BCG Vaccine: Protection Against Tuberculosis

What Is the BCG Vaccine and How Does It Work?

The BCG vaccine (Bacillus Calmette-Guerin) is a live attenuated vaccine derived from a weakened strain of Mycobacterium bovis that stimulates the immune system to develop protection against tuberculosis. It provides 70-80% protection against severe forms of TB in children, particularly TB meningitis and miliary tuberculosis.

The BCG vaccine was developed in the early 20th century by French scientists Albert Calmette and Camille Guerin, who weakened (attenuated) a strain of Mycobacterium bovis, a bacterium closely related to the tuberculosis bacterium. This process took 13 years of laboratory cultivation, after which the bacterium could no longer cause disease but could still trigger a protective immune response. The vaccine has been used since 1921 and remains one of the most widely administered vaccines in the world.

When administered, the live but weakened bacteria in the BCG vaccine replicate slowly in the body, stimulating the immune system to develop memory cells that can recognize and fight tuberculosis bacteria. This process involves the activation of T lymphocytes and macrophages, which are critical for controlling TB infection. Unlike vaccines that primarily stimulate antibody production, BCG primarily activates cell-mediated immunity, which is the key defense mechanism against intracellular pathogens like Mycobacterium tuberculosis.

The effectiveness of BCG vaccination varies considerably depending on geographic location and the form of TB being prevented. Studies consistently show that the vaccine provides excellent protection against the most severe forms of childhood tuberculosis, including tuberculous meningitis (infection of the membranes surrounding the brain) and miliary tuberculosis (disseminated TB throughout the body). However, protection against pulmonary TB in adults is highly variable, ranging from 0-80% in different studies and geographic regions.

Why BCG is primarily given to children

The BCG vaccine is most effective when administered early in life, ideally at birth or within the first few weeks of life. There are several important reasons for this focus on childhood vaccination. First, young children have a higher risk of developing severe, disseminated forms of tuberculosis if infected, due to their immature immune systems. The BCG vaccine specifically targets these severe forms, making it a crucial protective measure for this vulnerable population.

Second, the vaccine works best when given before any potential exposure to TB bacteria. Once someone has been exposed to or infected with TB, the vaccine's effectiveness is significantly reduced. In countries where TB is common, early vaccination ensures protection before inevitable environmental exposure. Third, the protective effect of BCG appears to wane over time, but the period of strongest protection coincides with the years of highest risk for severe childhood TB.

What BCG vaccination does not do

It is important to understand the limitations of BCG vaccination. The vaccine does not prevent infection with TB bacteria – vaccinated individuals can still become infected. Rather, it helps the immune system control the infection and prevents progression to severe disease. Additionally, BCG does not reliably prevent the most common form of adult TB (pulmonary tuberculosis), which is why countries with low TB incidence often do not include BCG in routine immunization programs.

Who Should Get the BCG Vaccine?

BCG vaccination is recommended for children at increased risk of tuberculosis exposure, including those under 6 years with family ties to high-TB countries, children with close TB contacts, and those planning extended stays (over 3 months) in TB-endemic areas. Many countries with high TB rates vaccinate all newborns.

The recommendations for BCG vaccination vary significantly between countries, reflecting differences in TB epidemiology and public health priorities. Understanding who should receive the vaccine requires considering both individual risk factors and national vaccination policies.

In countries where tuberculosis remains common (generally defined as incidence greater than 40 cases per 100,000 population per year), BCG vaccination is typically recommended for all newborns, ideally given at birth or as soon as possible thereafter. This universal approach ensures protection during the most vulnerable period of life and before potential exposure to TB in the community. Countries in Africa, Southeast Asia, and South America typically follow this approach, and the World Health Organization recommends BCG vaccination for all infants in high-burden settings.

In countries with low TB incidence, such as most of Western Europe, North America, and Australia, BCG vaccination is generally targeted to high-risk groups rather than given universally. The rationale is that the risks of adverse reactions outweigh the benefits in settings where TB is rare. In these contexts, specific groups are recommended for vaccination.

