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

< No estimate per pop 300 or more Estimated TB Incidence Rates, 2003 Global 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, million people [range: million] living with HIV as of end 2003

Reported Case Rate (per 100,000) HIV Is Changing Global TB Epidemiology Ivory Coast Botswana Malawi Zimbabwe Tanzania

Reported TB Case Rate in Botswana, 1975–2002, and HIV Prevalence in Antenatal Women, TB case rate (per 100,000) HIV seroprevalence (%)

Strategy and Framework Botswana and DOTS

TB Treatment--DOTS Strategy 1.Sustained Government Commitment to TB control 2. Microscopy-based Case Identification 4. Secure Supply of Quality 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 Disease History of TB

Progress towards 70% case detection Cases notified under DOTS (%) 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) DOTS detection rate (%) Treatment success (%) Cambodia Oman Sri Lanka Guatemala Peru Morocco Maldives Viet Nam Cuba Slovenia Solomon Is Uruguay Qatar Mongolia USA Jamaica Tanzania Venezuela Djibouti Chile Nicaragua 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 % among 6-10 y.o H. Rieder: Annual risk of infection with Mycobacterium tuberculosis. Eur Respir J 2005; 25:

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 TypesPatient has symptoms Patient infectious to others Diagnosis Latent TB Infection No Tuberculin skin test (TST) Active TB Disease YesYes – when in the lungs Sputum