This document summarizes a review study on tuberculosis conducted by Bashar M. Khazaal. It defines tuberculosis as an infectious disease caused by mycobacterium tuberculosis, which usually involves the lungs but can spread to other parts of the body. Risk factors, pathophysiology, clinical manifestations, diagnostic methods, complications, management, and drug-resistant forms like MDR-TB and XDR-TB are described. Diagnostic tests discussed include tuberculin skin test, chest X-ray, bacteriological examination, drug susceptibility testing using phenotypic and molecular methods, Quantiferon-TB, T-Spot TB, and PCR. Treatment involves a multi-drug regimen over several months and directly observed therapy to prevent drug resistance

1. Tuberculosis
review study by master degree student
Bashar M. Khazaal

2. Objectives:
• What are Tuberculosis??.
• What are the risk factors, etiology, pathophysiology and clinical
manifestations of TB ??.
• What are the diagnostic methods for TB ??.
• What are the complications and management of TB ??.
• What are Multi drug resistance TB ??.

3. Tuberculosis
• It is an infectious disease caused by mycobacterium
tuberculosis.
• Usually involves the lungs, but can involve other body parts.
• Very common cause of death from infectious diseases in the
world.

4. Tuberculosis
Risk factors :





Immuno-suppressed patients (e.g., HIV, Long term
Corticosteroids use)
Older adult in long term facilities ( e.g. jails, elderly homes)
IV injecting drug users
Persons at poverty level, with poor access to health care
services, homeless.
Health care workers in increased exposure to TB.

5. TB: Pathophysiology
• M. tuberculosis is a gram-positive, acid-fast bacillus.
• It spreads from person to person via airborne droplets produced
while talking or coughing.
• Brief exposure to tubercle bacilli rarely causes infection.
• TB is not usually highly infectious, transmission requires frequent,
close, or prolonged exposure

6. Tuberculosis: Pathophysiology
•
•
The very small droplets (1-5 µm) contain M. tuberculosis, remains
airborne indoors from minutes to hours.
When inhaled; they are lodged into the bronchioles and alveolus.
•
Factors that influence the likelihood of transmission
1.
2.
3.
4.
Number of organisms expelled into air
Concentration of organisms.
Length of time of exposure
Immune system of the exposed person

7. Tuberculosis:
Pathophysiology
•
•
-
M. tuberculosis replicates slowly over time.
It travels through lymphatic system to find a suitable
environment for growth primarily in the:
Upper lobes of the lungs
Kidneys
Epiphyses of the bones
Cerebral cortex
Adrenal glands

8. Tuberculosis: classifications
Latent TB: the bacteria
is inhaled , but there is
an active immune
system, the bacteria will
be capsulated for life,
and become inactive,
preventing the disease
to progress, so they are
not sick or showing any
symptoms, and they
cannot spread the
germs.
Active TB: if the initial
response of the immune
system was not
adequate, the body can
not maintain control of
the organism, and it
develops into infection,
so active bacteria are
multiplying and causing
clinical active disease.

9. Tuberculosis: clinical
manifestation
• Latent TB: usually asymptomatic, but have a positive
TST.
• Active TB: fatigue, malaise, anorexia, unexplained
weight loss, low-grade fevers, and night sweats.
• Frequent cough, produce mucoid or mucopurulent
sputum
• Hemoptysis is usually seen with more advanced cases.
• Dyspnea is unusual
• Acute exacerbations: high fever, chills, general flu-like
symptoms pleurisy pain and productive cough.

10. Tuberculosis: Diagnostic
studies
1. Tuberculin skin test (TST): Mantoux test: PPD 0.1 ml
is injected ID on the dorsal aspect of the forearm, and
then read by inspection palpation after 48-72 hour, for
presence or absence of indurations
2. Chest X-ray: presence of upper lob infiltrates, &
lymph nodes involvements ( but can not be
confirmative alone for TB)
3. Bacteriologic and other studies : microscopic
examination of stained sputum smear of acid-fast
bacillus( AFB testing).
- Other samples of suspected infected sites can be
taken as well. e.g.: gastric wash, CSF sample, fluids
from an effusion. Löwenstein‒Jensen medium
culturing.

11. Table 1. Components of Löwenstein‒Jensen medium
Components
measures
2.4 g
Monopotassium dihydrophosphate (KH2PO4), anhydrous
Magnesium sulfate (MgSO4 ·7H2O)
Magnesium citrate
L-Asparagine
Distilled water up to
Glycerol (ml) or pyruvatea (g)
Egg homogenate
Malachite green (2%)
pH (about)
0.24 g
0.6 g
3.6 g
600 ml
12 ml or 7.2 g
1000 ml
20 ml
6.8

13. Drug susceptibility testing
Drug susceptibility testing means testing to find out
which drugs the TB bacteria in a person are sensitive to,
and therefore whether the person has got drug resistant
TB. It is essential that if a person might possibly
have drug resistant TB, that this is discovered as soon as
possible, in order that the patient can be provided with
effective TB treatment. Historically drug susceptibility
testing has needed specific laboratory facilities and
trained personnel, and in addition has been a very
lengthy process.

14. Different types of drug susceptibility tests
• Phenotypic drug susceptibility tests
Conventionally TB drug susceptibility testing has been
phenotypic, involving the culturing of M. tuberculosis in the
presence of anti TB drugs in order to detect growth (indicating
drug resistance) or inhibition of drug (indicating drug
susceptibility).

