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
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

To be customized: 20 747 crashes, 2 September 11th, 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
 Global TB incidence is rising by 1%
annually
400 Africa – high HIV
Estimated annual TB incidence/100 000 pop.

300

Africa – low HIV

200
World
100 Eastern Europe

World excluding
0 Africa, E. Eur.ope

1990 1995 2000 2005

7
Global Tuberculosis Control. WHO Report 2006. [data to be revised annually]
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 smear-
negative.
• 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

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< 3% or less than 3 cases in one

3 - 10% year of surveillance
> 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
Adequate ventilation
– late or no treatment of cases. removes droplet nuclei.
Direct sunlight (ultraviolet
rays, or UV) kills tubercle
• For development of disease: 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

No infection 10–30% infection

90% LTBI 5–10% ACTIVE

TB within 2 years

10% TB during lifetime

10% TB within 1 year if HIV+
HIV− HIV+

85% pulmonary TB 33% pulmonary TB

15% extrapulmonary 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 Dead
phagocytes,
Bacteria reach lungs, necrosis
enter macrophages M. tuberculosis

Bacteria reproduce
in macrophages

Phagocytes,
Lesion begins to form T cells and
(caseous necrosis) B cells
Activated trying to
macrophages kill bacteria

Bacteria stop growing;

lesion calcifies Lesion Bacteria coughed
liquefies out in sputum

Immunosuppression
Spread to
blood/organs
Reactivation
24
DEATH
 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 B

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

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 to health system strengthening

a. 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, etc
c. 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 Intermediate laboratories
infrastructures

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
 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