What is Latent Tuberculosis?
Mycobacterium tuberculosis is a type of bacteria that can cause serious harm to humans. It usually causes diseases in the lungs but can spread and affect any part of the body. The infection can result in acute (sudden and severe), chronic (long-term), or latent (inactive but capable of becoming active) diseases. Tuberculosis is a disease that affects people globally, but it is particularly common and severe in low-income countries and among vulnerable groups. These include people who are homeless, in prison, or misuse drugs through injections. The cost of dealing with and treating the disease can put a serious financial strain on these communities.
In countries where people have higher incomes and tuberculosis is not widespread, public health programs concentrate on discovering and treating individuals with latent (inactive) tuberculosis (often shortened to TB). This is important because latent TB can become active at any time, causing a person to become sick and spread the disease to others. It is critical to identify and understand the characteristics of people with latent TB at risk of the disease becoming active for community health. However, this requires a delicate balance between the benefits of treatment and any possible negative effects.
For further information on the origins, causes, effects, physical impacts, examination and treatment of tuberculosis, you can read a related topic titled “Tuberculosis” on the StatPearls website.
What Causes Latent Tuberculosis?
The bacteria called Mycobacterium tuberculosis causes tuberculosis (TB). This bacteria belongs to a group known as mycobacteria. Other types of mycobacteria do not cause TB and are known as nontuberculous mycobacteria (NTM).
All mycobacteria, including the one that causes TB, are shaped like rods and have special cell envelopes that contain lots of mycolic acids. Mycolic acids are a type of fatty acid that make the cell envelope. Because of this unique structure, typical staining techniques don’t work to see them under a microscope. To see these bacteria, we use specific stains like auramine-rhodamine or Ziehl-Neelsen.
Mycobacteria need air to live and they grow slowly; it might take several weeks to get a positive result. To identify Mycobacterium tuberculosis from other bacteria, scientists usually look at its shape and other chemical features. Rapid tests, like nucleic acid amplification testing, also help identify this bacteria. It can also point out specific genetic sequences in the bacteria that might make them resistant to certain drugs.
Risk Factors and Frequency for Latent Tuberculosis
About a third of the world’s population has tuberculosis (TB), a condition that can be treated and cured. Still, it kills around 1.5 million people each year globally. TB is more common in low-income countries, especially India and sub-Saharan Africa. Other regions such as Eastern Europe also see high rates of TB.
On the other hand, countries with a lower number of cases, like the United States, have less than 100 cases per 100,000 people annually. In the U.S, most cases are found in those born outside the country.
There are more cases of TB in men than women. For instance, one study found that the rate of TB in the lungs was greater in men than in women. Also, about 12% of those newly diagnosed with TB globally also have HIV, a condition that can affect the results of TB tests due to its impact on the immune system.
Once exposed to the TB bacterium, between 5% and 15% of people will develop active TB at some point in their life. The infection can lie dormant for many years, but most people who will develop active TB do so within the first two years after exposure.
Signs and Symptoms of Latent Tuberculosis
People with latent TB infection, or a dormant form of tuberculosis, typically don’t present any symptoms. The process of determining if someone has latent TB consists of two parts – first, identifying those who need to be tested for latent TB and second, ruling out active TB disease.
If someone is at a high risk of latent TB becoming active, especially in countries where TB isn’t very common, or at high risk of a new TB infection, they should be tested. This also applies to people at moderate to high risk in places where TB is more common. It’s important to evaluate risk factors for latent TB becoming active. Such risk factors can include having a history of blood or organ transplants, dialysis, a specific type of lung disease known as silicosis, certain types of treatment like anti-tumor necrosis factor treatment, and HIV coinfection. Furthermore, anyone who has had contact with an actively infected TB patient, regardless of age, is at a much higher risk of new TB infection.
Active TB disease may be suggested by symptoms such as a persistent cough lasting over two weeks, breathing difficulty, blood in the sputum, chest pain, fever, night sweats, and weight loss. Individuals who are more exposed to TB patients, like prisoners, healthcare workers, homeless people, illicit drug users, people with silicosis, and people who have moved from countries with high TB occurrence to those with low prevalence should be on high alert.
During a physical examination, the focus should be on detecting signs of active TB. These signs could be weight loss, sputum containing blood, fever, and increased sweating. Other signs can occur in places outside the lungs, such as swelling of the lymph nodes, skin changes like erythema nodosum or panniculitis, pallor caused by anemia, and abnormalities in the membranes surrounding the brain and spinal cord, as well as in the belly lining and bones. Physical signs suggesting a higher likelihood of latent TB becoming active include the presence of tubes placed into blood vessels or connections made between arteries and veins for dialysis, signs of transplant and associated treatments, and changes due to the use of steroids.
