Explainer: Tuberculosis

World Tuberculosis (TB) Day (March 24) commemorates the date in 1882 when Dr Robert Koch announced his discovery of Mycobacterium tuberculosis (Mtb) – the bacteria that causes TB.

Every year 10 million people fall ill with tuberculosis (TB), and 1.5 million die from the disease worldwide, despite it being both preventable and curable. Currently, it’s the second-leading cause of death from infectious disease after COVID-19. It is also the leading cause of death among people with HIV.

Over 95% of cases and deaths are in developing countries. In 2020 just eight countries accounted for two-thirds of new TB cases: India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa.

Despite TB’s prevalence across the globe, it is not widely understood.

What is tuberculosis?

Historically, TB has also been known known by other names: phthisis, consumption, the white death and the great white plague. It’s a disease with a long history, and it has even been hypothesised that the genus Mycobacterium originated more than 150 million years ago

A sputum sample containing mycobacterium tuberculosis.
Photomicrograph of a sputum sample containing Mycobacterium tuberculosis. Mtb can attack any part of the body, but usually the lungs causing Tuberculosis. It is spread when infected individuals cough or sneeze, releasing microdroplets into the air that contain the bacteria, which others then inhale. Credit: Centers for Disease Control and Prevention (CDC)

Mtb are small bacillus – a genus of gram-positive, rod-shaped bacteria – that mainly affect the lungs. Mtb are transmitted through the air in aerosols (air droplets) when ill individuals cough, sneeze, spit or talk. It only takes the inhalation of a few bacteria to become infected.

However, TB infection doesn’t always lead to disease, as it can be controlled by the immune system. In fact, people who are infected, but not ill, cannot transmit the disease.

It’s estimated that about one-quarter of the world’s population is infected by Mtb, however only 5-15% of those will fall ill with active TB disease in their lifetime. But those with compromised immune systems – such as people living with HIV, malnutrition, or diabetes, or people who use alcohol and tobacco – have a higher risk of falling ill.

Active TB disease symptoms include cough with sputum (and blood at times), chest pains, fever, night sweats, weakness, and weight loss, but can be mild for many months when it first develops. This can lead to delays in seeking care as people are unaware that they have the disease, and this can lead to further transmission to others.

Treatment and prevention

Without proper treatment 45% of HIV-negative people with TB, and nearly all HIV-positive people with TB, will die.

But TB is preventable: the Bacillus Calmette-Guérin (BCG) vaccine is widely used to inoculate children against TB, but its effectiveness wanes over time. New research has found that administering the BCG vaccine with an antibody that blocks the activity of interleukin-10 (IL-10) improves long-term protection against the disease in mice. IL-10 is a molecule that typically helps to dampen excessive inflammation during infection but has been found to actually drive TB infection.

TB is also a curable disease, and drug-susceptible strains are treated with a standard six-month course of four antimicrobials: rifampicin, isoniazid, pyrazinamide and ethambutol. Unfortunately, antimicrobial resistance continues to be a public health threat with multi-resistant TB (MDR TB) becoming resistant to both rifampicin and isoniazid (which are the two most effective first-line anti-TB drugs).

Interestingly, the first randomised controlled trial undertaken was to treat TB with the antibiotic streptomycin in 1948.

Tuberculosis infection protects mice from developing COVID-19

Magnified image of a lung that is infected with the respiratory pathogens that cause tuberculosis (tb) and covid-19.
Magnified image of a lung that is infected with the respiratory pathogens that cause tuberculosis (TB) and COVID-19. The dense blue area in the upper left is infected with Mycobacterium tuberculosis (the cause of TB), while the brown area in the lower right is infected with SARS-CoV-2 (the cause of COVID-19). Credit: Erin S. Gloag, Rosas Mejia O et al., 2022, PLOS Pathogens, CC-BY 4.0

It turns out that TB infection might have some upsides, however, as TB and COVID-19 double infections are rare in humans. Now, a new study has shown that, in mice, the immune response mounted against TB prevents co-infection with COVID-19.

Researchers infected mice with Mtb and then exposed them to the virus that causes COVID-19 infection – SARS-CoV-2 (Cov2). Monitoring them for signs of infection the scientists found that mice chronically infected with TB showed no signs of COVID-19 infection, likely because the pre-existing immune response to TB prevented the virus from proliferating in the lungs.

This could happen because TB-infected lungs contain an array of innate immune cells which restrict COVID-19 proliferation, or because TB infection stimulates an adaptive immune response that cross-reacts with Cov2 and gives heterologous immunity (immunity that develops to one pathogen after exposure to non-identical pathogens).

This may explain why countries tend to have high rates of infection with COVID-19 or TB, but not both. The researchers suggest that future research will focus on this interaction in humans.

Tuberculosis doesn’t only infect humans

But TB isn’t just a disease that affects humans. Mycobacterium tuberculosis complex (MTC) are a genetically related group of Mycobacterium species that can cause TB in humans or other animals.

This complex has at least nine members, one of which is M. bovis which causes TB in cattle. M. bovis can jump the species barrier and cause tuberculosis-like infection in humans (through unpasteurised dairy products and aerosols) and other mammals including deer, goats, pigs, cats, dogs and, significantly, badgers.

Australia was officially declared free of bovine tuberculosis in 1997, after an eradication program that lasted more than 20 years. But this is not the case for other areas of the world, including in the UK, which was the subject of the 2021 SCINEMA International Science Film Festival documentary Grey Area.

Each year in the UK thousands of wild badgers (Meles meles) are killed in an attempt to control the spread of bovine TB, as they can carry and transmit the disease to cattle – though they are not considered the highest risk for disease spread.

Grey Area looks at both sides of the debate – considering the perspectives of cattle farmers (who must cull their TB-positive animals) and those who oppose removing wildlife from their ecosystem.

You can watch the documentary here.

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