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Module 2: Overview and Background
Learning Objectives
• Part 1– Describe TB global epidemiology– Explain 5-point DOTS strategy for effective TB control– Understand TB case definitions
• Part II– Explain how TB is transmitted– Describe active vs. latent TB– List risk factors for progression to active TB
25 - 49
50 - 99
100 - 299
< 10
10 - 24
No estimate
per 100 000 pop
300 or more
Estimated TB Incidence Rates, 2003Global Epidemiology
Adult prevalence %
15.0% − 39.0%5.0% − 15.0%1.0% − 5.0%0.5% − 1.0%0.1% − 0.5%0.0% − 0.1%not available
HIV Prevalence in Adults, 2003
UNAIDS Report on the Global HIV/AIDS Epidemic, 2004
38 million people [range: 35-42 million] living with HIV as of end 2003
0
100
200
300
400
500
600
700
19801983
19861989
19921995
19982001
Rep
ort
ed C
ase
Ra
te (
pe
r 10
0,0
00)
HIV Is Changing Global TB Epidemiology
Ivory Coast
Botswana
MalawiZimbabwe
Tanzania
Reported TB Case Rate in Botswana, 1975–2002,
and HIV Prevalence in Antenatal Women, 1992-2003
700
0
100
200
300
400
500
600
1975 1980 1985 1990 1995 2000
0
10
20
30
40
TB
cas
e ra
te (
per
100
,000
) HIV
serop
revalence (%
)
Strategy and Framework
Botswana and DOTS
TB Treatment--DOTS Strategy1. Sustained
Government Commitment to TB control
2. Microscopy-based Case Identification
4. Secure Supply ofQuality Drugs
3. Standardized Short Course Chemotherapy Under DOT
5. Case Registry, Monitoring & Evaluation
2HRZE(S)/4HR
“Enhanced DOTS”
• TB/HIV
• MDR TB
• Community TB Care
• Private Public Mix (PPM)
CASE DEFINITIONS HOLD THE PROGRAM TOGETHER
What is the of DOTS?
Case Definitions
• Purposes– Proper patient registration and case notification– Prioritize treatment of smear-positive cases
(the main source of infection in community)– Ensure cases on appropriate standardized
regimens– Evaluate cases according to site of disease,
bacteriology and treatment history– Permit cohort analysis of treatment outcomes
Matching diagnostic category and treatment regimens: Why?
• Avoid under-treatment of previously diagnosed cases
• Maximize cost-effective use of resources and minimize side effects by avoiding over-treatment
Determining the Case Definition
• Four factors– Disease Classification (i.e., is site of disease
(pulmonary, extrapulmonary or both?)– Bacteriology (i.e., smear status)– Patient Category ( determined by TB history—
i.e., is patient “new” or “retreatment”?)– Severity of TB disease (cavitary vs. non-cavitary)
First three factors recorded in register
Disease Classification and Smear-Status: PTB+ vs. PTB-
• PTB+ (Pulmonary TB smear-positive)–One AFB-positive smear; i.e. any patient with at least one positive smear result (irrespective of quantity of AFBs seen on microscopy)
Recommendations to improve the diagnosis of smear negative pulmonary and extrapulmonary TB among adults in HIV prevalent and resource constrained settings.Draft for discussion by Strategic and Technical Advisory Group of Stop TB Department of WHOJune 2006
Site of Disease: PTB+ vs. PTB-
• PTB- (smear-negative)Any pulmonary TB case that does not meet the definition
of being smear-positive. This includes:
1. Patients with three negative smear results and radiological findings and doctor’s decision to treat for TB
2. Patients with negative smear results and a positive culture result for M. tuberculosis
3. Patients who are unable to produce sputum and with highly suspicious radiological and clinical findings and doctor's decision to treat for TB
Severity of Disease
• Determinants include– Bacillary load– Extent of disease– Anatomical site
• Significant acute threat to life (e.g., pericardial dx)• Risk of severe handicap (e.g., spinal TB)• Or both (e.g., meningitis)• Miliary considered severe• EPTB can be “severe” or “less severe”
Registration Category: New
Determined by previous treatment history
NEW: Never had TB treatment or who has taken anti-TB treatment (ATT) < 1 month
RETREATMENT (3 types): Any patient who has taken > 1 month of ATT
Registration Category: Retreatment
RETREATMENT CASES
RELAPSE: A patient previously treated for TB who has been declared cured or treatment completed, and is diagnosed with bacteriologically-positive TB (smear- or culture-positive)
FAILURE: Patient started on re-treatment regimen after failing previous treatment
DEFAULT: A patient who returns to treatment, bacteriologically-positive, following a treatment interruption of two-months or more.