Testing for Latent Tuberculosis
There isn’t one specific test that can definitively tell us if Tuberculosis (TB) is active or not. To identify latent TB, we need signs of the immune system responding to TB and to confidently exclude the possibility of active TB.
Immune-Based Testing
Looking at your immune system’s response can provide valuable clues. Tests like the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA) are used. The TST and IGRA, however, aren’t reliable for detecting an active TB infection. For this, we use tools like mycobacterial culture and molecular methods.
The TST involves injecting a small volume of tuberculin antigens (a substance which provokes an immune response), and watching the immune response. If you’ve been exposed to TB, and your immune system is functioning normally, you’ll develop an area of hardness and possible redness on your skin. You’ll need to come back 2 to 5 days after getting the TST so a healthcare professional can check for this response.
However, the TST can sometimes give false-positive and false-negative results. A false-positive may happen in people who were vaccinated with the Bacille Calmette–Guérin (BCG) vaccine, have been exposed to environmental non-TB mycobacteria, or were previously exposed to TB but have cleared the infection. A false-negative could happen due to incorrect administration or interpretation of the TST, or in patients whose immune system is weakened.
The IGRA is a blood test that measures the immune system’s response to TB-specific substances not found in the BCG vaccine or most non-TB mycobacteria. This test is more specific to TB exposure than the TST but is also more expensive and time-consuming. It may give false-negative results in certain circumstances, such as in older adults and people with weakened immune systems. A false-positive may occur due to contamination of the specimen with live TB organisms. Sometimes, the result may be unclear, possibly due to a weakened immunity or autoimmune conditions.
Neither the TST nor IGRA are very useful for checking how well TB treatment is working. Testing of early morning sputum samples, where we look for the TB bacteria (Mycobacterium tuberculosis), is a more reliable way to detect active TB. If such a sample tests positive, it confirms that the person has an active TB infection and can infect others. Consequently, they need to be isolated and their contacts traced and tested.
Chest Radiography and Sputum Samples
A chest X-ray can help rule out active TB in people who aren’t showing symptoms of the disease. However, if the X-ray or symptoms indicate possible TB or some other condition, further testing will be needed. Some conditions can have symptoms similar to TB, including silicosis, cancer, sarcoidosis, autoimmune disorders, and several infections.
Treatment Options for Latent Tuberculosis
Tuberculosis (TB) is a bacterial infection that can be tough to treat because the bacteria that causes it is resistant to many antibiotics. When someone has latent TB, it means they house the bacteria but don’t exhibit symptoms. This type of TB is usually treated with one or two antibiotic drugs that are specifically effective against these bacteria.
On the other hand, treating active TB, particularly a type that affects the lungs, is more complicated. Usually, a combination of antibiotic drugs including rifampicin, isoniazid, pyrazinamide, and ethambutol are used for about two months. If tests show that the patient’s TB is sensitive to rifampicin and isoniazid, these two drugs may be continued for around four more months, while the use of pyrazinamide and ethambutol is stopped.
People who have been in close contact with patients suffering from TB that is resistant to many drugs are likely to harbor latent TB themselves, and are more at risk of developing a drug-resistant form of active TB. Despite this, there is still limited evidence to aid best practices in treating such individuals. As such, the approach to managing latent TB in these cases is often dependent on expert opinion and the careful evaluation of the treating doctor regarding the patient’s risk of developing drug-resistant TB.
The main goal of treating latent TB is to prevent it from turning into active disease. However, since most people with latent TB will never exhibit symptoms in their lifetime, the risks associated with the disease must be weighed against the potential health hazards of the treatment itself, especially liver toxicity which is a potential side effect of one of the antibiotics used, isoniazid. To help evaluate this balance of risks and benefits, a number of clinical tools have been developed for doctors to estimate the probability of accurate latent TB testing, the risk of latent TB reactivation, and the risk of severe liver toxicity from the treatment.
As for the drug regimen to treat latent TB, the three most commonly used methods are: rifampicin taken daily for 3 to 4 months, a combination of either rifampicin or rifapentine and isoniazid taken for 3 to 4 months, or taking isoniazid alone on a daily basis for 6 to 9 months. The choice among these options is usually based on factors like cost, effectiveness, how likely the patient is to stick to the treatment plan, and potential side effects, including liver toxicity.
