BCG Vaccine

Introduction
BCG, or bacille Calmette-Guerin, is a vaccine for tuberculosis (TB) disease. Many foreign-born
persons have been BCG-vaccinated. BCG is used in many countries with a high prevalence of TB to
prevent childhood tuberculous meningitis and miliary disease. However, BCG is not generally
recommended for use in the United States because of the low risk of infection with Mycobacterium
tuberculosis, the variable effectiveness of the vaccine against adult pulmonary TB, and the vaccines
potential interference with tuberculin skin test reactivity. The BCG vaccine should be considered only
for very select persons who meet specific criteria and in consultation with a TB expert.

Recommendations
Children. BCG vaccination should only be considered for children who have a negative tuberculin
skin test and who are continually exposed, and cannot be separated from, adults who

Are untreated or ineffectively treated for TB disease (if the child cannot be given long-term
treatment for infection); or

Have TB caused by strains resistant to isoniazid and rifampin.

Health Care Workers. BCG vaccination of health care workers should be considered on an
individual basis in settings in which

A high percentage of TB patients are infected with M. tuberculosis strains resistant to both
isoniazid and rifampin;

There is ongoing transmission of such drug-resistant M. tuberculosis strains to health care

workers and subsequent infection is likely; or

Comprehensive TB infection-control precautions have been implemented, but have not been
successful.

Health care workers considered for BCG vaccination should be counseled regarding the risks and
benefits associated with both BCG vaccination and treatment of Latent TB Infection (LTBI).

Contraindications
Immunosuppression. BCG vaccination should not be given to persons who are immunosuppressed
(e.g., persons who are HIV infected) or who are likely to become immunocompromised (e.g.,
persons who are candidates for organ transplant).
Pregnancy. BCG vaccination should not be given during pregnancy. Even though no harmful effects
of BCG vaccination on the fetus have been observed, further studies are needed to prove its safety.

Testing for TB in BCG-Vaccinated Persons

The tuberculin skin test (TST) and blood tests to detect TB infection are not contraindicated for
persons who have been vaccinated with BCG.
Tuberculin Skin Test (TST). BCG vaccination may cause a false-positive reaction to the TST, which
may complicate decisions about prescribing treatment. The presence or size of a TST reaction in
persons who have been vaccinated with BCG does not predict whether BCG will provide any
protection against TB disease. Furthermore, the size of a TST reaction in a BCG-vaccinated person
is not a factor in determining whether the reaction is caused by LTBI or the prior BCG vaccination.
(See below for specific guidance on skin test results.)
TB Blood Tests. Blood tests to detect TB infection, unlike the TST, are not affected by prior BCG
vaccination and are less likely to give a false-positive result.

Treatment for LTBI in BCG-Vaccinated Persons

Treatment of LTBI substantially reduces the risk that TB infection will progress to disease. Careful
assessment to rule out the possibility of TB disease is necessary before treatment for LTBI is started.
Evaluation of TST reactions in persons vaccinated with BCG should be interpreted using the same
criteria for those not BCG-vaccinated. Persons in the following high-risk groups should be given
treatment for LTBI if their reaction to the TST is at least 5 mm of induration or they have a positive
result using a TB blood test:

HIV-infected persons

Recent contacts to a TB case

Persons with fibrotic changes on chest radiograph consistent with old TB

Patients with organ transplants

Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15
mg/day of prednisone for 1 month or longer, taking TNF-antagonists)

In addition, persons in the following high-risk groups should be considered for treatment of LTBI if
their reaction to the TST is at least 10 mm of induration or they have a positive result using a TB
blood test:

Recent arrivals (less than 5 years) from high-prevalence countries

Injection drug users

Residents and employees of high-risk congregate settings (e.g., correctional facilities,

nursing homes, homeless shelters, hospitals, and other health care facilities)

Mycobacteriology laboratory personnel

Persons with clinical conditions that place them at high-risk for developing TB disease (e.g.,
diabetes)

Children less than 4 years of age, or children and adolescents exposed to adults in high-risk
categories

Persons with no known risk factors for TB may be considered for treatment of LTBI if their reaction to
the tuberculin test is at least 15 mm of induration or they have a positive result using a TB blood test.
Targeted skin testing programs should only be conducted among high-risk groups. All testing
activities should be accompanied by a plan for follow-up care for persons with TB infection or
disease.

