Tuberculosis (TB) is a chronic bacterial infection caused by Mycobacterium tuberculosis that typically forms granulomas in the lungs. It is treatable with a combination of anti-TB drugs over a 6-12 month period to kill both actively replicating and dormant bacilli. Diagnosis involves physical exam, chest x-ray, tuberculin skin test, and sputum culture. Risk factors include HIV infection, poverty, and crowded living conditions.

2. Definition
• A chronic bacterial infection caused by Mycobacterium
tuberculosis, usually characterized pathologically by the
formation of granulomas.
• The most common site of infection is the lung, but other
organs may be involved.
• TB is a bacterial infection treatable by anti-TB drugs.
• TB in many countries is compounded who have co-
infection with HIV .

3. Etiology
• TB is caused by tubercle bacilli which belong to the genus
Mycobacterium.
• These form a large group but only three relatives are obligate parasites
that can cause TB disease.
• The data show that M. tuberculosis was isolated in 99% of confirmed
cases.
• M.bovis in 0.4% and M. africanum in 0.5% that year.
• Mycobacterium species include :

4. • M. tuberculosis complex: M.tuberculosis, M. bovis. M. africanum
• Mycobacterium leprae: the cause of leprosy.
• Tuberculosis is caused by bacteria that spread from person to person
through microscopic droplets released into the air.
• This can happen when someone with the untreated, active form of
tuberculosis coughs, speaks, sneezes, spits.
• Although tuberculosis is contagious, it's not easy to catch

5. • You're much more likely to get tuberculosis from someone you live with
or work with than from a stranger.
• Most people with active TB who've had appropriate drug treatment
for at least two weeks are no longer contagious.
• HIV

6. SIGNSAND SYMPTOMS:
• Cough for 3 weeks or more/productive cough
• Sputum usually mucopurulent/purulent
• Haemoptysis
• Fever with night sweats
• Tiredness
• Weight loss
• Anorexia
• Malaise

7. TB Transmission
 TB is spread through tiny drops sprayed into the air when an infected
person coughs, sneezes or speaks, or another person breathes the air
into their lungs containing the TB bacteria.
 TB is not visible, and can only be seen under a microscope.
 TB droplets are more easily spread in areas with poor air circulation

8. Types of TB
• The lungs are the most common place for TB. This is known as
pulmonary TB.
• TB of the voice box is the second most common and is usually called
laryngeal TB.
• TB can infect the brain, kidneys, bones, and other areas.
• TB can also spread through the blood to other organs; this is called
miliary TB.

9. Cont.…
• TB infection of the lungs can fall into 2 categories of disease: Latent TB orActive TB.
• Latent TB means a person is infected by TB bacteria, but cannot infect others, and is
not coughing or appearing sick.
• Latent TB means the body’s immune system has contained the infection.
• Persons with latent TB are identified by a positive skin test (PPD).
• Persons who are not infected with Mycobacterium tuberculosis have a negative skin test
(PPD).
• When a person with a previously negative PPD, converts to a positive PPD, the conversion
indicates a recent infection with M. tuberculosis.

10. TB - Infection & Disease
Categories of TB - Active
• Active pulmonary and laryngeal TB means a person infected with the TB bacteria
is sick and can infect others unless they are taking medicine prescribed by their
physician to treat TB.
• Persons with active TB disease usually have some of the following symptoms: cough (
3 weeks or more), feel weak, have a fever, lose weight, experience night sweats,
cough up blood, or have chest pain when coughing.

11. RISK FACTORS:
The following are some of the risk factors of tuberculosis:
1. Low socio-economic status
2. Crowded living conditions
3. Disease that weakens immune system like HIV
4. Person or immunosuppressants like steroid health care workers
5. Migration from a country with a high number of cases
6. Alcoholism
7. Recent tubercular infections (within the last 2 years)

12. Pathophysiology

17. Diagnosis
1. Physical examination:
– Coughing
– Wheezing (Crackles)
– Swelling of lymph node (due to increasing T cell) in the neck and other
parts.
– Feeling uncomfortable during breathing.
2. Chest X-ray:
• Diagnose preliminary TB – to locate the infected area.
• Reactive TB (secondary TB due to reactivation of lesions).
– Diffuse nodules are present

18. 3. Mantoux skin test (Mst)/ Tuberculin skin test (TST):
• Purified protein derivative (PPD) obtained from mycobacterium 
administered in the skin.
• After 48 hours, observed skin.
• If skin raised bump over 0.2 inches (5mm)  MT is present.
• This test helps to identify people infected with M. tuberculosis but who have
no symptoms.

