Tuberculosis

What

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. Most infected people have latent tuberculosis infection, which means they are not ill and not infectious. People with tuberculosis disease, in contrast, are ill and usually infectious.

Who

BCG (bacille Calmette–Guérin) vaccine is recommended for:

• Aboriginal and Torres Strait Islander neonates
• some healthcare workers
• some travellers
• some Australian-born children of migrants
• young children born to parents with leprosy, or household contacts with leprosy

How

BCG vaccine is given by intradermal injection.

Aboriginal and Torres Strait Islander neonates in the Northern Territory, Queensland and northern South Australia are recommended to receive BCG vaccine.

BCG vaccination should be considered for healthcare workers who are at high risk of exposure to drug-resistant tuberculosis and who have a negative tuberculin skin test.

Young children who will be travelling to settings with high tuberculosis incidence are recommended to receive BCG vaccine, based on a risk assessment.

Some infants born in Australia to parents from countries with high tuberculosis incidence may be recommended to receive BCG vaccine, based on a risk assessment.

Young children who are born to parents with leprosy, have a family history of leprosy or have household contacts with leprosy are recommended to receive BCG vaccine, based on a risk assessment.

Why

The World Health Organization considers tuberculosis a global emergency. BCG vaccine is recommended for those at highest risk of tuberculosis.

Tuberculosis vaccines available in Australia

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Note: The only BCG vaccine registered for use in Australia has not been available for some time. Alternative unregistered vaccines may be available through special prescribing arrangements. See Vaccine information and consult state and territory guidelines. 

Dose and route

BCG vaccine is a single dose given by intradermal injection:

• In newborns and infants <12 months of age, the dose is 0.05 mL.
• In children ≥12 months of age and adults, the dose is 0.1 mL.

BCG revaccination is not recommended in any person because of a lack of evidence about efficacy.

BCG vaccine is available from state and territory tuberculosis services.

BCG vaccination procedures

Only medical or nursing staff who are trained in BCG vaccination procedures should administer BCG vaccine.

BCG vaccination steps are:

1. Use a short needle

Use a short (10 mm) 26–27 gauge needle with a short bevel. The risk of spillage can be minimised by using an insulin syringe that already has a needle attached.

2. Wear protective eyewear

These people should wear protective eyewear:

• the person giving the vaccine
• the person receiving the vaccine
• the parent or carer holding a small child who is receiving the vaccine

Eye splashes can ulcerate. If eyes are splashed, wash the eyes with saline or water immediately.

3. Identify the correct injection site

Inject BCG vaccine into the skin over the region where the deltoid muscle inserts into the humerus. This is just above the midpoint of the upper arm. This site is recommended to minimise the risk of keloid formation.

By convention, use the left upper arm, if possible. This can assist people who may later look for evidence of BCG vaccination.

4. Inject the vaccine intradermally

Stretch the skin between a finger and thumb. Insert the bevel into the dermis, bevel uppermost, to a distance of about 2 mm. The bevel should be visible through the transparent epidermis.

You should feel considerable resistance as you give the injection. If there is no resistance, the needle may be in the subcutaneous tissues.

A correct intradermal injection should raise a blanched bleb of about 7 mm diameter that looks like orange peel.

If the injection is not intradermal, withdraw the needle and repeat at a new site.

Response to BCG vaccination

After BCG vaccination, a small, red papule forms and ulcerates within 2–3 weeks of vaccination. The ulcer heals with minimal scarring over several weeks. Local lymph nodes may be swollen and tender.

More serious injection site reactions are less common. See Adverse events.

People who have latent or previous tuberculosis infection and receive BCG vaccine are likely to have an accelerated response. This is characterised by:

• induration within 24–48 hours
• pustule formation within 5–7 days
• healing within 10–15 days

Clinical trials have not shown a consistent relationship between the size of tuberculin reactions after BCG vaccination and the level of protection.

The tuberculin skin test is not recommended to show immunity after BCG vaccination.^9,10

Co-administration with other vaccines

People can receive BCG vaccine at the same time as, or at any time after, other inactivated vaccines.

