๐ Key Information Summary
- Tuberculosis is a nationally notifiable disease in Australia; cases are reported to the National Notifiable Diseases Surveillance System (NNDSS) and managed under state/territory public health legislation.
- Australia has a low TB incidence (~1,400 notifications/year), predominantly affecting overseas-born individuals, Aboriginal and Torres Strait Islander peoples in some jurisdictions, and immunocompromised populations.
- The tuberculin skin test (TST / Mantoux) and interferon-gamma release assays (IGRA; QuantiFERON-TB Gold Plus, T-SPOT.TB) are the principal screening tools for latent TB infection (LTBI); neither distinguishes active from latent disease.
- GeneXpert MTB/RIF Ultra (MBS-listed where available) is the preferred rapid molecular test for pulmonary TB, simultaneously detecting Mycobacterium tuberculosis complex and rifampicin resistance within 2 hours.
- Three sputum specimens (early morning preferred) for acid-fast bacilli (AFB) smear, culture, and drug susceptibility testing (DST) remain the diagnostic gold standard; culture results take 2โ6 weeks.
- Standard first-line treatment for drug-susceptible active TB is 2 months of isoniazid + rifampicin + pyrazinamide + ethambutol (HRZE) followed by 4 months of isoniazid + rifampicin (HR) โ total 6 months (RIPE therapy).
- Directly observed therapy (DOT) is recommended for all active TB cases and is mandated in several Australian jurisdictions; video-DOT (vDOT) is an acceptable alternative.
- Multi-drug-resistant TB (MDR-TB: rifampicin ยฑ isoniazid resistant) and extensively drug-resistant TB (XDR-TB) require specialist-led individualised regimens of 9โ20 months, often including bedaquiline and linezolid under compassionate/special access schemes.
- Latent TB infection treatment is recommended for high-risk groups including contacts of active cases, recent migrants from high-incidence countries, immunosuppressed patients (especially anti-TNF therapy or transplant), and HIV-positive individuals.
- Preferred LTBI regimens: 3-month weekly isoniazid + rifapentine (3HP, 12 doses), 4-month daily rifampicin (4R), or 6โ9 months daily isoniazid (6H/9H); choice depends on drug interactions, adherence potential, and liver function.
- HIV co-infection mandates early TB treatment with antiretroviral therapy (ART) initiated within 2 weeks for CD4 <50 cells/ยตL; monitor for immune reconstitution inflammatory syndrome (IRIS).
- Aboriginal and Torres Strait Islander peoples, particularly in the Northern Territory and Far North Queensland, have TB rates 5โ8 times the national average โ targeted screening, culturally safe care, and remote-area service delivery are essential.
- Hepatotoxicity monitoring: baseline and fortnightly liver function tests (LFTs) for the first 2 months of RIPE therapy; rifampicin has extensive cytochrome P450 drug interactions (especially with oral contraceptives, warfarin, antiretrovirals).
- Contact tracing is a public health priority: all close contacts of sputum smear-positive cases should be assessed within 48 hours; state/territory TB units coordinate screening and LTBI management.
Introduction & Australian Epidemiology
Tuberculosis (TB) is a chronic granulomatous infection caused by Mycobacterium tuberculosis complex (MTBC), with M. tuberculosis the principal human pathogen. Transmission occurs via inhalation of aerosolised droplet nuclei from patients with active pulmonary or laryngeal TB. The disease remains one of the leading infectious causes of death worldwide, with an estimated 10.6 million new cases and 1.3 million deaths annually (WHO Global TB Report 2023).
Australia maintains one of the lowest TB incidence rates among high-income countries, with approximately 1,300โ1,500 notifications per year (incidence ~5.5 per 100,000 population). However, the epidemiology is heterogeneous:
- Overseas-born individuals account for ~85% of all TB notifications, with the highest rates among those born in the Philippines, India, Vietnam, China, Nepal, and Myanmar. The median interval between arrival and diagnosis is 5โ8 years.
- Aboriginal and Torres Strait Islander peoples experience disproportionately high TB rates, particularly in the Northern Territory (15โ25 per 100,000) and Far North Queensland, often in remote communities with delayed presentation and challenging service access.
- Australian-born non-Indigenous individuals account for ~7% of notifications, with occasional outbreaks in congregate settings.
- Paediatric TB (<15 years) constitutes ~5% of notifications and frequently reflects recent transmission, necessitating urgent contact tracing.
- Drug-resistant TB accounts for ~2โ3% of culture-positive cases in Australia; MDR-TB remains uncommon but carries substantial morbidity and cost.
Notifiable disease: TB is notifiable under state and territory public health legislation in all Australian jurisdictions. Clinicians must notify the relevant public health unit within 24 hours (or the timeframe specified by local legislation). The National Notifiable Diseases Surveillance System (NNDSS) collates data nationally.
