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Tuberculosis Vaccine Screening Links T-cell Response To ALS Risk

People with negative responses to a tuberculin skin test a few years after being vaccinated against tuberculosis had a significant, 25% lower risk of developing amyotrophic lateral sclerosis (ALS) in their lifetime, according to a study in Norway.

Because a positive reaction is linked to the recruitment of T cells — a type of immune cell involved in memory immunity and responses to vaccines — these findings may support the role of T-cell responses in the development of ALS, its researchers said.

The study, "Tuberculin responses after BCG vaccination predict amyotrophic lateral sclerosis risk," was published in the journal Brain, Behavior, & Immunity – Health.

Immune system response to motor neuron damage known in ALS

In people with ALS, inflammatory cells such as T-cells and microglia are known to locate in brain and spinal cord regions where motor neurons are damaged. However, it remains unknown if this immune cell infiltration is an actual contributor to disease onset and progression, or if it is a consequence of other disease processes.

"If T cells play a primary role, one would expect to find evidence of altered regulation of T cell responses before ALS development," the researchers wrote.

To better understand T-cells' role in ALS, researchers at the University of Oslo and Akershus University Hospital used data from a compulsory screening program of people in a Bacillus Calmette–Guerin (BCG) vaccine drive to prevent tuberculosis. Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis bacteria that mainly affects the lungs.

Individuals were monitored regularly to determine if they had a positive immunological response to the vaccination and remained protected from tuberculosis, which was widespread in Norway in the early 20th century.

Monitoring was done using the tuberculin skin test, or TST, in which a small amount of tuberculin — a protein from the bacteria that causes tuberculosis — is injected into the skin. The skin reaction was evaluated for size, hard area, or swelling after a few days.

Usually, BCG vaccination results in a positive TST test, but some vaccinated people fail to develop an immune response against tuberculin, meaning their immune system is not equipped to fight the tuberculosis bacteria in case of an infection.

While seemingly unrelated, immune mechanisms involved in a TST response are relevant to ALS because both involve the recruitment of T-cells, enabling researchers to compare T-cell responses in people who later ended up developing ALS with those who didn't.

From the screening program data, the scientists identified nearly 325,000 people, born between 1910 and 1955, who received a BCG vaccination and had a TST examination one to 15 years afterwards.

Over a median of 40 years of follow-up, 496 of them developed ALS.

Negative skin test results indicate a weaker adaptive immune response

People with a negative TST result had a 25% lower risk of ALS, compared with those with a positive TST reaction, results showed. This association was observed throughout the follow-up, and it was still present four decades later.

Notably, the association between a negative TST test result and reduced ALS risk was even greater as the time between vaccination and TST decreased. For example, patients with a negative TST result within 10 years of vaccination were 33% less likely to develop the disease, and those with a negative test within five years of getting the vaccine were 43% less likely.

In a subgroup of 228,900 people who were vaccinated during adolescence (ages 12 to 17), researchers identified 275 cases of ALS over a median follow-up of 43 years. Regardless of the interval between vaccination and screening, patients in this group with a negative TST reaction had a 33% lower risk of developing ALS.

"We conclude that on population level, a weak secondary adaptive immune response, as measured by TST following BCG vaccination, is associated with low ALS risk several decades later. These results support a primary role for immune regulation in ALS development," the researchers wrote.

The inability to exclude possible confounding factors that could impact the risk for ALS was noted as a study limitation.

Gene Target For Tuberculosis Identified

For the first time, a gene linked to the disease tuberculosis has been identified which, is held to control the onset of the disease. The gene NRAMP1 is known to be involved in a number of other diseases like leprosy and rheumatoid arthritis.

Different forms of the gene are held to control the speed at which tuberculosis develops. Certain factors are already known to increase the speed at which people develop tuberculosis. HIV and tuberculosis are synergistic partners and appear to accelerate disease progression when they occur together.

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Tuberculosis is a very common disease, affecting about one-third of the world's population. Of the estimated two billion people infected, only 5%-10% actually develop tuberculosis disease in their lifetime. The other 90%-95% appear to contain the infection in a dormant state and do not manifest the disease for reasons not yet understood.

Understanding the basic pathways of pathogenesis such as these offers new targets and policies for disease prevention. This is just a starter kit. We still have a long way to go with respect to the cure and therapeutic intervention.

Tuberculosis Testing Involves More Than 600 Contacts, Says SNHD

No known additional active tuberculosis cases have developed — so far — from a person with active TB who was at 26 Clark County School District campuses and a training center in recent weeks, according to health officials.

