Mycobacterium Tuberculosis: 150 Million Years in the Making

tuberculosis-990x545If you were to ask the average person to name the worst epidemic diseases in history, they would probably start that list with bubonic plague, or the Spanish flu. Some would even list Ebola. Few, however, would think to mention tuberculosis. Moreover, while it is not a common infection in the modern industrialized world today, it is making a comeback, even here in the US, particularly in the South and South West.

Although it is possible for a healthy person to harbor the Mycobacterium that causes tuberculosis, the immune system can often prevent us from becoming symptomatic. For this reason, physicians make a distinction between two forms of tuberculosis. Latent tuberculosis can be thought of like a milder form of infection where you have a tuberculosis infection, but the bacteria remain in an inactive state and cause no symptoms. It is estimated that as many as 2 billion people have a latent form of tuberculosis.

Active tuberculosis often makes us very ill, and can easily be spread through coughing. It can occur in the first few weeks after infection with the tuberculosis bacteria, or it might occur years after infection. According to the Centers for Disease Control and Prevention, the symptoms of active tuberculosis according to the Mayo Clinic include coughing that lasts three or more weeks, coughing up blood, chest pain or pain with breathing or coughing, unintentional weight loss, fatigue, fever, night sweats or chills and a loss of appetite. It needs to be mentioned that coughing up blood should be immediately addressed with a physician.

Tuberculosis can also affect other organ systems, including kidneys, spine or brain. When tuberculosis occurs outside the lungs, signs, and symptoms, vary according to the organs involved. Tuberculosis of the spine may cause back pain, while tuberculosis in your kidneys might cause blood in the urine.

The pathogen that causes tuberculosis in humans is considered to have originated over 150 million years ago, according to scientists who have sequenced the genes of several forms of the pathogen. As the human species evolved over the past 3 million years, the tuberculosis bacterium was an ever-present companion. Moreover, as humans evolved, so did the tuberculosis pathogen. Scientists today considered modern members of the tuberculosis pathogen family most probably evolved from a common African ancestor between 15,000 and 40,000 years ago. It would appear that East Africa, long accepted as the ancestral home of humanity, is also the ancestral home of the tuberculosis bacilli.

Our earlier ancestors were wandering hunter-gatherers, and they had reached most of Europe and Asia easily, and while it is thought that the bearing straight provided a land bridge from Asia to North America, glacial ice blocked access to the New World, until approximately 50,000 years ago. There is, however, arguments that Monte Verde in Chile suggests human occupation in South America as far back as 33,000 years ago. As in Egypt, archaeological evidence of tuberculosis has been found in South America as well. Archaeologist and anthropologist have discovered evidence of tuberculosis in mummified remains from Peru, and tuberculosis DNA has been recovered from these tissues. While the Europeans may have brought smallpox and other infectious diseases to the Americas, science had demonstrated that tuberculosis was in the New World long before modern Europeans were.

Written records from Egypt documented tuberculosis over 5000 years ago, and archaeologist and anthropologist have discovered typical skeletal abnormalities of tuberculosis in mummies dating from the earliest kingdoms. Egyptian mummies unearthed exhibit Pott’s deformities, named after Percivall Pott, who presented the classic description of what was then known as spinal tuberculosis. Today, Pott’s disease or tuberculous spondylitis is a severe form of musculoskeletal tuberculosis that destroys the spine. These spinal deformities have been found in human remains from the European Iron Age and in mummified remains from Pacific coast of South America. There was also mention of tuberculosis noted in the books of Deuteronomy and Leviticus and was well-established in East Africa by the time the Europeans reach the area in the 1800s. Written records describing tuberculosis in the subcontinent suggest that it was well known nearly 4000 years ago, and similar text from China describe tuberculosis as early as 2400 years ago.

The disease was also known in classical Greece, and Hippocrates both recognized and understood it is clinical manifestation. In his book Of The Epidemics, he wrote that the disease was the most considerable and consumptive, and the only one that proves fatal to many people. Galen, the physician to the Roman emperor Marcus Aurelius, recommended treating tuberculosis with fresh air, warm milk, and sea voyages, apparently for the cool, moist air.

As Europe entered the Middle Ages, records of tuberculosis became sparse. While there is archaeological evidence from widespread areas throughout Europe for tuberculosis after the fall of the Roman Empire in the fifth century, little was written about the disease.

Throughout human history, tuberculosis has claimed millions of lives and reached epidemic proportions in both the old world and the new throughout human history. Learning the pathogenesis of tuberculosis began with the work of Théophile Laennec, the French physician, and inventor of the stethoscope in 1816, which pioneered its use in the investigation of what were then known as chest conditions. A few decades later, another French physician, Jean-Antoine Villemin, demonstrated the transmissibility of tuberculosis as a communicable disease. Then, in 1882 Robert Koch identified the bacillus as the agent causing tuberculosis.

It was not until 1907 that an Austrian physician and scientist by the name of Clemens Freiherr von Pirquet developed a skin test for tuberculosis, and after some refinement, it was used to test for latent tuberculosis in asymptomatic children. He is also remembered as contributing to the new field of bacteriology and immunology. Once the pathogenesis had been established, public health measures to combat the spread of tuberculosis emerged. Beginning in the late 1800s, sanatoriums began to appear where patients with tuberculosis could be isolated, and too often, forgotten.

Nevertheless, research for a cure was ongoing, and the Bacillus Calmette–Guérin Vaccine, or BCG was developed as a primary defense against tuberculosis, was broadly implemented following World War I. In countries where tuberculosis is still a common malady, the BCG vaccine is recommended in healthy babies as close to birth as possible. The modern era of tuberculosis treatment can be said to have the begun with the discovery of streptomycin in 1944, and improved by the discovery of isoniazid in the early 1950’s. Still, treatment of tuberculosis was a long process with an often-uncertain outcome.

Tuberculosis has plagued humanity for much of his existence and is thought to have killed more people than any other microbial pathogen. It has surged in many epidemics before receding, as other infectious epidemics have, but the vast amounts of time between epidemics defy even modern understanding of epidemic cycles, and still today we do not fully understand this disease. Even with treatment, recovery from tuberculosis today is at best 90%.

Today more than twenty drugs are available to treat tuberculosis. They are used in differing combinations, depending on circumstance. Most of these drugs are quite old, having been developed in the mid 20th century. Once a patient’s course of treatment is finished, they will continue to be tested for tuberculosis. Often more treatment is needed if tests show remaining bacteria, however, but most people respond well. Even when a patient us cured, it is possible to become infected again; therefore once treatment is completed, patients are informed to report new symptoms immediately.

Despite the treatments and preventions available, tuberculosis claims the lives of nearly 4,000 people every day worldwide. Just a very few notable persons who have died from tuberculosis include Egypt’s Tutankhamun (1323 BC), John Keats (1821), Emily Bronte (1847), George Orwell (1950), and Arline Feynman, the wife of famed physicist Richard Feynman (1945). Many more celebrities were treated and cured of tuberculosis.

March 24 is World Tuberculosis Day; an annual event meant to draw attention to the plight of millions of people around the world who continue to suffer and die from this preventable and curable disease. Think TB, is a movement that underscores that tuberculosis is often misdiagnosed because healthcare professionals do not consider tuberculosis as a diagnosis in developed nations.

For more information, please see the CDC’s Tuberculosis page at https://www.cdc.gov/tb/default.htm

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