Plague is an acute infectious disease caused by Yersinia pestis with an severe intoxication, fever, affection of lymphatic system and lungs. It belongs to the group of the extremely dangerous infections (quarantines).

Historic reference

Apparently, the word plague comes from the ancient Arabic word jumma which means bean.

During the last 2000 years, Y. pestis has caused social and economic devastation on a scale unmatched by other infectious diseases or by armed conflicts. It is generally considered that there have been three world pandemics of plague and credible estimates indicate that together these resulted in 200 million deaths. During these pandemics, the disease occurred in both the bubonic and pneumonic forms.

The first, the Justinian plague, occurred during the period AD 542 to AD 750. This pandemic is thought to have originated in Central Africa and then spread throughout the Mediterranean basin. The second pandemic started on the Eurasian border in the mid-14th century'. It is this pandemic which resulted in 25 million deaths in Europe and which is often referred to as the black death. This pandemic lasted for several centuries, culminating; in the Great Plague of London in 1665. The third pandemic started in China in the mid-19th century, spread East and West, in 87 ports, in almost all continents.

Eight epidemic breakouts of plague have been registered in Odessa. The biggest epidemic took place at 1812, when about 3000 people fell ill and more than 2000 people died. Professor Stefansky V. K. - the first head of the chair of infectious diseases in Odessa medical institute was one of the pioneers of using serum for the treatment of sick people.

World Health Organization (WHO) indicated plague, cholera, hemorrhagic fevers and small pox as internationally quarantinable infectious disease (most dangerous). As a class 1 notifiable disease, all suspected cases must be reported to, and investigated by, public health authorities and confirmed cases must be reported to the WHO in Geneva, Switzerland. During the period 1967-1993, the average worldwide incidence of plague was 1,666 cases. Although the incidence trend was downwards until 1981, there has been an apparent increase in the incidence of disease over the last decade, possibly because of more efficient diagnosis and reporting of cases. Even today, many cases of plague are not diagnosed and it is likely that the true incidence of disease is several times the WHO figures.

The Indian outbreak of plague in 1994. Despite the high incidence of plague in India during the first half of this century, the number of cases had declined since 1950, and the last recorded case occurred in 1966. However, between August and October 1994 two outbreaks of suspected plague occurred. One of bubonic plague in the Beed District of Maharashtra State, and the other of pneumonic plague in the city of Surat in Gujarat State. The Surat epidemic caused panic throughout India, resulting in a mass exodus of up to half a million people from the city, and attracted international media attention.

At the peak of the epidemic, over 6300 suspected cases were recorded. However, official figures released later indicated that only 876 presumptive cases of plague were identified (by serological testing for antibodies to Fl antigen of Y.pestis) and there were 54 fatalities. The cases were confined to six states in central and western India; none of the suspected cases in other states, such as Bihar, Punjab, Rajasthan and West Bengal, had positive serological markers for presumptive plague.


Yersinia pestis (bacillus pestis) Fig.1, the etiological agent of plague was first described by A. Yersen in 1894 in Hong-Hong, the International committee of systematization of bacteria (1982) referred it to Yersinia genus together with bacillus pseudotuberculosis and yersiniosis.

Fig.1. Yersinia pestis (bacillus pestis)


It is a short, oval bacillus with rounded ends occurring singly and in pairs. In the tissues a typical capsule may be observed, in cultures grown at 37 C material can be demonstrated by means of India ink preparations, but it no well-defined.

The organism is Gram-negative, and when stained with a weak stain (methylene blue) shows characteristic bipolar staining which is an important feature in identification.

In culture the plague bacillus is less typical. Longer forms are frequent and polar staining is less obvious. Pleomorphism is marked especially in old cultures, and involution or degeneration forms are particularly noticeable. These are markedlly enlarged, stain faintly and include globular, pear-shaped, elongated or irregular forms. In fact the microscopic picture of an old culture often suggested that of a yeast or mould. Involution in culture can be hastened by the presence of 3% sodium chloride and this has sometimes been utilized in identifying the organism.

In fluid culture the bacilli tend to be arranged in chains. The organism is non-motile and non-sporing.

Rodents are natural reservoir for plague infection. Yersen was the first who noticed the connection between a rats plague epizootic and a human epidemic. Bacillus pestis carriage was proved for black and gray rats and for such steppe rodents as gophers, marmots, sandworts, small mousekind rodents and others. There are almost 300 species and subspecies of basic sources and keepers of plague infection. Besides, during an epizootic among rodents, there can be found other mammals contaminated with plague - polecats, shrews, foxes, monkeys (makaky genus), domestic cats, one- and two-humped camels. Epizootics among rodents are kept by different species of fleas - carriers of plague infection.

It is now known that plague is not communicable from animal to animal by simple contact, but is readily communicated by fleas (Fig.2), which bite man, dogs and other animals. Conglomerate of Y. pestis block esophagus and pre-stomach of the flea. During the bite and sucking of blood bacilli regurgitate into the wound of object.

