TB Consensus Flashcards
TB caused by MDR strains that are also resistant to a fluoroquinolone and to at least one second-line injectable agent (amikacin, kanamycin, and/or capreomycin)
Extensively Drug-Resistant TB (XDR-TB)
Active TB disease caused by bacteria that are resistant to atleast 2 of the most commonly used drugs for treatment (ie INH and Rifampin)
Multidrug-resistant TB (MDR-TB)
What are the known virulence factors of M. tuberculosis?
cord factor (trehalose dimycolate), sulfatides, lipoarabinomannam (LAM)
cord factor - responsible for morphologic appearance of cells serpentine cords, assoc with ability of cells to produce disease
sulfatides - inhibit fusion of secondary lysosomes with bacilli-containing phagosomes within a macrophage
LAM- stimulates cytokine release from mononuclear cells
What is the doubling time of M. tuberculosis?
slow doubling time: 18-24 hrs
Culture is the gold standard for diagnosis of TB
- Which method allows for visualization of colony but with prolonged time of growth (3-4 wks) and low sensitivity?
- Which method allows for rapid detection (5-12 days) and susceptibility testing, increased sensitivity, and has the ability to distinguish MTBC from other species?
A. conventional culture
B. BACTEC TB System
- A
- B
- the only disadvantage of the BACTEC system is its radioactivity and its consequent expensive disposal
Of the following, which are the key elements in the primary defenses against TB?
a. antibodies
b. NK cells
c. T lymphocytes
d. PMNs
e. B lymphocytes
f. macrophages
C and F - T lymphocytes and macrophages
T lymphocytes produce pro-inflammatory cytokines that enhance macrophage intracellular killing
macrophages- phagocytosis, intracellular killing, cytokine production, and antigen presentation to T cell populations
What kind of hypersensitivity reaction is seen in the tuberculin skin test?
Delayed-type hypersensitivity reaction (Type IV)
- cells mediating this reaction are CD4-positive, producing mostly TH1 cytokines
Which immunologic reaction causes caseous necrosis?
Delayed type hypersensitivity reaction (DTH)
- local macrophages and nearby tissues die
- DTH and CMI (cell-mediated immunity) develop in the third stage of TB immunopathogenesis
At what stage of the immunopathogenesis of TB are the following lesions formed?
a. caseous necrosis
b. hematogenous spread
c. tubercle/granuloma formation
d. cavity formation
A. Stage 3
B. Stage 4
C. Stage 2
D. Stage 5
Stages of TB:
Stage 1: Macrophage ingestion of TB bacillus
Stage 2: Stage of symbiosis, unrestrained replication; TUBERCLE/GRANULOMA
Stage 3: Increase in # of bacilli, devt of CMI and DTH; CASEOUS NECROSIS
Stage 4: a) enlargement of tubercle/caseous center, HEMATOGENOUS SPREAD
Stage 4: b) stabilization and regression of tubercle
Stage 5: caseous center liquefaction, extracellular bacillary growth; CAVITY FORMATION
This lung lesion is seen on primary TB, usually located in the subpleural area of the upper segment of the lower lobe or lower segment of upper lobe. It consists of the primary pulmonary focus, infected lymph nodes, and associated lymphangitis
Ghon complex
- in most instances, the primary infection is controlled, with a positive TST as the only evidence of infection
- lesions of the Ghon complex heal by shrinkage, fibrous scarring, and calcification
What is the most clinically important form of disseminated TB analogous to bacterial sepsis?
miliary TB
- occurs when a caseous focus erodes into a blood vessel wall causing massive number of bacilli released into the bloodstream
In Wallgren’s Timetable of Tuberculosis, disease progression of TB was described, intially marked by a febrile period. How long does it take for the following complications to occur after initial infection?
a. Renal TB
b. miliary or meningeal TB
c. TB of bones and joints
a. Renal TB - 5-25 yrs
b. miliary or meningeal TB - 2-6 mos
c. TB of bones and joints- 1 yr
What are the lung findings suggestive of cavitation?
crepitant rales and decreased breath sounds over affected areas
What is the most common form of extrapulmonary TB in children?
Scrofula (TB adenitis)
- since cervical lymph nodes may be normally palpated in young children, diagnosis should be supported by a + TST and other criteria for diagnosis, eg excisional bx and culture or FNAB if indicated
- firm, painless, discrete and movable
- if untreated, it may either resolve or prigress to necrosis and caseation of the LN, and result in a draining sinus tract (scrofuloderma)
What is the most common type of TB of the nervous system?
Tuberculous meningitis
- usually involves CN III, VI, VII, optic chiasm, basal cisterns – usually leads to papilledema and HCP
What is the radiographic hallmark of initial disease in TB
Relatively large size of adenitis compared with the relatively insignificant size of the initial focus in the lungs
What is the most common chest radiograph findings in childhood TB?
lymphadenopathy and parenchymal abnormalities
Which lymph nodes in the lung are most often affected by primary TB?
the nodes in the right upper paratracheal area
- since the lymphatic drainage of the lungs occurs predominantly from left to right
Should PTB treatment be initiated in an asymptomatic child with findings of hilar adenopathy on chest radiograph?