19. 4. Sputum test:
• Sputum is collected and a microscopic examination is done.
• Staining the gram –ve acid-fast bacilli  confirms TB diagnosis.
• Sputum or other body secretion can be cultured for the growth of mycobacteria
to confirm the diagnosis.
5. Quanti FERON TB gold test:
• PPD obtained from M. species administered into the blood.
• Immune system produce IFN - ɤ (interferon ɤ).
• This interferon ɤ is measured  raised level indicates TB
• It can detect TB in a person having no symptoms.

20. Treatment

21. FIRST-LINE DRUGS:
1. Isoniazid(H)
2. Rifampicin(R)
3. Pyrazinamide(Z)
4. Ethambutol(E)
5. Streptomycin(S)

22. 1. ISONIAZID:
MOA: Isoniazid inhibits biosynthesis of mycolic acid, which is an
essential component of the mycobacterial cell wall and results in the
death of bacteria (tuberculocidal). It is active against both intracellular
and extracellular bacilli.
ADRs: Peripheral neuropathy, hepatotoxicity, skin rashes, arthralgia, GI
disturbances, psychosis and rarely convulsions.
Dose: 5-10mg/kg or a maximum dose of 300mg/day

23. 2. RIFAMPICIN:
MOA: Rifampicin binds to the beta subunit of the DNA-dependent RNA
polymerase enzyme and inhibits m-RNA synthesis in the bacteria. It has a
bactericidal effect. It is active against both intracellular and extracellular
bacilli.
ADRs: Hepatotoxicity, GI disturbances, flu-like syndrome, headache,
drowsiness, dizziness, nausea, vomiting, hypersensitivity reactions etc.
Dose: 15-20mg/kg or a maximum dose of 450-600mg/day

24. 3. PYRAZINAMIDE:
MOA: Pyrazinamide is converted to its active form/active metabolite
pyrazinoic acid by the enzyme pyrazinamide present in the mycobacteria.
This metabolite may inhibit the synthesis of mycolic acid by the
mycobacteria. It requires an acidic pH (5.5) for its tuberculocidal activity.
ADRs: Dose-dependent hepatotoxicity, anorexia, nausea, vomiting,
fever, skin rashes, malaise, urticaria, arthralgia etc.
Dose: 25-40mg/kg or a maximum dose of 3g/day

25. 4. ETHAMBUTOL:
MOA: Ethambutol inhibits mycobacterial arabinosyl transferase (encoded
by emb gene) enzyme, which is involved in the polymerization reaction of
the arabinoglycan, an essential component of the mycobacterial cell wall. It
is tuberculostatic and acts on fast-multiplying bacilli in the cavities. It is
also effective against atypical mycobacteria (mutation of emb gene).
ADRs: Optic neuritis, hypersensitivity reactions like skin rashes, itching
etc., fever, arthralgia, GI disturbances, headache, mental disturbances etc.
Dose: 15-25mg/kg or a maximum dose of 800-1200mg/day

26. 5. STREPTOMYCIN:
MOA: It irreversibly inhibits bacterial protein synthesis in at least 3
ways:
1. Interference with the initiation complex of peptide formation.
2. Misreading of m-RNA, causes incorporation of incorrect amino acids
into the peptide, resulting in a non-functional or toxic protein.
3. Breakup of polysomes into non-functional monosomes.
ADRs: Dose-related ototoxicity, nephrotoxicity, ataxia, vertigo, rashes,
fever, renal impairment etc.
Dose: 15mg/kg or a maximum dose of 0.75-1gm/day

27. SECOND-LINE DRUGS:
1. Ethionamide
2. Cycloserine
3. Para-amino salicylic acid
4. Rifabutine and rifapentine
5. Fluoroquinolones: ciprofloxacin, levofloxacin, moxifloxacin,
ofloxacin
6. Injectable drugs: capreomycin, kanamycin, amikacin
7. Newer drugs: bedaquiline, pretomanid

28. 1. ETHIONAMIDE:
MOA: Ethionamide upon oxidation with catalase-peroxidase is
converted to an active acylating agent, ethionamide sulfoxide, which in
turn activates inhA enoyl reductase and hence inhibits the synthesis of
mycolic acids. It is a tuberculostatic drug that is effective against both
intracellular and extracellular organisms.
ADRs: Intense gastric irritation, optic neuritis, hepatotoxicity.
Dose: 15mg/kg or a maximum dose of 0.75-1g/day

29. 2. CYCLOSERINE:
MOA: It inhibits the incorporation of D-alanine into peptidoglycan
pentapeptide by inhibiting the enzyme alanine racemase, which
converts L-alanine to D-alanine and finally inhibits mycobacterial cell
wall synthesis (tuberculostatic).
ADRs: CNS dysfunction including depression and psychosis, peripheral
neuropathy, seizures, tremors etc.
Dose: 15mg/kg or a maximum dose of 1g/day