Fig.2. Flea

Especially convincing are the experiments of the Indian Plague Commission, which clearly showed that, if fleas are excluded, healthy rats will not contract the disease, even if kept in intimate association with plague-infected rats. Young rats may even be suckled by their plague-stricken mothers and remain healthy. It suffices to transfer fleas from a plague-infected to a healthy animal, or to place the latter in a room in which plague rats had died recently and had been subsequently removed. The fleas that have left the body of the dead rats, try to found another host for living.

In ordinary circumstances the rat-flea completes its developmental cycle in from 14 days to 3 weeks, but in warm damp weather this may be shortened to 10 days. It requires ideal tropical conditions for propagation. The average life of a flea, separated from its host, is about ten days, but it is capable of remaining alive without food for two months, should the temperature of the air be low.

Human infection, however, is not always transmitted by fleas. In a small percentage of the bubonic cases, infection occurs after direct contact of skin with Bacillus pestis. Instances of such infection have occurred in barefooted individuals with small wounds of the feet from walking on floors or stepping on material infected with plague bacilli, or through abrasions on the hands of those who have performed autopsies on or handled the bodies of those who have died of plague, or who have shot and skinned rodents infected with plague.

Infection in primary human septicemic plague is usually acquired through the mucous membranes, particularly of the mouth and throat and the conjunctivae. Particles of infected sputum which have been accidentally coughed into the eye have produced human septicemic plague. Animals such as monkeys may be given primary septicemic plague by instilling a few drops of a culture of Bacillus pestis in the eye, or by rubbing a small amount of the culture on the mucous membranes of the gums without producing visible erosions. Infection of the mucous membranes of the mouth may occur also in man through the hands conveying infection, as might occur in individuals who have shot or skinned infected rodents.


Penetration of Yersinia pestis through skin (respiratory or gastrointestinal tract).

Involving of the lymph node (primary bubo).

Penetration into blood (bacteremia, generalization of the process, formation of methastases) also spreading through lymphatic system (secondary buboes).

Destructive effect of the toxin (general congestion of all organs of the body).


Morbid pathology

The main points noted in a plague autopsy are:

1) The marked involvement of the lymphatic system as shown by intense congestion and hemorrhagic edema of the lymphatic glands. Not only are the glands involved tributary to the site of inoculation, thus forming the primary bubo, but there is secondarily more or less inflammatory change in many of the lymphatic glands of body. There is also a marked periglandular edema, with hemorrhagic extravasations of the connective tissue surrounding the primary bubo, this mass being made up of a group of glands matted together by this periglandular exudate.

2) The marked destructive effect of the toxin of the plague bacillus, upon the endothelial cell lining of blood vessels as well as of lymphatic ones. This causes the extensive blood extravasations are characteristic of plague and shown by petechial spots, not only of the skin, but of the serous and mucous membranes as well throughout the body.

Microscopically there is a distension of the alveoli and bronchial passages with a hemorrhagic exudate. There is practically no fibrin in the alveolar exudate. The process seems to extend by continuity along the bronchi and bronchioles. Plague bacilli pack the exudate found in the bronchi and bronchioles. In a report on the autopsy findings of septicemic plague in Ceylon in cases where plague bacilli were demonstrated in smears and cultures from spleen and blood, Castellani noted especially meningeal congestion and some splenic enlargement.





Clinical manifestations

Incubation period of human plague varies usually from 2 to 10 days, but is generally from 3 to 4 days. In primary pneumonic plague it may not be over 2 or 3 days.

In bubonic plague premonitory symptoms are not usually observed, though occasionally there may be 1 or 2 days of malaise and headache. The onset, except in mild cases, is usually abrupt, with fever commonly accompanied by a moderate rigor or repeated shivering. The temperature rises rapidly to 39,4 C or 40 ˚C. sometimes even reaching 41,7 C. The pulse becomes rapid and the respirations increased. There is headache which is usually severe and mental dullness, and this condition is generally followed by mental anxiety or excitement. The patient may become maniacal. The skin is hot and dry, the face bloated, the eyes injected, and the hearing dulled. The tongue is usually swollen and coated with a creamv fur, or later with a brown or black layer. The symptoms usually complained of within the first 24 hours are very severe headache and backache. Burning in the throat or stomach, and nausea and vomiting may occur. Constipation is present as a rule. The pulse is either very small and thread-like or full and bounding. At times there may be acute delirium; at others, lethargy and coma. In children, convulsions usually occur. The urine is scanty and generally does not contain more than a trace of albumin and no casts. Later in the disease the albumin may increase somewhat, The high febrile stage lasts from 2 to 5 days or longer. The decline in temperature may be sudden or gradual. Cases that do well usually show a gradual fall of temperature, and after 14 days the temperature may be subnormal. Buboes, inflammatory enlargements of the lymph glands are sometimes the first sign to attract attention by their pain. They more often make their appearance from the second to the fifth day after the onset of the fever. The temperature frequently shows a decline when they appear.

