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Pulm > SM_178a: MTB, NTM, and Fungal Infections > Flashcards

SM_178a: MTB, NTM, and Fungal Infections Flashcards

1
Q

Describe the pathogenesis of TB

A

TB

  • Airborne droplet nuclei
  • Initial focus subpleural in the midlung zone
  • Ingested by alveolar macrophages
  • Infected macrophages carried to regional lymph nodes
  • May spread hemategenously to multiple sites
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2
Q

The immune response to TB involves _____, which are important for _____ and _____

A

The immune response to TB involves activated lymphocytes, which are important for cell mediated immunity and tissue hypersensitivity

  • Cell mediated immunity: resistance to infection
  • Tissue hypersensitivity: altered cellular reactivity, involving granuloma formation, tissue necrosis, and cutaneous delayed reaction to tuberculin that develop 3-9 weeks after infection
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3
Q

_____ are the histopathological feature most common in TB

A

Granulomas are the histopathological feature most common in TB

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4
Q

Describe granulomas in TB

A

Granulomas in TB

  • Characteristic structure: necrotic center if caseating, surrounded by macrophages, and surrounded by T cells
  • Cells within the ring of macrophages are lysed contributing to centralized necrosis (caseation)
  • Epitheliod cells: highly stimulated macrophages
  • Langhans giant cell: fused macrophages oriented around tuberculosis antigen with multiple nuclei in a peripheral position
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5
Q

Primary TB infection is most often characterized by only a _____ while a minority of patients have a _____

A

Primary TB infection is most often characterized by only a positive tuberculin skin test while a minority of patients have a Ghon complex

  • Ghon complex: necrosis and calification of the initial pulmonary focus (Ghon) focus and draining regional lymph nodes
  • Rarely, there is young progressive primary tuberculosis: kids, advanced HIV/AIDS
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6
Q

Latent tuberculosis infection is ______, and patients _____ spread TB during this time

A

Latent tuberculosis infection is presence of Mycobacterium tuberculosis infection without symptoms or evidence of TB disease, and patient cannot spread TB during this time

(all bacteria harborbed within a few infected macrophages within the granuloma)

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7
Q

Active tuberculosis involves the presence of ______, and people with active tuberculosis _____ spread the disease

A

Active tuberculosis involves the presence of symptoms or evidence of TB disease, and people with active tuberculosis can spread the disease

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8
Q

Reactivation tuberculosis occurs when ______

A

Reactivation tuberculosis occurs when extracellular bacterial levels increase when the immune system is unable to control infection

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9
Q

The best test to diagnose latent TB infection is ______

A

The best test to diagnose latent TB infection is interferon gamma release assay

(PPD skin testing requires follow-up visit, can have operator error, can cross-react with BCG and NTM, and is negative in 25% with active disease)

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10
Q

Primary TB occurs in _____ and involves _____

A

Primary TB occurs in childhood, elderly, and AIDS patients and involves lower or middle lung field and hilar/mediastinal adenopathy

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11
Q

Reactivation TB occurs in ______ and involves ______

A

Reactivation TB occurs in adolescence and adulthood and involves apical posterior lung localization, often with cavitation

(no hilar adenopathy)

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12
Q

Chest X-ray of someone with reactivation TB shows _____

A

Chest X-ray of someone with reactivation TB shows upper lobe infiltrate and cavitary infiltrate

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13
Q

Chest X-ray of someone with primary tuberculosis shows _____

A

Chest X-ray of someone with primary tuberculosis shows lower or middle lung field localization and hilar or mediastinal adenopathy

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14
Q

Describe the clinical presentation of TB

A
  • Fever, night sweats, weight loss, shortness of breath, and hemoptysis
  • Cough > 2 weeks
  • History of exposure to infectious TB or positive tuberculin skin test
  • CXR findings of granulomas
  • Acid-fast bacilli
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15
Q

Treatment of active tuberculosis involves ______ followed by ______

A

Treatment of active tuberculosis involves 2 months of RIPE therapy (rifampin, isoniazid, pyrazinamide, ethambutol) followed by 4 months of rifampin and isoniazid

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16
Q

Latent tuberculosis is treated with ______, ______, or ______

A

Latent tuberculosis is treated with daily isoniazed for 9 months, daily rifampin for 4 months, or isoniazid plus rifapentine weekly for 3 months

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17
Q

Why does active TB need to be treated with multiple drugs?

