The History of Tuberculosis Diagnostics

Mycobacterium tuberculosis (tuberculosis, or simply TB) has been with us for millennia. Records show at least as far back as 9,000 years, but molecular analysis suggest that human infections began possibly over 70,000 years ago, while it’s possible the species itself has been around for as long as 3 million years.

The illness was first named “tuberculosis” in 1834. It has gone by many names over the centuries—phthisis, the white plague, consumption—but regardless of the name, we know it has been endemic since ancient times. While these days it is well understood that active TB resides in the lungs and spreads through the air (as opposed to latent TB, which shows no symptoms and can’t be transmitted from one person to another, but which may develop into an active infection), this hasn’t always been the case. In the 1800s debates raged as to whether it was infectious, hereditary, a form of cancer—or even spread by vampires.

One thing that has remained unchanged as far back as historical records extend and irrespective of advances in modern healthcare is that TB has always been a major and persistent burden on public health. It has been associated with a high mortality rate for centuries, if not thousands of years.

8.2 million people were newly diagnosed with TB worldwide in 2023, a significant increase from 7.5 million new cases reported in 2022. In 2023 the disease was believed to be responsible for 1.25 million deaths, having supplanted COVID-19 and retaken its place on top of the list of the most deadly infectious diseases.

Thousands of years ago, the only way to diagnose TB was through symptoms. These same tuberculosis symptoms persist in patients today: coughing up blood, night sweats, and a fever. But then, as now, too many other viral or bacterial infections share similar symptoms and relying on symptoms alone has always been insufficient to diagnose the disease.

One of the most significant milestones in TB diagnosis came on March 24, 1882, when Dr. Robert Koch presented his discovery of M. tuberculosis to the Berlin Physiological Society. Dr. Koch later grew the organism in pure culture, which won him the Nobel Prize in 1905.

This milestone was followed by the standardization in 1908 of coating needles with tuberculin, an extract of the bacteria, and injecting it under the skin, which resulted in the formation of pupae, or small bumps, on patients that had been exposed to TB. Tuberculin skin tests (or TSTs) to this day remain recommended by the U.S. CDC, especially for the identification of latent TB. Chest x-rays also became a common form of TB diagnosis around the turn of the century, and are even still used today to visualize the physiological characteristics of an active TB infection.

In modern times, smear microscopy (growing a sputum sample from a patient suspected of containing TB in a culture, and then inspecting that culture under a microscope) using staining techniques from over a hundred years ago remains a common method of tuberculosis testing. TSTs followed by some form of imaging (e.g. an x-ray) are also commonly used, but all of these methods either require prohibitively long wait times, lack sensitivity, are subject to human error in interpretation, or a combination of all of the above.

The invention of PCR in the late 20 th century opened new doors for detection of TB, and today the World Health Organization (WHO) recommends molecular diagnostics as the preferred frontline testing option.

Despite this recommendation, fewer than 40% of all TB cases reported to the WHO in 2021 were detected using rapid molecular diagnostics. Many molecular options remain too expensive or too centralized, or just otherwise inaccessible to large swaths of infected populations.

An article published online in Nature in May 2023 identifies 7 transformations in TB diagnostics that the authors describe as critical to closing the TB diagnostics gap:

The authors emphasis the importance of changes such as shifting away from smear microscopy, of decentralizing molecular testing, lower-cost tests manufactured in low- and middle-income countries, and covering larger sections of the population in the years to come.

Platforms like the Co-Dx™ PCR point-of-care platform have the potential to play a key role in the revolution of TB diagnostics, helping to close the diagnostics gap and transform the diagnostics gap by making high-quality real-time PCR TB diagnostics available to more people in more places than ever before.

Other sources: https://asm.org/articles/2021/march/how-tb-diagnostics-have-evolved-since-the-second-c https://www.medicalnewstoday.com/articles/tuberculosis-history#how-old-is-tb https://www.cdc.gov/tb/worldtbday/history.htm https://pmc.ncbi.nlm.nih.gov/articles/PMC5432783/ https://globaltb.njms.rutgers.edu/abouttb/historyoftb.php https://www.cidrap.umn.edu/tuberculosis/who-report-shows-global-tuberculosis-cases-are-rising https://www.nature.com/articles/s41564-023-01365-3