Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Managing exudative pleural effusions in tuberculosis

  Pleural tuberculosis can present as an inflammatory, lymphocyte-predominant exudative effusion with relatively few bacilli in the fluid or sputum. Clinicians should suspect it in a patient with unilateral pleuritic pain, fever, weight loss, breathlessness or a persistent cough, especially when imaging shows an effusion without major parenchymal change. Older adults may have less fever and more fatigue, while pleural disease can be the first or only sign of infection.

  Management must do two jobs at once: relieve the effusion and identify or strongly infer its cause. Tuberculous pleuritis must be separated from parapneumonic empyema, malignancy, autoimmune pleuritis and pulmonary embolism because drainage, antimicrobials, corticosteroids and cancer investigations differ. Waiting for every test result can be unsafe when infection is septicaemic or respiratory compromise is developing.

  Once tuberculosis is clinically plausible, the effusion should not be treated as an isolated fluid problem. In Australia, notifiable-disease duties, public tuberculosis drug services, specialist respiratory or infectious-disease input and culturally safe follow-up all influence the pathway. These systems are particularly important for people with chronic lung disease, recent migrants and residents of remote communities.

  Recognising the clinical pattern

  Assessment should establish the tempo of symptoms, previous tuberculosis, immunosuppressive treatment, malignancy and possible occupational or household exposure. Fever, night sweats and weight loss support tuberculosis, although their absence does not exclude it. A small pleural effusion may cause disproportionate pain, while a large effusion may produce breathlessness without marked systemic illness.

  Thoracic ultrasound should accompany chest radiography because it can distinguish fluid from pleural thickening, identify loculations and guide thoracentesis. Computed tomography may show pleural nodularity, thickening or associated lung lesions, but it does not reliably establish the cause. Pleural fluid is usually clear or bloodstained; frank pus immediately raises the possibility of empyema.

  Breathlessness may also reflect smoking-related lung disease or environmental exposure. The APSR resource on air pollution impacts is useful when separating these causes from persistent symptoms caused by pleural disease.

  Establishing the diagnosis

  Diagnostic thoracentesis should provide fluid for cell count and differential, protein, lactate dehydrogenase, glucose, pH, cytology, acid-fast bacilli smear, mycobacterial culture and nucleic-acid amplification testing. Tuberculous fluid is usually lymphocyte-predominant, protein-rich and exudative, often with low glucose and high lactate dehydrogenase. Light’s criteria can identify an exudate but cannot determine its cause.

  Adenosine deaminase may support the diagnosis, particularly where tuberculosis incidence is high, but interpretation depends on local prevalence and the assay used. It can also rise with empyema, lymphoma and other inflammatory conditions, so it should not be used as a stand-alone test. A negative pleural smear or culture likewise does not exclude pleural tuberculosis because bacillary yield from fluid is low.

  Interferon-gamma release assays and tuberculin skin tests indicate infection but cannot reliably distinguish latent from active disease or prove that a pleural effusion is tuberculous. When fluid results remain inconclusive, image-guided pleural biopsy or medical thoracoscopy can provide tissue for histology, culture and molecular testing. Cytology should still be assessed carefully because malignancy and tuberculosis can coexist.

  Deciding when drainage is required

  Not every tuberculous effusion needs a chest drain. Therapeutic drainage is appropriate for a large symptomatic effusion, recurrent fluid, respiratory compromise or diagnostic sampling that cannot be obtained safely by thoracentesis. Pus, sepsis, loculation or failure to improve also favour active source control. Fluid should be removed gradually, with close observation for re-expansion pulmonary oedema.

  When pleural infection is severe, obtain microbiology before antibiotics where feasible, but do not delay treatment in an unstable patient. Empyema requires appropriate antibacterial therapy, drainage and management of any continuing source. If tuberculosis is strongly suspected, specialist-directed antituberculous therapy may begin after specimens have been collected rather than waiting for pleural biopsy.

