26. Tuberculosis. Flashcards
what is the pathoetiology of tuberculosis?
infected through respiratory droplets by close contacts
however from the time to exposure to the clinical stage disease can occur much faster (within 3-6 months) in children <2 years of age
Effective immune responses may lead to complete clearance, or Immediately after exposure and primary infection from an infectious TB case, there are generally no clinical or radiologic manifestations. It may be possible for humans to clear the pathogen
Progression depends on age
40-50 percent for children up tp 2 years old , so children under 2 years old are at the greatest risk for TB
also greatest risk for DISSEMINATION
5-10 years and above are the most protected age group , lowest risk of progressing disease
while adolescents - 10-15 years are the second most highest (10-20 percent)
bimodal distribution
what are the risk factors to TB?
Risk factors for TB exposure [15]
Working in the health care industry
Migration from countries with a high TB incidence (≥ 100 cases per 100,000 population) [16]
Frequent travel to countries with a high TB burden
Close contact with a patient with active TB infection
Crowded living conditions (e.g., prisons)
Homelessness
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latent - to secondary infection
children under 2 years of age and 10-15 years
immunocompromised - HIV - more progressive
chronic renal disease
malnutrition
diabetes
what re the different spectrum of TB in children ?
dormant
symptoms - mild , non specific , transient
thoracic radiology - possibly hilar lymphadenopathy
TST and IGRA - positive
microbiology - negative
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subclinical
symptoms - non
thoracic radiology - hilar lymph nodes and parenchymal lesions
TST and IGRA - positive
microbio - rarely positive
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non severe
symptoms - mild to moderate
TXR - present
TST and IGRA - positive
micro - may be positive
======== severe symptom - moderate to severe TXR - present TST and IGRA - positive micro - may be positive
what is the pathophysiology of TB ?
3 can be three possible routes TB can take :
1) elimination
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2) retention
the immune system surpasses the bacteria - but the bacteria remains viable - and leads to latent TB
If clearance occurs through T-cell independent mechanisms, IGRA and TST results should be negative. However, clearance may also occur through T-cell mediated immunity, which would manifest with positive IGRA/TST results. This latter phenomenon may explain why some people who are diagnosed as having latent TB infection (LTBI) ultimately have a low likelihood of ever developing active TB disease
= usually latent tB – is asymptomatic
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3) active infection
primary infection
it takes approximately 4–12 weeks after exposure for the adaptive immune responses to reflect evidence of TB infection, as measured by the IGRA/TST
During this period, there is local extension of the infection into the lung parenchyma, termed a Ghon focus ( granuloma) , which can manifest clinically with mild, self-limiting and non-specific respiratory symptoms
chest radiographs at this time may also demonstrate transient lymphadenopathy in the hilar and/or mediastinal regions; together with the Ghon focus this is termed a Ghon complex
this can be eliminated with the immune system without any help - GOING TO LATENT STAGE (bacteria in the granuloma and is viable)
usually 90 percent
in x ray - the ghon complex can be calcified
5 percent of population - primary infection is progressive
local progression - to TB pneumonia
and can also progress into disseminated TB- millets in the lungs - millary TB ( most frequent disseminated form of TB)
another 5 percent goes from the latent stage to reactivation - secondary TB- influenced by the immunity (esp cell mediated immunity - HIV , transplant , chemotherapy , IV drugs) or or exposure to TB from other person
what is the immune response in TB ?
cell mediated - which means no antibodies are produced
what are the clinical manifestation of TB ?
if latent - asymptomatic
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active
in young children disease progress rapidly after exposure
cough, wheezing or dyspnea
Lymph nodes may caseate or necrose, erupting into the airway leading to bronchopneumonia = cough, dyspnea, malaise and fever
Hypersensitivity reactions may also occur, including pleural effusions which may provoke symptoms of chest pain, fever and reduced endurance
hilar lymphadenopathy can block the bronchi - wheezing
weight loss - systemic
night sweats
possible hemotyisis
yellow-greenishsputum
Auscultation:rales ininvolved area
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The most commonly involved extra-thoracic sites are the peripheral lymph nodes or the central nervous system.
Lymphadenitis - in the cervical and supraclavicular regions with enlarged, painless lymph nodes. Examination typically reveals a solitary rubbery node that lacks erythema or warmth = periadenitis
Lymphadenitis: firm, mobile, and discrete lymph nodes
and with FISTULA FORMATIONS
Disease within the central nervous system represents the most serious complication of TB,
early stages, such as irritability, fever, anorexia, and occasionally, focal respiratory or gastrointestinal symptoms.
As disease progresses, findings of meningitis become apparent including vomiting, altered consciousness, convulsions, meningismus, cranial nerve palsies, or signs of raised intracranial pressure
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can also go adrenal TB , pericardial , pleural
clinical features for pericardial TB ?
clinical features for pericardial effusion , cardiac tamponade and pericarditis
clinical features of tuberculous pleurisy ?
and diagnostics ?
