What Is Tuberculosis? — The Sleeping Ember, and the Fire That Takes Months to Put Out

"Consider Getting Tested for Latent Tuberculosis"

The company health screening notice includes a latent tuberculosis test. Rumors also circulate that a tuberculosis patient appeared in the neighboring department. For anyone who thought of tuberculosis only as a disease of the past, both come as a surprise. You wonder why you are being told to get tested even though you are not coughing, and what "latent" means.

Tuberculosis remains a common disease today. In 2022 alone, an estimated 10.6 million new cases of tuberculosis occurred worldwide (PMID 39177079).

A bacterium is a tiny living thing made of a single cell, and some of them cause disease. Tuberculosis is an infectious disease caused when a bacterium called the tubercle bacillus enters the body.

The tubercle bacillus is the bacterium that causes tuberculosis, and it can stay asleep inside the human body for a long time. At the center of this article is one distinction. Having the tuberculosis bacterium enter the body and having that bacterium cause disease are different things. Active tuberculosis is a state where the tubercle bacillus multiplies and actually creates disease in the body.

This article follows what tuberculosis is while placing the tuberculosis situation in South Korea alongside it.

A Single Cough, Droplets Floating in the Air

When a person with active tuberculosis in their lungs coughs, very small droplets containing a few bacteria can be released into the air. Measuring 1 to 5 micrometers in diameter (where 1 micrometer is 1,000분의 1 millimeters), these droplets can travel down the airway all the way to the alveoli (PMID 40955937). Alveoli are tiny air sacs hanging like grape clusters at the ends of the airways, where oxygen and carbon dioxide are exchanged with the blood.

Airborne transmission is the path where very small droplets expelled by a patient float in the air, and the bacteria are transferred to someone who breathes in that air. Tuberculosis is primarily transmitted through this pathway (PMID 40707095). Such droplets are produced not only by coughing, but also by sneezing, talking, laughing, singing, and normal breathing (PMID 40955937).

For tuberculosis to be transmitted, a chain of links must connect. There must be a person whose disease has progressed enough for bacteria to be in the airway, live bacteria must be released into the air, those bacteria must survive in the outside environment, and the body of the person who inhales them must fail to fend them off. These links are influenced by the surrounding environment and how crowded people are (PMID 29112746).

Tuberculosis is most easily transmitted indoors where people live close together. This includes homes, schools, workplaces, and various means of transportation, as well as places like hospitals, shelters, correctional facilities, and nursing facilities (PMID 28361734). Anyone can become infected, but people living in places where tuberculosis is common are exposed more frequently (PMID 40057344).

Tuberculosis bacteria most commonly cause disease in the lungs, but they can cause disease in almost any part of the body (PMID 27784885).

Tuberculosis is transmitted by inhaling very small droplets carried in the breath and floating in the air, and it is most easily transmitted indoors where people live close together.

Germs That Entered Versus Germs That Became Disease

It is estimated that about one-quarter of the world's population has signs of being infected with the tuberculosis bacterium. When studies measured by blood tests are pooled together, the figure is 24.8% (PMID 31221810). Yet most of these people do not have tuberculosis. This is because even when infected with the tuberculosis bacterium, the body can trap the bacteria inside a small cluster (PMID 27784885).

Latent tuberculosis infection is a state where the tuberculosis bacteria have entered the body, but the body has trapped the bacteria so that there are no symptoms and they are not transmitted to others. It is called latent tuberculosis for short. A review article covering latent tuberculosis also describes this as an infection with no symptoms and no transmission to others (PMID 25077395).

Latent tuberculosis can be compared to an ember buried in ashes. There are neither flames nor smoke, but it is not out. Bacteria sleeping inside the body can turn into an active form that can be transmitted to others if immunity weakens (PMID 36982277).

When the sleeping bacteria wake up and cause disease, it becomes active tuberculosis. Among tuberculosis, the only kind that is transmitted to others is active tuberculosis that has formed in the lungs (PMID 27784885).