Key Australian organisations involved in TB control include state/territory TB services, the Australian Government Department of Health and Aged Care, the National Tuberculosis Advisory Committee (NTAC), the Royal Australian College of General Practitioners (RACGP), Lung Foundation Australia, and TB Alert Australia.
| Population Group | Estimated Incidence (per 100,000) | Key Risk Factors |
|---|---|---|
| Overseas-born (recent migrants) | 15โ30 | High-incidence country of origin, congregate living, delayed presentation |
| Aboriginal and Torres Strait Islander | 15โ25 (NT) | Remote residence, overcrowded housing, comorbidities (diabetes, smoking, harmful alcohol use) |
| Australian-born non-Indigenous | <1 | Immunosuppression, healthcare workers, outbreak exposure |
| Children (<15 years) | ~3 | Household contact with active TB, unvaccinated (BCG), malnutrition |
| People living with HIV | 20โ50 | CD4 <200, unsuppressed viral load, origin from high TB/HIV burden country |
Diagnosis
Diagnosis of TB requires a combination of clinical suspicion, microbiological confirmation, and radiological assessment. The diagnostic approach differs between pulmonary TB (PTB) and extrapulmonary TB (EPTB). Early and accurate diagnosis is critical for patient outcomes and public health control.
Clinical Suspicion
Consider TB in any patient presenting with:
- Persistent cough โฅ2 weeks, especially with haemoptysis
- Unexplained weight loss, night sweats, fever >2 weeks
- Chest imaging consistent with TB (upper lobe infiltrates, cavitation, lymphadenopathy)
- Risk factors: overseas-born from high-incidence country, HIV, immunosuppression, close contact with known TB case, incarceration, homelessness
Microbiological Investigations
Essential
Sputum AFB Smear (Ziehl-Neelsen or Auramine)
Collect โฅ3 early-morning specimens on consecutive days (minimum 5 mL each). Sensitivity 50โ80% in cavitary PTB; 10โ20% in non-cavitary/EPTB. Rapid turnaround (same day). Does not distinguish MTBC from NTM.
Essential
Sputum Mycobacterial Culture (Liquid & Solid Media)
Gold standard. Liquid culture (BACTEC MGIT 960) positive in 1โ3 weeks; solid media (Lรถwenstein-Jensen) in 4โ8 weeks. Provides isolate for full DST. All positive MTBC isolates in Australia undergo species confirmation and first-line DST via reference laboratories (e.g., Victorian Infectious Diseases Reference Laboratory, Qld Mycobacterial Reference Laboratory).
Essential
GeneXpert MTB/RIF Ultra (Xpert Ultra)
Automated NAAT detecting MTBC DNA and rifampicin resistance (rpoB gene mutations). Sensitivity 63โ90% (higher in smear-positive; lower in paediatric/EPTB). Specificity >98%. Turnaround ~2 hours. Available at major public hospitals and reference laboratories across Australia. Particularly valuable for rapid diagnosis and rifampicin resistance detection. Paediatric and EPTB specimens (pleural fluid, CSF, lymph node aspirate) can be tested.
Available
Tuberculin Skin Test (TST / Mantoux Test)
Intradermal injection of 5 TU PPD-S (Mantoux technique); read at 48โ72 hours. Induration โฅ5 mm considered positive in immunocompromised/close contacts; โฅ10 mm in high-risk populations; โฅ15 mm in low-risk. Limited by BCG cross-reactivity (particularly if BCG given >5 years prior) and two-visit requirement. Available in all Australian jurisdictions through TB services and some GP clinics.
Available
Interferon-Gamma Release Assay (IGRA)
QuantiFERON-TB Gold Plus (QFT-Plus) or T-SPOT.TB. Whole-blood ELISA (QFT-Plus) or ELISPOT (T-SPOT.TB) detecting IFN-ฮณ release in response to MTBC-specific antigens (ESAT-6, CFP-10; QFT-Plus also includes TB7.7). Single blood test โ no return visit required. Not affected by BCG vaccination. Sensitivity ~85โ90% for active TB (cannot rule out active disease). Specificity ~95โ98% (higher than TST in BCG-vaccinated). QFT-Plus is the preferred IGRA in Australia. MBS item 69376 (specialised pathology). Does not distinguish latent from active infection.
Referral
Line Probe Assay (LPA) โ GenoType MTBDRplus/sl
Molecular DST on smear-positive specimens or cultured isolates. Detects resistance to rifampicin, isoniazid (MTBDRplus), and fluoroquinolones/aminoglycosides/ethionamide (MTBDRsl). Available at reference laboratories. Results within 1โ2 days from smear-positive specimen. Used for rapid DST in suspected drug-resistant cases.
Referral
Whole-Genome Sequencing (WGS)
Increasingly performed by Australian reference laboratories for all culture-positive MTBC isolates. Provides comprehensive DST prediction, strain typing for epidemiological investigation, and identification of mixed infections. Replacing traditional phenotypic DST and MIRU-VNTR typing in several jurisdictions.
Chest Imaging
Chest X-ray (CXR) posteroanterior and lateral views are the first-line imaging investigation. Classic findings include:
- Upper lobe infiltrates (apical and posterior segments) โ most common
- Cavitary lesions โ highly suggestive, associated with high bacillary burden and infectivity
- Hilar and/or mediastinal lymphadenopathy โ common in paediatric TB and primary infection
- Pleural effusion โ unilateral, lymphocyte-predominant exudate
- Miliary pattern โ diffuse 1โ3 mm nodules in disseminated TB
- Fibrotic scarring, calcified granulomas, and Ghon complexes โ may indicate prior/healed TB
CT chest is indicated when CXR is equivocal, for staging extent of disease, detecting complications (bronchiectasis, aspergilloma), or evaluating mediastinal lymphadenopathy. High-resolution CT is particularly valuable in immunocompromised patients with atypical presentations.
