Tuberculosis

What is Tuberculosis?

Tuberculosis (TB) is a disease that can be prevented. This disease is caused by a bacteria called Mycobacterium tuberculosis. The World Health Organization has set a target of reducing the rate of TB by 90% between 2015 and 2035. Yet, TB remains difficult to detect, treat, and avoid. Before the COVID-19 pandemic, TB was the most common disease affecting people around the world. Unlike the virus that causes COVID-19, the bacteria that causes TB has been around for thousands of years.

Diagnosing TB is done using two different tests, the Mantoux skin test and an approach developed in 2014 known as the interferon-gamma release assay. However, these tests have their own limitations and can be difficult to interpret. This is complicated by the slow-growing nature of the TB bacteria and its often sparse presence in samples from the patient’s sputum (mixture of saliva and mucus coughed up from the lungs) and tissue.

To overcome these difficulties in diagnosing TB, new tests have been developed that work by identifying the bacteria’s genetic material. Yet, these tests are not widely available in many parts of the world where TB is most common. The best ways to use these tests are still being figured out, and newer tests are gradually being developed to improve accuracy.

Treating TB is also challenging. The most frequently used TB medicines, which were developed back in the mid-20th century, are still the first choice for treatment. Recently, new medications have been approved for treating TB for the first time in over 40 years. What treatment a patient gets, however, depends on factors such as the stage and location of the infection, the patient’s age and immune status, other health conditions, any side effects, potential drug interactions, and how resistant the bacteria is to drugs. The number of TB bacteria that are resistant to treatment is increasing, meaning newer combinations of drugs are often required. This, coupled with the long duration of treatment needed to completely eliminate the bacteria, poses a significant challenge. However, recent advancements have led to shorter treatment plans for latent TB that minimizes the side effects of the drugs and improves treatment adherence.

Despite these efforts, preventing TB worldwide remains an issue. The disease is easily spread, and situations such as poverty, overcrowding, and insufficient public health services increase the spread. Symptoms such as an ongoing cough might not be recognized as signs of TB, leading to high transmission rates. Eliminating the disease becomes even more challenging when areas most affected by TB lack sufficient healthcare resources, as was highlighted by the COVID-19 pandemic. In parts of the world where TB is relatively rare, many healthcare providers may not have much experience with the disease, and might not be familiar with its signs, diagnostics, and treatment methods.

What Causes Tuberculosis?

The tuberculosis family is a group of closely related viruses that cause disease in both humans and animals. The main type of this virus that affects humans is called M tuberculosis. Other types like M bovis, M africanum, and M canetii also infect humans. These bacteria live on oxygen, they don’t form spores or move on their own. The bacteria have a high concentration of fats in their cell walls, which helps them stick around or “stain” even when treated with acid and this could also be why they are so good at attacking the immune system. Tuberculosis bacteria grow slowly, generally taking about 20 hours to multiply.

It usually takes 3 to 8 weeks to see visible growth on lab testing plates, hence making it difficult to diagnose the disease early. Humans are the only known carriers of M tuberculosis, although other animals can get infected. Various types of the bacteria exist worldwide, which may affect their ability to cause disease.

These bacteria live inside the cells of the body, where they can cause disease that develops slowly over time. They also have the ability to remain dormant inside infected cells, where they might or might not cause disease. As per current knowledge, we don’t yet understand the cellular and immune system-related processes that cause these bacteria to become dormant or reactivate. This topic is an essential subject of research.

Risk Factors and Frequency for Tuberculosis

Tuberculosis (TB) is a disease that affects a huge number of people across the globe. Once infected, 90% of people develop a dormant form of the disease. Around 5% become seriously ill within the first two years of infection, with another 5% becoming sick at a later time. Certain factors increase the risk of the disease becoming active, such as a weakened immune system, smoking, and heavy alcohol use. The immune system could be weakened due to various reasons like:

• Older age
• Genetic diseases that lower immunity
• HIV
• Having an organ transplant
• Long-term use of corticosteroid drugs
• Certain cancer treatments
• Use of certain drugs that treat autoimmune disorders
• Malnutrition
• Diabetes

According to the World Health Organization (WHO), in 2022, TB caused 1.3 million deaths worldwide, a decrease from 1.4 million in 2020 and 2021. It is one of the deadliest diseases for those with HIV, causing 167,000 deaths in 2022. About 7.5 million people were diagnosed with TB in 2022 with the majority of these cases in Southeast Asia, Africa, and the Western Pacific. Globally, about 10.6 million people are currently living with active TB, and about a quarter of the world’s population is infected.

