Chapter 173: Tuberculosis

Leave the first rating

Terms in this set (93)

Rod shaped
NON spore forming
Microbiology of MTB
Thin aerobic bacterium
0.5 mci

Nocardia
Rhodococcus
Microorganisms other than Mycobacteria with
Legionella micdadei
Acid fastness
Isospora
Cryptosporidium

Droplet nuclei aerosolized by coughing, sneezing , speaking

---
Most common mode of transmission Tiny, dry rapidly
<5-10 microm, suspended in air, reach terminal airways

3,000 infectious nuclei/cough

Cavitary pulmonary disease

Most infectious TB patients have this kind of
pulmonary disease
AFB smear positive

False.
True or False.

Essentially noninfectious
Culture negative pulmonary TB and extra
pulmonary TB are likewise infectious
p. 1238

False

True or False Acquiring- exogenous

Acquring infection largely is determined by
Endogenous factors, while Developing the
disease Is governed by exogenous factors.
Crowding in poorly ventilated homes one of most important factors
Endogenous
Developing disease, innate immunologic and nonimmunologic defenses,
level at which cell-mediated immunity is functioning
 True
True or False.

p. 1239
Secondary TB is more infectious than primary
TB.
bacilli persist for years then reactivate (had undergone frequent cavitation)

True

TB highest during late adolescence and early adulthood

True or False

Women peaks 25-34

Age is an important determinant of risk of
disease after infection
Elderly: Opposite: higher in men

p. 1239

Most potent risk factor for TB among infected HIV coinfection

individuals

Binding of which receptor regulate Mannose receptor

postphagocytic events such as phagosome-
lysosome fusion and inflammatory cytokine
production?

Mycobacterial cell wall component that lipoglycan lipoarabinomannan

inhibits intracellular increase of Calcium
leading to impairment of Calcium/calmodulin
pathway (fusion of phagosome lysosome
function)?

Macrophages

T cells
Cell mediated immunity (2 types) essential in
- induce production of IFN-gamma cytokines (TH1)
TB
leads to activation fo Macrophages and monocytes and IL2

TH2---> produce IL4, IL5, IL13

False
True or False

Associated with protective immunity (TST positive less susceptible to NEW

Skin test reactivity is based on previously
MTB than TST negative) it is not guarantee protection against reactivation.
sensitized CD4+ T lymphocytes which is
associated with protection against reactivation.
p. 1241
 False

May be asymptomatic or not.

True or False.

---
Primary TB is always symptomatic.
Primary PTB
occurs soon after infection of tubercle bacilli
children

middle and lower zones

Most common sites of lung involvement in

p. 1241
Primary PTB

since most inspired air is distributed to middle and lower lung zones
Ghon focus found in the ___ location
-Forming lesion: GHON focus, PERIPHERAL, accompanied by TRANSIENT
hilar or paratracheal lymphadenopathy

Apical and posterior segments of upper lobes;

Lung involvement in Adult type PTB
Superior segments of the lower lobes

Hemoptysis that is caused by rupture of Rasmussen's aneurysm

dilated vessel in a cavity is called:

Fever

80% of cases
Most common symptom of PTB
low grade, intermittent

absence does not exclude TB

mild anemia
Leukocytosis
Most common Lab findings in PTB Thrombocytosis
Slightly elevated ESR/CRP
*Hyponatremia in others (SIADH)

In descending order

Lymph nodes
Pleura
Most common locations of extrapulmonary TB GU
Bones, Joints
Meninges
Peritoneum
Pericardium

True or False. True

Lymph nodes are the most common p. 1243

extrapulmonary TB sites in both HIV infected
and seronegative individuals.
 Posterior cervical
Supraclavicular

Most common sites of TB lymphadenitis *painless swelling (scrofula)

Dx:
FNAB (80%) yield or excision biopsy

Straw colored, at times hemorrhagic

Exudative
Protein >50% than serum (~4.6g/dL)
Normal to low glucose
Characteristics and diagnosis of TB effusion PH ~7.3 (occ <7.2)
WBC 500-6,000/microL0

Early: Neutrophilic, Late: Lymphocytic

Rare or absent mesothelial cells

True or False. Yes. Can be used as screening test.

ADA of pleural fluid, once negative, can rule

out TB.

Needle biopsy of pleura

TB effusion diagnostic modality that is
recommended over pleural fluid analysis
yields positive result in ~75% of cases

False.