Extrapulmonary TB (EPTB)
EPTB accounts for ~20โ25% of TB cases in Australia and can affect virtually any organ. Common sites and diagnostic approaches:
| Site | Proportion of EPTB | Key Investigations |
|---|---|---|
| Lymph node (TB lymphadenitis) | ~35% | Fine-needle aspirate or excision biopsy for histology, AFB smear/culture, GeneXpert. Most common EPTB site. |
| Pleural | ~20% | Thoracentesis: exudative, lymphocyte-predominant, low glucose, high ADA (>40 U/L strongly suggestive). Pleural biopsy (closed or thoracoscopic) for histology and culture. |
| Musculoskeletal (Pott's disease / spinal TB) | ~10% | MRI spine (modality of choice โ demonstrates vertebral body destruction, disc space narrowing, paravertebral abscess). CT-guided biopsy for culture. |
| Central nervous system (TB meningitis) | ~5% | Lumbar puncture: lymphocytic pleocytosis, elevated protein, low glucose (CSF:serum glucose <0.5). CSF GeneXpert (sensitivity ~50โ70%), CSF culture. CT/MRI brain for hydrocephalus, basal meningeal enhancement, tuberculomas. High mortality if untreated. |
| Genitourinary | ~8% | Early-morning urine ร3 for AFB culture (sterile pyuria). CT urogram. Renal biopsy if indicated. |
| Peritoneal / abdominal | ~5% | Ascitic fluid: lymphocyte-predominant exudate, elevated ADA. Laparoscopy with peritoneal biopsy โ high diagnostic yield. |
| Disseminated / miliary | ~5% | Blood cultures (in immunocompromised), bone marrow biopsy, liver biopsy, bronchoscopy with BAL. CT chest/abdomen. High mortality. |
TB meningitis is a medical emergency. Empirical anti-tuberculous therapy must not be delayed for culture confirmation. Dexamethasone should be initiated concurrently (0.4 mg/kg/day IV, tapered over 6โ8 weeks) โ shown to reduce mortality by ~30% in adults. Consult infectious disease and neurosurgery specialists urgently.
Active TB Treatment
Treatment of drug-susceptible active TB follows a standardised regimen of two phases: an intensive phase (4 drugs for 2 months) and a continuation phase (2 drugs for 4 months), totalling 6 months. Treatment should be initiated as soon as TB is clinically suspected, without awaiting culture confirmation. All treatment must be supervised โ directly observed therapy (DOT) is the standard of care in Australia.
Standard RIPE Regimen โ Drug-Susceptible Pulmonary TB
Isoniazid (H)
Isotamineยฎ ยท Generic ยท First-line anti-tuberculous
Adult dose
300 mg PO once daily (5 mg/kg, max 300 mg)
Paediatric dose
10 mg/kg PO once daily (range 7โ15 mg/kg, max 300 mg)
Route/Frequency
Oral, once daily (take on empty stomach)
Duration
6 months (intensive + continuation phase)
Renal adjustment
No adjustment required (dose after haemodialysis if applicable)
Hepatic adjustment
Use with caution; reduce dose or avoid in severe hepatic impairment (Child-Pugh C)
Key monitoring
LFTs at baseline, 2 weeks, then monthly. Peripheral neuropathy prevention: pyridoxine (vitamin B6) 25 mg daily โ particularly in malnourished, diabetic, pregnant, or HIV-positive patients.
PBS status
โ PBS General Benefit
Rifampicin (R)
Rifadinยฎ ยท Rimactanยฎ ยท Generic ยท First-line anti-tuberculous
Adult dose
600 mg PO once daily (8โ12 mg/kg, max 600 mg) for patients <50 kg: 450 mg once daily
Paediatric dose
15 mg/kg PO once daily (range 10โ20 mg/kg, max 600 mg)
Route/Frequency
Oral, once daily (take on empty stomach, 1 hour before or 2 hours after food)
Duration
6 months
Renal adjustment
No adjustment required for mildโmoderate CKD; reduce dose in severe CKD (limited data)
Hepatic adjustment
Avoid in severe hepatic impairment; potent CYP3A4 inducer โ extensive drug interactions
Key interactions
Reduces efficacy of oral contraceptives, warfarin, DOACs, corticosteroids, antiretrovirals (protease inhibitors, NNRTIs), methadone, anticonvulsants, many immunosuppressants. Contraceptive counselling mandatory.
PBS status
โ PBS General Benefit
Pyrazinamide (Z)
Generic ยท First-line anti-tuberculous
Adult dose
1,500 mg PO once daily (25 mg/kg, max 2 g) โ may be weight-banded: <50 kg: 1,000 mg; 50โ74 kg: 1,500 mg; โฅ75 kg: 2,000 mg
Paediatric dose
35 mg/kg PO once daily (range 30โ40 mg/kg, max 2 g)
Duration
2 months (intensive phase only)
Renal adjustment
eGFR <30 mL/min: reduce dose to 25 mg/kg three times/week; avoid if on haemodialysis
Key adverse effects
Hepatotoxicity (most hepatotoxic of first-line agents), hyperuricaemia (gout exacerbation), arthralgia, GI upset. Discontinue if ALT >5ร ULN or >3ร ULN with symptoms.
