SM_178a: MTB, NTM, and Fungal Infections Flashcards
Describe the pathogenesis of TB
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
The immune response to TB involves _____, which are important for _____ and _____
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
_____ are the histopathological feature most common in TB
Granulomas are the histopathological feature most common in TB
Describe granulomas in TB
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
Primary TB infection is most often characterized by only a _____ while a minority of patients have 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
Latent tuberculosis infection is ______, and patients _____ spread TB during this time
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)
Active tuberculosis involves the presence of ______, and people with active tuberculosis _____ spread the disease
Active tuberculosis involves the presence of symptoms or evidence of TB disease, and people with active tuberculosis can spread the disease
Reactivation tuberculosis occurs when ______
Reactivation tuberculosis occurs when extracellular bacterial levels increase when the immune system is unable to control infection
The best test to diagnose latent TB infection is ______
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)
Primary TB occurs in _____ and involves _____
Primary TB occurs in childhood, elderly, and AIDS patients and involves lower or middle lung field and hilar/mediastinal adenopathy
Reactivation TB occurs in ______ and involves ______
Reactivation TB occurs in adolescence and adulthood and involves apical posterior lung localization, often with cavitation
(no hilar adenopathy)
Chest X-ray of someone with reactivation TB shows _____
Chest X-ray of someone with reactivation TB shows upper lobe infiltrate and cavitary infiltrate
Chest X-ray of someone with primary tuberculosis shows _____
Chest X-ray of someone with primary tuberculosis shows lower or middle lung field localization and hilar or mediastinal adenopathy
Describe the clinical presentation of TB
- 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
Treatment of active tuberculosis involves ______ followed by ______
Treatment of active tuberculosis involves 2 months of RIPE therapy (rifampin, isoniazid, pyrazinamide, ethambutol) followed by 4 months of rifampin and isoniazid
Latent tuberculosis is treated with ______, ______, or ______
Latent tuberculosis is treated with daily isoniazed for 9 months, daily rifampin for 4 months, or isoniazid plus rifapentine weekly for 3 months
Why does active TB need to be treated with multiple drugs?
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)
Multi-drug resistant TB is resistance to at least ______ and ______
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
Most susceptible individuals develop ______ tuberculosis because an effective ______ immune response ______
Most susceptible individuals develop latent tuberculosis because an effective cellular immune response suppresses the disease
Extensively-drug resistant TB is resistance to ______ and ______ plus ______
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)
Treatment of MDR and XDR TB involves _____ of _____
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)
BGC vaccine _____ protect against TB infection but rather _____
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
Primary reservoir of ongoing TB transmission is _______
Primary reservoir of ongoing TB transmission is untreated active pulmonary tuberculosis
(cannot spread TB if have latent TB)
TB is transmitted from humans with _____ pulmonary disease via ______
TB is transmitted from humans with active pulmonary disease via cough productive of infectious particles
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
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
______ has allowed for the emergence of mutli-drug resistant TB which can be very difficult to treat
Incomplete adherence to the medication regimen has allowed for the emergence of mutli-drug resistant TB which can be very difficult to treat
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?
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
Describe the clinical manifestations and diagnosis of NTM lung disease
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
In contrast to TB, signs and symptoms of NTM are ______
In contrast to TB, signs and symptoms of NTM are often variable and non-specific
Describe the diagnostic criteria for NTM lung disease
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
Mycobacterium avium complex is associated with three major disease syndromes: _____, _____, and _____
Mycobacterium avium complex is associated with three major disease syndromes: pulmonary disease, disseminated disease (usually seen in advanced HIV/AIDS), and cervical lymphadenitis
MAC complex infection is acquired by _____ from the ______, not from ______
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
Disseminated MAC infection occurs in people with _____ and involves ______
Disseminated MAC infection occurs in people with HIV/AIDS and involves fever, sweats, and weight loss
Mycobacterium kansasii infections presents as ______
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)
Mycobacterium marinum, Mycobacterium chelonae-abscessus, and Mycobacterium fortuitum can cause ______ infection
Mycobacterium marinum, Mycobacterium chelonae-abscessus, and Mycobacterium fortuitum can cause cutaneous infection
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 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
Fungal pneumonia _______ and _____ usual empiric antibiotic therapy for pneumonia
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
What testing might diagnosis of fungal pneumonia involve?
