Tuberculosis

What

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. Most people who become infected with M. tuberculosis 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 children aged <5 years in some parts of Australia
• Healthcare workers with a high risk of exposure to tuberculosis
• Young children who will be travelling to settings with high tuberculosis incidence
• Some children born to parents from countries with high tuberculosis incidence
• Young children who are a household contact of a person with leprosy

How

BCG vaccine is given as a single dose by intradermal injection.

A tuberculin skin test pre-vaccination is recommended for some people prior to BCG vaccination, based on a risk assessment of the likely exposure to tuberculosis in the past.

Why

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

Tuberculosis vaccines available in Australia

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

See also Vaccine information for more details.

Note: The only BCG vaccine registered for use in Australia (BCG vaccine (Sanofi-Aventis Australia)) has not been available for some time.

Other BCG vaccines are available in Australia under a special prescribing arrangement (e.g. BCG Vaccine SSI [Statens Serum Institut, Denmark]). These vaccines can be used in the same manner as the registered unavailable vaccine. Contact state and territory public health authorities for more information on obtaining BCG vaccines. See also Public health management.

Please note that different vaccines may use different strains of M. tuberculosis which may differ slightly in antigenic properties. See Vaccine information.

Dose and route

BCG vaccine is a single dose given by intradermal injection. The standard dose is:

• 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.

If BCG is inadvertently given subcutaneously, there is no need to repeat vaccination as the vaccine will still have a protective effect. The person should be informed that they may be more likely to experience an injection site reaction, or regional lymph node involvement, but overall BCG is a very safe vaccine.

Only healthcare workers who are trained in intradermal vaccination procedures should administer BCG vaccine. See Administration of vaccines.

BCG revaccination is generally not recommended, because of a lack of evidence for increased efficacy.⁹

BCG vaccine may be available from state and territory tuberculosis services, and may be available through some travel medicine clinics.

BCG vaccination procedures

BCG vaccination steps are:

1. Wear protective eyewear

The following 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. Any irritation to the eye as a result of a should be followed up in the subsequent weeks, with an assessment by a medial practitioner and/or a specialist ophthalmologist.

2. 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.

3. Inject the vaccine intradermally

See Administration of vaccines for information on the intradermal vaccination technique.

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. An accelerated cutaneous reaction to BCG is not more severe than typical BCG reactions and have no long-term detrimental effect - it simply occurs more rapidly. 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.

Performing a TST to demonstrate immunity after BCG vaccination is not recommended.^10,11

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], varicella or yellow fever) either on the same day or at least 4 weeks apart.

For three months following a BCG vaccine, do not give any other vaccine in the same arm.

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 an attenuated live vaccine that is contraindicated in the following groups:

• people with inborn errors of immunity, including primary immunodeficiencies. See Inborn errors of immunity, including primary immunodeficiency
• people who are immunocompromised due to receiving immunosuppressive therapy, such as high doses of corticosteroids or other conventional immunosuppressive therapies, small molecular targeted therapies and biological therapies. For people receiving these medications, live vaccines should be administered at least 4 weeks before starting the treatment, if feasible, or after completing the therapies with an appropriate interval which the length of time can vary by agent. See Secondary (acquired) immunodeficiency due to medical therapies
• people with active malignancies involving bone marrow or lymphoid systems, any person with cancer receiving immunosuppressive therapy, or people who completed chemotherapy within the previous 3 months. See People with malignancies: recommendations for vaccination
• people who are anticipated to need an organ transplant, unless the potential benefit outweighs the risk of disease reactivation after transplant. If indicated, BCG vaccine should be given at least 4 weeks before transplant, provided the person is not severely immunocompromised at that time. See Solid organ transplant: recommendations for vaccination
• people undergoing haematopoietic stem cell transplant (HSCT). BCG is not recommended after HSCT. See Haematopoietic stem cell transplant: recommendations for vaccination
• people with HIV because of the risk of disseminated BCG infection.^12,13 However, BCG can be given to people with well-controlled HIV who are not severely immunocompromised. See People with HIV: recommendations for vaccination
• 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. See Vaccination for women who are planning pregnancy, pregnant or breastfeeding
• people who have previously had tuberculosis or a positive (≥5 mm) TST

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
• infants aged <6 months born to mothers who were treated with biological immunosuppressive therapies 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 Infants exposed to immunosuppressive therapy in utero or through breastmilk and Use of immunosuppressive therapy during pregnancy in Vaccination for women who are planning pregnancy, pregnant or breastfeeding