People can receive BCG vaccine and another live parenteral vaccine (such as MMR [measles-mumps-rubella] or yellow fever) either on the same day or at least 4 weeks apart.

People can receive BCG vaccine at any time in relation to oral live vaccines. These include rotavirus vaccine and oral poliovirus vaccine (in infants who have received it overseas).

Contraindications

BCG vaccine is contraindicated in people who have had anaphylaxis after any component of a tuberculosis vaccine.

BCG is a live vaccine that is contraindicated in the following groups:

• people with known or suspected HIV infection,¹¹ even if they are asymptomatic or have normal immune function. This is because of the risk of disseminated BCG infection^12,13
• people treated with corticosteroids or other immunosuppressive therapy. These therapies include monoclonal antibodies against tumour necrosis factor (TNF)-alpha, such as infliximab, etanercept and adalimumab. See Vaccination for people who are immunocompromised
• infants born to mothers who were treated with bDMARDs (biologic disease-modifying anti-rheumatic drugs) in the 3rd trimester of pregnancy. These medicines include TNF-alpha-blocking monoclonal antibodies. These infants often have detectable TNF-alpha-blocking antibodies for several months.^14-16 See also Use of immunosuppressive therapy during pregnancy in Vaccination for women who are planning pregnancy, pregnant or breastfeeding)
• people with congenital cellular immunodeficiencies, including specific deficiencies of the interferon-gamma pathway
• people with malignancies involving bone marrow or lymphoid systems (see People with cancer in Vaccination for people who are immunocompromised)
• people with any serious underlying illness, including severe malnutrition
• pregnant women. BCG vaccine has not been shown to harm the fetus, but receiving live vaccines in pregnancy is not recommended
• people who have previously had tuberculosis or a large (≥5 mm) reaction to a tuberculin skin test

Precautions

Defer BCG vaccination in the following groups:

• neonates who are medically unstable, until the neonate is in good medical condition and ready for discharge from hospital
• infants born to mothers who are suspected or known to be HIV-positive, until HIV infection of the infant can be confidently excluded
• people with active skin disease such as eczema, dermatitis or psoriasis at or near the site of vaccination
• people being treated for latent tuberculosis infection, because the therapy is likely to inactivate the BCG vaccine
• people with significant febrile illness, until 1 month after recovery

Vaccination before or after administration of immunoglobulin or blood products

People can receive BCG vaccine at any time before or after receiving immunoglobulin or any antibody-containing blood product. These preparations and BCG vaccines have minimal interaction.¹⁷ See also Vaccination for people who have recently received normal human immunoglobulin and other blood products.

The normal reaction to BCG vaccination is described in Vaccines, dosage and administration. About 5% of vaccinated people experience adverse events. 2.5% of vaccinated people develop injection site abscesses. 1% of vaccinated people develop lymphadenitis. Up to 1% of vaccinated people need medical attention.¹⁸

Other adverse events include: ¹⁹

• gross suppurative or generalised complications. Although these complications have been treated with anti-tuberculosis medicines, there is no consensus on how to manage them. Seek specialist advice from state or territory tuberculosis services
• keloid formation. This risk is minimised if the injection is no higher than the level of insertion of the deltoid muscle into the humerus
• disseminated BCG infection, but the risk is extremely low (1–4 cases per million vaccinated people)

Tuberculosis is caused by Mycobacterium tuberculosis and other organisms of the M. tuberculosis complex (M.TB complex): ²⁰

• M. tuberculosis — the cause of almost all tuberculosis in Australia²¹
• M. bovis
• M. microti
• M. canettii
• M. africanum

Pathogenesis

Infection usually occurs when a person inhales the tuberculosis bacteria, which reach the lungs. M. bovis can be ingested from unpasteurised milk.

If the person’s immune system can contain the bacteria, the person will be infected but not have disease. This is called latent tuberculosis infection.

