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22 March 2018

The End of Tuberculosis?

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Since 1990, mortality from tuberculosis has been reduced by almost half, but about two million people still die from it every year. Although it can be cured with antibiotics, patients are now facing a new obstacle: drug resistance. New vaccines based on training the immune system have kept the hope alive of eradicating the disease, as happened with smallpox.

Tuberculosis (TB) is an infectious disease that usually affects the lungs. It gets its name from the bacteria that cause it, Mycobacterium tuberculosis. It is transmitted from a sick person to a healthy person through the air, when the former coughs or sneezes.

A former hospital for tuberculosis in Ruppertshain, near Frankfurt. Credit: Michael König.

It was the German microbiologist Robert Koch who discovered the bacillus —bacterium with an elongated shape— that causes the disease. After having studied anthrax, Koch announced the discovery of M. tuberculosis on 24 March 1882. The microbiologist isolated the microorganism and grew it in a culture, inducing the disease in animals. The discovery earned him the Nobel Prize in Medicine in 1905.

Nimalan Arinaminpathy, a researcher at the School of Public Health at Imperial College London (United Kingdom), explains to OpenMind that: “At the beginning of the 20th century, TB care was mostly about taking people with TB (or ‘consumption’, as it was often then called) to TB sanatoria, which were well-ventilated facilities where patients could recover away from the general population.”

But these treatments had doubtful efficacy. It was not until the 1940s that the first antibiotics for the disease were developed. In 1943, American researchers Selman Waksman and Albert Schatz discovered streptomycin, the first effective drug against tuberculosis.

“This transformed TB from an effectively untreatable, effectively incurable, condition to a potentially treatable, curable condition,” summarises Richard H. Ebright, laboratory director at the Waksman Institute of Microbiology at Rutgers University (USA) to OpenMind.

Limitations to the treatment

As the molecular biologist remembers, from that moment on the sanatoriums were closed. The discovery of new drugs —isoniazid in 1951 and rifampicin in 1965— and their joint use, helped in the fight against tuberculosis.

This is a close-up of a Mycobacterium tuberculosis culture revealing this organism’s colonial morphology. Credit: CDC/Dr. George Kubica.

Nowadays, TB is treated with a combination of four antimicrobial drugs for six months, a long and expensive treatment for many patients, which in some cases they end prematurely. And not following the whole treatment contributes to creating drug resistance, one of the great obstacles to eradicating the disease. “We urgently need new ‘second-line’ drugs for treating patients with ‘multi-drug-resistant’ TB,” Arinaminpathy urges.

At present, there are three treatment problems according to Ebright: that it lasts too long, that it interferes with drugs to treat HIV (which hinders the recovery of these patients) and that there is an expansion of strains resistant to antibiotics. “We and others are actively seeking new, better anti-TB drugs that can overcome the above three limitations,” says the molecular biologist.

Train the immune system

In parallel with the development of the first drugs, the French researchers Albert Calmette and Camille Guérin devised the BCG vaccine (Bacilo Calmette-Guérin in their honour), designed to immunize newborns. Its application became widespread at the end of the Second World War.

A nurse talk with a mother in the waiting area of a hospital in Tanzania. The child must get the BCG vaccine. Credit: ICAP/Nathan Golon.

“Since then, we still have the same tools to deal with tuberculosis, which are not effective, and that’s why one third of the population is infected with Mtb and approximately 1.8 to 2 million people die of TB every year,” says Maziar Divangahi, professor of Department of Medicine, McGill University (Canada) to OpenMind.

Although there are several trials underway to validate the efficacy of new vaccines, they are not yet a reality. Divangahi and his team are working on a new path: ‘training’ the immune system to fight the bacteria. In a study published in the journal Cell, the scientists injected the BCG vaccine into the bone marrow of mice and managed to reprogram the stem cells, those responsible for generating the immune cells.

Thanks to this ‘training’, the macrophages —cells of the immune system that kill bacteria such as tuberculosis— managed to overcome the usual strategies of the bacillus and kill it. “Thus targeting the immune system is the only solution for globally reducing the rate of TB,” concludes the immunologist.

Difficult to eradicate

Although the World Health Organization has postulated the end of the epidemic by 2030, specialists claim that much more research is needed to achieve this and to improve the standard of living and health of large segments of the population. In 2016, only seven countries accounted for 64% of the mortality from the disease: India, Indonesia, China, the Philippines, Pakistan, Nigeria and South Africa.

Tuberculosis occurs in every part of the world, but the majority of cases are in Asia (61%) and Africa (26%). Credit: OMS

Could TB be eradicated like smallpox, a milestone that was achieved in 1980? “Extremely unlikely, considering that almost one third of human population is latently infected,” Mihai Netea, from the Department of Internal Medicine at the Radboud University Medical Centre in the Netherlands, tells OpenMind.

This means that many people have the bacteria but have not yet become ill or transmitted it. The problem is that when it develops, symptoms such as cough, fever or weight loss can be mild for many months, which causes it to go unnoticed, leading to it being transmitted before it is treated. Thus, unlike smallpox, TB is unlikely to be relegated to the past any time soon.

 

Laura Chaparro

@laura_chaparro

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