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. With the proper procedure less than 5% of vaccinated people experience adverse events; ~2.5% may develop a local injection site ‘cold abscess’ and ~1% regional lymphadenitis with/without ‘cold abscess’ formation.¹⁸

Other adverse events include:¹⁹

• local suppurative complications. This does not require treatment with anti-tuberculosis medicine unless there is perceived risk of disseminated BCG disease (see below), but BCG is inherently resistant to pyrazinamide and optimal treatment requires careful consideration;²⁰ it is best to 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 disease, but the risk is extremely low (1–4 cases per million vaccinated people) and it is only observed in people with immune compromise. Treatment with anti-tuberculosis medicines may be warranted, but BCG is inherently resistant to pyrazinamide and optimal treatment requires careful consideration;²⁰ it is best to seek specialist advice from state or territory tuberculosis services.

Tuberculosis is caused by Mycobacterium tuberculosis and other organisms of the M. tuberculosis complex (M.TB complex)²¹. M. tuberculosis is the cause of almost all tuberculosis in Australia²²

Pathogenesis

Infection usually occurs when a person inhales the tuberculosis bacteria, which reach the lungs. M. bovis can be ingested from unpasteurised milk, consumed in countries where M. bovis remains prevalent (not Australia)

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

If the bacteria overcome the immune system, which may occur after many years of immune control, the person develops active disease and may become infectious if pulmonary disease occurs.²³

Transmission

M. tuberculosis is usually transmitted by the airborne route. Factors affecting transmission include: ²³

• duration of exposure
• frequency of exposure
• proximity to the infected person (high-density or communal living situations may increase the risk of transmission)

Persons with extrapulmonary TB with no lung or larygneal involvement are not infectious.

Tuberculosis most commonly presents as lung disease, which accounts for 60% of notified tuberculosis cases in Australia.²⁴ Common symptoms of pulmonary tuberculosis are:

• cough
• fever
• fatigue
• weight loss
• coughing up blood (mainly in adults with late-stage pulmonary disease)

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.²⁵ 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 varies depending on age and immune status.

Groups more prone to rapidly progressive disease include:²¹

• young children (infants and children <5 years of age)
• elderly people
• people who are immunocompromised as a result of medical treatment, disease or adverse socioenvironmental circumstances.

Tuberculosis in Australia

In Australia, tuberculosis is an uncommon disease, with annual incidence remaining below 7 per 100,000 population since 1980s.²⁶

Most tuberculosis cases in Australia (more than 85%) occur in people who were born overseas, especially in countries with a high incidence of tuberculosis.^3,27See latest WHO Global Tuberculosis Report for up-to-date information.²⁸

The rate of multidrug-resistant (MDR) tuberculosis in Australia remains low (approximately 2% of bacteriologically confirmed cases with drug susceptibility testing available).²⁹

Tuberculosis in animals (Mycobacterium bovis) has been eradicated in Australia by screening and culling programs.³⁰

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. However, notifications of tuberculosis among Aboriginal and Torres Strait Islander people in some states and territories are disproportionately higher than for Aboriginal and Torres Strait Islander people and non-Indigenous people in other states.

Regions with higher rates of tuberculosis include:²⁴

• the Northern Territory
• Far North Queensland

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.³¹ In 2019, there were about 7.1 million incident cases of tuberculosis globally.²⁸

When reconstituted, BCG vaccine is a suspension of a live attenuated strain of M. bovis. Worldwide, many BCG vaccines are available, but they are all derived from the original strain selected by Calmette and Guerin, which was first tested in humans in 1921.³²

Sanofi-Aventis Australia markets the only BCG vaccine registered for use in Australia, although this vaccine is currently unavailable. See Vaccines, dosage and administration. Contact your state or territory health authority to access a BCG vaccine.

Efficacy of BCG vaccine

In children

BCG vaccination in young children provides:³³

• ~25% protection against tuberculosis infection
• ~70% protection against active tuberculosis
• >70% protection against severe forms of tuberculosis disease in young children, including miliary tuberculosis and tuberculosis meningitis.^34-38

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.³⁹  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 40 years, but protection is thought to decline over 10–20 years.¹⁹ Immune memory responses may remain for 10–50 years.^40-42

Other uses of BCG vaccine

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

BCG is also used as treatment for bladder cancer, but this is a different preparation that is instilled directly into the bladder.

The currently available vaccine, BCG Vaccine SSI, is presented in a multidose vial. For more information on use of multidose vials, see Administration of vaccines.

Transport according to National Vaccine Storage Guidelines: Strive for 5.⁴⁴ 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.

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