Tuberculosis (TB)

• Pathophysiology and epidemiology                                        

  

• Infection by one of the Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, or M. africanum. They are acid-fast bacilli (AFB), meaning their high-lipid, waxy coating make them difficult to decolorize with acids during staining.
• Respiratory transmission.
• In primary infection it enters the lungs and is engulfed by macrophages. The macrophages form granulomas (aka tubercles), which can become necrotic ('caseating'). There is often spread to local lymph nodes.
• It remains latent until reactivation (aka secondary infection, postprimary infection), which may occur during transient immunosuppression and/or physical stress. The lifetime risk of active TB among latent carriers is 10%.
• Can disseminate in blood or lymphatics to cause single organ or multiorgan ('miliary') disease, especially in kids and the immunosuppressed.

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• Signs and symptoms

  Overview:

  • Primary infection is usually asymptomatic, with active disease usually representing secondary reactivation.
  • Onset can be insidious and non-specific.
  • When symptoms occur, there are often systemic features: fatigue, malaise, fever, night sweats, weight loss, anorexia, and immunosuppression.

  Organ-specific TB

  Pulmonary TB:

  • Chronic productive cough ± haemoptysis, clubbing.
  • Can progress to pneumonia, pleural effusion, lobar collapse, and bronchiectasis.
  • Accounts for 60% of TB cases in UK.

  Genitourinary TB:

  • Frequency, dysuria, loin/back pain, haematuria.
  • Can progress to renal TB, salpingitis, epididymitis, and cystitis.
  • 2nd commonest TB presentation in UK.

  Others:

  • Skeletal TB: most commonly affects spine (Pott's disease). Can lead to vertebral collapse.
  • Skin TB (aka lupus vulgaris): rough nodules, often on the face or shin, which are +ve for AFB. Other TB skin manifestations include scrofula ('cold' cervical lymphadenopathy), erythema nodosum, and erythema multiforme.
  • Peritoneal TB: abdominal pain, diarrhoea, vomiting, ascites.
  • TB meningitis: neurological signs are usually preceded by weeks of systemic symptoms. TB can also cause tuberculomas: tubercles in the brain.
  • TB pericarditis: acute or constrictive pericarditis.

  Miliary TB

  Affects multiple organs so symptoms are varied; there are often retinal signs.

• Risk factors

  • Contact with infected individuals.
  • South Asian or African.
  • Homeless
  • Immunosuppressed, including HIV and extremes of age.

• Investigations

  CXR

  CXR is the first line investigation. Get it even in extrapulmonary TB.

  Primary infection findings:

  • Distinct Ghon focus in the middle zone, or an area of patchy consolidation. Sometimes the parenchymal focus is too small to detect.
  • Extra-parenchymal features: ipsilateral hilar lymphadenopathy (especially in kids), effusion (especially in adults).
  • These signs may resolve following successful immune response, leaving just calcified nodes in ⅓.

  Secondary infection findings:

  • Cavitating lesion (air-filled) in the apices, especially the right.
  • Other signs include patchy consolidation and linear or nodular opacities.

  Miliary TB findings:

  • Diffuse 1-10 mm shadows throughout lung fields.
  • The term 'miliary' is used to describe a CXR when there are more nodules than can be easily counted. Other causes include varicella pneumonia, miliary mets (e.g. thyroid or breast), or reticulonodular interstitial lung diseases such as coal worker's pneumoconiosis.

  Microbiology

  Getting samples:

  • Pulmonary: 3 sputum samples (including 1 early morning), ideally spontaneous. Otherwise induce with nebulized saline (airway irritant) or do bronchoalveolar lavage. In kids, gastric lavage is preferred to BAL as it is more sensitive.
  • Extrapulmonary: aspirate or biopsy lymph nodes, ascites, organs, pus, urine, or CSF.

