The Forgotten Pandemic
Humans have suffered from tuberculosis for thousands of years and, even today, the disease kills more than 1 million people each year. Yet diagnosing cases remains a challenge. Why?
This essay by Kamal Nahas is the first in a two-part series on tuberculosis. The second part — focused on vaccines and medicines — will be published next Sunday, concluding Issue 04 of Asimov Press.
The Most Deadly Infectious Disease
“Each successive episode of bleeding left him weaker than before,” wrote Mary Doria Russell of Doc Holliday, the gunslinging gambler, in her eponymous book, Doc. Published in 1971, the book contains unsparing descriptions of Holliday’s deteriorating medical condition. “‘You get used to it,’ Doc always said. ‘You can get used to anything.’ Used to the gnawing pain; used to the sudden taste of iron and salt; used to the struggle to pull air in as blood from his lungs rose.”
Doc suffered from tuberculosis, or TB, a bacterial disease caused by Mycobacterium tuberculosis. Both deadly and storied, the disease has earned many monikers — consumption, phthisis, and “the white plague” or “white death,” owing to the paleness of those afflicted. It killed Frédéric Chopin, Henry David Thoreau, Franz Kafka, and Eleanor Roosevelt. At its peak in the 19th century, TB is estimated to have caused one in four deaths in Europe and America.
M. tuberculosis has a complex lifecycle. Unsuspecting people inhale the bacteria, which travel down into the lungs. Immune cells, called macrophages, quickly attempt to destroy the microbes. But the microbes are wily prey, often killing the macrophages instead by secreting factors that trigger cell death. Other white blood cells cluster around the foreign invaders, forming a physical barrier, called a granuloma, that immures the pathogen. Macrophages in the cluster continue fighting the bacteria, and other immune cells arrive to reinforce the granuloma wall.
At this stage, the disease is still latent, and unsuspecting carriers typically experience no symptoms. It is not until M. tuberculosis erupts from the granuloma that it causes active disease. Persistent mucus, a bloody cough, exhaustion, emaciation, and fevers follow. Tuberculosis can also cause swollen lymph nodes, bone and joint pain, or seizures.
Nowadays, TB is relatively uncommon in the West,1 where it is mostly shrugged off as a disease of the past. But perhaps surprisingly, TB remains the deadliest infectious disease on the planet. Globally, it kills 1.2 million people a year, with the majority of fatalities occurring in Sub-Saharan Africa and South Asia. Malaria, in contrast, killed about 608,000 people in 2022.
TB remains so rampant because it is difficult to diagnose. Yet accurate diagnoses are the first step toward understanding the scale of the problem and treating TB early to halt its spread. So why haven’t we made more progress toward developing cheaper and more efficient ways to identify cases?
There are many reasons. In hard-to-reach places with poor access to healthcare, many people with symptomatic TB cannot receive a diagnosis due to cost, inadequate transport, or a lack of electricity to run tests. Researchers estimate that 2.9 million people with TB went undetected in 2019, but these estimates are uncertain due to inaccuracies in testing. And even when patients do get tested, those tests often produce false negatives when the bacterial load is too low to detect in sputum samples.
Additionally, some of the tools for diagnosing TB also lack the specificity required to assess antibiotic resistance. In 2019, physicians were unable to tailor effective antibiotic regimens for 39 percent of new TB cases because the assessments they relied on could not gauge which antibiotics the strains would be susceptible to.
Yet another challenge arises in deciding who qualifies for a TB diagnosis: With limited resources, healthcare workers tend to focus on people showing signs of the disease rather than seemingly healthy people who may carry the latent bacteria. Given this, physicians still don't grasp the degree to which asymptomatic spreaders transmit the pathogen.
In 2014, the World Health Organization (WHO) proposed an initiative called the End TB Strategy, aimed at reducing cases by 80 percent, deaths by 90 percent, and diagnostic/treatment costs by 100 percent by 2030. Regrettably, the initiative is not on track to meet any of those targets.
