tuberculosis%20-%20pulmonary
TUBERCULOSIS - PULMONARY
Tuberculosis (TB) suspect is any one who has signs or symptoms suggestive of TB (eg >2 weeks productive cough).
Definite TB is considered in patients with culture or molecular line probe assay positive for Mycobacterium tuberculosis, or in patients with at least 1 sputum smear positive for acid-fast bacilli.
TB cases are also classified based on the disease anatomical site, bacteriological results (including drug resistance), previous treatment history and patient's HIV status.
Pulmonary TB is a case of TB that involves the lung parenchyma.
Miliary TB is considered as PTB since lung lesions are also seen.
TB in the pleural effusion, mediastinal and/or hilar lymph nodes with no evidence of abnormalities in the chest x-ray are considered extrapulmonary TB.
Patients presenting with both PTB and extrapulmonary TB are classified as a case of PTB.

Diagnosis

  • Most common symptom of pulmonary tuberculosis (PTB) is cough ≥2 weeks that is productive & may be accompanied by both/either:
    • Respiratory symptoms: Shortness of breath, chest pains, hemoptysis
    • Constitutional symptoms: Loss of appetite, unexplained weight loss, fever, night sweats, fatigue
  • Important to ask about history of previous treatment w/ anti-TB drugs
    • Has higher risk for drug resistance, including multidrug-resistant tuberculosis (MDR-TB)

Evaluation

  • Basis of the management in each patient
New Patient
  • Patients who never had tuberculosis (TB) treatment or have taken anti-TB regimen for <1 month
  • Assumed to be drug susceptible unless the patient is from an area w/ high prevalence of Isoniazid resistance or if the patient had active TB after contact w/ a documented multi-drug resistant strain of TB (MDR-TB) patient
  • Patients who will have MDR-TB at any time during the therapy will be considered as a treatment failure
Previously Treated Patient
  • Has history of taking anti-TB drugs for ≥1 month & currently smear or culture positive again
  • Further subclassified based on the outcome of their most recent treatment course
    • Relapse: Patient has been cured or most recent prior treatment was completed
    • Failure: Most recent prior treatment has failed
    • Default: Treatment was interrupted for ≥2 consecutive months
  • Strongly determines resistance of drugs
    • Timely detection of multi-drug resistance (MDR) & start of MDR regimen w/ 2nd-line drugs gives a better likelihood of cure & prevents development & transmission of further resistance
    • Incidence of MDR is higher in previously treated patients than in new patients
      • Patients returning after defaulting or relapsing has lesser MDR rates than patients who had treatment failure
    • Patients w/ prior treatment failure should be given an empirical MDR regimen while waiting for the results if conventional drug susceptibility testing (DST) was used
      • Prevents clinical deterioration of the patient & decreases risk of transmission to contacts
    • National TB Control Program (NTP) should use country-specific drug resistance data of patient groups on failure, relapse & default to know the level of MDR
    • High MDR levels are noted in patients:
      • Treated in poorly operating NTP
      • Living w/ human immunodeficiency virus (HIV)
      • W/ type 2 diabetes mellitus
      • W/ history of using poor or unknown quality of anti-TB drugs
      • Exposed in institutions w/ high-prevalence rate or outbreak of MDR
      • W/ conditions associated w/ malabsorption or rapid-transit diarrhea
      • Whose prior regimen included Rifampicin throughout the course
      • Who still has positive sputum smear at mth 2 or 3 of treatment