PBS status
โ PBS General Benefit
Ethambutol (E)
Myambutolยฎ ยท Generic ยท First-line anti-tuberculous
Adult dose
800โ1,200 mg PO once daily (15 mg/kg, max 1.6 g). Commonly weight-banded: <50 kg: 800 mg; 50โ74 kg: 1,200 mg; โฅ75 kg: 1,600 mg
Paediatric dose
20 mg/kg PO once daily (range 15โ25 mg/kg, max 1.6 g). Use with caution in children <5 years (cannot reliably report visual symptoms).
Duration
2 months (intensive phase only, until DST confirms susceptibility to H and R)
Renal adjustment
eGFR <30 mL/min: 15โ25 mg/kg three times/week; dose after haemodialysis
Key adverse effects
Optic neuritis (dose-dependent): colour vision disturbance, reduced visual acuity. Baseline and monthly visual acuity and colour vision testing required. Contraindicated in pre-existing optic neuritis. Irreversible if not detected early.
PBS status
โ PBS General Benefit
Treatment Phases
Phase 1
Intensive Phase โ Months 1โ2
HRZE: Isoniazid + Rifampicin + Pyrazinamide + Ethambutol, all daily. Aims to rapidly reduce bacillary burden and render patients non-infectious. Ethambutol may be stopped once DST confirms susceptibility to isoniazid and rifampicin.
Duration: 2 months (minimum 56 doses supervised)
Phase 2
Continuation Phase โ Months 3โ6
HR: Isoniazid + Rifampicin, all daily. Eliminates remaining dormant bacilli and prevents relapse.
Duration: 4 months (minimum 112 doses supervised)
Total treatment duration: 6 months for drug-susceptible pulmonary TB (newly diagnosed, no CNS involvement). Extended to 9โ12 months for: TB meningitis, bone/joint TB, or delayed clinical/microbiological response. All doses should be given as directly observed therapy (DOT). Intermittent (thrice-weekly) regimens are no longer recommended by WHO or NTAC.
Directly Observed Therapy (DOT)
DOT is the standard of care for all active TB treatment in Australia. A healthcare worker or trained designee observes the patient swallow each dose. DOT significantly improves treatment completion rates and reduces the emergence of drug resistance. Options include:
- In-person DOT: at TB clinic, hospital, GP practice, community health centre, or patient's home
- Video DOT (vDOT): real-time or asynchronous video observation via smartphone โ increasingly used in Australian TB services, particularly for regional/remote patients. Validated by several Australian TB programmes.
- Family-administered therapy: accepted in some jurisdictions when formal DOT is not feasible, with regular clinical review
Monitoring During Active TB Treatment
| Parameter | Frequency | Action Thresholds |
|---|---|---|
| Liver function tests (ALT, AST, bilirubin, ALP) | Baseline, 2 weeks, then monthly (or more frequently if elevated) | Stop all hepatotoxic drugs if ALT >5ร ULN, or ALT >3ร ULN with symptoms (jaundice, nausea, abdominal pain). Reintroduce under specialist guidance with sequential reintroduction of agents. |
| Full blood count | Baseline, monthly | Thrombocytopenia (rifampicin โ intermittent dosing more common), neutropenia (isoniazid), anaemia |
| Serum creatinine / eGFR | Baseline, then as indicated | Pyrazinamide and ethambutol require renal dose adjustment |
| Visual acuity and colour vision (Ishihara plates) | Baseline, monthly during ethambutol therapy | Discontinue ethambutol immediately if visual changes detected |
| Serum uric acid | If symptomatic (joint pain) | Pyrazinamide-induced hyperuricaemia โ treat symptomatically with allopurinol if gout develops; do not routinely discontinue pyrazinamide |
| Sputum culture | Monthly until culture conversion (2 consecutive negative cultures) | Failure to convert by month 3 should prompt review of adherence, drug resistance assessment, and treatment modification |
| Weight and clinical assessment | Monthly | Dose adjustments based on weight changes; assess adherence and adverse effects |
Adherence Support
- Assign a case manager or TB nurse coordinator for every patient
- Address social determinants: housing, employment, transport, childcare, interpreter services
- Provide patient education about TB transmission, treatment rationale, and side effects
- Use blister-packed medication where available through TB services
Drug-Resistant TB
Drug-resistant TB is classified based on resistance patterns identified through phenotypic culture-based DST and/or molecular methods (GeneXpert, line probe assay, whole-genome sequencing). Australia reports ~30โ50 drug-resistant TB cases annually. Management of drug-resistant TB requires specialist expertise at designated TB centres and close collaboration with a multidisciplinary team including infectious diseases physicians, respiratory physicians, TB nurses, pharmacists, and public health authorities.
Critical safety alert: Never add a single agent to a failing regimen. If resistance is identified or treatment failure suspected, stop all TB medications and consult a TB specialist immediately. Monotherapy with any anti-TB drug promotes further resistance. All drug-resistant TB cases must be discussed at a national or state-level drug-resistant TB case conference.