15. • Molecular methods of drug susceptibility testing
Since resistance arises from genetic mutations, another
approach is to detect the mutations themselves. Many
mutations associated with resistance have been identified and
molecular tests to detect them have been developed. The
advantages of molecular methods of drug susceptibility
testing include rapid turnaround times, but the disadvantages
include a low sensitivity for some compounds, and a major
issue is cost.

16. 4. QuantiFERON-TB
•Originally developed in Australia to test cattle for M. bovis
infection
•Measures IFN-γ in stimulated whole blood.
•1st generation used purified protein derivative (PPD)
•2nd generation (QFT-Gold) uses ESAT-6 and CFP-10
•3rd generation (QFT-Gold in tube) uses ESAT-6, CFP-10 and
TB 7.7

17. • How does QuantiFERON-TB Gold In-Tube work?
The QFT-G is an indirect test for M. tuberculosis infection that is
based on measurement of a cell-mediated immune response.
A cocktail of 3 mycobacterial proteins (ESAT-6, CFP-10, and TB
7.7) stimulate the patient's T-cells in vitro to release
interferon-gamma, which is then measured using ELISA
technology.

18. BCG strains and the majority of other non-tuberculosis
mycobacteria do not harbor ESAT-6, CFP-10, and TB 7.7 proteins;
thus, patients either vaccinated with BCG or infected with most
environmental mycobacteria should test negative.

19. 5. T – spot TB test
measure a person’s immune reactivity to M. tuberculosis.
White blood cells from most persons that have been infected
with M. tuberculosis will release interferon-gamma (IFN-g) when
mixed with antigens (substances that can produce an immune
response) derived from M. tuberculosis.
To conduct the tests, fresh blood samples are mixed with
antigens and controls. The antigens, testing methods, and
interpretation criteria for QuantiFERON-TB differ (see Table 2).

20. Table2: Differences in Currently Available
QuantiFERON-TB
QuantiFERON-TB
Initial Process
T-Spot
Process whole blood Process peripheral blood
within 16 hours
mononuclear cells (PBMCs) within 8
hours.
M. tuberculosis Antigen Single mixture of
Separate mixtures of synthetic
synthetic peptides
peptides representing ESAT-6 & CFPrepresenting ESAT-6, 10
CFP-10 & TB7.7.
Measurement
IFN-g concentration
Number of IFN-g producing cells
(spots)
Possible Results
Positive, negative,
indeterminate
Positive, negative, indeterminate,
borderline

21. 6. PCR
Other mycobacteria are also acid-fast. If the smear is
positive, PCR or gene probe tests can distinguish M.
tuberculosis from other mycobacteria.

22. Tuberculosis: complications
1. Miliary TB: M.O can invade blood stream, & involve
many organs. it can be due to a primary disease, or
activation of LTB. patient either acutely ill with fever,
dyspnea and cyanosis, or chronically ill with weight loss,
fever, GI manifestations; hepatomegally ,
spleenomegally.
2. Pleural effusion & Empyema: effusion is caused by
bacteria in the pleural space. Empyema is less common.
3. Tuberculosis pneumonia: acute pneumonia
4. Other organ involvement: CNS; with inflammation of the
meninges, joints, bone, kidneys adrenal glands, LN, and

23. Tuberculosis: management
• Most patients can be treated on outpatient basis
• Hospitalization maybe needed for the severely ill
patients
• Mainstay (basis) is drug therapy
• Monitoring for complications is a key for successful
treatment

24. Tuberculosis: drug therapy
• Initial phase treatment: 4 drugs for 6 months
( isoniazid, rifampin, pyrazinamide, and ethambutol).
• Nursing consideration: pregnancy, liver damage,
and alcoholism should be kept under monitoring.
• DOT( directly observed therapy): is a new approach
to observe patients taking their medications,
especially useful for patients who might be having
compliance problems.

25. Tuberculosis: drug therapy
• In LTBI: drug therapy can be initiated to prevent it
from becoming active TB.
• Usually treatment is less expensive and of less
duration if started as preventive measure.
• In general it is isoniazid, and can be administered
once daily from 6-9 months .

26. WHAT ARE MDR-TB, XDR-TB AND RR-TB ?
TB organisms resistant to the antibiotics used in its treatment are
widespread and occur in all countries surveyed. Drug resistance
emerges as a result of inadequate treatment and once TB organisms
acquire resistance they can spread from person to person in the
same way as drug-sensitive TB.
• Multidrug-resistant TB (MDR-TB) is caused by organisms that
are resistant to at least the two most effective anti-TB drugs,
isoniazid and rifampicin.
• Extensively drug-resistant TB (XDR-TB) is a form of TB caused
by organisms that are resistant to isoniazid and rifampicin (i.e.
MDR-TB) as well as any fluoroquinolone and any of the second–line
anti-TB injectable drugs (amikacin, kanamycin or capreomycin).
• Rifampicin-resistant TB (RR-TB) is caused by organisms that
are resistant to rifampicin, with or without resistance to other
drugs. Both MDR-TB and XDR-TB are forms of RR-TB.
• These forms of TB do not respond to the standard six month
treatment with first-line anti-TB drugs and can take two years or
more to treat with drugs that are less effective, more toxic and
more expensive.

27. Tuberculosis: vaccine
• Bacille Calmette-Guerin (BCG): is a live attenuated
strain of mycobacterium bovis. It is given in parts of
the world where prevalence is high, or high risk of
exposure like health care workers.
• Other tuberculosis vaccines in development like
MVA85A, rBCG30, 72F fusion protein, ESAT6-Ag85b
fusion protein

28. Thanks
I hope you enjoyed with this
study.