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 - 4950 - 99100 - 299

< 1010 - 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

orte

d C

ase

Rat

e (p

er 1

00,0

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 c

ase

rate

(per

100

,000

) HIV seroprevalence (%

)

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 TB2. Patients with negative smear results and a positive

culture result for M. tuberculosis3. 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

BacteriologySite of Disease

History of TB

Progress towards 70% case detection

0

10

20

30

40

50

60

70

80

1990 1995 2000 2005 2010 2015

Cas

es n

otifi

ed u

nder

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 120DOTS detection rate (%)

Trea

tmen

t suc

cess

(%)

Cambodia

Oman

Sri Lanka

Guatemala

Peru

Morocco

MaldivesViet Nam

Cuba

Slovenia

Solomon Is

UruguayQatar

Mongolia

USA

Jamaica

Tanzania

VenezuelaDjibouti

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 LungsOnce 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.oH. 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