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)

• Challenges in diagnosing tuberculous pleurisy in Australia

  Tuberculous pleurisy is an extrapulmonary form of tuberculosis in which Mycobacterium tuberculosis affects the pleural space. It commonly presents with fever, night sweats, fatigue, weight loss and sharp chest pain, often accompanied by a unilateral pleural effusion. These findings can resemble bacterial pneumonia, malignancy, pulmonary embolism or autoimmune disease, making early recognition difficult.

  The diagnostic challenge is especially relevant in Australia, where overall tuberculosis rates are low but disease remains concentrated among people born in high-burden countries, recent arrivals and some remote communities. Clinicians in Sydney, Melbourne and Brisbane may encounter patients with relevant travel or migration histories, while teams in regional and remote areas may face delays in imaging, specialist review and laboratory testing.

  Why the clinical picture is easily missed

  Symptoms of pleural tuberculosis are often gradual rather than dramatic. A patient may report several weeks of malaise, reduced appetite, dry cough and pleuritic discomfort without the severe respiratory distress expected from a large effusion. Fever may be intermittent, and older adults or people with diabetes may show few constitutional symptoms.

  Chest radiography can reveal an effusion but rarely identifies its cause. Computed tomography may show pleural thickening, lymphadenopathy or pulmonary lesions, yet these findings are not specific. In Australia, a common assumption that tuberculosis is unlikely can further reduce clinical suspicion, particularly when a patient has no known exposure or does not volunteer a history of previous residence overseas.

  A careful history should cover country of birth, previous tuberculosis treatment, household exposure, time spent in crowded settings, immunosuppression and recent travel. This should be approached respectfully and without linking infection to ethnicity. HIV infection, anti-tumour necrosis factor therapy, chronic kidney disease, silicosis and poorly controlled diabetes can all increase the likelihood of reactivation.

  Limits of pleural fluid testing

  Thoracentesis is usually required when an unexplained exudative effusion is present. Tuberculous pleural fluid is commonly lymphocyte-predominant, with elevated protein and lactate dehydrogenase. However, these results overlap with lymphoma, metastatic cancer, fungal infection and some autoimmune conditions. Early disease can also produce a neutrophil-rich fluid profile, so cell count alone should not exclude tuberculosis.

  Adenosine deaminase, or ADA, may support the diagnosis when levels are high in a lymphocytic exudate. Its value depends on local disease prevalence and the differential diagnosis. False-positive results occur with empyema, lymphoma and some other inflammatory conditions. In a low-incidence setting such as Australia, an isolated raised ADA should therefore be interpreted alongside imaging, exposure risk and microbiology rather than treated as definitive proof.

  Smear microscopy has limited sensitivity because pleural tuberculosis is often paucibacillary. Nucleic acid amplification tests can provide rapid evidence, but a negative result on pleural fluid does not reliably rule out disease. Samples should be sent for mycobacterial culture, molecular testing, routine bacterial studies and cytology where appropriate, with sufficient volume collected before starting treatment whenever the patient is clinically stable.

  The role of pleural biopsy

  When fluid studies are non-diagnostic, pleural tissue may be the decisive investigation. Histology showing caseating granulomatous inflammation is strongly suggestive, although granulomas can occur in sarcoidosis, fungal infection and other disorders. Tissue should also be submitted for mycobacterial culture and molecular testing because histology alone cannot establish drug susceptibility.

  Image-guided core biopsy can be useful when focal pleural thickening is visible on CT or ultrasound. Medical thoracoscopy or video-assisted thoracoscopic surgery generally provides a higher diagnostic yield by allowing direct inspection and multiple targeted biopsies. The choice depends on local expertise, anaesthetic risk, imaging findings and access to respiratory or thoracic surgical services.

  This creates practical differences across Australia. A patient in metropolitan Melbourne or Sydney may receive rapid thoracic ultrasound, interventional radiology and thoracoscopy, whereas someone in the Northern Territory or far north Queensland may require transfer to Darwin, Cairns or another regional hub. Clear communication between rural clinicians, infectious diseases teams and laboratories helps prevent diagnostic drift during these transfers.

  Distinguishing tuberculosis from competing diagnoses

  Malignancy is a major alternative diagnosis in an adult with an unexplained pleural effusion, especially when there is weight loss or pleural nodularity. Cytology can detect metastatic adenocarcinoma but is less reliable for mesothelioma and some lymphomas. A negative cytology result should not end the investigation when the imaging or clinical course remains concerning.

  Parapneumonic effusion and empyema can produce fever, pleuritic pain, raised inflammatory markers and a lymphocyte shift later in the illness. Low pleural fluid pH, low glucose, loculations and pus favour complicated bacterial infection, but mixed infections are possible. Pulmonary embolism, connective tissue disease and drug-related pleuritis also need consideration, particularly when cultures remain negative.

  Australia’s multicultural healthcare environment makes communication central to safe assessment. Professional interpreters should be used when needed, rather than relying on family members to translate sensitive details about symptoms, migration, household exposure or previous treatment. Tuberculosis notification and contact investigation are coordinated through state and territory public health units, and early involvement can support both diagnosis and infection control.

  Making a reliable diagnostic pathway

  A practical pathway begins with chest imaging and ultrasound-guided aspiration, followed by Light’s criteria, differential cell count, pH, glucose, cytology, bacterial culture and dedicated mycobacterial testing. ADA can add useful evidence where available. Three respiratory samples for acid-fast bacilli testing may be appropriate when pulmonary involvement is suspected, even if the chest radiograph mainly shows an effusion.

  If suspicion remains high after an inconclusive fluid result, clinicians should pursue tissue diagnosis rather than repeatedly observing the effusion. Empirical therapy may be justified in selected patients after appropriate specimens have been obtained, but treatment decisions should involve respiratory medicine or infectious diseases specialists. Drug interactions, liver disease, visual monitoring and adherence support require planning once therapy begins.

  Clinicians should also consider barriers affecting the Australian local market, including pathology turnaround times, transport of specimens from remote areas and access to subsidised medicines through public tuberculosis services. A patient’s ability to attend follow-up, obtain transport and understand a lengthy multidrug regimen is part of diagnostic and treatment safety, not an administrative afterthought.

  Tuberculous pleurisy is easiest to miss when low national incidence is allowed to replace individual risk assessment. The practical safeguard is to investigate every unexplained lymphocytic exudative effusion systematically: take a respectful exposure history, obtain adequate fluid for culture and molecular testing, use ADA cautiously, and arrange pleural biopsy when uncertainty persists.

  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)