Definitions
| Category | Resistance Pattern | Approx. Proportion (Australia) | Min. Treatment Duration |
|---|---|---|---|
| Mono-resistant TB | Resistance to 1 first-line agent (e.g., isoniazid mono-resistance) | ~1.5% | 6โ9 months (modified regimen) |
| Poly-resistant TB | Resistance to โฅ2 first-line agents (not MDR) | ~0.5% | 9โ12 months |
| MDR-TB | Resistance to at least isoniazid AND rifampicin | ~1.5โ2% | 9โ18 months (BPaL regimen: 6โ9 months) |
| Pre-XDR-TB | MDR-TB + resistance to any fluoroquinolone | <1% | 12โ18 months |
| XDR-TB | MDR-TB + resistance to fluoroquinolone AND at least 1 of bedaquiline or linezolid | Rare | 18โ20+ months (individualised) |
Key Medications for Drug-Resistant TB
Bedaquiline
Sirturoยฎ ยท Diarylquinoline ยท Group A (WHO)
Adult dose
400 mg PO once daily for 2 weeks, then 200 mg PO three times/week (with food) for 22 weeks (total 24 weeks)
Paediatric dose
โฅ14 years: same as adults. <14 years: weight-banded dosing per WHO guidelines (granule formulation available)
Key monitoring
ECG at baseline, 2 weeks, and monthly (QTc prolongation). Hepatotoxicity. Drug interactions (CYP3A4 substrate โ avoid strong inhibitors/inducers).
PBS status
โ Not PBS-listed โ accessed via Special Access Scheme (SAS) Category A or compassionate use programme
Linezolid
Zyvoxidยฎ ยท Oxazolidinone ยท Group A (WHO)
Adult dose
600 mg PO or IV once daily
Paediatric dose
10 mg/kg PO/IV every 8 hours (max 600 mg/dose)
Duration
6โ9 months in BPaL regimen; up to 18โ20 months in individualised regimens
Key adverse effects
Myelosuppression (thrombocytopenia, anaemia, neutropenia), peripheral neuropathy, optic neuritis, serotonin syndrome (with SSRIs/MAOIs). Weekly FBC for first month, then monthly. Monitor visual acuity.
PBS status
โ PBS Authority Required โ for approved indications; TB use may require SAS
Pretomanid (Pa)
Dovpretยฎ ยท Pretomanid ยท Nitroimidazole ยท Group A (WHO)
Adult dose
200 mg PO once daily (with food) as part of BPaL regimen
Duration
6 months (BPaL regimen) or 6โ9 months (BPaLM โ with moxifloxacin)
Key monitoring
Hepatotoxicity, QTc prolongation, anaemia (hepatotoxic with linezolid โ dual monitoring essential). LFTs monthly.
PBS status
โ Not PBS-listed โ accessed via Special Access Scheme (SAS)
Moxifloxacin
Aveloxยฎ ยท Fluoroquinolone ยท Group A (WHO) โ if susceptible
Adult dose
400 mg PO or IV once daily
Key role
Core agent in MDR-TB regimens (BPaLM) when fluoroquinolone-susceptible. More potent than levofloxacin against MTBC. Also used in modified intensive phase for isoniazid mono-resistant TB.
Key monitoring
ECG (QTc prolongation), tendon toxicity, CNS effects (seizures, peripheral neuropathy). Avoid with QTc-prolonging agents.
PBS status
โ PBS Authority Required
BPaL / BPaLM Regimen (Shorter MDR-TB Regimen)
The WHO-recommended shorter regimen for MDR/RR-TB is BPaLM: Bedaquiline + Pretomanid + Linezolid + Moxifloxacin (when fluoroquinolone-susceptible) for 6 months. This represents a major advance, replacing 18โ20-month injectable-containing regimens. The TB-PRACTECAL and ZeNix trials demonstrated superior efficacy and safety compared to standard-of-care longer regimens.
- BPaL (without moxifloxacin): for pre-XDR-TB or fluoroquinolone-resistant MDR-TB โ 6โ9 months
- BPaLM: for fluoroquinolone-susceptible MDR/RR-TB โ 6 months
- All components accessed via Special Access Scheme (SAS) in Australia; cases managed at specialist TB centres with NTAC oversight
- Monthly sputum cultures throughout treatment; DST on all positive isolates
Isoniazid Mono-Resistance
For isoniazid mono-resistant TB (confirmed by DST), the recommended regimen is:
- Intensive phase (2 months): Rifampicin + Pyrazinamide + Ethambutol + Moxifloxacin (6RZE-Mfx)
- Continuation phase (4โ7 months): Rifampicin + Ethambutol ยฑ Moxifloxacin
- Total duration: 6โ9 months (extend if cavitary disease or delayed culture conversion)
National Drug-Resistant TB Case Conferences: All MDR/XDR-TB cases in Australia should be discussed at multidisciplinary case conferences convened by the National Tuberculosis Advisory Committee (NTAC) or equivalent state/territory body. Treatment decisions require specialist expertise and should not be initiated in primary care.
