Tuberculosis (TB) is the result of Mycobacterium tuberculosis infection to the lungs. In fact, the most common pulmonary manifestation of tuberculosis is pulmonary disease. Nevertheless, tuberculosis can manifest itself in many ways. As a whole, respiratory, gastrointestinal, lymphoreticular, central nervous, musculoskeletal, and reproductive systems are the targets of this bacteria, as well as the liver and skin. Indeed, even thousands of years back, TB has been circulating among people. However, the global fight against tuberculosis, such as eradication, has seen some promising results over the past few decades, especially since 2000. That is to say, every year there’s a 1.5% decrease in tuberculosis incidence, and a 22% reduction in TB mortality rate from 2000 to 2015 according to the WHO.

Causes of tuberculosis:

Without doubt, Mycobacterium tuberculosis is what causes the disease. This obligate-aerobic, facultative, non-spore-forming, non-motile organism has a very poor response to the Gram stain; therefore, it cannot be classified as gram-positive or gram-negative, and it goes under the “ghost cell” term. In comparison with other organisms, mycolic acid, cord factor, and wax-D are present in the cell wall as lipids making it acquire distinct features, such as:

• Multiple antibiotic resistance.
• Inability to stain due to lack of response to gram stain and other stains.
• Adaptability to extreme conditions resulting in survival under acidic or alkaline, and oxygen low conditions, as well as survival inside macrophages (intracellular).

Symptoms of tuberculosis:

• Persistent cough
• Difficulty breathing
• Chest pain
• Spitting blood coming from lungs or bronchial tubes
• Fever
• Weight loss
• Night sweats

Tuberculosis risk factors:

There were 1.7 million deaths attributed to TB in 2016; of the deaths related to TB, 22% occurred in people who were simultaneously infected with HIV. Knowing that only active tuberculosis is contagious, risk factors are:

• Immunosuppression: such as people having HIV/AIDS, and dealing with chronic immunosuppressive therapy such as steroids, monoclonal antibodies against tumor necrotic factor. Also, patients with primary immunodeficiency disorders, some cancers, diabetes, and kidney disease.
• Age: children are more prone to TB infection due to the nascent immune system.
  Social determinants: wars, poverty, and malnutrition.
• Work environment: construction, mining, and pneumoconiosis (silicosis resulting from excessive inhalation of silica dust).
• Traveling to or living in certain countries of the world: including Indonesia, India, China, Pakistan, Nigeria, South Africa and Latin America.
• Contact: being close to someone having active tuberculosis increase the risk of acquiring the disease via droplets inhalation.
• Tobacco smoking and substance using: Tobacco, drugs, and alcohol all increase the risk of having TB and death.

When to see a doctor:

Without doubt, see a doctor if you have any of the symptoms mentioned above. Thus, for people at a high risk of tuberculosis, the Centers for Disease Control and Prevention recommend a latent TB infection screening. People with high risk of tuberculosis include:

• Healthcare providers working with TB cases
• People who use IV drugs
• HIV/AIDS patients
• People exposed to TB rich areas
• People coming in close contact with TB patients
• Prisoners or people who work there due to closed space

Tuberculosis diagnosis:

Staining:

A Ziehl-Neelsen stain is one of the most frequently used methods for diagnosing tuberculosis. To initially stain the patients' sample, carbol fuchsin (pink color stain) is used, followed by acid-alcohol decolorization and counter-staining with methylene blue (usually blue). In a positive sample, the original carbol fuchsin color would stay, thus the term “alcohol and acid-fast bacillus”.

Tuberculin skin test with PPD:

There is insufficient specificity in this test, and patients must return for interpretation plus a chest x-ray for confirmation. Despite its relative sensitivity, the Mantoux reaction isn't very specific and can give false-positive reactions in individuals with previous BCG vaccination history.

Blood test:

The blood test measures how your immune system reacts to the TB bacteria. It is able to confirm or rule out latent or active tuberculosis. Most importantly, a one-time visit to the doctor is enough in this case. When you have recently received the BCG vaccine or are at high risk of TB infection but don't respond to a skin test, you might need a blood test.

Chest x-ray:

An x-ray of the chest is recommended to determine whether or not there is active disease in every screening test positive situation.

Culturing:

Sputum samples might be tested for tuberculosis bacteria, as well as to detect drug-resistant strains of TB. Indeed, this can help your doctor select the right medication for you. Meanwhile, a couple of weeks can go by before you receive the results of these tests.

