Tuberculosis (TB & LTBI)
Justin Denholm, Marion Bailes, Josh Francis
- Offer tests for latent TB infection (LTBI) to all people aged ≤35 years. Children 2-10 years may have had tests for LTBI as part of pre-departure screening.
- Screening and preventive treatment for LTBI people >35 years will depend on individual risk factors and jurisdictional requirements in the particular state or territory.
- Offer LTBI testing with the intention to offer preventive treatment and follow up.
- Use either the Tuberculin Skin Test (TST) or blood Interferon Gamma Release Assay (IGRA) to screen for LTBI.
- TST is preferred over IGRA for children <5 years of age.
- A positive TST is induration of ≥10mm in adults and children from refugee-like backgrounds; or ≥5mm in the setting of severe malnutrition, HIV infection, immunosuppression, or in children who are recent contacts of active TB cases.
- Ensure that a CXR has been performed during the migration process for those aged ≥11 years as per screening guidelines. If so, a post-arrival CXR is not required unless TST or IGRA are positive, or there are respiratory symptoms suggestive of active pulmonary TB disease.
- Refer individuals with a positive TST or IGRA to specialist TB services for assessment and exclusion of active TB, and consideration of treatment for LTBI.
Tuberculosis is a relatively uncommon infection in Australia. In 2013, the overall incidence of active TB was 5.5/100,000 population per year; however, nearly 90% of cases occur in overseas-born Australians, with a rate of 18.4/100,000 compared to 0.7/100,000 in non-indigenous Australian-born people. 31–33 Although people born in India, the Philippines, China and Nepal make up more than half of the overseas-born cases of active TB in Australia, the highest rates are in people born in humanitarian source countries.34
Immigrants born in high-incidence countries, including people from refugee-like backgrounds, are identified as high priority candidates for screening and treatment for LTBI.32,35 Post-arrival screening and LTBI treatment in those from a refugee-like background can prevent TB transmission in the community and limit the numbers of cases and deaths from TB. 36 Australia’s National TB Advisory Committee (NTAC) supports this approach.33
Transmission of TB occurs through inhalation exposure of aerosolised droplets from people with active respiratory TB. Often this is a household contact or family member, but often no specific exposure is identified. In most exposed people, infection is contained locally, without progression to active TB, with the organism remaining in a state of latency – LTBI. Active TB may be primary disease (occurring directly after initial infection) or reactivation disease (occurring after a latent period that may last many years). Primary disease is more common in children; reactivation disease is more common in adolescents and adults. For people with LTBI, the lifetime risk of active TB is 5–10%.32 The lifetime risk of TB reactivation for immigrant children less than 5 years of age has been estimated to be 17% and the lifetime risk of those with untreated HIV infection is estimated to be 100%.37 The risk of developing active TB following exposure is greatest in the 12–18 months following exposure.38 Thus if TB infection has been acquired in the period immediately prior to travel (e.g. in crowded living conditions, including refugee camps), people are at greatest risk of progressing to active TB soon after arrival in Australia. Australian data from 2003–2012 show 85% of active TB in overseas-born children was diagnosed within 5 years of arrival;35 however, other population data have found nearly 50% of cases of active TB occur more than 5 years after arrival.34
Although pulmonary disease is the most common presentation of active TB in adults and children, non-pulmonary active TB represents a higher proportion of all TB cases in immigrants compared to Australian-born people34 and active TB can present in almost any organ.
LTBI is common in children and adults from a refugee-like background in Australia. Australian studies of resettled refugee cohorts have reported prevalence figures for LTBI ranging from 7–71%.39–49 Australian data suggest the prevalence of active TB is generally <2% in adults from a refugee-like background,43,48,50 and 0–5% in children (for more information see prevalence tables).44,45,47,51
+ History and examination
Review the migration pathway, previous TB screening,17,18 and any past history of TB, TB treatment, or contact with active TB. Clarify the DHC19 in offshore arrivals, as the DHC includes live viral vaccines (LVV), which may influence the timing and interpretation of the TST if this test is used for screening.
Offshore humanitarian arrivals and those who have been in detention centres aged 11 years and older (at the time of arrival/detention) will have had a CXR, and children aged 2–10 years applying for humanitarian or onshore protection visas, or, from high TB prevalence countries will have had an IGRA or TST and further investigations if positive (from 2016). Asylum seekers arriving by plane are unlikely to have had a CXR and may not have had screening for active TB or LTBI.
