Module 1 Overview Tuberculosis the global emergency 1

Module 1 Overview: Tuberculosis, the global emergency 1

Learning objectives At the end of this module, you will be able to: • • comment on the worldwide and local TB epidemic; define MDR-TB and XDR-TB; explain the MDR-TB and XDR-TB problem; describe the forms of TB and how TB is transmitted; comment on methods for TB laboratory diagnosis; describe the new Stop TB Strategy; explain the role of the NTP and the role and functions of the laboratory network; • explain the importance of AFB microscopy, culture 2 and DST in TB control

Content outline • • TB overview Definition of MDR-TB and XDR-TB Transmission and forms of TB TB diagnosis: advantages and limitations of microscopy and culture • Risk of infection and disease in immunocompetent and HIV-infected people • Stop TB Strategy and the importance of culture and DST • The role of the national TB programme and the laboratory network 3

Tuberculosis in history Devastating effect on society • 100 years ago one in five of the population was destined to die of tuberculosis. • Families suffer psychologically, socially and economically. • TB is highly stigmatized, especially in women. • Chopin, Keats, the Brontes, Kafka and D. H. Lawrence all died from the disease [to be adjusted to locally famous people] 4

Global emergency 2006 • 1/3 of world’s population is infected with TB • 9. 2 million new TB cases annually • 7. 8 million on new cases annually in Asia and sub-Saharan Africa • TB kills 5000 people a day • 1. 7 million people die of TB each year To be customized: 20 747 crashes, 2 September 11 th, 1 Tsunami per day, or equivalent [data to be revised annually] 5

Estimated TB incidence rate, 2006 Africa has the highest TB rates per capita. China and India have the greatest number of TB cases. Estimated new TB cases (all forms) per 100 000 population No estimate 0 -24 25 -49 50 -99 100 -299 300 or more Global Tuberculosis Control. WHO Report 2008 [data and map to be revised annually] The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved

Estimated annual TB incidence/100 000 pop. Global TB incidence is rising by 1% annually Africa – high HIV 400 300 Africa – low HIV 200 World Eastern Europe 100 World excluding Africa, E. Eur. ope 0 1995 2000 Global Tuberculosis Control. WHO Report 2006. 2005 [data to be revised annually] 7

LOCAL country/region 8

Disturbing statistics • TB is the major cause of death in people living with HIV/AIDS. • TB kills more young women than any other disease. • More than 100 000 children will die from TB this year. • Hundreds of thousands of children will become TB orphans. 9

Why? • TB is a poverty-related disease that affects all countries in the world – but it is curable. • TB patients are still stigmatized. • The global epidemic is driven by: – HIV/AIDS epidemic – MDR-TB. 10

TB/HIV • • TB is a leading cause of HIV-related mortality and morbidity. HIV is the most important factor fuelling the TB epidemic in populations with high HIV prevalence • HIV influences TB evolution: the risk of developing TB is 5– 15% per year in HIV-TB infected individuals. • HIV modifies TB presentation: HIV-TB patients are often smearnegative. • TB worsens the prognosis of HIV infection. 11 Global Tuberculosis Control. WHO Report 2008. [map to be revised annually]

Antituberculosis therapy • Combination of 3 or 4 drugs to prevent resistance (standard regimens are recommended). • Rifampicin and Isoniazid are the key drugs. • DOTS (directly observed therapy, short-course). Inadequate treatment will lead to treatment failure 12

Drug resistance in tuberculosis • Resistance in a newly diagnosed TB case Patients never treated (or less than 1 month) • Resistance in previously treated TB cases Patients previously treated or having been treated for 1 month or more 13

MDR-TB and XDR-TB • MDR-TB Multidrug-resistant TB: strains resistant to isoniazid and rifampicin – high fatality rate – second-line drugs needed – long therapy (18 months): greater cost, more side-effects. • XDR-TB Extensively drug-resistant TB: strains resistant to isoniazid and rifampicin (MDR) and to: (i) any fluoroquinolone, and (ii) at least 1 of 3 injectable second-line drugs (capreomycin, kanamycin, amikacin). Could become incurable. 14

MDR-TB incidence among new cases , 1994 -2007 * Sub-national coverage in India, China, Russia, Indonesia. < 3% 3 -6 % >6% No data Anti-tuberculosis drug resistance in the world, WHO 2008 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved [map to be revised annually]

