Stay vigilant, stop tuberculosis, and pay attention to this “killer” that has been with mankind to this day

Human beings are lucky and sad. Fortunately, humans have the only high-level intelligence on earth. This is how humans can realize the smallness of life. Even if we invent sophisticated machinery and chemical drugs with extremely clever molecular structures, we have never really beaten the size of only humans. One billion, one in billions of bacteria.

Human beings are not the ruler of nature, and have never been the earliest creatures on this land. In the primitive ocean billions of years ago, when multicellular organisms struggled to survive and evolve, the ancestors of bacteria were already born. In the Cambrian period 500 million years ago, strange creatures such as weird worms, strange shrimps, and goblet worms were the protagonists in the ocean. Bacteria competed and multiplied cruelly; when dinosaurs, these cold-blooded and warm-blooded creatures spread all over the Cretaceous land When the early mammals of our ancestors could only compete with rodents for a limited living space, a large number of bacteria could infect countless species. And as the ancient apes came to the ground from a tree for the first time in Africa, they used the most shallow tools to smash the dried fruit shells, the fire of civilization was ignited, but the disease and death caused by bacteria were still not burned. When Homo sapiens migrated to all parts of the world and became the only extant species under the genus of man, it was not only assimilation and killing, but also this group of history may be much longer than human beings, and even the birth of life more than 2 billion years ago A kind of small life has been formed in the early stage-bacteria.

There are many kinds of ancient human infectious diseases, and tuberculosis is one of the oldest even if it is not the oldest human infectious disease. Some research papers on molecular genetics related to fossil samples and human genes speculate that the ancestors of tuberculosis may have the ability to infect human ancestors in East Africa 3 million years ago. During this period, the ancestors of all humans, Australopithecus australis, are in the early stage. Ape-man transition. Anthropological, archaeological, and genetic studies of Native Americans have found that American Indians have never lacked tuberculosis. These tuberculosis originated from the “death migration” of ancient humans out of Africa and across the frozen Bering Strait. The colonists It was not the first time that Mycobacterium tuberculosis came to America in 1492, but the European Mycobacterium tuberculosis that spread afterwards caused horrific killing and injury to the Indians.

The earliest direct archaeological evidence of human infection with tuberculosis comes from ancient human fossils in Germany and ancient Egyptian mummies, which are estimated to be more than 7,000 and 4,400 years ago. The earliest written records of tuberculosis can be found in the earliest extant classics of the great traditional Chinese medicine-“Huang Di Nei Jing”, in which the description of “five deficiency and five labors” accords with the obvious characteristics of tuberculosis. The same symptoms are also recorded in the Eastern Han Dynasty Zhang Zhongjing’s “Golden Chamber Synopsis” and Hua Tuo’s “Zhong Zang Jing”. Later, Hippocrates of ancient Greece, the father of modern western medicine, also named tuberculosis “phthisis”, which was widely used until the 19th century. The common name “consumption” is more often used in English, which is literally translated as “consumption”. It is an apt description of the image of the patient’s weight loss and weakness caused by the chronic consumption of tuberculosis. It is as vivid as the Chinese word “tuberculosis”. Mankind has long recognized the terrible transmission ability behind this “frailty”, and Hua Tuo’s “Zhong Zang Jing” in “Zhang Shi Lun” put forward the theory of “tuberculosis” infection. In 1834, a German doctor, Johann Lukas Schönlein, first referred to these types of lesions in various organs collectively as “tuberculosis”, that is, “tuberculosis”.

The plague has largely affected human history, and tuberculosis is no exception. The famous music poet Chopin was tortured by tuberculosis. At the last moment of his performance, he splattered blood and stained the keyboard. Finally, he regretfully left the last words of “please bring my heart back to the motherland”. He was only 39 years old. The well-known Austro-Hungarian writer Kafka has a melancholic and absurd style. Due to the deterioration of tuberculosis, the world lost the opportunity to read his unfinished three novels. This is the eternal regret of countless people. The famous British poet Keats had hemoptysis for the first time in 1820. He went to the warm Rome to recuperate but failed to save his illness. The life of literature ended in 1821. And the world-famous Princess Sissi had to leave her child and beloved Her Majesty Franz because of severe lung disease (a kind of tuberculosis that progressed very fast), and left the old-fashioned and depressing Habsburg royal court. Suffered from the disease several times to go to Corfu, Madeira and other places to recuperate. Before the era of antibiotics, the relatively scientific and most effective way to treat tuberculosis was to live in a sanatorium with warm, humid and fresh air. Bed rest and good nutritional support can make about half of the patients heal on their own, but most of them still face the threat of recurrence of tuberculosis.

Find the pathogen, the disease does not appear in a vacuum
The symptoms that may be contagious, incurable, and debilitating are the only medical scientists’ knowledge of tuberculosis for a long time. The speculation that tuberculosis is infectious has lasted for nearly a thousand years, but there are also many doctors who believe that tuberculosis is genetically predisposed from the clustering characteristics of family members. It was not until the middle of the 19th century that German doctor Klencke (in 1842) and French doctor Villemin (in 1865) successfully infected rabbits with necrotic tissue taken from tuberculosis patients, that people confirmed that tuberculosis was really an infectious disease.

