Mycobacteria (TB, leprosy, etc.) Flashcards
Mycobacterium tuberculosis is an tuberculosis is an upper or lower respiratory tract infection?
Initially this is a lower respiratory infection that can have consequences later on that indicate an upper respiratory infection especially with reactivation.
Is it possible that on initial exposure to mycobacterium tuberculosis, patients can immediately clear the pathogen?
Yes, infection due to tuberculosis is often through respiratory droplets and the bacteria can be immediately cleared or result in a primary infection, latent infection or reactivation of disease.
What type of stain is used to identify Mycobacterium tuberculosis?
Ziehl-Neelsen stain with carbol fuchsin (acid-fast stain).
What medium is used to culture Mycobacterium tuberculosis?
Lowenstein-Jensen agar.
What is the major virulence factor of M. tuberculosis that prevents phagosome-lysosome fusion?
Sulfatides.
Which virulence factor of M. tuberculosis contributes to granuloma formation and evasion of macrophages?
Cord factor.
What are the characteristics of a plural effusion for TB?
1) Turbid if chronic or with fibrinous strands and serosanguinous.
2) Exudative (protein > 0.5, LDH > 0.6, or greater than 2/3 the U/L for LDH)
3) ADA >40 U/L
4) Usually normal or slightly low (can be <60 mg/dL in advanced cases)
Why is ADA high with TB?
ADA is elevated in TB pleural effusion due to increased T-cell activation and macrophage response. ADA >40 U/L strongly suggests TB in a lymphocyte-predominant exudative effusion.
Which patient population is at increased risk of TB?
Prisoners, healthcare workers, recent immigrants within five years, close contacts with someone with TB, IV drug use, immunodeficiencies such as HIV/glucocorticoid use/hematologic malignancy.
What are the symptoms of primary tuberculosis?
Cough, night sweats, anorexia, and weight loss.
Are the symptoms of active TB and reactivation of TB similar?
Yes, active primary TB and reactivation TB share many symptoms, but reactivation TB is more likely to cause localized lung findings and systemic symptoms due to a stronger immune response. The cough associated with reactivation of TB tends to include hemoptysis, where this is a rare finding in primary TB infection.
What is the common radiologic finding in primary tuberculosis?
Ghon complex (calcified lung lesion that occasionally can be nearby pulmonary lymph nodes (hilar LAD).
What is the hallmark of miliary TB?
- Hematogenous dissemination leading to millet seed-like lesions.
- Can lead to organ failure and septic shock.
- Millet seed-like lesions in lungs.
- Can involved bones, adrenal glands, CNS, and GU (sterile pyuria).
- Diagnosis is with acid fast blood cultures and tissue biopsy (culture/NAA)
What is a clinical key of TB meningitis seen on CT?
Suspicion for tuberculous meningitis is typically raised when brain imaging reveals basilar meningeal enhancement.
TB meningitis will have what CSF findings?
Suspicion for tuberculous meningitis is typically raised when brain imaging reveals basilar meningeal enhancement and cerebrospinal fluid (CSF) examination shows the following:
- Elevated protein (>250 mg/dL, generally 100-500 mg/dL)
- Low glucose (<45 mg/dL)
- Lymphocytic pleocytosis (predominant)
- Elevated adenosine deaminase
What is the treatment regimen for active tuberculosis?
- RIPE: Rifampin, Isoniazid, Pyrazinamide, and Ethambutol.
- 4 months of isoniazid (plus B6) and rifampin.
Is intrathecal delivery of anti-TB medications required for TB meningitis?
- No.
- Isoniazid, rifampin, and pyrazinamide are all bactericidal with good CNS penetration.
- Intrathecal medications are not required.
What is unique about the treatment for TB meningitis that lowers morbidity and mortality?
Tuberculous meningitis is associated with a high risk of long-term neurologic sequelae. Prompt treatment reduces this risk, but many patients have permanent neurologic damage. Prolonged treatment is required with 2 months of 4-drug therapy (isoniazid, rifampin, pyrazinamide, and either a fluoroquinolone or injectable aminoglycoside), followed by 9-12 months of continuation therapy (isoniazid plus rifampin). Since treatment can cause transient worsening of central nervous system inflammation, patients with tuberculous meningitis are typically given 6-8 weeks of adjuvant glucocorticoid therapy (dexamethasone or prednisone). This significantly reduces morbidity and mortality.