The risk that a person with latent tuberculosis will progress to active tuberculosis over their lifetime is 5 to 10%, and half of that risk is concentrated within the first two years after infection (PMID 25077395). Stated the other way around, roughly nine out of ten people with latent tuberculosis never develop tuberculosis in their lifetime. However, this is a figure for all people with latent tuberculosis combined, and the risk is higher in people with the risk factors below. The risk of progressing to disease is high in the first few years after infection, and is also high in people who are malnourished, have suppressed immunity, smoke, drink alcohol, or have diabetes (PMID 40057344). HIV infection, which breaks down immunity, increases the risk of latent tuberculosis waking up by 20-fold (PMID 22363214).

Recently, instead of two compartments cleanly cut by a knife between latency and activity, it is viewed as a continuous band. On that band lies a stage where there are no symptoms, but it has already become a disease—in other words, tuberculosis that is not yet latent tuberculosis, but is not yet diagnosed. The share of this kind of tuberculosis transmitted to others is larger than previously thought (PMID 39887565). People who have tuberculosis may also have no symptoms (PMID 40057344). Therefore, the mere fact of having no symptoms does not tell you whether it is latent tuberculosis.

Tuberculosis bacteria entering the body and becoming a disease are different. Latent tuberculosis has no symptoms and is not transmitted to others, but like an unextinguished ember, it can later become a disease.

How Is Active Tuberculosis Found?

Cough, fever, night sweats, and weight loss are symptoms that can appear when tuberculosis becomes an active disease (PMID 27784885). However, some people have no symptoms, so doctors always keep the possibility of tuberculosis open (PMID 40057344).

A sputum test is an examination where phlegm coughed up from deep in the lungs is collected, and checked for tuberculosis bacteria. Active tuberculosis can be diagnosed promptly with a sputum test, using rapid molecular tests whenever possible. A chest X-ray is also helpful (PMID 40057344). When looking for drug-resistant tuberculosis, a culture test that grows the bacteria from sputum is the standard test, but results do not come out quickly, which can delay treatment, making molecular tests an accurate and rapid alternative (PMID 38697459).

The definitive diagnosis of active tuberculosis is made by a doctor based on sputum tests and imaging.

Two Tests That Look for Sleeping Embers

Latent tuberculosis bacteria cannot be directly confirmed at present. They are found indirectly through tests that measure the immune response the body has shown to tuberculosis bacteria (PMID 38095783).

The tuberculin skin test is a test where a small amount of substance obtained from tuberculosis bacteria is injected into the skin, and you return a few days later to see if that spot has swollen and become firm. The interferon-gamma release assay is a test where blood is drawn to measure whether the immune cells inside it release a substance called interferon-gamma when they encounter tuberculosis protein. Both tests are indirect tests that rely on the body's immune response to tuberculosis proteins, and there is no perfect test that serves as a gold standard (PMID 40891796).

These two tests cannot distinguish between latent tuberculosis and active tuberculosis (PMID 38017571). Because active tuberculosis often tests negative, they are not used to diagnose active tuberculosis (PMID 28233512).

A false positive is when a test mistakenly indicates that a disease is present when it is not. The skin test can yield false positives in people who have received the tuberculosis vaccine or who have encountered relative bacteria of the tuberculosis bacillus living in soil and water, and it requires multiple visits to the hospital. The interferon-gamma release assay reduces these weaknesses, but it costs money and requires blood processing (PMID 25077395). In people who have received the tuberculosis vaccine, the interferon-gamma release assay diagnoses latent tuberculosis more accurately (PMID 29901251).

Even if the result is positive, most people do not develop tuberculosis. In an analysis combining 40 studies that followed people at high risk for tuberculosis for over a year, the proportion of positive individuals who subsequently developed active tuberculosis was 4.5% for the interferon-gamma release assay and 2.3% for the skin test. The proportion of negative individuals who did not develop tuberculosis was 99.3% and 99.7%, respectively. In this analysis, the interferon-gamma release assay predicted disease development better than the skin test (PMID 32673595). Still, both tests have a weak ability to sort out which of the infected individuals will progress to disease (PMID 35257904).

