Properties

Pathogenesis

Clinical findings

Laboratory diagnosis

Treatment & Prevention

Mycobacteria tuberculosis

Obligate aerobe

Not seen in Gram stains.

Acid-fast bacilli: Ziehl Neelsen stain – carbol fuchsin stains bacteria red.

Grows slowly on Lowenstein Jensen medium.

Mycolic acid in cell wall.

Resistant to dehydration, acids and alkalis.

No animal reservoir; transmitted by respiratory aerosols.

Produces no exotoxins and does not contain endotoxin in its cell wall.

Primary infection:

- initial site of infection is in lung.

- taken up by alveolar macrophages in which they replicate.

- acute inflammatory response produces exudative lesions, which together with the draining lymph nodes, formed a Ghon complex.

Granulomatous lesions:

- after about 10 cells, T cell clones react to mycobacterial antigens expand & inflitrate lesions.

- granulomas: a central area of giant cells containing tubercle bacilli surrounded by a zone of epithelioid cells.

- a tubercle is a granuloma surrounded by fibrous tisue that has undergone central caseous necrosis.

- mycobacteria are not killed, merely walled off within granulomas which become surrounded with fibrosis & may calcify.

Primary lesions usually occur in lower lobes, whereas reactivation lesions usually occur in apices.

Spread of organism:

- erosion of tubercle into a bronchus, empty its caseous contents & spread the organism to other parts of lungs, to GI tract if swallowed, & to other persons.

- disseminate via bloodstream to many internal organs.

Disease: tuberculosis

Primary tuberculosis is usually asymptomatic, however in a minority of patients, the infection is not controlled by may lead to:

- progression of primary lung lesion.

- spread to pleural cavity with effusion.

- spread via bloodstream: meningitis, genitourinary tract including kidney infection, bone & joint, peritonitis.

- lymph nodes infected & enlarge especially in the neck.

Secondary tuberculosis:

- occurs many years after primary infection.

- precipitating factors: old age, diabetes, HIV, immunocompromised.

- upper parts of lungs are affected – cavitation caused by destruction of lung tissues.

- insidious fever.

- night sweats

- weight loss

- productive cough with blood-streaked sputum.

- hemoptysis.

- fatigue.

Miliary tuberculosis:

- myraid minute foci of infections in many organs: liver, bone marrow, spleen & kidneys.

- mycobacteria are widely disseminated via the bloodstream and granulomas grow all over the body.

Less common presentations:

- pneumonia not responsive to antibiotics.

- pyrexia of undetermined origin.

- neurological disease.

- paraplegia (spinal TB)

- ascites

- unexplained anemia

- chronic diarrhea

Hypersensitivity reactions: erythema nodosum.

Tuberculin skin test:

- due to delayed hypersensitivity reaction.

- assess immune status of patient.

- inject an extract of tubercle bacillus called purified protein derivative (PPD) into skin (Mantoux test).

- 5 tuberculin units is usually used.

- test is positive if 10mm of induration occurs 48-72 hours after intradermal injection.

- AIDS: a 5mm reaction is considered positive.

- positive results correlate with previous infection & with BCG immunization.

- negative reaction does not exclude tuberculosis.

Acid-fast staining of sputum is initial test.

For rapid screening, auramine stain, visualized with fluorescence microscopy  is used.

Culture:

- treatment with NaOH.

- material cultured on special media.

- organism identified by biochemical tests.

Luciferase assay detects drug-resistant organism.

First-line drugs:

- streptomycin

- isoniazid

- ethambutol

- rifampicin

- pyrazinamide

Second-line drugs:

- ethionamide

- amikacin

- ofloxacin

- cycloserine

Treatment regime:

- use of isoniazid, rifampicin, pyrazinamide.

- isoniazid & rifampin given for 6 months.

- pyrazinamide treatment stopped after 2 months.

- immunocompromised & AIDS patients: ethambutol is added & all 4 drugs given for 9-12 months.

Noncompliance of patients is major factor in allowing resistant organisms to survive.

Chemoprophylaxis with isoniazid for 6-9 months prescribed for:

- asymptomatic patients with positive PPD skin test.

