Tuberculosis: The Oldest Diseases To Affect Humankind

Tuberculosis (TB) identified as one of the oldest diseases to affect humankind, continues to remain one of the top ten causes of death worldwide (Grossman, 2014). It is more common among foreign born people from countries with a high incidence of TB including: Asia, Africa, Russia, Eastern Europe, and Latin America. Furthermore, it is found to predominant among populations with low income, limited access to health care, IV drug users, and among residents of high-risk congregate settings such as health care workers, nursing homes, correctional facilities, drug treatment facilities, and homeless shelters (Nachiappan et al.

, 2017). According to the World Health Organization (WHO) approximately 10 million people in 2017 became ill with TB, with 1.6 million succumbing to the preventable and curable disease (WHO, 2018).

On a national level, in 2017 a total of 9,093 TB cases were reported in the United States (U.S.), with a slight 1.8% decrease from 2016 (WHO, 2018). From a local standpoint, the Fresno County Department of Public Health (FCDPH) identified 62 active TB cases in 2016 thereby ranking Fresno County 8th in the state (FCDPH, 2016).

To reduce the number of TB cases worldwide the WHO released a 2015 campaign which served as a blueprint for countries to overall reduce the rate of TB by 80%, TB deaths by 90%, and to eradicate disastrous costs for TB-affected households by 2030 (WHO, 2018).

Lakhani and Sundaram in their research article, “Deep Learning at Chest Radiography: Automated Classification of Pulmonary Tuberculosis by Using Convolutional Neural Networks,” identified one of the barriers to the “End TB” campaign was the lack of radiology interpretation skills in many of the TB prevalent locations (Lakhani, 2017).

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The absence of these skills can be counterproductive to the screening efficacy and work-up since chest radiographs and rapid molecular diagnostics are the recommendations set forth by the WHO (Lakhani, 2017). To help combat this barrier researchers utilized deep convolutional neural networks (DCNNs) for detecting TB on chest radiographs. AlexNet and GoogleNet software’s were used to review 150 test cases, of the 150 cases disagreement between the two software’s were noted on 13 cases. A cardiothoracic radiologist reviewed and correctly interpret all 13 cases. This radiologist-augmented approach allowed for a sensitivity factor 97.3% sensitivity and 100% specificity (Lakhani, 2017).

The use of DCNN’s shows to be valuable in TB prevalent locations, although researchers found areas for improvement and considerations, by using the radiologist-augmented approach as an overread or where there is disagreement can improve overall accuracy and help expedite the implementation of DCNNs. History of Tuberculosis: Although TB is identified as being one of the oldest infectious diseases to haunt humanity the scientific breakthroughs that would make a difference on how we understand the disease did not occur until the end of the 19th century (Grossman, 2014). Rene Laennec, a French physician, would ultimately pay with his life at the age of 45 for his contributions to TB research after contracting the disease himself (Frith, 2014). With his invention of the stethoscope in 1816 he was able to correlate what he auscultated on live patients and compare that to the lesions found in his autopsied patients. It is important to note that TB was not known to be infectious until 1869 when Laennec’s colleague Jean Antoine Villemin, isolated the TB infected tissue and found when it was inoculated into rabbits they as well became sick and died to (Frith, 2014).

Despite the important findings of Laennec and Villemin, the most recognized name associated with advances in TB research was that of Robert Koch, a German physician and scientist, who won a noble peace prize for his work (Frith, 2014). With his new method of staining bacteria which made the bacteria more visible and easier to identify he was able to obtain bacteria in its pure culture form. In 1882 he released publication on tuberculosis noting that the bacteria come from tubercle bacillus. In 1896 Koch announced he believed the protein tuberculin that was derived from tubercle bacilli possessed curative properties (Frith, 2014). Although his hypothesis was proven wrong it did, however provide an important diagnostic tool, that we still use today known as the Mantoux tuberculin skin test (TST), discovered by Charles Mantoux in 1908 (Frith, 2014). Shortly after Koch’s discovery, another important figure came forth contributing to the field of diagnostics that being Wilhelm Roentgen. Wilhelm Roentgen, a German mechanical engineer and physicist, won a noble peace prize for his contributions to medicine due to his discovery of X-rays in 1895 (Frith, 2014). Roentgen’s discovery allowed physicians to diagnose and track the progression of the disease, a diagnostic tool that is still widely used today for the same reasoning (Frith, 2014). Pathogenesis of Tuberculosis:

