5 TB & Non-TB Mycobacterial Infections Flashcards
What percentage of the world population is infected with Tuberculosis?
33% or 2 billion 🤯
But over 90% of healthy persons infected NEVER become ill
Why is TB difficult to eradicate?
Spread of infection is a significant health problem
Rising numbers of MDR and XDR strains
Patients with inadequate treatment both remain infectious and offer opportunity for drug resistance development
TB is a common co-infection with …
HIV
How is TB transmitted?
Person-to-person through aerosol droplet nuclei
What happens to infants who get TB?
Hematogenous dissemination
Can result in meningitis and other symptoms
Why do older adults get TB?
Failure of immune system or possible deactivation of latent infection
Factors that effect the probability of TB infection
Exposure environment (crowded conditions)
Duration of exposure (prolonged)
Virulence of strain (varies)
Strains vary in abx susceptibility (MDR and XDR)
Risk factors for TB
Close contact of those with TB (esp children)
Residence in long-term care facility
Low income/inner city housing
Alcoholism or IVDU
Malnutrition
DM (30% increase over lifetime)
Silicosis
Immunosuppression
What are the three species that produce human tuberculosis?
Mycobacterium tuberculosis
Mycobacterium bovis (cattle)
• Consumption of unpasteurized milk or contact with infected animals
• Source of BCG vaccine
Mycobacterium africanum (west African countries) • 25% of cases • Opportunistic infection - esp in HIV • May be spread by food - no animal reservoirs defined
Describe Mycobacterium tuberculosis
Obligates aerobe
Rod shaped (bacillus), usually slender and slightly curved
Non-motile
Heat sensitive
Intracellular growth (in alveolar macrophages)
ACID-FAST (Ziehl-Neelsen or Kinyoun stains)
Mycobacterium tuberculosis doesn’t have classic virulence factors or toxins but these things help them out…
Mycolic acids in cell wall - long chain fatty acids prevent dehydration and may resist H2O2
Cord Factor - mycoside (glycolipid Mycolic acid + disaccharide)
Lipoarabinomannan (LAM) - inhibits cell-mediated immunity, scavenges reactive oxygen intermediates
What are the potential outcomes of TB infection?
Immediate resolution (NO active case of TB, b/c innate immune system able to clear bacteria)
Primary disease
Progressive Primary (Active) disease
Latent Infection
Endogenous reactivating/secondary disease
Areas surrounded by macrophages, multi-nucleated giant cells, fibroblasts and collagen fibers that harbor viable MTB cells
Granulomas
Structures become evident 2-6 weeks after infection
Over time, can form fibrotic tubercle and calcify (can see on CXR)
Describe someone with Latent TB
Healthy
Bacteria remain viable in lesions but are inactive
Patient does not have symptoms and are no risk to spread disease
BUT TREAT THEM!
Describe someone with deactivation or secondary TB
SSx present, patient is infectious
Begins insidiously - may be present weeks to months before diagnosis
Cough, weigh loss, fatigue, fever, night sweats, chest pain
Lesions
• Progression from caseous lesions with necrosis
• Erode and discharge TB bacilli into bronchi (infectious)
• Erode blood vessel —> hematogenous spread
Tell me about military tuberculosis
Results from lymphohematogenous spread of primary infection or via a latent focus with subsequent spread
How do we diagnose TB?
CXR consistent with TB
Skin test reactivity
Sputum stain/broth cuture to detect acid-fast bacteria
Rapid blood test based on release of IFN-gamma (stimulates isolated T-cells to produce IFN-gamma)
NEW: GeneXpert Rapid test (tests for MTB and Rifampin resistance)
What is TB prophylaxis
For exposed subjects - regimen depends on HIB status and whether or not agents is drug resistant
Isoniazid x 9 months
BCG vaccination in high endemicity areas
How is serial screen for TB usually performed?
Use of purified MTB protein derivative (PPD) in tuberculin skin test (Mantoux test)
Boosters identified by quick second administration
BCG recipients and NTM infections can lead to false positives
Describe Mycobacterium avium complex (MAC)
Weakly gram-positive aerobic bacilli
ACID-FACT
Ubiquitous - found in water (fresh, brackish, ocean and drinking), soil, and plants
Slow growing organisms
How are MAC infections acquired?
Enter body via ingestion of contaminated water or food
NO person-to-person transmission
NO patient isolation required
Opportunistic human pathogen - now the leading cause of NTM infection in HIV+ patients in US
What is the disease spectrum like for MAC?
Immunocompetent patients:
• Middle-aged and older males with history of smoking, can have cavitary lesions resembling TB
• Elderly female non-smokers - can have patchy or modular x-ray (Lady Windermere’s syndrome)
• Solitary pulmonary nodule
In AIDS patients:
• DISSEMINATED DISEASE - no organ spared as immune system collapses
How is MAC diagnosed?
Clinical illness consistent with NTM
Microscopy reveals acid-fast bacteria (must exclude other etiologies ie fungi and TB) - sterile site isolation of MAC significant
Chest X-rays - important for ID of pulmonary lesions
Final species ID by molecular techniques (ie PCR
How do we treat MAC?
Combination Abx therapy
Take HIV status into account:
HIV (-) patients - continue until sputum cultures are negative for 1 year
HIV(+) patients w/o MAC infection - chemoprophylaxis with CD4 <50, can discontinue 3 months after CD4>100
HIV(+) patients with MAC infection
• W/o immune reconstitution = lifelong treatment
• Begin Treatment for 2 weeks then anti-HIV HAART