+------------------+---------------------------------------------------+
| ![]              | Module 1                                          |
| (media/image1.jp |                                                   |
| eg){width="1.508 | **Overview: Tuberculosis, the Global Emergency**  |
| 3333333333333in" |                                                   |
| height="1.1354   |                                                   |
| 166666666667in"} |                                                   |
+------------------+---------------------------------------------------+

+-----------------+----------------------------------------------------+
|                 |                                                    |
+-----------------+----------------------------------------------------+
| **Purpose**     | To provide an overview of tuberculosis (TB) in the |
|                 | world and in your country                          |
+-----------------+----------------------------------------------------+
| **Prerequisite  | None                                               |
| Modules**       |                                                    |
+-----------------+----------------------------------------------------+
| **Learning      | At the end of this module, participants will be    |
| Objectives**    | able to                                            |
|                 |                                                    |
|                 | -   Explain the TB epidemic and the annual global  |
|                 |     TB burden                                      |
|                 |                                                    |
|                 | -   Describe the forms of TB and how TB is         |
|                 |     transmitted                                    |
|                 |                                                    |
|                 | -   Define and compare various methods of TB       |
|                 |     diagnosis, noting where each is most effective |
|                 |                                                    |
|                 | -   Explain the term NTP                           |
|                 |                                                    |
|                 | -   Describe the DOTS component of STOP TB         |
|                 |     strategy                                       |
|                 |                                                    |
|                 | -   Explain the importance of AFB microscopy in    |
|                 |     the DOTS program                               |
|                 |                                                    |
|                 | -   Describe levels of TB lab services.            |
+-----------------+----------------------------------------------------+
| **Content       | -   What is TB?                                    |
| Outline**       |                                                    |
|                 | ```{=html}                                         |
|                 | <!-- -->                                           |
|                 | ```                                                |
|                 | -   Transmission and forms of TB                   |
|                 |                                                    |
|                 | -   Risk of disease                                |
|                 |                                                    |
|                 | -   TB diagnosis                                   |
|                 |                                                    |
|                 | -   The role of the National TB Program            |
|                 |                                                    |
|                 | ```{=html}                                         |
|                 | <!-- -->                                           |
|                 | ```                                                |
|                 | -   Building and enhancing DOTS within the         |
|                 |     framework of the STOP TB strategy              |
|                 |                                                    |
|                 | ```{=html}                                         |
|                 | <!-- -->                                           |
|                 | ```                                                |
|                 | -   The importance of AFB microscopy in DOTS       |
|                 |     programs                                       |
|                 |                                                    |
|                 | -   Organization of laboratory services            |
+-----------------+----------------------------------------------------+
| **Handout and   | None                                               |
| Exercises**     |                                                    |
+-----------------+----------------------------------------------------+
| **Appendix**    | None                                               |
+-----------------+----------------------------------------------------+

##### 

#####  

##### Module 1: Overview: Tuberculosis, the Global Emergency

***Worldwide, 2.3 million people die of tuberculosis each year***.

In this early decade of the 21st century, the world remains challenged
by infectious disease and tuberculosis (TB) in particular. TB is the
typical disease of poverty. Of the 22 countries that have 80% of the
world\'s TB burden, 17 are classified as a low-income country. Annually,
2.3 million people still die from the disease, while increased deaths
due to drug-resistant TB, as well as co-infections of TB and human
immunodeficiency virus (HIV), produce even higher threats to world
health.

## WHAT IS TUBERCULOSIS?

Tuberculosis is an infectious and transmissible disease caused by
***Mycobacterium tuberculosis*** and occasionally by ***M. bovis***;
these two are the main pathogenic species within the ***M.
tuberculosis*** complex. These bacteria are also known as tubercle
bacilli because they produce characteristic lesions called tubercles.
When sputum specimens or other clinical specimens containing
mycobacteria are examined microscopically (after staining smears with
carbol fuchsin solution followed by acid decolorizing solution), the
tubercle bacilli and other mycobacteria retain the primary staining
reagent and appear red. This is due to their 'acid-fastness,' and hence
are referred to as acid-fast bacilli (AFB).