If the bacteria overcome the immune system, the person will have active disease and will usually be infectious.²²

Transmission

M. tuberculosis is usually transmitted by the airborne route. Factors affecting transmission include: ²²

• duration of exposure
• frequency of exposure
• proximity to the infected person

Tuberculosis most commonly presents as lung disease, which accounts for 60% of notified tuberculosis cases in Australia.²³ Common symptoms of pulmonary tuberculosis are:

• cough
• fever
• sweats
• weight loss
• coughing up blood

Extrapulmonary tuberculosis can occur in any part of the body. Tuberculosis lymphadenitis is the most common extrapulmonary manifestation.

Disseminated disease (miliary tuberculosis) and meningeal tuberculosis are more common in very young children. These are among the most serious manifestations of tuberculosis disease.¹⁹

Most people infected with M. tuberculosis remain asymptomatic. There is a 10% lifetime risk of developing clinical illness. Clinical disease can develop many years after the original infection. The risk can vary depending on age and immune status.

These groups are more prone to rapidly progressive or generalised infection:^20,24

• infants
• elderly people
• people who are immunocompromised as a result of medical treatment, disease or adverse socioenvironmental circumstances (such as malnutrition or alcoholism)

Tuberculosis in Australia

Approximately 1200 cases of tuberculosis are notified in Australia each year. The annual notification rate has been stable since 1985, at approximately 5–6 cases per 100,000 population.²

Most tuberculosis cases in Australia (more than 85%) occur in people who were born overseas, especially in:²

• China
• India
• Myanmar
• the Philippines
• Vietnam

The rate of multidrug-resistant (MDR) tuberculosis in Australia has been low (less than 2% of notified cases), but the proportion of identified MDR tuberculosis cases has increased since 2006.²¹

Tuberculosis in animals (Mycobacterium bovis) has been eradicated in Australia by screening and culling programs.²⁵

Tuberculosis in Aboriginal and Torres Strait Islander people

In most states and territories, rates of tuberculosis among Aboriginal and Torres Strait Islander people overall are comparable to rates among Australian-born non-Indigenous people.

Rates are higher in Aboriginal and Torres Strait Islander people in some regions, such as:²³

• the Northern Territory
• Far North Queensland
• northern South Australia

See Vaccination for Aboriginal and Torres Strait Islander people.

Screening for tuberculosis

Screening programs in Australia focus on:

• contacts of notified cases
• people at increased risk of tuberculosis infection, including refugees and healthcare workers

Tuberculosis in other countries

The World Health Organization declared tuberculosis a global emergency in 1993, and recent reports have reaffirmed the threat to human health.²⁶ In 2016, there were about 10.4 million incident cases of tuberculosis globally. Most of these cases (87%) were from 30 high-burden countries.²⁷

BCG vaccine is a suspension of a live attenuated strain of Mycobacterium bovis. Worldwide, many BCG vaccines are available, but they are all derived from the strain propagated by the Institut Pasteur, which was first tested in humans in 1921. ²⁸

Sanofi-Aventis Australia markets the BCG vaccine currently registered for use in Australia. See Vaccines, dosage and administration. This vaccine is currently unavailable.

Other BCG vaccines are available in Australia under a special prescribing arrangement. These vaccines include a product from the Serum Institute of India and another from Statens Serum Institut in Denmark. State and territory health authorities can advise on using other products. See also Public health management.

Efficacy of BCG vaccine

In children

BCG vaccination in children provides: ²⁹

• around 25% protection against tuberculosis infection
• around 70% protection against active tuberculosis
• around 55% protection against progression from infection to active disease

BCG vaccination in infants provides greater than 70% protection against severe forms of tuberculosis disease in young children. This includes miliary tuberculosis and tuberculosis meningitis. ^30-34

In adults

The efficacy of BCG vaccine against pulmonary disease in adults is less consistent, and has ranged from no protection to 80% in controlled trials. ³⁵  The reason for the wide variation is not clear, but it has been attributed to differences in:

• study quality
• BCG strains
• host factors, such as age at vaccination and nutritional status
• the prevalence of infection with environmental mycobacteria

Duration of protection

The duration of protection after BCG vaccination has been difficult to measure because the time between infection and disease can be decades. Benefit from infant vaccination has been found in studies with follow-up of up to 12 years, but protection is thought to decline over 10–20 years.¹⁹ Immune memory responses may remain for 10–50 years.^36-38

Other uses of BCG vaccine

BCG vaccination offers some protection against Mycobacterium leprae, which causes leprosy.⁵

Transport according to National vaccine storage guidelines: Strive for 5.³⁹ Store at +2°C to +8°C. Do not freeze. Protect from light.