Thanks to Louis Pasteur (the inventor of the pasteurization method), his experiments let people know that diseases and microorganisms do not spontaneously “generate from the air”, and scientists also judged that there must be a microorganism invisible to the naked eye. The spread of tuberculosis. Looking back at the thousands of years of struggle with tuberculosis in the history of human civilization, the real turning point is the identification of the pathogen of tuberculosis, that is, the discovery of Mycobacterium tuberculosis. After going through weird detours such as using grass roots, tree bark, insects to make medicines, and the touch of the king, humans have finally embarked on a rational path for tuberculosis prevention and control, and there is no need to fumble in the dark.

Among them, a German doctor named Robert Koch played an important role. High temperature and high pressure sterilization of experimental equipment and bacterial culture solution before use, and then smear the biological sample on the glass slide, press the cover glass after staining, and then observe under the microscope. Bacterial staining identification technology is commonplace today. However, in the 19th century, when Dr. Koch first proposed it, it caused a violent sensation. As a result, mankind has obtained an effective means of bacterial observation and identification and has been used to this day. These indispensable basic technologies have laid the cornerstone of modern microbiology.

Koch used these innovative technologies that he established himself to first discover the Bacillus anthracis that causes anthracnose, and introduced his advanced bacteriological new technologies at the Seventh International Medical Congress held in London in August 1881, which made his colleagues , Even the enemy Pasteur was greatly admired. As the premier catastrophic disease at the time, the etiology of tuberculosis attracted the attention of other doctors to Koch almost immediately, trying to use new technology as a way to find the cause of tuberculosis.

Technological innovation can sometimes directly bring about breakthrough progress. The fog on the tuberculosis pathogen has only persisted in the face of Koch’s new technology for less than 8 months. On the evening of March 24, 1882, Koch formally announced his discovery at an academic meeting of the Berlin Physiological Society: He used the method of sectioning/smear staining to observe from the tuberculosis tissue of artificially infected laboratory animals. When it comes to bacteria, the method of staining Mycobacterium tuberculosis is also introduced in detail. In May 1882, several creative doctors improved Koch’s detection technique and perfected the “acid-fast staining” technique for Mycobacterium tuberculosis that is still used in countless hospitals today. Since time immemorial, the “murderer” who has never been seen by the world has been placed in front of hundreds of experts in a very short period of time for people to circulate, and the detection method has also gone from inception to mature in a very short period of time. And still in use today, this is another unheard and incredible thing in human history, but it is not so surprising in the age of scientific discoveries.

In 1905, the Nobel Prize was awarded to Dr. Koch as expected to reward him for his pioneering work of revealing the face of Mycobacterium tuberculosis. In 1995, 90 years later, the World Health Organization designated March 24 when Dr. Koch first reported on Mycobacterium tuberculosis as “World Tuberculosis Day.”

Mycobacterium tuberculosis never rests or discriminates
From millions of years ago to today, although with continuous evolution and mutation, the lethality of Mycobacterium tuberculosis has declined and it can “better” coexist with humans, but its threat to humans has never been eliminated .

The struggle between Mycobacterium tuberculosis and humans has never stopped. It is like a tireless demon. It never rests or discriminates. It treats the backward and developed people equally, and continues to wreak havoc in the rural areas of Africa and Southeast Asia. I have traveled to world cities like London and Paris. In 1993, 28 years ago, humans first applied GPS navigation to civil aviation aircraft. The astronauts of the Space Shuttle Endeavour repaired the Hubble telescope, which could detect the world 14 billion light-years away, but it was the same year. Forced by the severe global tuberculosis epidemic, WHO declared a global tuberculosis emergency and called for global emergency mobilization to strengthen tuberculosis control. In 1995, 3 million people worldwide died of this disease, which was the year with the largest number of deaths from this disease. It greatly exceeded the tuberculosis epidemic in 1900. In the same year, the WHO designated March 24 every year as World Tuberculosis Day.

According to a report by the World Health Organization, 1.4 million people died of tuberculosis in 2019 (including 208,000 people living with HIV), a number exceeding the past 20 years (United Nations International Disaster Reduction Strategy “Poverty and Death: 1996-2015 Disasters” Mortality report) the total number of deaths due to natural disasters in the world. Globally, tuberculosis is one of the top ten causes of death and the leading cause of death from a single source of infection (more than HIV/AIDS).

According to WHO data, an estimated 10 million people worldwide will suffer from tuberculosis in 2019, including 5.6 million men, 3.2 million women, and 1.2 million children. Tuberculosis exists in all countries and age groups, which also shows that Mycobacterium tuberculosis is treated equally: humans are generally susceptible. Even with the most successful tuberculosis vaccine in these years-BCG, it can only reduce the infection rate of children and prevent children from becoming infected with Mycobacterium tuberculosis from severe conjugate diseases, such as tuberculous meningitis, hematologically disseminated tuberculosis, etc. Severe tuberculosis has very limited protection for adults.

