The Invisible and Invincible Invader:

 Mycobacterium tuberculosis

"Tuberculosis is as old as humanity itself — only by working together can we turn the tide against this ancient killer (Global Tuberculosis Report 2024, 2024)."

 

Introducing a Microbial Mastermind

Mycobacterium tuberculosis is a sneaky and resilient bacterium that causes tuberculosis (TB): a deadly disease that has taken millions of lives for decades (Kyu et al., 2018). This invader mainly affects the lungs but can also spread to other organs causing havoc (Baykan et al., 2022).

What makes it almost invincible? Their cell walls: made up of a complex mixture of components makes them resist many antibiotics and survive harsh circumstances (Batt et al., 2020). TB can get to a person by just a sneeze or a cough from an infected person as it spreads through air (Patterson & Wood, 2019). However, we still have a chance to defeat this invisible enemy by early diagnosis, effective treatment and preventive measures.

 

A Deadly Intruder on the Move

Tuberculosis is an airborne disease and can get transmitted easily (Dinkele et al., 2022). When a person infected with TB coughs, sneezes or even speaks, hundreds of tiny droplets containing Mycobacterium tuberculosis can get released in to the air and remain suspended for hours; mostly in crowded and poorly ventilated spaces (Patterson & Wood, 2019). And if someone inhale these droplets, these invisible enemies can enter to their lungs and cause infection. Therefore, it’s important to have proper ventilation and the use of masks can be helpful (Lee, 2016).

 

M. tuberculosis v Immune System

With the entry of this tiny pathogen, a microscopic battle is about to unfold inside the lungs. These invaders are taken up by alveolar macrophages: immune cells that works as the first line of defence in lungs (Hauwermeiren & Lamkanfi, 2023). Nevertheless, these pathogens hide inside the phagosome of these cells and inhibit the phagosome-lysosome fusion with the help of virulence factors. This leads to the survival and multiplication of bacteria (Queval et al., 2017).

After a few weeks, infected macrophages start to alert the immune system (Flynn et al., 2011). As response, immune cells like macrophages, dendritic cells, neutrophils and T-cells starts building a fortress called granuloma that can trap the bacteria and contain the infection (Ramakrishnan, 2012).

 

Figure 1: Typical Structure of a TB Granuloma. This diagram illustrates the different types of immune cells that make up a TB granuloma (Pai et al., 2016).

 

However, Mycobacterium tuberculosis knows exactly how to outsmart these immune strategies. They release chemical signals to attract weak immune cells that would make a barrier against killer T-cells from reaching them (Chandra et al., 2022). Inside this fortress, these invaders stay hidden and asleep for years. This is called latent TB. But if the immune system weakens due to factors like stress or illness, they strike back causing active TB disease (Zhai et al., 2019).

The immune system uses several steps to fight this smart and dangerous enemy.

•       CD4⁺ T cells release interferon gamma (IFN-γ) as signals to activate macrophages to kill the pathogen.
•        CD8⁺ T Cells kill infected cells.
•     Cytokines and chemokines coordinate the attack.
•       B-cells and antibodies help locate the pathogens (Liu et al., 2017).

Despite all these mechanisms, Mycobacterium tuberculosis is not ready to give up the fight. They inhibit dendritic cell activity, that prevents antigen presentation and thereby postpones T-cell activation (Mihret, 2012). They can also change the behaviour of macrophages from pro-inflammatory to anti-inflammatory and weaken the immunity (Refai et al., 2018). And if the fortress collapse, it will lead to lung damage and cavitation as its’ caseous core can flow into airways and destroy healthy tissue (Kayongo et al., 2023).

 

Detection Systems: How To Screen and Diagnose Tuberculosis

Ever wonder how to detect these invaders before someone gets sick? Screening tests like Mantoux tuberculin skin test (TST) can detect TB before they start showing symptoms. But it can give false positives to the individuals vaccinated with BCG (Muñoz et al., 2015). Interferon‑Gamma Release Assay (IGRA), that measures immune cells' response to TB antigens can give you more accurate results than TST (Lu et al., 2016). If the symptoms start showing, we can use chest x-rays and computer-assisted detection systems (CAD) for TB identification (Melendez et al., 2016).

If TB is suspected, the doctors can do confirmation tests like following.

•       Sputum smear microscopy (Ziehl–Neelsen) - a rapid, low-cost and a moderately sensitive test used often in clinical laboratories (Umair et al., 2020).
•        Mycobacterial cultures - more specific, accurate and detect small amounts of bacteria. However, these may take weeks to show results (Campelo et al., 2021).
•        Xpert MTB/RIF molecular test - provide results within 2 hours and can detect rifampicin resistance with high sensitivity and specificity (Boehme et al., 2011).

 

Counterattack on Tuberculosis with Treatments

We need treatments to overcome TB. Even though some strains are easily eliminated by drugs, some stay resistant and survives.

Drug‑Susceptible TB

Patients can be treated using a 6-month course of four key antibiotics—isoniazid, rifampicin, pyrazinamide, and ethambutol. And it can be shortened to just 4 months using combinations like rifapentine and moxifloxacin. It is important to take each dose to prevent drug resistance (Pai et al., 2016).

·                Drug‑Resistant TB

Figure 2 shows a treatment regimen for multi-drug resistant (MDR-TB) tuberculosis (Seung et al., 2015).

 

Figure 2: Design of a MDR-TB regimen (Seung et al., 2015).

Mapping the Enemy

WHO Global Tuberculosis Report 2024 confirms that TB has caused 10.8 million cases and 1.25 million deaths in 2023 which is highly concerning (Global Tuberculosis Report 2024, 2024). There is a significant risk of disease activation because approximately one-third of the world's population carries latent TB, and in places like sub-Saharan Africa and South Asia, up to 50% of people do. The threat is worsened by HIV and malnutrition, and rising drug-resistant TB strains (Semba et al., 2010).

TB is not only a medical problem; our social structures and surroundings have a significant impact on it. TB risk is increased by poverty, overcrowding, humidity, air pollution, and inadequate health services. We need better living conditions, cleaner air, and more competent public health services that target disadvantaged people if we are to effectively fight tuberculosis (Liyew et al., 2024).

 

Conclusion

Despite its long history, TB is still a deadly and sneaky threat in the modern world. Millions of people are affected to this day even with the improvements in diagnosis and treatment. We can fight TB by understanding how it spreads and survives within the lungs. There’s a chance to end this global threat with the help of ongoing research and public health projects. However, awareness, action and dedication are much needed.

References

 

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