Why the meaning of the same positive result differs depending on who it came from is covered in "What a Test Actually Tells You — An Introduction to Sensitivity, Specificity, and Pretest Probability".

The two tests only look for the immune trace of having encountered tuberculosis bacteria; they cannot tell on their own whether you currently have the disease or will develop it in the future.

A Fire Put Out Over Several Months

Tuberculosis takes longer to treat than other infectious diseases. Until recently, standard treatment for drug-susceptible tuberculosis was 6 to 9 months (PMID 38548262). Today, most people with active tuberculosis can be cured with 6 months or less of treatment, while drug-resistant tuberculosis may require longer treatment (PMID 40057344). Antibiotics are drugs that kill bacteria or stop them from growing, and they do not work against viruses. Tuberculosis treatment typically uses multiple antibiotics together over a long period (PMID 27784885). A drug combination established about 40 years ago still cures the majority of people with tuberculosis (PMID 38705792).

Among the tuberculosis bacteria inside the body, there is a mixed group that endures without dying easily even when exposed to drugs. Experts believe that shortening treatment requires an approach that quickly eliminates even this group (PMID 36211964). Comparing it to a fire, even after the surface flames die down, you must put out the remaining embers.

Antibiotic resistance occurs when bacteria become able to withstand an antibiotic, making that drug ineffective. Since tuberculosis bacteria are also bacteria, tuberculosis drugs becoming ineffective is likewise antibiotic resistance. The endurance mentioned earlier is different from this resistance, but the same review notes that the bacterial activity driving this endurance can eventually lead to the development of resistance (PMID 36211964). The 6-month treatment for drug-susceptible tuberculosis is an important treatment where taking every dose of medication is crucial to avoid relapse and resistance (PMID 36982277). Continuing to take medication for months is not easy, and the risk of drug-resistant tuberculosis bacteria emerging grows accordingly (PMID 38548262).

Multidrug-resistant tuberculosis is tuberculosis caused by tuberculosis bacteria that have become resistant to both of the two best-working drugs used to treat tuberculosis. 4.6% of tuberculosis patients worldwide have multidrug-resistant tuberculosis, and multidrug-resistant tuberculosis requires a long treatment of 9 to 24 months with treatment outcomes that are less favorable than drug-susceptible tuberculosis (PMID 31526739).

Resistance develops through multiple pathways. A 2004 review cited incomplete and inadequate treatment as the most important cause of multidrug-resistant tuberculosis (PMID 15520486). Poverty, difficulty accessing proper treatment, and failing to continue treatment through to the end have all played a part in generating resistant bacteria (PMID 36982277). Today's drug-resistant tuberculosis is driven jointly by the ongoing transmission of resistant bacteria from person to person, and by the de novo development of resistance inside an individual's body (PMID 36211964).

The treatment of drug-resistant tuberculosis is also changing. In the past, a long treatment involving injectable drugs was necessary, but now an approach using oral medications over 6 months has emerged (PMID 38705792). Meanwhile, resistance to newly introduced drugs is also increasing (PMID 39887565).

At the center of successful tuberculosis treatment is person-centered care that simultaneously addresses factors like nutritional deficiency, smoking, and alcohol consumption while properly managing other conditions such as diabetes. Even after treatment ends, aftereffects are common, so care must continue (PMID 40057344). Millions of people live with reduced breathing function long after overcoming tuberculosis, yet this issue remains less well-known (PMID 39887565).

Tuberculosis treatment is a long process of using multiple drugs together for several months, and failing to continue it through to the end increases the risk of relapse and resistance.

Putting Out a Sleeping Ember Before It Catches

Among people in close contact with tuberculosis patients, those who received preventive treatment had a 49% lower overall risk of developing active tuberculosis. This is the result of an analysis pooling observational cohorts that followed 439,644 such people across 32 studies for a median of 2.7 years. Rather than being a randomized trial, it compared people who received preventive treatment with those who did not by matching individuals with similar conditions. Among people who tested positive on a skin test or an interferon-gamma release assay, the risk was 80 to 91% lower depending on their age group. The drop in risk was greater in areas where tuberculosis is common (69%) than in areas where it is rare (42%). This analysis excluded contacts of patients with drug-resistant tuberculosis (PMID 38734022).

