MYCOBACTERIUM TUBERCULOSIS Flashcards
INTRODUCTION
Mycobacterium tuberculosis complex:
1Mycobacterium tuberculosis
2Mycobacterium africanum
3Mycobacterium bovis
4Mycobacterium canettii
5Mycobacterium microti
6Mycobacterium caprae
Obligate aerobe
Non-spore-forming
Non-motile rod
Lipid rich cell wall contains mycolic acid—50% of cell wall dry weight
Diseases by M.tb
++Tuberculosis
—Pulmonary
Primary
Post-primary
—Extrapulmonary
1.Miliary
2.TB Spine (pott)
3.Genitourinary TB
4.TB meningitis
5.TB peritonitis
6.GIT TB
7.Cutaneous TB (Scrofuloderma)/TB 8.lymphadenitis (scrofula)
9.TB pericarditis
TRANSMISSION
—Transmission is AIRBORNE
Droplet nuclei are spread by coughing, sneezing, or speaking.
The tiny droplets dry rapidly; the smallest (<5µm) may remain suspended in the air for several hours and may reach the terminal air passages when inhaled.
—There may be as many as 3000 infectious nuclei per cough
RISK FACTORS
- Immunosuppression (HIV, Haematological malignancies, Immunosuppressive medication)
- Chronic diseases (Diabetes mellitus, chronic kidney disease)
- Co-habitation with an active case of TB
Healthcare workers - Drug/alcohol abuse
- Travel to endemic regions
PATHOGENESIS
—Inhalation of droplet nuclei
—Engulfed by alveolar macrophages
—Replicate within macrophages for 2-3 weeks
—Primary pulmonary tuberculosis
Primary tuberculosis is the form of disease that develops in a previously unexposed and therefore unsensitized, person. Clinically significant disease develops in about 5% of newly infected people
-Usually exogenous
-The initial focus is usually subpleural and in the midlung zone (the lower parts of the upper lobes and the upper parts of the lower and middle lobes)
-Infected macrophages are carried by lymphatics to regional (hilar, mediastinal, and sometimes supraclavicular or retroperitoneal) lymph nodes-Ghon complex
-Ranke complex (parenchymal and mediastinal calcific foci).
-tiny calcific deposits (Simon’s foci)
-Simulates acute bacterial pneumonia with consolidation of the lobe, hilar adenopathy, and pleural effusion
-Lymphohematogenous dissemination following primary infection may result in the development of tuberculous meningitis and miliary tuberculosis
-In 95% of cases, infection is contained, no apparent disease
-Granuloma become dormant and sealed off by scar tissue
—latent tuberculosis infection
Surviving bacilli may reactivate years later—-secondary infection
-Erosion of granuloma and surrounding tissue
-The greatest known risk factor for progression of latent infection to active tuberculosis is HIV infection
-Bacilli spread through air passages from cavities to other parts of the lung
-reactivation tuberculosis
-Endogenous
-Apical-posterior localization with a tendency to cavitation and progression
-These lesions may undergo caseation, liquefaction, fibrosis, and frequently cavity formation, and bronchogenic spread
-Spread beyond the pulmonary system – direct, haematogenous, lymphatic
extrapulmonary tuberculosis
-Lymphadenitis is the most frequent presentation of extrapulmonary tuberculosis, usually occurring in the cervical region (“scrofula”)
CLINICAL FEATURES
Primary pulmonary TB
-⅔ are asymptomatic
-Symptoms mild, including low-grade fever
Radiography – hilar adenopathy
Pleural effusion, consolidation
Reactivation TB
-90% of TB cases in adults
-Fever, cough, weight loss, night sweats
Chest pain, dyspnea, haemoptysis
-CXR- Apical-posterior lung infiltrates, effusions, hilar adenopathy
-5% with active PTB have normal CXR
INVESTIGATIONS AND DIAGNOSIS
A.Latent TB
1.Positive result on either
Tuberculin Skin Test (TST) or
2.Interferon gamma release assay (IGRA)
In absence of features of active TB
B.Active TB
Established by a combination of
1.Epidemiological (exposure, travel, contact)
2.Clinical (chronic cough, weight loss, etc)
3.Radiographic (infiltrates, cavitation , etc)
4.Microbiological (sputum smear, culture, etc)
5.Histopathologic (caseating granuloma)
FOCUSING ON 5 INVESTAGATIVE MEASURES (1ST 2 FOR LATENT AND 3 FOR ACTIVE)
1.)Tuberculin skin test/ Mantoux test
