Mycobacterium Characteristics and Clinical Characteristics Flashcards
Mycobacterium Species: What are the major human pathogens?
M. tuberculosis
Tuberculosis (TB)
- M. leprae
Leprosy - M. avium-intracellulare complex (MAC)
Common infection in AIDS patients - M. bovis
Primarily an animal pathogen
Human disease caused by consumption of unpasteurized milk
General Characteristics about Mycobacterium: - Morphology - stain protocol? - unique feature of the genome? Unique features of its cell wall?
- Morphology: aerobic bacilli
- Staining: Acid Fast Positive - Mycobacterium resist de-colorization by acid alcohol
- Genome: G+C rich
- Cell Wall: Lipid Rich; Mycolic Acids; PPD; Cord factor
Other: slow growth; non motile
Characteristics attributable to the cell wall?
- Acid-fastness
- Clumping - when growing in liquid media
- Antibiotic resistance
- Antigenicity
- Slow growth
Classification of Pathogenic Mycobacteria Species
1) M. TB Complex: M TB, M. bovis, M. africanum
2) M. Laprae
3) Other: Non TB Mycobacteria (NTM) divided into: slow growing (>7 day), fast growing (<7 days)
Unique Biochemical Rxns of M. tb vs M. bovis
• M. Tuberculosis ○ Niacin Positive ---unique to M. Tb ○ Nitrate Reductase positive • M. bovis ○ Niacin Negative ○ Nitrate Reductase positive
What lab tests can be done for Mycobacterium species indentification:
• Ribotyping:
○ A species specific molecular probe
○ Amplification of hypervariable regions of the 16S rRNA genes
• BACTEC Culture system ○ Use of Radioactive carbon ○ But very expensive
Microscopic Observation Drug Susceptibility (MODS) assay
○ M. Tb grows faster in liquid medium
○ Cord formation can be visualized in liquid with auramine rhodamine fluoroescent stain
○ Can also test drug susceptibility
Describe the normal host immune response to M. Tb –
- what MHC is important?
- what cells are important?
- what cytokines and receptors are important ?
- Phagocytosis of the mycobacteria (now intracellular)
- lysosome and phagosome fusion and acidification
- Presentaiton of antigen on MHC II to CD4
- macrophage secretion of IL-12
- Differentiation of TH1 cells
- Cytokines: TNF alpha, and IFN gamma
- activation of the macrophage -
- Cells and cytokines lead to formation of granuloma (Type IV hypersensitivity reaction aka DTH) to contain the mycobacterium
How does the mycobaterium hinder some of the host immune response ?
- Prevents acidification of the lysosome
- Prevents fusion of the lysosome/phagosome
- Slow growth – can hide in granulomas and remain latent
Describe the early pathogenesis of TB?
- how is TB transmitted - where does it multiply?
- what’s unique about this process ?
- Week 1 - inhalation of droplet;
- week 2 - bacilli multiple within macrophages
- Week 3 - CD4 cells infiltrate, cytokine release macrophage activation
- week 4 - Granulomas
- the progression of the disease is over the course of weeks; the bacteria divide very slowly
What are some diagnositc tests for TB?
- PPD (Tb Skin Test = TST) —- will elicit DTH reaction to previous exposure to PPD.
False positive if patient has had BCG vaccine - Interferon gamma Release Assay (IGRA); Quantiferon TB Gold Assay:
Measure the amount of INF secreted in response to M. TB specific antigens
able to differentiate from BCG
By what mechanism does M. Tb display drug resistance?
M. Tb only displays drug resistance by point muations
not inherited via plasmids or transposons
Name 3 Anti-TB drugs and their mechanism of action
Isoniazid – inhibition of mycolic acid synthesis
Rifampin – Bind to and inhibit RNA polymerase.
Streptomycin (an aminoglycoside) – bind 30s rRNA; disrupting protein synthesis
M. leprae - lab features?
- Stain
- morphology
- unique molecular and defensive feature
- other unique quality in the lab …
- Stain: Acid fast
- Morphology - Bacilli; obligate intracellular
- PGL -1 (phenolic glycolipid specific to M. leprae) - protects bacilli within macrophages by scavenging for radicals and super-oxide anions
- cannot be cultured in vitro in the lab
in vivo cultures in mice and armadillos
How does host immune response to M. leprosy determine the outcome?
TH1 dominant response – Tuberculoid leprosy; good granulomas contain the bacteria
TH2 Dominant response – Lepromatous leprosy; diffuse disease
Diagnostic Tests for M. leprae
- Lepromin Skin Test: Tuberculoid patients form DTH reaction
- Antibodies: can be used for diagnosis, but offer no protective measures
What is another name for Leprosy?
Hansen’s Disease
How is leprosy transmitted?
What is an indeterminate lesion?
Transmitted: droplets from the nose and mouth; during close and frequent contacts with untreated persons
only 5% of persons exposed will develop an indeterminate lesion
75% of these persons will heal spontaneously
25% of the 5% will have tubuerculoid or lepromatous symptoms
What is the Hallmark presentation of leprosy?
What are the unique clinical features of tuberculoid leprosy vs lepromatous leprosy?
What are the classic facial features?