What is the treatment for active TB in a pregnant patient?
Pregnant patients with an upper lobe cavitary infiltrate and acid-fast bacilli in sputum likely have active pulmonary tuberculosis (TB). Pregnant women with active TB require treatment as untreated infections carry significant risk for the mother, fetus, and close contacts. Treatment usually involves 3-drug therapy with isoniazid (INH), rifampin (RIF), and ethambutol for 2 months followed by INH and RIF for 7 additional months. All 3 of these medications cross the placenta but are not associated with significant fetal toxicity. Pyrazinamide, part of the 4-drug TB treatment given to nonpregnant individuals, is generally not administered in pregnancy due to uncertain teratogenic properties and little contribution to overall TB treatment efficacy. Pregnant women undergoing treatment for TB should also receive pyridoxine (vitamin B6) supplementation to prevent INH-induced neurotoxicity. Counseling about medication side effects and monthly monitoring for disease response and drug-associated hepatitis are required.
What consideration is given for latent TB?
Those with no symptoms and a normal chest x-ray are considered to have latent tuberculosis infection (LTBI). LTBI is noninfectious, and individuals may continue their normal daily lives without restrictions.
What are the major risk factors for reactivation of latent tuberculosis?
HIV, immunosuppression, and TNF-alpha inhibitor therapy.
What extrapulmonary condition is associated with TB of the spine?
Pott disease.
What diagnostic test is used to screen for TB and involves an intradermal injection?
Purified protein derivative (PPD) skin test.
What type of hypersensitivity reaction is tuberculin skin test (PPD)?
Type IV HSR (Th1 Mediated)
A PPD is considered positive in those with high risk of TB if the induration size is greater than …?
5 mm
Who are considered high risk individuals for TB?
HIV, recent TB contact, immunocompromised, transplant recipients, evidence of prior TB infection (lung calcification, fibrosed regions, nodular regions).
The PPD may be false-negative in patients with
CD4+ counts < 200/mm3 (HIV), patients on immunosuppressants, as well as those who have Sarcoidosis.
A PPD is considered positive in those with intermediate risk of TB if the induration size is greater than …?
10 mm
A PPD is considered positive in those with normal risk of TB if the induration size is greater than …. ?
15 mm (in any individual)
Who are considered moderate risk individuals for TB?
Recent immigrants (<5 years) from TB-endemic areas
Injection drug users
Residents & employees of high-risk settings (eg, prisons, nursing homes, hospitals, homeless shelters)
Mycobacteriology laboratory personnel
Higher risk for TB reactivation (eg, diabetes, prolonged corticosteroid therapy, leukemia, end-stage renal disease, chronic malabsorption syndromes)
Children age <4, or those exposed to adults in high-risk categories
What is unique to the TB testing process for healthcare personnel employment?
Most organizations recommend 2-step pre-employment testing for LTBI because exposure to TB several years prior may results in a false-negative initial tuberculin skin testing. Therefore, individuals with negative initial skin test should have repeat testing in 1-3 weeks. Patients with a positive tuberculin skin test do not require repeat skin testing.
What is the time requirement for returning to work if the health screen is positive, but there are no signs of active infection?
All healthcare personnel should receive regular (eg, annual) screening for tuberculosis (TB) with a tuberculin skin test or interferon-gamma release assay. Personnel who have a skin test with ≥10-mm induration at 48 hours are likely to be infected with Mycobacterium tuberculosis and should undergo a chest x-ray. Those with no chest x-ray abnormalities and no symptoms, such as a chronic cough, weight loss, night sweats, are considered to have latent tuberculosis infection (LTBI), which is noninfectious. LTBI screening should only be offered if treatment would be considered because, for most patients, the lifetime risk of advancing to active TB is small (5%-10%). Treatment (eg, 6-9 months of isoniazid) should be offered to affected individuals who are at higher risk of developing active TB (eg, immunosuppressed individuals) or those who reside (eg, inmates) or work (eg, HCP) in high-risk congregate settings. Because LTBI is noninfectious, affected individuals, including HCP, may continue to work without restrictions (even if they decline or do not complete treatment). Additionally, they do not require precautions (eg, N95 mask) or a full course of treatment to continue working. Health care personnel (HCP) should be screened for tuberculosis on a regular basis. Infection is likely if skin testing shows ≥10-mm induration at 48 hours. Those with no symptoms and a normal chest x-ray are considered to have latent tuberculosis infection (LTBI). LTBI is noninfectious, and individuals may continue their normal daily lives without restrictions. However, because HCP work in congregant settings, treatment (eg, isoniazid) should be offered.
