Immigrant Health Service

Tuberculosis screening

  • Background

    Tuberculosis (TB) is due to infection with Mycobacterium tuberculosis. Approximately one third of the world's population is infected, although only 5 - 10% of people with infection develop TB disease.[1] Transmission occurs by exposure to aerosolised droplets from people with respiratory infection.

    • TB disease may be primary disease (occurring directly after initial infection) or reactivation disease (occurring after a latent period that may be many years). Primary disease is the more common form in children, reactivation disease is the more common form in adolescents and adults Following exposure, the risk of progression to TB disease is highest in young children ( <5 years, especially <2 years).
    • TB disease is most commonly pulmonary disease (up to 85% of TB disease in adults and 75% in children).
      • Children are more likely to develop disseminated or non-pulmonary TB disease than adults; infants are particularly prone to miliary TB and TB meningitis.
    • Children with pulmonary TB disease are rarely infectious due to their pattern of disease, low bacillary load and lack of coughing force.
    • From November 2015, additional migration TB screening has been introduced for children (if they: are applying for a Humanitarian or onshore protection visa, OR from a high TB prevalence country, OR declare previous household contact, using either interferon-gamma release assay IGRA or tuberculin skin test TST) with further investigation for TB if positive. Otherwise the visa health assessment includes a chest x-ray (CXR) in those aged 11 years and older.[2]
    • Post-arrival screening for TB is part of the initial refugee health assessment.
      • TB screening requires a history, examination and a TB screening test (e.g. TST (Mantoux test) or IGRA - see notes below on screening tests in different ages).
        • A positive TB screening test result does not distinguish between TB infection and TB disease.
        • A negative TB screening test result does not exclude either TB infection or TB disease.
    • Latent TB infection (LTBI) refers to evidence of TB infection (i.e. a positive TB screening test) without evidence of TB disease (based on history, examination, CXR and other investigations as clinically indicated). Clinically this is an asymptomatic child with a normal examination, positive screening test and a normal CXR.
      • In children with LTBI - the lifetime risk of developing TB disease is around 10%, although it is higher in young children ( <5 years, especially <2 years) (see online TST/IGRA interpreter and TB risk calculator for estimations).                             

    Prevalence

    LTBI is common in refugee children/young people. Australian data suggest the prevalence of a positive TST (10mm or greater) in refugees from Africa, Europe and the Middle East is 25-55%.[3-6] TB disease has been found in 1.7-3.3% of refugee children attending a refugee service in NSW.[3,4]

    Assessment

    • Contacts/previous screening: Assess past history of TB, contact history (including family/household history), pre-departure screening (and results), and health undertakings (generated by offshore medical screening).
      • Often a contact history will emerge after initial screening results are positive, it is usually wise to repeat the entire TB history, explaining that onshore screening cannot affect visa status may be important.
      • Consider additional factors that will affect TB screening tests - TST should not be completed within 4 weeks of live viral vaccines (which may have been given pre-departure).
    • Symptoms: Ask about cough, other respiratory symptoms, fevers, nightsweats, malaise, loss of weight/poor weight gain, other localising symptoms and BCG history.
    • Consider comorbidities that might affect the risk for disease progression (low vitamin D, HIV) or tolerance for preventive/full treatment (hepatitis, Helicobacter pylori, poor nutrition).
    • Assess social circumstances and family understanding. TB is still associated with significant stigma within many communities. Families need to understand the process of screening and the next steps in management.
    • Examination. Perform a full physical examination and document the presence and location of a BCG scar; sites vary with country of origin - check deltoids, forearms, thighs, scapulae (both sides).
      • Consider TB in lymph nodes if they are >1 cm diameter in the neck, >1.5 cm in the axilla and >2 cm in the groin and do not improve with a 1 week of anti-staphylococcal antibiotics.[7]