Latent TB Infection (LTBI)
Latent TB infection (LTBI) is defined as a state of persistent immune response to MTBC-specific antigens (detected by TST or IGRA) without evidence of active disease. Approximately 5โ10% of individuals with LTBI will progress to active TB during their lifetime, with higher rates in immunocompromised populations. Treatment of LTBI is a key TB elimination strategy in Australia, targeting high-risk populations to prevent reactivation.
Indications for LTBI Treatment
Treatment of LTBI is recommended for the following groups (highest priority first):
Highest Priority
Must Treat
- Close contacts of active pulmonary/laryngeal TB (especially within 2 years of exposure)
- HIV-positive individuals with positive TST/IGRA
- Patients initiating anti-TNF therapy (infliximab, adalimumab, etanercept) or other biologics with TB reactivation risk
- Transplant candidates/recipients with positive TST/IGRA
- Silicosis patients
- Children <5 years who are close contacts
Active TB must be excluded before starting LTBI treatment
High Priority
Strongly Recommended
- Recent migrants (<2 years) from high-incidence countries with positive TST/IGRA
- Healthcare workers with positive TST/IGRA (especially new converters)
- Patients starting immunosuppressive therapy (corticosteroids โฅ15 mg/day prednisolone โฅ4 weeks, chemotherapy, JAK inhibitors)
- Chronic renal failure / dialysis patients
- Diabetes mellitus with positive TST/IGRA
Chest X-ray required before treatment to exclude active disease
Moderate Priority
Consider Treatment
- Children 5โ15 years with positive TST/IGRA and risk factors
- Overseas-born individuals with positive TST/IGRA (individual risk assessment)
- Prisoners and homeless individuals
- Aboriginal and Torres Strait Islander peoples in high-incidence settings
Shared decision-making with patient recommended
LTBI Treatment Regimens
3HP โ Isoniazid + Rifapentine
3-month weekly regimen (12 doses) ยท Short-course preferred
Adult dose
Isoniazid 900 mg + Rifapentine 900 mg PO once weekly for 12 doses. Weight-banded: 32.1โ50 kg: INH 750 mg + RPT 750 mg
Paediatric dose
โฅ2 years: weight-banded dosing per WHO/CDC tables (INH + RPT combination tablets available)
Key advantages
Shortest regimen (3 months), highest completion rates (~90%), suitable for DOT. Preferred by NTAC for most patients โฅ2 years.
Key limitations
Rifapentine interactions (CYP3A4 inducer โ similar to rifampicin). Contraindicated with protease inhibitors, efavirenz requires dose adjustment. Monthly LFTs in patients with liver disease. Not suitable for active TB or drug-resistant TB contacts.
PBS status
โ Not PBS-listed in Australia โ sourced through TB services or SAS
4R โ Rifampicin
Rifadinยฎ ยท 4-month daily rifampicin regimen
Adult dose
Rifampicin 600 mg PO once daily for 4 months (120 days)
Paediatric dose
15 mg/kg PO once daily (max 600 mg) for 4 months
Key advantages
Better hepatotoxicity profile than isoniazid monotherapy. Shorter than 6H/9H. Suitable for isoniazid-intolerant patients. Good option when drug interactions with rifapentine are a concern.
Key limitations
Significant CYP3A4 drug interactions (as with all rifamycins). Baseline and monthly LFTs. Orange discolouration of body fluids. Contraceptive counselling essential.
PBS status
โ PBS General Benefit
6H or 9H โ Isoniazid
Isotamineยฎ ยท 6 or 9-month daily isoniazid regimen
Adult dose
Isoniazid 300 mg PO once daily for 6 months (182 days) or 9 months (270 days)
Paediatric dose
10 mg/kg PO once daily (max 300 mg) for 6โ9 months
Key advantages
No rifamycin drug interactions. Suitable when rifampicin/rifapentine contraindicated (e.g., transplant recipients on calcineurin inhibitors). 6H preferred over 9H (similar efficacy, better completion).
Key limitations
Longer duration reduces completion rates (~60โ70%). Isoniazid hepatotoxicity (risk increases with age >35, alcohol, pre-existing liver disease). Peripheral neuropathy โ co-prescribe pyridoxine 25 mg daily.
PBS status
โ PBS General Benefit
Monitoring During LTBI Treatment
| Regimen | Baseline LFTs | Routine LFT Monitoring | Additional Monitoring |
|---|---|---|---|
| 3HP | Yes | Monthly if risk factors for hepatotoxicity; not routinely required in low-risk patients | Clinical assessment at each DOT visit (symptoms of hepatitis) |
| 4R | Yes | Monthly | FBC if symptomatic |
| 6H / 9H | Yes | Monthly in patients >35 years, alcohol use, liver disease, or concomitant hepatotoxic drugs | Visual symptoms (rare with isoniazid alone) |
Immunosuppressed patients with LTBI: Patients starting anti-TNF therapy, transplant immunosuppression, or high-dose corticosteroids require LTBI treatment BEFORE or concurrent with immunosuppression initiation. Ideally complete treatment before starting immunosuppression; if this is not possible, start LTBI treatment at least 1 month prior to biologic therapy. Discuss with TB specialist and treating immunologist/rheumatologist.