- children exposed to patients with tuberculosis.

- immunocompromised patients with positive PPD skin test.

Prevention:

- BCG vaccine: live attenuated stain of M.bovis induces partial resistance.

- pasteurization of milk & destruction of infected cattle.

- isolation of infected patients.

Mycobacteria leprae

Not been grown artificial media or cell culture.

Optimal temperature for growth is 30C.

Grows preferentially in skin & superficial nerves.

Infection is acquired by prolonged contact with patients with lepromatous leprosy, who discharge M.leprae in large numbers in nasal secretions & from skin lesions.

Common in developing countries where over-crowding and poor hygiene are prevalent.

Organisms replicates intracellulary within:

- skin histiocytes.

- endothelial cells.

- Schwann cells of nerves.

Tuberculoid leprosy:

- cell-mediated response limits organism’s growth.

- very few acid-fast bacilli seen.

- granulomas containing giant cells form.

Lepromatous leprosy:

- cell-mediated response is poor.

- skin & mucous membrane lesions contain large numbers of organisms.

- foamy histiocytes are formed.

Disease: leprosy

Incubation period averages several years, onset of disease is gradual.

Tuberculoid leprosy:

- hypopigmented macular skin lesions.

- thickened superficial nerves.

- anesthesia of the skin lesions occur.

Lepromatous leprosy:

- multiple nodular skin lesions, resulting in typical leonine facies.

- many organs infected.

Nerve damage occurs in both forms & can lead to sensory & motor losses; repeated unnoticed trauma results in much damage to hands & feet.

Blindness occurs for a number of reasons.

Disfiguring appearance of disease due to:

- skin anaesthesia results in burns & other traumas, which become infected.

- resorption of bone leads to loss of features such as nose & fingertips.

- inflitration of skin & nervs leads to thickening & folding of skin.

Lepromatous leprosy:

- bacteria are present.

- easily seen in nasal scrapings & split skin smears.

- perform acid-fast stain of skin lesions or nasal scrapings.

Tuberculoid leprosy:

- few organisms seen.

- appearance of granulomas sufficient for diagnosis.

No serologic tests are useful.

False-positive serologic tests for syphilis occur frequently.

Tuberculoid leprosy:

- dapsone

- rifampin

Lepromatous leprosy:

- dapsone

- rifampin

- clofazimine

Treatment is given for at least 2 years until the lesions are free of organisms.

Prevention:

- isolation of all lepromatous patients.

- chemoprophylaxis with dapsone for exposed children.

Atypical Mycobacteria Group I

Photochromogens: pigment produced after light exposure.

M.kansaii causes lung disease clinically resembling tuberculosis.

Swimming pool granuloma:

- caused by M.marium

- warty lesions of elbows or knees sometimes spread along lymphatics.

- usually self-limiting

Tetracycline

Atypical Mycobacteria Group II

Scotochromogens: pigment produced even in dark.

M.scrofulaceum:

- natural habitat is environmental water sources.

- isolated as saprophyte from human respiratory tract.

- enters through oropharynx & infects draining lymph nodes.

Scrofula:

- a granulomatous cervical adenitis, usually in children.

M.ulcerans: Buruli ulcer with hard nodule breaking down to form an ulcer.

Surgical excision of infected lymph nodes.

Early lesion: excision.

Later: excision + skin grafing.

Atypical Mycobacteria Group III

Nonchromogens: no pigment.

M.avium & M.intracellulare: widespread in environment water & soil.

Cause pulmonary disease clinically indistinguishable from tuberculosis.

Clarithromycin

Rifampicin

Ethambutol

Clofazimine

Rifabutin (prevent disease in AIDS patients).

Atypical Mycobacteria Group IV

Rapid growing

M.fortuitum &M.chelonei: saprophytes found in soil & water.

Infections occur mainly in immunocompromised & those with prosthetic heart valves & hip joints.

Causes skin & soft tissue infections.

Infections of bone, joint, tendon sheath or bursa may also occur after trauma, or injections.

Amikacin + Doxycycline + surgical excision.