Isoniazid is an antibiotic that fights against TB specifically by blocking the production of some vital components of the bacterial cell. Although it is pretty affordable, it has a higher risk of side effects. Rifampicin and rifapentine, part of rifamycins, a group of antibiotics, are known to inhibit DNA activity of a wide range of bacteria, including TB. Rifapentine, a long-lasting form of rifampicin, can be taken once a week.
The effectiveness of these latent TB treatment strategies can range from 60% to 90% success rates and can offer that protection for up to 19 years. However, for people with HIV living in areas with a high TB occurrence rate, the best length of time for latent TB treatment isn’t well-verified due to the possibilities of multiple exposures leading to TB and the changes of the immune system due to HIV.
What else can Latent Tuberculosis be?
Latent TB infection is a tricky condition to diagnose. Doctors cannot rely on a single test for an accurate diagnosis. Instead, they must thoroughly evaluate a patient’s medical history, x-ray results, and results from immunological tests. People with this form of TB do not show any symptoms, they are only spotted because of screening. When doctors are determining whether a person has latent TB, they also have to consider whether the patient might be suffering from active TB or NTM infections. Both of these conditions can cause false positives in immune-based tests.
Let’s break down some of the diagnoses doctors have to consider:
- Active Tuberculosis Disease: To rule this out, doctors need to see that the patient shows no symptoms of active TB and has a normal chest x-ray. If they’re still not sure, they might collect early morning sputum samples for tests including stain, culture, and nucleic amplification tests. They may also require extra tests like imaging, biopsy, or a spinal tap if there are signs of TB in other parts of the body.
- Resolved Tuberculosis Infection: Sometimes, patients who show no symptoms but have tests showing prior exposure to TB might have already had TB and either been treated or cleared the infection naturally. It’s crucial for doctors to collect detailed information about previous exposures and treatments. Doctors then weigh the risks and benefits for each patient when deciding whether to treat for latent TB infection.
- Bacille Calmette–Guérin (BCG) Vaccination: The TST test isn’t just specific to tuberculosis, which means that it might give a false-positive for people who have been vaccinated with BCG.
- Nontuberculous Mycobacterial Infection: Similar to BCG vaccination, TST isn’t just specific to tuberculosis, it might show a false-positive for those exposed to environmental NTM like M avium-intracellulare complex, M scrofulaceum, and M kansasii.
What to expect with Latent Tuberculosis
Latent TB infection treatment works by eliminating the TB bacteria before they can cause active tuberculosis. The established treatment regimens for latent TB infection have a success rate between 60% and 90%. Without treatment, between 5% to 15% of people with latent TB infection will eventually develop active TB during their lifetime.
Certain factors related to the individual, the TB bacteria, and the environment can increase a person’s risk. However, it’s impossible to predict with absolute certainty which people with latent TB infection will go on to develop TB disease. As a result, 90% of patients treated for latent TB infection may experience the side effects of treatment without gaining any benefit from it. Thus, deciding to start therapy for latent TB infection requires a careful assessment of each patient’s situation.
Possible Complications When Diagnosed with Latent Tuberculosis
It’s crucial to limit the risks associated with treating latent TB infection. One effective way of doing this is by regularly checking liver function in patients who are more likely to experience liver toxicity. These check-ups can happen during routine clinic visits or case management meetings.
Despite worries about increasing drug resistance due to the treatment of latent TB infection, extensive systematic meta-analyses haven’t confirmed these worries to be valid. However, it would still be beneficial to have drug resistance surveillance systems in place, just in case such an outcome occurred.
Key points:
- Maintaining liver function is critical in treatment for latent TB infection.
- Regular check-ups are made to monitor potential liver toxicity.
- Concerns of increased drug resistance due to treatment has yet to be proven by systematic meta-analyses.
- It’s recommended to have surveillance systems for monitoring possible drug resistance.
Preventing Latent Tuberculosis
Taking your medications correctly and consistently is very important in effectively treating dormant TB infection. Medical professionals have recently begun recommending simpler medication routines that take less time, to make it easier for patients to stick to their treatment plan. The chances of patients taking their medicine regularly also improve with support from peers, help from case managers, and educational resources.
It’s important to understand what TB infection is and why treatment is so important. When patients understand their condition, they are more likely to engage in their treatment plan and take their medication regularly. Patients should be informed about potential side effects that can accompany the treatment, like hepatotoxicity, which means harmful effects on the liver. They should also be told when to get more medical help.
