TUBERCULOSIS
Dr. Mohammed Farouq
ETIOLOGY
Mycobacterium tuberculosis
Mycobacterium avium
Mycobacterium bovis [rare]
CHARACTERISTICS
curved rods
obligate aerobes
acid-fastness
EPIDEMIOLOGY
High Risk Factors:
– Infants
– overcrowding and bad hygiene
– Immunosuppresive states
lymphoma
viral illness: measles, HIV
drugs eg. steroids
TRANSMISSION
Person to person
Inhalation of
contaminated
droplets from an
infected adult
INCUBATION PERIOD
2 - 8 weeks
INFECTIVITY (source of infection)
Adolescents and adults
Young children (rare)
– Tubercle bacilli are sparse in the
endobronchial secretions
– cough is weak or absent
CLINICAL MANIFESTATIONS
INFECTION (Latent TB Infection)
Preclinical stage of infection
– No clinical features
– Normal CXR
– PPD-positive only
DISEASE (Active TB)
Clinicalmanifestations are present
(Symptoms and signs or chest x-ray
findings)
Pulmonary Disease
Primary Pulmonary Disease
Hilar adenopathy
Primary (‘Ghon’)complex
Parenchymal focus
– 70% subpleural
– Localized, nonspecific infiltrate
Regional lymphadenitis
– hilar adenopathy
– Asymptomatic
– Nonproductive cough and mild dyspnea
– Some infants have failure-to-thrive
Complicated Primary Pulmonary Disease
Parenchyma
Progressive Primary Pulmonary Disease
High fever
severe cough with sputum production
weight loss, and night sweats ( common)
diminished breath sounds, crepitations
Complicated Primary Pulmonary Disease
Regional lymph nodes
Tracheobronchial lymph node disease
– focal hyperinflation wheezing
– atelectasis
Endobronchial disease
– collapse-consolidation or segmental tuberculosis
Complicated Primary Pulmonary Disease
Pleural Effusion
6-12 months after the infection
usually > 6 years
Asymptomatic local pleural effusion with
primary disease
Larger effusions occur later
radiographic resolution often takes months.
The tuberculin skin test is positive in 70–80%
of cases
The prognosis is excellent
Reactivation Tuberculosis
Rare in children, localized to the lungs (upper lobes)
Fever, malaise, weight loss, night sweats, productive
cough, chest pain
Physical examination findings usually are minor or
absent,
Highly contagious
Systemic Disease
Miliary tuberculosis
2–6 mo after the primary infection
common in infants and young children
onset is insidious or acute
anorexia, weight loss
low-grade fever later high
lymphadenopathy &hepatosplenomegaly(50%)
progressive pulmonary disease
– (respiratory distress, pneumothorax,
pneumomediastinum)
Miliary tuberculosis
meningitis(20–40%)
Choroid tubercles occur in 13–87%
tuberculin skin test is nonreactive in up to
The
40%
Early sputum or gastric aspirate cultures have
a low sensitivity.
Biopsy of the liver or bone marrow offer better
yield
Adenopathy
TB adenitis
within 6–9 months
– tonsillar, anterior cervical, submandibular, and
supraclavicular nodes
– epitrochlear, axillary, inguinal
early: firm, discrete, nontender
later: matting, feel fixed to underlying or
overlying tissue
The tuberculin skin test is usually reactive.
The chest radiograph is normal in 70% of cases.
Culture of lymph node tissue yields the organisms in
about 50%
TB adenitis
Differential diagnosis
– pyogenic infection
– nontuberculous mycobacteria (NTM)
– cat-scratch disease
– Toxoplasmosis
– Tumor
– branchial cleft cyst
– cystic hygroma
CNS Disease
Meningitis
Common in children between 6 mo and 4 yr
of age.
Gradual onset.
Lethargy, headache, vomiting, seizures.
Cranial nerve palsies, focal neurologic signs.
decerebrate posturing, death.
Meningitis
The tuberculin skin test is nonreactive in up
to 50%
20–50% of children have a normal chest
radiograph
CSF analysis
– Leukocyte count 10 to 500 cells/mm3
(lymphocytes)
– Glucose less than 40 mg/dl
– Protein level is elevated
Tuberculomas
The tuberculin skin test is usually reactive
Chest radiograph is usually normal
Surgical excision
Corticosteroids
CT scan or MRI of the brain
Angiographic studies (avascular)
Other Systems
Abdominal T.B
– Peritonitis
– Mesenteric adenitis: obstruction, perforation
– malabsorption, fistula formation,
Bone and Joint Disease
– spine Pott’s disease
– Hip, knee
Cutanenous
Ocular
DIAGNOSIS
History
Physical examination
Tuberculin Skin Tests
( Mantoux tuberculin skin test)
Demonstration of Acid Fast Bacilli
– (Ziehl-Neelsen stain)
Culture
– sputum/gastric washings
– Pleural fluid, CSF, urine
– Biopsy material
DIAGNOSIS
Radiological Examination
– CXR, CT, MRI, IVP
Increased ESR, anemia, lymphocytosis
QuantiFERON (LTBI)
POLYMERASE CHAIN REACTION (PCR)
employs a DNA probe
only for smear-positive respiratory tract
secretions
sensitivity is similar to that for culture.