TB Vaccine (BCG)
Bacille Calmette-Gurin (BCG) is a vaccine for tuberculosis (TB) disease. This vaccine is not widely
used in the United States, but it is often given to infants and small children in other countries where
TB is common. BCG does not always protect people from getting TB.
BCG Recommendations
In the United States, BCG should be considered for only very select people who meet specific
criteria and in consultation with a TB expert. Health care providers who are considering BCG
vaccination for their patients are encouraged to discuss this intervention with the TB control
program in their area.
Children
BCG vaccination should only be considered for children who have a negative TB test and who are
continually exposed, and cannot be separated from adults who
Are untreated or ineffectively treated for TB disease, and the child cannot be given long-term

primary preventive treatment for TB infection; or

Have TB disease caused by strains resistant to isoniazid and rifampin.

Health Care Workers

BCG vaccination of health care workers should be considered on an individual basis in settings in
which

A high percentage of TB patients are infected with TB strains resistant to both isoniazid and
rifampin;

There is ongoing transmission of drug-resistant TB strains to health care workers and

subsequent infection is likely; or

Comprehensive TB infection-control precautions have been implemented, but have not been
successful.

Health care workers considered for BCG vaccination should be counseled regarding the risks and
benefits associated with both BCG vaccination and treatment of latent TB infection.
Testing for TB in BCG-Vaccinated People
Many people born outside of the United States have been BCG-vaccinated.
People who were previously vaccinated with BCG may receive a TB skin test to test for TB infection.
Vaccination with BCG may cause a positive reaction to a TB skin test. A positive reaction to a TB
skin test may be due to the BCG vaccine itself or due to infection with TB bacteria.
TB blood tests (IGRAs), unlike the TB skin test, are not affected by prior BCG vaccination and are
not expected to give a false-positive result in people who have received BCG.
For children under the age of five, the TB skin test is preferred over TB blood tests.
A positive TB skin test or TB blood test only tells that a person has been infected with TB bacteria. It
does not tell whether the person has latent TB infection or has progressed to TB disease. Other
tests, such as a chest x-ray and a sample of sputum, are needed to see whether the person has TB
disease.

BCG vaccine
The formulation of international requirements for the manufacture and control of BCG
vaccine was first considered by the WHO Expert Committee on Biological Standardization in
its thirteenth report. In its fourteenth report, the Committee requested WHO to make
arrangements as soon as possible for the formulation of such requirements. These
requirements were approved by the WHO Expert Committee on Biological Standardization at
its eighteenth meeting and appeared as Annex 1 to its report.
Mycobacterium tuberculosis (Mtb), the ethiological agent of tuberculosis (TB), is a leading cause of
human disease and death, particularly in developing countries. In the global context, TB in intimately
linked to poverty, and control of TB is ultimately a question of justice and human rights. In some areas
with a high burden of TB, existing strategies for TB control are currently overwhelmed by the rising
numbers of cases of TB occurring in parallel with or the HIV/AIDS pandemic. Emerging mycobacterial
drug resistance is further complicating the situation. After decades of steady decline, the incidence of
TB is also increasing in industralized countries, mainly as the result of outbreaks in particularly
vulnerable groups.
The bacille Calmette-Gurin (BCG) vaccine has existed for 80 years and is one of the most widely
used of all current vaccines, reading >80%of neonates and infants in countries where it is part of the
national childhood immunization programme. BCG vaccine has a documented protective effect against
meningitis and disseminated TB in children. It does not prevent primary infection and, more
importantly, does not prevent reactivation of latent pulmonary infection, the principal source of bacillary
spread in the community. The impact of BCG vaccination on transmission of Mtb is therefore limited.
The biological interaction between Mtb and the human host is complex and only partially understood.
Recent advances in areas such as mycobacterial immunology and genomics have stimulated research
on numerous new experimental vaccines, but it is unlikely that any of these urgently need vaccines will
be available for routine use within the next few years. In the meantime, optimal utilization of BCG is
encouraged.