When is a PPD recommended as part of prenatal care?
The PPD skin test is only indicated in pregnant women with one or more of the following risk factors: known case of HIV infection, close contact with individuals suspected of having tuberculosis, immigration from a highly endemic region, homelessness, living or working in prisons or mental health care facilities, certain non-infectious diseases that increase the risk of tuberculosis (e.g. diabetes mellitus, cancer, alcohol use disorder, intravenous drug use).
(+) PPD with (-) X-ray is managed with … ?
Isoniazid for 9 months
other forms of treatment for latent TB:
Isoniazid and rifapentine for 3 months or rifampin for 4 months
active TB (RIPE) is managed with … ?
2 months of RIPE: Rifampin, Isoniazid, Pyrazinamide, and Ethambutol
and
4 months of isoniazid and rifampin
Following a (+) PPD, first order what diagnostic test?
a chest x-ray
differentiates between active and latent TB
In the United States, a PPD is considered negative in healthy patients with low likelihood of TB if the induration size is <
15 mm
the cutoff for intermediate-risk patients (e.g. healthcare workers, recent immigrants) is < 10 mm
Why should individuals who are to be started on a TNF-α inhibitors (e.g. infliximab) receive a PPD test?
Inhibition of TNF-α via immunosuppression drugs causes lack of TNF-α –> lack of granuloma –> lack of containment of tuberculosis –> resultant reactivation of tuberculosis
Interferon-γ release assay (IGRA) has (greater/fewer) false positives from BCG vaccination than PPD testing?
fewer
IFN-γ release assay tests cell mediated response by seeing if macrophages release IFN-γ when presented with antigen.
These assays don’t get false positives from patients who are BCG vaccinated, thus are the preferred methods of testing for these patients.
Is Interferon-γ release assay (IGRA) is influenced by prior BCG vaccination?
No
If someone has prior BCG vaccination, performing a PPD test is not appropriate given the high false-positive rate in such individuals
Regardless, you interpret the PPD screen ignoring the fact that the patient has had a BCG vaccine.
Is latent TB transmissible to others?
No. People with LTBI do not transmit TB to others. Regardless treatment should still be offered.
Isoniazid can be given as a monotherapy for tuberculosis ONLY when there is a(n)
positive PPD and a negative chest x-ray
What is the next step in management for a healthy patient with 16-mm induration at 48 hours following PPD testing, normal chest X-ray, and no acid-fast bacilli?
9 months of isoniazid and pyridoxine (B6)
What is the next step in management for an asymptomatic patient that has a 12-mm induration two days after a PPD injection? The patient has no TB risk factors.
No additional intervention required
in the US, an induration size of < 15 mm is considered negative in healthy patients with low likelihood of TB
What is the next step in management for an HIV patient who has an 8-mm induration at 48 hours following PPD testing and a normal chest X-ray?
9 months of Isoniazid and pyridoxine (B6)
this patient should be treated for latent TB (> 5 mm)
What can be used besides CXR for active TB infection
Sputum cultures taken at various times
Test with AFB smear, mycobacterium culture and NAA test
What is seen on CXR for patients with a primary TB infection?
hilar lymphadenopathy
patients are usually asymptomatic with possibly fever, cough, and fatigue
primary TB infection is typically diagnosed with … ?
PPD or IFN y release
Reactivation of TB has what characteristic CXR?
pulmonary infiltrate in the upper lobe
diagnosis should be with CXR and sputum.
when can a patient come out of isolation while being treated for TB?
- After 2 weeks on medication and improving with 3 consecutive AFB smears.
- Patients treated for active TB are considered noninfectious when 3 consecutive acid-fast bacilli sputum smears are negative (8-24-hour intervals and ≥1 early morning samples).
What is the characteristic temperature preference for Mycobacterium leprae?
Cooler temperatures, often affecting the skin and extremities.
What type of stain is used to identify Mycobacterium leprae?
Acid-fast stain, specifically using carbol fuchsin (Ziehl-Nelson).
High concentration of mycolic acid.
What is the main non-human reservoir for Mycobacterium leprae in the United States?