Latent tuberculosis treatment is a treatment in which people take medicine before tuberculosis bacteria sleeping inside the body can cause illness, aiming to prevent them from progressing to active tuberculosis. Before starting this treatment, it is essential to confirm that the person does not have active tuberculosis (PMID 38095783). For countries with high or upper-middle incomes and a tuberculosis incidence rate of below 100 per 100,000 population per year, World Health Organization (WHO) guidelines specify taking a chest X-ray before treatment to make that confirmation (PMID 26405286).

In the same analysis, one case of tuberculosis was prevented for every 9 to 34 positive contacts treated, and that number varied by age. Looking at all contacts regardless of whether they tested positive, one case was prevented for every 29 to 43 treated in places where tuberculosis is common, and for every 213 to 455 treated in places where it is rare (PMID 38734022). The statement that the risk fell by a certain percentage is a different question from how many people need to be treated for one person to suffer less, and this distinction is untangled in "If the Risk Was Cut in Half, How Many Fewer People Got Sick? — Relative and Absolute Risk".

The risk is especially large for young children. In an analysis gathering 46 studies of children in close contact with tuberculosis patients, it was estimated that 19.0% of children under age five who had a positive infection test and received no preventive treatment developed tuberculosis within 2 years. Among children with a positive infection test, those who received preventive treatment had a 91% lower risk. This analysis also pooled observational cohorts, matching children who received preventive treatment with those who did not based on similar conditions. However, 83% of the tuberculosis cases in children under five were diagnosed within 90 days of the date children in close contact with a patient were first examined, leading the authors to conclude that many of these cases may not have been prevented by preventive treatment (PMID 32199484).

Latent tuberculosis treatment also takes several months. Because the treatment period is long and medicines can sometimes be hard to tolerate, few people finished the course, and both patients and doctors frequently considered the risk of drug side effects greater than the risk of tuberculosis waking up (PMID 29901251). The 2020 guidelines from the National Tuberculosis Controllers Association and the U.S. Centers for Disease Control and Prevention (CDC) place shorter 3- to 4-month regimens ahead of longer 6- to 9-month regimens. The reason is that the shorter regimens have good efficacy and safety, and yield higher completion rates (PMID 32053584).

When broken down by test type, the results diverge. In the previous analysis gathering people at high risk for tuberculosis, among people who tested positive on the interferon-gamma release assay, the rate of developing the disease in the untreated group was 3.09 times that of the treated group. In people who tested positive on the skin test, the difference between the two groups was not distinct (1.11 times) (PMID 32673595). In the analysis pooling contacts, the risk was lower by a greater margin in those who received preventive treatment among individuals who tested positive on either of the two tests (PMID 38734022).

Whether to treat latent tuberculosis is decided by weighing together the limitations of testing, the risk of advancing to disease, the side effects of the drugs, and the ability to take them to completion, and which regimen to use is also chosen to fit the individual's circumstances (PMID 29238270).

Latent tuberculosis treatment is a treatment intended to reduce the onset of disease before a sleeping ember can become an illness, and whether to undergo it is decided by weighing risk and burden together.

BCG — A Vaccine That Protects Babies, and Is Inconsistent for Adults

BCG is a tuberculosis prevention vaccine created based on the bacteria that cause tuberculosis in cows. As of a 2018 review, BCG was the only tuberculosis vaccine approved for human use, and it is effective in protecting babies and young children from severe forms of tuberculosis, such as tuberculosis that spreads throughout the body or develops in the membrane wrapping the brain (PMID 29341430).

The effect varies greatly by age. In an analysis pooling people who had close contact with tuberculosis patients across 26 studies, looking at tuberculosis overall, the BCG shot given at birth clearly prevented tuberculosis only in children under five years of age. The authors concluded that while BCG is effective at preventing tuberculosis in young children, it is not effective in adolescents and adults (PMID 35961354).