30. 3. PARA-AMINO SALICYLIC ACID (PAS):
MOA: It is structurally similar to P-amino benzoic acid (PABA) and
sulfonamides. It shows similar action of sulphonamide. PAS inhibits
folate synthase enzyme, which is essential for the conversion of PABA
to dihydro folic acid (DHFA) and inhibits the synthesis of cell walls
(tuberculostatic activity).
ADRs: GI effects like nausea, anorexia, epigastric pain, diarrhoea,
fever, joint pain, hepatosplenomegaly, hepatitis, granulocytopenia,
adenopathy, peptic ulcers, gastric haemorrhage etc.
Dose: 200mg/kg or a maximum dose of 10-12g/day

31. 4. RIFABUTINE & RIFAPENTINE:
MOA: They are derived from rifamycin and related to rifampicin & show a
similar mechanism of action of rifampicin i.e., bacterial RNA polymerase
enzyme inhibitors. These are weak enzyme inducers of CYT P450 enzymes.
ADRs: Hepatotoxicity, GI disturbances, flu-like syndrome, nausea,
headache, vomiting, drowsiness, dizziness, hypersensitivity reactions etc.
Dose: 300mg/day

32. 5. FLUOROQUINOLONES:
MOA: They are active against typical and atypical mycobacteria. They
inhibit bacterial DNA synthesis by inhibiting bacterial topoisomerase-II
(DNA gyrase) and topoisomerase-IV. They have tuberculocidal activity.
ADRs: Nausea, vomiting, diarrhoea, headache, dizziness, skin rashes,
photosensitivity, damage growing cartilage, tendon rupture, insomnia
etc.
Dose:
• Ciprofloxacin-750mg, BD, PO
• levofloxacin-500mg, OD, PO
• Moxifloxacin-400mg, OD, PO
• Ofloxacin-400mg, BD, PO

33. 6. INJECTABLE DRUGS:
MOA: These are aminoglycosides and their mechanism of action
is similar to streptomycin.
ADRs: Ototoxicity, nephrotoxicity, fever, rashes etc.
Dose:
• Capreomycin-15mg/kg or a maximum dose of 0.75-1g/day
• Kanamycin-15mg/kg or a maximum dose of 0.75-1g/day
• Amikacin-15mg/kg or a maximum dose of 1g/day

34. 7. NEWER DRUGS:
a) BEDAQUILINE:
MOA: Bedaquiline binds to oligomeric and proteolipid subunit-c of
mycobacterial ATP synthase, leading to the inhibition of ATP synthesis
and death of bacteria (tuberculocidal).
ADRs: Increased QT interval, abnormal and fatal heart rhythm
(increased risk of death), nausea, joint pain, headache and increased liver
enzymes.
Dose: 100mg oral

35. b) PRETOMANID:
MOA: It is a bicyclic nitroimidazole-like molecule. It is active against
both replicating and non-replicating organisms. It inhibits mycolic acid
synthesis through unknown molecular mechanisms and inhibits cell wall
synthesis (like isoniazid).
ADRs: No ADRs are noticed. It is relatively safe, well-tolerated and
efficacious.
Dose: 100-200mg/day

36. TREATMENT REGIMEN:
The recommended standard regimen for respiratory and most other
forms of tuberculosis in the UK is:
1. Rifampicin, Isoniazid, Pyrazinamide and Ethambutol for the initial 2
months (initial phase).
2. A further 4 months of Rifampicin and Isoniazid (continuous phase).

37. Contd...
• INITIATION PHASE
• 2-3 months
• 4-5 drugs
• Rapidly kills bacilli
• Isoniazid
• Rifampicin
• Ethambutol
• Pyrazinamide
• CONTINUOUS PHASE
• 4-6 months
• 2-3 drugs
• Eliminates remaining bacilli
• Prevents relapse
• Isoniazid + pyridoxine
• Rifampicin

38. DIRECTLY OBSERVED THERAPY (DOT):
 DOT, where the patient is observed taking their anti-tuberculous
medication by a health care professional.
 But it is not needed for more cases of active TB. A risk assessment
for treatment adherence should be undertaken in all patients and DOT
regimens considered where non-adherence to treatment might be a
problem.
• e.g. In the street or shelter-dwelling homeless people with active TB
and in patients with a history of non-adherence (individuals with
chronic alcohol or other social problems).
• Advantages: High cure rate, decreased drug resistance, ADRs
can be monitored

39. • Multi Drug-resistant TB: it is caused by bacteria that are resistant to
at least isoniazid and rifampicin., the most effective anti-TB drugs.
• These results from either primary infection with resistant bacteria or
may develop in the course of the patient’s treatment.
• XDR-TB is a form of Tb caused by bacteria that are resistant to
isoniazid and rifampicin as well as fluoroquinolone and any second
line anti TB inject able drugs including amikacin, kanamycin or
capreomycin.