Tuberculosis

Where does TB come from?

-Airdroplets, which come from an infected person -We inhale these droplets and they go to the lungs -->go to alveolus -Macrophages will recognize these by PAMP and come in to pick them up (phagosome fuse w/ lysosome--> phagolysosome)

Case 3 How would we know if this patient's TB infection was multi-drug resistant? (What historical information would you want/need, for example?)

-Culture (Look to see where he lives) and sensitivities What other questions would you ask? -have you been tested for TB in the past -if so, did he finish his treatment

Secondary TB (reactive TB)

-happens from getting sick with something else making this thing come out of its latent stage Spreads: 1. upper lobe of lung why? b/c there is more O2 pressure 2. Disseminated (rest of body) -Brain~ meninges (patient present with meningitis) -vertebral body (pott disease) Presentation: -Fever -******Sweats -cough (non productive/productive) -weight loss (why? b/c of hypermetabolic state due to fever)

From case 4 Explain BCG vaccine and describe its effectiveness

-it prevents pulmonary TB but NOT disseminated TB

For case 3 What is the natural history of disseminated TB infection?

-meninges -vertebra -liver -spleen -adrenal

How do we prevent spread of M. tuberculosis in the hospital?

-negative pressure room (pulls air in-> out through HEPA filter)

What key virulence factors contribute to pathogenesis of M. tuberculosis infection?

-stops phagosome-lysosome fusion -mycobacteria multiply in phagosome -if inhibit macrophage function, you need a th1 response Th0 1. peptide presented to APC 2. CD3 and B7 3. IL-12 --> Th-1 cells

A radiology technician is undergoing new employee health screening at a hospital. A purified protein derivative (PPD or tuberculin skin test [TST]) is placed. When he returns 72-hours later, the clinic nurse measures an induration of 17mm at the site of the injection. He has been healthy and takes no medications. A chest x-ray reveals a Ghon complex. What is the most likely diagnosis? A. Active pulmonary tuberculosis B. Latent tuberculosis C. Secondary tuberculosis D. Latent tuberculosis E. Extrapulmonary tuberculosis

B. Latent tuberculosis

For case 2 Why did this patient not receive a PPD test?

Better tests: -IGRA -Sputum for culture (this will help us determine which drug to treat with) Hx: of BCG vaccine (increase risk of false positive TST) -this is a cross-reaction with the tuberculin antigen

A 42-year-old man who recently immigrated to the US from Cambodia presents with a 2-week history of fever, night sweats, a 15-lb weight loss, and a cough productive of bloody sputum. Granulomatous lesions can be visualized on a chest radiograph. What of the following stains would be most helpful in visualizing the most likely organism causing this patient's infection? A. Grocott-Gimori methenamine silver stain B. Gram stain C. Auramine rhodamine D. India ink E. KOH

C. Auramine rhodamine

Standard first line therapy for active tuberculosis starts with 2 months of treatment with which of the following? A. Isoniazid B. Isoniazid and rifampin C. Isoniazid, rifampin, ethambutol, and pyrazinamide D. Levofloxacin, bedaquilen, and lineazolid

C. Isoniazid, rifampin, ethambutol, and pyrazinamide

A 55 year old woman comes to the physician because of fevers for 2 weeks. She works as a nurse and recently returned from a charity work trip to india, where she worked in the medically-underserved rural community. A tuberculin skin test 3 months ago prior to her trip showed an induration of 3mm. Physical examination is unremarkable. An x-ray of the chest shows right-sided hilar lymphadenopathy. A sputum culture showed acid-fast bacilli. which of the following immunologic processes most likely occurred first? A. transportation of bacterial peptides to regional lymph nodes B. Formation of a nodular tubercle in the lung C. Replication of bacteria within alveolar macrophages D. Fusion of phagolysosomes in neutrophils E. Production of interferon-gamma by T-helper cells F. Migration of T-helper cells to the lungs

C. Replication of bacteria within alveolar macrophages

What kinds of tools do we use to identify Mycobacteria spp.?

Culture: -acid fast stain -lowenstein jensen -middle brook we would not use a gram stain because it can't get through the waxy cell wall

The tuberculin skin test (TST or purified protein derivative (TST)) is a screening tool used to determine if a person has been exposed to Mycobacterium tuberculosis. Which cell type is primarily responsible for reacting to injected antigens and releasing mediators that resulted in the skin manifestations? A. Endothelial cells B. Macrophages C. Mast cells D. CD4+ Th1 T cells E. CD8 T cells

D. CD4+ Th1 T cells

A 28 year old man comes to the physician for a pre-employment examination. He has no history of serious illness and takes no medications. A screening blood test is performed in which peptides are added to the sample to stimulate in vitro production of interferon-gamma, which is the measured using an enzyme-linked immunosorbent assay (this is basically saying IGRA). This test is most likely to be helpful in diagnosing infection with which of the following pathogen? A. Human immunodeficiency virus B. staphylococcus aureus C. Hepatitis B virus D. Mycobacterium tuberculosis E. Clostridioides difficile F. Legionella pneumophila

D. Mycobacterium tuberculosis

For case 2 What risk factors for secondary/reactivation TB does he have?