Children recommended for BCG vaccination

• Infants and children under 6 years from families that have recently arrived from or maintain close ties to countries where TB is common
• Children and adolescents up to 18 years who have close contact with a person known to have active tuberculosis
• Children and adolescents up to 18 years who are planning to live for more than 3 months in a country with high TB prevalence
• Newborns in households where a family member has a history of TB or ongoing TB risk factors

Healthcare workers and laboratory personnel who may be exposed to TB can also be considered for BCG vaccination in some settings, though this practice varies by country. Adults who have already been exposed to TB (as determined by tuberculin skin test or interferon-gamma release assay) generally do not benefit from BCG vaccination.

Children who have moved from another country

Vaccination programs differ between countries, which means children born abroad may have different immunization histories. If your child was born in another country, it is important to consult with healthcare providers to review their vaccination records and determine whether BCG vaccination has already been given or is needed. BCG vaccination leaves a characteristic scar on the upper arm, which can sometimes help determine vaccination status when records are unavailable.

How Is the BCG Vaccine Administered?

The BCG vaccine is given as a single intradermal injection into the upper arm, where the vaccine must be placed precisely into the dermis (not the muscle). The injection creates a small raised area that develops into the characteristic BCG reaction over the following weeks to months.

Unlike most vaccines that are administered into muscle (intramuscular) or under the skin (subcutaneous), BCG must be given intradermally – directly into the dermis, the middle layer of the skin. This precise technique is essential for proper immune response development and for minimizing adverse reactions. Healthcare providers administering BCG require specific training in the intradermal injection technique.

The standard site for BCG injection is the outer upper arm, at the insertion point of the deltoid muscle. In some countries, the shoulder or thigh may be used, particularly in young infants. The vaccine is given using a fine needle (typically 25-26 gauge) at a shallow angle to the skin surface, creating a small bleb (raised area) of about 6-8mm diameter that indicates successful intradermal placement.

The injection process itself is quick – the actual administration takes only a few seconds. Children may experience a brief stinging sensation as the vaccine is delivered, but this discomfort typically subsides within minutes. Unlike many other vaccinations, BCG does not usually require pain relief measures, though comfort measures like breastfeeding immediately after vaccination can help soothe infants.

What to expect immediately after vaccination

Immediately after the injection, a small pale raised area (wheal) approximately 6-10mm in diameter should be visible at the injection site. This is a normal sign that the vaccine has been correctly placed in the dermis. The wheal typically disappears within 30 minutes to a few hours. The injection site may be slightly pink or red for the first few days, which is a normal inflammatory response.

No special care is needed for the injection site in the first few days. You can bathe or shower normally, though it is advisable to gently pat the area dry rather than rubbing it. There is no need to cover the injection site with a bandage unless there is active discharge (which comes later in the healing process).

What Happens After BCG Vaccination?

After BCG vaccination, a characteristic skin reaction develops over several months: initial redness progresses to a lump at 2-3 weeks, which may become a pustule that opens into an ulcer before healing with scar formation. This process takes 2-6 months and indicates successful vaccination.

The skin reaction following BCG vaccination is unlike any other vaccine reaction and can be concerning to parents who are unfamiliar with what to expect. Understanding the normal progression of the BCG site helps distinguish normal reactions from complications requiring medical attention.

The first few days after vaccination

In the first few days following BCG vaccination, the injection site may show minimal changes – perhaps slight redness or a small firm area. Some children experience mild soreness or swelling at the injection site, which is similar to reactions from other vaccines. Fever after BCG vaccination is uncommon and usually mild if it occurs. If your child develops fever, standard fever management measures (such as appropriate doses of paracetamol/acetaminophen) can be used if needed.

Two to six weeks after vaccination

The characteristic BCG reaction typically begins to develop 2-3 weeks after vaccination. A small red lump (papule) appears at the injection site. On lighter skin, this appears red or pink; on darker skin tones, the color change may be less noticeable, but the raised lump is still evident. This papule gradually enlarges over the following weeks and may reach the size of a pea (approximately 7-10mm in diameter).

The papule often develops into a pustule – a raised bump filled with whitish-yellow fluid. This pustule may appear alarming but is a normal part of the immune response to the vaccine. The pustule typically ruptures spontaneously after several weeks, leaving a small open wound (ulcer). This ulceration is not an infection requiring antibiotics – it is the expected course of BCG vaccination.