    Screening

    • The TST is the preferred first line screening test in children aged <5 years, although it is less reliable in those aged <6 months. The TST can be used at all ages, and where TST are required for younger children in the family, it is usually efficient to use TST for all children in the family. Check for recent (within 4 weeks) live viral vaccines (see below).
      • A false negative result may occur with very recent exposure, active disease, immunosuppression and within 4 weeks of live viral vaccines.
      • A false positive result may occur as a result of previous BCG immunisation (particularly if given after early infancy) or exposure to non-tuberculous mycobacteria.
    • Interferon-gamma release assays (IGRA) such as QFN-GIT® and T-SPOT-TB® are not suitable as first line screening tests in younger children.
      • Multiple studies have found a proportion of children have a negative IGRA with a positive TST.
      • IGRA tests are only Medicare billable based on certain criteria (see below), this may represent a significant cost to refugee background families.
      • IGRA testing may be used as additional information in the specialist setting.
    • Routine use of both IGRA and TST in primary screening is not recommended.
    • Children aged 2-10 years may have had pre-departure screening for TB. 
      • If screening results are available and valid (i.e. a positive or negative result for those who had IGRA screening) 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.
    • All children with a positive TST (or IGRA) need a CXR, films should be sent with the child if completed in primary care.
    • Children with respiratory symptoms and a normal CXR may need a CT chest.[8]

    TST - technical aspects

    • Document presence and location of BCG scar.
    • Intradermal injection (26-G/27-G 10 mm needle, bevel up) of 5 tuberculin units (TU) purified protein derivative (PPD).
      • 5 TU PPD = 0.1 ml of 50 TU/ml solution.
    • Given in the left forearm at the junction of the upper and middle thirds.
    • Read at 48 - 72 hours (up to 5 days).
      • Measure induration (not erythema) in the transverse axis.
    • Less reliable in children aged <6 months.
    • Do not administer within 4 weeks of Live Attenuated Vaccines (LAV) such as MMR or VV vaccines (note MMR and other vaccines may be given as part of pre-departure medical screening in refugee entrants).
    • Do not give if previous TB disease (likely to cause large reaction) or previous large reaction to TST.

    TST - interpretation

    A positive result is:

    • 5 mm or greater in children who are household contacts of someone with active TB disease.
    • 10 mm or greater in children with a history of close contact, or who are from an endemic area.
    • 15 mm or greater (always considered positive).

    Although some authors suggest using a cut-off of 15 mm or greater for a positive test result if the child has had a BCG in the preceding 5 years; BCG is usually given in early infancy, and the risk of progression to TB disease is greatest in children aged <5 years. Most experts would recommend preventive treatment for children aged <5 years with a TST of 10 mm or greater and no evidence of TB disease. It is safest to ignore BCG immunisation when interpreting the TST.

    IGRA - new MBS guidelines

    From May 2017, the MBS item 69471 for IGRA testing has been amended, allowing MBS rebate for IGRA testing in the following situations:

    • Exposure to confirmed case of active TB.
    • HIV infection.
    • Commencing/commenced TNF-inhibitor therapy.
    • Commencing/commenced renal dialysis.
    • Silicosis.
    • Is/about to be immunocompromised (due to other condition or medical treatment).

    Management

    LTBI

    • In children with LTBI, 6 months preventive treatment with isoniazid (INH) reduces the risk of developing TB disease by 50 - 90%.[9]
      • Isoniazid 10 mg/kg (maximum 300 mg) daily for 6 months (available in 100mg tablets only, no syrup form).
      • Consider vitamin B6 in addition in breastfed infants, adolescents and children with poor nutrition. B6 is used routinely in adults on INH therapy. Dose is 5-25 mg/day (not/kg).
    • INH complications (mainly hepatitis) occur most frequently in adults >35 years, especially if comorbid alcohol intake. It is usually well tolerated in children and adolescents. Other (rare) side effects include immediate type reactions, peripheral neuritis (prevented by B6, increased risk with poor nutrition) GIT upset and haematological problems. Check product information (may require intranet access).
      • Check hepatitis status before commencing INH - if hepatitis and abnormal LFTs discuss with a gastroenterologist and an infectious diseases specialist, alternative regimens may be considered.
      • Discuss alcohol intake with adolescents.
    • Compliance is a major issue in long-term prophylaxis. Discuss the risks and benefits with families, this may take some time. It is not appropriate to start treatment if the family are unsure whether they want to proceed, or they are unsure if they can manage 6 months duration of medications.
      • If multiple children in the family require preventive treatment, it is practical to treat them all at the same time.
      • If the family declines INH prophylaxis, provide information on the risks of TB, but no specific follow-up is required unless symptomatic, or contact with adult with pulmonary TB disease.
    • Safe prescribing
      • Medications need to be clearly labelled, colour coding can be helpful.
      • Picture based dosing instructions may be helpful - see easidose.
      • All doses and medication safety issues need to be discussed with an interpreter.

