27.28. Tuberculosis and other pulmonary infections Flashcards
What is tuberculosis?
It is an infectious disease caused by Mycobacterium tuberculosis, a slow-growing bacteria.
What is the mechanism of infection of tuberculosis?
It is usually by inhalation of aerosols containing TB, through close contact with patients with active TB infection.
What is latent TB infection?
It is a dormant M. tuberculosis infection, typically due to intact innate and cellular immune responses.
What are the other strains of the tuberculosis complex?
They are M. bovis, M. africanum
What are the high-risk groups for TB?
- HIV patients,
- close contacts,
- patients with old healed apical fibronodular lesions,
- IV drug users,
- immigrants from high prevalence countries,
- those in correctional institutions, nursing homes, and mental institutions.
How does prolonged exposure to TB increase the risk of infection?
It increases the risk of infection by 30-50% in people living in the same household.
What are the other routes of TB infection?
Intestines (unpasteurized milk) and skin (open wound, tuberculosis verrucosa cutis – butchers, pathologists).
What is the pathomechanism of TB infection?
- Granulomatous inflammation
- TB antigens activate lymphocytes and NK cells which produce IFN-gamma
- Macrophages differenciate into epitheloid cells and multinucleated giant cells : enclose the bacteria like a wall
What is the pathophysiology of primary TB?
New TB infection → entry of M. tuberculosis into macrophages → survives because of the inhibition of both phagosome maturation and phagolysosome fusion.
What happens following replication of M. Tuberculosis in the alveolar macrophages in primary TB?
The released bacteria attacks uninfected macrophages to spread infection.
What causes central caseous necrosis and tissue damage in primary TB?
Destruction of M. tuberculosis-infected macrophages causes central caseous necrosis and tissue damage → granuloma limits the spread of infection.
What is a Ghon focus?
A granuloma typically located in the middle and lower lobes
What is a Ghon complex?
- A Ghon focus + enlarged lymph nodes + lymphatic vessels connecting the two, which means that the lymph nodes become infected as well.
- It can be seen on a CXR as a more extensive area of inflammation than the Ghon focus alone.
What is the disease progression of TB with a sufficient immune response?
The granulomas in the Ghon complex undergo fibrosis and calcification to form the Ranke complex, which is radiologically detectable.
What is the disease progression of TB with a deficient immune response?
Progressive primary TB causing progressive lung disease, bacteremia, and miliary TB (disseminated TB).
What is post-primary (secondary) TB?
It is the reactivation of TB due to weakening of the immune response (e.g. HIV).
What are the clinical features of TB?
- Cough, initially dry, later productive (cheesy),
- fever,
- night sweats,
- weight loss
- hemoptysis.
What is the difference between primary and post-primary TB?
Primary TB is the initial infection, while post-primary TB is the reactivation of TB due to weakening of the immune response.
What are the diagnostic follow-ups in suspected tuberculosis?
- History (try to find exposure to TB),
- chest X-ray,
- general lab tests,
- bacteriology.
What are the lab signs of tuberculosis?
ESR, CRP, neutrophilia, lymphopenia, hypoalbuminemia, anemia, impaired liver function, hyponatremia, low iron, and increased ferritin.
What are the auscultation findings in tuberculosis?
- Rales
- Lung consolidation (very clear sounds)
- wheezing as peribronchial and endobronchial airway obstruction develops
What is the main rule for tuberculosis on chest X-ray?
TB can induce any pattern of X-ray shadowing, including upper lung zone fibronodular pattern and upper lung zone fluffy coalescence.
What percentage of TB patients have lower zone involvement?
Less than 15%.
Are pleural effusions common in reactivation-type pulmonary TB?
No, they are uncommon.
What is the significance of morning sputum in TB diagnosis?
It is used to detect the presence of TB bacteria in the patient’s respiratory secretions, after testing with Ziehl Neelsen stain.
How many consecutive days should morning sputum be taken for TB diagnosis?
Three.
What is the preferred method of obtaining respiratory secretions if the patient cannot provide morning sputum?
Gastric lavage.
Will TB bacteria be destroyed by gastric acid?
No.
What are the more invasive measurements that can be done if morning sputum or gastric lavage is not available?
Bronchial wash and bronchoalveolar lavage.
What is a special requirement for blood samples taken for TB diagnosis?
A special hemoculture container is needed.
What is the gold standard for diagnosing latent TB?
Lewenstein-Jensen (solid medium).
What are the pros and cons of Lowenstein Jensen?
- More sensitive
- But takes 8 weeks
How long does it take for liquid medium to diagnose latent TB?
2-3 weeks.
What does a positive culture and negative sputum sample indicate in TB diagnosis?
Latent TB.
What skin test can be used for TB?
Tuberculin skin test (Mantoux).
What is the hypersensitive response to the tuberculin skin test?
Edema >10mm.
What does anergic response to the tuberculin skin test indicate?
Susceptibility to TB or immunocompromised.
What factors affect the interpretation of the tuberculin skin test?
BCG vaccination, prior infection, immune system
What is the Quantiferon TB test?
It is a test that isolates mononuclear cells from a patient’s blood sample and checks if they produce IFN-gamma in the presence of MTBC antigens, indicating sensitization to TB.
What are the advantages of the Quantiferon TB test over the tuberculin skin test?
It is more sensitive and specific than the tuberculin skin test and is not positive in non-TB cases.
What is the first-line treatment for TB?
