Tuberculosis

Question 1

What is TB?

Answer 1

• Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis.
• In many cases, M tuberculosis becomes dormant before it progresses to active TB.
• It most commonly involves the lungs and is communicable in this form, but may affect almost any organ system including the:
  
  • lymph nodes
  • CNS
  • liver
  • bones
  • genitourinary tract
  • gastrointestinal tract.

Question 2

What is the aetiology of TB?

Answer 2

The development of TB requires infection by M tuberculosis and inadequate containment by the immune system.

• Patients infected with M tuberculosis who have no clinical, bacteriological, or radiographic evidence of active TB are said to have latent TB infection.
• Active TB may occur from re-activation of previously latent infection or from progression of primary infection.
• Transmission of TB occurs from individuals infected with pulmonary (and rarely laryngeal) disease.
• Infection results from the inhalation of aerosolised droplets containing the bacterium.
• The likelihood of transmission depends on the infectivity of the source case (e.g., smear status and extent of cavitation on CXR), the degree of exposure to the case (e.g., proximity, ventilation, and the length of exposure), and susceptibility of the person in contact with an infected case.
• HIV-infected individuals are at greater risk of re-activation as well as progression to primary TB.
• Other groups at increased risk for the development of active TB include persons with recent tuberculin skin test conversion (TST), the homeless, injection drug users, cigarette smokers, and immunocompromised individuals (e.g., people with diabetes, prolonged corticosteroid therapy, end-stage renal disease (ESRD), malnutrition, or haematological malignancies)

Question 3

Name some risk factors for TB

Answer 3

• exposure to infection
• immunosuppression
• silicosis
• malignancy
• birth in an endemic country
• HIV in appropriate areas

weak:

• malignancy
• ESRD (end stage renal disease)
• intravenous drug use
• malnutrition
• alcoholism
• diabetes
• high-risk congregate settings
• low socio-economic status or black/Hispanic/Native American ancestry
• age
• tobacco smoking

Question 4

Summarise the epidemiology of TB

Answer 4

• According to WHO data, TB is the ninth leading cause of death worldwide, and is the leading cause of death from a single infectious agent.
• In 2016, an estimated 10.4 million people developed TB, and there were an estimated 1.3 million TB deaths among HIV-negative people and 374,000 TB-related deaths among HIV-positive people.
• More than half of all cases (56%) were in five countries: India, Indonesia, China, the Philippines, and Pakistan, and the majority of deaths (85% of HIV-negative and HIV-positive TB deaths) were in the WHO African Region and South-East Asia Region.
• TB is particularly devastating in areas with high prevalence of HIV infection.
• The lungs are the main site of infection with M tuberculosis.
• In the US, an estimated 9.5 million people have latent TB infection.
• In 2016, 9272 cases of TB were reported, with an incidence rate of 2.9 cases per 100,000 people, a 3.6% decline from the previous year.
• The TB case rate was 1.1 per 100,000 for US-born people and 14.7 for foreign-born people.
• The percentage of cases occurring in foreign-born people increased to 68.5% of the national case total.
• This percentage has risen steadily since 1993.
• Asian people continued to have the highest case rate (18.0 per 100,000 people) among all racial or ethnic groups in the US

Question 5

What are the presenting symptoms of TB?

Answer 5

• cough
  
  • Duration over 2 to 3 weeks; initially dry later productive. Outpatient study found that only 50% of patients had cough over 2 weeks.
• fever
• anorexia
• weight loss
• malaise

Question 6

What are some uncommon presenting symptoms of TB?

Answer 6

• pleuritic chest pain
  
  • May suggest pleuritic involvement.
• haemoptysis
• psychological symptoms
• abnormal chest auscultation
  
  • Chest examination may be normal in mild/moderate disease. Possible findings include crackles, bronchial breath sounds, or amphoric breath sounds (distant hollow breath sounds heard over cavities).
• asymptomatic
• dyspnoea
  
  • A late finding in the setting of extensive lung destruction or effusion.
• clubbing
• erythema nodosum

Question 7

What are the signs of TB O/E?

Answer 7

uncommon

• clubbing

Question 8

What are some primary investigations for ?TB

Answer 8

• CXR
  
  • First-line test.
  • Is almost always abnormal in immunocompetent individuals. Typically presents as fibronodular opacities in upper lobes with or without cavitation
  • = abnormal typical for TB; abnormal atypical for TB; or normal
• sputum acid-fast bacilli (AFB) smear
  
  • ​Sputum may be spontaneously expectorated or induced (with appropriate precautions to prevent transmission), and 3 specimens should be collected (minimum 8 hours apart, including an early morning specimen, which is the best to detect M tuberculosis
  • The examiner looks for AFB (the stained dye remains even after exposure to acidic media) consistent with M tuberculosis. Other organisms, especially non-tuberculous mycobacteria (e.g., M kansasii and M avium), are positive on AFB stain. Thus, a positive AFB smear is not specific in populations with low TB prevalence.
  • If sputum is positive for AFB, the results will be graded from 1+ to 3+ or 4+ depending on number of organisms seen and grading scale. Smear positivity and its grading may help estimate the degree of infectiousness and burden of TB. In the US, sensitivity is 50% to 60%
  • = positive for acid-fast bacilli (AFB)
• sputum culture
  
  • The most sensitive and specific test. Should always be performed as it is required for precise identification and for drug susceptibility testing.
  • Growth on solid media may take 4 to 8 weeks; growth in liquid media may be detected in 1 to 3 weeks. Growth on solid media if positive is reported on quantitation scale (1+ to 4+).
  • While on treatment, the patient should have sputum cultures performed at least monthly until 2 consecutive cultures are negative
  • = positive; no growth; or other mycobacteria
• FBC
  
  • Leukocytosis (without left shift) and anaemia each seen in 10%.[33] Other abnormalities include elevated monocyte and eosinophil counts. Pancytopenia may be seen in disseminated disease
  • = raised WBC; low Hb
• nucleic acid amplification tests (NAAT)
  
  • DNA or RNA amplification tests for rapid diagnosis. May be used on sputum or any sterile body fluid. Several commercial tests are available. Results available in <8 hours in the laboratory.
  • Useful in smear-positive disease to confirm that observed mycobacteria are M tuberculosis (95% sensitivity, 99% specificity) and in smear-negative disease for rapid diagnosis (50% sensitivity, 95% specificity
  • = positive forM tuberculosis

Question 9

What are some possible secondary investigations for ?TB

Answer 9

• gastric aspirate
  
  • ​Used in patients unable to produce sputum (e.g., young children). Based on overnight collection of bronchial secretions in the stomach
  • = positive for AFB
• bronchoscopy and bronchoalveolar lavage (BAL)
  
  • ​Many studies demonstrate that BAL and sputum induction have similar sensitivities. BAL may be indicated in patients in whom sputum induction is unsuccessful or in whom smear and NAAT are negative
  • = positive for AFB
• tuberculin skin testing (TST)
• interferon-gamma release assays (IGRAs)
• empirical treatment
• susceptibility testing
• genotyping
• HIV test
• CT of chest
• Xpert MTB/RIF