2. TUBERCULOSIS
DEFINITION:
• Tuberculosis is defined as a highly contagious disease caused by the
bacterium called Mycobacterium.
• TB is more common in people with immune system problems , such as
AIDS, than in general population.
3. AETIOLOGY
It is caused by tubercle bacilli, which belong to the genus Mycobacterium.
Mycobacterium species include:
M. tuberculosis
M. bovis
M. africanum
INCUBATION PERIOD
The incubation period from infection to demonstrable primary lesion or significant tuberculin reaction
ranges from 2-10 weeks.
Latent infection may persist for lifetime.
4. TYPES
Latent TB: This refers to the condition when a person has TB infection but
the bacteria remains inactive in the body and causes no symptoms. Latent
TB is not contagious but has a chance of becoming active.
Active TB: This refers to the condition when TB bacteria multiply in the body
and develop symptoms of TB. If the lungs are infected the infection can be
spread easily.
5. TRANSMISSION:
Transmission occur through exposure to tubercle bacilli in air borne droplet
nuclei produced in people with pulmonary or respiratory tract TB during
expiratory efforts such as coughing or sneezing.
In general, only respiratory forms of TB are infectious.
FACTORS INCREASING RISK OF ACTIVE TB:
o HIV positive
o Injecting drug users
o Solid organ transplantation
o CKD or receiving haemodialysis
o Receiving anti-TNF alpha treatment
o Silicosis
6. DRUG RESISTANT TB:
MDR-TB
It is caused by bacteria that are resistant to at least isoniazid and rifampicin, the most effective
anti-TB drugs.
MDR-TB results from either primary infection with resistant bacteria or may develop in course of a
patient’s treatment.
XDR-TB
It is a form of TB caused by bacteria that are resistant to isoniazid and rifampicin, that is, MDR-TB, as
well as any fluroquinolone and any of the second line anti-TB injectable drugs including amikacin,
kanamycin or capreomycin (WHO,2010).
7. DIAGNOSIS:
Symptoms:
Cough for 3 weeks or more
Sputum usually mucopurulent or purulent
Haemoptysis not always a feature
Fever may be associated with night sweats
Tiredness
Weight loss
Malaise
CLINICAL DIAGNOSIS
Microbiological: Direct microscopy of sputum is the simplest and quickest method by looking for acid-fast
bacilli. A minimum of 3 sample one of which should be early morning should be collected.
8. TUBERCULLIN TESTING
It is used to detect latent TB. The standard test consist of an intradermal
injection
Of 2TU of Stanens Serum Institute (SSI) tuberculin RT23 in 0.1 ml solution for injection.
The results are read 48-72hrs later.
A diameter of induration of less than 6mm is negative.
An induration of between 6 and 15mm may be due to previous TB infection or BCG vaccination.
An induration of more than 15mm is strongly suggestive of TB infection or disease.
CHEST RADIOGRAPHY
Cavitation may be seen , the incidence can vary between 10% and 30%.
9. DRUG CLASSIFICATION:
First line
drugs
Second line drugs
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
Fluoroquinolones Other oral drugs Injectable drugs
Ofloxacin
Levofloxacin
Moxifloxacin
Ciprofloxacin
Ethionamide
Prothionamide
Cycloserine
Terizidone
Paraamino-
salicylic acid
Rifabutin
Thiacetazone
Kanamycin
Amikacin
Capreomycin
ANTITUBERCULAR DRUGS
10. TREATMENT:
The recommended standard treatment regimen for respiratory and most other
forms of TB are:
Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol for the initial 2 months (initial
phase).
A further 4 months of Rifampicin and Isoniazid (continuation phase).
A longer period of treatment than the standard 6 month is needed for meningeal TB and
where there is direct spinal cord involvement.
DOTS (Directly observed therapy) : The treatment of a TB infected patient in the direct
observation of a physician or nurse.
11. Pregnancy:
Standard therapy should be given , although streptomycin should not be used as it may
be ototoxic to fetus.
Renal disease:
Patients with renal disease may be given AKT-4 as these drugs are predominantly
eliminated by non-renal routes. Ethambutol undergo extensive renal elimination and therefore dose
reduction is needed.
Liver disease:
Monitoring of liver enzymes is recommended in patients with liver failure or
alcoholics because rifampicin, isoniazid and pyrazinamide are all potentially hepatotoxic.
TREATMENT OF TB IN SPECIAL CIRCUMSTANCES:
TB in children:
Ethambutol should not routinely be used in young children who could be unable to report
visual disturbances.
12. MECHANISM OF ACTION
a) ISONIAZID (INH)
INH
Reactive metabolite Forms adduct with NADP Inhibit DHF
R’ase
Forms adduct with NAD
Inhibit
DNA
Inhibit InhA and KasA
synthesis
Inhibit mycolic acid synthesis
Inhibit cell wall synthesis
Catalase peroxide
13. b) RIFAMPICIN
Rifampicin interrupts RNA synthesis by binding to beta subunit of mycobacterial DNA-
dependent RNA polymerase.( encoded by rpoB gene), the mammalian RNA polymerase does not
bind to rifampicin.
c) PYRAZINAMIDE
It is chemically similar to INH, it is converted to an active metabolite pyrazinoic acid
encoded by pncA gene .This get accumulated in acidic medium and inhibit mycolic acid synthesis.
d) ETHAMBUTOL
Ethambutol inhibits arabinosyl transferases (encoded by embAB gene) involved in
arabinogalactan synthesis thereby interfering with mycolic acid incorporation in cell wall.
14. ADVERSE REACTION:
Rifampicin: It is usually well tolerated.
Gastro-intestinal upset, fever and rash can occur.
It will colour the urine orange-red with approximately 4 h of a dose.
Isoniazid: Fever, skin rashes and dose dependent peripheral neuropathy.
Peripheral neuropathy is probably due to depletion of vit. B6 , hence
pyridoxine supplementation at a dose of 10-25mg/day is given.
Pyrazinamide: Can cause hepatitis.
Ethambutol: Ocular toxicity is the most important side effect.
15. Inhalation of droplet infected with M.tuberculoisis
Enters the upper airways
Primary defense mechanism gets activated
Mucus producing goblet cells and cilia tries to push the
microorganism out ( but fails)
M . tuberculosis enters the alveoli
Alveolar macrophages engulf the microorganism (phagocytosis)
PATHOPHYSIOLOGY