In this essay, the first in a two-part series on TB, we dive into the history of this disease and its mismanagement while highlighting key breakthroughs that have partially thwarted this persistent pandemic in the West.
An Ancient Malady
The M. tuberculosis bacterium has been around longer than we have. Early forms of the disease infected great apes in East Africa an estimated three million years ago. For reference, the oldest human species, Homo habilis, came into the picture roughly two million years ago. The current lineage of M. tuberculosis has plagued our species for 15 to 20 thousand years. Archaeologists have found evidence of ancient Egyptian mummies carrying the pathogen’s DNA, including some that had developed Pott’s disease — a bending of the spine brought on by TB spreading to bones. The disease also tormented the ancient Greeks and Romans, with Hippocrates noting: “Those who spit up frothy blood bring this up from the lung.”
Tuberculosis cases surged during the Industrial Revolution as people began crowding indoors, where airborne bacteria could concentrate and spread with ease. People across social classes succumbed to the disease. When artists and poets began to fall ill, tuberculosis even became a glamorized and coveted infirmity.
“How pale I look!” wrote the poet, Lord Byron. “I should like, I think, to die of consumption … because then the women would all say, ‘see that poor Byron — how interesting he looks in dying!’”
While some were busy romanticizing the disease, others were working hard to understand it. In 1882, German physician Robert Koch discovered the bacterial culprit behind TB by staining a tubercular mass taken from an animal lung and examining it under a microscope. From this, “very fine rod-like forms became apparent,” he wrote. Identifying the bacteria behind the pathogen would later set the stage for many upcoming diagnostics, treatments, and even a vaccine. But doctors explored numerous uninformed remedies in the interim.
Upon discovering the bacterium behind TB, Koch began searching for cures. In 1890, he experimented with gold compounds, such as gold cyanide, which killed the bacteria in pure lab cultures. Koch and others later tested these same compounds in animals, but found them to be unsafe. In fact, animals with TB lived longer if they didn’t receive the gold compounds; even with a dose 1,000-times greater than what was needed to kill the microbes in lab cultures, guinea pigs couldn’t clear TB from their systems.
Today, scientists would halt clinical research on drugs with these properties, but back then, many researchers put stock in the “magic bullet” theory proposed by Paul Ehrlich, a German biologist. He recognized that some molecules bind tightly to bacteria and reasoned that toxic compounds could be used as antimicrobial drugs if they similarly targeted the bacteria while minimizing collateral damage to the body. Ignoring the failed animal experiments, some researchers administered “gold bullet” compounds to TB patients. In 1912, German clinicians gave an amalgam of gold cyanide to 20 patients with a skin TB infection. “We cannot say anything yet about definite healing,” they said. In the end, their experiment failed to cure the participants.
Researchers next put intense exercise to the test. Perhaps unsurprisingly, many patients struggled with stamina. Changing tack yet again, healthcare workers reasoned that plenty of rest and sunshine would help. Beginning in the early 20th century, people with TB would travel to “sanatoriums” for extended stays where they could focus on recovery. Depictions of these sanatoriums abound in literature.
In the novel, The Magic Mountain, Thomas Mann’s Berghof sanatorium captures the ambiance, sitting at the top of a hill like a luxury hotel, surrounded by fields and meadows. Each patient had a private suite and balcony to absorb sunlight for at least two hours each day. Describing such a sanatorium in Doc, Russell writes: “There were stories of remission and even cures — some undoubtedly exaggerated, but others that sounded legitimate. With rest, a nutritious diet, and moderate amounts of healthful wine, convalescence in that climate seemed possible.”
Doctors physically examined the chests of their sanatorium patients, looking for signs of disease and recovery. They felt for tenderness or abnormalities and tested the percussion of the lungs by striking the chest wall with their fingers. A drum-like sound meant that there was air in the lungs — a good sign. But a dull or flat sound suggested blood drenched the lung cavity or that there was an obstruction by a solid mass.
Chest X-rays gave doctors additional insight into the inflamed granulomas within the lungs. “The chest cavity was bright, but one could make out a web of darker spots and blackish ruffles,” Mann wrote.
