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But I’ve had my BCG, I can’t have TB!

17/10/2019

 
“I think my patient has TB but they have had BCG in the past so I was wondering what might mimic TB?” asked the junior doctor.
 
“They could have TB” replied the Microbiologist.
 
“But they’ve had their BCG” replied the junior doctor, gosh he’s not listening, he’s probably playing spider solitaire, thought the junior doctor, as he could hear clicking in the background.
 
“Yes, but they could still have TB” repeated the Microbiologist.
 
Deep inhale… “Yes, but they have a BCG scar on their arm, they have been immunised in the past, so they can’t have TB” stated the junior doctor firmly.
 
You’d think the junior’s right, wouldn’t you? But I’m blogging on it so, who is right? Can you get TB having been immunised with BCG? Let’s talk about BCG first…
BCG vaccine
​What is BCG?
BCG (Bacillus Calmette Guérin) is a live attenuated form of the bacterium Mycobacterium bovis. BCG was first used in humans all the way back in 1921. It was developed in 1908 by two French Bacteriologists, Albert Calmette and Camille Guérin. Since its discovery, BCG has been given to over 3 billion people making it the most widely used vaccine in the World.
 
The bacterium in the vaccine has been weakened so that when it is injected into a human it triggers an immune response without causing an infection. M. bovis is part of what is known as the Mycobacterium tuberculosis bacteria complex or MTB complex; this is a group of similar bacteria which can all cause tuberculosis-like illness in humans. The immune response to M. bovis provides protection from M. bovis infection as well as the other MTB complex bacteria, especially M. tuberculosis. It also protects against the cause of leprosy (M. leprae), Buruli ulcer (M. ulcerans) and M. avium which are all mycobacterial infections.
 
Weirdly, since 1977, BCG vaccine has also been used in the treatment of bladder cancer. In this form of immunotherapy BCG is instilled directly into the bladder. I have always struggled to understand why someone originally thought it would be a good idea to stick M. bovis into a person’s bladder, as this surely couldn’t have been done by accident!
 
How is BCG administered?
In my experience BCG is one of the trickiest vaccines to give. It has to be injected intradermally near the deltoid muscle insertion of the upper left arm, which is difficult, especially in wriggly babies. Essentially the small needle is inserted almost parallel to the skin with the bevel face up and when the bevel is covered the 0.05-0.1ml of BCG is injected so that a small bleb is raised (what’s a bleb!!?? see below Editor Chief in Charge…). Take it from me, this is not easy; sometimes the patient moves and the needle comes back out, sometimes they move and it goes further in. Back in my paediatric days I had to give hundreds of BCGs and it would give me nightmares!
Bleb BCG vaccine
​Usage in the UK
There is currently no routine vaccination program with BCG in the UK. Back in the day BCG was given to all teenagers but now BCG vaccination is only targeted at groups at high risk of developing tuberculosis (TB):
  • Newborns born in the UK with parents or grandparents who were born in a country with an incidence of TB ≥ 40/100,000 population
  • Children <5 years old who were not vaccinated at birth but born in the UK and have parents or grandparents who were born in a country with an incidence of TB ≥ 40/100,000 population
  • Children <5 years old who live in an area of the UK with an incidence of TB ≥ 40/100,000 population
  • Children 6-16 years old who live in an area of the UK with an incidence of TB ≥ 40/100,000 population need to be tested and shown negative for previous exposure to TB before vaccination is given
  • Children <16 years old born in a country with an incidence of TB ≥ 40/100,000 population need to be tested and shown negative for previous exposure to TB before vaccination is given
 
So how do you get TB if you have been immunised with BCG?
 
Efficacy
It might surprise people to know that the BCG vaccination is not actually that effective at preventing TB! No vaccination is 100% effective but a systematic review of BCG vaccine showed overall protection from TB infection was only 19%. This went as high as 28% for people vaccinated within a few days of birth (BCG is more effective the earlier in life it is given) but even a 28% efficacy still seems pretty rubbish, so why is BCG given?!
 
Well the reason for giving the vaccine is to prevent “TB disease” where the bacterium causes symptoms and tissue destruction (e.g. damage caused by cavitation of lung tissue or destruction of a joint).
 
If a vaccinated person acquires M. tuberculosis bacterium the body’s response is to immediately “contain” the bacterium (often walled off within a small area of tissue usually within the lung which presents with no symptoms) thus the “containment” prevents dissemination of the bacterium throughout the body (e.g. pulmonary TB’s chronic cough, TB meningitis’ headache or TB septic arthritis’ joint pain). Therefore you can still get TB if you have had the BCG vaccine (similar to being colonised but as the infection is walled off it poses no risk to the individual or others); unvaccinated people would be more likely to get TB disease and present with symptoms and tissue destruction.
 
Studies from the UK have shown BCG to be 70-80% effective at preventing TB disease. However this still means that 20-30% of vaccinated people who acquire TB will develop symptoms.
BCG vaccine
Click for larger image
​BCG is also very good at preventing TB from disseminating and therefore reduces mortality from TB.
 
Oddly, there are lots of studies that have shown that the closer you move towards the Equator the less effective BCG is; in some equatorial countries BCG provides no protection. It’s not clear why this happens but the main theory is that populations around the Equator have a higher rate of non-tuberculous mycobacterial exposure which may modify the immune response in people given BCG, therefore they don’t react to the vaccine.
 
How long does BCG protection last?
The average duration of protection from TB disease of BCG given around birth is 10-15 years. After this, protection begins to wain but some studies have shown that partial protection can occur up to 50-60 years. So my BCG vaccination back in the 1980s probably no longer protects me from TB, and as I did not grow up in a high risk population (small village in Sussex) I probably didn’t need it in the first place! However if I have come into contact with TB (which I would have working around respiratory wards) it may mean I have not contracted or disseminated my TB and I might be in the lucky percentage that has cover for 50-60 years? I therefore still think BCG has a value.
 
Complications
BCG is a live vaccine and shouldn’t be given to any person at risk of opportunistic infections or who is immunocompromised. In this situation the BCG’s M. bovis bacterium can cause disseminated BCG infection, which can be life-threatening.
 
The most common complication, occurring in 95% of recipients of BCG, is a localised reaction; a bluish-red papule occurs accompanied by pain and swelling which may become ulcerated in 70% of recipients but both usually heal after about 6 weeks leaving a small scar. The BCG scar everyone is familiar with! So the scar isn’t from kids punching the vaccination site then?!? No, and that is not encouraged, but telling teenagers not to do something usually has the opposite effect!
 
A more rare complication is localised extension or dissemination of BCG to cause osteitis (inflammation of bone) or osteomyelitis (infection of bone). This is reported to occur in 30 per million vaccinations. This infection should be treated like any other disseminated M. bovis infection.
 
So, is BCG a useful vaccine? It reduces the incidence and mortality from TB BUT it doesn’t stop everyone getting TB disease; REMEMBER 20% of vaccinated people who acquire TB will develop symptoms. So if you see a patient who you think might have TB but they have been vaccinated then you might still be right, they could still have TB! And, if you have had your BCG remember it doesn’t prevent you from getting TB either.

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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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