  Investigations:

  • Microscopy, culture, and sensitivities. AFB smear and microscopy usually involves Ziehl-Neelsen staining, which is around 65% sensitive. Culture in a Lowenstein-Jensen medium typically takes 4-8 weeks and is around 80% sensitive.
  • Nucleic acid amplification tests (NAAT) allow diagnosis a week earlier than culture, with a similar sensitivity.
  • PCR for rifampicin resistance.
  • Histology of biopsies for caseating granuloma.

  Immunological testing

  Methods:

  • Mantoux (aka PPD): a tuberculin skin test. A delayed hypersensitivity response to tuberculin develops from 2-10 weeks after primary infection. Also +ve post BCG vaccination.
  • Interferon gamma release assays (IGRA): Quantiferon Gold or T-spot. Measures T cell response (IFN-γ release) to TB antigens. More specific than tuberculin skin tests.

  Uses and limitations:

  • Both are around 80% sensitive.
  • Cannot distinguish between latent and active TB, so especially limited for individuals from endemic regions.
  • More useful for screening contacts than diagnosis. Mantoux usually first, then confirmed with IGRA, or use IGRA first in those with previous BCG.

  Other investigations

  • HIV screening.
  • Basic bloods – FBC, LFT, U&E – may show systemic and extrapulmonary disease, and are required for baseline values before starting treatment.
  • Imaging for suspected extrapulmonary TB: CT/MRI (CNS, abdo, bone), US (pericardial, lymph node, GU), XR (bone).

• Management

  Active TB

  Infection control:

  • Notify public health authorities.
  • Screen close contacts.
  • For pulmonary TB, isolate patient in a single room, ideally negative pressure, for first 2 weeks of treatment. Have them wear mask if they leave the room.
  • Masks and gowns for healthcare workers are only needed for aerosol-generating procedures like sputum induction or bronchoscopy, or for multidrug-resistant TB.

  Drug treatment:

  • Treat before confirmation by culture if clinical suspicion is high. Consider continuing treatment even if culture is negative but clinical signs are strong.
  • 6 months treatment with RIPE: Rifampicin and Isoniazid throughout, and Pyrazinamide and Ethambutol for the first 2 months (4 for 2, 2 for 4).
  • Add further 6 months of dual therapy for meningeal TB.
  • Add steroids for meningeal and pericardial disease.
  • Consider directly observed therapy (DOT) to increase adherence.

  Latent TB

  Offer treatment to those with latent infection plus any 1 of:

  • Close contacts with active TB.
  • At high risk of progression to active TV: immunosuppressed, aged <5 years, alcoholic, IVDU, diabetes, or CKD
  • Immigrants from high incidence countries.
  • Healthcare workers.

  Drug options:

  • 3 months isoniazid + rifampicin.
  • 6 months isoniazid monotherapy if need to avoid rifampicin e.g. on antiretrovirals.

  Prevention

  Mantoux/IGRA screening for:

  • Healthcare workers who are unvaccinated or from high incidence countries.
  • Close contacts (household, partner) of people with active TB.
  • Immigrants from high incidence countries.

  Actions:

  • If -ve, give BCG.
  • If +ve, assess for active TB and treat latent/active TB as needed.
  • In older immigrants, benefits of BCG (if age >35) and latent TB treatment (if age >65) may be smaller so are not routinely indicated.

  BCG vaccine:

  • Reduces infection risk by 25% and active TB risk by 70% (in children).
  • In addition to those identified through screening, give to children at risk i.e. high risk UK areas, family from high risk countries.
  • Also offer to those at risk through occupational exposure e.g. vets who handle TB-prone animals, prison staff, long-term foreign travellers.

• Side effects of TB medication

  • Rifampicin: hepatitis (so stop if ↑BR), orange urine/tears, P450 inducer (inactivates warfarin and contraceptive pill), flu-like symptoms.
  • Isoniazid: hepatitis, agranulocytosis, P450 inhibitor. Peripheral neuropathy can result from pyridoxine depletion, so give supplements to all.
  • Ethambutol: optic neuritis. Colour vision goes first, so check it using Ishihara charts before starting.
  • Pyrazinamide: hepatitis, arthralgia.