16 MAY 2025 ausdoc. com. au

Therapy Update

The disease is often under-recognised in low-prevalence countries such as Australia.

Although up to 25 % of the world’ s population will be infected with M. tuberculosis in their lifetime, the disease is often under-recognised in low-prevalence countries such as Australia. 1 Newer diagnostic modalities, such as interferon gamma release assays( IGRAs) and nucleic acid amplification tests( NAATs), such as GeneXpert, have increased the speed and accuracy of diagnosis. Short-course therapy with first-line antimicrobials is well tolerated with high cure rates, however emerging drug resistance presents a challenge. This clinical practice review will examine these issues, and update clinicians on diagnosis, testing and treatment strategies for tuberculosis( TB).

Nomenclature

Latent TB describes asymptomatic patients with immunological evidence of prior infection with M. tb, but who do not have evidence of current active disease. Active TB describes patients who have current evidence of TB-related disease, which may include symptoms and radiological changes consistent with active TB, in conjunction with isolation of M. tb on microbiological culture, or with newer molecular techniques.

Who to suspect

Pulmonary TB is the most common form of active disease, representing approximately 80 % of cases globally. Patients classically present with sub-acute onset of cough, haemoptysis, weight loss and night sweats, although some patients have minimal symptoms.

An understanding of epidemiological risk factors is essential to identifying those at risk. The yearly incidence of active TB among overseas-born Australians is 18.5 per 100,000; compared with 0.9 per 100,000 in the general Australian population. Certain epidemiological subgroups also have higher incidences of TB. Aboriginal and Torres Strait Islander populations have a significantly higher incidence of TB than the background rate in Australia( 3.6 / 100,000). Table 1 describes the most recent available data for Australian TB notifications, demonstrating the country of birth of patients diagnosed with TB in Australia. 2

In patients with epidemiological risk factors presenting with non-pulmonary symptoms, extrapulmonary

Table 1. Notified cases and rates of tuberculosis for frequently reported countries of birth, 2015-18, by residency status

Estimated rate per 100,000 immigrants

India 33 110 60 220 592,310 37 199 Philippines 10 84 42 143 277,510 52 554 Vietnam 15 86 18 127 256,310 50 182

China 16 54 15 90 650,700 14 67 Nepal 52 11 14 80 94,470 85 151 Indonesia 13 17 18 50 85,700 58 316 Afghanistan 0 22 12 35 59,730 59 316 Papua New Guinea 2 10 17 31 34,600 92 432 Myanmar 20 7 29 36,900 79 338 Pakistan 7 12 7 28 84,340 33 265 Malaysia 10 7 9 28 173,680 16 92 Thailand 3 15 8 27 79,040 34 153 Sri Lanka 2 16 2 22 134,500 16 92 Bangladesh 0 16 2 22 134,500 16 64 New Zealand 0 17 1 20 568,290 4 7 Other overseas born 43 209 62 326 Total overseas born 208 706 294 1276 Australian born 161 Unknown country of birth 1 Total 1438 Adapted from Tuberculosis notifications in Australia, 2015-18 2

Respiratory

Professor Kwun Fong is a respiratory and sleep physician in the department of thoracic medicine, The Prince Charles Hospital, and the University of Queensland Thoracic Research Centre, Brisbane, Queensland.

Dr Thomas Knowlman is a sleep medicine fellow at Sunshine Coast University Hospital, Queensland.

Dr Geoffrey Eather is a respiratory and sleep physician in the department of respiratory, sleep and mycobacterial medicine, Princess Alexandra Hospital, Brisbane, Queensland.

WHO incidence rate per 100,000 population in country of origin

TB warrants consideration( see table 2). The most common site of extrapulmonary disease is isolated lymph node involvement. Less common sites include disease of the pleura( presenting as pleural effusion), bones and joints, genitourinary tract( presenting most commonly with chronic lower urinary tract symptoms), meningeal disease( presenting with meningitis) or peritoneal disease.

In patients with typical presentations who have recently immigrated from an area with endemic TB, the diagnosis is generally recognised promptly. However, pitfalls can arise in those with more distant epidemiological exposure. Reactivation can occur in patients exposed decades ago, particularly in the context of waning immunity. This will be discussed below.

Active tuberculosis

When to test Patients who present with the symptoms outlined previously, or suggestive radiological findings, should undergo further testing for active TB. This is particularly true for patients with a history of residing in an endemic area, and those known to have been in contact with an infectious case of TB.

How to test If pulmonary TB is suspected, chest X-ray is indicated if not already performed. Features on chest X-ray that should raise suspicion include focal opacities of the upper lobe( s), or less commonly in the lower lobes( often in the apical lower lobe segments). Cavitation may be present.

The appropriate next step in investigation of these patients is testing sputum samples, collected on three consecutive days, for the presence of acid-fast bacilli. Evaluation of these samples comprises an initial direct smear to identify acid-fast bacilli, followed by laboratory culture for up to six weeks. 3, 4

The speed and accuracy of diagnosis can also be increased by utilising NAAT, which is a molecular test that uses PCR amplification to identify DNA specific for M. tb. 5 This is highly accurate in confirming TB on sputum smear-positive cases, and can be diagnostic in those with negative sputum smears, in whom a definitive diagnosis was previously delayed by up to six weeks while awaiting microbiological culture results.

NEED TO KNOW

Consider tuberculosis( TB) in those with sub-acute onset of respiratory symptoms and with epidemiological risk factors.

Consider screening asymptomatic patients with epidemiological risk factors for latent TB, if they are at risk of reactivation.

Sputum testing is the mainstay of diagnosis for pulmonary TB. Novel testing methods are improving the speed and accuracy of microbiological detection.

Be aware of TB medication interactions and side effects, to aid prompt recognition and investigation of adverse drug events.

All patients with active TB should be managed in consultation with the local respiratory department or TB control unit.

NAAT-based testing also identifies mutations that confer rifampicin resistance. This allows a more rapid presumptive diagnosis of rifampicin-resistant TB, with an associated high likelihood of multidrug-resistant TB, prior to the results of laboratory phenotypic susceptibility testing. Furthermore, NAAT can be used on sputum smear-positive cases to distinguish between TB and infection with non-TB mycobacterium( NTM).

Further testing such as bronchoscopy is not required in most cases, but can be utilised when suspicion of TB remains high despite negative sputum testing.

For those with suspected extrapulmonary TB, diagnosis relies on sampling the suspected site of infection. In cases of suspected pleural TB, this includes aspiration of pleural fluid or direct pleural biopsy. Adjunctive tests such as adenosine deaminase testing on pleural fluid can suggest a diagnosis of pleural TB but are not diagnostic in the absence of microbiological confirmation. For suspected TB at other sites, direct sampling is indicated, including aspiration or biopsy of a lymph node in those with TB lymphadenitis and sampling of other sites including urine, CSF, tissue aspiration / biopsy at the affected site of soft tissue infection( such as soft tissue abscess). TB NAAT can also be performed on extrapulmonary samples, including pleural fluid, CSF, urine, and peritoneal fluid, although sensitivity for extrapulmonary sites is not as well established when compared with sputum testing.

How to treat All patients with active TB should be managed in conjunction with the regional TB control unit. The unit will