Armadillos (rarely).
Primarily transmitted through respiratory droplets from infected people.
What type of immune response is associated with tuberculoid leprosy?
A strong TH1 cell-mediated immune response.
It leads to the containment of the bacteria within macrophages.
How does tuberculoid leprosy typically present on the skin?
As well-demarcated, slightly elevated, hypopigmented, hairless, hypoesthetic skin macules or plaques.
What type of immune response is predominant in lepromatous leprosy?
A TH2 humoral immune response.
The TH2 response leads to failed containment of the bacteria, leading to dissemination of the bacteria to various parts of the body.
Leads to a higher risk of human-to-human transmission.
What are the common neurological manifestations of lepromatous leprosy?
“Glove and stocking” neuropathy, with sensory loss in the extremities.
Palpable nerves with neuropathy.
Characterized by loss of sensitivity to temperature and pain in the extremities
What is the facial deformity commonly seen in advanced lepromatous leprosy?
Leonine facies.
Thickening of the skin, loss of eyebrows and eyelashes, nasal collapse, and nodular earlobes.
What is the treatment regimen for tuberculoid leprosy?
Dapsone and rifampin for 6-24 months.
What is the treatment regimen for lepromatous leprosy?
Dapsone, rifampin, and clofazimine for 2-5 years.
How is lepromatous leprosy transmitted between humans?
Through prolonged, close contact over many months.
What test can differentiate tuberculoid from lepromatous leprosy?
Tuberculoid leprosy presents with well-demarcated, hairless plaques, while lepromatous leprosy presents with poorly demarcated raised lesions.
The lepromin skin test (positive in tuberculoid leprosy, negative in lepromatous leprosy).
Lepromatous leprosy is associated with what type of immune system?
A weaker immune response.
These infections have a more widespread lesions, and a higher bacterial load.
What are the two distinct clinical presentations of M. leprae infection?
Tuberculoid leprosy
and
Lepromatous leprosy.
What is the diagnostic tool to classify the type of leprosy in a person already diagnosed with the disease?
The lepromin skin test.
Inactivated Mycobacterium leprae is injected under the skin.
It is a diagnostic tool to classify the type of leprosy in a person already diagnosed with the disease. A positive result, where a nodule forms, indicates a stronger cellular immune response, typically seen in tuberculoid leprosy. A negative result, where no nodule forms, indicates lepromatous leprosy, which is associated with a weaker immune response, more widespread lesions, and a higher bacterial load.
How does tuberculoid leprosy typically present on the skin?
Lepromatous leprosy often manifests with poorly demarcated diffuse hypopigmented erythematous papules, macules, nodules, and plaques.
How is leprosy diagnosed?
skin biopsy with an acid fast stain.
What stain is used to detect acid-fast mycobacteria such as Mycobacterium avium complex (MAC)?
Carbol fuchsin stain.
Why are mycobacteria acid-fast?
Due to their high mycolic acid content in the cell wall.
What immune system feature do mycobacteria evade by forming granulomas?
They invade macrophages and form granulomas to escape immune detection.
What does MAC stand for in nontuberculous mycobacteria?
Mycobacterium avium complex (M. avium and M. intracellulare).
What are the TB-like symptoms caused by MAC infections?
Cough, fatigue, night sweats, shortness of breath, and weight loss.
MAC generally causes pulmonary disease in patients with …. ?
HIV
COPD
Bronchiectasis
In which immunocompromised population is disseminated MAC disease common?
Patients with advanced HIV and a CD4 count <50.
What is the recommended treatment for MAC infections?
A macrolide (e.g., clarithromycin or azithromycin)
combined with
ethambutol and rifabutin
What is the prophylactic treatment for HIV patients with CD4 counts <50 who are not on ART?
A macrolide (e.g., azithromycin) and initiation of ART.
What skin condition is commonly caused by Mycobacterium marinum in aquarium handlers (fresh and salt water)?
Skin infections.
What infection is caused by Mycobacterium scrofulaceum, most commonly in children?
Cervical lymphadenitis.
How is Mycobacterium marinum typically transmitted?
Through direct contact with contaminated water or infected animals like fish.
Mycobacterium marinum is treated with …. ?
Clarithromycin
with
ethanmbutol or rifampin
Infection with Mycobacterium ______ can also mirror TB.
Mycobacterium kansaii
