Tuberculosis (TB) is an ancient disease that has affected humans for thousands of years. It is caused by the bacterium Mycobacterium tuberculosis. TB primarily affects the lungs and is transmitted through inhaling droplets from infected individuals. While many who are exposed will not become infected, one third of the world's population is estimated to be infected with the latent form of TB. Active pulmonary TB is most commonly transmitted through coughing or sneezing. While treatment exists, TB remains one of the leading infectious disease causes of death worldwide.

1. By Dr Waleed Arshad

2. History of TB An Old Disease
 TB is an ancient disease. Signs of skeletal TB (Pott
disease) have been found in remains from Europe
from Neolithic times (8000 BCE), ancient Egypt (1000
BCE), and the pre-Columbian New World.
 TB was recognized as a contagious disease by the time
of Hippocrates (400 BCE), when it was termed
"phthisis" (Greek from phthinein, to waste away).
 In English, pulmonary TB was long known by the term
“consumption.”
 German physician Robert Koch discovered and
isolated M tuberculosis in 1882.

3. OBJECTIVES
 Defination
 The burden of disease
 Etiology
 Mode of transmission
 Latent TB infection vs TB Disease
 Pathogenesis
 Primary Pulmonary TB
 Secondary Pulmonary TB
 Milliary TB
 Clinical Presentation
 Diagnosis
 Treatment
 Prevention

4. Definition
 The World Health Organization (WHO) defines TB as
“An infectious bacterial disease caused
by Mycobacterium tuberculosis, which most
commonly affects the lungs. It is transmitted from
person to person via droplets from the throat and
lungs of people with the active respiratory disease”

5. The Burden of Disease
 TB is one of the world most widespread and deadly illness. Mycobacterium
Tuberculosis the organism that causes tuberculosis infection and disease ,
infects one third of population.
 In 2014, there was 9.6 million new cases of tuberculosis worldwide with 1.5
million cases dying of the disease.
 Pakistan ranks 5th among the 30 high TB burden countries. It accounts for
approximately 2/3rd of the TB burden of the Eastern Mediterranean Region
(EMR) of the World Health Organization based on nationwide population-
based TB prevalence survey carried out in 2010/2011, estimated TB
prevalence rate (all forms and all ages) was 342 cases in 100,000 population
and TB incidence rate was 275 TB cases per 100.000 populations.
 According to W.H.O estimates, mortality rate of TB was 26 deaths per 100,000
populations in 2015(Global TB Report 2016).
 DRTB estimates are based on the Natonal drug resistance survey,
conducted in 2012/13. Estimated proportion of MDR in new TB cases is 3.7%.
Proportion of MDR in retreatment cases is 18% based on surveillance data.

6. Etiology
Mycobacterium tuberculosis
A. is the most common causative organism of
pulmonary tuberculosis.
B. Non-spore forming, non motile,
pleiomorphic, weakly gram-positive, curved rod
about 2-4 um long.
C. Mycolic acid present in its cell wall which makes It
resist decolourization with acid and Alcohol so
hence known as Acid Fast Bacteria.
D. Appear beaded or clumped in stained
clinical specimens or culture media .
E. Grow best at 37-41 c.and Grow slowly, their
generation time being 12-24 hour.
Rare causes other than TB
o M.avium intracellularie complex(MAC) especially
in patients wih AIDS and underlying lung disease.

7.  Airway droplets: the main mode
of transmission from person
infected with pulmonary TB to
others by respiratory droplets.
 Ingestion: Less frequently
transmitted by ingestion of
mycobacterium bovis found in
unpasteurized milk products.
 Direct inoculation (in skin
tuberculosis)
 Transplacental route(rare route).
MODE OF TRANSMISSION

8. MODE OF TRANSMISSION
 Pulmonary TB is a Disease of Respiratory
Transmission, patients with active disease expel bacilli
into the air by:
 Coughing
 Sneezing
 Shouting
 Or any other way that will expel bacilli into the air.

9. MODE OF TRANSMISSION
 Millions of tubercle bacilli in lungs
( mainly in cavities).
 Coughing projects droplets nuclei
into the air that contain tubercle
bacilli.
 One cough can release 3,000
droplet nuclei.
 One sneeze can release tens of
thousands of droplet nuclei.
 As few as five M. tuberculosis
(MTB) bacilli are necessary for
human infection

10. MODE OF TRANSMISSION
Optimal conditions for transmission include:
 Overcrowding.
 Poor personal hygiene.
 Poor public hygiene.

