Plague is a bacterial disease. What is plague? Historical facts about cholera

plague doctor in the middle ages

For hundreds of years now, people have associated the plague with a special disease that claims the lives of millions of people. Everyone knows the destructive ability of the causative agent of this disease and its lightning-fast spread. Everyone knows about this disease; it is so ingrained in the human mind that everything negative in life is associated with this word.

What is plague and where does the infection come from? Why does it still exist in nature? What is the causative agent of the disease and how is it transmitted? What forms of the disease and symptoms exist? What does the diagnosis consist of and how is treatment carried out? Thanks to what kind of prevention is it possible to save billions of human lives in our time?

What is plague

Experts say that plague epidemics were mentioned not only in historical reference books, but also in the Bible. Cases of the disease were regularly reported on all continents. But what is of greater interest is not epidemics, but pandemics or outbreaks of infection, widespread throughout almost the entire territory of the country and covering neighboring ones. In the entire history of human existence, there have been three of them.

1. The first outbreak of plague or pandemic occurred in the 6th century in Europe and the Middle East. During its existence, the infection has claimed the lives of more than 100 million people.
2. The second case of the disease spreading over a large area was in Europe, where it arrived from Asia in 1348. At this time, more than 50 million people died, and the pandemic itself is known in history as the “plague - the Black Death.” It did not bypass the territory of Russia either.
3. The third pandemic raged at the end of the 19th century in the East, mainly in India. The outbreak began in 1894 in Canton and Hong Kong. A large number of deaths were recorded. Despite all the precautions taken by local authorities, the number of deaths exceeded 87 million.

But it was during the third pandemic that it was possible to thoroughly examine the dead people and identify not only the source of infection, but also the carrier of the disease. French scientist Alexandre Yersin found that humans become infected from sick rodents. Several decades later, an effective vaccine against the plague was created, although this did not help humanity completely get rid of the disease.

Even in our time, isolated cases of plague are recorded in Russia, Asia, the USA, Peru, and Africa. Every year, doctors discover several dozen cases of the disease in various regions, and the number of deaths ranges from one to 10 people, and this can be considered a victory.

Where does the plague occur now?

Foci of infection in our time are not marked in red on a regular tourist map. Therefore, before traveling to other countries, it is better to consult an infectious disease specialist where the plague is still found.

According to experts, this disease has not yet been completely eradicated. In which countries can you get the plague?

1. Isolated cases of the disease are found in the USA and Peru.
2. The plague has practically not been recorded in Europe for the last few years, but the disease has not spared Asia. Before visiting China, Mongolia, Vietnam and even Kazakhstan, it is better to get vaccinated.
3. On the territory of Russia, it is also better to play it safe, because several cases of plague are registered here every year (in Altai, Tyva, Dagestan) and it borders on countries that are dangerous in terms of infection.
4. Africa is considered a dangerous continent from an epidemiological point of view; most modern severe infections can be contracted here. The plague is no exception; isolated cases of the disease have been reported here over the past few years.
5. The infection also occurs on some islands. For example, just two years ago, the plague struck several dozen people in Madagascar.

There have been no plague pandemics over the last hundred years, but the infection has not been completely eradicated.

It has long been no secret that the military is trying to use many especially dangerous infections, which include the plague, as biological weapons. During World War II in Japan, scientists developed a special type of pathogen. Its ability to infect people is tens of times greater than that of natural pathogens. And no one knows how the war could have ended if Japan had used these weapons.

Although plague pandemics have not been recorded for the last hundred years, it was not possible to completely eliminate the bacteria that cause the disease. There are natural sources of plague and anthropurgic, that is, natural and artificially created in the process of life.

Why is the infection considered particularly dangerous? Plague is a disease with a high fatality rate. Before the vaccine was created, and this happened in 1926, the mortality rate from various types of plague was at least 95%, that is, only a few survived. Now the mortality rate does not exceed 10%.

Plague agent

The causative agent of the infection is yersinia pestis (plague bacillus), a bacterium of the genus Yersinia, which is part of the large family of enterobacteria. In order to survive in natural conditions, this bacterium had to adapt for a long time, which led to the peculiarities of its development and life activity.

1. Grows on simple available nutrient media.
2. It comes in different shapes - from thread-like to spherical.
3. The plague bacillus in its structure contains more than 30 types of antigens, which help it survive in the body of the carrier and humans.
4. It is resistant to environmental factors, but dies instantly when boiled.
5. The plague bacterium has several pathogenicity factors - these are exotoxins and endotoxins. They lead to damage to organ systems in the human body.
6. You can fight bacteria in the external environment using conventional disinfectants. Antibiotics also have a detrimental effect on them.

Paths of transmission of plague

This disease affects not only humans; there are many other sources of infection in nature. The greatest danger is posed by sluggish variants of plague, when the affected animal can overwinter and then infect others.

Plague is a disease with natural focality, affecting, in addition to humans, other creatures, for example, domestic animals - camels and cats. They become infected from other animals. To date, more than 300 types of bacteria carriers have been identified.

Under natural conditions, the natural carriers of the plague pathogen are:

• gophers;
• marmots;
• gerbils;
• voles and rats;
• Guinea pigs.

In urban environments, special species of rats and mice are the reservoir of bacteria:

• pasyuk;
• gray and black rat;
• Alexandrovskaya and Egyptian species of rats.

The carrier of plague in all cases is fleas. Infection of a person occurs through the bite of this arthropod, when an infected flea, not finding a suitable animal, bites a person. Just one flea can infect about 10 people or animals during its life cycle. Human susceptibility to the disease is high.

How is the plague transmitted?

1. Transmissible or through the bites of an infected animal, mainly by fleas. This is the most common way.
2. Contact, which is infected during the cutting of carcasses of sick domestic animals, as a rule, these are camels.
3. Despite the fact that primacy is given to the transmissible route of transmission of plague bacteria, the nutritional route also plays an important role. A person becomes infected by eating food contaminated with the infectious agent.
4. The methods of penetration of bacteria into the human body during plague include the aerogenic route. When a sick person coughs or sneezes, they can easily infect everyone around them, so they need to be kept in a separate box.

Pathogenesis of plague and its classification

How does the plague pathogen behave in the human body? The first clinical manifestations of the disease depend on the method of penetration of bacteria into the body. Therefore, there are different clinical forms of the disease.