True or False.
less common

TB empyema is a common complication of TB

Tx surgical draining adjunct to chemotherapy
effusion.

if with severe pleural fibrosis and restrictive lung disease, do decortication.

Pyuria
Hematuria
UA findings GU TB

*CULTURE NEGATIVE pyuria in acidic urine should arise suspicion of TB

Culture of __ urine specimens yield definitive 3, 90%

diagnosis in ___% of cases

Biopsy or culture of specimens by Dilation and curettage

Females>Males
*Fallopian tubes, endometrium
Diagnosis of Genital TB
Males
Epididymis

almost half of cases, there is disease of urinary tract

 Weight bearing joints

Spine 40%
> 2 or more adjacent vertebral bodies
Most commonly affected sites in Skeletal TB --> Upper thoracic spine CHILDREN
--> Lower thoracic and upper lumbar vertebrae in adults

Hips 13%
Knees 10%

True or False False

Skeletal TB cold abscess affects intervertebral Skeletal TB--> late disk,

disk early, whereas in pyogenic bacterial
osteomyelitis, disk is involved late. Pyogenic-- Early disk--> rapid sclerosis

Synovial biopsy and tissue culture

Altho fluid culture is positive, the above two may be necessary to establish
Diagnostics to establish TB of the knee
it.

p. 1244

1-2 weeks
Evolution/symptomatology of CNS TB may
develop over ___ Weeks
(longer course than bacterial meningitis)

base of the brain

Due to pronounced meningeal involvement of
this section of the brain, patients typically have
Ocular nerves
paresis of cranial nerves (particularly ____) and
involvement of cerebral arteries leading to
*ultimately evolve into coma, with hydrocephalus and intracranial
focal ischemia.
hypertension

CSF TB gene expert

Preferred initial diagnostic option with
sensitivity of up to 80% in CNS TB
p. 1245

CSF culture
Gold standard of TB meningitis
Lumbar tap cornerstone

High Leukocyte ct 1000/mcroL

Early neutrophilic, late lymphocytic
CSF analysis of TB meningitis protein 1-8g/L
Low glucose
But all can be normal

CT or MRI finding CNS TB Hydrocephalus, abnormal enhancement of basal cisterns or ependyma


Glucocorticoids in CNS TB
Sites most commonly involved in GI TB
True or False
IN TB peritonitis, culture of ascitic fluid
establishes diagnosis.
True or False.
Glucocorticoids have proven mortality benefit
in CNS and Tuberculous pericarditis
Pathognomonic lesion of Miliary TB in eye
examination
True or False.
Sputum smear is often positive in cases of
Miliary TB.
Chronic complication of TB which oN CXR
appears as thickened pleura and presence of
fungus ball inside cavity
Recommended Duration of glucocorticoid
treatment in Tuberculous meningitis
One study advocated this regimen:
1) Dexamethasone 0.4 mg/kg/d IV with tapering by 0.1 mg/kg/wk until 4th
week (when 0.1 mg/kg/d was administered); followed by
2) 4mg/d PO with tapering by 1mg/wk until 4th wk (when 1mg/d was
administered)
As per WHO:
Adjuvant glucocorticoid with either Dexamethasone or Prednisolone can
be used, tapered over 6-8 weeks
Terminal Ileum
Cecum
False
Yield of direct smear and culture relatively Low
BIOPSY (with specimen best obtained by laparoscopy) is often needed to
establish diagnosis.
p. 1245
False.
Only in CNS TB
NO mortality Benefit in pericardial TB p. 1245
CONFLICTING statements
- WHO currently recommends initial adjuvant glucocorticoid tx may be
used
- IDSA 2016 - glucocorticoids should NOT be routinely administered
Choroidal tubercles (~30% of cases)
Other features of CNS TB
Meningismus <10% of cases
False,
NEGATIVE in most cases
Chronic Pulmonary aspergillosis
Tx
Itraconazole >=6 months
Surgical removal is risky except in simple aspergilloma
p. 1246
Start then taper over 6-8 weeks
Level of CD4+ in which primary TB like pattern <200/microL
is atypical in HIV- associated TB

Typical presentation and findings on CXR of upper lobe infiltrates + cavitation and without significant lymphadenopathy
TB patients whose immunity is only partially or pleural effusion
compromised

<200microl/L

Atypical presentation of PTB seen in late

Primary TB like pattern:
stages of HIV at a level of _____
Diffuse interstitial and subtle infiltrates
Little or no cavitation, pleural effusion and intrathoracic lymphadenopathy

