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MYCOBACTERIA Jaime A. Santos

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MYCOBACTERIAJaime A. Santos

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MYCOBACTERIA: CHARACTERISTICS

thin,nonmotile and nonspore forming rods

obligate aerobes

slow growing

cell wall has high lipid content and mycolic acid

generally catalase positive

acid-fast

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MYCOBACTERIA: CHARACTERISTICS

thin,nonmotile and nonspore forming rods

obligate aerobes

slow growing

cell wall has high lipid content and mycolic acid

generally catalase positive

acid-fast

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CLASSIFICATION

Mycobacterium

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CLASSIFICATION

Mycobacterium

M. tuberculosis complex

MOTT (Nontuberculous) M. leprae

M. tuberculosisM. bovis

M. microtiM. africanum

Runyon 1 to IV

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M. TUBERCULOSIS

optimal growth:  37 C/ 5-10% CO2/ pH 6.0-7.6.

in vivo, it can use a variety of enzymes for anaerobic metabolism

requires complex media such as Löwenstein Jensen doubling time of ~18 hours.  Colonies visible in 3-6 weeks

multiplies intracellularly in phagosome and prevents phagolysosome fusion

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M. TUBERCULOSIS CELL WALL

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M. TUBERCULOSIS CELL WALL

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VIRULENCE FACTORS

Mycolic acid glycolipids and trehalose 6,6 dimycolate  (cord factor)- cause granuloma formation

Catalase, peroxidase and lipoarabinomannan - help resist the host cell oxidative response 

Sulfatides and trehalose dimycolate- toxic to animal models

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MAGNITUDE OF TB PROBLEM

>1/3 of world’s population infected

8-9 million new cases annually

3 million deaths annually

~1.3 million of these new cases are in children with ~500 thousand deaths annually

Philippines ranks no.1 in Western-Pacific

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PATHOGENESIS

2 - 6 wksCMI

BACILLI INHALED

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IMMUNE RESPONSE

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IMMUNE RESPONSE

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IMMUNE RESPONSE

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IMMUNE RESPONSE

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CLINICAL MANIFESTATIONS

asymptomatic

fever

cough >3 weeks

chest pain

hemoptysis

lymphadenpathy

other symtoms and signs depending on the organ involved e.g. CNS, bone, renal

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CHILDHOOD TB

asymtomatic ~50%

cough/wheezing > 2 weeks

fever > 2 weeks

painless cervical and/or other lymphadenopathy

poor weight gain

failure to make a quick return to health after an infection e.g. measles,tonsillitis or pertussis

failure to respond to appropriate antibiotics as in AOM or pneumonia

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DIAGNOSIS

SIGNS AND SYMPTOMS

HISTORY OF EXPOSURE

CHEST X-RAY

TUBERCULIN TEST

BACTERIOLOGIC DIAGNOSIS: SMEAR, CULTURE, PCR

HISTOLOGIC

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CHEST X-RAY

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CHEST X-RAY

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CHEST X-RAY

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TUBERCULIN TEST

Mantoux test

0.1 ml of solution containing or equivalent to1g ( 5 TU PPD-S)

read at 48-72 hours using ballpoint pen method

results recorded in mm

delayed-type hypersensitivity

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TUBERCULIN TEST

Mantoux test

0.1 ml of solution containing or equivalent to1g ( 5 TU PPD-S)

read at 48-72 hours using ballpoint pen method

results recorded in mm

delayed-type hypersensitivity

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CULTURE

incubated at 35° to 37° C in an atmosphere of 5 to 10% CO2

cultures should be examined weekly for 8 weeks.

solid media e.g. Lowenstein-Jensen allows visualization of colony morphology but requires 3-4 weeks

broth systems detecting 14C labelled CO2 (BACTEC) require only 5-12 days

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ANTI-TB DRUGS

isoniazid (H) - 5 to 10 mg/kg ( max 300 mg)

rifampicin (R) - 10 to 15 mg/kg (max 600 mg)

pyrazinamide (Z) - 15 to 30 mg/kg (max 2 gm)

ethambutol (E) - 15 to 25 mg/kg (max 2.5 gm)

streptomycin (S) - 20 to 30 mg/kg (max 1 gm)

second-line drugs

PROBLEM OF DRUG RESISTANCE

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MOTT

Nontuberculous mycobacteria (NTM) are soil and water organisms

noncommunicable

Disease develops in setting of trauma/surgery or immunosuppression.

INH resistant

Diagnosis is by acid fast staining of the specimen; followed by culture and/or 16s rRNA probes culture

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RUNYON CLASSIFICATION

Group Growth Pigment Examples Disease

I slow yellow-orange on light(photochromogen)

1. M. kansasii2. M. marinum

1. similar to TB2. swimming pool

granuloma

II slowyellow-orange in light

or dark(scotochromogen)

M. scrofulaceum cervical adenitis

III slow no pigment M. avium intracellulare complex (MAC)

similar to TB, esp. in AIDS

IV rapid (5 days) no pigment M. fortuitumM. cheilonae

soft tissue, lung, bone, CNS, eye infections

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MYCOBACTERIUM LEPRAE

cannot be cultured

can be grown in armadillos or in mouse footpads

optimal T for M. leprae is lower than core body temp, so it grows on skin and superficial nerves

found in macrophages and Schwann cells.

complex cell wall has lipoarabinomannan (LAM) & a unique M. leprae-specific phenolic glycolipid (PGL-1).

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MYCOBACTERIUM LEPRAE

cannot be cultured

can be grown in armadillos or in mouse footpads

optimal T for M. leprae is lower than core body temp, so it grows on skin and superficial nerves

found in macrophages and Schwann cells.

complex cell wall has lipoarabinomannan (LAM) & a unique M. leprae-specific phenolic glycolipid (PGL-1).

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LEPROSY

anesthetic plaques, and asymmetric peripheral nerve

trunk involvement, paucibacillary

symmetric skin nodules, plaques,

leonine (i.e., lion-like) facies, loss of

eyelashes and body hair, multibacillary

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LEPROSY

lepromatoustuberculoid

anesthetic plaques, and asymmetric peripheral nerve

trunk involvement, paucibacillary

symmetric skin nodules, plaques,

leonine (i.e., lion-like) facies, loss of

eyelashes and body hair, multibacillary

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LEPROSY (HANSEN’S DISEASE)

M. leprae causes leprosy, which is also known as Hansen’s Disease.

The incubation period for leprosy is 5-7 years. Prolonged exposure

required to become infected

8 million infected with 600,000 new cases annually

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LEPROSY (HANSEN’S DISEASE)

M. leprae causes leprosy, which is also known as Hansen’s Disease.

The incubation period for leprosy is 5-7 years. Prolonged exposure

required to become infected

8 million infected with 600,000 new cases annually

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LEPROSY AND THE IMMUNE SYSTEM

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DIAGNOSIS

clinical signs

lepromin skin test (mainly of immune status)

biopsy and histology

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TREATMENT

dapsone, rifampin, clofazimine, and either ethionamide or prothionamide

Paucibacillary cases (tuberculoid and borderline tuberculoid) x 6 months, dapsone alone is usually given for up to 3 years after disease inactivity

lepromatous or borderline lepromatous leprosy may require primary treatment for 3 years, with dapsone alone continued for the rest of the patient's life

antiinflammatory drugs; wound care

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Thank you!