XDR-TB estimates among MDR-TB cases, 2002 -2007 * Sub-national averages applied to Russia < 3% or less than 3 cases in one year of surveillance 3 - 10% > 10% Report of at least one case No data Anti-tuberculosis drug resistance in the world, WHO 2008 The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved [map to be revised annually]

TB/HIV and MDR/XDR problem in your country • Customize at country level with the local situation OR • It could be just a discussion presenting the previous slides [data to be revised annually] 17

Overview of TB infection, diagnosis and control 18

What is TB? TB is an infectious disease that affects mainly the lungs (pulmonary TB, or PTB) but can also attack any part of the body (extrapulmonary TB, or EPTB) 19

TB transmission (infection) Person-to-person via airborne transmission in confined environment 20

Risk factors • For infection (LTB): Duration and intensity of contacts with an active pulmonary case – poor housing/overcrowding – late or no treatment of cases. • For development of disease: Adequate ventilation removes droplet nuclei. Direct sunlight (ultraviolet rays, or UV) kills tubercle bacilli. Individual's susceptibility (including smoking), HIV status/ immunodeficiency increases the risk of progressing to active disease. Overall, only about 10% of infected people become sick with TB, half of them within the first year after infection; the other half will become sick years later. 21

Tuberculosis infection versus active disease Inhalation (1– 5 μm Ø) droplet infection 10– 30% infection No infection 5– 10% ACTIVE TB within 2 years 90% LTBI 10% TB during lifetime 10% TB within 1 year if HIV+ HIV− 85% pulmonary TB 15% extrapulmonary TB HIV+ 33% pulmonary TB 33% extrapulmonary TB 33% both 22

Tuberculosis infection outcome HIV- HIV+ 1. 7 billion people TB infected Progression to active disease is accelerated in HIV+ 8. 4 million new TB cases, 1. 6 million TB deaths each year 23

Steps in the development of tuberculosis Inhalation of bacteria Bacteria reach lungs, enter macrophages Dead phagocytes, necrosis M. tuberculosis Bacteria reproduce in macrophages Lesion begins to form (caseous necrosis) Activated macrophages Bacteria stop growing; lesion calcifies Immunosuppression Reactivation Lesion liquefies Phagocytes, T cells and B cells trying to kill bacteria Bacteria coughed out in sputum Spread to blood/organs DEATH 24

Cause of TB TB is caused by Mycobacterium tuberculosis and occasionally by other species belonging to the TB complex (M. bovis, M. africanum ). TB complex bacilli are also known as tubercle bacilli. A A: ZN staining 1000 x B B: Fluorescent staining, 400 x 25

Diagnosis of TB by microscopy • Mycobacteria retain the primary stain even after exposure to decolorizing acid–alcohol, hence the term “acid-fast bacilli” (AFB). • Ziehl-Neelsen • Fluorescence • M. tuberculosis bacilli can be found singly, in clumps or in clusters. They are usually beaded and long bacilli. 26

Smear microscopy definition of a TB case • New definition in 2007: “person with al least one smear-positive sample (1 AFB is sufficient) out of a total of two examined” • The definition can be applied to countries performing microscopy under satisfactory quality assurance programmes 27

Advantages of smear microscopy • • • Rapid Robust Cheap Accessible to the majority of patients Does not require extensive infrastructure 28

Limitations of smear microscopy • Low sensitivity: 104– 105 bacilli/ml. • Detects both dead and viable bacilli. • Does not distinguish tubercle bacilli from other mycobacteria. 29

Advantages of culture • Detects small numbers of bacilli (as few as 10 bacilli/ml, depending on the technique used). • Improves case detection: often 30 -50% over microscopy. • Provides definitive diagnosis of EPT. • Confirms diagnosis of TB in HIV+ patients. • Allows species identification. • Allows DST and drug resistance surveys. • Allows epidemiological studies. 30

Limitations of culture • • High cost. Slow growth of M. tuberculosis: delays results. More sensitive to technical deficiencies. Greater need for infrastructure: – qualified staff – equipment – additional safety measures. 31

