WHO says we can 'write the final chapter in the story of TB.' How close are we?

The head of the World Health Organization is eager to wipe out one of the oldest and deadliest diseases.

Last week Tedros Adhanom Ghebreyesus declared: "We have an opportunity that no generation in the history of humanity has had: the opportunity to write the final chapter in the story of TB."

It's a story that began thousands of years ago. One history of TB notes: "Fragments of the spinal column from Egyptian mummies from 2400 BCE show definite signs of tuberculosis."

But as events of 2023 illustrate, there are a few chapters still to be written before Tedros's dream could come true.

Encouraging news about a familiar drug

A promising way to prevent the spread of drug-resistant tuberculosis was announced at the Union World Conference on Lung Health on Thursday in Paris.

Two clinical trials, conducted in South Africa and Vietnam, looked at levofloxacin, one of the antibiotics most commonly used to treat people who've developed drug-resistant TB. Now there's strong evidence that taking the drug can reduce the risk of developing drug-resistant strains of the bacterial disease by about 60%. Researchers say the treatment was safe and effective in both children and adults living in environments with high exposure to multi-drug resistant strains, like the two countries where the trials took place.

"Yes, you can actually prevent drug-resistant TB," says Dr. Anneke Hesseling, a TB researcher and pediatrician at Stellenbosch University who was the overall principal investigator for one of the trials. "So that is very compelling. It's like giving an effective vaccine to kids.

Hesseling hopes the new data will inform global TB guidelines going forward.

Pandemic setbacks ...

But the challenges of conquering TB remain daunting — and the pandemic is partly to blame.

As the World Health Organization puts it: "The COVID-19 pandemic has reversed years of progress made in the flight to end tuberculosis."

The focus on SARS-CoV-2 disrupted the ability of health systems to diagnose and treat people with TB – and has meant fewer resources "for essential TB services" as well as for the development of future treatments.

In a new report, WHO painted a bleak picture of the disease's toll.

Globally an estimated 10.6 million people fell ill with TB in 2022, up from 10.3 million in 2021. Before the pandemic, TB had been on the downswing.

And even though COVID dislodged TB from the notorious title of "deadliest infectious disease" based on annual death counts –TB did remain a major killer, with 1.3 million TB-related deaths in 2022.

What's more, it looks as if in 2023, with COVID deaths waning, TB could regain its top berth, says Dr. Anand Date, chief, global TB at the Centers for Disease Control and Prevention.

... and challenges that lie ahead

Other findings illustrate what a challenge it will be to fulfill Tedros's prediction:

• The U.N.'s has been to reduce TB-related deaths by 75% in the ten years from 2015 to 2025 is far from being realized. From 2015 to 2022, TB-related deaths fell only 19%.
• Of the 30 million people with TB who are targeted for preventive treatment, only 52% received such care.
• Fund-raising is lagging. In 2018, WHO set a goal of $13 billion in annual global funding for essential TB services in low- and middle-income countries during the United Nations General Assembly first-ever high-level meeting on tuberculosis. The current assessment: Less than half of that amount is available on a yearly basis.

This spring, an expert panel convened this spring by the Gates Foundation (which is a funder of NPR and this blog), discussed what needs to be done to better vanquish TB. Among the concerns is the way the disease is diagnosed.

The most common diagnostic method is 130 years old – and not highly effective. Health workers use a microscope to check sputum samples for the telltale rod-shaped bacteria that indicate TB. (Sputum is the mix of saliva and mucus coughed up from the respiratory tract.)

The microscope method is in wide use because it's the least expensive way to diagnosis TB, says Dr. Madukar Pai, head of epidemiology, biostatistics and occupational health at McGill University. Newer molecular lab tests are more sensitive to picking up an infection and can also test for drug resistance in sputum samples, he says. In a 2023 commentary in Nature Microbiology, Pai notes that "although the World Health Organization recommends molecular diagnostics as the preferred frontline testing option, only 38% of all notified cases in 2021 were tested with a WHO-recommended rapid molecular diagnostic at initial diagnosis.

As for vaccines – the only one available is effective only in infants and small children and offers roughly a 70% rate of protection..

But it's not given to older kids and adults. And if they do contract TB, access to the best drugs is spotty.

Even though there's a six-month regimen of oral drugs effective for most forms of TB, many countries can't afford to provide this type of care, says Dr. Date. The less expensive alternative is a yearlong course of 20 daily pills plus several shots. Side effects can include psychosis, extreme vomiting and loss of hearing. Patients often stop the arduous longer treatment courses, says Carole Mitnick, a professor of global health and social medicine at Harvard Medical School, "leaving them at risk for developing harder to treat [drug] resistant TB and for exposing others to the infection."

A patent expiration is welcomed by advocates

At least one drug may soon be more affordable for lower income countries.

This year the patent was due to expire on one of the more effective drugs in the six-month regimen: bedaquiline. That would mean a less expensive generic version could be manufactured.

In September, after a summer of pressure from advocacy groups and their allies, Johnson & Johnson announced that it wouldn't enforce secondary patents it took out on the drug, based on a small modification. Those patents would have meant no generic versions in the immediate future.

The news was welcomed as a boon for wider availability of the drug. According to Doctors Without Borders, "bedaquiline is the backbone of almost all treatment combinations newly recommended by the World Health Organization (WHO) for drug resistant TB" and is the most expensive in the 6-month oral regiment, "accounting for $272 out of the total $570 price. J&J currently prices the drug at $1.50 a day for an adult. That should fall to 50 cents per day and should free up more funds in lower- and middle-income countries to treat TB with the regimen," says Christophe Perrin, a pharmacist with MSF.

Another key weapon in the fight against TB will also be more affordable moving forward. The GeneXpert, a rapid laboratory diagnostic test made by Cepheid, tests a patient's sputum and can both detect TB and determine if it is resistant to certain drugs for TB. With such results, health providers avoid wasting time on drugs that won't work, Pai says. Advocacy groups were successful this year in getting Cepheid to drop its price this summer.

But it's still not an ideal test. Pai says the ultimate best test will be a home test like the ones developed for COVID-19 which could deliver comparable results to the Cepheid product.

And then ... there's $$

Developing a home test would of course take money.

And advocates are well aware of the funding shortfalls.

Mel Spigelman, president of the TB Alliance, a nonprofit working on treatments, says "the greatest barrier" to progress is "lack of funding and investment" –needed for research and development of diagnostics, drugs, health infrastructure – and vaccines.

The CDC's Date says increased funds could speed up testing of about 15 to 20 vaccines now in the pipeline, including one, M72, which is 50% effective in ongoing clinical trials. Emilio Emini, CEO of the Bill & Melinda Gates Medical Research Institute, which will conduct a late-stage clinical trial for M72 starting early next year, says, "one quarter of the global population is latently infected with TB and each year 10 million of these people develop active tuberculosis resulting in 1.5 million deaths. Given the numbers, a vaccine with even 50% efficacy can have substantial public health impact."

Ari Daniel of NPR also contributed to this story.

Fran Kritz is a health policy reporter based in Washington, D.C., and a regular contributor to NPR. She also reports for the Washington Post and Verywell Health. Find her on Twitter: @fkritz

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