TB Diagnosis _ Tuberculosis Test _ Healthcare Professionals _ TB _ Tuberculosis

8/13/2019 TB Diagnosis _ Tuberculosis Test _ Healthcare Professionals _ TB _ Tuberculosis

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Tuberculosis

T-SPOT.TB

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Guidelines

The Learning Zone

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The World Health Organization

(WHO) estimates that more than

one third of the worlds population is

infected with Mycobacterium

tuberculosis.

Tuberculosis

Tuberculosis disease is caused by a bacterium that can affect any

part of the body, but most comm only the lungs. Only TB of the lung

or throat can be infectious and is generally transmitted by

prolonged and/or frequent contact with an infected individual who

is coughing bacteria droplets into the surrounding air. The bacteria

are breathed in through the lungs , but can travel in the blood to

other organs which become infected. Diagnosis of these non-

pulmonary forms can be m ore difficult, as the person will no t have

the cough so commonly associated with TB.

A few years ago TB was thought to be a dis eas e of the past,

particularly in the developed world. However,the diseas e has now

made a dramatic comeback for a number of reasons. It is now

often described as a global epidemic.

TUBERCULOSIS INFECTION AND TUBERCULOSIS DISEASE

Tuberculosis infection (latent TB infection) occurs when people

carry Mycobacterium tuberculosisbacilli i n their body but the

bacteria are being controlled by the infected person 's imm une

system and so are still in sm all numbers. These bacteria do not

cause d iseas e or any TB symptom. Individuals with latent TBinfection are not infectious.They wouldbe negativeto mos t TB

tests including culture, Nucleic Acid Amplification Tests (NAAT),

and sm ear microscopy. Small nodules are occasionally seen on

chest x-ray. Until recently the only test capable of identifying LTBI

has been the tuberculin skin test.

Tuberculosis disease (active disease) occurs when the bacterial

load is increased and overcomes the body's immune defence.

Tuberculosis disease may be infectious and can be identified by

one or more of the following symptoms:

severe cough for 2 or more weeks (often involving blood loss)

weight loss

night sweats

poor appetite

weakness or fatigue (tiredness)

chills

fever

pain in the area infected

Active diseas e can often (but not always) be identified by culture,

sm ear m icroscopy, NAAT or chest x-ray. The number of peop le with

active TB at a given time is just the tip of the iceberg, as many more

are infected with TB and are therefore at a risk of developing the

disease.

To view the relationship between active disease and latent

infection click on the thumbnail.

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IMPORTANCE OF IDENTIFYING LATENT TB INFECTION (LTBI)

TB control methods are based on three strategies:

1. Vaccination using BCG is used in the developing to world

and has limited use in the developed world.

2. The diagnosis and treatment of active disease is important

for individuals who have TB and it also reduces the onward

transmis sion of the disease.

3. The diagnos is and treatment of Latent TB Infection (LTBI).

Most of the cases of active disease occur through the conversion o f

LTBI to active dis ease. Therefore the European framework for

tuberculosis control and elim ination in countries with a low

incidencerecently recommended that "Tuberculosis control and

elimination strategies m ust aim at diminishing the incidence and

prevalence of latent infection to reduce the pool of those with

tuberculosis infection from which future cases of tuberculosis will

emanate1."

Latent infection can only be reduced by firstly identifying those who

are infected. This is achieved by testing specific groups with a:

Greater risk of transmitting the diseas e (healthcare workers,

military personnel, imm igrants, contacts of index cases)

Higher risk of progression to active disease

(immunocompromised subjects, including HIV infected, renal

patients, transplant patients, haematological disorders and

those taking immunosuppress ive drugs).

Once people with l atent infection have been identified they can be

given preventative therapy which will e liminate the Mycobacteria

tuberculosisand s o prevent conversion to active disease and

eliminate the onward progression of the disease.

1Broekm ans J, et al Eur Respir J 2002; 19: 765-775

Diagnostics for Tuberculosis: Global Dem and and Market

Potential /TDR, FIND SA. WHO 2006: p. 21.

DIAGNOSTIC TESTS FOR DETECTING LATENT TUBERCULOSIS

Previously, the only test available to diagnose latent TB infection

has been the tuberculin skin test (TST). The test has rem ained

more or les s unm odified for the last 60 years. Desp ite its

inaccuracies, the TST is still being used to identify patients latently

infected with tuberculosis.

The T-SPOT.TBblood tes t offers a 21s t century alternative the TST

providing greater accuracty, convenience and logis tical

advantages.

DIAGNOSTIC TESTS FOR DETECTING ACTIVE TUBERCULOSIS
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People who are suspected of having active TB may be given a

number of different tests to confirm the damage caused by the

infection or to identify the organism s res ponsible for the infection.

Skin test

The tuberculin skin test described previously is sometimes used

for active tuberculosis , with the sam e limitations . The skin test can

only identify if a person has or does not have TB infection, it doesn't

differentiate between latent and active TB. If the test is negative it is

used as a rule out test indicating that the symptoms are not

caused by TB.

The skin test often remains posi tive for life after initial infection with

TB, and therefore the test can be false positive in patients

succes sfully treated for TB in the pas t.