Caring for the BCG wound

When the BCG site becomes an open ulcer, proper wound care becomes important. The wound may produce significant discharge (weeping) and can take several weeks to dry completely. Here are the key principles for caring for the BCG wound:

• Keep the wound clean and dry: Allow air to reach the wound as much as possible
• Use only loose, breathable dressings: If the wound is weeping significantly, a loose gauze or textile bandage can be applied. Avoid tight bandages, plastic dressings, or adhesive plasters that trap moisture
• Do not apply ointments, creams, or antiseptics: These can interfere with the normal healing process and are not necessary
• Do not apply wound powder: This can irritate the wound and slow healing
• Showering is acceptable: Brief water exposure from showering is fine – just pat the area dry gently afterward
• Avoid soaking: Refrain from bathing in a tub or swimming while the wound is open

Timeline for complete healing

The total healing time for the BCG site varies considerably between individuals but typically takes 2-6 months. Some children heal within 8 weeks, while others may take up to 6 months for complete healing. When the wound heals, it leaves a small, slightly depressed scar, usually 2-10mm in diameter. This BCG scar is permanent and serves as evidence of previous vaccination.

Lymph node swelling

It is common for the lymph nodes in the armpit (axillary lymph nodes) on the same side as the vaccination to become slightly enlarged in the weeks following BCG vaccination. This swelling is a normal immune response and typically resolves on its own within weeks to a few months. The swollen lymph nodes are usually not tender and do not require treatment unless they become very large (greater than 3cm) or show signs of suppuration (pus formation).

How Effective Is the BCG Vaccine?

BCG vaccine effectiveness varies by the type of tuberculosis and geographic region. It provides 70-80% protection against severe childhood TB forms (meningitis, miliary TB), but protection against adult pulmonary TB ranges from 0-80% depending on location. Protection is strongest in the first 10-15 years after vaccination.

The effectiveness of BCG vaccination has been studied extensively over the past century, and understanding the nuances of its protective effects is crucial for both healthcare policy and individual decision-making. The vaccine's performance varies significantly depending on several factors, including the type of TB being prevented, the age at vaccination, and geographic location.

Where BCG excels is in protecting against the most severe forms of tuberculosis in children. Multiple studies and meta-analyses consistently show that BCG vaccination provides approximately 70-80% protection against tuberculous meningitis and miliary (disseminated) tuberculosis. These severe forms of TB, while relatively rare, can be devastating – particularly tuberculous meningitis, which can cause permanent neurological damage or death even with treatment. For this reason alone, BCG vaccination represents a crucial intervention for at-risk children.

The vaccine also provides good protection against other forms of childhood TB, including lymph node TB (tuberculous lymphadenitis) and other extrapulmonary forms. Studies suggest approximately 50-60% protection against these conditions, though the evidence is less consistent than for the severe disseminated forms.

Variable protection against pulmonary TB

The most puzzling aspect of BCG vaccination is its highly variable effectiveness against pulmonary TB, particularly in adults. Studies conducted in different parts of the world have shown effectiveness ranging from 0% to 80%, with no clear explanation for this dramatic variation. Several theories have been proposed to explain this phenomenon.

One leading theory involves prior environmental exposure to non-tuberculous mycobacteria. In tropical regions where these bacteria are common in soil and water, natural exposure may either interfere with BCG's immune-stimulating effects or provide a baseline level of immunity that masks the vaccine's benefit. Another theory involves differences between BCG vaccine strains used in different countries, as the original BCG has evolved into multiple daughter strains with potentially different immunogenic properties.

Regardless of the explanation, the practical implication is that BCG cannot be relied upon to prevent adult pulmonary TB, which is the most common form of the disease and the main driver of TB transmission. This limitation is why BCG alone is not considered sufficient for TB control in any setting and must be part of a comprehensive approach including early diagnosis, treatment, and infection control.

Duration of protection

Studies following vaccinated individuals over many years suggest that BCG protection is strongest during the first 10-15 years after vaccination. Protection appears to wane gradually thereafter, though some degree of immunity may persist for much longer. This pattern aligns well with childhood vaccination, as the years of strongest protection coincide with the period of highest risk for severe childhood TB.