There are several forms of tuberculosis, however Mycobacterium tuberculosis hominis (M. tuberculosis) is the most common (Grossman, 2014). The rod-shaped bacteria possess a waxy exterior making the bacteria more resistant to destruction thereby permitting it to persevere in old necrotic and calcified lesions while remaining capable of reinitiating growth (Grossman, 2014). Although, M. tuberculosis has the capability of infecting nearly every organ in the body it is predominantly found to infect the lungs due to the high affinity the bacteria have for oxygen rich environments (Grossman, 2014). It is important to note that not everyone infected with M. tuberculosis will not develop its active form known as latent TB. Latent TB does not produce any symptoms, those with latent TB typically have a positive TB skin test reaction or a positive blood test, although an individual with latent TB may convert under the right circumstances. On the other hand, active TB develops when the hosts immune system cannot stop the overgrowth of the bacteria which is commonly seen in HIV/AIDS population (Grossman, 2014). People often present with a cough that lasts 3 weeks or longer, chest pain, coughing up blood, weakness or fatigue, unexplained weight loss, no appetite, chills, fever, and night sweats (Grossman, 2014). M. tuberculosis being an airborne infection spreads via micro respiratory droplets, which can remain in the air for several hours (Nachiappan et al., 2017).

Coughing, sneezing, and talking within confined spaces create an environment with the potential to enter a host and trigger a cell-mediated immune response (Nachiappan et al., 2017). According to Nachiappan et al., “Not all individuals exposed to tuberculosis get infected. The probability of transmission to another individual depends on the infectiousness of the tuberculosis source, the environment and duration of exposure, and the immune system is inadequate at controlling the initial infection” (Nachiappan et al., 2017). Once the bacteria are introduced to a host it makes it way down the respiratory tract finding itself settling within the alveoli, where alveoli macrophages begin to engulf the bacteria. Unfortunately, due its waxy exterior it withstands being killed, however the initial encounter by alveoli macrophages continue to signal out a cell-mediated immune response thus containing the infection (Grossman, 2014). As the tubercli multiply the macrophages damage the bacteria and present their antigens to T lymphocytes resulting in an increase in lytic enzymes where they can aid in the destruction of the mycobacterium (Grossman, 2014). Once the lytic enzymes are released they have the potential to damage lung tissue, the entire process results in the growth of gray-white lesion called Ghon focus (Grossman, 2014).

The lesions can be found in the subpleural area of the upper segments of the lower lobes or in the lower segments of the upper lobes. High levels of the organism cause a hypersensitivity reaction resulting in the central portion of the Ghon focus to undergo soft, caseous necrosis. During this time the tubercle bacilli begin to drain along the lymphatic channels into the tracheobronchial lymph nodes (Grossman, 2014). The blend of the primary lung lesion (Ghon focus) and lymph node granulomas is known as the Ghon complex. Once the complex begins to heel it becomes fibrous and calcified which is visible radiographically (Grossman, 2014). Diagnosing Tuberculosis: The most commonly used diagnostic tool include the tuberculin skin test and chest x-ray (Grossman, 2014). Nachiappan et al., identified the vital role imaging plays in the diagnosis of TB in their research article titled “Pulmonary Tuberculosis: Role of Radiology in Diagnosis and Management” (Nachiappan et al., 2017). According to the algorithm provided by Nachiappan et al., when there is suspicion or concern for active TB chest radiographs should be obtained as part of the initial work-up (Nachiappan et al., 2017).