Hallmark: Anesthetic skin lesions + thickened peripheral nerve
Tuberculoid: few lesions; single but progressive nerve involvement
Lepromatous: many symmetrical lesions; can be erythematous, papulosquamous
several nerves involved. Slow progression
The Neuritis can lead to deformity
Facial Features: cold facials regions are attacked
- loss of eye brows; saddle nose deformity; ear lobe nodules
Diagnosis of Leprosy
- Physical Examination: skin and nerves
- Skin Bx: acid fast bacilli
Treatment of Leprosy (3 drugs)
Multi Drug Therapy: Dapsone, Rifampicin, Clofazimin
Prevention of Leprosy
Rifampicin to those in close contact
BCG immunizations
TB Epidemiology:
- Transmission
- Risk factors
Transmission: Inhalation of droplets from infectious adults with pulmonary or pulmonary TB
Risk Factors:
- The degree of illness of the patient (lungs with cavitations have more bacteria)
- The contact: frequency of exposure, over crowding, poor ventilation, occupational setting
Describe the Natural Course of TB
- what is a characteristic feature of primary TB
- What are the risk factors for TB disease (either primary progressive vs reactivation)
- 70% of persons exposed to TB will not get sick -
- 30% will develop primary TB
- 90% of primary TB cases will be properly contained in granulomatous reaction – Latent TBI
of these: reactive risk depends on immune state of the person with LTBI - 10% will continue as TB disease
- Characteristic feature of primary TB: Ghon Focus (lesion in the lung); Ghon Complex (lung + infected LN)
Risk Factors: Recent Acquisition/exposure risks;
Immunocompromised: HIV, old or young, DM, ESRD, malignancy
Genetic immunodeficiency: INF gamma, IL-12, IL-23
Upon Clinical Presentation: Differentiate between LTBI and Active Pulmonary TB disease
LTBI: Asymptomatic; normal Physical Exam
CXR may be normal, or show old granuloma
TST/IGRA - Positive
Sputum Culture - Negative
Active TB Disease: pulmonary and Systemic Symptoms Abnormal pulmonary findings CXR: Consolidation; Cavity or Pleural effusion TST/IGRA - Positive or Negative Sputum culture: Positive
Treatment Of Latent TBI
§ Preferred: □ Isoniazid daily x 9 month § Alternative: □ Isoniazid daily x 6 month □ Rifampin daily x 4 months □ Isoniazid and Rifapentine weekly x 3 months
Active Pulmonary TB:
- primary TB imaging
- progressive primary TB imaging
- post - primary TB imaging
Primary: Hilar LAD; Lower lung infiltrates; CXR normal in 15% of patients
Progressive Primary: Confluent, well defined consolidation; always LAD;
Reactivation: Consolidation with Cavitation; CXR abnormal; some lung destruction may be present
What are the two forms of CNS Extra-pulmonary TB?
- Basilar Meningitis:
CSF - lymphocytes; high protein; low glucose
Subacute course of fever, HA, AMS (meningococcal meningitis – acute onset) - Tuberculoma – granuloma in the brain
Extra-Pulmonary TB:
- TB of Spine (what’s the other name, what are the manifestations)
- Miliary TB (why is it called this? what is it?)
TB of the Spine = Pott’s Disease
- anterior vertebral column disease
- Vertebral column collapse (Gibbus formation)
Miliary TB — widspread hematogenous disease; most severe form of TB;
organs: lung, liver, spleen, bone marrow, CNS
Radiology Hallmark: millet seed like lesions
What are the first line treatments for TB:
- • Isoniazid (INH) • Rifampin (RIF) • Pyrazinamide (PZA) • Ethambutol (EMB) • Streptomycin (special indications only)
what are the second line treatments of TB?
- Fluoroquinolones (Levofloxacin, Moxifloxacin)
* Injectables (Capreomycin, Kanamycin, Amikacin)
Describe the Treatment regimen of TB?
what vitamin is always given during this therapy?
- Department of health will get involved
- 6 months of Multi Drug therapy for pulmonary, pan-sensitive TB
(Do i have to know this?
Intensive 2 months: Isoniazid, Rifampin, Pyrazinamide, Ethambutol
Continuation 4 months: Isoniazid, Rifampin
• Vitamin B 6 always given with INH to prevent nerve damage
Describe the 2 forms of drug resistance in TB
• Multi-Drug Resistance (MDR):
Resistance to isoniazid and rifampin
• Extensive Drug Resistance (XDR): MDR + resistance to 2nd line drugs (Fluoroquinolones + ³ 1 injectable )
Non TB Mycobacteria:
- where are they found?
what is unique about transmission?
Not transmitted person to person
found ubiquitously in water, soil and plants
Clinical Manifestations of NTM
-
○ Pulmonary - – most common
§ M. avium/intracellulare (MAC), M. kansasii, M. abscessus
○ Lymphadenitis ○ Skin and soft tissue --- ○ Health Care Associated - Associated with surgery, injections or cosmetic procedures, catheters - Rapid growers (M. abscessus, M. fortuitum) ○ Disseminated disease § Predominantly M. avium and M. intracellulare (MAC) § Occurs in HIV-infected patients with CD4 < 50 cells/mm3
Treatment of NTM
• Treatment of NTM ○ Combination therapy § Macrolides (azithromycin or clarithromycin) § Ethambutol § Rifampin § Aminoglycosides ○ Difficult ○ Go by sensitivities