True or False. False

Sputum smears are more often positive in HIV hence Traditional diagnostic methods difficult
TB patents

Lymphatic
Most common forms of Extrapulmonary TB in Disseminated
HIV Pleural
Pericardial

Immune reconstitution inflammatory syndrome

This constitutes exacerbations of systemic
manifestations of TB that develops ____ months 1-3 months after initiation
after ART initiation
More common in advanced immunosuppression and ETB

Risk of IRIS increases with earlier ART is started, lower baseline count

___ treatment and ____ baseline CD4 count

CNS TB

Group of patients where IRIS can result to **

serious complications and death Recall: Death due to IRIS is relatively infrequent

p. 1246

lower zones

Infiltrates, if can be seen in patients with HIV

p.146
coinfected with TB, will likely be seen in ___
lungs
________
*Recall in typical TB- middle and lower zones
 Low sensitivity 40-60%

collect 2 sputum specimens in the morning

AFB microscopy in TB limited role in urine and gastric lavage fluid, may yield false negative result
while commensal mycobacteria -> false positive

p. 1247

Mycobacterial culture will require ___ weeks for 4-8 weeks

growth to be detected

Repeat TB gene expert.

In a suspected case of TB meningitis, CSF TB ** TB gene expert should always be the initial diagnostic test where TB
gene expert was negative. What is your next meningitis is suspected, if positive treat, if negative should be followed up
plan of action? by additional testing

p. 1248

Diagnostic test recently recommended by Lateral -flow urine lipoarabinomannan assay

WHO for patients with TB symptoms and CD4
count <=100 or with unknown CD4count who *but this should not be used as screening test
are HIV positive

- Immunosuppressed Patients
- overwhelming TB

*recall: Pathophysio: response of stimulation by T cells in the skin rather

then recirculating memory T cells
in these populations, probably Sobrang immunocompromised hindi na
maka mount ng response
False negative TST can be seen in:
p. 1249

False positive:
-infections with nontubercuolous mycobacteria
- BCG vaccine

*recall: PPD large number of proteins conserved in various species

-infections with nontubercuolous mycobacteria

- BCG vaccine

False positive TST seen in *recall: PPD large number of proteins conserved in various species

Weakness of TST for LTBI: unable to distinguish between LTBI and active
disease

This is the phenomenon of serious TST Boosting phenomenon

conversion resulting from boosting reactivity
on a subsequent TST ____ weeks after the initial 1-5 weeks
test.
 ethambutol
Which among HRZE is not bactericidal?
p. 1250

Pyridoxine 10-25mg/day

Risk factors for Vit B6 deficiency

Alcoholics
Prevention of Isoniazid neuropathy Malnourished
Pregnant, lactating women
CKD
DM
HIV

sputum smear is positive >= 3 months on treatment

Treatment failure
obtain smear 2, 5 and 6 months

False

True or False
Both not recommended for routine follow up purposes but CXR at the end
of treatment may be useful for comparative purposes should symptoms of
After completion of treatment, repeat Sputum
recurrent TB occur months or years later.
AFB and CXR to monitor complications.

P. 1252

Most common adverse reaction significant Hepatitis

among tb patients

Pyrazinamide
Hyperuricemia and Arthralgia: SE of which
AntiTB drug
Treat with acetylsalicylic acid

On followup with TB medications, Uric acid No. D/c only if the patient develops gouty arthritis
rose to 10mg/dL. Patient is asymptomatic. Will
you discontinue this drug? p. 1252

Side effect of which antiTB drug: Rifampin

Autoimmune thrombocytopenia
You are suspecting treatment failure upon
positive smear follow up after 3 months of
treatment with your patient. He presented to
ER with severe cough and sputum production,
fever, chills, and marginal BP.
What will you do?
a) Wait for result of resistance testing and
continue regimen
b) Add 2-3 drugs to current regimen
c) discontinue current regimen and start with
another 2-3 drugs
True or False
Patients who have completed 6 months and
declared to have relapse will have high risk of
acquired resistance.
Primary vs Acquired drug resistance
Treatment of patients with isoniazid-resistant
disease
MDR TB is resistant to
2 WHO recommended approaches for MDR
TB treatment regimen
MDR TB drugs that can cause QTc
prolongation
B
Cardinal rule: always to add more than one drug, preferably 2-3 at a time
to a failing regimen, and starting an empirical regimen for MDRTB is
warranted.
Changes in regimen can be postponed until release of resistance results
(will come out in a few days)
p. 1253
False.
acquired resistance uncommon among strains who relapse following
proper completion of standard 6- months regimen
p. 1253
Primary- at the outset infected by a drug-resistant strain
Acquired- develops in the infecting strain during treatment
p. 1253
RZEL (levofloxacin) x 6 months
> Do not include fluroquinolone unless Rifampin resistance is ruled out
at least isoniazid and rifampicin
*most difficult to treat since these 2 are the most potent in the drug
combination
"MDR is resistant to at least HR"
1) shorter standardized regimen x 9-12 mos OR
2) longer regimen of 18-24 months optimal combination acc to standard
design
Bedaquiline
Delamanid
QTc prolongation is BaD
*do not give in patients with QTC interval>500ms or history of ventricular
arrhythmias
 False