**TRANSMISSION AND FORMS OF TUBERCULOSIS**

Tuberculosis affects the lungs in more than 80% of cases (these are
called pulmonary TB or PTB). TB spreads from the primary lung lesions to
other parts of the body via the blood stream and lymphatic and bronchial
systems or by direct extension. In this way it may affect any organ,
causing extra-pulmonary TB. Diagnosis of extra-pulmonary TB (EPTB) is
often difficult and should be made by a physician. Not all of the cases
of EPTB are sputum smear-negative. It is, therefore, recommended to
check the sputum of EPTB patients.

Transmission of the bacilli from person to person occurs almost
exclusively by air. The primary source of infection is a person with PTB
who coughs and spreads the infected droplets. Pulmonary lesions may
contain on the order of a billion AFB. Transmission of tuberculosis
generally occurs in poorly ventilated closed areas. After an infected
person coughs, microaerosols known as droplet nuclei can remain
suspended in the air for long periods of time. Adequate ventilation
removes these nuclei. Direct sunlight (ultraviolet rays, or UV) kills
tubercle bacilli, but the bacilli can survive in darkness or in a humid
environment for several hours, and even days.

  -----------------------------------------------------------------------
  ***The higher the number of infectious sources spreading bacilli within
  a community, the greater the transmission.***

  -----------------------------------------------------------------------

A susceptible individual has a higher risk of infection when there is
continual and prolonged exposure to a person with sputum smear-positive
PTB in a confined space. The risk of transmission of the infection from
person with smear-negative PTB is lower.

## RISK OF DISEASE

Development of disease following infection also depends on the
individual\'s susceptibility. Overall, only about 10% of infected people
get sick with TB, half of them within the first year after infection;
the other half will become sick years later.

# TB DIAGNOSIS

**Smear microscopy**

Early laboratory diagnosis of tuberculosis still relies on the
examination of stained smears. For universal application in
resource-limited countries, microscopy of sputum smears is the best
choice among diagnostic methods. The technique is simple, inexpensive,
and efficient in detecting those cases of pulmonary tuberculosis that
are most infectious. Since its yield is highly dependent on execution,
the technician or even auxiliary personnel performing smear microscopy
is the most important element in the fight against TB for the majority
of the population in these countries. In high HIV prevalence countries,
patients may have disseminated disease with fewer AFB in their sputum.
Smears may be negative or may require even more careful screening to
identify low numbers of AFB.

**Culture**

Bacteriological culture provides a definitive diagnosis of tuberculosis.
The primary advantage of culture over sputum microscopy is that culture
can detect far fewer numbers of bacilli (\~10 bacilli/ml of sputum for
culture versus \~5,000 bacilli/ml of sputum for microscopy). This method
increases the potential of diagnosing treatment failures, EPTB, and TB
in children where numbers of bacilli may be very small. In addition,
culture distinguishes between viable and non-viable bacilli.

In settings where capacity exists and microscopy is optimized, culture
procedures should be introduced. Where HIV/TB is high in incidence,
culture is recommended. Culture is essential to obtain the necessary
growth required for drug susceptibility testing.

Limitations of culture include the following:

-   Getting results takes a long time (weeks)

-   It is technically more difficult than smear microscopy

-   In comparison to smear microscopy, increased resources are needed

-   Increased safety measures, including the use of biological safety
    cabinets, are essential.

**THE ROLE OF THE NATIONAL TUBERCULOSIS PROGRAM (NTP)**

The National Tuberculosis Control Program (NTP) is a joint effort of the
government and the community aimed at reducing, and in the long term
eliminating, suffering due to TB. The objectives of the NTP are to
reduce mortality, morbidity, and disease transmission while avoiding the
development of drug resistance. This is accomplished by using technical
knowledge and health resources available in the country.

The NTP accomplishes its objectives by

-   Early detection of infectious cases, and

-   Appropriate treatment until the illness is cured.