The effect of preventing pulmonary tuberculosis in adults varied widely from study to study. Some places showed clear protection, like a trial in England, while other large trials showed no meaningful effect. The effect was larger the farther the location was from the equator. There is evidence that BCG's effect lasts up to 10 years and weakens over time, but a few studies suggest it protects longer than that (PMID 24021245).

Although BCG is used all over the world, it has not suppressed the global epidemic of tuberculosis (PMID 27784885). The effectiveness of currently used vaccines is limited (PMID 40057344). Among new vaccine candidates, some have yielded encouraging results, and larger trials are underway to confirm them (PMID 39887565). As we saw earlier, a skin reaction test may yield false positives in people who have received the BCG vaccine.

While BCG has a clear effect in preventing severe tuberculosis in young children, its effect in preventing tuberculosis in adolescents and adults varies greatly across studies and is limited.

Tuberculosis in Korea — A Disease That Shrank Among the Young, and Remained Among the Elderly

In 2016, the incidence rate of tuberculosis in Korea was 77 per 100,000 people, and the mortality rate was 5.2 per 100,000 people; both were the highest among member countries of the Organisation for Economic Co-operation and Development (OECD) (PMID 30081621).

The same report notes that tuberculosis incidence dropped significantly among teens and twenty-somethings in Korea, and credits that largely to school-based tuberculosis screenings and contact investigations conducted over the past few years. On the other hand, tuberculosis incidence among older adults remained high and actually increased compared to the previous decade. Older adults accounted for 42% of tuberculosis patients and 82% of tuberculosis deaths. Treatment success rates have been gradually increasing through programs such as managing treatment discontinuation and applying health insurance to diagnosis and treatment (PMID 30081621).

A Korean study published in 2024 notes that as tuberculosis incidence has decreased rapidly, the importance of latent tuberculosis has grown further (PMID 39048302). In the evidence this article relies on, the figures for Korea's incidence and mortality rates are from 2016.

In 2016, Korea's tuberculosis incidence and mortality rates were the highest among OECD member countries, and while they had already decreased significantly among teens and young adults by that time, they remained high among older adults, accounting for a large share of patients and deaths. A 2024 Korean study notes that tuberculosis incidence has decreased rapidly since then (PMID 39048302).

When a Coworker in Your Office Is Diagnosed with Tuberculosis

Imagine that a colleague who works on the same floor has been diagnosed with pulmonary tuberculosis. We can trace this situation using what we have looked at so far.

The workplace is one of the indoor settings where tuberculosis can be transmitted (PMID 28361734). Contact investigation is the process of finding people who have spent time close to an active tuberculosis patient to see whether they have the disease or are infected with the tuberculosis bacteria. Contacts of a tuberculosis patient are a group with a high risk of developing tuberculosis, and that risk is greatest in the first year after contact. Pooling studies from high-income countries, the proportion of contacts who had active tuberculosis at the time of testing was 1.4%, and the proportion with latent tuberculosis was 28.1%, with wide variation across studies (PMID 22936710). Because these are proportions identified at the time of testing, it does not mean that all of those infections were transmitted by the current patient.

The testing splits into two paths. One path looks at whether disease is present right now by asking about symptoms, checking chest X-rays, and doing a sputum test if needed. The other path looks for signs of past encounters with the tuberculosis bacteria through a skin test or an interferon-gamma release assay. As we saw earlier, this second path of testing cannot sort out whether disease is present right now, so the first path is needed separately.