In the United States, there were 9,615 new cases of TB reported in 2023, an increase from 8,300 cases in 2022. This is a trend of increasing numbers after nearly three decades of decline. Most cases appeared in non-US-born individuals and across all age groups spread across 40 states and the District of Columbia. An important point to note is that most of these cases are not from recent infections but from the reactivation of dormant TB. Also, TB is seen to have a minimal risk among US-born individuals compared to certain racial and ethnic groups reflecting persistent health disparities.

The COVID-19 pandemic has had a severe impact on the fight against TB both in the US and around the world. Healthcare professionals have been focused on treating COVID-19, leading to fewer diagnosed cases of both dormant and active TB. This has resulted in a decrease in cases of TB in 2020, which may also be due to the decline in global migration during the pandemic. Globally, we can estimate that half a million more people died from TB between 2020 and 2022 than would have been expected if the pandemic hadn’t disrupted health services.

Increased cases of both latent and active TB since 2021 or 2022 is likely due to a backlog of cases that were not diagnosed during the pandemic. The global concern, however, is drug-resistant TB, with about 13% of new cases and 17% of repeat cases resistant to some standard TB drugs.

The various types of drug-resistant TB include:

• Rifampicin-resistant TB that might also be resistant to other TB drugs, including isoniazid
• Isoniazid-resistant TB that is not resistant to rifampicin
• Multidrug-resistant TB (MDR-TB) which is resistant to both main TB drugs, rifampicin and INH
• Extensively drug-resistant TB, which is resistant to several key drugs

Around half a million new cases globally in 2018 showed resistance to multiple drugs, a situation that threatens global public health. Because of the complexity of treating and managing these drug-resistant strains, there has been a push to intensify treatment programs.

Signs and Symptoms of Tuberculosis

Tuberculosis, or TB, is a disease that causes symptoms like cough, fever, weight loss, sweating at night, and feeling generally unwell. These symptoms can be quite common to other illnesses, making TB harder to diagnose.

Doctors in areas where TB is common might suspect it more readily, but in places where TB is rare, it might not be the first diagnosis doctors consider. TB isn’t always in the lungs; it can show up anywhere in the body, which makes it even trickier to diagnose.

When assessing a patient, doctors look for risk factors such as past TB history, known contact with someone who has TB, the patient’s country of origin, their travel history, family history, exposure at home or work, weakened immune system, and whether the person’s immune system isn’t working as well as it should.

People who carry the TB bacteria but aren’t sick display no symptoms; this is known as latent TB. TB can also be active but still not cause symptoms in the early stages.

As active TB disease progresses, patients may start to experience a cough, fever, night sweats, weight loss, and cough up blood before seeking out medical advice. Depending on how far along the TB disease is, a doctor examining the patient’s lungs might not find anything abnormal, or might find consolidated areas, inflamed airways, or cavities.

Chronic TB disease can cause extensive damage to the lungs, potentially leading to chest deformities due to loss of lung volume. If TB bacteria infect an organ other than the lungs, symptoms will vary.

Here are the key points to remember:

• Cough
• Fever
• Weight loss
• Night sweats
• Feeling unwell
• Latent TB causes no symptoms
• Early active TB might not cause symptoms
• Later stages of active TB might include symptoms such as coughing up blood
• Chest deformities in chronic TB
• Unusual symptoms if TB bacteria are in other organs

Testing for Tuberculosis

Tuberculosis (TB) can be a challenging disease to diagnose. The type of TB (whether it’s dormant, active in the lungs, or has spread to other parts of the body) can vary the diagnosis approach. Currently, the best way to confirm a case of TB involves a mix of imagining techniques, microbiology, molecular tests, biomarkers, and seeing how the body responds to certain tests.

When someone comes to the clinic suspecting symptoms of TB, their doctors will begin taking some tests to confirm the diagnosis. However, the results from these tests may confuse, sometimes, because different factors can affect the sensitivity and exactness of diagnostic tests. These factors include age, how well the patient’s immune system is working, how well they follow test procedures, how good the collected specimen is for the test, and the patient’s risk factor, to name a few.

Regarding imaging tests specifically, they could show both normal and abnormal formations that do not necessarily indicate TB. Without a firm verification provided by a culture exam (a lab test that checks a sample of body fluids or tissue for bacteria, yeast, and other microorganisms), the diagnosis of TB is assumed based on how closely patient symptoms match with typical TB signs, as well as indirect markers of infection. Thus, misdiagnosis could happen based on where the patient lives or where they come from.