Not yet. Since hilar adenopathy has very low specificity (36%), it should not be the sole basis for initiating treatment.
When is radiographic clearing expected to occur after institution of therapy for TB?
6 mos to 2 yrs after institution of therapy
- in the first three mos of treatment, worsening of radiographic findings may be observed in 1/3 of pediatric pxs
Lesions in chronic pulmonary TB tend to localize in which part of the lung?
apical and posterior segments of the upper lobes, involving the right lung more than the left
- lymph node enlargement is no longer a feature
What is the most common radiographic manifestation of reactivation pulmonary TB?
local exudative TB
- focal or patchy heterogeneous consolidation involving the apical and posterior segments of the upper lobes and the superior segments of the lower lobes
What is the radiologic hallmark of reactivation TB?
cavitation
What is the most diagnostic radiological change in pulmonary TB during infancy and childhood?
“millet-seed” densities of miliary TB
What is the PHEMISTER Triad, which is characteristic of TB arthritis?
- juxtaarticular osteoporosis
- peripherally located osseus erosions
- narrowing of interosseus space
How is rheumatoid arthritis radiographically differentiated from TB arthritis?
- relative preservation of the joint space is also highly characteristic of TB arthritis
- early loss of articular space is more typical of rheumatoid arthritis
In a non-contrast and enhanced CT, what is the most specific finding in the diagnosis of CNS TB?
basal cistern hyperdensity
What is the most common complication of TB meningitis?
communicating hydrocephalus
Which cranial nerves are commonly affected in cases of TB meningitis?
cranial nerve 2,3,4, and 7
How are tuberculomas different from TB abscess?
Tuberculomas
- well circumscribed masses
- commonly multiple
- commonly affects frontal/parietal lobes
TB abscess
- occurs when caseous center of tuberculoma liquefies
- clinically worse than tuberculomas
- usually larger and solitary
What is the most common radiographic manifestation of abdominal TB?
lymphadenopathy
- most commonly involved: mesenteric, omental, and peripancreatic lymph nodes
- demonstrate peripheral enhancement with central areas of low attenuation in a contrast-enhanced CT
What is the most common clinical manifestation of abdominal TB?
Peritonitis
Which vaccines may cause suppression of the tuberculin reaction in the Mantoux test?
Live virus vaccines: MMRV, OPV, Oral typhoid, Rotavirus
- postpone TST at least 4-6 weeks from vaccination
Primary prophylaxis for TB is recommended for which kind of patients?
For patients exposed to M. tuberculosis without infection or active disease
Objective is to prevent onset of infection
Secondary prophylaxis for TB is recommended for which kind of patients?
For patients with LTBI.
Objective is to prevent progression of infection to active disease
Give the recommended regimen:
(+) TB exposure
a. < 5 yo
b. >= 5 yo
3 H
- prophylaxis for children >5 yo is recommended for the immunocompromised and undernourished child
- reevaluate after 3 mos, classify as infection/disease and revise treatment accordingly
Give the recommended regimen:
PPD conversion within past 1-2 yrs
(-) CXR
LTBI
9H
Give the recommended regimen:
PPD (+) not due to BCG
(-) CXR, (-) previous treatment
LTBI
9H
Give the recommended regimen:
PPD (+) with healed/stable lesion
(-) previous treatment
LTBI
9H
Give the recommended regimen:
PPD(+) with stable/healed lesion
(+) previous treatment
At risk for reactivation due to measles, pertussis, etc.