  Routine corticosteroids and routine intrapleural fibrinolytics are not recommended for a simple tuberculosis-associated effusion. Fibrinolytic or deoxyribonuclease protocols may occasionally be considered for selected loculated empyemas, but their use in tuberculous fluid requires specialist assessment because of bleeding risk. Persistent fever should prompt review of the diagnosis, drainage adequacy, drug tolerance and alternative causes.

  Treating drug-susceptible pleural tuberculosis

  Drug-susceptible pleural tuberculosis generally requires six months of therapy: two months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by four months of isoniazid and rifampicin. Treatment should be supervised by a respiratory or infectious-disease specialist and adjusted if culture or molecular testing identifies resistance. The local public health program should be involved early.

  In Australia, standard antituberculous medicines are generally supplied and dispensed through state and territory tuberculosis services or associated public hospital pharmacies rather than being routinely self-purchased from community chemists. This arrangement supports uninterrupted treatment and direct clinical oversight. Clear advice is needed about missed doses, vomiting, pregnancy, HIV and other conditions that can alter drug safety or duration.

  Patients require baseline and regular liver-function testing, assessment for visual acuity and colour discrimination while taking ethambutol, and monitoring for neuropathy, hypersensitivity and drug interactions. Rifampicin can turn urine, sweat, saliva and tears orange-red and may reduce the effect of medicines such as warfarin, anticonvulsants and some antiretroviral therapies. Pyridoxine is often provided for patients at risk of isoniazid-related neuropathy.

  Preventing complications and monitoring recovery

  Acute deterioration may reflect expanding empyema, pulmonary oedema after drainage, respiratory failure or progression of the underlying infection. Severe hypoxaemia requires urgent assessment, and a new neurological symptom during treatment may indicate an immune-related complication or drug toxicity. Chest pain, fever and rising inflammatory markers should not automatically be attributed to the original effusion.

  Significant adverse effects include drug-induced liver injury, ethambutol optic neuropathy, peripheral neuropathy and severe hypersensitivity. Patients should receive written instructions describing which symptoms require same-day review and should not stop the regimen without advice. Prescribers should also review complementary medicines, alcohol use and interactions that may become important as the regimen changes.

  Tuberculous pleuritis can leave pleural fibrosis, thickening or restrictive impairment even after the infection is controlled. Follow-up should assess symptoms, oxygenation, examination and appropriate imaging, with further investigation for persistent fever, weight loss or progressive pain. Residual thickening alone does not prove ongoing active disease, but new or enlarging abnormalities should be reassessed for malignancy, empyema or recurrent tuberculosis.

  Coordinating care and completing the pathway

  Sydney and Melbourne report many tuberculosis cases because of their size and substantial migrant communities, while rates remain disproportionately high among Aboriginal and Torres Strait Islander communities, particularly in some remote areas of the Northern Territory and Western Australia. For patients in shared homes, student accommodation or dependent workplaces, contact assessment should focus on sustained close exposure rather than brief contact on trains and trams. Pleural tuberculosis is generally less infectious than active pulmonary disease.

  Remote care requires reliable specimen transport, access to imaging and links with Aboriginal Medical Services, local hospitals and services such as the Royal Flying Doctor Service. Telehealth can support review, but it should not substitute for urgent assessment of sepsis or respiratory compromise. Interpreters, cultural safety and practical help with transport are integral to reliable treatment.

  Tuberculosis is notifiable under the relevant state or territory public health legislation. Clinicians must notify suspected or confirmed cases, after which public health teams may coordinate contact tracing, infection-control advice and directly observed treatment where indicated. Community pharmacies are a familiar first stop for coughs, but ordinary cough medicines do not treat tuberculosis; persistent cough, night sweats, fever or weight loss needs medical assessment.

  The practical takeaway is to regard a suspected tuberculous pleural effusion as a coordinated medical and public-health problem: obtain adequate fluid or pleural-tissue testing, drain complicated infection promptly, provide the full evidence-based drug course under specialist supervision, and connect the patient with notification, contact assessment, culturally appropriate support and structured follow-up.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)