Classification System for TB
Class Type Description
0 No TB exposure No history of exposure
Not infected Negative reaction to tuberculin skin test
1 TB exposure History of exposure
No evidence of infection Negative reaction to tuberculin skin test
2 TB infection Positive reaction to tuberculin skin test
No disease Negative bacteriologic studies (if done)
No clinical, bacteriological, or radiographic
evidence of active TB
3 TB, clinically active M. tuberculosis cultured (if done)
Clinical, bacteriological, or radiographic
evidence of current disease
4 TB History of episode(s) of TB
Not clinically active or
Abnormal but stable radiographic findings
Positive reaction to the tuberculin skin test
Negative bacteriologic studies (if done)
and
No clinical or radiographic evidence of
current disease
5 TB suspected Diagnosis pending
Tuberculin Skin Test (PPD)
intradermal injection of 0.1 ml.
Containing 5 tuberculin units (TU) of purified
protein derivative (PPD) stabilized with Tween
80.
The amount of induration in response to the
test should be measured by a trained person
48–72 hr.
PPD-Host-related Factors
Very young age.
Malnutrition.
immunosuppression.
Overwhelming tuberculosis.
Corticosteroid therapy.
10%-50% of those with meningitis or
disseminated disease.
Poor technique or misreading the results.
False-positive reactions
cross-sensitizationto antigens of
nontuberculous mycobacteria (NTM)
Previous vaccination with BCG( 5 mm Induration POSITIVE
For adults and children at the highest risk of infection
– recent contact with infectious persons
– clinical illnesses consistent with
tuberculosis
– HIV infection or other immunosuppression
Interpretation Of The PPD Skin Test
>10 mm Induration Positive
children less than 3 yr of age
Interpretation Of The PPD Skin Test
>15 mm Induration -> Positive
For low-risk persons, especially those residing in
communities where the prevalence of tuberculosis is low
Administering the Tuberculin Skin Test
• Inject intradermally 0.1 ml of 5
TU PPD tuberculin
• Produce wheal 6 mm to 10 mm
in diameter
• Do not recap, bend, or break
needles, or remove needles from syringes
• Follow universal precautions for infection control
Reading the Tuberculin Skin Test
• Read reaction 48-72 hours after
injection
• Measure only induration
• Record reaction in millimeters
TREATMENT
USE MULTIPLE DRUGS
Bactericidal Drugs
– Isoniazid,
– rifampin,
– Streptomycin
– Pyrazinamide
Bacteriostatic Drugs
– ethambutol at low doses
– ethionamide
– cycloserine
ISONIAZID (INH).
daily dose of 10 mg/kg
metabolized by acetylation in the liver
– Peripheral neuritis
– Hepatotoxicity
– increase phenytoin levels
– interacts with theophylline
– hemolytic anemia in patients with glucose-6-
phosphate dehydrogenase deficiency
– lupus-like reaction with skin rash and arthritis.
RIFAMPIN (RIF)
orange discoloration of urine and tears
gastrointestinal disturbances
hepatotoxicity
thrombocytopenia
influenza-like syndrome
render oral conceptives ineffective
interacts with several drugs, including quinidine, sodium
warfarin, and corticosteroids
PYRAZINAMIDE (PZA)
30 mg/kg/24 hr
– Arthralgias
– arthritis, or gout
– hepatotoxicity
STREPTOMYCIN (STM).
given intramuscularly
when initial INH resistance is suspected
when the child has a life-threatening form of tuberculosis
– Toxicity to the vestibular and auditory portions
of the 8th cranial nerve.
– Renal toxicity
contraindicated in pregnant women
ETHAMBUTOL (EMB)
25 mg/kg/24 hr EMB has some bactericidal activity
treatment of drug-resistant disease
– optic neuritis
OTHER DRUGS
Aminoglycosides (kanamycin and amikacin)
Capreomycin
Cycloserine
Ciprofloxacin and ofloxacin are fluoroquinolones
Pulmonary tuberculosis
6 mo of INH and RIF
supplemented during the first 2 mo by PZA
administration be directly observed
If community rate of INH resistance > 5–10%
– add a 4th drug— STM, EMB, or ETH
Extrapulmonary tuberculosis
same as for pulmonary tuberculosis
9–12 mo
– bone and joint tuberculosis
– Tuberculous meningitis
Drug-Resistant Tuberculosis
Types of drug resistance
– Primary resistance
– Secondary resistance
Treatment For Drug-Resistant
Tuberculosis
at least three and usually four or five drugs
should be administered initially
for INH-resistant tuberculosis
– Treat for 9 months with RIF, PZA, and EMB
INH and RIF resistance are present
– Treat for 12–18 months
Corticosteroids
tuberculous meningitis
endobronchial tuberculosis
pericardial effusion
pleural effusion
severe miliary tuberculosis
prednisone 1–2 mg/kg/24 hr in 1–2 divided doses for 4–
6 wk with gradual tapering.
Supportive Care
Adequate nutrition
REGULAR FOLLOWUP
TREATMENT OF LTBI
9 mo of daily INH therapy
PREVENTION
Bacille Calmette-Guérin Vaccination
intradermal injection
– Local ulceration
– regional suppurative adenitis occur in 0.1–1%
– Osteitis is a rare
– disseminated BCG infection
BCG is 50%–80% effective in disseminated and
meningeal tuberculosis