A

Cavities contain large numbers of bacteria, and resistant variants of bacteria pre-exist in the bacterial population, so lower the chance of total resistance and increase chance of successful treatment by using a multi-drug regimen

(resistance to regimen is a product of the probabilities of resistance to any individual drug)

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18
Q

Multi-drug resistant TB is resistance to at least ______ and ______

A

Multi-drug resistant TB is resistance to at least isoniazid and rifampin

  • Primary: patient initially infected by MDR-TB
  • Acquired: poor adherence to treatment, allowing for selection of resistant bacteria
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19
Q

Most susceptible individuals develop ______ tuberculosis because an effective ______ immune response ______

A

Most susceptible individuals develop latent tuberculosis because an effective cellular immune response suppresses the disease

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20
Q

Extensively-drug resistant TB is resistance to ______ and ______ plus ______

A

Extensively-drug resistant TB is resistance to isoniazid and rifampin plus fluoroquinolones and any one of the second-line anti-TB injectable drugs (amikacin, kanamycin, or capreomycin)

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21
Q

Treatment of MDR and XDR TB involves _____ of _____

A

Treatment of MDR and XDR TB involves direct observation therapy of ≥ 4 active drugs guided by susceptibility testing

(costs are much higher than treating regular TB)

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22
Q

BGC vaccine _____ protect against TB infection but rather _____

A

BGC vaccine does not protect against TB infection but rather prevents serious disease in kids

  • Not effective for adults
  • Booster doses do not help
  • If someone has symptoms of TB, treat them as if they have TB regardless of whether they had the BCG vaccine
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23
Q

Primary reservoir of ongoing TB transmission is _______

A

Primary reservoir of ongoing TB transmission is untreated active pulmonary tuberculosis

(cannot spread TB if have latent TB)

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24
Q

TB is transmitted from humans with _____ pulmonary disease via ______

A

TB is transmitted from humans with active pulmonary disease via cough productive of infectious particles

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25
Q

Inhaled TB droplet nuclei cause ______ in the mid or lower lungs and spread via ______ to regional lymph nodes and via blood to other parts of body before an effective cell-mediated response develops

A

Inhaled TB droplet nuclei cause primary pneumonia in the mid or lower lungs and spread via lymphatics to regional lymph nodes and via blood to other parts of body before an effective cell-mediated response develops

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26
Q

______ has allowed for the emergence of mutli-drug resistant TB which can be very difficult to treat

A

Incomplete adherence to the medication regimen has allowed for the emergence of mutli-drug resistant TB which can be very difficult to treat

27
Q

A 25 year old medical student from Turkey presents with a positive tuberculin skin test (22 mm induration). He reports that he received the BGC vaccination in childhood. What do you advise him?

A

Either

  • Chest X-ray to rule out active TB and offer treatment for latent TB

OR

  • Confirm the test with interferon gamma release assay -> if positive, rule out active TB and offer treatment for latent TB
28
Q

Describe the clinical manifestations and diagnosis of NTM lung disease

A

NTM lung disease

  • Signs and symptoms are often variable and nonspecific: chronic cough, sputum production, and fatigue
  • Disease is difficult to diagnose without multiple positive respiratory cultures
  • Recovery from NTM from a single sputum sample is not proof of NTM disease, especially when AFB smear is negative and NTM are present in low numbers
29
Q

In contrast to TB, signs and symptoms of NTM are ______

A

In contrast to TB, signs and symptoms of NTM are often variable and non-specific

30
Q

Describe the diagnostic criteria for NTM lung disease

A

Diagnosis of NTM

  • Clinical: pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or CT scan that shows multifocal bronchiectasis with multiple small nodules AND exclusion of other diagnoses
  • Microbiologic: ≥2 positive culture results from sputum or positive culture results from bronchoalveolar lavage or transbronchial or other lung biopsy showing granulomatous inflammation or +AFB and positive culture for NTM
31
Q