- X-ray or CT
- Histopathology
- Culture
- Bronchoalveolar lavage
- Serology
- Serum
- Urine
Endemic mycoses include _____, ______, and ______
Endemic mycoses include histoplasmosis (Histoplasma capsulatam), blastomycosis (Blastomyces dermatidis), and coccidioidomycosis (Coccidioides immitis and Coccidioides posadasii)
Endemic fungal infections are acquired via ______
Endemic fungal infections are acquired via inhalation of infectious conidia
When endemic fungi are identified in clinical cultures, they are ______
When endemic fungi are identified in clinical cultures, they are almost always the true pathogen
Presentation of endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis) is
Presentation of endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis) is acute pneumonia, chronic pneumonia, or disseminated infection
(can also be asymptomatic)
The characteristic tissue response to Histoplasma capsulatum is _____
The characteristic tissue response to Histoplasma capsulatum is caseating or non-caseating granulomas
Histoplasmosis is common in the ______
Histoplasmosis is common in the Ohio and Mississippi River valleys
(associated with disruption of soil)
Rapid diagnosis of histoplasmosis can be made by ______
Rapid diagnosis of histoplasmosis can be made by polysaccharide antigen detection in urine, serum, BAL fluid
(serology is not helpful with diagnosis)
Blastomycosis is common in the ______
Blastomycosis is common in the North Central Great Lakes
(risk factor is exposure to soil)
The characteristic pathological finding associated with blastomycosis is ______
The characteristic pathological finding associated with blastomycosis is broad-based budding yeast
Definitive diagnosis of blastomycosis requires _____
Definitive diagnosis of blastomycosis requires recovery in culture
Coccidioidomycosis is common in ________
Coccidioidomycosis is common in the Southwestern U.S.
(exposure to soil is risk factor)
The characteristic pathological finding of coccidioidomycosis is _______
The characteristic pathological finding of coccidioidomycosis is spherules of endospores
The most frequent means of diagnosing primary coccidioidomycosis is _____
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)
Fungal pathogens associated with opportunistic infection include ______ and ______
Fungal pathogens associated with opportunistic infection include Aspergillus (aspergillosis) and Pneumocystis jirovecii (Pneumocystis pneumonia)
Occur in immunocompromised people
Patients who have _____ are at high risk for invasive aspergillosis
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)
____ is highly sensitive for diagnosis of aspergillosis
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)
Definitive diagnosis of aspergillosis requires ______
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)
Describe the important points about Aspergillosis
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
Patients who have _____ are at high risk for Pneumocystis infection
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
Laboratory diagnosis of Pneumocystis pneumonia is made via _____ and _____
Laboratory diagnosis of Pneumocystis pneumonia is made via hypoxemia or elevated LDH
Describe the important points about Pneumocystis
Pneumocystis
- Person-to-person transmission
- Associated with immunosuppression: advanced HIV infection (CD4 < 200), corticosteroid, anti-rejection therapy
- Diffuse pulmonary infiltrates and hypoxemia
Describe radiographic findings of Pneumocystis pneumonia
- CXR: diffuse bilateral symmetrical interstitial infiltrates
- Chest CT: patchy ground glass attenuation
How are endemic fungal infections acquired?
Inhalation of infectious conidia
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?
North Central Great Lakes region of the U.S. (blastomycosis)
The CT finding associated with angioinvasive Aspergillus infection is ______
The CT finding associated with angioinvasive Aspergillus infection is halo
Test for ______ BAL samples of someone with angioinvasive Aspergillus infection
Test for galactomannan BAL samples of someone with angioinvasive Aspergillus infection