LTBI is by definition asymptomatic and non-infectious.
Classic clinical symptoms of active pulmonary TB include chronic cough and haemoptysis. However, active TB may present with non-specific symptoms, including fever, malaise and weight loss or failure to thrive/poor growth in children, night sweats and lymphadenopathy. In the early stages of active pulmonary TB, respiratory symptoms may be absent.52
Consider comorbidities that might affect risk for disease progression (e.g. low vitamin D, HIV infection), tolerance for preventive treatment (e.g. hepatitis with older age), or ability to access health services (e.g. literacy, household location, competing priorities).
Ensure active TB has been excluded, through history, examination, and CXR and other investigations where appropriate.
If active TB is suspected refer for urgent specialist assessment and ensure appropriate infection control precautions. Neither TST nor IGRA should be used to exclude active TB in adults or children.
All people from a refugee-like background aged ≤35 years, including children, should be screened for LTBI, ideally within one month of arrival in Australia, unless screening has been completed pre-departure. However, the risk of developing active TB persists (even decades after arrival), and screening should be offered at whatever stage individuals are identified and assessed.53
Testing for LTBI should be performed with the intention to offer preventive treatment, taking into account the risks and benefits of preventive treatment; however, practice differs between different jurisdictions, and some states and territories will screen all new arrivals, including those over 35 years.
Investigation for LTBI is completed with either the TST or (blood) IGRA. TST is preferred to IGRA for children less than 5 years of age.
There is no indication to perform both tests. Neither test is ‘gold standard’ and individual factors may determine which test is preferred54 e.g. IGRA testing may be preferable in people with a history of BCG vaccination after infancy (BCG >1 year old) and/or people who have had the BCG vaccine more than once. In HIV-infected adults IGRA tests perform similarly to TST in identifying latent TB.55 Logistic factors may also influence testing decision, with IGRA requiring blood sampling, while TST requires a return visit for test reading, and should not be completed within 4 weeks of LVV. Testing may not be available outside hospitals or TB services. IGRA is not currently Medicare-rebatable unless the person is immunosuppressed.
A positive TST is considered to be induration of ≥10mm in recent immigrants from high TB prevalence countries (i.e. many adults and children from refugee-like backgrounds); or ≥5mm in the setting of severe malnutrition, HIV infection, immunosuppression or in children who are recent contacts of active TB. A positive IGRA is defined by the manufacturer’s guidelines.*
* For the TST: a false negative result may occur with very recent exposure, active TB, immunosuppression, HIV, malignancy, viral infection, in older adults, and within 4 weeks of LVV (consider pre-departure screening in offshore arrivals). A false positive result may occur as a result of exposure to non-tuberculous Mycobacteria or previous BCG immunisation (particularly if given after early infancy); however, in practice, it is usually advisable to disregard the BCG when interpreting the TST.
For IGRAs: A false negative result may occur with very recent exposure, TB disease, and immunosuppression, although IGRA are less likely to be a false negative in HIV compared to the TST. A false positive result may occur with some non-tuberculous Mycobacteria. An indeterminate result can be due to a low positive control or a high negative control. In this situation the IGRA can be repeated once, and/or a TST considered.
+ Management and referral
People with a positive TST or IGRA should be referred to clinicians with experience in TB for assessment and repeat CXR (for radiological signs of current or past TB), unless there is a recent (within 3 months) CXR available for review. Baseline LFTs should be performed prior to commencing treatment for LTBI.
Treatment for LTBI is only undertaken after active TB has been excluded, and should be administered by experienced clinicians, in communication with a coordinated TB service. Treatment of LTBI has been shown to significantly reduce the individual risk of subsequent active TB,32 and LTBI treatment is recommended unless contraindicated. Relative contraindications include liver disease, older age and in patients where adherence is likely to be problematic.
The first line preventive treatment of LTBI is 6–9 months of isoniazid (10mg/kg up to 300mg daily, pregnancy category A).32,37
Shorter course regimens, particularly those including rifamycins (pregnancy category C), are also effective.32
Treatment is generally well tolerated, although adverse effects including hepatotoxicity are well described, especially in people over 35 years, and/or people with pre-existing liver conditions.56 A study of newly arrived refugees in Australia found high rates of LTBI treatment acceptance.57 When people are offered LTBI treatment, it is essential they understand the difference between LTBI and active TB, the pros and cons of treatment, and the duration of treatment. Provide language appropriate (and/or visual) information on treatment and side effects, and check patient understanding through teach-back techniques where possible.
