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Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis1
Transmission and Pathogenesis of Tuberculosis
Journey of the TB bacillus
Objectives
• Describe the basic pathophysiology and transmission of Mycobacterium tuberculosis and use this knowledge to inform clinical care
• Identify features that increase an individual’s risk of progression from TB infection to active TB disease
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis2
M. tuberculosis complex (M.tb)
M. tuberculosisM. africanumM. canettii (rare)M. bovis (cattle)M. orygis (herd animals)M. microti (rodents)M. caprae (sheep/goats)M. pinnipedii (seals/sea lions)M. suricattae (meerkats)M. mungi (mongoose)
The etiology
Source: NIAID image 18139
Human pathogens
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Characteristics of M. tuberculosis
• Slightly curved, rod shaped bacilli
• 0.2 ‐ 0.5 microns in diameter; 2 ‐ 4 microns in length
• Thick lipid (mycolic acid) cell wall
• Acid fast bacilli (AFB) ‐ resists decolorization with acid/alcohol
• Multiplies slowly (~ every 18‐24 hours)
• Aerobic and non‐motile
• Metabolism can slow to the point of dormancy and remain in this state for decades
Source: CDC/ Dr. George P. Kubica,
1979
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Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis3
Transmission of TB
Transmission of TB
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis4
Transmission of TB
Transmission of TB
Droplet nuclei
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Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis5
Transmission Factors
The likelihood of transmission relates directly to:• Bacteria load and index case
factors– Sputum smear (+) – Cavitation on chest X‐ray– Symptoms (e.g., cough) and social activities
• A contact’s exposure time – On average, 1‐5% of household
contacts are found on initial evaluation to have active TB
– 20‐30% of close contacts may have TB infection
• Environmental factors
TB Index Case
TB Case
TB Contacts
TB Contacts
TB Cases
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Transmission Infection
• Inhaled droplet nuclei containing TB bacilli travel to alveoli
• Bacilli are engulfed by local macrophage
– Killed by macrophage (no infection)
– Multiply and overwhelm the macrophage disseminate to other sites
10
© ITECH, 2006
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis6
DISSEMINATION: Spread of TB to Other Parts of the Body
1. Lungs (85% all cases)
2. Pleura
3. Central nervous system
• spine, brain, meninges
4. Lymph nodes
5. Genitourinary system
6. Bones and joints
7. Disseminated (miliary)© ITECH, 2006
TB Pathogenesis
• About 3 weeks after infection, a cell‐mediated TH1 response is mounted, activating macrophages to become bactericidal
• Mature TH1 cells, both in lymph nodes and in the lung, produce IFN‐gamma
• IFN‐gamma stimulates formation of the phagolysosome in infected macrophages, creating an inhospitable acidic environment for M.tb
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Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis7
TB Pathogenesis (2)
• Immune system activated
– Granuloma formation may occur containing the bacilli (latent TB infection)
– Unable to contain and progression to primary tuberculosis occurs (~ 5%)
Small, et al NEJM 2001 13
Primary Tuberculosis
• Tuberculosis that results from the initial M. tuberculosis infection
• Radiological features depend on:– Age– Underlying immune status– Prior TB exposure
• Distribution: Any lobe (slight lower lobe predominance)
• Presentations include:– Air‐space consolidation
– Cavitation is uncommon (< 10%)
– Miliary pattern
– Adenopathy is common (esp. in children and persons with HIV)
Right hilar adenopathy in a child contact 14
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis8
TB Pathogenesis (3)
Small, et al NEJM 2001
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Latent TB infection (LTBI) or active TB disease?
What features distinguish one from the other?
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Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis9
Latent TB Infection (LTBI)• Inactive tubercle bacilli in the body
• Tuberculin skin test or interferon‐gamma release assay (IGRA) test results usually positive
• Chest x‐ray usually normal
• Sputum smears and cultures negative
• No symptoms
• Not infectious
• Not a case of TB
Active TB Disease• Active tubercle bacilli in the body
• Tuberculin skin test or interferon‐gamma release assay (IGRA) test results usually positive
• Chest x‐ray may be abnormal
• Sputum smears and cultures may be positive
• Symptoms such as cough, fever, weight loss
• May be infectious before treatment
• A case of TB
Source: CDC. Transmission and Pathogenesis of Tuberculosis. Self‐Study Modules on Tuberculosis. US Department of Health and Human Services. Atlanta, GA; 2008: 14. 17
TB Pathogenesis: Infection‐Disease Spectrum
Gideon and Flynn. Immunol Res. 2011 August ; 50(0): 202–212
PPD=purified protein derivative; TST= tuberculin skin test; IGRA= interferon gamma release assay; CM= central memory; EM= effector memory
PPD/TST +
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis10
Distribution
• Apical / posterior segments of upper lobes
• Superior segments of lower lobes
• Isolated anterior segment involvement is unusual (think M. avium complex or other disease)
Can this be TB?Typical Pattern: Reactivation, Post‐primary TB
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Reactivation/Post‐primary TBPatterns of disease
• Air‐space consolidation
• Cavitation, cavitary nodule
• Endobronchial spread
• Miliary
• Bronchostenosis
• Tuberculoma
• Pleural effusions
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Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis11
TB Risk Assessment
TB Risk Assessment
• Evaluate for risk factorsthat increase chance:
– that person may have LTBI (high prevalence)
– for progression of LTBI to disease (high risk)
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis12
High prevalence for LTBI
• Known contact to person with TB disease
• Persons who live or spend time in certain congregate settings – nursing homes,
– correctional institutions,
– homeless shelter,
– drug treatment centers
• Persons born in countries with high prevalence of TB
High Risk for Progression
• Newly infected close contacts
• HIV‐infected persons
• Persons with a history of prior, untreated TB or fibrotic lesions on chest radiograph
• Underweight or malnourished persons
• Injection drug users
• Extremes of age (very young or very old)
Persons more likely to progress from LTBI to TB disease include:
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis13
High Risk for Progression (2)
Persons with certain medical conditions such as:
• Silicosis
• Diabetes mellitus
• Chronic renal failure or on hemodialysis
• Solid organ transplantation
• Carcinoma of head or neck
• Gastrectomy or jejunoileal bypass
Persons taking immunosuppressive agents:• Steroids
• Cancer chemotherapy
• Cyclosporine
Persons taking blocking agents against Tumor Necrosis Factor‐Alpha; some examples include:• Etanercept (Enbrel®)
• Infliximab (Remicade®)
• Adalimumab (HumiraTM)
• Golimumab (Simponi®)
• Certolizumab pegol (Cimzia®)
High Risk for Progression (3)
Tuberculosis in Nursing: Prevention, Treatment, and Infection ControlJune 27-28, 2018Curry International Tuberculosis Center
Transmission and Pathogenesis14
Take home points
• People with latent TB infection (LTBI) can be treated to prevent development of TB disease
– This is a critical aspect to achieve TB Elimination
• Detecting LTBI early and providing treatment helps prevent new cases of TB disease
• You too can be a part of halting TB’s journey here in the U.S. ‐
1) Know risks for infection and disease
2) Encourage and facilitate testing and treatment
Questions?
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