Even if a coworker tests positive, among the people who tested positive in the previous analysis, only a minority went on to develop tuberculosis (PMID 32673595). Because the test only shows signs of having encountered the bacteria and does not tell you when that encounter happened, a test alone cannot reveal whether that positive result is an infection from the current contact or an old infection. If it is a new infection from the current contact, half of the lifetime risk of developing the disease, which is 5–10%, is concentrated in the first 2 years after infection (PMID 25077395). In an analysis pooling contacts of patients with drug-susceptible tuberculosis, the risk was much lower for the group among the positive individuals who received preventive treatment (PMID 38734022). If the patient's tuberculosis is drug-resistant, the preventive treatment for contacts also changes to match that resistance (PMID 38095783). The World Health Organization guidelines mentioned earlier place contacts of pulmonary tuberculosis patients into the group strongly recommended for systematic latent tuberculosis testing and treatment (PMID 26405286). South Korea's incidence rate of 77 people in 2016 also falls below the line of 100 drawn by these guidelines. A coworker confirmed not to have active tuberculosis and judged to have latent tuberculosis does not transmit tuberculosis to others (PMID 25077395).

The diagnosed coworker's illness is one that can be cured in most cases with treatment lasting 6 months or shorter (PMID 40057344). Tuberculosis has long carried a stigma, and one review suggests that if paired with new political will and broader access to good care, we can make the illness, death, and stigma long associated with tuberculosis a thing of the past (PMID 30904262).

A doctor evaluates what your test result means and whether you should receive latent tuberculosis treatment by looking at the result together with that person's risk (PMID 29238270).

Where to Look Further

Current tests are still not accurate enough to tell apart which of the people with latent tuberculosis will progress to active disease (PMID 35257904). New vaccines to prevent adult pulmonary tuberculosis are also still being evaluated (PMID 39887565).

Why a single test result has different meanings for different people can be found in "What a Test Actually Tells You — An Introduction to Sensitivity, Specificity, and Pretest Probability", and how to read the effects of preventive treatment separately as percentages and head counts in "If the Risk Was Cut in Half, How Many Fewer People Got Sick? — Relative and Absolute Risk".

Where the alveoli are located and how breath moves in and out are covered in another piece in this series, "How Do We Breathe? — An Upside-Down Tree, and the Leaves Where Air Meets Blood". The differences between bacteria and viruses, what antibiotics do and do not work against, and the story of resistance are picked up by "How Do a Cold, the Flu, and Pneumonia Differ? — An Infection That Stays in the Entryway, and One That Reaches the Inner Room". How the lung damage left behind by tuberculosis connects to chronic obstructive pulmonary disease is taken up by "What Is COPD? — A Balloon That Won't Empty, and the Breath That Leaves in the First Second", and the traces of tuberculosis left on screening CT scans by "Lung Cancer and Low-Dose CT Screening — Reading a Small Spot in the Picture Over Time".