11. MODE OF TRANSMISSION
 Large droplets settle to the ground quickly.
 Smaller droplets form " droplet nuclei" of 1-5 μm in
diameter, only TB-containing particles small enough
to reach the vulnerable environment of the alveolar
space (typically <5–10 μm) are considered infectious.
After inhalation, these infectious particles deposit
preferentially in the dependent lower half of the lung,
where they subsequently initiate a primary focus of
infection.
 Droplet nuclei can remain airborne.

12. Not Everyone Who is Exposed to
TB Will Become Infected
No Infection(70%) Early Progression(5%)
Adequate Inadequate
Exposure Non Specific Immunological Defences
Immunity
Inadequate
Adequate
Infection(30%) Containment(95%)
Latent TB

13. High Risk For Progression
 Persons more likely to progress from LTBI to TB
disease includes:
 HIV infected persons
 Persons with a history of prior, untreated TB or fibrotic
lesions on CXR
 Recent TB infection (within the past 2 years)
 Injection drug users
 Age ( very young or very old)
 Patients with certain medical conditions ( DM, chronic
renal failure, Hemodialysis, Solid Organ Transplantation,
Cancer, Malnourished patients, Silicosis.

14. LTBI vs TB DISEASE
LTBI TB Disease
 Tubercle bacilli in the body
 TST and QFT-Gold results
usually positive.
 CXR usually normal.
 Sputum smear and culture
negative.
 No Symptoms.
 Not infectious.
 Not a case of TB
 Tubercle bacilli in the body.
 TST and QFT-Gold results
usually positive.
 CXR usually abnormal.
 Sputum smear and culture
positive.
 Symptoms such as cough,
fever, weightloss.
 Often infectious before
treatment.
 A Case of TB.

15. Spread of TB to other parts of body
 Lungs (85% of all
cases)
 Pleura
 CNS
 Lymph nodes
 Genitourinary system
 Bones and joints
 Disseminated ( eg
miliary).

16. PATHOGENESIS
 The bacilli implant in areas of high partial pressure of oxygen:
 Lung
 Renal cortex
 Reticule endothelial system
 The principal cause of tissue destruction from M tuberculosis
infection is related to the organism's ability to incite intense host
immune reactions to antigenic cell wall proteins. This is known
as the primary infection, the patient will heal and a scar will
appear in the affected loci.
 There will also be a few viable bacilli/spores may remain in these
areas( particularly in the lung), the bacteria at this time goes into
a dormant state, as long as the person's immune system remains
active and functions normally.
 When a person immune system is depressed, a secondary
reactivation occurs. 85-90% this reactivation occurs in the lungs.

17. PATHOGENESIS
 About 90% of those infected with mycobacterium
tuberculosis are asymptomatic (latent TB infection),
with only a 10% lifetime chance that latent infection
will progress to TB disease.
 Tuberculosis is classified into:
 A. Primary pulmonary TB
 B. Secondary pulmonary TB
 C. Miliary TB
 D. Extra pulmonary TB ( CNS, Bones, joints, adrenal,
renal etc...)

18. PRIMARY PULMONARY TB
 Primary pulmonary TB is an infection of persons who
have not had prior contact with the tubercle bacillus.
 Inhaled bacilli are commonly deposited in alveoli
immediately beneath the pleura, usually in the lower
part of the upper lobes or the upper part of the lower
lobes.
 When inhaled, droplet nuclei are deposited in
terminal airspaces of the lung.
 Macrophages ingest the bacilli and transport them to
regional lymph nodes.

19. PRIMARY PULMONARY TB
 The primary infection
characteristically produces a
" Ghon complex" formed of:
1. Ghon focus: small area of
pneumonic consolidation about 1-3
cm in diameter, subpleural in
location present in the base of the
upper lobe or apex of the lower lobe.
2. Tuberculous lymphangitis: of the
draining lymphatic channels
3. Tuberculous lymphadenitis: of the
tracheobronchial nodes which are
enlarged, matted together and their
cut surface show areas of caseous
necrosis.