NTP goals:

-   Detect at least 70% of new smear-positive cases

-   Cure at least 85% of newly-detected cases of smear-positive TB

-   Reduce prevalence and deaths due to TB.

In countries with a high TB burden, the fight against TB can be
successfully conducted within the setting of a National Tuberculosis
Program using the WHO recommended building and enhancing DOTS within the
framework of the STOP TB strategy. The WHO TB strategy should be
integrated into the country's general health service.

[Role of the laboratory --]{.smallcaps} Laboratories form the foundation
of the national tuberculosis control programme and are one of the first
points of contact for tuberculosis suspects. Confidence or mistrust of
TB suspects and patients in the health system and the NTP will be
initiated at this point. A well performing laboratory network plays a
crucial role in TB control. By responding quickly and providing quality
services, the laboratory network will enable the early diagnosis of TB,
hence decreasing transmission, enabling appropriate treatment of
disease, monitoring treatment outcome and minimizing the risk of
possible complications, including death.

***NO LABS = NO DIAGNOSIS = NO TREATMENT = NO DOTS = NO TB CONTROL***

### 

### 

### 

### 

### **DOTS COMPONENT OF STOP TB STRATEGY**

DOTS is the internationally recommended strategy for TB control in
response to the global TB emergency.

This plan combines the following five elements:

-   Sustained political commitment to increase human and financial
    resources and make TB control a nationwide priority integral to the
    national health system;

-   Access to quality-assured TB bacteriology services for case
    detection among persons presenting with, or found through screening
    to have, symptoms of TB (most importantly, prolonged cough);

-   Standardized short-course chemotherapy for all patients with TB
    under proper case management conditions, including patient support
    during the treatment;

-   An uninterrupted supply of quality-assured drugs and laboratory
    reagents; and

-   A recording and reporting system that provides an outcome assessment
    of all patients and an assessment of the program's overall
    performance.

### **IMPORTANCE OF ACID-FAST BACILLI (AFB) MICROSCOPY IN DOTS PROGRAMS**

The DOTS program uses AFB microscopy as the main technique for diagnosis
of tuberculosis, as well as follow-up of patients during treatment.
Other techniques are considered complementary and should be based on the
specific TB epidemiological situation.

####### **1. Diagnosis** 

The emphasis on AFB-microscopy for diagnosis of TB is justified for
individuals as well as for the community (disease control). Persons with
smear-positive pulmonary TB (PTB) are usually sick and seek treatment.
These patients will rarely be cured without proper treatment. Therefore,
smear-positive cases are the primary sources of infection in
communities.

**2. Treatment follow-up**

The evolution of the disease during treatment, declaration of cure or
failure, and also relapse can best be monitored by bacteriological
methods. Clinical criteria are unreliable. It is seldom possible to
diagnose relapse by means of X-ray.

For follow-up, culture is more reliable than AFB microscopy because
microscopy will show all AFB, alive or dead, while culture will detect
only living bacilli that form colonies. Declaration of failure on smear
evidence will be more accurate when it is based on repeated positive
smears. Smear diagnosis of relapsing cases will, in general, be
reliable.

Culture cannot easily replace smears for follow-up since *M.
tuberculosis* grows very slowly. Repeating a smear examination after 2
weeks (in case of a doubtful result) will yield an answer before a
culture could.

Smear microscopy will continue to be used for diagnosis and follow-up in
DOTS programs. It is an excellent tool for these purposes when it is
correctly performed and the results are properly interpreted and used.
This requires excellent technique and laboratory services delivering
correct and interpretable (i.e., quantified) results, which will depend
mainly on the sincere effort of technicians performing this simple but
so important task. Of equal importance is close collaboration between
AFB microscopy laboratories and the TB program (NTP) as well as the
involvement of clinicians to support and promote laboratories and to
make optimal use of the results.

**ORGANIZATION OF LABORATORY SERVICES**

**Levels of laboratory services**

Tuberculosis laboratory services should be included within the
integrated tuberculosis control programs, which in turn should form part
of the overall primary health care programs of countries.