Having penetrated the body, the pathogen penetrates through the bloodstream into the nearest lymph nodes, where it remains and multiplies safely. It is here that the first local inflammation of the lymph nodes occurs with the formation of a bubo, due to the fact that blood cells cannot fully destroy bacteria. Damage to the lymph nodes leads to a decrease in the body's protective functions, which contributes to the spread of the pathogen to all systems.

Later, Yersinia affects the lungs. In addition to infection of lymph nodes and internal organs by plague bacteria, blood poisoning or sepsis occurs. This leads to numerous complications and changes in the heart, lungs, and kidneys.

What types of plague are there? Doctors distinguish two main types of disease:

• pulmonary;
• bubonic.

They are considered the most common variants of the disease, although conditionally, because bacteria do not infect any specific organ, but gradually the entire human body is involved in the inflammatory process. According to severity, the disease is divided into mild subclinical, moderate and severe.

Plague symptoms

Plague is an acute natural focal infection caused by Yersinia. It is characterized by clinical signs such as severe fever, lymph node damage and sepsis.

Any form of the disease begins with general symptoms. The incubation period of the plague lasts at least 6 days. The disease is characterized by an acute onset.

The first signs of plague in humans are as follows:

• chills and almost lightning-fast increase in body temperature to 39–40 ºC;
• severe symptoms of intoxication - headaches and muscle pain, weakness;
• dizziness;
• damage to the nervous system of varying severity - from stupor and lethargy to delirium and hallucinations;
• The patient's coordination of movements is impaired.

The typical appearance of a sick person is characteristic - a reddened face and conjunctiva, dry lips and a tongue that is enlarged and covered with a thick white coating.

Due to the enlargement of the tongue, the speech of a plague patient becomes unintelligible. If the infection is severe, the person’s face is puffy with a blue or cyanotic tint, and there is an expression of suffering and horror on the face.

Symptoms of bubonic plague

The name of the disease itself comes from the Arabic word “jumba”, which means bean or bubo. That is, it can be assumed that the first clinical sign of the “Black Death”, which our distant ancestors described, was an increase in lymph nodes that resembled the appearance of beans.

How does bubonic plague differ from other variants of the disease?

1. The typical clinical symptom of this type of plague is bubo. What is he? - This is a pronounced and painful enlargement of the lymph nodes. As a rule, these are single formations, but in very rare cases their number increases to two or more. The plague bubo is most often localized in the axillary, groin and cervical region.
2. Even before the appearance of the bubo, the sick person develops pain so severe that he has to take a forced position of the body to alleviate the condition.
3. Another clinical symptom of bubonic plague is that the smaller the size of these formations, the more pain they cause when touched.

How are buboes formed? This is a long process. It all starts with pain at the site of the formation. Then the lymph nodes enlarge here, they become painful to the touch and fused with fiber, and a bubo gradually forms. The skin over it is tense, painful and becomes intensely red. Within approximately 20 days, the bubo resolves or reverses its development.

There are three options for the further disappearance of the bubo:

• long-term complete resorption;
• opening;
• sclerosis.

In modern conditions, with the right approach to treating the disease, and most importantly, with timely initiation of therapy, the number of deaths from bubonic plague does not exceed 7–10%.

Symptoms of pneumonic plague

The second most common type of plague is its pneumonic form. This is the most severe variant of the development of the disease. There are 3 main periods of development of pneumonic plague:

• elementary;
• peak period;
• soporous or terminal.

In recent times, it was this type of plague that claimed the lives of millions of people, because the mortality rate from it is 99%.

The symptoms of pneumonic plague are as follows.

More than 100 years ago, the pneumonic form of plague ended in death in almost 100% of cases! Now the situation has changed, which is undoubtedly due to the correct treatment tactics.

How other forms of plague occur

In addition to the two classic variants of the course of the plague, there are other forms of the disease. As a rule, this is a complication of the underlying infection, but sometimes they occur independently as primary ones.

1. Primary septic form. The symptoms of this type of plague are slightly different from the two options described above. The infection develops and progresses rapidly. The incubation period is shortened and lasts no more than two days. High temperature, weakness, delirium and agitation are not all signs of a disorder. Inflammation of the brain and infectious-toxic shock develop, followed by coma and death. In general, the illness lasts no more than three days. The prognosis for this type of disease is unfavorable, and recovery is almost non-existent.
2. A mild or mild course of the disease is observed with the cutaneous variant of the plague. The pathogen enters the human body through damaged skin. At the site of introduction of the plague pathogen, changes are observed - the formation of necrotic ulcers or the formation of a boil or carbuncle (this is inflammation of the skin and surrounding tissue around the hair with areas of necrosis and discharge of pus). Ulcers take a long time to heal and a scar gradually forms. The same changes can appear as secondary changes in bubonic or pneumonic plague.

Diagnosis of plague

The first stage in determining the presence of infection is epidemic. But it is easy to make a diagnosis when several cases of the disease have arisen with the presence of typical clinical symptoms in patients. If the plague has not been encountered in a given area for a long time, and the number of cases is counted in single units, diagnosis is difficult.

When an infection begins to develop, one of the first steps in determining the disease is the bacteriological method. If plague is suspected, work with biological material to detect the pathogen is carried out under special conditions, because the infection spreads easily and quickly in the environment.

Almost any biological material is taken for research:

• sputum;
• blood;
• buboes are punctured;
• examine the contents of ulcerative skin lesions;
• urine;
• vomit.

Almost everything that the patient secretes can be used for research. Since the plague disease in humans is severe and the person is very susceptible to infection, the material is taken in special clothing and cultured on nutrient media in equipped laboratories. Animals infected with bacterial cultures die within 3–5 days. In addition, when using the fluorescent antibody method, the bacteria glow.

Additionally, serological methods for studying plague are used: ELISA, RNTGA.

Treatment

Any patient with suspected plague must be immediately hospitalized. Even if mild forms of infection develop, the person is completely isolated from others.

In the distant past, the only method of treating plague was cauterization and treatment of the buboes, and their removal. In an attempt to get rid of the infection, people used only symptomatic methods, but without success. After identifying the pathogen and creating antibacterial drugs, not only the number of patients decreased, but also complications.

How is this disease treated?