While treatment of LTBI is recommended and should be encouraged, it is not compulsory and people should be reassured that their visa status/asylum claim will not be affected if they decide not to proceed.32 In this situation, advise patients to seek early review for symptoms of active TB, and consider CXR 6–12 monthly for 2 years if there is a high index of suspicion of recent exposure (within 2 years).
People receiving LTBI treatment should be reviewed regularly to reinforce understanding of treatment and side effects, and to encourage adherence. They should be educated to stop their isoniazid and to contact their healthcare providers immediately if they develop adverse treatment effects (i.e. rash, anorexia, nausea, vomiting, abdominal discomfort, persistent fatigue and weakness, dark-coloured urine, pale stools or jaundice). Isoniazid can cause peripheral neuropathy in people who are malnourished. This can be prevented by concomitant administration of pyridoxine (6.25-25mg/day, by age, not per kg). People with baseline abnormal liver function should have routine periodic laboratory testing, an asymptomatic rise in LFTs is not uncommon (10–20%), and may not require treatment cessation.32
+ Special considerations in children
Following exposure to TB, children may develop either LTBI or uncontrolled primary infection. Young children have the greatest risk of developing active TB after exposure, and also have the greatest risk of developing severe/disseminated TB, including TB meningitis.38,59
Clinical indicators of active TB are often subtle in children and a careful history and examination is required, including measurement of growth parameters. Symptoms include chronic cough, malaise, and weight loss/failure to thrive.60
All children should be screened for LTBI and assessed for clinical features of active TB. TST is the preferred test for latent TB in children under 5 years. IGRA testing in this age group is associated with an increased proportion of indeterminate results.61
New pre-departure TB screening protocols for children applying for humanitarian visas were introduced at the end of 2015 (IGRA or TST testing for children aged 2-10 years with follow-up of positive results). If screening results are available and valid (i.e. a positive or negative result for those who had IGRA testing), and children are reviewed soon after arrival, children do not need repeat LTBI testing unless there are additional clinical risk factors. Repeat testing (and ideally test using TST in those < 5 years) in children with indeterminate or failed IGRA testing. Ensure testing for LTBI in children who have not had previous LTBI screening, or where results are not available. Children <2 years will not have had pre-arrival LTBI screening and should be screened using TST on arrival.
Neither TST nor IGRA should be used to exclude active TB in children, but a positive result on either test indicates TB infection. All children with a positive TST or IGRA should be referred to clinicians with experience in TB for assessment to review/complete a CXR. Children aged <11 years who arrived before the end of 2015 will not have had a CXR as part of offshore/detention screening. From 2016, children aged 2-10 years with positive pre arrival LTBI screening will have had a CXR prior to arrival.
All children with LTBI (where active TB has been excluded) should be offered preventive treatment for LTBI.
All children <5 years with current/recent household contact with active pulmonary TB should be discussed urgently with local TB programs, irrespective of any available screening test results.
Children who have recent contact with active TB cases should be managed by a specialist TB service. Those without previous screening will typically have a baseline TST, and if negative (after active TB is excluded) commence isoniazid until a repeat TST at 3 months (‘break of contact’ to look for TST conversion) when further decisions are made around ongoing management. Management of children who have had prior screening will depend on the clinical scenario.
The investigation and treatment of active TB and LTBI in children should be undertaken by specialist paediatric and TB services with experience in the management of paediatric TB. Coordinated management of all family and household contacts by the same service is recommended, and has been shown to improve treatment adherence.62
+ Considerations in pregnancy and breastfeeding
Consider pregnancy when organising a CXR in women of childbearing age. CXR may be deferred in asymptomatic pregnant women. Neither pregnancy nor breastfeeding is a contraindication to the use of isoniazid (category A) preventive therapy in the setting of individuals at risk of progression to active TB. Infants are at significantly higher risk of developing active TB following TB exposure, and preventing active disease in women with young children is a priority. Pregnant or breastfeeding women with suspected active TB should be referred urgently to a specialist TB service.
+ Links and resources