True or false regarding ART and TB treatment:
ART initiation in the context of TB treatment
depends on CD4 count.
ALL HIV infected TB patients regardless of CD4 T cell count are candidates
for ART optimally initiated as soon as possible after the diagnosis of TB
AND
within the FIRST 8 weeks of TB treatment
ART should be started within the first 2 weeks of TB treatment for
profoundly immunocompromised
CD4<50

False
True or False.
Standard 6 month regimen equally efficacious
HIV infected patients whether on antiTB
medications or not have shown to derive But if the patient cannot receive ART, prolong the maintenance phase by 3
benefit from longer course of chemotherapy more months
with TB drugs.
p. 1255

Rifampin
This antiTB drug is a potent inducer of the
Cytochrome P450 system that lowers the
*in these cases, may substitute with Rifabutin with lower enzyme inducing
serum levels of HIV protease inhibitors and
capacity
some non nucleoside reverse transcriptase
inhibitors
p. 1256

In cases of hepatic disease, under supervision:

Isoniazid, Rifampin
Anti TB drugs ___ and __ can be used under
supervision, while ___ should be avoided. Avoid: Pyrazinamide

Patients with severe hepatic disease can be Ethambutol, streptomycin (and possibly another drug e.g fluoroquinolone)
given this drug combination: if required

False
True or False
TB treatment is not a contraindication as most of the drugs will be present
Treatment of TB is contraindicated during in small quantities only
breastfeeding.
p. 1256

HRE x 2 months, then HR x 7 months

Streptomycin contraindicated- may cause 8th cranial nerve damage

Treatment of choice for pregnant women
WHO has recommended routine use of Pyrazinamide ifor pregnant women
but is not recommended in the US due to insufficient data on safety during
pregnancy.

2-4 weeks
Treating TB patients for ___ may render them
already noninfectious
p. 1256
Local tissue response to BCG vaccine begins 2-3 weeks
____ weeks after vaccination, while scar 3 months
formation and healing occurs within ___ months

False
True or False
SHOULD NOT RECEIVE, also infants with unknown status displaying HIV
BCG vaccination is indicated in HIV infected symptoms, who are from HIV infected moms
adults and children
p. 1257

Administer 5 tuberculin units

Read reaction 48-72h thereafter

Cut off: CHECK INDURATION not erythema diameter

>=5mm cutoff for:

- HIV infected
- Recent close contacts of infectious cases
Mantoux reaction/PPD
- Organ transplant recipients
- previously untreated persons with CXR of fibrotic lesions (consistent of
old TB)
- persons receiving drugs that suppress immune system
-High risk medical conditions (silicosis, ESRD on HD)

others >=10mm at risk

low risk >=15mm(but TST not indicated unless for employment reasons)

HIV infected
Recent TB contacts
Organ transplant
previously untreated persons with CXR of fibrotic lesions (consistent of old
TB)
Immunosuppressant drugs (glucocorticoids, ant TNF)
High risk medical conditions (silicosis, ESRD on HD)
WHO recommendations on who to test and
treat for LTBI

Consider LTBI testing and treatment for

- prisoners
- healthcareworkrs
-immigrants from countries with high TB burden
-homeless
-illicit drug users

Isoniazid 5mg/kg (up to 300mg/day) 9 months - optimal

* in the absence of reinfection, protective effect is lifelong
LTBI treatment duration:

But cost-benefit, WHO now recommending 6 months

What you must do all the time prior to LTBI Exclude or rule out active TB to prevent development of resistance
treatment:
 Drug: Rifampin

ADE: Neutropenia, thrombocytopenia

Drug Rifampin

ADE: Acute tubular necrosis and interstitial

nephritis