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Transcript of Tb
MYCOBACTERIAJaime A. Santos
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
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
CLASSIFICATION
Mycobacterium
CLASSIFICATION
Mycobacterium
M. tuberculosis complex
MOTT (Nontuberculous) M. leprae
M. tuberculosisM. bovis
M. microtiM. africanum
Runyon 1 to IV
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
M. TUBERCULOSIS CELL WALL
M. TUBERCULOSIS CELL WALL
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
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
PATHOGENESIS
2 - 6 wksCMI
BACILLI INHALED
IMMUNE RESPONSE
IMMUNE RESPONSE
IMMUNE RESPONSE
IMMUNE RESPONSE
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
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
DIAGNOSIS
SIGNS AND SYMPTOMS
HISTORY OF EXPOSURE
CHEST X-RAY
TUBERCULIN TEST
BACTERIOLOGIC DIAGNOSIS: SMEAR, CULTURE, PCR
HISTOLOGIC
CHEST X-RAY
CHEST X-RAY
CHEST X-RAY
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
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
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
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
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
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
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).
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).
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
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
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
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
LEPROSY AND THE IMMUNE SYSTEM
DIAGNOSIS
clinical signs
lepromin skin test (mainly of immune status)
biopsy and histology
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
Thank you!