Therefore, TB laboratory services should be organized according to the
three levels of general health services:

-   Peripheral laboratory

-   Intermediate laboratory

-   Central laboratory

In terms of complexity, the activities performed at each level are
different:

**Peripheral laboratories** should be capable of performing smear
microscopy using the Ziehl-Neelsen (ZN) staining reagent technique for
sputum specimens.

**Intermediate laboratories**, in addition to performing the laboratory
functions of the peripheral laboratories, should be capable of providing
supervision, monitoring, training and quality assurance to peripheral
laboratories. If resources permit, they may also do culture.

**Central laboratories** are the highest level of service and should be
capable of performing microscopy, mycobacterial culture, and drug
susceptibility testing as well as species identification.

Responsibilities of the central laboratory include the following:

-   Organizing and providing training for laboratory staff

-   Organizing and providing quality assurance and proficiency testing
    for intermediate and peripheral laboratories

-   Conducting surveillance of tuberculosis drug resistance

-   Participating in epidemiological and operational research

+-----------------+----------------------------------------------------+
| **Key message** | -   Tuberculosis is an infectious disease          |
|                 |     affecting millions of people annually.         |
| ![](m           |                                                    |
| edia/image2.wmf | -   Transmission is via the air, and mainly from   |
| ){width="1.1701 |     smear-positive cases, whose detection and      |
| 388888888888in" |     treatment is essential for control of the      |
| height="0.83194 |     disease.                                       |
| 44444444445in"} |                                                    |
|                 | -   Microscopy is the main diagnostic technique in |
|                 |     resource-limited countries. Although simple to |
|                 |     do, it requires highly committed staff to      |
|                 |     reach its full efficiency.                     |
|                 |                                                    |
|                 | -   DOTS is the global strategy to control TB. One |
|                 |     of the main elements of the strategy is        |
|                 |     detection of disease by quality-assured        |
|                 |     mycobacteriology.                              |
|                 |                                                    |
|                 | -   TB control is organized in the NTP, which      |
|                 |     integrate laboratory services at peripheral,   |
|                 |     intermediate, and central levels.              |
+-----------------+----------------------------------------------------+

+-----------------+----------------------------------------------------+
| > ![](m         | Module Review: Module 1                            |
| edia/image3.wmf |                                                    |
| ){width="1.0in" |                                                    |
| >               |                                                    |
| height="0.96041 |                                                    |
| 66666666667in"} |                                                    |
+=================+====================================================+
| > Find out how  |                                                    |
| > much you have |                                                    |
| > learned by    |                                                    |
| > answering     |                                                    |
| > these         |                                                    |
| > questions.    |                                                    |
+-----------------+----------------------------------------------------+
| > What is TB    |                                                    |
| > and how is it |                                                    |
| > transmitted?  |                                                    |
+-----------------+----------------------------------------------------+
| > What are the  |                                                    |
| > international |                                                    |
| > targets to    |                                                    |
| > control TB?   |                                                    |
| >               |                                                    |
| > \_\_\_        |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
+-----------------+----------------------------------------------------+
| > Why is        |                                                    |
| > microscopy    |                                                    |
| > the most      |                                                    |
| > effective     |                                                    |
| > diagnostic    |                                                    |
| > technique in  |                                                    |
| > r             |                                                    |
| esource-limited |                                                    |
| > settings?     |                                                    |
| >               |                                                    |
| > \_\_\_        |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
+-----------------+----------------------------------------------------+
| > What is DOTS? |                                                    |
| >               |                                                    |
| > \_\_\_        |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
+-----------------+----------------------------------------------------+
| > What is the   |                                                    |
| > role of the   |                                                    |
| > National      |                                                    |
| > Tuberculosis  |                                                    |
| > Control       |                                                    |
| > Program?      |                                                    |
| >               |                                                    |
| > \_\_\_        |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
| \_\_\_\_\_\_\_\ |                                                    |
| _\_\_\_\_\_\_\_ |                                                    |
+-----------------+----------------------------------------------------+