In 1884, German bacteriologist Georg Gaffky developed a prognostic index to monitor the progress of sanatorium patients. Reasoning that disease severity would depend on the abundance of M. tuberculosis bacteria in the patient, he based his prognostic on the density of these bacteria in sputum samples. Physicians placed patients on a scale of 0 to 10, ascribing a low number to those with fewer bacteria. However, doctors discovered that bacterial numbers did not closely correlate with severity, and by the 1970s, they moved away from Gaffky’s scale.
For those patients who failed to recover with rest and sunshine, physicians tried collapsing a TB-ridden lung by performing an artificial pneumothorax, in which they infused nitrogen gas into the chest cavity — but not into the lungs — using a hypodermic needle. The air applied pressure to the lung, squashing it down in an attempt to flatten the walls of cavities hollowed out by the infection, encouraging them to seal. Physicians in North America and Europe widely adopted this method. In The Magic Mountain, patients receiving this treatment joined what they dubbed the “Half-Lung Club.”
The nitrogen air pockets would slowly absorb into the body, making the relief granted by an artificial pneumothorax only temporary. Long-term TB sufferers would receive a thoracoplasty instead, whereby doctors would remove up to eight ribs to compress the chest wall and permanently flatten a lung. Neither of these lung-squashing methods actually cured the disease.
Since such ineffective historic interventions, scientists have developed better methods to diagnose, monitor, and treat TB patients, but the shortcomings of our modern-day arsenal still hold us back from reaching the high bar set by the End TB Strategy.
Track and Trace, Far and Wide
TB abounded in urban environments during the Industrial Revolution, and today, crowded and often unsanitary cities in lower-income countries act as similar hot spots for transmission. Dhaka, the capital city of Bangladesh and one of the world’s most densely populated urban areas, has the highest disease incidence in the country. However, people living in industrialized areas generally have better access to healthcare facilities, where physicians can run tests from chest radiography to microbial and immunological assays.
This means that in some countries, the situation flips, and people living in rural areas with poor access to healthcare are at greater risk of catching the disease, slipping under the radar, and spreading it to others. In China, for example, 80 percent of the population resides in rural areas, and people who live outside cities catch TB 1.8 times more often than urban dwellers.
Living in rural areas can impede diagnoses for multiple reasons. Let’s consider the life of Enzokuhle, a fictitious South African man whose experience seeking a TB diagnosis we’ll use for the purpose of demonstration. Enzokuhle resides in a remote community near Vlaklaagte in an underpopulated and underdeveloped region. Too far from the nearest town to commute on foot, he makes a living at a nearby gold mine. Gold miners in South Africa work in overcrowded conditions and experience the highest rates of TB in the world.
Enzokuhle began to experience a mild cough a couple of weeks back. It now takes a downward turn, becoming bloody and unrelenting. Fever and malaise hinder Enzokuhle’s ability to work, and he worries that his unidentified illness is contagious. Enzokuhle desperately needs a TB test to know whether or not to pursue treatment, but many obstacles stand in his way.
Enzokuhle would seek out a local nurse or doctor if he could, but they tend to live in developed areas rather than remote settlements like his. In South Africa, a country with a large number of TB cases, 46 percent of people live in rural areas, but only 19 percent of physicians do. Healthcare professionals are in short supply, causing long waits. The earliest that Enzokuhle can book an appointment in the nearest town is months away. He also has to navigate around a shortage of transportation options, inadequate roads, and the cost of travel. One survey found that people in Zambia spend an average of 16 percent of their monthly income on medical travel.
The costs of diagnostic tests, which range from a single dollar to several hundred, can deter patients, too. In Malawi, it costs about two-and-a-half months of typical monthly wages for patients to get tested for TB, and Enzokuhle doesn’t make enough to cover such expenses. Others may not have the opportunity to pause work for medical travel, because then they’d lose even more money.
People living off the grid have two options for getting tested. They can either travel to a healthcare facility, or providers can come to them to collect samples. In South Africa, traditional healers are more numerous than medical doctors, so healthcare providers work with them to disseminate tests upon visiting isolated communities. This may be Enzokuhle’s best chance of being tested.