BCG vaccine must be reconstituted. Add the entire contents of the diluent container to the vial and shake until the powder completely dissolves. Reconstituted vaccine is very unstable. Use within 4–6 hours.

The product information for BCG vaccine states that reconstituted vaccine must be used within 8 hours. The National Tuberculosis Advisory Committee guidelines¹ recommend that any unused vaccine be discarded after 4–6 hours.

The product information for BCG vaccine states that the vaccine is contraindicated in people with generalised skin disease such as:

• eczema
• furunculosis
• atopic dermatitis
• other exudative or inflammatory dermatologic conditions

The Australian Technical Advisory Group on Immunisation recommends deferring BCG vaccination in people with active skin disease at or near the site of vaccination.

1. National Tuberculosis Advisory Committee. The BCG vaccine: information and recommendations for use in Australia – National Tuberculosis Advisory Committee update October 2012. Communicable Diseases Intelligence 2013;37:E65-72.
2. Toms C, Stapledon R, Coulter C, Douglas P, National Tuberculosis Advisory Committee. Tuberculosis notifications in Australia, 2014. Communicable Diseases Intelligence 2017;41:E247-63.
3. World Health Organization (WHO). Tuberculosis (TB): tuberculosis data (accessed Apr 2018). 
4. Smith BB, Hazelton BJ, Heywood AE, et al. Disseminated tuberculosis and tuberculous meningitis in Australian-born children; case reports and review of current epidemiology and management. Journal of Paediatrics and Child Health 2013;49:E246-50.
5. Zodpey SP, Bansod BS, Shrikhande SN, Maldhure BR, Kulkarni SW. Protective effect of Bacillus Calmette Guerin (BCG) against leprosy: a population-based case-control study in Nagpur, India. Leprosy Review 1999;70:287-94.
6. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). [erratum appears in MMWR Morb Mortal Wkly Rep. 2015 Mar 13;64(9):259]. MMWR. Recommendations and Reports 2013;62(RR-4):1-34.
7. Starr S, Berkovich S. Effects of measles, gamma-globulin-modified measles and vaccine measles on the tuberculin test. New England Journal of Medicine 1964;270:386-91.
8. National Tuberculosis Advisory Committee. Position statement on interferon-γ release assays in the detection of latent tuberculosis infection. Communicable Diseases Intelligence 2012;36:125-31.
9. Menzies D. What does tuberculin reactivity after bacille Calmette-Guérin vaccination tell us? Clinical Infectious Diseases 2000;31 Suppl 3:S71-4.
10. Hart PD, Sutherland I, Thomas J. The immunity conferred by effective BCG and vole bacillus vaccines in relation to individual variations in induced tuberculin sensitivity and to technical variations in the vaccines. Tubercle 1967;48:201-10.
11. Hesseling AC, Marais BJ, Gie RP, et al. The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children. Vaccine 2007;25:14-8.
12. Hesseling AC, Cotton MF, Fordham von Reyn C, et al. Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants. International Journal of Tuberculosis and Lung Disease 2008;12:1376-9.
13. Mansoor N, Scriba TJ, de Kock M, et al. HIV-1 infection in infants severely impairs the immune response induced by Bacille Calmette-Guérin vaccine. Journal of Infectious Diseases 2009;199:982-90.
14. Cheent K, Nolan J, Shariq S, et al. Case report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's disease. Journal of Crohn's and Colitis 2010;4:603-5.
15. Mahadevan U, Terdiman JP, Church J, et al. Infliximab levels in infants born to women with inflammatory bowel disease. Gastroenterology 2007;132 Suppl 2:A144.
16. Mahadevan U, Miller JK, Wolfe DC. Adalimumab levels detected in cord blood and infants exposed in utero. Gastroenterology 2011;140 Suppl 1:S61-2.