1. The basis of treatment is antibacterial therapy using tetracycline antibiotics in the appropriate dose. At the very beginning of treatment, maximum daily doses of drugs are used, with a gradual reduction to minimum doses if the temperature normalizes. Before starting treatment, the sensitivity of the pathogen to antibiotics is determined.
2. An important step in the treatment of plague in humans is detoxification. Patients are injected with saline solutions.
3. Symptomatic treatment is used: diuretics are used in case of fluid retention, hormonal substances are used.
4. They use therapeutic anti-plague serum.
5. Along with the main treatment, supportive therapy is used - heart medications, vitamins.
6. In addition to antibacterial drugs, local anti-plague medications are prescribed. Plague buboes are treated with antibiotics.
7. In the case of the development of a septic form of the disease, plasmapheresis is used daily - this is a complex procedure for purifying the blood of a sick person.

After completion of treatment, approximately 6 days later, a control study of biological materials is carried out.

Prevention of plague

The invention of antibacterial drugs would not solve the problem of the emergence and spread of pandemics. This is just an effective way to cope with an already existing disease and prevent its most dangerous complication - death.

So how did they defeat the plague? - after all, isolated cases per year without declared pandemics and a minimal number of deaths after an infection can be considered a victory. A big role belongs to proper disease prevention. And it began when the second pandemic emerged, back in Europe.

In Venice, after the second wave of the spread of the plague back in the 14th century, while only a quarter of the population remained in the city, the first quarantine measures were introduced for arrivals. Ships with cargo were kept in port for 40 days and the crew were monitored to prevent the spread of infection so that it did not penetrate from other countries. And it worked, there were no more new cases of infection, although the second plague pandemic had already claimed most of the population of Europe.

How is infection prevented today?

1. Even if isolated cases of plague occur in any country, all those arriving from there are isolated and observed for six days. If a person has some signs of the disease, then prophylactic doses of antibacterial drugs are prescribed.
2. Plague prevention includes complete isolation of patients with suspected infection. People are not only placed in separate closed boxes, but in most cases they try to isolate the part of the hospital where the patient is located.
3. The State Sanitary and Epidemiological Service plays a major role in preventing the occurrence of infection. They annually monitor outbreaks of plague, take water samples in the area, and examine animals that may be a natural reservoir.
4. In areas where the disease develops, plague carriers are destroyed.
5. Measures to prevent plague in areas where the disease appears include sanitary and educational work with the population. They explain the rules of behavior for people in the event of another outbreak of infection and where to go first.

But even all of the above was not enough to defeat the disease if a vaccine against the plague had not been invented. Since its creation, the number of cases of the disease has sharply decreased, and there have been no pandemics for more than 100 years.

Vaccination

Today, to combat the plague, in addition to general preventive measures, more effective methods are used that have helped to forget about the “Black Death” for a long time.

In 1926, Russian biologist V.A. Khavkin invented the world's first vaccine against plague. Since its creation and the beginning of universal vaccination in hotbeds of infection, plague epidemics have become a thing of the past. Who is vaccinated and how? What are its pros and cons?

Nowadays, they use lyophilisate or live dry vaccine against plague; this is a suspension of live bacteria, but of the vaccine strain. The drug is diluted immediately before use. It is used against the causative agent of bubonic plague, as well as pneumonic and septic forms. This is a universal vaccine. The drug diluted in a solvent is administered in various ways, which depends on the degree of dilution:

• apply it subcutaneously using a needle or needle-free method;
• cutaneously;
• intradermally;
• They even use the plague vaccine by inhalation.

Prevention of the disease is carried out for adults and children starting from the age of two.

Indications and contraindications for vaccination

The plague vaccine is given once and protects for only 6 months. But not every person is vaccinated; certain groups of the population are subject to prevention.

Today, this vaccination is not included as mandatory in the national vaccination calendar; it is done only according to strict indications and only to certain citizens.

Vaccination is given to the following categories of citizens:

• to everyone who lives in epidemically dangerous areas, where the plague still occurs in our time;
• health workers whose professional activities are directly related to work in “hot spots”, that is, in places where the disease occurs;
• vaccine developers and laboratory workers exposed to bacterial strains;
• Preventive vaccination is given to people at high risk of infection who work in hotspots of infection - these are geologists, workers of anti-plague institutions, shepherds.

Prophylaxis with this drug should not be given to children under two years of age, pregnant and lactating women if the person has already developed the first symptoms of plague, and to anyone who has had a reaction to a previous vaccine administration. There are practically no reactions or complications to this vaccine. The disadvantages of such prophylaxis include its short effect and the possible development of the disease after vaccination, which is extremely rare.

Can plague occur in vaccinated people? Yes, this also happens if an already sick person is vaccinated or the vaccination turns out to be of poor quality. This type of disease is characterized by a slow course with sluggish symptoms. The incubation period exceeds 10 days. The condition of the patients is satisfactory, so it is almost impossible to suspect the development of the disease. Diagnosis is facilitated by the appearance of a painful bubo, although there is no inflammation of the tissues or lymph nodes around. In case of delayed treatment or its complete absence, the further development of the disease fully corresponds to its usual classical course.

The plague is currently not a death sentence, but just another dangerous infection that can be dealt with. And although in the recent past all people and health workers were afraid of this disease, today the basis of its treatment is prevention, timely diagnosis and complete isolation of the patient.

The plague disease, which humanity encountered about one and a half thousand years ago, previously caused large outbreaks of morbidity, claiming tens and hundreds of millions of lives. History does not know anything more merciless and devastating, and so far, despite the development of medicine, it has not been completely possible to cope with it.

What is plague?

Plague is a disease in humans of a naturally focal infectious nature, in many cases resulting in death. This is a highly contagious pathology, and susceptibility to it is universal. After suffering and curing the plague, stable immunity is not formed, that is, the risk of re-infection remains (however, the second time the disease is somewhat milder).

The exact origin of the name of the disease has not been established, but the word “plague” translated from Turkish means “round, bump”, from Greek – “shaft”, from Latin – “blow, wound”. In ancient and modern scientific sources you can find such a definition as the disease bubonic plague. This is due to the fact that one of the distinctive signs of the disease is a bubo - a rounded swelling in the inflamed area. However, there are other forms of infection without the formation of buboes.

Plague is a pathogen

For a long time it was not clear what caused bubonic plague; the pathogen was discovered and associated with the disease only at the end of the 19th century. It turned out to be a gram-negative bacterium from the family of enterobacteria - the plague bacillus (Yersinia pestis). The pathogen has been well studied, several subspecies have been identified and the following features have been established:

• can have different shapes - from thread-like to spherical;
• long-term preservation of viability in the secretions of sick people;
• good tolerance to low temperatures and freezing;
• high sensitivity to disinfectants, sunlight, acidic environment, elevated temperatures;
• contains about thirty antigenic structures, secretes endo- and exotoxins.