Determining the Case Definition
TB CASES
Severity of Disease
Extra-pulmonary
Smear-negative
Pulmonary
Smear-positive
NO
YES
New
Return after default
Relapse
Failure
Bacteriology
Site of DiseaseHistory of TB
Progress towards 70% case detection
0
10
20
30
40
50
60
70
80
1990 1995 2000 2005 2010 2015
Ca
ses
no
tifi
ed
un
der
DO
TS
(%
)
average rate of progress: target 2013
accelerated progress:target 2005
WHO target 70%
DOTS begins 1991
WHO, 2000
2003 Case Detection and Treatment Success Rates (WHO)
70
80
90
100
50 60 70 80 90 100 110 120
DOTS detection rate (%)
Tre
atm
ent
succ
ess
(%)
Cambodia
Oman
Sri Lanka
Guatemala
Peru
Morocco
MaldivesViet Nam
Cuba
Slovenia
Solomon Is
UruguayQatar
Mongolia
USA
Jamaica
Tanzania
Venezuela
Djibouti
ChileNicaragua
Target zone
Bosnia & Hezegovina
Hong Kong
DR Congo
El Salvador
Fiji
French Polynesia
Italy
Kazakhstan
Kenya
Kyrgyzstan
Latvia Lebanon
Malta
Marshall Is
Portugal
St Lucia
Samoa
South Africa
Tonga
Tunisia
Turks & Caicos Is
BOTSWANA
Transmission and Pathogenesis
Transmission of M. tuberculosis
•Expelled when person with infectious TB coughs, sneezes, speaks, or sings
•Spread by droplet nuclei
•Close contacts at highest risk
•Transmission occurs from person with infectious (active) TB disease, not latent TB infection
Cough: 100 km/hr!!!Sneeze 150 km/hr!!!
It’s all about VELOCITY
TB in the Lungs
Once TB bacilli is inhaled some bacilli reach the alveoli, where they are ingested by macrophages. Infection begins with the multiplication of tubercle bacilli within these alveolar macrophages.
Some of the bacilli spread through the bloodstream when the macrophages die; however, the immune system response usually contains the bacilli and prevents the development of disease.
Probability TB Will Be Transmitted
•Environment in which exposure occurred
•Infectiousness of person with TB
•Duration of exposure
•Virulence of the organism
Annual Risk of Infection (ARI)
ARI is defined as a calculated average from an observed prevalence
of infection, approximating the incidence of infection.
• Methodology
-Sample of school-age children
-Tuberculin skin tested (Mantoux test)
• Used to estimate the percentage of new TB
infections each year
-Accounts for responses to non-tuberculous
mycobacterium and BCG
• TST+ prevalence in Botswana in 1989 7.7%
among 6-10 y.o
H. Rieder: Annual risk of infection with Mycobacterium tuberculosis. Eur Respir J 2005; 25:181-185
Pathogenesis
•10% of infected persons with normal immune systems will develop TB (lifetime risk)
HIV strongest risk factor for development of TB
- HIV infection increases the risk of developing TB disease 7% to 10% each year
In addition to HIV there are other health conditions that increase the risk of developing TB disease.
Other Conditions That Increase Risk of Progression to TB Disease
•Recent infection •Substance abuse (alcohol and
recreational drugs)•Diabetes mellitus•Silicosis•Malnutrition•Smoking•Some malignancies•Prolonged corticosteriod therapy•Other immunosuppressive therapy•Chest radiograph suggestive of
previous TB disease
Conditions That Increase the Risk of Progression to TB Disease (cont.)
•Cancer of the head and neck
•Hematologic and reticuloendothelial diseases
•End-stage renal disease
•Intestinal bypass or gastrectomy
•Chronic malabsorption syndromes
•Low body weight (10% or more below the ideal)
Latent TB Infection vs. Active TB Disease
TB Types Patient has symptoms
Patient infectious to
others
Diagnosis
Latent TBInfection
No No Tuberculin skin test
(TST)
Active TB Disease
Yes Yes – when in the lungs
Sputum