20. PRIMARY PULMONARY TB
PATHOGENESIS
 Spread if infection will take place by:
 Local spread: to the surrounding lung tissue and
pleura.
 Lymphatic spread: along bronchi, leading to
tuberculous bronchopneumonia. and
lymphangitic spread to Hilar and paratracheal
nodes leading to enlargement of these structure.
 Hematogenous spread: leading to miliary TB or
isolated organ TB or miliary TB of the lung.

21. FATE OF PRIMARY TUBERCULOSIS
 No progression
 Healing by fibrosis and calcification
 Ghons complex after undergoing
progressive fibrosis produces radiologically
detectable calcification called as Ranke
complex.(often the only residua of primary
infection).
 Progressive primary tuberculosis
 Primary miliary tuberculosis
 Dissemination to organs like liver, spleen,
kidney, .

22. COMPLICATIONS OF
PRIMARY TUBERCULOSIS
 Collapse/ consolidation
 Bronchiectasis
 Obstructive emphysema
 Broncholith
 Erythema nodosum
 Phlyctenular conjunctivitis
 Pleural effusion
 Miliary TB
 Progressive primary tuberculosis

23. SECONDARY TUBERCULOSIS
 Secondary(cavitary) TB usually results
from reactivation of a dormant,
endogenous tubercle bacilli in a
sensitized patient who has had
previous contact with the tubercle
bacillus.
 In some cases the disease is caused by
reinfection with exogenous bacilli.
 The lesion begins as a tubercle
(containing central area of necrosis
surrounded by granulomatous tissue
containing the Langerhan giant
cell)the micro-organisms searching for
a high oxygen tension, usually settle in
the apical portion of one or both lungs.

24. FATE OF SECONDARY TUBERCULOSIS
 Healing by fibrosis with dystrophic calcification occurs
in most cases when the dose of infection is small,
virulence of the organism is low and the patient
resistance is good.
 Spread of infection occurs when the patient resistance
is poor and the virulence of the organism is high,
spread occurs directly by lymphatic,natural passages
and blood stream.
 Fibrocaseous tuberculosis with cavitation occurs with
moderate dose of the organism and moderate
resistance of the patient.

25. Primary TB Secondary TB
 Mainly occurs in children but can
occasionally occurs in elderly and
adults.
 Mainly Asymptomatic or with
minimal symptoms and may goes
unrecognized.
 Septum for AFB is rarely positive.
 Associated with hypersensitivity
phenomenon ( erythema
nodosum).
 Site of involvement on is the lower
portion of the upper lobe and the
upper portion of the lower lobe.
 On CXR : an area of consolidation
or pleural effusion.
 Non infectious.
 Mainly occurs in adults.
 Symptomatic.
 Usually positive.
 Not associated with hypersensitivity
reactions.
 Apex of both lungs and the upper
portion of the lower lobe.
 Typically cavitary lesion over the
apex.
 Highly infectious in sputum positive
cases.

26. MILIARY TUBERCULOSIS
Extensive infection via hematogenous spread.
In lung: lesions are either microscopic or small, visible
foci (2mm) of yellow white consolidation scattered
through out lung parenchyma.
 Miliary pulmonary disease can cause pleural
effusion, tuberculous empyema or obliterative fibrous
pleuritis.
Extra pulmonary miliary tuberculosis is most
prominent in the liver, spleen, bone marrow, adrenals,
meninges, kidneys, fallopian tubes and epididymis but
can involve any organ.

27. MILIARY TUBERCULOSIS
OF SPLEEN
The Cut Surface shows numerous grey white granulomas.

28. EXTRA PULMONARY TUBERCULOSIS
 In tissues or organs seeded hematogenously.
 Commonly involved organs include:
 Intestinal tuberculosis (Primary, Secondary and
hyperplastic).
 Meninges (Tuberculous meningitis)
 Kidneys (Renal tuberculosis)
 Adrenals (Addison disease)
 Bones (Osteomyelitis)
 Vertebrae (Pott disease)
 Fallopian tube (salpingitis).