Plague - ways bacteria penetrate the human body

It is important to know how the plague is transmitted from person to person, as well as from other living beings. The plague bacillus circulates in natural infectious foci in the bodies of animal carriers, which include wild rodents (gophers, marmots, voles), gray and black rats, house mice, cats, lagomorphs, and camels. The carriers (distributors) of pathogens are fleas of various types and several types of blood-sucking ticks, which become infected with the pathogen when feeding on sick animals containing the plague bacillus in the blood.

A distinction is made between transmission of the pathogen through fleas from animal carriers to humans and from person to person. We list the possible ways of plague entering the human body:

1. Transmissible– entry into the bloodstream after the bite of an infected insect.
2. Contact– when a person who has microtrauma on the skin or mucous membranes comes into contact with the bodies of infected animals (for example, when cutting carcasses, processing hides).
3. Nutritional– through the mucous membrane of the gastrointestinal tract when eating meat from sick animals that have not undergone sufficient heat treatment, or other contaminated products.
4. Contact and household– when touched by a sick person, in contact with his biological fluids, using utensils, personal hygiene items, etc.
5. Aerosol– from person to person through the mucous membranes of the respiratory tract when coughing, sneezing, or close conversation.

Plague - symptoms in humans

The place of introduction of the pathogen determines what form of the disease will develop, with damage to which organs, and with what manifestations. The following main forms of human plague are distinguished:

• bubonic;
• pulmonary;
• septic;
• intestinal.

In addition, there are such rare forms of pathology as skin, pharyngeal, meningeal, asymptomatic, and abortive. Plague disease has an incubation period of 3 to 6 days, sometimes 1-2 days (in the case of a primarily pulmonary or septic form) or 7-9 days (in vaccinated or already recovered patients). All forms are characterized by a sudden onset with severe symptoms and intoxication syndrome, manifested in the following:

• high body temperature;
• chills;
• headache;
• muscle-joint pain;
• nausea;
• vomit;
• severe weakness.

As the disease progresses, the patient's appearance changes: the face becomes puffy, hyperemic, the whites of the eyes turn red, the lips and tongue become dry, dark circles appear under the eyes, the face expresses fear and horror (“plague mask”). Subsequently, the patient's consciousness is impaired, speech becomes unintelligible, coordination of movements is impaired, delusions and hallucinations appear. In addition, specific lesions develop, depending on the form of the plague.

Bubonic plague - symptoms

Statistics show that bubonic plague is the most common type of disease, which develops in 80% of those infected when pathogenic bacteria penetrate through the mucous membranes and skin. In this case, the infection spreads through the lymphatic system, causing damage to the inguinal lymph nodes, and in rare cases, the axillary or cervical ones. The resulting buboes can be single or multiple, their size can vary from 3 to 10 cm, and in their development they often go through several stages:

Pneumonic plague

This form is diagnosed in 5-10% of patients, while the plague disease develops after aerogenic infection (primary) or as a complication of the bubonic form (secondary). This is the most dangerous variety, and specific signs of plague in humans in this case are observed approximately 2-3 days after the onset of acute intoxication symptoms. The pathogen infects the walls of the pulmonary alveoli, causing necrotic phenomena. Distinctive manifestations are:

• rapid breathing, shortness of breath;
• cough;
• secretion of sputum - initially foamy, transparent, then streaked with blood;
• chest pain;
• tachycardia;
• drop in blood pressure.

Septicemic form of plague

The primary septic form of plague, which develops when a massive dose of microbes enters the bloodstream, is rare, but is very severe. Signs of intoxication occur at lightning speed, as the pathogen spreads to all organs. Numerous hemorrhages are observed in the skin and mucous tissues, conjunctiva, intestinal and renal bleeding, with rapid development. Sometimes this form occurs as a secondary complication of other types of plague, which is manifested by the formation of secondary buboes.

Intestinal form of plague

Not all experts distinguish the intestinal variety of plague separately, considering it as one of the manifestations of the septic form. When intestinal plague develops, the following signs of the disease in people against the background of general intoxication and fever are recorded:

• sharp pain in the abdomen;
• repeated bloody vomiting;
• diarrhea with mucous-bloody stools;
• Tenesmus is a painful urge to have a bowel movement.

Plague - diagnosis

Laboratory diagnostics, carried out using the following methods, play a significant role in diagnosing “plague”:

• serological;
• bacteriological;
• microscopic.

For research, they take blood, punctures from buboes, discharge from ulcers, sputum, oropharyngeal discharge, and vomit. To check for the presence of the pathogen, the selected material can be grown on special nutrient media. In addition, X-rays of the lymph nodes and lungs are taken. It is important to establish the fact of an insect bite, contact with sick animals or people, and visiting areas where plague is endemic.

Plague - treatment

If a pathology is suspected or diagnosed, the patient is urgently hospitalized in an infectious diseases hospital in an isolated box, from which direct air outflow is excluded. Treatment of plague in humans is based on the following measures:

• taking antibiotics, depending on the form of the disease (Tetracycline, Streptomycin);
• detoxification therapy (Albumin, Reopoliglyukin, Hemodez);
• the use of drugs to improve microcirculation and repair (Trental, Picamilon);
• antipyretic and symptomatic therapy;
• maintenance therapy (vitamins, heart medications);
• – with septic lesions.

During the period of fever, the patient must remain in bed. Antibiotic therapy is carried out for 7-14 days, after which control studies of biomaterials are prescribed. The patient is discharged after complete recovery, as evidenced by receiving a three-fold negative result. The success of treatment largely depends on the timely detection of plague.

Measures to prevent plague from entering the human body

To prevent the spread of infection, nonspecific preventive measures are taken, including:

• analysis of information on the incidence of plague in different countries;
• identification, isolation and treatment of people with suspected pathology;
• disinfection of transport arriving from plague-prone regions.

In addition, work is constantly carried out in natural foci of the disease: counting the number of wild rodents, examining them to identify the plague bacterium, exterminating infected individuals, and fighting fleas. If even one patient is detected in a locality, the following anti-epidemic measures are carried out:

• imposing a quarantine with a ban on the entry and exit of people for several days;
• isolation of people who have been in contact with plague patients;
• disinfection in areas of disease.