The STOP TB Strategy – 2009 1. Pursue high-quality DOTS expansion and enhancement a. Political commitment with increased and sustained financing b. Early detection, and diagnosis through quality-assured bacteriology c. Standardised treatment, with supervision and patient support d. An effective drug supply and management system e. Monitoring & evaluation system, and impact measurement 2. Address TB-HIV, MDR-TB and other challenges a. Scale–up TB/HIV collaborative activities b. Scale-up prevention and management of multidrug-resistant TB c. Address TB contacts, the poor and other highly vulnerable groups, prisoners, refugees, etc 3. Contribute a. b. c. to health system strengthening Participate in improvement of health policies, human resources, financing, supplies, service delivery, and information Innovate, introducing the Practical Approach to Lung Health (PAL), infection control, upgraded laboratory networks, etc Adapt successful approaches from other fields and sectors 4. Engage all care providers a. Involve all public, voluntary, corporate and private providers through Public-Private Mix (PPM) approaches b. Promote use of the International Standards for TB Care (ISTC) 5. Empower people with TB, and communities a. Pursue advocacy, communication, and social mobilization b. Foster community participation in TB care c. Promote the Patients' Charter for Tuberculosis Care 6. Enable and promote research a. Conduct programme-based operational research and introduce new tools into practice b. Advocate, and participate in research to develop new diagnostics, drugs and vaccines

Strengthening diagnostic services to reach the global targets by increasing the number of laboratories performing cultures and DST 2006 – 2010 1. 50% of the global population has access to culture and DST. 2. National policy on culture and DST is developed and implemented in all countries. 2010 – 2015 Scale-up efforts to ensure that: 1. culture and DST are accessible to more than 5 billion people; 2. DST is carried out for all previously treated TB patients. 33

National tuberculosis programme (NTP) The NTP is a joint effort of the government and community which aims to achieve TB control at country level. The objectives of the NTP are: –to reduce mortality, morbidity and disease transmission and avoid the development of drug resistance; –in the long term, to eliminate the suffering caused by TB. 34

TB diagnostic services The aims of TB laboratory diagnostic services within the framework of an NTP are : ‒diagnosis of new cases; ‒monitoring of tuberculosis treatment; ‒management of failure cases. 35

TB diagnostic services should be linked as a “laboratory network” Central laboratory Adapted to local situation and infrastructures Intermediate laboratories Peripheral laboratories 36

Peripheral laboratory • Technical – preparation and staining of smears – ZN microscopy and recording of results – internal quality control. • Administrative – – receipt of specimens and dispatch of results cleaning and maintenance of equipment maintenance of laboratory register management of reagents and laboratory supplies. 37

Intermediate laboratory All the functions of the peripheral level, plus: • Technical – – fluorescence microscopy (optional) digestion and decontamination of specimens culture and identification of M. tuberculosis (DST ? ) procurement of reagents for microscopy in peripheral laboratories. • Managerial – training of microscopists – supervision of peripheral staff for microscopy – external quality assessment (EQA) of microscopy of peripheral laboratories. 38

Central laboratory • Country, provincial or state level • Services for TB diagnosis – sputum smear microscopy – culture and identification of M. tuberculosis – drug susceptibility testing. • Support for the laboratory network – advice on procurement – organization of and participation in training, supervision, EQA of sputum smear microscopy – coordination and supervision. • Other activities – participation in operational research – development of TB laboratory guidelines, setting of national standards, and implementation of policies – drug resistance surveillance. 39

True and false exercise 1. The HIV epidemic is the major factor affecting the global TB situation. 2. TB is incurable in the majority of cases. 3. MDR-TB leads to high fatality rates. 4. All infected people will develop active TB. 5. TB is transmitted by infectious aerosols. 6. Culture and microscopy have similar sensitivity. 7. The laboratory network plays a key role in TB control in the country. 40

Module review: take-home messages Ø Ø Ø Ø TB is a poverty-related disease affecting millions of people annually. Not all infected individuals will develop the disease. MDR- and XDR-TB and TB/HIV are threats to TB control globally. Transmission is airborne, mainly from pulmonary smear-positive TB cases, whose detection and treatment are essential for control of the disease. Microscopy is the main diagnostic technique in resource-limited countries. Although simple and rapid, it lacks sensitivity for the diagnosis of most TB/HIV patients and does not address drug resistance issues. Culture is a more sensitive technique than microscopy and can help to increase the detection rate. DOTS is a key component of the global strategy to stop TB. TB control is organized in national tuberculosis programmes (NTPs), which integrate laboratory services at peripheral, intermediate and 41 central levels.

Self-assessment • • What is TB and how is it transmitted? What is the global burden of TB? What are MDR-TB and XDR-TB? What are the advantages of culture over microscopy? • What is the role of the National Tuberculosis Programme? 42