17. Connelly Smith K, Orme IM, Starke JR. Tuberculosis vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. Philadelphia, PA: Elsevier Saunders; 2013.
18. Turnbull FM, McIntyre PB, Achat HM, et al. National study of adverse reactions after vaccination with bacille Calmette-Guérin. Clinical Infectious Diseases 2002;34:447-53.
19. World Health Organization. BCG vaccines: WHO position paper – February 2018. Weekly Epidemiological Record 2018;93:73-96.
20. Fitzgerald DW, Sterling TR, Haas DW. Mycobacterium tuberculosis. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015.
21. Lumb R, Bastian IB, Jelfs PJ, et al. Tuberculosis in Australia: bacteriologically-confirmed cases and drug resistance, 2011. A report of the Australian Mycobacterium Reference Laboratory Network. Communicable Diseases Intelligence 2014;38:E369-75.
22. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of Tuberculosis Elimination. Introduction to the Core Curriculum on Tuberculosis: what the clinician should know. 6th ed. Atlanta, GA: Centers for Disease Control and Prevention; 2013. 
23. Barry C, Konstantinos A, National Tuberculosis Advisory Committee. Tuberculosis notifications in Australia, 2007. Communicable Diseases Intelligence 2009;33:304-15.
24. Plant AJ, Krause VL, Condon JR, Kerr C. Aborigines and tuberculosis: why they are at risk. Australian Journal of Public Health 1995;19:487-91.
25. Ingram PR, Bremner P, Inglis TJ, Murray RJ, Cousins DV. Zoonotic tuberculosis: on the decline. Communicable Diseases Intelligence 2010;34:339-41.
26. World Health Organization (WHO). The End TB Strategy: global strategy and targets for tuberculosis prevention, care and control after 2015. Geneva: WHO; 2014. 
27. World Health Organization (WHO). Tuberculosis [fact sheet]. 2018 (accessed May 2018). 
28. Wittes RC. Immunology of bacille Calmette-Guérin and related topics. Clinical Infectious Diseases 2000;31 Suppl 3:S59-63.
29. Roy A, Eisenhut M, Harris RJ, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ 2014;349:g4643.
30. Bourdin Trunz B, Fine PE, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. The Lancet 2006;367:1173-80.
31. Colditz GA, Berkey CS, Mosteller F, et al. The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 1995;96:29-35.
32. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. International Journal of Epidemiology 1993;22:1154-8.
33. Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis: meta-analysis of the published literature. JAMA 1994;271:698-702.
34. Brewer TF. Preventing tuberculosis with bacillus Calmette-Guérin vaccine: a meta-analysis of the literature. Clinical Infectious Diseases 2000;31 Suppl 3:S64-7.
35. Barreto ML, Pereira SM, Ferreira AA. BCG vaccine: efficacy and indications for vaccination and revaccination. Jornal de Pediatria 2006;82(3 Suppl):S45-54.
36. Aronson NE, Santosham M, Comstock GW, et al. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: a 60-year follow-up study. JAMA 2004;291:2086-91.
37. Sterne JA, Rodrigues LC, Guedes IN. Does the efficacy of BCG decline with time since vaccination? International Journal of Tuberculosis and Lung Disease 1998;2:200-7.
38. Weir RE, Gorak-Stolinska P, Floyd S, et al. Persistence of the immune response induced by BCG vaccination. BMC Infectious Diseases 2008;8:9.
39. National vaccine storage guidelines: Strive for 5. 3rd ed. Canberra: Australian Government Department of Health and Ageing; 2019. https://www.health.gov.au/resources/publications/national-vaccine-storage-guidelines-strive-for-5
40. Communicable Diseases Network Australia (CDNA). Tuberculosis (TB): CDNA national guidelines for the public health management of TB. Canberra: Australian Government Department of Health; 2015.