Mycobacteria: TB Flashcards
Mycobacteria
mycolic acid exterior, arabinogalactan, peptidoglycan
Steps for acid fast staining
1- carbolfuchsin, steam over boiling water for 8 minutes 2- decolorize 3- rinse with water 4- counterstain with methylene blue 5- rinse to remove excess methylene blue 6- dry
M. tuberculosis bacteriology
What are important structural components?
almost uniquely acid-fast
M. tuberculosis grows in vitro, but very slowly, and requires special nutrients
Humans are natural host and reservoir
Can be intra- or extracellular
Mycobacteria produce no toxins
Drug resistance is chromosomal; no known plasmids
Resistant to acid and alkali, environmentally hardy
Obligate aerobe
Important structural components:
Mycolic acids: acid fastness
Wax D: adjuvant (used in Freund’s)
Phosphatides: caseation necrosis
Cord factor (trehalose dimycolate): virulence, microscopic serpentine appearance
Phtiocerol dimycocerosate: lung pathogenesis
Pathogenic in guinea pigs
Pathogenesis of M. tuberculosis
How does it establish infection?
Transmitted primarily by inhalation of infected aerosols; rarely transdermal or GI infection
Aerosols are extremely infectious: <10 organisms can initiate infection
Alveolar macrophages phagocytose the inhaled bacilli.
Naïve macrophages are unable to kill the intracellular mycobacteria
M. tuberculosis proliferates within mononuclear phagocytes, traveling to extrapulmonary sites, where it can establish latent (immunocompetent) or active (peds, HIV+, immunosenescence) extrapulmonary infection: Lymph nodes Kidney Bones Meninges
Swallowing infectious sputum infects GI
Mycobacterium bovis – cow/milk
Immunocompetent hosts develop latent/dormant infection: only 5-10% lifetime risk of active TB
Current or later immunosuppression allows reactivation.
Non-TB infections may activate quiescent TB.
Measles
Varicella
Pertussis
M. Tuberculosis pathogenesis
What terminates the unimpeded growth of the M. tuberculosis 2-3 weeks after initial infection
A cell-mediated immune (CMI) response terminates the unimpeded growth of theM. tuberculosis2-3 weeks after initial infection. 2 parts:
CD4 helper T cells activate some infected macrophages to kill intracellular bacteria
CD8 suppressor T cells lyse other infected macrophages → caseating granulomas (“tubercules”)
Mycobacteria cannot continue to grow within these granulomas, so the infectious process pauses (latency).
TNF plays an important role in maintaining latency: Patients receiving TNF-alpha antagonists (Remicade) may reactivate.
M. Tb pathogenesis
85% of active TB includes lungs
The most common site of the primary lesion is within alveolar macrophages in subpleural regions of the lung.
Bacilli proliferate locally and spread through the lymphatics to a hilar node, forming the Ghon complex, launch from there to the bloodstream
The Ghon complex, typical of pulmonary tuberculosis, consists of a parenchymal focus and hilar lymph node lesions. The detailed section of the diagram shows typical features of tuberculous granuloma: central caseous necrosis surrounded by epithelioid cells, multinucleated giant cells, and lymphocytes. From Damjanov, 2000.
M. Tb pathogenesis
Lesions that develop around mycobacterial foci can be either proliferative or exudative. Both types of lesions develop in the same host:
Proliferative lesions develop where the bacillary load is small and host cellular-immune responses dominate.
Exudative lesions predominate when large numbers of bacilli are present and host defenses are weak. These loose aggregates of immature macrophages, neutrophils, fibrin, and caseation necrosis are sites of mycobacterial growth.
What are risk factors for infection and poor outcome?
Risk factors for infection:
Crowded at-risk environments (prisons, hospitals, homeless shelters)
HIV
Risk factor for poor outcome is immunosuppression: Uncontrolled HIV (inadequate HAART) Steroids IFNɣ deficiency TNF-alpha antagonists (Remicade) Age <5yrs
TB cases in the US are at an all-time low but XDR strains are disproportionately represented here.
Classic active TB presentation
presents with cough, weight loss (“consumption”), fever, night sweats, hemoptysis, and chest pain
Chest radiograph:
Cavity formation - Indicates advanced infection, associated with a high bacterial load
Noncalcified round infiltrates - May be confused with lung carcinoma
Pulmonary TB
Homogeneously calcified nodules (usually 5-20 mm) - Tuberculomas; represent old infection rather than active disease
HIV+ Xray may look normal despite symptoms and sputum+
Fiberoptic bronchoscopy is the most effective procedure for obtaining cultures (bronchoalveolar lavage)
Tb extrapulmonary tuberculosis
Extrapulmonary involvement in 20% of patients
60% of these are sputum-negative w/ normal chest radiograph.
Nonpulmonary symptoms mimic a wide variety of diseases
Rb scrofula (reactivation in lymph node)
Painless, enlarging, or persistent mass. Cervical lymph node affected in 2/3. Systemic symptoms include fever/chills, weight loss, or malaise.
~95% of mycobacterial cervical infections in adults are caused byMycobacterium tuberculosis
Peds: trend is reversed: 92% of cases due to atypical mycobacterium (acquired by putting contaminated objects in their mouths)
Useful tests are PPD and fine-needle aspiration for culture
Surgery should be considered only after antibiotic treatment is well underway
Genitourinary TB
Most common site for extrapulmonary infection?