In the past cognition, tuberculosis is more of a disease of poverty and backwardness. It is often associated with messy, crowded slums, small labor dormitories with hundreds of people living together, and assembly line factories that are one after another and only stand upright. . And these living environments have been improved in the past 100 years of development. The declining incidence and mortality of tuberculosis have been attributed to the BCG vaccine, new screening methods and effective drugs. The most important factor is the improvement of the economic development level of the country and the people’s living and working conditions. Dr. Ye Hui, deputy chief physician of the Infectious Disease Center of West China Hospital of Sichuan University, said frankly, “We know that there are usually three links in eliminating infectious diseases: eliminating the source of infection, cutting off the route of transmission, protecting the susceptible, and economic development and working and living hygiene. Improving conditions is an important part of cutting off the route of transmission.”

At present, tuberculosis is ranked second in the number of cases and deaths among China’s legally reported Class A and B infectious diseases, second only to AIDS. The transmission is strong and the infection rate is high, but the onset of tuberculosis is not rapid. Most of the incubation period of tuberculosis bacteria in the human body will last for several years, and some people will not even develop the disease for life, and become carriers of the walking pathogen. For most people, if the immune function declines due to some reasons, the risk of tuberculosis will be greatly increased. “In recent years, the main high-risk groups include HIV patients, long-term immunosuppressive patients, people over 65 years of age, and diabetic patients. In healthy people, those with weakened immunity will also have an increased risk of developing tuberculosis. The places where mycobacteria are transmitted are relatively closed surveillance places such as schools, nursing homes, and prisons. Poor ventilation, lack of disinfection and sun exposure will increase the risk of transmission of Mycobacterium tuberculosis.”

Drug-resistant bacteria are frequent, and non-standard treatment is the culprit
Bacterial drug resistance is a very serious problem. This is the inevitable survival direction of bacteria as human medical scientists progress. Mycobacterium tuberculosis is no exception. For a long period of time, the invention of multiple anti-tuberculosis drugs has greatly reduced the death rate of tuberculosis. Countless people no longer need to repeat the fate of those artists and writers in the Enlightenment era. It seems that tuberculosis is no longer worthy of attention. But the discovery of drug-resistant tuberculosis bacterium makes people panic to realize that the “white plague” has never gone far.

“In 2019, 3.3% of new tuberculosis cases and 17.7% of relapsed cases worldwide were infected with Mycobacterium tuberculosis that is resistant to multi-drug or certain anti-tuberculosis drugs. Worldwide, China, India, and Russia are global The three countries with the highest share of drug resistance burden. According to the 2019 data, the incidence of new drug-resistant tuberculosis in China is 7.1%, and the incidence of drug-resistant tuberculosis in returning patients is 23%, which is higher than the global average.” The epidemic of tuberculosis is undoubtedly one of the major challenges facing the prevention and control work in the future.

Under normal circumstances, the treatment time for drug-resistant tuberculosis is 18-24 months, or even 3 years, far exceeding the half-year treatment cycle of ordinary tuberculosis. At the same time, there is a wide gap in the cost of drugs required for treatment, and the cost of drug-resistant tuberculosis may be 100 times or more than the cost of ordinary tuberculosis treatment. If the patient fails to adhere to the long-term standard treatment, it may develop extensively drug-resistant tuberculosis, making it more difficult to cure.

According to Dr. Ye, there are two main factors leading to the frequent occurrence of drug-resistant tuberculosis. The first is that the treatment is not timely and the treatment is not standardized. “Intermittent medication is very likely to produce MDR-TB. But not all MDR-TB are transformed from ordinary tuberculosis. Some people are already multi-drug-resistant once they become ill. Drug tuberculosis”. The second is the patient’s compliance problem. If the patient does not or refuses to follow the doctor’s instructions for the full course of treatment during the treatment process, it will also greatly increase the probability of drug-resistant infections.

“Currently, the form of drug resistance of Mycobacterium tuberculosis is very severe, and the difficulty of clinical diagnosis and treatment is relatively high, and it also puts forward higher requirements on the clinical treatment of doctors.” The core strategy is to standardize treatment, pay attention to pathogenic examination, and Improve patient compliance. “At present, we emphasize on individualized and standardized treatment for patients, and assist patients to receive standardized treatment under the full supervision of doctors. This is not only responsible for the patient, but also protecting the people around the patient. “Combined treatment, full and adequate treatment.” It is the principle of treatment.” On the other hand, in addition to the traditional sputum smear culture and tuberculin experiment, the pathogenic examination also needs to use molecular biology and other methods to identify the type of Mycobacterium tuberculosis infected in time, so that the drug can be used It is more accurate and avoids wrong, ineffective, and inefficient drug treatment to increase the probability of drug-resistant tuberculosis. Adequate treatment can also prevent the spread of drug-resistant strains. Dr. Ye said frankly, “Patient education is also very important. Improving compliance and cooperating with standard treatment will inevitably improve the treatment effect.”