Don’t forget about tuberculosis

Case scenario

Hans, a 21-year-old male, recently migrated to Australia from a tuberculosis-endemic country and has been diagnosed with latent TB after a positive tuberculin skin test. His doctor prescribed daily isoniazid for 9 months, and Hans has come to you querying the need to take the pyridoxine that he was also prescribed to take with the isoniazid, dismissing it as ‘just a vitamin’. Hans uses insulin for type 1 diabetes (well controlled) but is otherwise well.

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Introduction

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection.^1,2 After a person is infected, TB is usually held in check by the immune system (latent TB infection), however it can progress to active TB disease, which can be fatal.^3–5

Though now rare in Australia, cases are still seen, and pharmacists should understand TB, and its management, as early diagnosis and appropriate management prevents disease transmission.²

Epidemiology

TB was the second most deadly infectious disease worldwide in 2022 (behind COVID-19), causing an estimated 1.3 million deaths.¹

TB is now uncommon in Australia, and transmission is rare.³ Public health initiatives (including screening, early diagnosis and prompt management) have reduced the Australian TB death rate from 108.5 per 100,000 in 1907 to 0.3 per 100,000 in 2000.^3,6

Nearly 90% of the approximately 1,400 cases each year are in those born overseas, and Aboriginal and Torres Strait Islander peoples are disproportionately affected. ^7,8

Aetiology and risk factors

Mtb is spread by inhalation of airborne infectious respiratory particles.^1,9 After Mtb enters the lungs, granulomas contain the infection (latent TB).^10,11 Latent TB is asymptomatic, non-infectious and can be lifelong.^2,3

In immunocompetent patients, 5–10% of cases progress to active TB; this is higher in some patient groups (e.g. immunocompromised, children).^2,3,11 Progression may occur from weeks to decades after initial infection.³

Active TB usually causes disease in the lungs (pulmonary TB), however other organs can be affected (extrapulmonary TB).^3,4

Key risk factors for initial TB infection include contact with active TB patients, the bacterial load of infected respiratory droplets, being born in or travel to TB-endemic countries, being a member of some Aboriginal and Torres Strait Islander communities with high TB incidence, and living in overcrowded conditions.^2,3,11

Key risk factors for progression to active TB include age (children and elderly), malnourishment, human immunodeficiency virus (HIV), diabetes, renal failure and immunocompromise.^2,3

Clinical features

Active pulmonary TB symptoms may include^2,3:

• cough (particularly if duration is >2 weeks)
• fever
• unexplained weight loss
• tiredness
• generally feeling unwell
• haemoptysis.
  

Extrapulmonary TB presents with varied symptoms dependent on the site of disease, and may present alongside pulmonary TB.^3,4

Diagnosis

TB is a national notifiable disease and is suspected in populations at high risk of exposure, such as close contacts of active cases and migrants.^3,5

Latent TB can be diagnosed with a positive tuberculin skin test (also known as a Mantoux test) or a TB-specific interferon gamma release assay, together with patient history and assessment.^2,4,12

If active pulmonary TB is suspected, investigations include a chest X-ray and sputum microscopy. Sputum can be tested for drug susceptibility and drug resistance.^3,4

Treatment

Key considerations

Management of active TB is usually handled by specialised TB services, however there is scope for latent TB to be treated in community settings.^3,12 Certain patients should be referred for specialist care, including pregnant and breastfeeding patients, extrapulmonary TB, and in cases of drug-resistance.^3,4,12,13

Infection control measures, including isolation and management of contacts, should be followed as per relevant protocols.³

Successful treatment requires appropriate pharmacological management and adherence.³ Drug resistance can occur, with 11–12% of Australian cases (2019–2022) having resistance to first-line agents.¹³ The treatment of drug-resistant TB requires expert management and is outside the scope of this article.⁴

Adherence is vital to prevent the development of resistant strains and spread of TB and may be improved by directly observed therapy (DOT), where patients are observed taking their medicines by trained healthcare professionals.^3,4,14 Examples of when DOT may be indicated include when nonadherence is likely and in the treatment of drug-resistant TB.^3,4

Before starting treatment, the patient’s weight should be recorded, liver and renal function assessed, alcohol use and hepatotoxic medicines reviewed, and visual acuity and colour vision checked. Full blood count, HIV and hepatitis (B and C) tests are also performed.⁴ Contraception should be discussed with patients of childbearing age using certain treatments (see Table 1).^4,15

Close ongoing monitoring during treatment, including adherence and for medicine adverse effects (e.g. visual changes and liver damage) is essential (see Table 1). Appropriate guidelines should be followed.⁴

Where possible and indicated, monthly sputum samples are tested (until culture-negative) and repeated at the end of treatment.⁴ Monitoring and ongoing follow-up, including repeat imaging, should occur as per relevant guidelines.^1,9,17

Pharmacists should refer to local and national guidelines (e.g. the Communicable Diseases Network Australia [CDNA] guidelines), and specialised resources such as the Therapeutic Guidelines, for comprehensive information regarding TB and its management.

Treatment of latent TB

For latent TB, the goal of treatment is to reduce risk of progression to active TB.⁴ Potential regimens include either^4,12:

• isoniazid daily for 6–9 months (PBS listed for this indication)
• rifampicin daily for 4 months
• rifampicin plus isoniazid daily for 3 months
• rifapentine (available via the Special Access Scheme) plus isoniazid weekly for 3 months.

Treatment of active TB

For active TB, the goals of treatment are bacterial eradication, minimisation
of disease transmission and complications, and the prevention of relapse and drug resistance.¹⁶

In fully drug-susceptible TB, initial cure rate with standard regimens is high, with >98% cured and a 5-year relapse rate of <1%.⁴

Standard short-course therapy

The standard short-course therapy for active pulmonary drug-susceptible TB is⁴:

• isoniazid, rifampicin, ethambutol and pyrazinamide daily for 2 months
• followed by isoniazid and rifampicin for a further 4 months.