Mycobacterium avium complex is associated with three major disease syndromes: _____, _____, and _____

A

Mycobacterium avium complex is associated with three major disease syndromes: pulmonary disease, disseminated disease (usually seen in advanced HIV/AIDS), and cervical lymphadenitis

32
Q

MAC complex infection is acquired by _____ from the ______, not from ______

A

MAC complex infection is acquired by inhalation or ingestion from the environment, not from person-to-person spread

  • Treatment involves azithromycin + rifampin + ethambutol for 12-18 months and amikacin for the first 2-3 months
33
Q

Disseminated MAC infection occurs in people with _____ and involves ______

A

Disseminated MAC infection occurs in people with HIV/AIDS and involves fever, sweats, and weight loss

34
Q

Mycobacterium kansasii infections presents as ______

A

Mycobacterium kansasii infections presents as pulmonary infection that mimics pulmonary TB

  • Acquired from the environment
  • Not transmitted from person to person
  • Treatment involves rifampin and ethambutol for ≥ 18 months (≥ 12 months after respiratory cultures are negative)
35
Q

Mycobacterium marinum, Mycobacterium chelonae-abscessus, and Mycobacterium fortuitum can cause ______ infection

A

Mycobacterium marinum, Mycobacterium chelonae-abscessus, and Mycobacterium fortuitum can cause cutaneous infection

36
Q

A 63 year old woman presents with chronic cough, weight loss, and bronchiectasis on chest CT. Which of the following supports diagnosis of NTM?

A. Household contact with active NTM infection
B. Positive tuberculin skin test

C. Isolation of MAC from 1 of 3 sputum specimens

D. Isolation of Mycobacterium gordonae from BAL

E. Isolation of Mycobacterium abscessus from BAL

A

A 63 year old woman presents with chronic cough, weight loss, and bronchiectasis on chest CT. Which of the following supports diagnosis of NTM?

A. Household contact with active NTM infection - no, acquired from environment
B. Positive tuberculin skin test - no, that is for TB

C. Isolation of MAC from 1 of 3 sputum specimens - need 2 positive samples

D. Isolation of Mycobacterium gordonae from BAL - not a real bacterium

E. Isolation of Mycobacterium abscessus from BAL

37
Q

Fungal pneumonia _______ and _____ usual empiric antibiotic therapy for pneumonia

A

Fungal pneumonia mimics bacterial pneumonia and non-infectious pulmonary diseases (e.g. lung cancer, vasculitis, and drug toxicity) and does not respond to usual empiric antibiotic therapy for pneumonia

38
Q

What testing might diagnosis of fungal pneumonia involve?

A
  • X-ray or CT
  • Histopathology
  • Culture
  • Bronchoalveolar lavage
  • Serology
  • Serum
  • Urine
39
Q

Endemic mycoses include _____, ______, and ______

A

Endemic mycoses include histoplasmosis (Histoplasma capsulatam), blastomycosis (Blastomyces dermatidis), and coccidioidomycosis (Coccidioides immitis and Coccidioides posadasii)

40
Q

Endemic fungal infections are acquired via ______

A

Endemic fungal infections are acquired via inhalation of infectious conidia

41
Q

When endemic fungi are identified in clinical cultures, they are ______

A

When endemic fungi are identified in clinical cultures, they are almost always the true pathogen

42
Q

Presentation of endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis) is

A

Presentation of endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis) is acute pneumonia, chronic pneumonia, or disseminated infection

(can also be asymptomatic)

43
Q

The characteristic tissue response to Histoplasma capsulatum is _____

A

The characteristic tissue response to Histoplasma capsulatum is caseating or non-caseating granulomas

44
Q

Histoplasmosis is common in the ______

A

Histoplasmosis is common in the Ohio and Mississippi River valleys

(associated with disruption of soil)

45
Q

Rapid diagnosis of histoplasmosis can be made by ______

A

Rapid diagnosis of histoplasmosis can be made by polysaccharide antigen detection in urine, serum, BAL fluid

(serology is not helpful with diagnosis)

46
Q

Blastomycosis is common in the ______

A

Blastomycosis is common in the North Central Great Lakes

(risk factor is exposure to soil)

47
Q

The characteristic pathological finding associated with blastomycosis is ______

A

The characteristic pathological finding associated with blastomycosis is broad-based budding yeast

48
Q

Definitive diagnosis of blastomycosis requires _____

A

Definitive diagnosis of blastomycosis requires recovery in culture

49
Q

Coccidioidomycosis is common in ________

A

Coccidioidomycosis is common in the Southwestern U.S.