Some researchers have investigated whether revaccination (giving a second BCG dose) could restore or enhance protection in adolescents or adults. However, multiple studies have failed to demonstrate meaningful benefit from revaccination. For this reason, the World Health Organization and most national vaccination programs do not recommend BCG booster doses.

What Are the Side Effects and Risks?

BCG vaccine side effects are primarily local: the expected skin reaction (lump, pustule, ulcer, scar) and possible mild lymph node swelling. Serious adverse events are rare (about 1-2 per million vaccinations in immunocompetent individuals) but can include disseminated BCG infection in immunocompromised individuals.

Understanding the distinction between expected reactions and true adverse effects is crucial for BCG vaccination. The skin reaction described in the aftercare section – progressing from papule to pustule to ulcer to scar – is an expected outcome, not a side effect. This reaction indicates successful vaccination and is considered a sign that the immune system is responding appropriately.

Common and expected reactions

Beyond the local skin reaction, other common occurrences include mild swelling of the axillary (armpit) lymph nodes on the same side as the vaccination. This lymphadenopathy occurs in approximately 1-10% of vaccinated individuals and typically resolves spontaneously within 1-3 months. As long as the swelling is less than 3cm and there are no signs of suppuration, no treatment is needed.

Mild systemic symptoms such as low-grade fever, irritability, and decreased appetite may occur in the first few days after vaccination but are uncommon. These symptoms, when they occur, are typically mild and self-limiting.

Uncommon adverse effects

More significant adverse effects are uncommon but can occur. Suppurative lymphadenitis (lymph node infection with pus formation) occurs in approximately 1-5 per 1,000 vaccinations. This condition presents with a significantly enlarged lymph node (greater than 3cm), often with overlying skin changes and eventual drainage. While concerning, it usually resolves with conservative management (needle aspiration if needed) and rarely requires surgical excision.

Local abscess formation at the injection site can occur, particularly if the vaccine was inadvertently administered subcutaneously rather than intradermally. These abscesses may require drainage but generally heal without long-term complications.

Rare serious adverse effects

Disseminated BCG infection is the most serious potential complication of BCG vaccination. This occurs when the vaccine bacteria spread throughout the body, causing disease in multiple organs. Fortunately, this complication is extremely rare in healthy, immunocompetent individuals – approximately 1-2 cases per million vaccinations. However, it occurs more frequently in individuals with compromised immune systems, particularly those with severe primary immunodeficiency disorders or advanced HIV infection with very low CD4 counts.

This risk is why BCG vaccination is contraindicated in people with known immunodeficiency and why routine HIV testing may be recommended before BCG vaccination in settings with high HIV prevalence. For HIV-exposed infants born to HIV-positive mothers, vaccination recommendations depend on the infant's HIV status and the local TB burden – healthcare providers should be consulted for individual guidance.

Who Should Not Receive the BCG Vaccine?

BCG vaccination is contraindicated in people with compromised immune systems (including HIV with low CD4 counts), those with active tuberculosis, pregnant women, and individuals who have had severe reactions to previous BCG vaccination. Testing for TB infection may be recommended before vaccination in certain circumstances.

Because BCG is a live vaccine containing attenuated (weakened) bacteria, it has specific contraindications that differ from many other vaccines. The bacteria in the vaccine, while unable to cause disease in healthy individuals, can potentially cause serious illness in people whose immune systems cannot control even weakened pathogens.

Absolute contraindications

Immunodeficiency is the most important contraindication for BCG vaccination. This includes:

• Primary (congenital) immunodeficiency disorders, particularly those affecting T-cell function
• HIV infection with significant immunosuppression (specific CD4 thresholds vary by age and national guidelines)
• Current immunosuppressive treatment, including high-dose corticosteroids, chemotherapy, or biological agents
• Recent solid organ or bone marrow transplantation
• Known or suspected family history of immunodeficiency in the absence of testing to exclude the condition

Active tuberculosis or history of TB is a contraindication because the vaccine offers no benefit to someone already infected, and vaccination could theoretically interfere with diagnosis or treatment.