For prophylactic purposes, people who have been in contact with plague patients are given anti-plague serum in combination with antibiotics. Vaccination against plague to a person with a live plague vaccine is given in the following cases:

• when you are in natural foci of infection or are about to travel to a disadvantaged area;
• during work involving possible contact with sources of infection;
• when a widespread infection is detected among animals in the vicinity of populated areas.

Plague - incidence statistics

Thanks to the development of medicine and the maintenance of interstate preventive measures, the plague rarely occurs on a large scale. In ancient times, when no cure for this infection was invented, the mortality rate was almost one hundred percent. Now these figures do not exceed 5-10%. At the same time, how many people have died from the plague in the world recently cannot but be alarming.

Plague in human history

The plague has left devastating traces in the history of mankind. The following epidemics are considered the largest:

• “The Plague of Justinian” (551-580), which began in Egypt and killed more than 100 million people;
• the Black Death epidemic (XIV century) in Europe, brought from Eastern China, which claimed about 40 million lives;
• plague in Russia (1654-1655) – about 700 thousand deaths;
• plague in Marseille (1720-1722) – 100 thousand people died;
• plague pandemic (late 19th century) in Asia – more than 5 million people died.

Plague today

Bubonic plague is now found on every continent except Australia and Antarctica. Between 2010 and 2015, more than 3 thousand cases of the disease were diagnosed, with death observed in 584 infected people. The most cases were registered in Madagascar (more than 2 thousand). Foci of the plague have been recorded in countries such as Bolivia, the USA, Peru, Kyrgyzstan, Kazakhstan, Russia and others. Regions of Russia endemic for plague are: Altai, East Ural region, Stavropol region, Transbaikalia, Caspian lowland.

What is the plague and why is it called the Black Death?

Plague is a serious infectious disease that leads to large-scale epidemics and often ends in the death of the sick person. It is caused by Iersinia pestis, a bacterium that was discovered at the end of the 19th century by the French scientist A. Yersin and the Japanese researcher S. Kitazato. At the moment, the causative agents of plague have been studied quite well. In developed countries, plague outbreaks are extremely rare, but this was not always the case. The first plague epidemic described in the sources occurred in the 6th century on the territory of the Roman Empire. Then the disease claimed the lives of about 100 million people. 8 centuries later, the history of the plague repeated itself in Western Europe and the Mediterranean, where more than 60 million people died. The third large-scale epidemic began in Hong Kong at the end of the 19th century and quickly spread to more than 100 port cities in the Asian region. In India alone, the plague led to the death of 12 million people. Due to its severe consequences and characteristic symptoms, the plague is often called the “Black Death”. It really does not spare either adults or children and, in the absence of treatment, “kills” more than 70% of infected people.

Nowadays, the plague is rare. However, there are still natural foci around the globe where infectious agents are regularly detected in rodents living there. The latter, by the way, are the main carriers of the disease. Deadly plague bacteria enter the human body through fleas, which are looking for new hosts after the mass death of infected rats and mice. In addition, the airborne route of transmission of infection is known, which, in fact, determines the rapid spread of plague and the development of epidemics.

In our country, plague-endemic regions include the Stavropol region, Transbaikalia, Altai, the Caspian lowland and the Eastern Ural region.

Etiology and pathogenesis

Plague pathogens are resistant to low temperatures. They are well preserved in sputum and are easily transmitted from person to person by airborne droplets. When a flea bites, a small papule filled with hemorrhagic contents (skin plague) first appears on the affected area of ​​skin. After this, the process quickly spreads through the lymphatic vessels. They create ideal conditions for the proliferation of bacteria, which leads to the explosive growth of plague pathogens, their fusion and the formation of conglomerates (bubonic plague). Bacteria may enter the respiratory system with further development of the pulmonary form. The latter is extremely dangerous, as it is characterized by a very fast current and covers vast territories due to intensive spread between members of the population. If treatment for plague begins too late, the disease turns into a septic form, which affects absolutely all organs and systems of the body, and in most cases ends in the death of a person.

Plague - symptoms of the disease

Symptoms of the plague appear after 2 to 5 days. The disease begins acutely with chills, a sharp increase in body temperature to critical levels, and a drop in blood pressure. These signs are subsequently joined by neurological symptoms: delirium, loss of coordination, and confusion. Other characteristic manifestations of the Black Death depend on the specific form of infection.

• bubonic plague - enlarged lymph nodes, liver, spleen. Lymph nodes become hard and extremely painful, filled with pus, which eventually breaks out. Incorrect diagnosis or inadequate treatment of plague leads to the death of the patient 3-5 days after infection;
• pneumonic plague - affects the lungs, patients complain of coughing, copious discharge of sputum, which contains blood clots. If treatment is not started in the first hours after infection, then all further measures will be ineffective and the patient will die within 48 hours;
• septic plague - symptoms indicate the spread of pathogens throughout literally all organs and systems. A person dies within a day at most.

Doctors also know the so-called minor form of the disease. It is manifested by a slight rise in body temperature, swollen lymph nodes and headache, but usually these symptoms disappear on their own after a few days.

Treatment of plague

Diagnosis of plague is based on laboratory culture, immunological methods and polymerase chain reaction. If a patient is diagnosed with bubonic plague or any other form of this infection, he is immediately hospitalized. When treating plague in such patients, medical facility personnel must take strict precautions. Doctors should wear 3-layer gauze bandages, protective glasses to prevent sputum from getting on the face, shoe covers and a cap that completely covers the hair. If possible, special anti-plague suits are used. The compartment in which the patient is located is isolated from other premises of the institution.

If a person is diagnosed with bubonic plague, he is administered streptomycin intramuscularly 3-4 times a day and tetracycline antibiotics intravenously. In case of intoxication, patients are advised to use saline solutions and hemodez. A decrease in blood pressure is considered as a reason for emergency treatment and resuscitation measures in the event of an increase in the intensity of the process. Pneumonic and septic forms of plague require increasing doses of antibiotics, immediate relief of intravascular coagulation syndrome, and administration of fresh blood plasma.

Thanks to the development of modern medicine, large-scale plague epidemics have become very rare, and currently the mortality rate of patients does not exceed 5-10%. This is true for cases where treatment of the plague begins on time and complies with established rules and regulations. For this reason, if there is any suspicion of the presence of plague pathogens in the body, doctors are obliged to urgently hospitalize the patient and alert the authorities involved in controlling the spread of infectious diseases.

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The causative agent of plague is the plague bacillus. And the main reservoir of infection in nature are rodents and lagomorphs.

Predators that hunt animals of these species can also spread the infection.

