11 Tuberculosis

Question 1

Epidemiology of tuberculosis

Answer 1

1. More than 1/3 of overall population worldwide harbors the bacterium
2. Second leading infectious cause of death, especially among those with HIV

Question 2

Patients with a high prevalence of Tuberculosis (from highest to lowest risk)

Answer 2

Immigrants from high-prevalence countries
Patients with the human immunodeficiency virus
Residents and staff of prisons or shelters for the homeless
Alcoholics and illicit drug users
Elderly and nursing home patients

Question 3

Tubercles and Ghon complex

Answer 3

Tubercles are granulomas and are a sign of primary infection and may progress to caseation necrosis and calcification.

These tubercles create a protective area for bacterial growth.

In the lung, the Ghon complex is a tubercle, appearing as a calcified hilar lymph nodes.

Question 4

Remarks on tuberculin skin test

Answer 4

aka Mantoux skin test

Becomes positive 1 to 2 months after initial exposure

The test interpretation is between 48 and 72 hours after administration. Results are less reliable after 72 hours, with repeat testing required.

A negative tuberculin skin test does not rule out the disease, because 20% of patients with active TB have a negative test result

Question 5

The most common extrapulmonary site of tuberculosis

Answer 5

Lymphatic system - painless lymphadenopathy
(i.e., scrofula, cervical lymphadenitis)

Question 6

≥5-mm induration in skin test is positive in

Answer 6

Patients with Close contact with a TB-infected individual
Patients with abnormal CXR suggestive of healed TB

Patients with HIV
Patients with organ transplants
Patients with other immunosuppressed patients receiving equivalent of prednisone >15 mg/day for >1 month

Question 7

≥10-mm induration in skin test is positive in

Answer 7

Children <4 y/o
High-prevalence groups (immigrants, long-term care facility residents, persons in local high-risk areas)
Patients with conditions that increase the risk of progression to active disease (silicosis; diabetes; carcinoma of the head, neck, or lung)
Injection drug users

Question 8

Remarks on IGRAs

Answer 8

Interferon-y release assays
1. The test seeks the response to peptides present in all M. tuberculosis proteins, which trigger the release of interferon-y by the infected host

2. These proteins are absent in the bacillus Calmette-Guerin vaccine and in most nontuberculous mycobacteria
3. IGRA has a Sp of >95% and Sn 90% for latent tuberculsois
4. Results in 16 to 24 hours
5. Cannot distinguish between latent and active infection, and it may be falsely negative in immunocompromised patients

Question 9

Remarks on CXR in tuberculosis

Answer 9

1. No singular findings are pathognomonic for primary tuberculosis.
2. The most common finding is a normal CXR, especially in immunocompromised patients.

Question 10

Remarks on cavitary pulmonary tuberculosis

Answer 10

1. Ue prolonged therapy in immunocompromised patients, patients with cavitary pulmonary tuberculosis and positive sputum culture after 2 months of therapy
2. Start or maintain therapy while awaiting smear and culture results on all patients with suspicious findings of active tuberculosis, notably cavitary lesions or known previous infecdtion with new weakness or fevers
3. The yield of sputum smears and cultures is lower in children because of difficulty in obtaining adequate samples in addition to lower incidence of cavitary disease
4. Patients with cavity have a bacterial load of up to 10^11 bacilli/gram, making it highly contagious. (Lond, 2012)

Question 11

Best method for confirming diagnosis of tuberculosis

Answer 11

Sputum or other tissue cultures for M. tuberculosis are the best method of confirming diagnosis and the most specific test for the disease, detecting as few as 10 bacteria/mL

Question 12

Remarks on NAAT

Answer 12

NAAT will remain positive in the setting of adequate therapy, as it detects dead and live organisms, making it best used for diagnosis of tuberculosis

A negative NAAT result cannot exclude tuberculosis.

Question 13

Remarks on tuberculosis management.

Answer 13

In most cases, antituberculous medications will not be started in the ED unless done in consultation and for classic cases.

Question 14

Major adverse effect of isoniazid

Answer 14

Hepatotoxicity
If serum transaminases are >5x the upper limit of normal or if serum bilirubin is >3 mg/dL, stop anti-TB medications

Question 15

A portion of patients treated for TB worsen after the initiation of anti-TB medications. This effect is called

Answer 15

Paradoxical reaction
or immune reconstitution syndrome
More commonly seen in those with HIV infection, specifically with CD4 ≤50 cells/mm3
Hypercalcemia is a unique finding in paradoxical reactions.

Question 16

Isoniazid

Answer 16

5 mg/kg PO (300 mg)
Hepatitis, peripheral neuropathy

Question 17

Rifampin

Answer 17

10 mg/kg PO (600 mg)
Hepatitis, thrombocytopenia

Question 18

Pyrazinamide

Answer 18

15-30 mg/kg (2 grams)
Hepatitis, arthralgia, hyperuricemia

Question 19

Ethambutol

Answer 19

15-20 mg/kg (1.6 grams)
Retrobulbar neuritis, peripheral neuropathy

Question 20

May cause exacerbation of porphyria

Answer 20

Rifapentine
*may also cause thrombocytopenia
*only for HIV-negative patients

Question 21

Used for patients who cannot tolerate rifampin

Answer 21

Rifabutin

Question 22

Treatment of latent TB

Answer 22

Isoniazid for 9 months

Question 23

Strongest known risk factor for tuberculosis

Answer 23

HIV infection
- Once active tuberculosis develops, the risk of rapid progression and drug resistance is higher in the HIV patient
- Successful treatment with antiretroviral therapy lowerst he rate of tuberculsois and reduces the incidence of extrapulmonary involvement
- For these reasons, physicians considering a diagnosis of tuberculosis should obtain HIV testing to provide early diagnosis and therapy

Question 24

Remarks on MDR TB

Answer 24

These forms are highly infectious, with conversion rates approaching 50% in those exposed.

Treatment of MDR TB is challenging as INH provides the strongest bactericidal action, and RIF has important action against dormant bacilli.

Question 25

XDR TB

Answer 25

Resistance to INH, RIF, any fluoroquinolone, and at least one injectable second-line medication

Question 26

Miliary tuberculosis

Answer 26

1. Classic miliary tuberculosis shows diffuse nodules on radiographs (1 to 3 mm) in a patient with positive laboratory testing or by demonstration of mycobacteria in multiple organs.
2. Miliary disease during primary tuberculosis is generally more rapid and severe, often presenting with multiorgan failure, shock, and ARDS.

Question 27

Remarks of tuberculous meningitis

Answer 27

1. Often are not accompanied by neck stiffness or irritation; this is in contrast with findigns in other forms of bacterial meningitis.
2. CSF:
   - lymphocytic pleocytosis
   - elevated protein
   - increased opening pressures
   - CSF-to-protein ratio of <0.5
3. Cranial CT may be normal in 30% of patients with mild CNS disease.
4. Tuberculous meningitis often seeds after a miliary infection
5. Adjunctive corticosteroids reduce complicatons.