The current Therapeutic Guidelines or relevant local guidance should be utilised.³ 

Duration of therapy may be variable (such as when response is unsatisfactory). Children can often be treated with the standard short-course therapy.⁴

See Table 1 for key adverse effects and details regarding these medicines. For detailed information please refer to appropriate references.

Treatment of extrapulmonary TB

Without concurrent lung disease, extrapulmonary TB is not contagious.⁴ Many types can be treated with standard short-course therapy, but expert advice should be sought.⁴

Vaccination

Vaccination for TB has limited application in countries where the incidence of TB is low.³

In Australia, the Bacille Calmette-Guérin (BCG) attenuated live vaccine is recommended for certain at-risk groups, such as Aboriginal and Torres Strait Islander children <5 years old in some areas of Australia, healthcare workers at high risk of exposure, young children travelling to countries with high TB incidence, and some children born to parents from high TB incidence countries.¹⁸

Knowledge to practice

As TB is now rare in Australia, pharmacists are unlikely to see TB in their regular practice. However, it is important that pharmacists understand the clinical features of TB, its risk factors and its management, as prompt and appropriate treatment aims to minimise disease transmission and the development of complications.

Conclusion

TB is an infectious disease that has massive mortality globally; however, due to public health initiatives is mostly eradicated in Australia. Despite this, cases can still occur, and pharmacists should be aware of TB and its recommended treatment to ensure appropriate management.

Key points

• TB is the second leading cause of death by infection worldwide. Although now rare in Australia, cases are still seen.
• Treatment of TB can involve complex medication regimes, and adherence is essential.
• Pharmacists should understand the clinical features of TB, its risk factors and appropriate management to ensure quality use of medicines and to assist in achieving best possible patient outcomes.

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References

1. World Health Organisation. Global tuberculosis report 2023 Geneva: World Health Organization. 2023. At: www.who.int/teams/global-tuberculosis-programme/tb-reports 
2. Anastasios K. Testing for tuberculosis. Australian Prescriber 2010;33(1):12 
3. Communicable Diseases Network Australia. Tuberculosis CDNA National Guidelines for Public Health Units 2022. 2022. At: www.health.gov.au/resources/publications/tuberculosis-cdna-national-guidelines-for-public-health-units?language=en 
4. Tuberculosis. Therapeutic Guidelines.; [updated 2022 Aug]. At: https://tgldcdp.tg.org.au/viewTopic?etgAccess=true&guidelinePage=Antibiotic&topicfile=tuberculosis. 
5. Australian Government Department of Health and Aged Care. Nationally Notifiable Diseases. 2024. At: www.health.gov.au/topics/communicable-diseases/nationally-notifiable-diseases
6. NHMRC. History of tuberculosis control in Australia. At: www.nhmrc.gov.au/about-us/resources/impact-case-studies/history-tuberculosis-control-australia 
7. Coorey NJ, Kensitt L, Davies J et al. Risk factors for TB in Australia and their association with delayed treatment completion. Int J Tuberc Lung Dis 2022;26(5):399–405. 
8. Trauer JM, Cheng AC. Multidrug‐resistant tuberculosis in Australia and our region. Med J Aust 2016;204(7):251–3. 
9. World Health Organisation. Tuberculosis: World Health Organisation. 2023. At: www.who.int/news-room/fact-sheets/detail/tuberculosis 
10. Pai M, Behr MA, Dowdy D, et al. Tuberculosis. Nat Rev Dis Primers 2016;2:16076. 
11. Narasimhan P, Wood JG, Macintyre CR, et al. Risk factors for tuberculosis. Pulm Med 2013;2013:828939. 
12. Denholm J, Baker A, Timlin M. Latent tuberculosis in the general practice context. Australian Journal for General Practitioners. 2020;49:107–10. 
13. Stapledon R, Donnan E and the National Tuberculosis Advisory Committee. Australian recommendations for the management of drug-resistant tuberculosis, 2023. Communicable Diseases Intelligence 2023;47. At: www1.health.gov.au/internet/main/publishing.nsf/Content/458DD8840E8C9332CA25891F0015C89D/$File/australian_recommendations_for_the_management_of_drug_resistant_tuberculosis_2023.pdf 
14. Wright CM, Westerkamp L, Korver S et al. Community-based directly observed therapy (DOT) versus clinic DOT for tuberculosis: a systematic review and meta-analysis of comparative effectiveness. BMC Infect Dis 2015;15(1):210. 
15. Rossi S, ed. Australian Medicines Handbook. Australian Medicines Handbook 2024; [updated 2024 Jul]. At: https://amhonline.amh.net.au/ 
16. Sterling T. Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection. UpToDate; [updated 2024 Apr]. At: www.uptodate.com/contents/treatment-of-drug-susceptible-pulmonary-tuberculosis-in-nonpregnant-adults-without-hiv-infection  
17. Communicable Diseases Branch, Queensland Health. Treatment of tuberculosis in adults and children – Version 4.0 September 2023. At: www.health.qld.gov.au/clinical-practice/guidelines-procedures/diseases-infection/diseases/tuberculosis/guidance/guidelines 
18. Australian Government Department of Health and Aged Care. Australian Immunisation Handbook – Tuberculosis. 2023. At:  https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/tuberculosis 

Our author

Victor Senescall (he/him) BPharm (Hon), MPS, AACPA, Barts is a credentialled pharmacist who has worked in community and aged care settings providing medicine reviews and is a PhD student studying receptor pharmacology.

Our reviewer

Morna Falkland BPharm