The carrier of plague is a flea, whose bite infects a person. Human lice and ticks can also transmit the infection.

Penetration of the plague bacillus into the human body is also possible when processing the skins of infected animals or when eating the meat of an animal suffering from the plague.

The disease is transmitted from person to person by airborne droplets.

Humans are highly susceptible to plague infection!

Plague symptoms

There are many types of plague, but the most common is the bubonic form.

The plague is characterized by a sharp, sudden onset with severe chills and increased body temperature. They are accompanied by dizziness, weakness, muscle pain, nausea and vomiting.

The nervous system suffers; patients are frightened, restless, may become delirious, and tend to run away somewhere.

Coordination of movements, gait, and speech are impaired.

Bubonic plague is characterized by the development of a plague bubo. In the area where it appears, the patient experiences severe pain. A bubo gradually forms, a dense tumor with indistinct edges, sharply painful when touched. The skin over the bubo is initially of normal color, hot to the touch, then becomes dark red, with a bluish tint, and glossy.

There is also an increase in other groups of lymph nodes and secondary buboes are formed.

If left untreated, the buboes fester, then open and transform into fistulas. Then they gradually heal.

Complications of the plague

In most cases, the disease is complicated by DIC syndrome, that is, disseminated intravascular coagulation.

10% of patients have gangrene of the feet, fingers or skin.

Diagnosis of plague

Diagnosis of plague is based on epidemiological data. Currently, all natural plague foci are strictly registered. Characteristic clinical manifestations of the disease are also important for making a diagnosis. A bacterioscopic examination of bubo punctate and ulcer discharge is also carried out.

Treatment of plague

First of all, a person sick with plague must be hospitalized in an infectious diseases hospital.

The main drugs in the treatment of the disease are antibacterial agents.

A patient who has recovered from the plague is discharged from an infectious diseases hospital after complete recovery, the disappearance of symptoms of the disease and a threefold negative result of bacteriological culture.

For bubonic plague, discharge is carried out no earlier than 1 month from the moment of recovery.

Recovered people are registered at the dispensary for 3 months after the disappearance of the last signs of the disease.

They also belong to the Ancient World. Thus, Rufus from Ephesus, who lived during the time of Emperor Trajan, referring to more ancient doctors (whose names have not reached us), described several cases of definitely bubonic plague in Libya, Syria and Egypt.

The Philistines did not calm down and for the third time transported the trophy of war, and with it the plague, to the city of Ascalon. All the Philistine rulers later gathered there - the kings of the five cities of Philistia - and they decided to return the ark to the Israelites, because they realized that this was the only way to prevent the spread of the disease. And chapter 5 ends with a description of the atmosphere that reigned in the doomed city. “And those who did not die were smitten with growths, so that the cry of the city went up to heaven” (1 Sam.). Chapter 6 depicts the council of all the rulers of the Philistines, to which priests and soothsayers were called. They advised to bring a trespass offering to God - to put gifts in the ark before returning it to the Israelites. “According to the number of the rulers of the Philistines, there are five golden growths and five golden mice that devastate the land; for the execution is one for all of you and for those who rule you” (1 Sam.). This biblical legend is interesting in many respects: it contains a hidden message about an epidemic that most likely swept through all five cities of Philistia. We could be talking about the bubonic plague, which affected people young and old and was accompanied by the appearance of painful growths in the groin - buboes. The most remarkable thing is that the Philistine priests apparently associated this disease with the presence of rodents: hence the golden sculptures of mice “ravaging the earth.”

There is another passage in the Bible that is considered to be a record of another instance of the plague. The Fourth Book of Kings (2 Kings) tells the story of the campaign of the Assyrian king Sennacherib, who decided to devastate Jerusalem. A huge army surrounded the city, but did not take control of it. And soon Sennacherib withdrew without a fight with the remnants of the army, in which the “Angel of the Lord” struck 185 thousand soldiers overnight (2 Kings).

Plague epidemics in historical times

Plague as a biological weapon

The use of the plague agent as a biological weapon has deep historical roots. In particular, events in ancient China and medieval Europe showed the use of the corpses of infected animals (horses and cows), human bodies by the Huns, Turks and Mongols to contaminate water sources and water supply systems. There are historical reports of cases of ejection of infected material during the siege of some cities (Siege of Kaffa).

Current state

Every year, the number of people infected with plague is about 2.5 thousand people, with no downward trend.

According to available data, according to the World Health Organization, from 1989 to 2004, about forty thousand cases were recorded in 24 countries, with a mortality rate of about 7% of the number of cases. In a number of countries in Asia (Kazakhstan, China, Mongolia and Vietnam), Africa (Congo, Tanzania and Madagascar), and the Western Hemisphere (USA, Peru), cases of human infection are recorded almost every year.

At the same time, on the territory of Russia, over 20 thousand people are at risk of infection every year in the territory of natural foci (with a total area of ​​more than 253 thousand km²). For Russia, the situation is complicated by the annual identification of new cases in states neighboring Russia (Kazakhstan, Mongolia, China), and the importation of a specific carrier of the plague - fleas - through transport and trade flows from the countries of Southeast Asia. Xenopsylla cheopis .

From 2001 to 2006, 752 strains of the plague pathogen were recorded in Russia. At the moment, the most active natural foci are located in the territories of the Astrakhan region, the Kabardino-Balkarian and Karachay-Cherkess republics, the republics of Altai, Dagestan, Kalmykia, and Tyva. Of particular concern is the lack of systematic monitoring of the activity of outbreaks located in the Ingush and Chechen Republics.

In July 2016, in Russia, a ten-year-old boy with bubonic plague was taken to the hospital in the Kosh-Agach district of the Altai Republic.

In 2001-2003, 7 cases of plague were registered in the Republic of Kazakhstan (with one death), in Mongolia - 23 (3 deaths), in China in 2001-2002, 109 people fell ill (9 deaths). The forecast for the epizootic and epidemic situation in the natural foci of the Republic of Kazakhstan, China and Mongolia adjacent to the Russian Federation remains unfavorable.

At the end of August 2014, an outbreak of plague occurred again in Madagascar, which by the end of November 2014 had claimed 40 lives out of 119 cases.

Forecast

Under modern therapy, mortality in the bubonic form does not exceed 5-10%, but in other forms the recovery rate is quite high if treatment is started early. In some cases, a transient septic form of the disease is possible, which is poorly amenable to intravital diagnosis and treatment (“fulminant form of plague”).

