Unmasking Tuberculosis

Unmasking Tuberculosis: Medications, Revolutionary Detection Methods, and Diagnostic Innovations

Tuberculosis is a disease that is common to us as people all around the world know about it. It is a disease not only bound to only one state or one country or one continent but it has its effects all around the world. According to WHO, a total of 1.5 million people died from TB in 2020, TB is the 13 th leading cause of death and the second leading infectious killer after COVID-19. If we go through official reports published by WHO there will be many deaths, many affected, and many seriously ill patients from different age groups from all around the world. It is estimated that one-third of the population of the world is affected by the tuberculosis bacteria Mycobacterium tuberculosis. Although many people affected by Mycobacterium tuberculosis are meant to have Latent Tuberculosis we will give details about it.

Pathology

Now let us discuss how this disease Tuberculosis is spread from person to person and in an individual body. As Tuberculosis is spread by the bacteria Mycobacterium tuberculosis. Mycobacterium tuberculosis is a bacteria that

survives with oxygen requirement. It is basically an aerobic bacteria that require enough oxygen for its survival and its metabolic process. So, tuberculosis is spread from person to person by sneezing, coughing, or by saliva exchange. If a person has affected with the bacteria Mycobacterium tuberculosis then if he sneezes the person near him/her inhales the bacteria in the air through his/her nose and reaches to the lungs in the lungs we have a mucus layer although the tuberculosis bacteria can avoid mucus layer it reaches deep airways in lungs that is alveolar layer. There we have macrophages which eat foreign materials entering our body. The actual work of macrophages is that they phagocytize them or they package them into spaces which we generally call phagosomes. In most cases of bacteria what happens is that the phagosome fuses with a lysosome to produce a hydrolytic enzyme that can break down any biochemical molecule. This is how generally macrophages act to any foreign substances. But in the case of Tb the bacteria

mechanism is a little bit tricky what happens in that case is when inside the macrophages it produces a protein PI3P phosphatase which totally inhibits this fusion of phagosome with lysosome and then the enzyme will not

get formed as a result the Tb bacteria mycobacterium survives and it spreads and proliferates to different parts of lungs and then to body causing a localized infection Primary Tb. Like at this stage what happens most people

don’t get signs as they are asymptomatic and even if they get they just get mild flu-like symptoms. So what the population thinks is that it is just a common cold or flu anything so they don’t get a difference between Tb and all those diseases.

About 3 weeks after initial infection/primary Tb, cell- mediated immunity kicks in, and immune cells surround the site of TB infection, creating a granuloma, essentially an attempt to wall off the bacteria and prevent it from
spreading. The tissue inside the middle dies as a result, a process referred to as caseous necrosis, a bit like cheese.

This area is known as a “Ghon focus”.TB also gets to hilar lymph nodes, either carried over by immune cells through the lymph or by direct extension of the Ghon focus infection, and causes caseation there as well, and together, this caseating tissue and associated lymph node make up the characteristic “Ghon complex”. Ghon complexes are usually subpleural and occur in the lower

lobes of the lungs. The tissue encapsulated by the granuloma undergoes fibrosis, and often calcification, producing scar tissue that can be seen on x-ray, this calcified ghon complex is called a “Ranke complex”. In many cases even though they are walled up from all sides they are still alive, but they’re just dormant. If and when a person’s immune system becomes compromised, like with AIDS or with aging, the Ghon focus can become reactivated, and the infection can spread to either one or both upper lobes of the lungs, it’s thought that this is because oxygenation is greatest in these areas, and TB being an aerobe, prefers areas of greater oxygenation. Since they were previously exposed, the immune system’s memory T cells quickly release cytokines to try and control the new outbreak, which forms more areas of caseous necrosis, this time, though, it tends to cavitate, or form cavities, which can allow the bacteria to disseminate, or spread through airways and lymphatic channels to other parts of the lungs, which can cause bronchopneumonia; but it can also spread via the vascular system and infect almost every other tissue in the body, called systemic miliary TB.

Tb on spreading to other parts of the body creates severe complications and severe complicated disease. Kidneys get affected which may result in sterile pyuria. It might spread to the brain causing meningitis and may also spread to lumbar vertebrae causing Pott disease. These are the cases if the disease spreads to different body parts and it may cause certain complications but it can be stopped from being complicated upon getting tested at a proper time.

Testing

How Tb is detected? There are several ways to detect Tb and there are certain stages of detection. The test of Tb often begins with a purified protein derivative which often in general is called the tuberculin skin test or the mantoux test. In this test, the person is injected with tuberculin a component of bacteria between the layer of the dermis. If the person is exposed to Tb then the immune system reacts to the system and produces a small reaction where the tuberculin is injected and it’s considered to be a positive test. A positive tuberculin test means the person once got exposed to Tb doesn’t differentiate between active or latent Tb.

As an alternative to tuberculin skin tests, there are also interferon-gamma release assays (or IGRAs) that look for evidence in the blood of previous exposure to TB proteins. Also, the IGRA is more specific to TB rather than other types of mycobacterial infections and is unlikely to be positive as a result of having a BCG vaccine in the past, a vaccine that protects against TB. And this is a pretty useful feature of IGRAs since the BCG vaccine is given to many children around the world to prevent disseminated TB. creates a large enough area of induration (rather than just redness), it’s considered to be a positive test

After doing a screening test with PPD or IGRA, anyone with a positive result typically gets a chest X-ray to look for signs of active TB disease. In patients with symptoms like fevers, night sweats, weight loss, coughing up blood, or hemoptysis. It’s important to collect samples from either the sputum, or via a bronchoalveolar lavage, which is where a bronchoscope is inserted through the mouth or nose into the lungs, fluid is squirted, and then the fluid is
collected. These samples can get sent to the lab for staining, culture, and PCR to look for evidence of mycobacterium tuberculosis.

Medication

If there is a detection of Tb in some individuals then there must be proper medication to solve the problem Treatment of latent TB infection typically involves using a single drug for a prolonged period of time—the most common

approach is Isoniazid for 9 months. Treatment of active TB disease is typically done with different combinations of anti-TB antibiotics, like isoniazid, rifampin, ethambutol, and pyrazinamide, result in patients being non-infectious to others usually within a few weeks.

Recent Research/Future Aspects

In recent times there are certain developments in the medication of Tb. Like every organism on this planet is following the evolution process so are these bacteria they mutate and form many strains like CDC1551 and H37Rv. A team led by Lobelia Samavati, M.D., professor in the Center for Molecular Medicine and Genetics in the School of Medicine Samavati's research group has worked for more than 15 years to develop technology for the detection of antibodies in various respiratory diseases. Her lab has developed a novel non-sputum-based technology and has discovered several novel immune epitopes that differentially bind to specific immunoglobulin (IgG) in TB- infected subjects. The levels of epitope-specific IgG in serum can differentiate active TB from LTBI subjects, healthy controls, and other respiratory diseases. This technology can be used as a simple serum assay non- sputum-based serological POC- TB test, which is highly specific and sensitive to differentiate active TB from LTBI. So to cope with these mutants researchers are founding new solutions to detect them and for their medications which can be summarized in the next part of this article. Still, there is a time and there when this disease may be eradicated totally from this developing world.

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Unmasking Tuberculosis