Study helps explain how a parasitic worm increases TB risk

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Studies have shown that infection with helminths – a form of parasitic worm – can increase susceptibility to tuberculosis in those with a latent form of the disease. Now, new research sheds light on why this is, opening the door to new strategies to prevent the disease.

[Head of a tapeworm]
Helminths are worm-like parasites that commonly reside in the gastrointestinal tract of humans.

Study author Shabaana A. Khader, PhD – associate professor of molecular microbiology at Washington University in St. Louis – and colleagues publish their findings in The Journal of Clinical Investigation.

According to the World Health Organization (WHO), around a third of the world’s population is infected with latent tuberculosis (TB), meaning they have been infected with the bacteria that causes it – Mycobacterium tuberculosis – but have not yet become ill with the disease.

There is a 10% lifetime risk of becoming ill from TB for individuals infected with its bacteria, though previous research has shown this risk increases for people who are also infected with helminths.

Helminths are worm-like parasites that commonly reside in the gastrointestinal tract of humans. Examples of helminths include hookworms and whipworms. Helminth infections are most common in developing countries; they are often transmitted through eggs present in human feces, which contaminate soil in areas of poor sanitation.

Around 1.5 billion people worldwide are infected with soil-transmitted helminth infections, according to WHO, and many of these infections occur in places with high prevalence of TB, such as sub-Saharan Africa.

“Scientists and doctors have known that having both infections – this parasitic worm and tuberculosis – results in increased susceptibility to severe lung disease than having TB alone,” says Khader. However, the mechanisms behind this association have been unclear.

“If we don’t understand why co-infection increases the susceptibility to TB, it is difficult to know how to deal with the situation,” Khader notes.

Molecule produced by helminth eggs increases TB susceptibility

Researchers have hypothesized that the helminth parasite increases susceptibility to TB by impairing the immune response required to prevent TB development.

However, in their study, Khader and colleagues found that a molecule produced by the eggs of the parasite – called arginase-1 – is to blame for increased TB susceptibility, rather than the parasite itself.

In laboratory mice, the researchers found that the eggs of the helminth parasite produced a signal that led inflammatory immune cells to produce arginase-1, which the team found drove inflammation rather than blocking the immune response that stops latent TB from progressing.

On analyzing mice that were engineered to have immune cells unable to produce arginase-1 and that were infected with both TB and the parasitic worm, they found no inflammatory response was produced.

“When you knock out this immune cell’s ability to make arginase-1, you change the whole dynamic of the disease,” explains Khader. “Without the arginase, the inflammatory immune cells don’t come into the lungs. In other words, you can make the immune system behave like the parasite is not there.”

Hope for new preventive treatments for TB

Next, the team assessed blood samples and chest X-rays of humans who were infected with both the parasitic worm and TB.

They found that patients with higher arginase activity in the blood had greater lung damage than those with lower activity.

Fast facts about TB

  • Last year, around 9.6 million people worldwide fell ill with TB and 1.5 million died from the disease
  • More than 95% of TB deaths occur in low- and middle-income countries
  • Between 2000-14, around 43 million lives were saved through TB diagnosis and treatment.

Learn more about TB

The researchers note that in mice infected with both the parasitic worm and TB, there was not a strong correlation between increased lung damage and the amount of TB bacteria present, further suggesting that the parasite is independently triggering its own inflammatory response to increase TB susceptibility.

These findings, the team says, suggest that inexpensive, widely available anti-parasitic medication could be used to prevent TB in areas where both the helminth parasite and TB are common.

What is more, the researchers say the findings may help push forward the development of a new vaccine for TB, though they note they did find evidence in their study that a person’s immune response is dependent on individual genetics.

“If we’re making vaccines, we need to ask whether the new vaccines will work if someone is having one type of immune response versus another,” says Khader. “We plan to test vaccines in co-infections with both parasites and TB to see if such a vaccine could be effective even when the body mounts an immune response that is inflammatory rather than protective.”

Earlier this year, Medical News Today reported on a study suggesting a common medication used to treat glaucoma could also be effective against TB.