Alternatively, Enzokuhle could seek out a local NGO that provides tests — but only if such groups work in the region. A few of these NGOs have emerged in South Africa, such as TB Alliance and SANTA, the South African National Tuberculosis Association. Other countries grappling with TB have set up similar initiatives. Around 5,000 miles away from Enzokuhle, in India, one such NGO, a group of over 15,000 community volunteers, runs a project called Axshya (meaning TB-free in Sanskrit) that seeks to educate remote communities about the disease to combat stigma, pinpoint symptoms, and test and treat people in their communities.
Axshya runs a common TB diagnostic called a sputum test — similar to the one used for the Gaffky scale in 20th-century sanatoriums. Once patients cough up enough bacteria-ridden mucus from their airways, the volunteers add a red stain called carbol fuchsin that dyes the membranes of all microbes but remains bound to M. tuberculosis’ surface following a wash.2 This is one of the cheapest tests available, making it more viable for people like Enzokuhle who struggle to journey far from their homes. However, the red-painted bacteria are only visible under a microscope, so healthcare workers must transport the samples to a laboratory to determine the results. As a consequence, secluded settlements cannot run these tests independently and must rely on NGOs or other healthcare workers to visit and ship off their samples, the results of which can take months to receive.
Other TB tests exist, but most also rely on laboratory access. Interferon gamma release assays pick up an immune response to the infection. They are named after interferon gamma, a pro-inflammatory molecule released by T cells. If the cells previously crossed paths with TB bacteria in an infected person, they become primed to release this molecule upon reencountering one of the pathogen’s antigens. Healthcare workers can isolate T cells from a patient, mix it with an antigen, and monitor interferon gamma release to determine if the patient has the bacterium. Running these tests relies upon several harder-to-access machines, such as incubators to maintain the cells at body temperature, shaking platforms to mix test reagents, and spectrophotometers to detect interferon gamma in the samples.
Since Enzokuhle cannot travel easily to a medical center equipped with a diagnostic laboratory, another option is to shrink down the testing equipment and bring it to him. The diagnostic company Cepheid has done just that. Using a polymerase chain reaction (PCR), Cepheid’s test makes numerous copies of a gene specific to M. tuberculosis known as rpoB, which codes for part of its RNA polymerase.
PCR testing normally relies on laboratory equipment, such as kits to split open the bacteria and release their DNA, a centrifuge to separate DNA from other components in the cell, and a thermal cycler that controls the temperature and timing of the DNA synthesis reaction — but Cepheid has packaged all of these into a table-top machine called a GeneXpert® System, negating the need for a large, sterile laboratory and trained personnel. Clinicians just insert a sputum sample, press a button, and wait two to three hours for the results.
As low-fi as the GeneXpert® System is compared to other methods, it and other compact PCR tests still require a power supply. This means they are unavailable to approximately 700 million people with no access to electricity. The majority of people without power live in Sub-Saharan Africa, where TB is rampant. Fortunately, Enzokuhle lives in a settlement with power, but he knows people in a nearby region with no energy source that would not benefit from this method. Budgeting remains a barrier, too. In 2023, each GeneXpert System cost clinics about 19,000 U.S. dollars. With no health insurance and limited income, Enzokuhle decides not to shell out 260 South African Rand (roughly 15 U.S. dollars) for an individual PCR test.
However, there is one TB test that does not require electricity, expensive equipment, or access to a laboratory and does not leave patients or providers with a huge bill — the tuberculin skin test. This test can take place in Enzokuhle’s home. It involves injecting a protein derivative from the bacteria, called tuberculin, under the skin to see if T cells react to it. Should Enzokuhle have M. tuberculosis in his system, his T cells will recognize the antigen and mount an intense immune response at the injection site, leaving behind a red and swollen bull’s-eye.