29. CLINICAL PRESENTATION OF TB
 Signs and Symptoms
Patients typically present with weight loss, fatigue, a
productive cough, fever, and night sweats
 Physical Examination
Dullness to chest percussion, rales
Auscultation revealed vocal fremitus sound
 Laboratory Tests
Moderate elevations in the white blood cell (WBC)
count with a lymphocyte predominance.

30. CLINICAL PRESENTATION OF TB
Chest Radiograph:
• Patchy or nodular infiltrates in the apical areas of
the upper lobes or the superior segment of the lower
lobes.
• Cavitation that may show air-fluid levels as the
infection progresses.
CT scan: To diagnose TB that has spread throughout
the body (miliary TB) and to detect lung cavities
caused by TB.
MRI: This test looks for TB in the brain or the spine.

31. DIAGNOSIS
FINDINGS ON CXR OF PRIMARY
PULMONARY TUBERCULOSIS
 Lymphadenopathy is the hallmark of primary disease in childhood,
seen in up to 90% of cases.
 Usually affects the hilum and right paratracheal regions.
 Bilateral adenopathy occurs in one third of cases.
 Adenopathy usually seen in association with parenchymal
consolidation or atelectasis.
 Lymphadenopathy can be the only manifestation of TB in young
children
 Adenopathy resolves slowly, and nodal calcification may occur six
months after the initial infection.
 Pleural effusion may occur in a minority of cases.

32. CHEST RADIOGRAPHY
Bilateral advanced pulmonary TB showing cavitary area in right upper lung.

33. CHEST RADIOGRAPHY
 Abnormalities often seen in
apical or posterior segments of
upper lobe or superior segments
of lower lobe.
 May have unusual appearance
in HIVpositive persons.
 Cannot confirm diagnosis of
TB!

34. CHEST RADIOGRAPHY
 No chest X-ray pattern is absolutely typical
of TB.
 10-15% of culture-positive TB patients not
diagnosed by X-ray.
 40% of patients diagnosed as having TB on
the basis of x-ray alone do not have active
TB.

35. SPECIMEN COLLECTION
Obtain 3 consecutive morning sputum specimens for
smear examination and culture and quantity of
sputum atleast 5ml.
Persons unable to cough up sputum
 induce sputum
 bronchoscopy
 gastric aspiration
Follow infection control precautions during specimen
collection.

36. SMEAR EXAMINATION
 Strongly consider TB in patients with smears
containing acidfast bacilli (AFB).
 Results should be available within 24 hours of
specimen collection.
 Presumptive diagnosis of TB.
 Not specific for M. tuberculosis since non
tuberculous mycobacteria may colonize the airway
and are increasingly recognized to cause clinical
illness in patients with underlying structural lung
disease.(MAC complex infection).

37. AFB SMEAR
Mycobacterium tuberculosis (stained red with
ZiehlNeelson stain) in sputum.

38. CULTURES

39. OTHER TESTS
Nucleic Acid Amplification Testing (NAAT-TB)
• not only detect M.tuberculosis but it also identifies
Resistance Markers (NAAT-R).
• Sensitivity/specificity high for smear positive specimens,
85-97% for both.
• Sensitivity fall in smear negative specimen to 66% so
should not be ordered in patients with low pretest
probability of mycobacterial infection.
 Pleural Fluid Adenosine Deaminase levels
• greater then (70 units/L) in a pleural fluid have approx
90% sensitivity and specificity for Pleural Tb.

40. TREATMENT

41. TUBERCULOSIS TREATMENT
 The standard "short" course treatment for tuberculosis (TB), is
isoniazid, rifampicin, pyrazinamide, and ethambutol for two months,
then isoniazid and rifampicin alone for a Minimum of additional four
months, with treatment to extend atleast 3 months beyond
documentation of coversion of sputum cultures to negative for
M.tuberculosis.
 For latent tuberculosis, the standard treatment is six to nine months of
isoniazid alone.
 If the organism is known to be fully sensitive, then treatment is with
isoniazid, rifampicin, and pyrazinamide for two months, followed by
isoniazid and rifampicin for four months. Ethambutol need not be
used.
 In pregnancy pyrazinamide should patient should receive isoniazid an
d rifampicin along with ethambutol for 4-8 weeks and if susceptibility
of INH and RMP is demonstrated then EMB can be discontinued and
INH and RMP may be given twice a week for a total of 9 months of
therapy.

