
negatively impacts HIV
HIV+ individuals infected with TB are 30x
more likely to develop TB disease
TB is leading cause of death among HIV+,
accounting for ~40% of AIDS deaths
HIV increases the prevalence of active TB
in HIV- and HIV+ populations
Multidrug-Resistant TB
(MDRTB)
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Defined as resistance to INH and RIF
Caused by inconsistent or partial treatment of
susceptible TB (primary)
Cure rates <70% cause the epidemic and drug
resistance to increase
Drugs are more toxic and expensive, and less
effective; treatment more difficult/expensive, and
more likely fatal in developing world
Poorly supervised, incomplete treatment is worse
than no treatment at all: Prevention of MDRTB is
the primary strategy to address MDRTB
USAID TB Strategy
• Support for the STOP TB Initiative
• Establishment of field sites/programs to serve
as models for innovative wide-scale TB control
• Investigation/implementation of potential
technologies and methodologies for TB
prophylaxis, diagnosis, and treatment
• Support for surveillance to monitor TB trends
and identify MDRTB strains before they
become widespread
USAID Expanded Response
• Continued investments in global and regional
partnerships:
– support for the Stop TB initiative
– continued work with other USG agencies
– Global partnership to develop new anti-TB drugs
– Global Drug Facility
– New International coalition of organizations and
agencies including KNCV, IUATLD, WHO, CDC,
ALA/ATS to provide TA/develop TB expertise
– Continued support for coordinated research to
optimize diagnostics and treatment regimens
USAID Expanded Response
• Expanded research investments
– rapid and sensitive TB diagnostic tests
– increase funding, work with our partners to
mobilize efforts and expertise of PH workers,
industry, academic researchers, donors,
other partners in lab/OR components
– Target collaborative efforts to develop costeffective TB drugs and combination therapies
– Potential expansion to vaccine development
USAID Expanded Response
• Focused, expanded programs in key
countries, targeting
– countries of greatest need, defined by TB
burden
– countries with high HIV/AIDS prevalence
– countries at risk of escalating MDR
epidemics
TB Country Programs
USAID - 2001
New/Expanded Country Programs
DR Congo
Ethiopia
Kenya
Malawi
Senegal
Uganda
Cambodia
India*
Indonesia
Philippines*
Russia*
Brazil
Dominican Republic
Haiti
Mexico
On-Going Programs
South Africa, Bolivia, El Salvador, Honduras, Peru, Central Asian
Republics, Ukraine, Romania, SE Europe Regional
*Existing program
Partners/Implementers
• Current
– WHO, CDC, Fogarty/NIH, IUATLD, Gorgas
Institute, MSH/RPM, PATH, QAP, FHI
– TBCTA (TB Coalition for Technical
Assistance)
• Potential
– NGOs (MSF, DOW, MERLIN)
– Foundations, World Bank, US Model Centers
Global Programs/Mechanisms
• Global/Bureau umbrella agreements
with WHO and CDC
• Multiple agreements to address
technical areas: RPM, PATH, TBCTA
• New interagency alliances under
development for drug procurement/
management/development
• Standard indicators already developed
Common Health Assumptions
not applicable to TB
• Access is necessary but NOT sufficient
– Drugs
– Services
• Not every health center/NGO site
appropriate as TB care center
• Poor program is worse than no program
at all
Priorities of TB Control
• Make sure the person completes TB
treatment!
• Do not cause drug resistance; a poor
TB program is worse than no TB
program!