People considered at high risk of TB should get screened to check whether they have latent (inactive) TB. These people include patients with HIV, close contacts of individuals with active TB, patients starting specific kinds of therapy, dialysis patients, organ or bone marrow transplant recipients, those with certain occupational exposures, and people living in areas with high TB prevalence, among others.

Multiple tests are available for screening latent TB. Most common ones are the Mantoux test, IGRA, or TBSTs. These tests work by checking your immune system’s response to TB bacteria. In the United States, IGRAs are often the preferred test, with Mantoux test being the alternative in case IGRAs are too costly or unavailable. The choice mainly depends on available resources and ease of use.

However, these tests are not always accurate. They can produce false-negative results, particularly in patients with weakened immune systems. False-positive results can also occur due to previous TB exposure or vaccination or due to certain types of mycobacteria. The IGRA tests are generally more sensitive in identifying TB in patient coinfected with HIV compared to traditional Mantoux tests.

Imaging techniques, such as X-rays and CT scans, can provide valuable support during the diagnosis process. Still, their interpretation can be complicated due to the variety of possible findings and the different stages of the disease.

Laboratory tests like cultures and acid-fast bacilli smears are often used to confirm TB diagnoses. Some molecular tests can provide quick confirmation of TB, but the correct choice and interpretation of these tests depend on multiple factors like TB prevalence in the area, the goal of testing, patient population, costs, available resources, and pretest probability.

When it comes to active TB disease, the gold standard for diagnosis confirmation is via a culture. However, this method often faces practical difficulties due to the challenge of obtaining a proper samples, the frequent scarcity of bacteria, and the slow growth of the organism. Thus, often, the diagnosis is presupposed based on pre-test parameters along with evidence from imaging techniques, molecular tests, and biomarkers.

To sum up, diagnosing TB can be a complicated process that requires a combination of multiple tests and procedures. This process could be influenced by various factors and requires a careful interpretation considering the patient’s overall health status and risk factors.

Treatment Options for Tuberculosis

Latent infections, such as tuberculosis, cannot be predicted from progressing to an active state by just using a skin test and blood tests. Studies suggest that the risk of becoming active is highest in the first two years of catching the infection and it’s less likely for reactivation after ten years post infection. There is still an ongoing debate on whether it is necessary to treat latent TB in low risk patients. However, World Health Organization (WHO) recommends treatment for latent TB based on the probability of it turning into a full-blown disease, especially in high risk groups.

In attempting to manage latent TB infection, the Centers for Disease Control and Prevention (CDC) recommend a preferred preventive treatment plan, although some individuals might experience symptoms of a systemic drug reaction (which often disappears within the first month of treatment). Proceeding with treatment helps reduce the probability of a full-blown case in high risk individuals. There are also recommended alternatives by WHO for TB preventative therapy for those who may have presumably been in close contact with individuals carrying the drug resistant form of TB, which is multi-drug resistant tuberculosis (MDR-TB). Research is ongoing to determine the efficiency and safety of certain drugs as part of the therapy.

The end goal of anti-TB therapy is to completely rid the body of the disease and prevent the transmission of the disease. Standard treatment guidelines are followed globally, although they may vary in duration based on individual characteristics. Managing TB can be quite challenging as there are numerous factors to consider including the presence of other diseases, age, pregnancy, and breast feeding. Adhering strictly to TB treatment plan is crucial for successful treatment.

Until 2022, standard treatment for pulmonary TB involved an intensive phase of therapy of about two months which involves the use of a combination of four drugs; INH, rifampin, ethambutol, and pyrazinamide. This is then followed by a continuation phase where a two-drug combination which is used for another four months. In certain cases, treatment extension could be required such as in persons who are malnourished, smokers or with HIV or other immune suppressing conditions.

Treating drug-resistant tuberculosis is more complicated than treating drug-susceptible tuberculosis. More extended treatment regimens which range from 18 to 21 months and often feature different drugs are usually employed for the treatment of the former. New treatments are reorganized and can include agents such as delamanid, bedaquiline, pretomanid, and others.

A live vaccine made from a strain of the mycobacteria, Bacille Calmette-Guerin (BCG), provides some protection against TB in infants and children. However, its efficacy decreases with time and it doesn’t provide protection to adults. Even though it’s recommended by WHO, use of the vaccine can also cause false-positive TSTs. In instances where the patient has a discordant result (TST-positive/IGRA-negative), majority of the experts’ consensus leans towards starting the TB preventive therapy a few weeks prior the onset of the immunosuppressing intervention.