Public health aspects

Human TB has existed for thousands of years. No country is TB-free, and the disease is
endemic in most poor countries of the world. It is estimated that about one-third of the
current global population is infected asymptomatically with Mtb, of whom 5-10% will
develop clinical disease during their lifetime. According to WHO estimates for 2001, there

are 16-20 million cases of TB worldwide, with more than 8 million new cases and over 1.8
million deaths each year. Most new cases and deaths occur in developing countries where
infection is often acquired in childhood. The annual risk of TB infection in children in highburden countries is estimated to be 0.5-2%. Childhood deaths from TB are usually caused
by meningitis or disseminated disease.
Co-infection with Mtb and HIV has been shown to be a lethal combination. In areas of subSaharan Africa where HIV is most prevalent, the annual incidence of TB has risen to more
than 300 cases per 100 000 inhabitants. In some of these places, nearly 50% of the HIVinfected population is co-infected with TB and more than two-thirds of TB patients are
infected with HIV. For HIV-infected persons, the liftime risk of developing TB disease is as
high as 30-50%. In some parts of south-east Asia, an estimated 20-25% of TB cases will
be directly attributable to HIV within the next few years. In most industrialized countries,
decades of declining TB incidence halted towards the end of the 20th century when
increasing annual numbers of TB cases were recorded. In several regions of the former
Soviet Union, the recent rise in TB incidence has been dramatic. In industrialized settings,
new cases of TB usually occur in the elderly. In recent years, however, TB has also been
found increasingly in immigrants from endemic countries, in HIV-positive individuals and
in socially deprived groups including drug-dependent individuals and prisoners.

BCG (Tuberculosis)

Pierre Virot

Tuberculosis (TB) kills or debilitates more adults aged between 15 and 59 years than any
other disease in the world. TB is caused by Mycobacterium tuberculosis, an intracellular
pathogen of the genus Mycobacterium that includes some 55 species, half of which may
cause disease in humans.

BCG Vaccines (Tuberculosis)

In order to prevent further deviation from the original BCG, lyophilized seed lots of the
vaccine strains have been kept by WHO since 1956. Vaccine strains are prepared from
seed-lot material by growing the bacilli in an artificial medium, harvesting, concentrating,
homogenizing, and the preparation is then lyophilized.

Bacillus Calmette-Guerin (BCG) Vaccine

pronounced as (ba sil' us kal' met gay rayn')

WHY is this medicine prescribed?

HOW should this medicine be used?
What SPECIAL PRECAUTIONS should I follow?
What SIDE EFFECTS can this medicine cause?
What should I do in case of OVERDOSE?
What OTHER INFORMATION should I know?
Brand names
Other names

WHY is this medicine prescribed?

BCG vaccine provides immunity or protection against tuberculosis (TB). The
vaccine may be given to persons at high risk of developing TB. It is also used
to treat bladder tumors or bladder cancer.
This medication is sometimes prescribed for other uses; ask your doctor or
pharmacist for more information.

HOW should this medicine be used?

Your doctor or a health care provider will administer this medicine. When
used to protect against TB, it is injected into the skin. Keep the vaccination
area dry for 24 hours after receiving the vaccine, and keep the area clean
until you cannot tell the vaccination area from the skin around it.
When used for bladder cancer, the medicine flows into your bladder through
a tube or catheter. Avoid drinking fluids for 4 hours before your treatment.
You should empty your bladder before treatment. During the first hour after
the medication is infused, you will lie on your stomach, back, and sides for
15 minutes each. Then you will stand, but you should keep the medication in
your bladder for another hour. If you cannot keep the medication in your
bladder for the entire 2 hours, tell your health care provider. At the end of 2
hours you will empty your bladder in a seated manner for safety reasons.
Your urine should be disinfected for 6 hours after the medication is
administered. Pour a similar amount of undiluted bleach in the toilet after
you urinate. Let it stand for 15 minutes before flushing.
Various dosing schedules may be used. Your doctor will schedule your
treatment. Ask your doctor to explain any directions you do not understand.

When the vaccine is given to protect against TB, it usually is given only one
time but may be repeated if there is not a good response in 2-3 months.
Response is measured by a TB skin test.

What SPECIAL PRECAUTIONS should I follow?

Before receiving BCG vaccine,

tell your doctor and pharmacist if you are allergic to BCG vaccine or any other
drugs.

tell your doctor and pharmacist what prescription and nonprescription

medications you are taking, especially antibiotics, cancer chemotherapy agents,
steroids, tuberculosis medications, and vitamins.

tell your doctor if you have had a recent smallpox vaccination or if you have
had a positive TB test.

tell your doctor if you have an immune disorder, cancer, fever, an infection,
or an area of severe burns on your body.

tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking BCG vaccine, call your doctor
immediately.

What SIDE EFFECTS can this medicine cause?

BCG vaccine may cause side effects. Tell your doctor if any of these
symptoms are severe or do not go away:

swollen lymph nodes

small red areas at the site of injection. (These usually appear 10-14 days
after injection and slowly decrease in size. They should disappear after about 6
months.)

fever

blood in the urine

frequent or painful urination

upset stomach

vomiting