(exposure to soil is risk factor)

50
Q

The characteristic pathological finding of coccidioidomycosis is _______

A

The characteristic pathological finding of coccidioidomycosis is spherules of endospores

51
Q

The most frequent means of diagnosing primary coccidioidomycosis is _____

A

The most frequent means of diagnosing primary coccidioidomycosis is serologic testing (highly specific)

(urine and serum antigen testing also useful, cultures grown on media are infectious)

52
Q

Fungal pathogens associated with opportunistic infection include ______ and ______

A

Fungal pathogens associated with opportunistic infection include Aspergillus (aspergillosis) and Pneumocystis jirovecii (Pneumocystis pneumonia)

Occur in immunocompromised people

53
Q

Patients who have _____ are at high risk for invasive aspergillosis

A

Patients who have prolonged and profound neutropenia are at high risk for invasive aspergillosis

(patients with normal pulmonary host defenses very rarely develop disease despite routine exposure to the organism)

54
Q

____ is highly sensitive for diagnosis of aspergillosis

A

Chest CT is highly sensitive for diagnosis of aspergillosis

  • Single or multiple nodules with or without cavitation
  • Patchy consolidation or peribronchial infiltrates
  • Halo sign: nodule with surrounding ground glass infiltrate (hemorrhage into area surrounding fungal infection)
55
Q

Definitive diagnosis of aspergillosis requires ______

A

Definitive diagnosis of aspergillosis requires recovery of Aspergillus in culture of tissue or BAL fluid

(note histopathology shows septate hyphae with acute angle 45º branching)

56
Q

Describe the important points about Aspergillosis

A

Aspergillosis

  • Acquired by inhalation from environment
  • Distinguish colonization from infection
  • Invasive infection associated with prolonged neutropenia
  • Vascular invasion, crosses tissue planes
  • Cavitary nodular pulmonary infiltrates
57
Q

Patients who have _____ are at high risk for Pneumocystis infection

A

Patients who have defects in cellular and humoral immunity are at high risk for Pneumocystis infection

  • Advanced HIV (CD4 < 200)
  • Prolonged, high dose corticosteroid therapy
  • Anti-rejection therapy
58
Q

Laboratory diagnosis of Pneumocystis pneumonia is made via _____ and _____

A

Laboratory diagnosis of Pneumocystis pneumonia is made via hypoxemia or elevated LDH

59
Q

Describe the important points about Pneumocystis

A

Pneumocystis

  • Person-to-person transmission
  • Associated with immunosuppression: advanced HIV infection (CD4 < 200), corticosteroid, anti-rejection therapy
  • Diffuse pulmonary infiltrates and hypoxemia
60
Q

Describe radiographic findings of Pneumocystis pneumonia

A
  • CXR: diffuse bilateral symmetrical interstitial infiltrates
  • Chest CT: patchy ground glass attenuation
61
Q

How are endemic fungal infections acquired?

A

Inhalation of infectious conidia

62
Q

A 57 year old male presents with fever, cough, and a dense infiltrate on CXR. BAL cytology shows broad-based budding yeast. Where did he likely acquire this infection?

A

North Central Great Lakes region of the U.S. (blastomycosis)

63
Q

The CT finding associated with angioinvasive Aspergillus infection is ______

A

The CT finding associated with angioinvasive Aspergillus infection is halo

64
Q

Test for ______ BAL samples of someone with angioinvasive Aspergillus infection

A

Test for galactomannan BAL samples of someone with angioinvasive Aspergillus infection

Pulm (32 decks)

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