Robert Koch, the German physician who discovered M. tuberculosis, accidentally developed this nearly-ubiquitous diagnostic back in 1890. He aimed to develop a treatment for tuberculosis by isolating extracts from dead bacteria and administering them to patients under the skin. This therapy didn’t have the desired outcome; his subjects quickly developed chills, fever, and vomiting. This was probably because their immune systems, which had already been fighting the bacteria, suddenly faced an excess of its antigens, causing it to overreact. With careful refinement, however, this technique evolved into a milder TB skin test.
Logistic considerations aside, the various diagnostics for TB are generally error-prone, with a range in accuracy from 67 to 100 percent. Test quality is usually measured by two factors: sensitivity and specificity. Sensitivity refers to the share of people with the pathogen that are correctly identified as positive. The sputum test isn’t very sensitive in children because they often struggle to cough up enough mucus for healthcare workers to detect the bacterium, resulting in false-negatives. This diagnostic only catches 7 percent of cases in children under 15 and 1 percent of cases in children aged four and under. Even in adults, sputum may only contain a few of the microbes, but at least 1,000 bacteria per milliliter of sputum are needed to detect the pathogen. As a result, the test only catches about 75 percent of cases.
The PCR test, which Enzokuhle wasn’t able to afford, is the most sensitive tool and often picks up infections where the sputum tests fail. Even if the sample contains a few M. tuberculosis bacteria, the PCR will double up their DNA many times over, thus amplifying the signal and making them impossible to miss.
Tests that detect an immune response to the bacterium, namely the tuberculin skin test and interferon gamma release assays, can also have problems with sensitivity. These diagnostics are especially poor for people with compromised immunity, such as individuals with inadequately treated HIV, or AIDS patients, who lack enough T cells to mount an immune response against the bacteria. HIV/AIDS and TB often overlap geographically, such as in South Africa, rendering these tests less useful there. However, Enzokuhle undergoes an HIV test at the same time (as is common practice in South Africa), and it comes back negative.
In Enzokuhle’s case, the results of his tuberculin skin test — the red swollen lump — comes in sooner than his sputum test that has to be shipped to a laboratory. With the skin test confirming his suspicion that he has contracted TB, Enzokuhle is all set to begin treatment. That is … until the sputum results come back negative.
The discrepancy between the tests might lie with the other quality-control factor: specificity — the share of people who don’t have the pathogen that are correctly identified as being negative, such as people who are infected by other microbes. Both the tuberculin skin test and the sputum test fall short in this regard. Exposure to harmless bacterial species closely related to M. tuberculosis can yield a false-positive result. Because of how similar they are in structure to M. tuberculosis, their membranes retain the red stain in the sputum test, and they can prime T cells against their protein derivatives, thereby skewing the results of the skin test.
This same challenge appears in another, more unusual test: In some Sub-Saharan African countries, such as Mozambique, technicians train the African Giant Pouched Rat to sniff out M. tuberculosis from a batch of sputum samples, scratching the floor of their cage when they come across a sample carrying the microbes. The rats are speedier diagnosticians than the laboratory technicians who care for them, but, just like with the standard sputum tests, they struggle to distinguish the pathogen from “wild” strains of mycobacteria.
People who received the Bacillus Calmette–Guérin (BCG) vaccine, which is recommended to nearly everyone in South Africa, also expose their T cells to tuberculin, leading to false positive skin tests. This is because the BCG vaccine consists of a live bacterium, called Mycobacterium bovis, which has been cultured outside the body enough times to render it poorly adapted for infection. So although it provides some protection, the vaccine is too close a relative of M. tuberculosis, meaning it can muddle the results of most widely-accessible TB diagnostics.
The interferon release assay, an aforementioned method for identifying TB, has better specificity. That’s because the assay uses M. tuberculosis antigens that are missing from related bacteria or the BCG vaccine, meaning only T cells that previously encountered the pathogen can mount a detectable immune response.
Even so, the GeneXpert® Systems PCR test boasts the best specificity overall because it makes use of three primers (i.e. short strands of DNA that cause the gene-doubling reactions), serving as a form of three-factor authentication, ensuring the system copies the correct gene and not one present in a related bacterial species. Newer GeneXpert® Systems even come with an extra layer of specificity in that they can detect genes that confer resistance to antibiotics, allowing physicians to make better-informed decisions about treatment regimens.