Nuclear Amplification and Gene-Based Tests:

Genexpert and DR-MTB are examples of new diagnostic methods for tuberculosis. To clarify, these methods help identify the bacteria or bacteria particles using DNA-based molecular techniques.

How to prevent tuberculosis:

To avoid infection by TB:

Vaccination: It is common to give infants bacille Calmette-Guerin (BCG) vaccinations in countries where tuberculosis is more prevalent. However, the BCG isn’t effective in adults in the United States.

Wearing mask: If you're near a patient or work in the healthcare industry, it increases your risk of infection. Thus, keeping a mask can always protect you.

Washing hands frequently: Not only this is very necessary not to just avoid TB, but also other diseases too.

To avoid transmitting the infection to others:

Try to stay indoors: During the first weeks of going through treatment, it's important to avoid places full of people such as work or school.

Wear a mask: First three weeks of treatment must always pass while you keep a mask on around people.

Ventilation of the bedroom: Fresh air helps removing all the built-up germs in a closed space.

Covering mouth: Laugh, cough or sneeze while using a tissue to minimize droplets spreading.

Treatment of tuberculosis:

The mainstay of TB treatment is combination therapy. Certainly, monotherapy is not suitable to treat tuberculosis. To illustrate, typical anti-TB medication regimen includes these drugs "First line medication":

• Isoniazid
• Rifampicin
• Rifabutin
• RIfapentine
• Ethambutol
• Pyrazinamide

It is always advisable to add Vitamin B6 to Isoniazid to prevent neural damage. Also, Rifampicin, Isoniazid, Ethambutol and Pyrazinamide are given together in a 4-drug regimen for two months or six months. Moreover, patients taking isoniazid must have a liver function test. In addition, patients taking Ethambutol need to monitor for retinopathy.

In case of Tuberculosis drug resistance:

According to A 2016 study, more than 5% of 10.4 million deaths related to TB are resistant to at least two of the first-line drugs. Hence, these drugs are taken for 20 to 30 months.

• Injectable aminoglycosides (Amikacin, Kanamycin, and Streptomycin)
• Injectable polypeptides (Capreomycin and Viomycin)
• Oral or injectable fluoroquinolones (Levofloxacin, Moxifloxacin, Ofloxacin and Gatifloxacin)

In case of multi-drug resistant TB:

All the previously mentioned drugs are important for treatment in addition to Bedaquiline and Linezolid.

Side effects of medication:

Above all, following up and monitoring these side effects is vital for a successful treatment. As a matter of fact, most of these side effects can be managed with close monitoring or by adjusting the dose. Therefore, a close monitoring of these side effects or an adjustment to the dose can typically manage most of them.

Isoniazid:

• Increase in aminotransferases that’s asymptomatic
• Hepatitis
• Hypersensitivity
• Peripheral neurotoxicity

Rifampin and Rifapentine:

• Vomiting
• Nausea
• Pruritis
• Hepatotoxicity
• Orange bodily fluids

Rifabutin:

• Hepatotoxicity
• Uveitis
• Neutropenia
• Polyarthralgia

Ethambutol:

• Retrobulbar neuritis

Pyrazinamide:

• Nausea
• vomiting
• Hepatotoxicity
• Polyarthralgia
• Rash
• Photosensitive dermatitis
• Acute gouty arthritis

Complications:

The active disease usually affects your lungs, but you can also develop tuberculosis elsewhere in your body. Without treatment, the disease is deadly. In short, some TB complications are:

• Back pain 
• Stiffness
• Arthritis at the hips or knees, known as Tuberculosis arthritis
• Meningitis swelling that stays for weeks
• Cardiac tamponade where the heart can't pump blood effectively
• Kidney or liver issues

References:

-Adigun R, Singh R. Tuberculosis. [Updated 2022 Jan 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

-Mayoclinic “Tuberculosis”

-Koch A, Mizrahi V. Mycobacterium tuberculosis. Trends Microbiol. 2018 Jun;26(6):555-556. doi: 10.1016/j.tim.2018.02.012. Epub 2018 Mar 23. PMID: 29580884.

-Suárez I, Fünger SM, Kröger S, Rademacher J, Fätkenheuer G, Rybniker J. The Diagnosis and Treatment of Tuberculosis. Dtsch Arztebl Int. 2019 Oct 25;116(43):729-735. doi: 10.3238/arztebl.2019.0729. PMID: 31755407.

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