Infection

The causative agent of plague is resistant to low temperatures, preserves well in sputum, but at a temperature of 55 ° C it dies within 10-15 minutes, and when boiled, almost instantly. The gate of infection is damaged skin (with a flea bite, as a rule, Xenopsylla cheopis), mucous membranes of the respiratory tract, digestive tract, conjunctiva.

Based on the main carrier, natural plague foci are divided into ground squirrels, marmots, gerbils, voles and pikas. In addition to wild rodents, the epizootic process sometimes includes so-called synanthropic rodents (in particular, rats and mice), as well as some wild animals (hares, foxes) that are the object of hunting. Among domestic animals, camels suffer from the plague.

In a natural outbreak, infection usually occurs through the bite of a flea that previously fed on a sick rodent. The likelihood of infection increases significantly when synanthropic rodents are included in the epizootic. Infection also occurs during hunting of rodents and their further processing. Massive diseases of people occur when a sick camel is slaughtered, skinned, butchered, or processed. An infected person, in turn, is a potential source of plague, from which the pathogen can be transmitted to another person or animal, depending on the form of the disease, by airborne droplets, contact or transmission.

Fleas are a specific carrier of the plague pathogen. This is due to the peculiarities of the digestive system of fleas: just before the stomach, the flea’s esophagus forms a thickening - a goiter. When an infected animal (rat) is bitten, the plague bacterium settles in the flea’s crop and begins to multiply intensively, completely clogging it (the so-called “plague block”). Blood cannot enter the stomach, so the flea regurgitates the blood along with the pathogen back into the wound. And since such a flea is constantly tormented by a feeling of hunger, it moves from owner to owner in the hope of getting its share of blood and manages to infect a large number of people before dying (such fleas live no more than ten days, but experiments on rodents have shown that one flea can infect up to 11 hosts).

When a person is bitten by fleas infected with plague bacteria, a papule or pustule filled with hemorrhagic contents (skin form) may appear at the site of the bite. The process then spreads through the lymphatic vessels without the appearance of lymphangitis. The proliferation of bacteria in macrophages of the lymph nodes leads to their sharp increase, fusion and formation of a conglomerate (“bubo”). Further generalization of the infection, which is not strictly necessary, especially in the conditions of modern antibacterial therapy, can lead to the development of a septic form, accompanied by damage to almost all internal organs. From an epidemiological point of view, it is important that plague bacteremia develops, as a result of which a sick person himself becomes a source of infection through contact or transmission. However, the most important role is played by the “screening out” of infection into the lung tissue with the development of the pulmonary form of the disease. From the moment plague pneumonia develops, the pulmonary form of the disease is already transmitted from person to person - extremely dangerous, with a very rapid course.

Symptoms

The bubonic form of plague is characterized by the appearance of sharply painful conglomerates, most often in the inguinal lymph nodes on one side. The incubation period is 2-6 days (less often 1-12 days). Over the course of several days, the size of the conglomerate increases, and the skin over it may become hyperemic. At the same time, an increase in other groups of lymph nodes appears - secondary buboes. The lymph nodes of the primary focus undergo softening; upon puncture, purulent or hemorrhagic contents are obtained, microscopic analysis of which reveals a large number of gram-negative rods with bipolar staining. In the absence of antibacterial therapy, festering lymph nodes are opened. Then gradual healing of the fistula occurs. The severity of the patients' condition gradually increases by the 4-5th day, the temperature may be elevated, sometimes a high fever immediately appears, but at first the condition of the patients often remains generally satisfactory. This explains the fact that a person sick with bubonic plague can fly from one part of the world to another, considering himself healthy.

However, at any time, the bubonic form of plague can cause generalization of the process and turn into a secondary septic or secondary pulmonary form. In these cases, the condition of the patients very quickly becomes extremely serious. Symptoms of intoxication increase by the hour. The temperature after severe chills rises to high febrile levels. All signs of sepsis are noted: muscle pain, severe weakness, headache, dizziness, congestion of consciousness, up to its loss, sometimes agitation (the patient rushes about in bed), insomnia. With the development of pneumonia, cyanosis increases, a cough appears with the release of foamy, bloody sputum containing a huge amount of plague bacilli. It is this sputum that becomes the source of infection from person to person with the development of the now primary pneumonic plague.

Septic and pneumonic forms of plague occur, like any severe sepsis, with manifestations of disseminated intravascular coagulation syndrome: minor hemorrhages may appear on the skin, bleeding from the gastrointestinal tract is possible (vomiting of bloody masses, melena), severe tachycardia, rapid and requiring correction ( dopamine) drop in blood pressure. Auscultation reveals a picture of bilateral focal pneumonia.

Clinical picture

The clinical picture of the primary septic or primary pulmonary form is not fundamentally different from the secondary forms, but the primary forms often have a shorter incubation period - up to several hours.

Diagnosis

The most important role in diagnosis in modern conditions is played by epidemiological anamnesis. Arrival from zones endemic for plague (Vietnam, Burma, Bolivia, Ecuador, Karakalpakstan, etc.), or from anti-plague stations of a patient with the signs of the bubonic form described above or with signs of the most severe - with hemorrhages and bloody sputum - pneumonia with severe lymphadenopathy is for doctor of first contact is a sufficiently serious argument for taking all measures to localize the suspected plague and accurately diagnose it. It should be especially emphasized that in the conditions of modern drug prevention, the likelihood of illness among personnel who have been in contact with a coughing plague patient for some time is very small. Currently, there are no cases of primary pneumonic plague (that is, cases of infection from person to person) among medical personnel. An accurate diagnosis must be made using bacteriological studies. The material for them is the punctate of a suppurating lymph node, sputum, the patient’s blood, discharge from fistulas and ulcers.

Laboratory diagnosis is carried out using a fluorescent specific antiserum, which is used to stain smears of discharge from ulcers, punctate lymph nodes, and cultures obtained on blood agar.

Treatment

In the Middle Ages, the plague was practically not treated; actions were reduced mainly to cutting out or cauterizing the plague buboes. No one knew the real cause of the disease, so there was no idea how to treat it. Doctors tried to use the most bizarre means. One such drug included a mixture of 10-year-old molasses, finely chopped snakes, wine and 60 other ingredients. According to another method, the patient had to take turns sleeping on his left side, then on his right. Since the 13th century, attempts have been made to limit the plague epidemic through quarantines.

