Overview: Tuberculosis, the global emergency

Module 1

1

Learning objectivesAt 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 and DST in

TB control

2

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

[data to be revised annually]

To be customized: 20 747 crashes, 2 September 11th, 1 Tsunami per day, or equivalent

5

Estimated TB incidence rate, 2006

Estimated new TB cases (all forms) per 100 000 population

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

No estimate

0-24

50-99

300 or more

25-49

100-299

Africa has the highest TB rates per capita. China and India have the greatest number of TB cases.

Global Tuberculosis Control. WHO Report 2008 [data and map to be revised annually]

0

100

200

300

400

1990 1995 2000 2005Est

imat

ed a

nnua

l TB

inci

denc

e/10

0 00

0 po

p. Africa – high HIV

Africa – low HIV

World

Eastern Europe

World excluding Africa, E. Eur.ope

Global TB incidence is rising by 1% annually

7[data to be revised annually]Global Tuberculosis Control. WHO Report 2006.

LOCAL country/region

8

• 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.

Disturbing statistics

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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.

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• 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 smear-negative.

• TB worsens the prognosis of HIV infection.

TB/HIV• TB is a leading cause of HIV-related mortality and morbidity.

• HIV is the most important factor fuelling the TB epidemic inpopulations with high HIV prevalence

[map to be revised annually]11

Global Tuberculosis Control. WHO Report 2008.

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

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MDR-TB and XDR-TB

• MDR-TBMultidrug-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-TBExtensively 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

< 3%

3-6 %

> 6 %

No data

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

* Sub-national coverage in India, China, Russia, Indonesia.

MDR-TB incidenceamong new cases , 1994-2007

Anti-tuberculosis drug resistance in the world, WHO 2008

[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

* Sub-national averages applied to Russia

< 3% or less than 3 cases in one year of surveillance3 - 10%

> 10%

No data

Report of at least one case

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XDR-TB estimatesamong MDR-TB cases, 2002-2007

Anti-tuberculosis drug resistance in the world, WHO 2008

[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

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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)

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TB transmission (infection)

Person-to-person

via

airborne transmission

in

confined environment

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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: 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.

Adequate ventilation removes droplet nuclei.

Direct sunlight (ultraviolet rays, or UV) kills tubercle

bacilli.

21

Inhalation (1–5 μm Ø)droplet infection

10–30% infection

90% LTBI 5–10% ACTIVETB within 2 years

10% TB during lifetime10% TB within 1 year if HIV+

85% pulmonary TB15% extrapulmonary TB

No infection

33% pulmonary TB33% extrapulmonary TB33% both

HIV− HIV+

Tuberculosis infection versus active disease

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Tuberculosis infection outcome

1.7 billion people TB infectedProgression to active disease is

accelerated in HIV+

8.4 million new TB cases, 1.6 million TB deaths each year

HIV- HIV+

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Bacteria coughedout in sputum

Inhalation of bacteria

Bacteria reach lungs,enter macrophages

Bacteria reproducein macrophages

Lesion begins to form(caseous necrosis)

Activatedmacrophages

Bacteria stop growing; lesion calcifies

Immunosuppression

Reactivation

Lesionliquefies

Deadphagocytes,necrosis

M. tuberculosis

Phagocytes,T cells andB cellstrying tokill bacteria

DEATH

Spread toblood/organs

Steps in the development of tuberculosis

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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: ZN staining 1000x B: Fluorescent staining, 400x

Cause of TB

A B

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• 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.

Diagnosis of TB by microscopy

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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

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Limitations of smear microscopy

• Low sensitivity: 104–105 bacilli/ml.• Detects both dead and viable bacilli.• Does not distinguish tubercle bacilli from other

mycobacteria.

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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 enhancementa. Political commitment with increased and sustained financing b. Early detection, and diagnosis through quality-assured bacteriologyc. Standardised treatment, with supervision and patient supportd. An effective drug supply and management systeme. Monitoring & evaluation system, and impact measurement

2. Address TB-HIV, MDR-TB and other challengesa. Scale–up TB/HIV collaborative activitiesb. Scale-up prevention and management of multidrug-resistant TBc. Address TB contacts, the poor and other highly vulnerable groups, prisoners, refugees, etc

3. Contribute to health system strengtheninga. Participate in improvement of health policies, human resources, financing, supplies, service delivery, and

information b. Innovate, introducing the Practical Approach to Lung Health (PAL), infection control, upgraded laboratory

networks, etcc. Adapt successful approaches from other fields and sectors

4. Engage all care providersa. Involve all public, voluntary, corporate and private providers through Public-Private Mix (PPM) approachesb. Promote use of the International Standards for TB Care (ISTC)

5. Empower people with TB, and communitiesa. Pursue advocacy, communication, and social mobilizationb. Foster community participation in TB carec. Promote the Patients' Charter for Tuberculosis Care

6. Enable and promote researcha. Conduct programme-based operational research and introduce new tools into practiceb. 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 –20101. 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 –2015Scale-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.

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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.

TB diagnostic services

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Central laboratory

Intermediate laboratories

Peripheral laboratories

TB diagnostic services should be linked as a “laboratory network”

Adapted to local situation and

infrastructures

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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.

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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.

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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 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 central levels. 41

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