LTBI
1-2 H
Give the recommended regimen:
PPD(+) with stable/healed lesion
(+) previous treatment
At risk for reactivation due to conditions/drugs inducing immunosuppression (IDDM, leukemia, chronic dialysis)
LTBI
H, for the duration of immunosuppression
Give the recommended regimen:
HIV infection/persons at risk for infection but HIV status unknown
12H
Give the recommended regimen:
New smear-negative pulmonary TB
Less severe forms of extrapulmonary TB
Active TB Disease
2HRZ/4HR(6HE)
Give the recommended regimen:
New smear positive pulmonary TB
Active TB disease
2HRZE(S)/4HR(6HE)
- 2HRZE/6HE regimen is associated with a higher rate of treatment failure and relapse
Give the recommended regimen:
New smear negative pulmonary TB with extensive parenchymal involvement
Active TB disease
2HRZE(S)/4HR(6HE)
- 2HRZE/6HE regimen is associated with a higher rate of treatment failure and relapse
Give the recommended regimen:
Severe forms of extrapulmonary TB (other than TB meningitis)
Active TB disease
2HRZE(S)/4HR(6HE)
- 2HRZE/6HE regimen is associated with a higher rate of treatment failure and relapse
Give the recommended regimen:
Severe concomitant HIV disease
Active TB disease
2HRZE(S)/4HR(6HE)
- 2HRZE/6HE regimen is associated with a higher rate of treatment failure and relapse
Give the recommended regimen:
TB meningitis
Active TB disease
2HRZS/4HR
- Streptomycin replaces ethambutol in the treatment of TB meningitis
- some experts recommend 9-12 mos treatment for TB meningitis, given the serious risk of disability and mortality
Give the recommended regimen:
Miliary TB
Active TB disease
2HRZS/7-10HR
Give the recommended regimen:
Previously treated smear-positive pulmonary TB; relapse treatment after interruption treatment failure
Active TB disease
2HRZES-1HRZE / 5HRE
Give the recommended regimen:
TB of the bones and joints
Active Tb disease
2HRZS/7-10HR
- experts recommend 9 mos of treatment for TB of bones and joints because of difficulties of assessing treatment response
Give the recommended regimen:
pregnant women with active TB disease
2HRZE/4HR or 2HRE/4HR (6-9 mos)
+ pyridoxine (25 mg/day)
- safety of pyrazinamide in pregnancy is not well established, but WHO recommends its use for 2 mos
- Avoid streptomycin and other aminoglycosides (ototoxic)
- If on tx already, continue but avoid streptomycin and fluoroquinolones
- breastfeeding is encouraged
Give the recommended regimen:
Pregnant woman with LTBI
9H
- treat without delay
Give the recommended regimen:
Newborn whose mother has LTBI (asymptomatic, tuberculin positive, negative CXR)
Do not separate from mother
Give BCG at birth
Give the recommended regimen:
Newborn whose mother has current TB disease, but has undergone treatment for 2 wks or more
Mother is presumed no longer contagious at this point. Baby should receive 3H then undergo TST If TST (-), D/C H, give BCG If TST (+), complete H for 9 mos
Give the recommended regimen:
Infant whose mother has current TB disease but has not received treatment
Separation is recommended until infant has received H(R), and mother has undergone appropriate therapy Start INH Send placenta for AFB staining and TBCS Do TST If TST (+), CXR (-) treat with 6H(R) If TST (-), CXR (-), 3H(R)
Give the recommended regimen:
Newborn with congenital TB
2HRZS / 4-7HR
Give the recommended regimen:
In a patient with active TB but with liver impairment
Remove INH from regimen
6-9 RZE or
Remove pyrazinamide
2HRE/7HR
In advanced cases, only Rifampicin (less hepatotoxic) can be combined with ethambutol, fluoroquinolone, cycloserine and other injectable drugs for 12-18 mos
In severe, unstable liver disease
18-24 mos SAFE (Streptomycin, Another second line drug, Fluoroquinolones, Ethambutol)
A. In children, which subset of TB-infected population is at increased risk for progression to TB disease?
B. Which subset is at increased risk for disseminated disease?
A. infants and postpubertal adolescents
B. children less than 4 y/o
What factors promote development and maintenance of latency (LTBI)?
- low O2 and nutrient in granulomas
- local production of TNF alpha and nitric oxide
What are the key risk factors for TB?
household contact with newly diagnosed smear positive case
age less than 5 yrs old
HIV infection
immunocompromised state - major risk
In the pathogenesis of TB, affected hilar and lymph nodes enlarge, sometimes compressing the bronchi to produce atelectasis of the distal lung, collapsing the middle lobe, resulting in what syndrome?
middle lobe syndrome
Infection associated with (+) TST, no symptoms, no roentgenographic manifestations
LTBI
What are the stages of TB meningitis?
Symptoms begin gradually 3 wks after primary TB process
Stage 1: irritability - apathy, vomiting, headache
Stage 2: convulsive - meningeal sxs, CN palsies
Stage 3: paralytic - posturing
What are the signs of TB meningitis on CT scan?
basilar enhancement
communicating HCP
cerebral edema
early focal ischemia
Enlarged caseous and calcified mesenteric lymph glands on roentgenogram of the abdomen, described as “shadows of increased density”
tabes mesenterica
- mesenteric nodes become matted and result in adhesions –> intestinal obstruction –> compress portal vein –> ascites and dilatation of superficial abdominal veins
When is detectable tuberculin reactivity expected (positive TST) from the time of TB exposure?
8-10 wks after TB exposure
- a negative test result obtained less than 8 wks after exposure is unreliable for excluding TB infection.
- repeat TST at 3 mos after a (-) TST in a TB symptomatic child or any child 4 yrs and below
What are the main causes of false positive reactions to PPD?
nontuberculous mycobacteria
BCG vaccination
- 6-12 wks after BCG, tuberculin reaction develops (TST+)
- 5 yrs after BCG, tuberculin rxn wanes
What may cause a false negative TST reaction?
- infection: measles, mumps, chickenpox, bacterial infections
- vaccine: live-attenuated vaccines (MMRV, OPV, RV, oral typhoid)
- corticosteroids
- nutritional factors
- postpone TST at least 4-6 wks from a live-vaccine administration, BUT it may be given simultaneously provided they are injected on different sites
- delay TST for 2 mos after infection with measles, mumps, chickenpox, or whooping cough