• Treating non-pulmonary cases and
those infected without active disease
are of lesser public health importance
With TB, treatment is more
than treatment, treatment is
prevention
Role of Rifampicin
• Necessary for short-course treatment
• Essential for at least first 2 months of regimens
• Bactericidal for rapidly dividing and slow-growing
organisms
• Prevents emergence of resistance to other drugs
• Intermittent treatment more effective than daily
treatment in animal model; equally effective in
clinical trials
Role of Isoniazid
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Mainstay of anti-TB treatment
Life saving in TB meningitis
Bactericidal for rapidly dividing organisms
Prevents emergence of resistance to other
drugs
• Intermittent treatment more effective than daily
treatment in animal model; equally effective in
clinical trials
• Safe and effective for preventive treatment
DOTS can reduce the TB burden
Annual percentage decline in incidence/prevalence
0
-5
-10
-15
-20
-25
Edinburgh
Beijing
New York
Peru
Cuba
S. Korea
Uruguay
Chile
TB: the leading single infectious
cause of death in SE Asia
800
Number of deaths (1000s)
Deaths from infectious
agents in South-East
Asia
700
600
500
400
300
200
100
0
Tuberculosis
HIV
Measles
STD
Malaria
Tropical
Diseases
33
TB is a Leading Killer of
Women
Deaths among
women
605,000
538,000
493,000
101,000
48,000
Tropical
Diseases
STD
Maternal
Mortality
Malaria
TB
Diagnosis of pulmonary TB
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Patients with TB feel ill and seek care promptly
Active case finding is unnecessary and
unproductive
Microscopy is appropriate technology, indicating
infectiousness, risk of death, and priority for
treatment
X-ray is non-specific for TB diagnosis
Serological and amplification technologies (PCR,
etc.) currently of no proven value in TB control
Proportion of pulmonary TB
patients with positive AFB smears
70
60
HIV
Negative
AFB positivity in
TB patients
Early HIV
50
40
30
20
10
0
Late HIV
Prompt treatment of infectious
cases reduces spread of TB
• Smear-positive patients usually seek care
• Smear-positive patients are 4-20 times more
infectious
• Untreated, a smear-positive patient may infect
10-15 persons/year
• Smear-positive patients are much more likely
to die if untreated
Rouillon A. Tubercle 1976;57:275-99
Severe and less severe forms of
extra-pulmonary TB
Severe
Less Severe
Meningitis
Lymph nodes
Miliary
Pleural effusion (unilateral)
Pericarditis
Bone (excluding spine)
Bilateral or extensive
pleural effusion
Peripheral joint
Spinal
Intestinal
TB/HIV, A Clinical Manual, World Health Organization 1996
Role of Pyrazinamide
• Essential for 6- and 8-month regimens
• No benefit if given > 2 months
• Relatively ineffective at preventing
emergence of resistance to other drugs
Pyrazinamide essential for first two
months of 6/8-month treatment
Relapses (%)
100
Relapses
80
60
40
20
3.4%
10.3%
0
Pyrazinamide
Am Rev Respir Dis 1987;136:1339-42
No Pyrazinamide
Role of Ethambutol/
Streptomycin
• Prevent emergence of resistance to
other drugs given
• Hasten sputum conversion
• Bacteriostatic or weakly bactericidal
against rapidly dividing organisms
Relapse rates low with directly
observed treatment in both HIV(+)
and HIV(-) patients
Relapse (%)
100
80
60
Relapse rates
40
20
3%
5%
HIV-uninfected
HIV-infected
0
Am J Respir Crit Care Med 1996:154:1034-38
Adverse reactions to anti-TB
drugs
Drugs
Isoniazid
Adverse reactions
Peripheral neuropathy
 Hepatitis
Gastroentestinal (anorexia, nausea,
Rifampicin
Pyrazinamide
Ethambutol
vomiting, abdominal pain)
 Hepatitis
Reduced effectiveness of oral
contraceptive pill
 Joint pains
 Hepatitis
Optic neuritis
Auditory &vestibular nerve damage
Streptomycin
(also tofoetus)
Renal damage
Management of Drug Logistics
CHOICE
Quantification
Financing
USE
Information
for user &
for consumer
Management
of Stocks
DISTRIBUTION
STORAGE
Re-packaging
Transportation
Adequate buffer stocks must be
maintained at
national, state/regional, and local levels
PURCHASE
Tender bids
Order
Quality Control