We fear the coronavirus that is currently running rampant across the globe, claiming almost 800,000 lives as of this writing and infecting almost 23 million people. But among the infectious diseases, a king still sits on his throne uncontested and is as cruel now as he was in the time of his discovery.
While curable and preventable, The World Health Organization’s 2020 Fact sheet details that tuberculosis killed 1.5 million people worldwide in 2018 alone, with an estimated 10 million people infected. Global Health Authorities has projected in their Sustainable Development Goals that they plan to end the TB Pandemic in the year 2030. While TB incidence is falling at 2% each year it still has to increase by 4-5% to reach some intended milestones. The continued threat of Multi-Drug Resistant Tuberculosis remains a hindrance.
The coronavirus seem to be a herald of death, akin to Marvel Comic’s the Silver Surfer, and Tuberculosis is Galactus. As it spreads through the world and thins down the medical resources, the deadlier beasts are having a resurgence. While due attention to research and medicine on Tuberculosis has not halted, the lockdowns, particularly across parts of Africa, Asia and Latin America, have raised overwhelming obstacles to patients who must travel to obtain diagnoses or drugs. Fear of COVID-19 have kept away patients struggling with TB to seek medical attention, and those who are trying to get their medication and treatment may fail to do so due to limitations in travel and deliveries in hard struck areas.
Let’s take a look on the basics of tuberculosis and why it’s aptly named in the medical field as “The Great Pretender”
The World Health organization estimates 2 billion people worldwide are infected with the bacteria, Mycobacterium Tuberculosis. That is a lot of people, but note that not all these people have symptoms.
The vast majority of these people aren’t even aware they are infected, this is because the immune system may have the ability to contain it, so it remains dormant and non-contagious, possibly even till the end of people’s lives. This differentiates tuberculosis into two, which is Latent Tuberculosis, and Active Tuberculosis infection in which the latter produces symptoms and has the ability to spread. At some point a person with latent Tuberculosis will have his or her immune system compromised with other diseases or old age that tuberculosis breaks away and becomes active.
The infectious agent of Tuberculosis, which is a Mycobacteria is quite interesting. Its name is derived from its Mycolic Acid which covers its cell wall. This in turn is detected by various laboratory diagnostics – specifically in the Zeihl Neelsen Staining technique which turns it bright red since it holds unto the red Fuschin dye after rinsing the specimen with ethanol – this reaction is termed “Acid-Fast stain” in the medical field.
The cell wall is hardy – it resists disinfectants and survives surfaces for months at a time.
Our immune system have developed various defense mechanisms to combat pathogens. Tuberculosis is usually transmitted through aerosol exposure of the lungs and mucous membranes. When a pathogen is inhaled, the lining in our upper airways usually produce mucous that pathogens stick to and then they get expelled.
In the unfortunate event that pathogens get deeper into our lungs, alveolar macrophages, the lungs’ local phagocytes – warriors of our immune system that include white blood cells – “devour” these pathogens and then fuse them inside with an organelle called a lysosome which breaks down and kills the bacteria. Tuberculosis however, evades this using weapons of its own.
One, its waxy layer shields it from break down, two the lysosome won’t fuse with the ingested TB bacteria because the bacteria creates signals that stop the process. Ultimately the TB bacteria replicates and multiplies inside the macrophage that was supposed to destroy it and burst out of it.
The first signs of infection are now seen, this is known as primary Tuberculosis. It may sound bad but most people in this stage may be asymptomatic and only have mild flu-like illnesses. About three weeks, cell-mediated immunity kicks in and the portion of the lung that is infested with the TB bacteria is walled off to prevent it from spreading, creating what is now called a granuloma – the tissue inside this walled off portion dies forming what is called a Caseuos Necrosis, which looks like Cheese.
This cheesy area is known as the Ghon focus, named after the pathologist who coined it. As the caseation of the tissues spread through the hilar lymph nodes, it is now called the Ghon complex – this mostly spreads into sub pleural areas or the lower lobes of the lungs. These complexes eventually hardens through fibrosis and calcification and can be seen in chest x-rays as scar tissue. This calcification is now called the Ranke complex – From Ghon Focus to Ghon complex to Ranke complex.