Special Populations
HIV Co-Infection
TB is the leading cause of morbidity and mortality in people living with HIV globally. In Australia, ~3โ5% of TB notifications have HIV co-infection. TB may present atypically in HIV (less cavitation, more mediastinal lymphadenopathy, miliary/ disseminated disease, lower sputum AFB smear positivity).
- Treatment: Standard HRZE regimen (same doses). Avoid thrice-weekly intermittent therapy โ increased risk of acquired rifampicin resistance in HIV. Daily dosing essential.
- ART timing: Initiate antiretroviral therapy (ART) within 2 weeks if CD4 <50 cells/ยตL; within 8 weeks if CD4 โฅ50. Earlier ART reduces mortality but increases IRIS risk.
- IRIS (Immune Reconstitution Inflammatory Syndrome): Occurs in 10โ25% of TB/HIV co-infected patients starting ART. Manifests as paradoxical worsening (new lymphadenopathy, expanding CNS lesions, worsening respiratory symptoms) 1โ4 weeks after ART initiation. Manage with continuation of TB treatment + ART; corticosteroids (prednisolone 1.5 mg/kg/day tapered over 4 weeks) for severe IRIS.
- Drug interactions: Rifampicin drastically reduces levels of protease inhibitors (PIs) โ never co-administer. Use efavirenz-based ART (or dolutegravir with dose adjustment to 50 mg BD) with rifampicin. Rifabutin (150 mg three times/week) may substitute rifampicin when ART includes PIs or cobicistat.
- TB meningitis: Dexamethasone should be used in HIV-positive patients (contrary to earlier concerns, benefit demonstrated).
- Rifabutin dose with efavirenz: 450 mg PO daily (increased from standard 150 mg). โ PBS Authority Required
- LTBI in HIV: Treat all HIV-positive individuals with LTBI regardless of TST/IGRA induration size. Preferred regimen: 3HP or 4R (avoid 9H if possible due to lower completion rates).
Pregnancy & Breastfeeding
Active TB in pregnancy poses significant risks to both mother and fetus (pre-term birth, low birth weight, congenital TB โ rare). Treatment must not be delayed. Untreated TB carries greater risk than medication exposure.
- First-line treatment in pregnancy: Isoniazid + Rifampicin + Ethambutol for 9 months (2HRE + 7HR). Pyrazinamide is generally avoided in Australian practice during the first trimester (limited safety data, though WHO recommends its use). Pyridoxine supplementation mandatory (50 mg/day in pregnancy).
- Contraindicated agents: Aminoglycosides (streptomycin, amikacin, kanamycin) are teratogenic (ototoxicity) โ absolutely contraindicated in pregnancy.
- Breastfeeding: All first-line TB drugs are compatible with breastfeeding at standard doses. Infant receives sub-therapeutic doses via breast milk โ not sufficient for treatment or protection. Continue DOT during breastfeeding.
- LTBI in pregnancy: Treatment may be deferred until after delivery in low-risk LTBI (low risk of progression). In high-risk LTBI (recent contact, HIV-positive, immunosuppressed), isoniazid monotherapy is preferred โ defer until after the first trimester. Avoid rifampicin/rifapentine in LTBI during pregnancy.
- Neonatal management: If mother has active TB at delivery, investigate infant (CXR, TST at 4โ6 weeks if no immediate treatment indicated). If mother has untreated/infectious TB, start infant on isoniazid prophylaxis pending investigation results. BCG vaccination recommended for all infants of mothers with active TB (after excluding active TB in infant).
Children
Paediatric TB (<15 years) is predominantly paucibacillary, making microbiological confirmation challenging. Diagnosis often relies on clinical features, contact history, TST/IGRA, and imaging. Children are more likely to develop disseminated and meningeal TB.
- Treatment โ drug-susceptible TB: HRZE for 2 months followed by HR for 4 months (total 6 months). Doses are weight-based (see drug cards above). Fixed-dose combination (FDC) dispersible tablets are preferred (WHO formulation) โ available through TB services.
- Dose adjustments: Children metabolise drugs faster; weight-based dosing per kg is essential. Regular weight checks (monthly) for dose adjustment. Pyrazinamide 35 mg/kg (not 25 mg/kg as in adults).
- TB meningitis in children: HRZE for 2 months + HR for 10 months (total 12 months). Dexamethasone for 4 weeks in children >14 years (limited evidence in younger children but commonly used). Ethambutol can be used at 20 mg/kg despite concerns about visual monitoring โ benefits outweigh risks in TB meningitis.
- LTBI in children: TST preferred over IGRA in children <5 years (IGRA sensitivity may be reduced). Treatment: 3HP (โฅ2 years) or 3โ4 months of isoniazid + rifampicin (3HR/4HR) or 6โ9H. Children <5 years who are close contacts should start empiric LTBI treatment pending TST results (consider treatment for 2โ3 months, then TST โ if negative, can stop).
- Adherence: DOT essential. Involve parents/caregivers. Address school attendance, psychosocial impact.
Immunosuppressed Patients
Immunosuppression increases the risk of LTBI reactivation (up to 10โ15% per year with anti-TNF therapy vs 5โ10% lifetime in immunocompetent). Key considerations for specific groups:
- Anti-TNF therapy (infliximab, adalimumab, etanercept, certolizumab): Screen ALL patients for LTBI (IGRA preferred) before initiating biologic therapy. Treat LTBI before or concurrent with biologic. Re-screen annually if ongoing high-risk exposure.