Unsure how to proceed with a positive skin test and a negative sputum test, Enzokuhle makes the difficult decision to pay for a GeneXpert® System test to resolve the matter. It comes back positive, and the doctor assures him the result is accurate. He may have had too few bacteria in his sputum sample to test positive. Fortunately for Enzokuhle, the PCR test does not spot any antibiotic resistance genes, and the doctor prescribes him a routine course of antibiotics, which should clear the infection in six months.
A Muddied Epidemiology
At the population level, exaggerated statistics, unreported fatalities, and a blind spot for transmission prevent us from fully grasping TB’s burden.
The skin test is correct in Enzokuhle’s case, but it fails for many other patients, skewing our global understanding of TB’s spread. The skin test often fails for patients who have previously been vaccinated or infected by certain bacterial species, producing false positives as often as 40 percent of the time. Some scientists at the University of Cambridge argue that incorrect interpretations of the skin test contributes to one of the most widespread misconceptions about the disease — that roughly two billion people (or one-quarter of the globe) harbor the pathogen in a latent state for many years or even for the rest of their lives. This apocryphal view leads some to believe that the unassuming bacteria could at any point erupt into full-blown disease.
In reality, the number of people carrying M. tuberculosis with no signs of disease is probably lower, although updated estimates are not yet available. Modeling suggests that nine out of ten people will naturally clear the pathogen with the help of their immune system within a decade, and most will clear the infection in under two years. This busts the myth that latent infections are lifelong. What’s more, 98 percent of TB cases appear within two years of infection, revealing that M. tuberculosis does not often wait to cause disease several years down the line.
The reported number of deaths from TB — 1.2 million people each year — is also inaccurate, creating a false impression that the disease is actually less lethal than it really is. People with inadequately treated HIV infections experience a drop in their T cells, which fight infected cells and contribute to the granuloma that prevents M. tuberculosis from spreading. AIDS patients are more likely to develop active TB as a result, and many succumb to the bacterial infection, but their death certificates only report AIDS as the cause to avoid double-counting. In 2019, one in three people who died of AIDS also had TB, creating a gap of 208,000 TB-related deaths. Combined with the knowledge that the number of asymptomatic carriers is likely exaggerated, the threat of lethality posed by this microbe becomes more alarming.
One of the goals of the End TB Strategy is to reduce new cases by 80 percent before 2030, but they are falling short of this target by 9 percent. Asymptomatic spreaders could partly contribute to this shortfall. Healthcare professionals often reserve diagnostic tests and treatments for the unwell. This creates a blind spot in the disease’s epidemiology as researchers lack a sense of scale for the impact posed by people who show no outward signs of sickness.
When the WHO compared TB prevalence data among asymptomatic and symptomatic people in nine Asian countries, they discovered that 34–68 percent of people with positive sputum tests showed no TB symptoms. Researchers at John Hopkins University argued that undetected, subclinical TB could account for up to 10 percent of prevalence — as many as 10 million people — based on the proportion of individuals who test positive in a microbiological assay but show no symptoms. Carriers often host copious volumes of the bacteria, at least 10,000 microbes for each milliliter of sputum, which is high enough to transmit them through the air, even by breathing alone. Sometimes symptoms like coughing are easily mistaken for a common cold, and patients often wait for such symptoms to pass before seeing a physician and getting tested. This lag time further exacerbates transmission.
With so many people suffering from the active form of the disease, healthcare workers have deprioritized screening for latent infections. However, tracking the dormant disease might prove essential for quashing TB cases. Ultimately, there is a massive need to develop a new slate of diagnostics sensitive enough to pick up latent infections but inexpensive enough to be readily available.
TB Tests of Tomorrow
Physicians often identify M. tuberculosis by viewing sputum smears under a microscope. But increasingly, scientists have begun experimenting with a principle from astronomy, rather than microbiology, to gain deeper insight into patient infections.