Diabetes mellitus -Obese

A critical factor in the pathogenesis of infection with Mycobacterium tuberculosis is the ability of the organism to do which of the following? A. Adhere tightly to epithelial cells B. Infect and destroy respiratory epithelial cells C. Alter cAMP levels in respiratory epithelial cells D. Induce immune suppression through infection of T cells E. Lyse secretory IgA F. Inhibit phagosome lysosome fusion and replication in macrophages

F. Inhibit phagosome lysosome fusion and replication in macrophages

For case 3 What is the cause of the patient's enlarged liver and spleen? What would you expect to see on gross pathology of both organs?

Granulomas, what do these look like? -caseating necrosis

Prevention of TB

Hygiene & good living conditions Vaccination TB surveillance Health literacy

For case 2 Why does this manifestation of TB infection have a predilection for upper lung lobes?

Increase O2 -more perfusion in lower lobes: more ventilation in upper loads

For case 2 What risk factors for primary infection are evident in his medical history?

India

For case 3 How would you describe this patient's TB infection?

Miliary

Case 3 A 23-year-old homeless, HIV positive man is seen by his physician because of fever and progressive dyspnea over the past several weeks. Upon physical examination, generalized lymphadenopathy is noted and the patient's spleen and liver are palpably enlarged. Lung auscultation reveals a few scattered crackles bilaterally. Chest X-ray is performed and shown in the accompanying image.

Notes: -considering this man is homeless, this tell us that his nutrition and hygiene are not good -means that his exposure is higher

Case 2 A 42-year-old man, who emigrated from India asa college student and often returns home to visitfamily, reports to his physician for follow-up of his diabetes mellitus. Diagnosed 6 years ago, his DM has been difficult to control because of persistent obesity and significant degenerative arthritis of his knees that makes it difficult to exercise. Today he states that he has not been feeling well for weeks. He wakes up at night drenched in sweat and has started coughing episodically during the day. Two days ago, he coughed up blood. His appetite is reduced, and he feels tired all the time. Upon physical examination, vital signs are within normal limits. He has lost 15# since his last visit 3 months ago. Crackles are heard on lung examination over the right upper lung field.

Notes: -diabetes mellitus (generally people with this. is considered immunocompromised) -Night drenched in sweat is a HUGE INDICATION for secondary reactive TB -As well as lost 15 lbs -We get coughing up of blood due to tissue damage -If we hear crackles, this indicated that the alveolar is inflamed and has exudate

From case 4 How would you describe this patient's TB infection?

Pott disease

Case 1 A 23-year-old woman reports to her physician for a physical examination prior to joining an international medical mission project for the next year. She denies any complaints and her past medical history is unremarkable. She enthusiastically shares with the physician that she joined a church mission trip to Indonesia 6 months ago and "got hooked". Physical examination is entirely normal. A chest X-ray, required for the work physical, is shown in the accompanying image.

Primary TB (latent)

Primary TB

Results in a Ghon complex (ghon focus + hilar lymph nodes) -Occurs in the middle and lower lobes of the lung WHy? b/c of airflow 90% of individuals host immune response can control the infection in the ghon complex 10% of individual host immune response fails and results in pleural effusion

For case 2 How would you describe this patient's TB infection?

Secondary reactive TB

For case 2 Describe the pathophysiology, including immunology, of reactivation TB.

Th1 response no longer containing disease

Case 4 A 45-year-old woman reports to her physician with severe upper lumbar back pain that is interfering with activities of daily living, ongoing for 4 months. She emigrated from China 10 years ago. She denies any other complaints and has no other known medical problems. Upon examination, vital signs are all within normal limits. Lungs are clear. The following findings are noted upon spine examination and follow-up imaging. Her CXR in the office reveals only some subtle apical scarring. Patient reports that she received BCG as a child in China. PPD is 15 mm of induration at 50 hours. IGRA is positive.

This is disseminated TB Notes: -subtle apical scarring means they had TB before BCG -"a vaccine w/ a bovine strain"

How are Mycobacteria spp. different from other bacteria?

Waxy cell wall

For case 2 What was the likely source of the patient's infection?

primary latent

How long does it take to culture M. tuberculosis?

weeks (up to 4)

Case 1 After viewing the CXR, the physician orders a PPD test that is applied in the office. The patient returns at 72 hours and the area of induration measures 20 mm. Interferon Gamma Release Assay is positive. • Describe the immunology of the PPD test. • What does the IGRA assess? • In what parts of the world is TB most prevalent? (Dr. Elci showed you!) • Why is she not sick? What do we call this TB illness? • What preventive measures would you take?

• Describe the immunology of the PPD test. Th1 -> interferon gamma-> macrophages-> cytokines-> tissue response • What does the IGRA assess? interferon gamma • In what parts of the world is TB most prevalent? (Dr. Elci showed you!) global south • Why is she not sick? What do we call this TB illness? -immune cells are working -Primary latent TB • What preventive measures would you take? -Rx x 4 months for Riframpin