42. DRUGS(1ST LINE)
 All first-line anti-tuberculous drug names have a
standard three-letter and a single-letter abbreviation
and Doses:
1. isoniazid is INH or H.
Dose: (5mg/kg Max: 300mg/dose)
2. rifampicin is RMP or R.
Dose: (10mg/kg Max:600 mg/dose)
3. ethambutol is EMB OR E.
Dose: (14.5-21.1 mg/kg Max: 1.6g/dose)
4. pyrazinamide is PZA or Z.
Dose: (18.2-26.3mg/kg Max: 2g/dose)
5. Streptomycin is STM or S.

43. SIDE EFFECTS OF 1ST LINE ATT.
 ISONIAZID :
 RIFAMPIN :
 Pyrazinamide :
 ETHAMBUTOL:
STREPTOMYCIN:
Peripheral neuropathy,
hepatitis, rash, mild CNS effect.
Hepatitis, fever, rash, flu like illness,GIT
Upset, bleeding problems,renal failure.
Hyperuricemia, hepatotoxicity, rash, GIT
upset, Joint aches.
Optic Neuritis(reversible with
discontinuance of drug; rare at
15mg/kg):rash.
8TH Nerve damage, nephrotoxicity.

44. DRUGS(2ND LINE)
 There are six classes of second-line drugs (SLDs) used for
the treatment of TB. A drug may be classed as second-line
instead of first-line for one of two possible reasons: it may
be less effective than the first-line drugs.
 aminoglycosides: e.g., amikacin (AMK), kanamycin(KM);
 polypeptides: e.g., capreomycin, viomycin,enviomycin;
 fluoroquinolones: e.g., ciprofloxacin (CIP), levofloxacin,
moxifloxacin (MXF);
 thioamides: e.g. ethionamide, prothionamide
 cycloserine (the only antibiotic in its class);
 p-aminosalicylic acid (PAS or P).

45. DRUGS(3RD LINE)
 considered "third-line drugs" not very effective or
because their efficacy has not been proven .
o Rifabutin is effective, but is not included on the WHO list
because for most developing countries, it is impractically
expensive.
1. rifabutin
2. macrolides: e.g., clarithromycin (CLR);
3. linezolid (LZD);
4. thioacetazone (T);
5. thioridazinea;
6. arginine;
7. vitamin D;
8. R207910.

46. DRUGS
Drug Resistent TB.
is resistent to one first line ATT either isoniazid or
rifampicin.
Multi-drug resistant TB (MDR-TB)
is defined as resistance to the two most effective first-
line TB drugs: rifampicin and isoniazid.
Extensively drug-resistant TB (XDRTB)
• is resistent to isoniazid,rifampicin plus
fluoroquinolones and atleast one of the three injectable 2nd
line drugs(amikacin, kanamycin and capreomycin).
• One special cocern for HIV positive person with XDRTB
is that in them mortality rate is very high.

47. MONITORING AND DOTS.
 DOTS stands for "Directly Observed Therapy,
Shortcourse“ and is a major plan in the WHO
global TB eradication programme.
 The DOTS strategy focuses on five main points of action.
1. These include government commitment to control TB.
2. diagnosis based on sputum-smear microscopy tests done
on patients who actively report TB symptoms.
3. direct observation short-course chemotherapy treatments.
4. a definite supply of drugs.
5. standardized reporting and recording of cases and
treatment outcomes.

48. PREVENTION
 TB prevention and control takes two parallel
approaches.
 In the first, people with TB and their
contacts are identified and then treated.
 Identification of infections often involves
testing high-risk groups for TB.
 In the second approach, children are
vaccinated to protect them from TB.

49. VACCINATION
 Many countries use Bacillus Calmette-Guérin (BCG)
vaccine as part of their TB control programs, especially for
infants. According to the W.H.O., this is the most often
used vaccine worldwide, with 85% of infants in 172
countries immunized in 1993.
 BCG provides some protection against severe forms of
pediatric TB
 unreliable against adult pulmonary TB,
 Currently, there are more cases of TB on the planet than at
any other time in history.
 urgent need for a newer, more effective vaccine that would
prevent all forms of TB—including drug resistant strains—
in all age groups and among people with HIV.