- Transplant recipients: Pre-transplant LTBI screening mandatory. 4R or 9H preferred (3HP has insufficient data in transplant). Post-transplant TB may present atypically โ low threshold for investigation.
- Chronic corticosteroid use (โฅ15 mg/day prednisolone โฅ4 weeks): Screen for LTBI. Consider LTBI treatment. Monitor during immunosuppression for TB reactivation.
- Haematological malignancy / chemotherapy: High risk of reactivation and disseminated TB. Screen before chemotherapy. IGRA may be falsely negative in profound immunosuppression.
- Dialysis patients: Higher LTBI prevalence; IGRA preferred (TST may be falsely negative). Consider LTBI treatment with careful hepatotoxicity monitoring.
- Drug interactions: Rifampicin and rifapentine interact with calcineurin inhibitors (tacrolimus, cyclosporin), corticosteroids, and many transplant medications โ use isoniazid monotherapy for LTBI or consult transplant physician for dose adjustment with rifamycins.
Renal Impairment
- Isoniazid: No dose adjustment; give after haemodialysis on dialysis days
- Rifampicin: No dose adjustment for mildโmoderate CKD
- Pyrazinamide: eGFR <30: reduce to 25 mg/kg three times/week; avoid in haemodialysis
- Ethambutol: eGFR <30: 15โ25 mg/kg three times/week; dose after haemodialysis
- Streptomycin: Avoid if possible; if used, extended dosing intervals and therapeutic drug monitoring essential
- Linezolid: No dose adjustment in renal impairment but enhanced toxicity risk โ monitor FBC more frequently
Hepatic Impairment
- Child-Pugh A: Standard doses with close LFT monitoring (weekly initially)
- Child-Pugh B: Avoid pyrazinamide if possible (RE regimen: rifampicin + ethambutol for 9โ12 months). Close monitoring.
- Child-Pugh C: Avoid all hepatotoxic agents if possible. Regimen of rifampicin + ethambutol + fluoroquinolone ยฑ aminoglycoside under specialist guidance. Consider hepatology referral.
- Chronic hepatitis B/C: Not a contraindication to standard TB treatment but requires baseline and frequent LFT monitoring. Antiviral therapy for chronic HBV should be initiated before or concurrent with TB treatment to reduce risk of HBV reactivation (rifampicin may interact with some antivirals).
Contact Tracing
Contact tracing is a core public health function managed by state/territory TB services. It is the most effective strategy for identifying undiagnosed active TB and LTBI in Australia.
1
Identify Contacts
List all close contacts (household, intimate, prolonged indoor exposure โฅ8 hours) and casual contacts. Prioritise by proximity and duration of exposure.
2
Initial Assessment (within 48 hours for smear-positive cases)
CXR, symptom screen, IGRA (preferred) or TST. If symptomatic or CXR abnormal: sputum for AFB smear and GeneXpert. Children <5 years: TST at 4โ6 weeks post-exposure (if IGRA negative initially and no treatment started).
3
Manage Active TB
If active TB diagnosed: commence treatment immediately, notify public health unit, begin contact tracing for that case (second-generation contacts).
4
Manage LTBI
If LTBI identified (positive IGRA/TST, normal CXR, asymptomatic): offer treatment per LTBI regimen guidelines above. Document and ensure treatment completion.
5
Follow-Up
Repeat testing at 8โ12 weeks post-exposure if initial IGRA/TST negative (window period). Serial CXR for high-risk contacts. Case closure once all contacts assessed and managed.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander peoples experience TB rates 5โ8 times higher than the non-Indigenous Australian-born population, with the highest incidence in the Northern Territory (15โ25 per 100,000) and Far North Queensland. TB control in Indigenous communities requires culturally safe, community-led approaches that address the complex social determinants of health driving transmission and delayed diagnosis.
Closing the Gap: Reducing TB rates in Aboriginal and Torres Strait Islander peoples is a priority under the National Agreement on Closing the Gap (Target 1: Close the life expectancy gap by 2031) and the Australian Government's TB Strategy. Investment in community-controlled health services, housing, culturally safe care, and workforce development is essential to achieving TB elimination in Australia.
๐ References
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- 7. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Canberra: Australian Government Department of Health; 2023. Available from: immunisationhandbook.health.gov.au
- 8. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework. Canberra: AIHW; 2023.
- 9. Nyang'wa BT, Berry C,";";"; et al. A 24-week, all-oral regimen for rifampin-resistant tuberculosis. N Engl J Med. 2022;387(25):2331โ2343. (TB-PRACTECAL trial)
- 10. Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893โ902. (ZeNix trial โ BPaL regimen)
- 11. Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365(23):2155โ2166. (PREVENT TB / iAdhere trial)
- 12. National Tuberculosis Advisory Committee (NTAC). Guidelines for Australian Mycobacteriology Laboratories. Communicable Diseases Intelligence. 2023.
- 13. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017;64(2):111โ115.
- 14. World Health Organization. WHO Operational Handbook on Tuberculosis. Module 1: Prevention โ Tuberculosis Preventive Treatment. Geneva: WHO; 2020.
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