Bacteria causing human tuberculosis. Mycobacterium leprae

Question 1

General features and habitat of Mycobacterium Tuberculosis

Answer 1

No Gram staining (due to special lipid-rich cell wall)- acid-fast bacteria

Rod shape

Reservoir- human lungs

Question 2

Biochemical Properties of Mycobacterium Tuberculosis

Answer 2

Cell wall is rich in lipids (e.g. mycolic acids)- about 60%, hydrophobic and very resistant
Obligate aerobe

Question 3

Pathogenesis of Mycobacterium Tuberculosis

Answer 3

Transmitted by respiratory droplets (human to human)

Facultative intracellular (most important virulence factor)- multiplication in macrophages

Cord factors (glycolipids- trehalose dimycolate, in cell wall)- seen as serpentine shape in vitro Causes formation of granulomas; inhibit the spreading but allow bacteria to stay in host

Sulfatides (sulfolipids in cell wall)-
Inhibit phagosome-lysosome fusion, allowing intracellular surviving

Question 4

Clinical Features Tuberculosis

Answer 4

Primary Tuberculosis (affects middle or lower lobe and hilar lymph node)

Ghon complex = hilar lymphadenopathy with caseating granulomas
The granulomas are composed of activated macrophages with necrotic center (tubercle) Can undergo fibrosis (calcification) which then referred as Ghon-Ranke complex
Often resolve (with fibrosis) and becomes latent infection (associated with children)

Generally asymptomatic

Leads to positive PPD Test (Purified Protein Derivative) A.K.A Tuberculin Skin Test-
Wheal will be formed due to type 4 HS (DTH) if exposed to TB or if received vaccine

Secondary (Reactivated) Tuberculosis (affects upper lobe and apex of lung)
Only in 5-10% with latent infection, associated with immunosuppressed patients such as HIV, old age and cancer. Due to down-regulation (inhibition) of TNF􏰅 release. Symptoms:

Fever with purulent coughs or hemoptysis (bloody coughs)- contains bacteria
Night sweating
Malaise, pain in chest and weight loss (cachexia, due to TNF alpha)
Reactivation can also manifest in extra-pulmonary TB:

Pott’s disease (“Tuberculotic Osteomyelitis”)- demineralization of the vertebrae and soft
tissue swelling causing pain, which can progress to abscess and spinal deformities

Meningitis basilaris- serous inflammation of the meninges

Tuberculoma cavitary lesion- “hole-like” lesion; usually in the apex of the lung

Systemic (Miliary) Tuberculosis (can occur after primary or secondary tuberculosis; lethal) Extra-pulmonary hematogenous dissemination- bacteria spread through the lymphatics to the hilar or mediastinal lymph nodes and into the blood stream via macrophages, affecting: Meningitis basilaris (CNS), kidney, bones, spleen, bone marrow, intestine and eventually lungs

Question 5

Diagnosis of Mycobacterium Tuberculosis

Answer 5

Acid-Fast staining (Ziehl-Neelsen staining)- take-up carbol fuchsin by mycolic acids Mycobacteria stains red, everything else (background) is stained blue

Culture- from sputum specimen (taken early morning, pre-treated with 2% NaOH) Recommended to make 2 solids (long-term cultivation prone to fail) and 1 liquid culture

Lowenstein-Jensen medium (solid, slant): glycerol, asparagine, egg, potato extract,
malachite-green and antibiotics, grows very slowly (6-8 weeks, division every ~18h)

Sula or Dubos (liquid, broth-based): malachite-green, clumps seen at bottom

BacTec- early detection (3-21 days) method of CO2 production with radioactive carbon

Question 6

Treatment of Mycobacterium Tuberculosis

Answer 6

Often develops resistance (especially due to long treatment)- MDR or XDR

First line drugs (‘RIPES’):
Rifampin, Isoniazid (INH), Pyrazinamide, Ethambutol and Streptomycin

Second line drugs (‘FACEP’):
Fluoroquinolones, Aminoglycosides (given parenterally), Cycloserine, Ethionamide and Para-Aminosalicyclic acid (PAS)