What else can Tuberculosis be?

If someone is showing signs of tuberculosis (TB) for a long time, there are several other conditions the doctor might want to rule out:

• Infections that can’t be easily traced back to a cause
• Persistent, unexplained fevers
• Various types of lung infections including bacterial, nontuberculous mycobacteria, viral, fungal, and parasitic
• Neoplasias, such as lung, blood disorders, metastatic tumors, kidney, peritoneal, and gastrointestinal
• Diseases triggered by the body’s immune system attacking itself
• A condition called sarcoidosis, which causes clusters of inflammatory cells in different parts of your body
• Reactions to medications

What to expect with Tuberculosis

The success rate of treating patients with TB, who can follow a prescribed treatment plan, can exceed 95%. The outcome might shift depending on factors like how far the disease has progressed, delayed treatment, other pre-existing health conditions, age, requirement for artificial breathing support, resistance to medication, and harmful effects of drugs.

Research indicates that new treatment methods are likely to help boost outcomes for patients being treated for drug-resistant TB.

According to the World Health Organization’s 2018 estimates, the following success rates were observed for TB treatment:

* 85% for people with new and relapsed TB
* 76% for people coinfected with HIV
* 57% for people with MDR-TB, a form of TB that is resistant to multiple drugs

Sadly, over 80% of deaths related to TB occur in low- and middle-income countries. Throughout 2022, the WHO estimated around 1.13 million deaths among people without HIV and about 167,000 deaths among HIV positive individuals. It’s significant to note that TB is the primary cause of death in HIV patients.

Moreover, it’s estimated that around 15% of patients with drug-resistant TB die from the infection, and out of these, 26% deaths are due to extensively drug-resistant TB (XDR-TB), a more severe form of the disease. For untreated individuals without HIV, the lifetime chances of dying from TB could be as high as 70%.

However, it’s quite challenging to predict the outcome of untreated TB. Several factors like variable healthcare resources around the world, individuals not getting treatment, the rise of drug-resistant strains, and differing underlying health conditions make it difficult to estimate. Furthermore, relying on data from before modern chemotherapy may not give us an accurate picture due to differences in data collection and patient selection.

Possible Complications When Diagnosed with Tuberculosis

The complications that can arise from tuberculosis (TB) are dependent on where the infection is in the body. These complications are seen more often in people who are at risk due to issues such as poverty, malnutrition, and war. People with compromised immune systems due to HIV or other conditions, those on long-term immune-suppressing medication (like steroids or certain antibodies), or individuals with a poorly developed immune system are also at a higher risk. Furthermore, people who have jobs where they’re exposed to harmful substances, like in mining or construction, are at risk too.

During the treatment of TB in the lungs, complications can include the collection of pus in the lungs, a collapsed lung, severe difficulty in breathing, and abnormal dilation of the bronchi among other problems. If TB has spread throughout the body, it can lead to complications like meningitis, bone tumors, and bone destruction. Many of the acute complications of TB can result in long-term health issues. Even though TB is a common disease with around 155 million survivors worldwide in 2020, we don’t know much about the complications that can occur after the infection.

When TB affects the brain, it can lead to various problems:

• Lung-related issues like extensive lung damage, severe difficulty in breathing, and sometimes needing surgery to remove damaged parts of the lung.
• Lung infection with a specific type of fungus
• A condition in which abnormal proteins build up in organs (Systemic amyloidosis)
• Damage to specific nerves in the neck

Preventing Tuberculosis

The process of eradicating tuberculosis (TB), a dangerous lung disease, faces several roadblocks. These include:

1. Social situations such as poverty and overcrowding, which can make the disease spread more easily.
2. Lack of political interest and support in addressing the issue.
3. The signs and symptoms of TB might not always be clear and specific, which makes it harder to identify the disease.
4. The disease may not show any symptoms at all, which is known as asymptomatic TB.
5. Doctors might not always think of TB when they are trying to determine what’s causing a patient’s symptoms.
6. The tests used to detect TB are not always accurate, which means they might miss some cases (lack of sensitivity) or incorrectly identify TB when it’s not really present (lack of specificity).
7. People often don’t know enough about TB, which is referred to as TB illiteracy.
8. TB treatment involves taking a lot of pills for a long time, which can be hard for patients. The treatment may also cause unpleasant side effects.
9. TB patients sometimes fail to take their medications as directed, which can make treatment less effective.
10. There may not be enough resources devoted to public health outreach to effectively fight TB.
11. We don’t currently have strong enough vaccines that can prevent TB infection.