"Towards Eradicating Tuberculosis: Progress, Challenges, and the Ongoing Battle Against an Ancient Foe"

In the bustling clinics of Mumbai, India, where dedicated doctors scrutinize chest x-rays of tuberculosis patients, a global call for the eradication of this age-old and lethal infectious disease echoes. The head of the World Health Organization (WHO), Tedros Adhanom Ghebreyesus, recently declared an unprecedented opportunity for humanity: "We have the opportunity to write the final chapter in the story of TB."

This narrative traces back thousands of years, with evidence of tuberculosis found in fragments of the spinal column from Egyptian mummies dating back to 2400 BCE. However, despite this long history, the latest events of 2023 reveal that there are still chapters to be written before Tedros's visionary dream can become a reality.

A ray of hope emerged at the Union World Conference on Lung Health in Paris, where a promising development in the fight against drug-resistant tuberculosis was unveiled. Clinical trials in South Africa and Vietnam examined the effectiveness of levofloxacin, a commonly used antibiotic for drug-resistant TB. The results showed strong evidence that this drug could reduce the risk of developing drug-resistant strains by approximately 60%. Dr. Anneke Hesseling, a prominent TB researcher and pediatrician at Stellenbosch University, emphasized the significance of this breakthrough, likening it to providing an effective vaccine to children.

However, amidst these encouraging strides, the challenges in conquering TB loom large, exacerbated in part by the ongoing COVID-19 pandemic. The World Health Organization highlights the pandemic's detrimental impact, stating that it has reversed years of progress in the fight against tuberculosis. The focus on combating SARS-CoV-2 has disrupted health systems' ability to diagnose and treat TB patients, diverting essential resources away from TB services and hindering the development of future treatments.

In a sobering new report, the WHO paints a bleak picture of the toll that tuberculosis continues to take on global health. As the world grapples with the dual challenges of TB and the lingering effects of the pandemic, the journey to eradicate this ancient foe remains both compelling and complex.

"Navigating the Complex Landscape: Challenges and Innovations in the Battle Against Tuberculosis"

In 2022, a staggering 10.6 million individuals worldwide were diagnosed with tuberculosis, marking an increase from the previous year's 10.3 million cases. This surge came as a disruption to the downward trend TB had been experiencing prior to the COVID-19 pandemic. While the global focus shifted towards combatting the novel coronavirus, tuberculosis, though no longer holding the title of the "deadliest infectious disease" based on annual death counts, continued to exert its deadly toll with 1.3 million TB-related deaths in 2022.

As the world emerges from the grip of the pandemic, Dr. Anand Date, Chief of Global TB at the Centers for Disease Control and Prevention, warns that TB could regain its position as a leading cause of death in 2023, with COVID-19 deaths gradually diminishing.

Addressing the challenges in fulfilling the World Health Organization's vision to "write the final chapter in the story of TB," experts convened by the Gates Foundation in spring 2023 delved into the hurdles that must be overcome. A crucial concern discussed was the outdated diagnostic method for TB, which has remained largely unchanged for 130 years. Health workers rely on microscopic examination of sputum samples, searching for the characteristic rod-shaped bacteria indicating TB. Dr. Madukar Pai of McGill University emphasizes that while this method is widely used due to its cost-effectiveness, it lacks the sensitivity of newer molecular lab tests. These advanced tests not only detect infections more accurately but also identify drug resistance in sputum samples.

In a commentary published in Nature Microbiology, Dr. Pai highlights a stark reality: despite the World Health Organization's endorsement of molecular diagnostics as the preferred frontline testing option, only 38% of notified TB cases in 2021 underwent WHO-recommended rapid molecular diagnostics at initial diagnosis.

The uphill battle against TB is further complicated by limitations in available vaccines. The existing vaccine, effective only in infants and small children, provides approximately 70% protection. However, it is not administered to older children and adults. Additionally, if they do contract TB, access to optimal drugs remains inconsistent.

As the world grapples with the resurgence of TB and the need for innovative solutions, the journey towards conquering this ancient disease proves to be a multifaceted and challenging endeavor.