In very fortunate cases, after the scar formation, the bacteria is killed off by the immune system and that’s it, a patient may live on TB free for the rest of his or her life with a scarred portion of the lung to prove triumph. In other cases they only remain walled off, and are very much alive – which is the common path for latent tuberculosis. When the patient becomes immunocompromised such as with AIDS or old age, the ghon complex “reactivates” and spreads upward.
One factor of TB Bacteria is that it is an aerobe, or oxygen hungry, and the upper lungs are high in oxygen and therefore they are attracted to it after the primary infection on the lower portions. When this happens, know that the body has already encountered TB and is therefore quick to recognize this new outbreak and proceeds to tackle them – unfortunately these may actually help the bacteria to disseminate.
The further cavitation and necrosis in the lungs opens pathways of the TB bacteria to go through the lymphatic or vascular system – when this happens, it’s known as Systemic Miliary TB. This is where Tuberculosis gets it’s moniker of the “great pretender” as it affects various organs (even multiple organs at once) It may affect the kidney causing painful urination as a symptom, it may affect the brain and cause TB meningitis, it may affect the vertebrae and cause Pott’s disease, the adrenal glands and causes Addison’s disease, the liver causing Hepatitis, the cervical lymph nodes in the neck causing what’s known as a scrofula – some patients only go to consults for these symptoms and do not even know they went through the first stages of TB infection in the first place, which cannot be blamed on them since some primary TB infections are very mild they can be mistaken for flu.
TB is being tested using a tuberculin test, in which a person is injected with a TB component in the skin to check for a reaction. Within 2-3 days if the area injected reacts and forms a large area of induration (this usually has a measurement) and not just a rash, it is a positive test – a positive test however cannot differentiate active or latent TB and only assures that the patient has been infected at some unknown point in time.
There is also other tests that are very specific for TB, like the interferon gamma release assay (IGRA) which checks for TB proteins in the blood. A patient who had a BCG vaccine in infancy is more likely to have a negative test result, since BCG vaccines prevent TB. After obtaining a positive result with any of these diagnostic tests for TB, a chest x-ray may be followed to determine if a TB infection is active.
For patients with symptoms and are highly suspected of TB, like sputum production, fever, night sweats and coughing up blood – a sample may be taken and cultured, via sputum collection or bronchioalveolar lavage. These samples are sent to the lab for staining, culture and PCR to detect TB.
Treatment for TB varies for latent and active infection, it also varies for age. For latent infection, it’s usually Isoniazid for 9 months. For active infection, a combination of multiple antibiotics, also for many months. Treatment regimens for TB will always have an elaboration on strict compliance due to the threat of Multi Drug Resistant and Extremely Drug Resistant TB surfacing across the globe – which would be extremely hard to eradicate if it disseminates. With this the World Health Organization devised a control strategy called directly observed treatment, short-course (DOTS, also known as TB-DOTS) which is also being applied in the Philippines in their National TB-DOTS program.
Delays in Diagnosis
In the hopeful and fortunate future where the world has defeated COVID-19, there will more likely be several problems left in its wake. The lockdowns would have left most of Infectious Diseases undiagnosed and untreated, leading to a chain of events which starts with failure or late diagnoses – late treatment – More spread and then Death for the already rampant infectious Diseases such as TB and HIV.
The advancements in medicine used to combat these infectious diseases became a boon in the war against the coronavirus, yet to win this war, we may have opened Pandora’s Box in the process. Most of the machines used to diagnose HIV and TB were retrofitted for coronavirus diagnoses as of the moment, leading to less detected cases for other Infectious diseases already rampaging across the globe. The coronavirus pandemic has resulted in sharp drops in diagnoses of TB: a 70% decline in Indonesia, 50% in Mozambique and South Africa, and 20% in China, according to the World Health Organization.
Tuberculosis will more likely surge in the days after the COVID-19 pandemic, but one thing for certain is that it has a cure, it is treatable, and it can be dealt with. While it may be hard, and the battle against this tyrant king may drag further than expected, a TB free world is not an impossible undertaking.