When astronomers use telescopes to view the stars, they don’t only capture an image of the stellar masses: They also collect the spectra of wavelengths that the stars absorb and emit, providing insight into their elemental makeup. The new TB diagnostics do something similar — they allow scientists to capture spectra from M. tuberculosis, revealing details about infections that could guide the course of treatment.
Engineers at Khon Kaen University in Thailand are developing one such technique based on Raman scattering, a phenomenon in which compounds excited with one wavelength of light emit photons in a different part of the electromagnetic spectrum. The wavelength of emitted light depends on the properties of the compound, and a solution of different compounds produces a complex spectrum resembling hills and valleys.
The team hypothesized that sera from TB patients, carrying biomolecules produced by M. tuberculosis, would produce a unique spectrum. To test this theory in a small proof-of-concept study, they recruited four groups of people: 26 who had active TB infection; 20 with latent TB, meaning they showed no TB symptoms but tested positive by other methods; 34 people with no signs of infection despite exposure to TB patients; and 38 healthy volunteers.
After isolating sera from the blood of these four groups and drying out the samples, they excited them with a green laser and collected their Raman spectra. From a distance, the spectra of all four groups looked identical, as one would expect for sera mostly composed of the same material, namely blood proteins and lipids. But upon closer examination, the hills and valleys for each group differ in height, highlighting the individual differences caused by either the bacteria or the immune factors tackling the infection.
The researchers argue that the signature landscapes produced could allow for more precise and detailed diagnoses in the future, discriminating between active, latent, and cleared TB infections. This could correct the record on the disease’s epidemiology and help catch and treat the condition before it has a chance to spread.
This test is still only a proof-of-concept, and the engineers will have to contend with the constraint that Raman spectroscopy relies on complex equipment when they come to package the test as diagnostic. They could face similar obstacles as the compact PCR tests: unusable in places with no electricity and prohibitively expensive for patients like Enzokuhle.
Engineers at Stanford University may have a different answer. They built a portable, affordable microscope called Octopi with a range of imaging modalities useful for diagnostics, including Raman spectroscopy. Octopi uses Raman scattering to discriminate between M. tuberculosis bacteria that confer resistance to any one of four commonly prescribed antibiotics, which could quickly inform physicians about the best treatment options.
Scientists have come a long way from tapping their fingers against the chest of a patient to listen for signs of TB. And while some of the antiquated diagnostics, including the sputum test and the skin test, remain widely used, researchers have invented new techniques with better sensitivity and specificity. Now, inventors are tackling the next diagnostic challenge. Using Raman spectroscopy, they can collect more information from a single test, including the stage of the pathogen’s lifecycle or its drug resistance.
With the increased understanding of TB’s epidemiology that these novel diagnostic tests offer, we inch closer to controlling the illness. Yet better diagnostics will not suffice. In part two, we delve into the limitations posed by current vaccines and antibiotic treatments. We also discuss the potential for alternatives. As with the next-gen diagnostics under development, these provide hope that one day TB may fade into a relic of art, novels, and romantic poetry.
Thanks to Saloni Dattani, Xander Balwit, Devon Balwit, Niko McCarty, and Merrick Pierson Smela for editing drafts of this essay.
Kamal Nahas is a researcher-turned-journalist based in Oxford, UK, who covers stories in biology, health, and technology.
Cite: Nahas, Kamal. “The Forgotten Pandemic.” Asimov Press (2024). DOI: https://doi.org/10.62211/62ur-55df
Although TB tends to be less common in the West, it has a higher prevalence among incarcerated individuals as crowded prison conditions might aid the spread of the airborne pathogen.
The mucus samples from sputum tests can spread M. tuberculosis to healthcare workers if the diagnostic facility lacks adequate biosafety precautions. However, scientists at Harvard University and Massachusetts Institute of Technology are looking to urine as a safer testing alternative. Urine rarely carries M. tuberculosis bacteria but often holds some of its biomarkers that filter through the kidneys.
Thank you for that excellent summary.