Radiological examinations - Chest x-ray and CT scan

Ches t x-ray is us ed to check for lung abnormalities in peop le who

have symptoms o f TB disease. The resul ts of a chest x-ray may be

suggestive of TB; however the technique is not specific as m any

other diseas es can produce s imilar features. Even experienced

radiologis ts often have difficulty in determining the caus e of some

abnorma lities. Therefore the results from a ches t x-ray cannot

confirm that a person has TB disease (i.e. the test is imperfect as

a rule in' test). Like the skin test it is difficult to distinguis h pas t,

cured TB from current active disease s ince scarring in the lungs

remains after a previous TB infection (even if the patient is

completely cured).

TB chest x-ray (left) and CT scan (right)

The chest x-ray also has poor sensitivity; in the early stages of

disease, the damage to the lungs may not yet have become

sufficiently marked to be detectable so people who have active TB

are mis sed. It is therefore an imperfect rule out' test. Clearly thechest x-ray is com pletely useless as either a rule in or a rule out

test if the TB is not in the lungs. So in the 40% of all cases of active

TB where the disease is not found in the lungs (extra or non-

pulmonary TB) the chest x-ray is o f no use .

In some hospitals Computerised Tomography (CT Scan) and

Magnetic Resonance Imaging (MRI) have proved us eful for

imaging tuberculosis lesions, particularly those in the brain and

spine. CT scans are therefore often used to identify non-pulmonary

TB.

Smear Microscopy

The sim plest laboratory test is the examination of sputum for the

detection of acid-fast bacilli (AFB). This diagnos tic test is cheap

(reagents cost less than 3 per test) and is performed in minutes.

However, the WHO estimates that it only identifies 35% of patients

with active TB. As the test identifies cell s s uspended in liquid

sam ples it has particular difficulty in detecting many forms of non-

pulmonary TB which occur in a variety of organs in the body. This

test will als o identify acid fast bacilli other than M. tuberculosisso

its specificity is no t 100%.

Desp ite these shortcomings it is s till the front line tool for active TB

diagnos is, partly because the more de finitive culture techniques

take longer and because it can also determine if a person is

infectious. It is argued that while AFB bacilli are found in the

sputum the patient can continue to pass on the disease to other

people.

In some countries (Germany and Japan for instance) patients are


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kept in hospi tal until there are no AFB visib le in the sputum as they

are then considered not to be infectious. Sputum smear is thus

one method that can be used to m onitor an active TB patient's

respons e to therapy.

Ziehl-Neelsen acid fast stain

The MTB are the small red rod shaped organisms. Auramine

fluorescence s tains are a newer adaptation of this test. It requires

fluorescence microscopy but is a little more s ensitive as the

fluorescence is easier to see than the coloured stain.

Culture

Culture techniques are s till seen as the gold standard for active TB

as they are extremely sensitive, so long as l ive mycobacteria can

be obtained in the sam ple. It is therefore the "gold standard" test

which is used for comparison with other methods when calculating

sens itivity in active disease. M. tuberculosis can be cultured from a

variety of specim ens including sputum, Central Spinal Fluid (CSF),

pleural effusion, bronchoalveolar lavage (BAL), gastric aspirate etc

and can thus be us ed to detect pulmonary as well as

non-pulmonary disease. By asses sing the effect of antibiotics on

the cultured bacilli, this technique can also identify the antibiotic

sus ceptibility of the particular s train of TB infecting the patient. It is

therefore the ma in method for identifying if a person has multi-drug

resis tant (MDR) TB. However, it is not always poss ible to obtain

mycobacteria in the sam ple, especially in non-pulmonary TB so

culture is not a sensitive test. If performed correctly it should have

very high s pecificity and can di stinguis h M. tub erculosisfrom other

mycobacteria. A drawback of this tes t is the time to resu lt which

can be anything from 2 to 6 weeks.

NAAT

Nucleic acid amp lification tests (NAATs), such as polymeras e

chain reaction (PCR), are a relatively new development in active TBtesting. Even though NAAT techniques can m agnify even the

sm allest amounts of genetic material, the sam ple used s till has to

contain a certain number of TB bacilli and this is not always

poss ible, particularly with non-pulm onary TB where s ensitivity can

be as low as 60%. To increase the number of bacilli in the sample,

and hence improve the sens itivity of the test, the laboratory will

often culture the sample, to allow the bacil li to mu ltiply, before

carrying out the PCR test. This can take several

days or weeks. The ma in use of NAAT is no t to diagnose TB per

se, but to rule out infections caused by atypical m ycobacteria in a

sputum sm ear positive patient, before culture results are known.

This helps treatment to be initiated quickly, with the therapy then

being tailored to the patient based on the culture results obtained

6weeks later.

More recently NAATs have been used to identify MDR TB as

mutations in the DNA of MTB which confer drug resis tance have

been dis covered. These methods are quicker than culture but

generally only identify resis tance to rifampicin and isoniazid.

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TB Diagnosis _ Tuberculosis Test _ Healthcare Professionals _ TB _ Tuberculosis