Stopping the Tuberculosis Pandemic
“Years of neglect have led to an unbearable situation in which TB kills more than 4,000 people a day—more than HIV and malaria combined—and still too few decision makers, donors, and stakeholders care about TB.”
- Lucica Ditiu, MD, Executive Director, Stop TB Partnership
“So I can't show you how, exactly, health care is a basic human right. But what I can argue is that no one should have to die of a disease that is treatable."
- Paul Farmer, MD, PhD, American medical anthropologist and physician
Each year, tuberculosis (TB) afflicts 10 million people and kills 1.5 million—making it the world's top infectious disease killer. Yet it is a preventable and curable disease.
On September 22, 2023, at a “high-level meeting on the fight against tuberculosis” at the United Nations (UN), applause broke out when world leaders, representatives of civil society, and other stakeholders approved a declaration to advance efforts to stop TB by 2030. As I’ve written on TB before, see February 5, 2020 post, “TB or Not TB: Is Tuberculosis Finally on Its Way Out?,” in this week’s Germ Gems post, I summarize recent advances in TB management and provide an assessment of what it’s going to take to achieve the UN’s goal to stop the TB pandemic by 2030.
Recap of TB. TB is an incredibly interesting and very complex bacterial infection caused by Mycobacterium tuberculosis, the tubercle bacillus. The typical symptoms of TB include:
a persistent cough that lasts more than three weeks and usually brings up phlegm, which may be bloody
high temperature (fever)
tiredness and fatigue
loss of appetite.
It is an ancient disease. Scientists recently discovered TB in the remains of people who died in Syria 10,000 years ago indicating that it’s even older than originally thought. (See “The surprising, ancient origins of TB, humanity’s most deadly disease” New Scientist, June 2021.) For thousands of years, TB has been a global scourge killing massive numbers of people. For example, in the 1700s, it caused 25% of all deaths. It has been called “the White Plague” due to the paleness of patients or “consumption” because many of its victims were severely emaciated.
The tubercle bacillus (Mycobacterium tuberculosis) that causes TB is transmitted from person to person mainly by respiratory droplets. Very rarely, however, other routes of infection can occur. This is because M. tuberculosis, which starts out in the lungs, can disseminate early on in infection throughout the body, seeding many organs, including the brain, kidneys, gastrointestinal tract, heart, skin, and bone marrow, where it lays dormant for years. For example, in August 2023 an outbreak of TB was reported in five patients who had received contaminated bone graft material.
It is this lifestyle of M. tuberculosis that makes TB so tricky to manage, that is, in addition to causing disease (illness), the tubercle bacillus much more commonly causes an asymptomatic infection called “latent TB infection (LTBI).” It’s estimated that roughly one quarter of the world’s population is infected, the vast majority of whom have LTBI. If cell-mediated immunity becomes compromised, for example, by immunosuppressive medications, HIV infection, or old age, the tubercle bacillus can reactivate and cause serious illness.
Recent advances. In the past several years, scientists have made significant progress in diagnosing, treating and preventing TB.
In the diagnostic arena, rapid molecular diagnostic tests, such as the Xpert MTB/RIF and Truenat assays are available. Both have high diagnostic accuracy and improve early detection of TB, including rifampin-resistant strains. In addition, there is an interferon gamma release assay (IGRA) used to identify TB infection, including LTBI.
While newer approaches to treating TB such as immune activation and phage therapy are showing promise, right now antibiotic therapy is recommended for treating both active TB and LTBI. Isoniazid and rifampin are the antibiotics most commonly used. But, multiple drug-resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB]) are a challenge— one of the most urgent challenges facing global TB control. And even when there is an effective and lifesaving drug for drug resistant TB, cost can be an issue. Recently, pressure from activists, such as YouTube star John Green, persuaded the pharmaceutical giant Johnson and Johnson to lower the cost of its patented drug betaquiline (a lifesaving medicine for drug-resistant TB).
If the goal is to stop TB by 2030, advances in TB prevention are of utmost importance. The BCG vaccine may prove beneficial. This vaccine has broad immunological properties. (I discussed these in my July 21, 2021 Germ Gems post, “BCG—the Most Widely Used Vaccine in the World: Can It Be Useful in the Battle Against COVID-19?” Subsequent studies showed that multi-dose BCG had a 92% efficacy versus placebo against COVID-19.) In a rhesus monkey TB model, recent studies showed that when the BCG vaccine is administered intravenously it conferred robust protection against TB.
A vaccine effective specifically against pulmonary TB may also be on the horizon. On June 28, 2023, in the article “’Gamechanging’ TB vaccine within reach of $500 million pledge to run final trials,” the Open Society Foundation reported that the Bill & Melinda Gates Foundation and Wellcome Trust would provide funding to advance a very promising M72/AS01E (M72) TB vaccine through a Phase III clinical trial. If proven effective, M72 could be the first new vaccine in more than 100 years to prevent pulmonary TB.
Social determinants of TB. TB kills about 4,300 people per day most of whom live in poverty. Many do not have access to health care or even sufficient food. To achieve the U.N.’s goal to stop TB by 2030, food may be a key part of the solution.
In the August 19, 2023 Lancet article, “Food: the tuberculosis vaccine we already have,” the authors provide a convincing case that inexpensive nutritional interventions are an integral component of TB elimination. In the same Lancet issue, other researchers provide further support for this premise with evidence from a field-based, randomized controlled trial in India that showed that nutrition intervention was associated with a substantial reduction (39-48%) in the incidence of TB.
When reading these articles, my mind flashed back to the incredible career of Dr. Paul Farmer, a Harvard University anthropologist, infectious diseases specialist, and global health expert. (Farmer died prematurely at the age of 62 in Rwanda in February 2022.) In his 1999 book, Infections and Inequalities: The Modern Plagues, Farmer spelled out the profound impact of poverty and inequality on infections, such as TB and HIV/AIDS. Unfortunately, there isn’t a vaccine against poverty. If one were to be discovered, it would not only help the UN achieve its goal of stopping TB by 2030 but it would garner an unlimited number of Nobel Prizes.