Laboratory Tests

Sputum Smear Microscopy
  • At least 2 sputum samples should be submitted by all tuberculosis (TB) suspects for microscopy
    • Patient must submit at least 1 early-morning sputum sample which usually has the highest yield
    • 2 sputum samples submitted on the same day are comparable to 2 consecutive days-sputum specimens
      • W/ similar sensitivity (63-64%) & specificity (98%) rates
  • Recommended also for patients w/ chest X-ray suggestive of TB
  • Pulmonary tuberculosis (PTB) cases w/o results of sputum smear are classified as “smear not done”
  • Also used in monitoring treatment response of patients
  • Fluorescence microscopy preferred over conventional microscopy because of its higher sensitivity & better time efficiency
Smear-positive pulmonary tuberculosis (PTB)
  • Considered smear-positive if ≥1 sputum smear specimens at the start of treatment in countries w/ well functioning external quality assurance (EQA) system are positive for acid-fast bacilli (AFB) 
  • In countries w/ no functional EQA, a smear-positive PTB is considered when:
    • ≥2 initial sputum smear exams are positive for AFB, or
    • 1 sputum smear exam is positive for AFB w/ abnormalities consistent w/ active PTB in chest X-ray, or
    • 1 sputum smear positive for AFB w/ culture positive for M tuberculosis
Smear-negative pulmonary tuberculosis (PTB)
  • Considered in patients w/ negative sputum smear but w/ positive culture for M tuberculosis or when at least 2 sputum samples at the start of treatment in countries w/ a functional EQA system are negative for AFB
    • To confirm the diagnosis of TB, sputum culture for M tuberculosis is advised in patients who live in areas w/ human immunodeficiency virus (HIV) prevalence of >1% in pregnant women or ≥5% in TB patients that have smear-negative sputum
  • Also regarded in patients who are being treated by a clinician w/ a full course of anti-TB regimen w/ abnormalities in chest X-ray consistent w/ active PTB, & patient is either positive for HIV or if w/ negative or unknown HIV status that lives in area of low HIV prevalence, has no improvement in response to a course of broad-spectrum antibiotics (excluding anti-TB drugs & fluoroquinolones & aminoglycosides)
Rapid Molecular Tests
  • Nucleic acid amplification tests (NAATs) are recommended for better detection of M tuberculosis
  • Older NAATs have low sensitivity & w/ negative predictive value for smear-negative & extrapulmonary TB
Xpert MTB/RIF
  • A highly sensitive & specific cartridge-based fully automated NAATs for the detection of M tuberculosis & Rifampicin resistance
    • 68% sensitive, 99% specific when compared to sputum culture; 88% sensitive & 98% specific when compared w/ smear microscopy
    • 94% pooled sensitivity, 98% pooled specificity for Rifampicin resistance
    • 84.9% sensitive for extrapulmonary TB (eg lymph nodes, lung aspirates)
    • 79.5% sensitive for CSF analysis for TB meningitis
  • Recommended as an initial diagnostic tool for the following:
    • Suspected TB patients able to produce sputum samples
    • Adult patients w/ risk factors for multi-drug resistance
    • Adult patients w/ comorbidities (HIV infection, immunocompromised)
    • Pediatric patients suspected to have multidrug resistance or HIV-associated TB rather than using other diagnostic tests (eg sputum smear testing, culture, drug susceptibility tests)
    • CSF examination of patients suspected to have TB meningitis
  • Recommended as a confirmatory test for suspected TB patients w/ negative sputum smear microscopy results
  • May also be used as an initial diagnostic tool for non-sputum specimens (gastric lavage fluid, other non-respiratory specimens) from patients at high risk for extrapulmonary TB
Interferon-Gamma Release Assay (IGRA)
  • A diagnostic blood test used to identify a patient’s immune reactivity to M tuberculosis
  • May be considered for the initial diagnosis of children suspected to have TB; not recommended for the initial diagnosis in adults
  • Tuberculin testing still preferred over IGRA for patients belonging to low-middle class families
Tuberculin Skin Testing (Mantoux Method)
  • Recommended for the initial diagnosis of children suspected to have TB, but w/ no history of contact w/ persons w/ active TB disease
  • Not recommended as an initial diagnostic tool for adults
  • Also used as a screening exam for pediatric patients in contact w/ persons w/ active PTB
  • >5 mm diameter of induration in immunocompromised children or >10 mm induration diameter in healthy pediatric patients w/ or w/o BCG vaccination is positive for tuberculin testing
  • A positive skin test is not conclusive of an active TB disease; other confirmatory tests should be performed
Culture
  • Used for definitive diagnosis of TB in patients w/ negative sputum smear, especially in areas w/ high HIV prevalence
  • Also advised in patients in whom drug resistance is likely considered
  • Liquid culture & rapid species identification is preferable than solid-based methods alone
    • Liquid system detects mycobacteria more & increases the case yield by 10%, & provides DST result w/in 10 days as compared to solid media
Drug Susceptibility Testing (DST)
  • Ideally done to all patients at the start of the treatment to identify & provide the most appropriate therapy
  • Should be done at or prior to the start of treatment in:
    • New patients who had active TB after contact w/ a documented multidrug-resistant tuberculosis (MDR-TB) patient
    • All previously treated patients, especially in patients w/ sputum smear-positive after 3 months therapy, treatment failure, patients lost to follow-up, & those w/ disease relapse after treatment
    • Patients living w/ HIV
    • HIV-infected TB patients w/ CD4 counts <200 cells/mm3
    • All new patients in countries w/ >3% MDR-TB level in new patients
  • Should be performed for at least Isoniazid & Rifampicin
  • Conventional DST provides result w/in a week for liquid media or month for solid media; therefore, patients should be given empirical regimen while awaiting the results
    • Shorter waiting time for DST results may stop continued spread of multidrug-resistant (MDR), prevent increase of resistance, & avoid increased risk of patient defaulting from treatment due to adverse effects of unnecessary empiric drugs
Xpert MTB/RIF (please see above)

Line-Probe Assay
  • A rapid molecular-based DST that provides result for Isoniazid or Rifampicin w/in 1-2 days which can be used in deciding the treatment appropriate for the patient
  • Confirmatory diagnostic tool for sputum smear positive patients & culture-positive TB isolates
  • Not to be used as an initial test for TB detection; should be used together w/ culture & drug susceptibility testing
Phenotypic Drug Susceptibility Testing for Anti-TB Drugs
  • Testing for all fluoroquinolones & injectable aminoglycosides are recommended for Rif-resistant & MDR-TB patients

Imaging

Chest X-ray
  • Sensitive but nonspecific test to detect tuberculosis (TB) [98% sensitive, 75% specific for any abnormality suggestive of TB]
  • Cannot establish the diagnosis of TB alone
  • Used to evaluate patients w/ negative sputum smears &/or negative Xpert MTB/RIF, & identify other possible diagnosis
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