Most common site for extrapulmonary infection
TB almost always reaches the kidneys during the primary infection but does not present clinically; may be 20yrs of latency before symptoms
Genital tuberculosis is usually secondary to renal tuberculous infection.
Females with genital tuberculosis may present with infertility, menstrual disorders, and pain, usually infected fallopian tube.
Pregnancy is unusual in the presence of genital tuberculosis. When pregnancy occurs, spontaneous abortion or ectopic pregnancy usually results.
Intravenous urography best option for identification of renal, ureteric, and bladder tuberculosis
Also detectable by ultrasonography, CT scanning, or MRI
CT scanning useful for assessment of renal function and severity of the disease, may also detect the involvement of other abdominal organs
All findings may be normal – small areas of calcification are difficult to detect. “Sterile pyuria” is suggestive
Surgical care: both infection and healing can block tubes
CNS TB
Visualize by magnetic resonance imaging (MRI) with gadolinium enhancement
MRI is the most sensitive test for detecting the extent of leptomeningeal disease and is superior to computed tomography (CT) scanning in detecting parenchymal abnormalities, such as tuberculomas, abscesses, and infarctions.
Cerebrospinal fluid (CSF) analysis is usually used to detect a decreased glucose level, elevated protein levels, and a slight pleocytosis. Results of CSF polymerase chain reaction (PCR) assays may be diagnostic.
Skeletal TB
Two main manifestations:
Arthritis of one joint
Pott disease (spinal infection): back pain, stiffness, paralysis of lower extremities
If suspect Pott, CT/MRI but do not delay treatment: paralysis can become permanent
GI Tb
Rare Abdominal pain Weight loss Anemia Fever with night sweats Obstruction Palpable mass Radiograph for calcified granulomas CT scans show mesenteric lymphadenopathy with a hypoattenuating center suggestive of necrosis. Exploratory surgery
Miliary Tb
~1.5% of TB cases
Hematogenous spread of TB throughout body, many tiny noncalcified foci of infection appear “like millet seeds” in lung on chest Xray
Miliary form more likely to develop right after primary infection, less likely as a reactivation
Highest risk in very young and old (65y)
Fatal if untreated
History of cough and respiratory distress
Lymphadenopathy
Hepatosplenomegaly
Tachypnea
Cyanosis
Subtle: papular, necrotic, or purpuric lesions on the skin or choroidal tubercles in the retina.
Tiny nodules best visualized by chest Xray w/ bright spotlight, lateral Xray, chest CT
Begin treatment on first suspicion: one week of delay increases mortality
Tb meningitis
Develops in 5-10% of children younger than 2 years
Nuchal rigidity
Altered deep tendon reflexes
Lethargy
Cranial nerve palsies
Special pediatric considerations
Special Pediatric Considerations TB in a child indicates recent transmission: track the contacts and index case Unusual sites: Middle ear Skin Ocular structures
Rule out TB if presents w/ pneumonia, pleural effusion, or a cavitary or mass lesion in the lung, failure to thrive, significant weight loss, or unexplained lymphadenopathy
Gastric aspirates are used in lieu of sputum in children younger than 6 years. (Don’t cough forcefully enough to bring up sputum)
Begin treatment as soon as samples have been taken for culture. Pediatric TB can be lethal before TST turns positive.
M. Tb Diagnosis
look at slide 50 for sizes
Tuberculin skin test by purified protein derivative (PPD, TST)
Positivity develops 2-10wks post-infection.
Alternative: IFNɣ release assay using TB peptides (IGRA) blood test doesn’t require 2nd visit and is specific for TB, not vaccine
Either PPD or IRA may be false-negative if patient is badly immuno- suppressed or late in the course of TB
HIV+ patients must be regularly screened for TB and vice versa.
Sputum smears and culture are very specific but not very sensitive – repeat often
Urinalysis and urine culture can be obtained for patients with genitourinary complaints.
Cultures are needed for antibiotic resistance testing, but molecular (rRNA probe and PCR) tests are available for faster +/-
Traditional antibiotic resistance tests take 3-4wks because of TB’s slow doubling time; check for local alternatives – DNA sequencing or microscopic-observation methods are faster, can be as good depending on the reagents&personnel
TB bacteremia can be detected from blood cultures, particularly in immunosuppressed patients, but special media are required – alert lab
M. tuberculosis Prevention
Keep at hospital for first two weeks of treatment if patient lives:
with immunocompromised persons
with children younger than 5 years
in a communal residence type of facility (eg, homeless shelter, senior citizen facility, jail, prison)
Alternate: home rest w/ TB mask
Control HIV (HAART), diabetes (insulin), underweight (better diet)
Good housing and nutrition are disproportionately helpful – healthy CMI drives TB latent (no new infections!). Population load of TB can be significantly decreased by improved standard of living even without access to antibiotics.
M. Tb prevention
BCG vaccine:
Live attenuated M. bovis
prevents up to 70% of symptomatic infections -> forces into latency, doesn’t cure
seldom used in US
Watch for 3-6mm PPD+ if vaccinated abroad or in military: can differentiate w/ IGRA
NOT for immunocompromised