The first-line treatment for TB includes Rifampicin, Isoniazid, Pyrazinamide and Ethambutol. (RIPE)
What are the side effects of Rifampicin?
- Hepatotoxicity,
- exanthemas,
- hemolytic anemia,
- renal insufficiency,
- secretion of orange-colored fluids.
What are the side effects of Isoniazid?
The side effects of Isoniazid include hepatotoxicity, neurotoxicity, and MAO inhibition.
What are the side effects of Pyrazinamide?
- Hepatotoxicity,
- hyperuricemia (jaundice),
- photosensitive dermatitis
- polyarthralgia.
Should Pyrazinamide be avoided in pregnancy?
Yes.
How often should Pyrazinamide be administered in renal failure?
Every other day.
What are the side effects of Ethambutol?
Optic neuritis (vision problems), peripheral neuritis.
Can Ethambutol be given in pregnancy?
Yes.
What is the usual 6-month treatment plan for TB?
2 months of 4 drugs (intensive phase), followed by 4 months of isoniazid and rifampicin (continuation phase).
What is the duration of treatment if the therapeutic response is not adequate?
It can be prolonged to 12 months.
What are the second-line treatments for TB?
Streptomycin, kanamycin, amikacin, cycloserine, ethionamide, PAS, and levofloxacin.
PAS : para-aminosalicylic acid
What are the side effects of Levofloxacin?
GI symptoms, QT prolongation, photosensitivity.
Can Levofloxacin be given in pregnancy and renal failure?
Yes.
What are the side effects of Ethionamide at a dose of 1g/day?
Nausea and hepatotoxicity.
What are the side effects of PAS at a dose of 12-15g/day?
GI symptoms, hepatotoxicity, coagulopathy, and hypothyroidism.
What is the recommended dose range for Levofloxacin or Moxifloxacin in TB treatment?
500-1000mg/day.
What is drug-resistant TB?
TB that is resistant to one first-line agent.
What is multidrug-resistant (MDR) TB?
TB that is resistant to isoniazid and rifampicin.
What is extensively drug-resistant (XDR) TB?
MDR TB plus resistance against fluoroquinolones and on second-line IV drug (amikacin, kanamycin).
When can we presume resistance in MDR-(XDR) TB treatment?
If there is no clinical improvement after 1-2 months of treatment, we can presume resistance even before the culture results.
What is the recommended duration of treatment for MDR-(XDR) TB?
At least 18-24 months with 4 effective drugs, preferably with DOT (directly observed therapy).
What is the recommended drug regimen for MDR-(XDR) TB treatment?
Effective first-line drug plus fluoroquinolones plus daily administered IV drug plus effective second-line agent.
What is Pneumocystis jirovecii pneumonia (PCP)?
It is an opportunistic fungal lung infection that occurs in almost exclusively immunocompromised individuals.
What are the risk factors for PCP?
- HIV infection,
- primary immunodeficiency disorder,
- immunosuppressive treatment.
What are the clinical features of PCP?
- Fever,
- dyspnea,
- nonproductive cough,
- fatigue,
- weight loss,
- chills,
- may progress to respiratory failure.
What are the diagnostic tests for PCP?
- Lab test -> beta-glucan (occurs in cell wall of most fungi), CD4 count (HIV),
- Imaging -> CXR: diffuse, bilateral, symmetrical interstitial infiltrates extending from the perihilar region (butterfly pattern),
- Histopathology: (confirmatory test) -> Induced sputum and bronchoalveolar lavage.
What is the treatment for mild to moderate PCP?
Oral TMP/SMX.
What is the treatment for moderate to severe PCP?
IV TMP/SMX.
What is the prophylaxis for patients with HIV infection with low CD4 cell count?
for asp. and pcp prevention
Low dose TMP/SMX.
What is Aspergillosis?
It is the collective term for diseases caused by the mold species in the genus Aspergillus (opportunistic pathogen).
What is the etiology of Aspergillosis?
Most common : Aspergillus fumigatus + Aspergillus flavus.
What is aspergillosis?
Aspergillosis is the collective term for diseases caused by the mold species in the genus Aspergillus.
How is aspergillosis transmitted?
Aspergillosis is transmitted through airborne exposure to mold spores that settle on a source of nutrition, dust, or plants.
What are the risk factors for aspergillosis?
The risk factors for aspergillosis include severe immunosuppression or neutropenia, as well as preexisting bronchopulmonary conditions such as asthma or CF.
neutropenia : low blood count of neutrophils
What is Aspergillus bronchopulmonary aspergillosis (ABPA)?
- Aspergillus bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction caused by exposure to Aspergillus that occurs in patients with CF or asthma
- It is characterized by asthmatic symptoms and productive cough with brown bronchial mucous casts.
What is chronic pulmonary aspergillosis?
- Chronic pulmonary aspergillosis is a long-term Aspergillus infection which can manifest as an aspergilloma, a opportunistic infection of a preexisting cavitary lesion,
- It is characterized by hemoptysis and dyspnea.
What is invasive aspergillosis?
Invasive aspergillosis is a severe form of aspergillosis which manifests with severe pneumonia and septicemia with potential involvement of other organs, and is characterized by dry cough, hemoptysis, pleuritic chest pain, and tachypnea.
What are the diagnostic methods for aspergillosis?
- chest X-ray, CT scan,
- culture of Aspergillus in sputum or bronchoalveolar lavage,
- skin test for Aspergillus antigen,
- elevated IgE levels in ABPA,
- elevated galactomannan antigen test in invasive aspergillosis.