Pregnancy is considered a contraindication for BCG vaccination, primarily due to theoretical concerns about the live vaccine and the general principle of avoiding unnecessary interventions during pregnancy. However, inadvertent vaccination during pregnancy (before pregnancy was recognized) has not been associated with harm to the fetus.

Generalized septic skin conditions or burns are contraindications because of the risk of secondary infection and impaired wound healing at the vaccination site.

Situations requiring caution or deferral

Vaccination should be temporarily deferred in individuals with acute illness and fever until recovery. Minor illnesses without fever are not a reason to delay vaccination. For individuals receiving immunosuppressive therapy, BCG vaccination may be considered after an appropriate interval following cessation of treatment – typically 3-6 months depending on the medication, though guidance should be sought from the treating physician.

For infants born to HIV-positive mothers, the approach depends on the infant's HIV status. In many settings, BCG vaccination is deferred until HIV status is confirmed negative through appropriate testing. In high-TB burden settings where delay poses significant risk, vaccination may proceed in HIV-exposed but presumed uninfected infants – local guidelines should be followed.

What Is Tuberculosis and Why Is Prevention Important?

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that primarily affects the lungs but can spread to other organs. TB kills approximately 1.3 million people annually worldwide. Children under 5 are particularly vulnerable to severe forms. BCG vaccination is one component of TB prevention alongside early diagnosis and treatment.

To understand the importance of BCG vaccination, it helps to understand the disease it protects against. Tuberculosis remains one of the world's most significant infectious disease threats, causing more deaths than any other single infectious agent. The World Health Organization estimates that approximately 10 million people develop active TB disease each year, with about 1.3 million deaths – making TB prevention a global public health priority.

Tuberculosis is caused by Mycobacterium tuberculosis, a slow-growing bacterium that has evolved to survive within human cells, particularly the immune cells called macrophages. This intracellular lifestyle makes TB particularly challenging to treat and control. The bacteria are spread through the air when a person with pulmonary TB coughs, sneezes, or speaks, releasing tiny infectious droplets that can be inhaled by others.

How TB infection progresses

When TB bacteria are inhaled, the immune system typically responds by containing the bacteria within structures called granulomas. In most cases (approximately 90-95% of infected adults), the bacteria remain contained in this latent state – the person is infected but not sick and cannot spread the disease to others. Latent TB can persist for years or even a lifetime without causing illness.

In some cases, however, the bacteria overcome immune control and begin multiplying, causing active TB disease. This is more likely in people with weakened immune systems (such as HIV infection, diabetes, malnutrition, or immunosuppressive treatment) and in young children whose immune systems are still developing. Active pulmonary TB causes symptoms including persistent cough, fever, night sweats, weight loss, and can be fatal without treatment.

Severe TB in children

Children, particularly those under 5 years old, face special risks from TB infection. Their immature immune systems are less able to contain the bacteria, leading to more rapid progression to active disease. More concerning, young children are at higher risk of developing disseminated forms of TB where the bacteria spread through the bloodstream to multiple organs.

Tuberculous meningitis occurs when TB bacteria infect the membranes surrounding the brain and spinal cord. This devastating complication can cause permanent neurological damage including hearing loss, developmental delays, and paralysis, even with treatment. Mortality rates for TB meningitis in children approach 20-30% even with optimal treatment. Miliary tuberculosis, another disseminated form, occurs when bacteria spread throughout the body, affecting multiple organs simultaneously.

These severe childhood forms of TB are precisely what BCG vaccination protects against most effectively. While the vaccine cannot prevent all TB infection, its ability to reduce the risk of these life-threatening complications makes it a crucial intervention for at-risk children.

The global TB burden

TB disproportionately affects people in low- and middle-income countries, with eight countries accounting for two-thirds of global cases: India, Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa. However, TB can occur anywhere, and migration and travel mean that TB risk factors must be considered globally.

Drug-resistant TB poses an increasing challenge, with strains resistant to first-line medications and even extensively drug-resistant strains that are difficult and expensive to treat. Prevention through vaccination, combined with early diagnosis and complete treatment of active cases, remains essential for controlling TB globally.