—Intradermal 0.1ml of 5 Tuberculin units of Purified Protein Derivative (PPD) into the volar surface of the forearm
-PPD invokes a delayed hypersensitivity reaction
—Diameter of induration is measured after 48 – 72 hours
—Induration of 5 – 15 mm is interpreted as positive depending on clinical risk factors
5mm or more :– Positive for
-HIV positive patient
-Recent contact of TB case
—10mm or more: positive for
-Recent arrivals (< 5yrs) from high prevalent countries
-Injection drug users
—15mm or more: Positive for
Person with no known risk factor for TB
[Mantoux test interpretation]
>False positive can result from
-BCG vaccination
-Infection with non-tuberculous mycobacteria
-Tampering with injected area :- swelling
> False negative from
-HIV
-Steroid use
-Malnutrition
-Sarcoidosis
-CKD
Mantoux test interpretation
Positive Mantoux test without features of active TB suggests Latent TB infection
2) Interferon gamma release assay (IGRA)
>Advantages of IGRA over Mantoux test<
1.) Differentiates M.tuberculosis infection from previous BCG vaccination and most non-tuberculous mycobacteria
2.) Single visit (as opposed to Mantoux which requires patient to come back after 48-72 hours)
3) Chest radiography
Indicated for all persons being investigated for latent TB infection and active TB
Active PTB:- 1.infiltrates, 2.cavitation, 3.fibrosis, 4.hilar and mediastinal lymphadenopathy, 5.lesions (miliary), 6.pleural effusions, 7.tuberculoma etc
4) Smear microscopy for ATB
Can be carried out on all clinical specimens
—The most rapid and inexpensive method of TB diagnosis
Methods include
A.) Carbolfuchsin method (e.g. Zeihl-Neelsen, Kinyoun)
B.) Fluorochrome method
T.B.C
Zeihl-Neelsen (ZN) staining technique & CULTURE
- Heat-fix the dried smear
- Cover the smear with carbol fuchsin stain.
- Heat the stain until vapour just begins to rise (i.e. about 60 C). Do not overheat. 4. Allow the heated stain to remain on the slide for 5 minutes.
- Wash off the stain with clean water.
- Cover the smear with 3% acid alcohol for 5 minutes or until the smear is sufficiently decolorized, i.e. pale pink
- Wash well with clean water.
- Cover the smear with malachite green stain for 1–2 minutes
- Wash off the stain with clean water.
10.Wipe the back of the slide clean, and place it in a draining rack for the smear to air-dry (do not blot dry). - Examine the smear microscopically, using the x100 oil immersion objective.
B) Fluorochrome method (ADVANTAGES)
1.easy to perform
2.cost effective
3.rapid detection of acid-fast bacilli in clinical specimens
4.can be viewed at lower magnification
- CULTURE
—Gold standard for laboratory confirmation of TB
—Culture media include
Egg based (Lowenstein-Jensen, Petragnani)
—Growth is faster in liquid media and allows detection in 1-3 weeks
—Samples of sputum or tissue require((Decontamination, Liquefaction, Centrifugation and Neutralization)
1. initial decontamination remove fast-growing non-mycobacterial organisms
2. Liquefaction to allow access of decontaminants to nonmycobacterial organisms and media nutrients to surviving mycobacteria.
3. N-acetyl-L-cysteine in 1% sodium hydroxide solution
4.Centrifugation for concentration
5. Neutralization by buffer
TREATMENT
First-line drugs
-Isoniazid
-Rifampicin
-Ethambutol
-Pyrazinamide
Second-line drugs
-aminoglycosides
-polypeptides
-Fluoroquinolones
Third line drugs
Rifabutin
Macrolides
—Primary resistance: occurs in persons who do not have a history of previous treatment and these individuals are initially infected with resistant organisms.
—Secondary resistance: occurs during therapy for TB, either because the patient was treated with an inadequate regimen or because the patient did not take the prescribed regimen appropriately (non adherence).
—Multidrug resistant TB (MDR-TB) – resistant to at least Isoniazid and Rifampicin
—Extensively drug resistant TB (XDR-TB) – resistant to at least Isoniazid and Rifampicin, a Quinolone, and one of the 2nd line injectables (amikacin, kanamycin, capreomycin)
—Treatment is with Pretomanid, bedaquiline and linezolid (Nix-TB)