If the chest radiograph comes back negative and the individual tests negative for HIV, then there is no need to continue further diagnosis. However, if the chest radiograph is positive and is HIV negative then the next step is sputum AFB smear and culture X3 (Nachiappan et al., 2017). For HIV positive patients, a chest radiograph should be ordered, but the results should not be used to guide treatment, because this population may have a normal chest radiograph with active TB. Once active TB is identified treatment should begin immediately in both populations (Nachiappan et al., 2017). Although clinical manifestations may not match findings from chest radiographs or computed tomographic (CT) it should still warrant for airborne isolation until further workup such as sputum cultures are obtained (Nachiappan et al., 2017). It is important to note that those who have a positive skin test will mostly like have a positive skin test for the rest of their lives, but it does not necessarily mean the person has active TB. What it does indicate is that the person has had an exposure at some time or another, however the body’s cell-mediated immunity against the organism has developed.

As previously noted chest radiography is not always effective in developing countries as a form of diagnostics due to the lack of proper interpretation. In the study conducted by Lakhani and Sundaram they were able to identify which software works more efficiently in recognizing TB. The software used considers “machine learning approaches using a combination of textural abnormality and shape detection” (Lakhani & Sundaram, Pg. 575, 2017). Additional diagnostic tools include Quantiferon-TB Gold (QFT-TB Gold), which is used to detect active and latent TB by measuring interferon-y (associated with cell-mediated immunity) (Grossman, 2014). This test can be expensive but has a quick 24-hour test result turnaround (Grossman, 2014). Definitive diagnosis of active TB includes sputum cultures, acid-fast stain, gastric aspirations, or bronchial washings (Grossman, 2014). Treatment: Villemin’s discovery of TB being an infectious disease led to the first established isolation sanitariums to help treat tuberculosis. One interesting method of treating TB at these sanitariums was to induce a pneumothorax in the infected lung, a process that took place under fluoroscopy (Bushong, 2017). Due to the increased level of exposure it was reported the incidence of radiation induced breast cancer was as high as 10:1 (Bushong, 2017).

Fortunately, lesser extreme methods to treat TB where developed with the use of antibiotic therapy during the 1940’s. Today there are a total of 10 drugs approved by the U.S. Food and Drug Administration (FDA) to treat TB, of the approved drugs the first line of treatment includes: Isoniazid (ING), Rifampin (RIF), Ethambutol (EMB), and Pyrazinamide (PZA). To effectively treat TB, it is necessary the full course of antibiotic therapy be taken as prescribed which can be as short as 6-9 months. Not completing the full course can result in the development of resistant TB thereby unnecessarily compromising organs involved with metabolism and filtration such as the liver and the kidneys (Grossman, 2014). According to Grossman & Porth there are two groups of people who meet criteria for treatment those with active TB, or those who have been exposed to someone with active TB. Prophylactic treatment is recommended for those who have been infected with TB but do not display its active form. This group includes: people with a positive skin test result who have had close contact with an active TB case, previously negative test that has converted to a positive test within 2 years, those who have a history of untreated or inadequately treated TB, people who signs of TB on chest radiographs without evidence of active TB, those with special risk factors such as immunocompromised or long term treatment with steroids, people with positive HIV test or have AIDS, and those who are 35 years or younger with a positive reaction (Grossman, 2014).

The only vaccination to combat the development of TB bacillus Calmettee-Guerin (BCG), was first administered in 1921. The vaccine is still utilized today but only to those who work or live in TB prevalent locations. In conclusion, radiography continues to be used as a method to diagnosis and monitor TB treatment progression in both developed and under developed countries. Despite the efforts introduced by the WHO to reduce the rates of death and TB cases it is necessary as Lakhani et al., pointed out to better equip TB prevalent locations with better means to accurately identify active TB cases. Lakhani et al., proposed software which can aide in the identification of TB with high efficacy. Along with improved screening and diagnostic tools, education and prevention are necessary components in reducing the number of TB cases thereby reducing the number of deaths worldwide.