Question 7

Prevention of Mycobacterium Tuberculosis

Answer 7

BCG (Bacillus Calmette-Guérin) vaccine- live attenuated vaccine of M. bovis (given at 0-4mo)

Prophylaxis (in patient with latent TB)- Rifampin and Isoniazid (INH), used for 9 months

Question 8

Other Mycobacteria:

Answer 8

Mycobacterium bovis
BCG (Bacillus Calmette-Guérin) vaccine- live attenuated vaccine of M. bovis (given at 0-4mo) Prophylaxis (in patient with latent TB)- Rifampin and Isoniazid (INH), used for 9 months

Infects cattle

Humans become infected by ingesting contaminated milk

Childhood scrofuloderma (A.K.A “tuberculosis cutis colliquativa”)- skin lesions characterized by enlarged, caseous cervical lymph nodes
Used for making BCG vaccine (live attenuated)

Mycobacterium africanum

Also causes human tuberculosis

Question 9

General features of Mycobacterium leprae and habitat

Answer 9

No Gram staining- acid-fast bacteria 
Rod shape (“cigar-like”)

Reservoir- armadillo (in the U.S.) and also Mangabey monkeys

Question 10

Biochemical Properties

Answer 10

Thrive at cool temperature- in cooler body parts (e.g. extremities, peripheral nerves)

Obligate intracellular- in histiocytes (skin macrophages), endothelial cells, Schwann cells

Question 11

Pathogenesis

Answer 11

Transmitted by nasal discharge, inhalation, penetrating wounds Human-to-human contact from untreated lepromatous leprosy patients

Long incubation time of 10-15 years

Question 12

Tuberculoid Leprosy General info

Answer 12

Benign form- hardly infectious

Question 13

Cell Mediated Immunity of Tuberculoid Leprosy

Answer 13

Strong cell-mediated response

Prominently TH1

Question 14

Lepromin Test of Tuberculoid Leprosy

Answer 14

Positive (+)

Question 15

Number of Organisms in Tissue of Tuberculoid Leprosy

Answer 15

None or few bacteria in skin biopsy

Question 16

Clinical Symptoms of Tuberculoid Leprosy

Answer 16

Few sharp-edged, hypo-pigmented, demarcated skin lesions
Erythema nodosum leprosum is absent
Thickened peripheral nerves with complete sensory loss
Amputation of fingers, hands or feet
− Granulomas formations

Question 17

Nerve Involvement of Tuberculoid Leprosy

Answer 17

Asymmetric nerve involvement (neuropathy)

Question 18

Treatment of Tuberculoid Leprosy

Answer 18

Rifampin and Dapsone- for 1⁄2 a year

deputy sheriff with rifle

Question 19

Lepromatous Leprosy General info

Answer 19

Malignant form- very infectious

Question 20

Cell Mediated Immunity of Lepromatous Leprosy

Answer 20

Weak cell mediated response, more humeral response Prominently TH2 promotes humeral response

Question 21

Lepromin Test of Lepromatous Leprosy

Answer 21

Negative

Question 22

Number of Organisms of Lepromatous Leprosy

Answer 22

Many bacteria in skin biopsy and some in blood

Question 23

Clinical Symptoms of Lepromatous Leprosy

Answer 23

Many papules, nodules and poorly demarcated skin lesions

Erythema nodosum leprosum is extensive

“Lion-face” (facial deformity)- eyebrows loss, nostril deformed

Infiltrated nerves (lack of enlargement) with segmented loss

Amputation of nose, fingers

Question 24

Nerve Involvement of Lepromatous Leprosy

Answer 24

Symmetric nerve involvement (neuropathy)

Question 25

Treatment of Lepromatous Leprosy

Answer 25

Rifampin, Dapsone and Clofazimine- for 1 year

deputy sheriff with rifle and a cloth

Question 26

Diagnosis

Answer 26

Acid-Fast staining (Ziehl-Neelsen staining)- take-up carbol fuchsin by mycolic acids

Not culturable on media- only in mouse footpad or armadillo (lower body temperature)

Lepromin Skin Test- positive in tuberculoid type but negative in lepromatous