More than 600 contacts have been identified as part of the investigation, according to the Southern Nevada Health District.

"This is currently a contact investigation, not an outbreak investigation," said health district spokeswoman Jennifer Sizemore. "We are notifying people they need to get tested because they may be infected with latent TB not necessarily sick with active TB disease."

Testing has begun for students and staff at more than a dozen schools who had close contact with the infected person, according to the health district.

Principals at 26 CCSD schools sent letters to parents last week to advise them of an active tuberculosis case on campus, but all letters were referring to the person who visited their campus, Sizemore said.

Some staff members and the entire student body at Ruthe Deskin Elementary School in the northwest valley will be tested in January because of the amount of potential exposure to the infected person, Sizemore said.

Some students and staff at 17 other campuses and the training center who had close contact with the infected person will be tested starting this week. In most cases, people at each school who had close contact with the infected person will be tested, Sizemore said.

An earlier unrelated active TB case at Palo Verde High School is being investigated with testing of those who had close contact scheduled for January, Sizemore said.

A Las Vegas family doctor detailed a wide scope of tuberculosis facts and possible scenarios for community members to be aware of.

"A TB outbreak is serious in that we as Americans are not vaccinated like many in other countries (due to cost of the vaccine, efficacy and its potential interference with TB skin test reactivity/results), so we're vulnerable," wrote Dr. Daliah Wachs, a board-certified family practitioner in Las Vegas and host of a syndicated talk show about medicine.

The scenarios range widely from health officials "caught it extremely early" to "hundreds of people may have been exposed and could then spread the potentially fatal disease to colleagues, family and friends," Wachs says.

Wachs answered critical questions about TB, treatment and other factors:

What is tuberculosis?

Tuberculosis has been one of the deadliest lung infections in history. With recent medical advances, death rates have drastically dropped, but currently a fourth to a third of the world's population is infected with TB and worldwide it ranks in the top three causes of death. TB, known earlier as consumption, was discovered in 1882 by Robert Koch. It is caused by the bacteria, Mycobacterium tuberculosis. It's an acid-fast staining bacteria (significant for diagnosis purposes) and it needs oxygen to survive, hence the lungs offer the perfect environment for the pathogen to grow.

How is TB passed?

TB is passed by aerosol/droplet transmission so when someone coughs, sneezes, or passes respiratory fluid they could transmit TB. It may also grow on contaminated surfaces.

What are the symptoms of TB infection?

Symptoms may include acute or chronic cough, coughing up blood (hemoptysis), pain with coughing and/or breathing, weight loss, fatigue, fever, night sweats, chills and loss of appetite.

How is TB diagnosed?

If a patient has any of the above symptoms the first test needed is a chest X-ray which may show an effusion (fluid), consolidation (area of the lung obscured with fluid/infection infiltrate) lymphadenopathy (lymph node swelling). Ghon's lesions (a necrotic, calcified focus of infection) and/or a Ghon's complex (a Ghon's lesion with lymph node involvement) may be seen as well.

Cultures of the sputum/mucous can be done but they take four to six weeks. Acid-fast staining can be done on the sputum which will give a quicker diagnosis.

The Mantoux, purified protein derivative (PPD) skin tests are given subcutaneously in the arm and read 48-72 hours later, looking for a red marking.

Two steps are done a week apart to ensure against false negatives.

But even more efficient is the QuantiFERON blood test.

Can TB spread?

Yes, 15-25 percent of the cases can be extrapulmonary. Meaning "beyond the lung," one could have extrapulmonary TB, with infections affecting the gastrointestinal tract, genitourinary tract, lymph nodes and lining of the brain.

Sometimes TB may disseminate throughout the lungs and body, this is called Miliary TB. Miliary TB can spread to the above areas as well as heart, brain, and bone.

TB may also become "latent" and reactivate at a later date.

Conditions that foster spread

From a community standpoint, since TB is spread by aerosol/droplet transmission it can spread easily, especially during the cough/cold/COVID season.

Who is at risk for acquiring TB?

High risk populations include: Healthcare workers, prisoners, homeless shelters, nursing homes, those dependent on alcohol, chronically debilitated, those with HIV, immunocompromised children and adults.

Contact Marvin Clemons at mclemons@reviewjournal.Com. Dr. Wachs radio show can be heard locally on KDAWN, (101.5 FM) from 8 to 10 p.M. Weeknights.

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