Intensive (pleuritic) chest pain
Dyspnea
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x ray ultrasound or CT - effusions and pleural thickening thoracocentesis - lights criteria ph <7.4 glucose <60mg/dl increase adenosine deaminase lymphocyte rick micro - acid fast staining , pcr , culture sputum smear
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therapeutic throcacentiseis along with usual treatmnet
in chest auscultation what are the sounds ?
percussion
Dullness over areas of consolidation
Hyperresonance over areas of cavitation
auscultation
Amphoric breath sounds over areas of cavitation
Rhonchi
Crackles
Diminished breath sounds over areas of consolidation
diagnosis of TB
accurate diagnostic test for pediatric TB
TB is often a clinical diagnosis and given the poor sensitivity of our current diagnostic tools, a negative test does not rule out disease in children
TB is often a clinical diagnosis and given the poor sensitivity of our current diagnostic tools, a negative test does not rule out disease in children -
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golden standard is culture
Most children <7 years do not have the tussive force and/or the oromotor coordination to produce a good-quality expectorated sputum specimen on command
Semi-invasive techniques such as gastric aspiration/lavage or sputum induction (using hypertonic saline) with or without nasopharyngeal aspiration may be required
string test in which a gelatin capsule containing a nylon string is swallowed and later retrieved for TB culture. The procedure is tolerable for children who can swallow
up to 6 weeks for positive growth - not fast enough
can use PCR testing
microbio
gram positive - but does not stain well
ziehl Nielsen stain - acid fast bacilli appears pink
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smear microscopy and NAATs are much faster than culture however ensitivity is even further reduced
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chest x ray
Primary TB (middle/lower lobes) = Hilar lymphadenopathy (can be unilateral or bilateral
ghon complex - finenodularopacities
consolidation
cavitation
pleural effusion
Reactivation TB: fibrocaseous cavitary lesions in upper lobes
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in extrapulmonary TB, site-specific specimens for TB culture are often collected, such as cerebrospinal fluid (CSF), lymph node aspirates and other tissue specimens
what is the diagnosis for latent TB ?
this is to identify individuals who will benefit from treatment
This includes children < 5 years
HIV positive, taking immunosuppressant drugs,
close contact with individuals who have TB,
are residents or employees in high-risk settings
abnormal chest x-ray
diabetes, CKD
immunodiagnostics are not able to distinguish between latent infection and active disease.
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TST - tuberculin skin test / mantoux test
test delayed hypersensitivity
PPD injected intradermally on the volar surface of forearm resulting in wheal formation
Positive TST indicates active TB or latent TB
≥ 5 mm is considered positive in:
Close contacts of patients with TB
HIV infection
Individuals with clinical or radiographic evidence of active or prior TB
Individuals with organ transplants or receiving immunosuppressive therapy
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≥ 10 mm is considered positive in:
Individuals who have moved within the last 5 years from a high TB burden country
Individuals living or working in high-risk settings (e.g., homeless shelters, prisons)
Intravenous drug users
Mycobacteriology laboratory workers
Individuals with illnesses such as diabetes and CKD
Children < 5 years of age
Children who have had contact with adults in high-risk categories
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≥ 15 mm is considered positive in all other individuals
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IGRA
Tests cell-mediated immunity against M. tuberculosis-specific antigens by measuring the amount of IFN-γ released by T cells
Blood is drawn into tubes coated with M. tuberculosis-specific antigens
ELISA test measures the amount of IFN-γ released by T cells after antigen exposure.
No differentiation between active and latent TB
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negative test of TST or IGRA does not rule out TB
what are the limitations of TST ?
False positives resulting from either of the following:
Prior BCG vaccination
Exposure to nontuberculous mycobacteria
False negatives in any of the following: Sarcoidosis Immunosuppressed state Young children Recent TB infection (within 6–8 weeks) Recent live-virus vaccine Disseminated TB
which is the preferred test in individuals who have had previous BCG vaccines ?
IGRA
what is the preferred test Preferred test in children < 5 years of age ?
Preferred test in children < 5 years of age!!!!
what is the treatment of TB?
Because of the slow growth of mycobacteria and the dormant state of many bacilli, the duration of treatment is quite lengthy
treatment of latent TB requires 3–9 months, depending on whether a mono-therapy or combination therapy approach is used.
the “short course” regimen for active TB requires 6 months
more severe forms of TB including TB meningitis and drug-resistant TB require 12+ months of therapy
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latent TB
No clinical or radiological evidence of TB
Traditional treatment of LTBI typically includes 9-months of isoniazid daily with pyridoxine for breast
breastfeeding infants
isoniazid and rifapentine once weekly for 3 months is safe and effective in children aged 2–17 years
or 4 months daily rifampicin
9 months daily isoniazid
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primary tb
isoniazid, - 10 mg/kg/
rifampin, - 15 mg/kg
pyrazinamide - 35 mg/kg
ethambutol - 20 mg/kg
for the first two months,
followed by four months of isoniazid and rifampicin
daily