Source Papers

• "Diabetes as a risk factor for tuberculosis disease." (2024) — PMID 39177079 — An estimated 10.6 million TB cases in 2022, with roughly 25% of the world's population infected. (Used only in the introduction for the scale of the disease)
• "Transmission of Mycobacterium Tuberculosis." (2025) — PMID 40955937 — Main transmission occurs through inhalation of 1 to 5 µm droplet nuclei reaching the alveoli; coughing, sneezing, talking, laughing, singing, and normal breathing all generate droplet nuclei.
• "Tuberculosis infection prevention and control." (2025) — PMID 40707095 — TB is transmitted primarily via the airborne route through 1 to 5 µm droplet nuclei.
• "Tuberculosis Infectiousness and Host Susceptibility." (2017) — PMID 29112746 — Transmission requires a source patient advanced enough to have bacilli in the airways, aerosol emission of live bacilli, survival in the environment, and host defense failure, with environmental factors and crowding playing a role.
• "Tuberculosis in Enclosed Populations." (2017) — PMID 28361734 — Transmission is most efficient in indoor close-contact settings such as healthcare facilities, shelters, correctional facilities, nursing homes, homes, schools, workplaces, and transportation.
• "Tuberculosis." (2025) — PMID 40057344 — Anyone can be infected, but exposure is high in high-incidence regions; risk of disease increases in the first few years after infection and with malnutrition, immunosuppression, smoking, alcohol use, and diabetes; it can be asymptomatic; diagnosed using sputum tests (rapid molecular tests) with chest X-ray support; treated mostly in 6 months or less; person-centered care; post-treatment sequelae are common; current vaccine effectiveness is limited.
• "Tuberculosis." (2016) — PMID 27784885 — Primarily a pulmonary pathogen but can cause disease in almost any site; transitions from a state trapped inside granulomas (latent) to a symptomatic (cough, fever, night sweats, weight loss), infectious state; only active pulmonary TB is infectious; long treatment with multiple antimicrobials; BCG is used mainly to prevent life-threatening TB in infants and young children but is ineffective at controlling global epidemics.
• "The global prevalence of latent tuberculosis: a systematic review and meta-analysis." (2019) — PMID 31221810 — Global latent TB prevalence is 24.8% by IGRA and 21.2% by TST at 10 mm, infecting a quarter of the world's population.
• "Update on latent tuberculosis infection." (2014) — PMID 25077395 — Latent TB is an asymptomatic, non-infectious infection; lifetime risk of disease is 5 to 10%, with half occurring in the first 2 years; TST requires multiple visits and has false positives from BCG and environmental mycobacteria, while IGRA has limitations in cost and blood processing.
• "Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets." (2023) — PMID 36982277 — Dormant bacilli progress to transmissible active disease when immunity weakens; the 6-month drug-susceptible TB treatment requires strict adherence to avoid relapse and resistance; poverty, difficult access to treatment, and non-adherence contribute to the emergence of resistant strains.
• "Tuberculosis and HIV co-infection." (2012) — PMID 22363214 — HIV increases the risk of latent TB reactivation by 20-fold.
• "Tuberculosis: An Update for the Clinician." (2025) — PMID 39887565 — TB is a spectrum rather than a binary of latent versus active; the contribution of subclinical TB to transmission is larger than expected; new vaccine candidates are encouraging, with larger trials underway; drug resistance is increasing; post-TB lung disease leaves millions of survivors with persistent respiratory impairment.
• "Multidrug-resistant tuberculosis." (2024) — PMID 38697459 — Culture is the reference test but is not rapid, causing treatment delay, whereas molecular techniques are a sensitive and specific alternative.
• "Tuberculosis Preventive Treatment." (2024) — PMID 38095783 — Latent TB cannot be confirmed microbiologically and is identified indirectly through immune-based tests (TST and IGRA); active disease must be ruled out before preventive treatment, and the goal of preventive treatment is to halt progression.
• "Interferon-γ release assay." (2026) — PMID 40891796 — TST and IGRA are not gold standards and are indirect tests that rely on the host adaptive immune response to M. tuberculosis protein antigens.
• "From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning." (2023) — PMID 38017571 — TST and IGRA only distinguish between infected and healthy individuals, failing to differentiate between latency and active disease.
• "Tuberculosis Associated with HIV Infection." (2017) — PMID 28233512 — TST and IGRA are frequently negative in active TB and are not used to evaluate active disease.
• "Latent tuberculosis infection: Opportunities and challenges." (2018) — PMID 29901251 — Disease progression among infected individuals is relatively low; IGRA is more accurate, especially in BCG-recipients; completion rates are low due to long treatment and tolerability issues; both patients and physicians perceive toxicity risks as greater than reactivation risks.