"Affordability and Accessibility: Striving for Equitable TB Treatment Amidst Funding Challenges"

While a six-month regimen of oral drugs stands as an effective treatment for most forms of tuberculosis, the financial constraints faced by many countries hinder their ability to provide this type of care, according to Dr. Date. The more economical alternative involves a yearlong course comprising 20 daily pills and several shots, a grueling process with potential side effects such as psychosis, extreme vomiting, and loss of hearing. Carole Mitnick, a professor of global health and social medicine at Harvard Medical School, notes that the challenges posed by these arduous longer treatment courses often lead patients to discontinue, placing them at risk for developing more challenging drug-resistant TB and exposing others to infection.

A ray of hope emerges as the patent for one of the more effective drugs in the six-month regimen, bedaquiline, was due to expire this year. The expiration would pave the way for a more affordable generic version to be manufactured. In a significant move, Johnson & Johnson announced in September that it would not enforce secondary patents on bedaquiline, a decision celebrated by advocacy groups. Bedaquiline, described by Doctors Without Borders as the backbone of the World Health Organization's recommended treatment combinations for drug-resistant TB, currently accounts for a significant portion of the regimen's cost. With the expected price drop from $1.50 to 50 cents per day, more funds are anticipated to become available in lower- and middle-income countries for comprehensive TB treatment.

Another crucial tool in the fight against TB, the GeneXpert, a rapid laboratory diagnostic test by Cepheid, is poised to become more affordable. This test not only detects TB but also determines drug resistance, enabling health providers to avoid ineffective drug treatments. While advocacy groups successfully lobbied for a price reduction this summer, there's recognition that an ideal test would mirror the home tests developed for COVID-19. However, the development of such a home test requires funding, and advocates are acutely aware of the financial shortfalls that must be addressed in the ongoing battle against tuberculosis.

"Breaking the Funding Barrier: Paving the Way for Progress in Tuberculosis Research and Treatment"

Mel Spigelman, the president of the TB Alliance, a nonprofit dedicated to advancing tuberculosis treatments, identifies a critical obstacle to progress: the "greatest barrier" lies in the insufficient funding and investment required for research and development in diagnostics, drugs, health infrastructure, and vaccines. According to Spigelman, addressing this financial shortfall is paramount to overcoming the challenges posed by tuberculosis.

Dr. Date from the Centers for Disease Control and Prevention (CDC) emphasizes that increased funds could expedite the testing of approximately 15 to 20 vaccines currently in the pipeline. Among these, the vaccine M72, which has shown a 50% efficacy in ongoing clinical trials, holds particular promise. Emilio Emini, CEO of the Bill & Melinda Gates Medical Research Institute, shares plans for a late-stage clinical trial for M72, set to commence early next year. He underscores the urgency by revealing that a quarter of the global population is latently infected with TB, with 10 million of these individuals developing active tuberculosis each year, resulting in 1.5 million deaths. Emini asserts that even a vaccine with 50% efficacy can have a substantial public health impact given the staggering global numbers.

As the world grapples with the persistent challenges posed by tuberculosis, the need for increased funding emerges as a linchpin for advancing research, developing effective treatments, and ultimately curbing the impact of this pervasive disease. This story, contributed to by Ari Daniel of NPR, sheds light on the importance of financial support in the ongoing battle against tuberculosis. Fran Kritz, a health policy reporter based in Washington, D.C., and a regular contributor to NPR, the Washington Post, and Verywell Health, can be found on Twitter at @fkritz.

In conclusion, the battle against tuberculosis stands at a crucial juncture where progress hinges significantly on overcoming the formidable barrier of inadequate funding. Mel Spigelman, president of the TB Alliance, underscores the urgent need for financial investment across research, drug development, diagnostics, health infrastructure, and vaccines. Dr. Date from the CDC highlights the potential acceleration of vaccine testing with increased funds, pointing to promising candidates like M72, which has demonstrated a 50% efficacy in ongoing clinical trials.

Emilio Emini, CEO of the Bill & Melinda Gates Medical Research Institute, emphasizes the staggering global impact of tuberculosis, with a quarter of the population latently infected and 10 million developing active tuberculosis annually, resulting in 1.5 million deaths. The prospect of a vaccine, even with modest efficacy, could have substantial public health implications given the scale of the challenge.

As the world grapples with the persistent threat of tuberculosis, the call for increased financial support echoes loudly. It is a clarion call to stakeholders, policymakers, and global communities to recognize the urgency of bolstering resources, enabling researchers and organizations to make strides in diagnostics, treatments, and preventive measures. The journey toward eradicating tuberculosis requires a united front, with funding as the linchpin for turning the tide against this ancient and persistent global health challenge.