    LTBI - alternative medication regimens

    • The NTAC position statement on treatment of LTBI notes possible alternative regimens for treatment of LTBI.
      • Rifampicin 10 mg/kg (maximum 600 mg) daily for 4 months (available in 150 mg, 300 mg, 600 mg tablets and 20 mg/ml liquid, cytochrome P450 inducer - also consider drug interactions) - can be used if intolerant to INH or infection by a suspected/known INH-resistant organism.
      • Rifampicin 10 mg/kg (maximum 600 mg) daily AND Isoniazid 10 mg/kg (maximum 300 mg) daily for 3 months.  

    Other clinical scenarios

    TB disease

    TB disease is usually managed by a respiratory or infectious diseases physician.  Standard treatment for pulmonary TB disease is 6 months of multi-agent therapy, longer durations are used for some extrapulmonary sites and for multi-drug resistant TB disease. Tuberculosis disease is a notifiable condition. If a diagnosis of TB disease is made, perform HIV testing after appropriate counselling. See Victorian guidelines, and Therapeutic guidelines (via RCH Library).

    TB disease in a family/household member

    Discuss with infectious diseases or respiratory physician. Other family members need assessment of their TB status. This will usually occur through the local TB program, check this follow-up is in place.

    • The main risk is where the contact is an adult with pulmonary disease, particularly smear positive disease. Details of the index cases smear status and organism sensitivity should be recorded.
    • Contacts need screening/assessment after the index case is diagnosed.
      • If the initial screen is negative; children <5 years typically start INH prevention therapy (depending on the sensitivity of the index case). The TST is repeated after 10 weeks - 3 months (break of contact) to look for conversion. In children <2 years a complete course of prevention therapy may be given, regardless of the break of contact TST result.
      • Consider BCG immunisation in children with negative break of contact screening.
      • Children aged <6 months should be placed on INH and a Mantoux performed at 6 months of age.
      • Refer to Victorian guidelines[1] for further details.

    Latent TB in a family/household member

    • Screen other family members.
    • In children <16 years, who have a negative screen, and have not had BCG (and who do not have contraindications) consider BCG vaccination. In children <6 months old, consider TST at 6 months later, and BCG at that point.

    BCG vaccination

    Bacillus Calmette Guerin (BCG, an attenuated strain of M. bovis) has been used to vaccinate against TB since 1921 and there is 80% coverage worldwide.[10] It does not protect against infection, overall protection against all forms of disease is around 50% with greater protective effect against death from TB (71%) and TB meningitis (64%).[11] The reported efficacy against pulmonary TB varies widely (0-~80%).[10] It offers good protection against leprosy.

    • BCG vaccination causes a scar in 75%[1]-99%[12] recipients.
    • BCG is usually given in the neonatal period in developing countries (which has less impact on TST results compared to BCG given later in childhood).
    • Vaccination causes a small papule which normally ulcerates in 2-3 weeks and heals in several weeks.
    • Contraindications: previous TB disease, Mantoux test >5 mm diameter, HIV infection, immunosuppression, pregnancy, fever and generalised skin disease.
    • Adverse events include injection site abscess in around 2.5% and lymphadenitis in around 1%, which may require anti-tuberculous drugs if severe. Adverse events are probably less likely with experienced providers.
    • Further information is available in the  Australian Immunisation Handbook.[13]
    • In Victoria, BCG is currently only available in a multidose vial, and at present only administered at RCH and MMC. See: further information about BCG clinics for children and about the BCG vaccine.
    • Parent handout:  BCG vaccination (English only).

    Resources

    References

    Immigrant health resources. Initial: Georgie Paxton and Sarath Ranganathan, January 2007. Revisions: Georgie Paxton. Last updated March 2018. Contact: georgia.paxton@rch.org.au