• "Interferon-γ release assays or tuberculin skin test for detection and management of latent tuberculosis infection: a systematic review and meta-analysis." (2020) — PMID 32673595 — In 40 studies of high-risk groups totaling 50,592 individuals, positive predictive values were 4.5% for IGRA and 2.3% for TST, and negative predictive values were 99.7% and 99.3%, with IGRA showing better predictive power; the incidence rate ratio of disease in untreated versus treated groups was 3.09 for IGRA positivity and 1.11 for TST positivity.
• "The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection." (2022) — PMID 35257904 — Current tests have low accuracy in identifying who will progress from infection to disease.
• "Tuberculosis treatment-shortening." (2024) — PMID 38548262 — Standard treatment for drug-susceptible TB has until recently been 6 to 9 months, longer than other infectious diseases, and prolonged medication increases the risk of resistance.
• "Update on the treatment of tuberculosis." (2024) — PMID 38705792 — A 40-year-old drug combination still cures the vast majority of cases, and drug-resistant TB has shifted from long treatments with injectable drugs to 6-month oral regimens.
• "Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management." (2022) — PMID 36211964 — The burden of drug-resistant TB is driven by a combination of ongoing transmission and the evolution of resistance within patients; shortening treatment requires regimens that rapidly eliminate all bacillary populations and reduce drug tolerance.
• "Management of drug-resistant tuberculosis." (2019) — PMID 31526739 — Multidrug resistance = resistance to the two most effective drugs (rifampicin and isoniazid), accounting for 4.6% of global TB patients, requiring 9 to 24 months of treatment with less favorable outcomes.
• "Multidrug-resistant tuberculosis." (2004) — PMID 15520486 — Incomplete and inadequate treatment is the most important factor in multidrug resistance.
• "Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies." (2024) — PMID 38734022 — Across 439,644 contacts in 32 cohorts with a median of 2.7 years, preventive treatment effectiveness was 49%, TST/IGRA positivity had age-specific aHRs of 0.09 to 0.20, positive NNTs were 9 to 34, high-burden aHR was 0.31 vs low-burden 0.58, and overall contact NNTs were 29 to 43 vs 213 to 455, based on observational cohorts with propensity score matching, excluding drug-resistant TB contacts.
• "Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries." (2015) — PMID 26405286 — WHO guidelines for low-incidence countries strongly recommend systematic testing and treatment for pulmonary TB contacts, with chest X-ray to rule out active disease before treatment.
• "The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis." (2020) — PMID 32199484 — Among 137,647 exposed children, the 2-year cumulative incidence in infected, untreated children under 5 was 19.0%, preventive treatment effectiveness in infected children was 91%, and 83% of disease in children under 5 was diagnosed within 90 days, which may not have been prevented by preventive treatment.
• "Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020." (2020) — PMID 32053584 — Short-course 3- to 4-month rifamycin-based regimens are preferred over 6 to 9 months of isoniazid alone due to efficacy, safety, and higher completion rates.
• "Treatment of Latent Tuberculosis Infection." (2017) — PMID 29238270 — Treatment decisions weigh test limitations, disease risk, side effects, and medication adherence together, and regimens are chosen based on individual circumstances.
• "Tuberculosis vaccines: Opportunities and challenges." (2018) — PMID 29341430 — BCG is the only TB vaccine licensed for humans, effective in preventing severe miliary and meningeal TB in infants and children, with variable effectiveness in adults.
• "Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis." (2022) — PMID 35961354 — Across 26 cohorts totaling 68,552 individuals, infant BCG showed significant protection only under age 5, concluding it is effective in young children but ineffective in adolescents and adults.
• "Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis." (2013) — PMID 24021245 — Adult pulmonary TB protection ranges from marked protection in the UK MRC trial to no effect in the Chingleput trial, being greater the further from the equator, lasting up to 10 years and decreasing over time.
• "Tuberculosis control in the Republic of Korea." (2018) — PMID 30081621 — In 2016, the incidence rate was 77 per 100,000 and mortality was 5.2, the highest in the OECD; the decrease in those in their teens and twenties is thanks to school screening and contact investigations, while elderly incidence remains high and increasing, accounting for 42% of patients and 82% of deaths, alongside rising treatment success rates.
• "Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program." (2024) — PMID 39048302 — TB incidence is declining rapidly in Korea, highlighting the growing importance of latent TB. (Used only for a single sentence of background description)
• "Contact investigation for tuberculosis: a systematic review and meta-analysis." (2013) — PMID 22936710 — Across 108 studies in high-income countries, active TB among contacts was 1.4% and latent TB was 28.1%, with substantial heterogeneity; incidence peaks in the first year, making contacts a high-risk group.
• "Tuberculosis." (2019) — PMID 30904262 — Improving access to high-quality, person-centered care can consign TB illness, death, and stigma to the past.