A turning point in plague treatment was reached in 1947, when Soviet doctors were the first in the world to use streptomycin to treat plague in Manchuria. As a result, all patients who were treated with streptomycin recovered, including a patient with pneumonic plague, who was already considered hopeless.

Treatment of plague patients is currently carried out using antibiotics, sulfonamides and medicinal anti-plague serum. Prevention of possible outbreaks of the disease consists of carrying out special quarantine measures in port cities, deratization of all ships that sail on international flights, creating special anti-plague institutions in steppe areas where rodents are found, identifying plague epizootics among rodents and combating them.

Anti-plague sanitary measures in Russia

If plague is suspected, the sanitary-epidemiological station of the area is immediately notified. The notification is filled out by the doctor who suspects an infection, and its forwarding is ensured by the chief physician of the institution where such a patient was found.

The patient should be immediately hospitalized in the infectious diseases hospital. A doctor or paramedical worker of a medical institution, upon discovering a patient or suspected of having the plague, is obliged to stop further admission of patients and prohibit entry and exit from the medical institution. While remaining in the office or ward, the medical worker must inform the chief physician in a way accessible to him about the identification of the patient and demand anti-plague suits and disinfectants.

In cases of receiving a patient with lung damage, before putting on a full anti-plague suit, the medical worker is obliged to treat the mucous membranes of the eyes, mouth and nose with streptomycin solution. If there is no cough, you can limit yourself to treating your hands with a disinfectant solution. After taking measures to separate the sick person from the healthy, a list of persons who had contact with the patient is compiled in a medical institution or at home, indicating the last name, first name, patronymic, age, place of work, profession, home address.

Until the consultant from the anti-plague institution arrives, the health worker remains in the outbreak. The issue of its isolation is decided in each specific case individually. The consultant takes the material for bacteriological examination, after which specific treatment of the patient with antibiotics can begin.

When identifying a patient on a train, plane, ship, airport, or railway station, the actions of medical workers remain the same, although the organizational measures will be different. It is important to emphasize that isolation of a suspicious patient from others should begin immediately after identification.

The head doctor of the institution, having received a message about the identification of a patient suspected of plague, takes measures to stop communication between the hospital departments and clinic floors, and prohibits leaving the building where the patient was found. At the same time, organizes the transmission of emergency messages to a higher organization and the anti-plague institution. The form of information can be arbitrary with the obligatory presentation of the following data: last name, first name, patronymic, age of the patient, place of residence, profession and place of work, date of detection, time of onset of the disease, objective data, preliminary diagnosis, primary measures taken to localize the outbreak, position and the name of the doctor who diagnosed the patient. Along with the information, the manager requests consultants and the necessary assistance.

However, in some situations, it may be more appropriate to carry out hospitalization (before establishing an accurate diagnosis) in the institution where the patient is at the time of the assumption that he has plague. Therapeutic measures are inseparable from the prevention of infection of personnel, who must immediately put on 3-layer gauze masks, shoe covers, a scarf made of 2 layers of gauze that completely covers the hair, and protective glasses to prevent splashes of sputum from entering the mucous membrane of the eyes. According to the rules established in the Russian Federation, personnel must wear an anti-plague suit or use special means of anti-infective protection with similar properties. All personnel who had contact with the patient remain to provide further assistance to him. A special medical post isolates the compartment where the patient and the personnel treating him are located from contact with other people. The isolated compartment should include a toilet and a treatment room. All personnel immediately receive prophylactic antibiotic treatment, continuing throughout the days they spend in isolation.

Treatment of plague is complex and includes the use of etiotropic, pathogenetic and symptomatic agents. Antibiotics of the streptomycin series are most effective for treating plague: streptomycin, dihydrostreptomycin, pasomycin. In this case, streptomycin is most widely used. For the bubonic form of plague, the patient is administered streptomycin intramuscularly 3-4 times a day (daily dose of 3 g), tetracycline antibiotics (vibromycin, morphocycline) intramuscularly at 4 g/day. In case of intoxication, saline solutions and hemodez are administered intravenously. A drop in blood pressure in the bubonic form should in itself be regarded as a sign of generalization of the process, a sign of sepsis; in this case, there is a need for resuscitation measures, administration of dopamine, and installation of a permanent catheter. For pneumonic and septic forms of plague, the dose of streptomycin is increased to 4-5 g/day, and tetracycline - to 6 g. For forms resistant to streptomycin, chloramphenicol succinate can be administered up to 6-8 g intravenously. When the condition improves, the dose of antibiotics is reduced: streptomycin - up to 2 g / day until the temperature normalizes, but for at least 3 days, tetracyclines - up to 2 g / day daily orally, chloramphenicol - up to 3 g / day, for a total of 20-25 g. Biseptol is also used with great success in the treatment of plague.

In case of pulmonary, septic form, development of hemorrhage, they immediately begin to relieve disseminated intravascular coagulation syndrome: plasmapheresis is performed (intermittent plasmapheresis in plastic bags can be carried out in any centrifuge with special or air cooling with a capacity of 0.5 l or more) in the volume removed plasma 1-1.5 liters when replaced with the same amount of fresh frozen plasma. In the presence of hemorrhagic syndrome, daily administration of fresh frozen plasma should not be less than 2 liters. Until the acute manifestations of sepsis are relieved, plasmapheresis is performed daily. The disappearance of signs of hemorrhagic syndrome and stabilization of blood pressure, usually in sepsis, are grounds for stopping plasmapheresis sessions. At the same time, the effect of plasmapheresis in the acute period of the disease is observed almost immediately, signs of intoxication decrease, the need for dopamine to stabilize blood pressure decreases, muscle pain subsides, and shortness of breath decreases.

The team of medical personnel providing treatment to a patient with pneumonic or septic form of plague must include an intensive care specialist.

see also

• Inquisitio
• Plague (group)

Notes

1. Disease Ontology release 2019-05-13 - 2019-05-13 - 2019.
2. Jared Diamond, Guns, Germs and Steel. The Fates of Human Societies.
3. , With. 142.
4. Plague
5. , With. 131.
6. Plague - for doctors, students, patients, medical portal, abstracts, cheat sheets for doctors, disease treatment, diagnosis, prevention
7. , With. 7.
8. , With. 106.
9. , With. 5.
10. Papagrigorakis, Manolis J.; Yapijakis, Christos; Synodinos, Philippos N.; Baziotopoulou-Valavani, Effie (2006). “DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens” . International Journal of Infectious Diseases. 10 (3): 206-214.