The affected gland is often hard and painful to the touch. In fatal cases, it may retain these characteristics; in others it suppurates. The average size of the bubo is from a walnut to an egg. Generally the plague bubo at the onset is hard to the touch and very painful. Often at the time of onset of the bubo, pain in it is the symptom of all others of the disease most complained of. In rare instances, however, the pain may not be marked. Usually if the bubo is in the groin the pain is sufficient so that the patient lies in bed with the thigh flexed and the leg drawn up to relieve any pressure on the inflamed glands while if the bubo is in me axillary region the affected arm is held away from the side. The bubo may terminate by resolution, suppuration, or induration (Fig.3).

Fig.3. Ruptured plague bubo


If the bubo suppurates, the gland becomes at first more swollen and the overlying skin gradually more inflamed and tense during the first week. Later the gland begins to soften and necrosis then occurs more quickly. Frequently the whole center of the gland breaks down into an abscess cavity and perforation then occurs, revealing a cavity with dark scarlet or bright red walls. Later the walls become reddish yellow in appearance and emit whitish-yellow pus. On microscopical examination of the pus normal and degenerating plague bacilli are found and many polymorphonuclear leucocytes and degenerating endothelial cells. The bacilli are often seen engulfed in phagocytic cells. In the later stages the buboes often become secondarily infected with other microorganisms, particularly the pus cocci. Rarely the bubo does not perforate for several weeks. Sometimes its suppuration is accompanied by much sloughing of the skin in the vicinity when fairly large ulcers result with indurated infiltrated margins. In some instances the lesions may heal in from a week to ten days, but with larger buboes sometimes complete cicatrization does not occur for a month or two. In many other cases the bubo terminates by resolution. The tenderness, and periglandular infiltration then gradually decrease, the overlying and adjacent skin becomes softer, and the glands may eventually return almost to their normal size with but moderate induration about them. In other instances an enlarged cicatricial node remains at the site of the bubo.

Buboes appear in 75 % of the cases. In the cases in which buboes are present, they occur in the inguinal glands in approximately 65 to 70 %, in the axillary. 15 to 20 %, and the cervical, 5 to 10 %. Carbuncles appear in about 2 %, in which there are reddened indurated patches of skin, which subsequently necrose. The spleen is frequently moderately enlarged, but often cannot be palpated. Hemorrhages from the stomach and intestine are not uncommon, and when the disease is complicated with the pneumonic form they may occur from the lung. Epistaxis is also not infrequent. The blood usually shows a leucocytosis of forty thousand or more the increase being in the polymorphonuclear leucocytes. The plague organism can be isolated front the blood in about forty-five per cent of the bubonic cases.



The attack of high fever lasts generally three to five days or longer, but the patient may die earlier. If however, he lives for five days there is greater chance of recovery. If the bubo suppurates recovery may be delayed from two or three weeks to a month.


The onset of pneumonic plague is usually somewhat abrupt; prodromal symptoms are rare. The disease usually begins with chilly sensations, but a distinct rigor is unusual. Epistaxis is also rare. There is headache, loss of appetite, an increase in the pulse rate, and fever. Within from twenty-four to thirty-six hour after the onset, the temperature usually has reached 39,4 C or 40 C, and the pulse 110 to 130 or more beats per minute. Cough and dyspnoe appear within twenty-four hours after the onset of the first symptoms. The cough is usually not painful. The expectoration is at first scanty, but soon becomes more abundant. The sputum at first consists of mucus which shortly becomes blood-tinged. Later the sputum becomes much thinner and of a bright red color; it then contains enormous numbers of plague bacilli in almost pure culture. The typical rusty sputum of croupous pneumonia was not observed. The conjunctiva become injected, and the tongue coated with either a white or brownish layer. The expression is usually anxious, and the face frequently assumes a dusky hue. Labial herpes is very uncommon. The patients sometimes complain of pain in the chest, but usually this is not severe. Apart from the disturbances due to the dyspnoe and their anxiety for their condition, they usually appear to suffer but little and usually do not complain of pain. In the later stages of the disease, the respirations become greatly increased and the dyspnoe usually very marked, the patients frequently gasping for air for several hours before death. Cyanosis is then common.

The signs of cardiac involvement are always marked in the advanced cases, the pulse becoming gradually more rapid, feeble, and running; finally it can not be felt.

Septicemic plague occur during the course of bubonic plague, always occurs in pneumonic plague, and may occur as a form of primary infection. When primary septicemic plague results, the infection has usually occurred through the mucous membrane of the mouth and throat, death resulting from septicemia before macroscopic lesions are visible in the lymphatic glands or lungs. Nevertheless, at autopsy, at least some of the lymphatics are usually found to be enlarged, congested, and even hemorrhagic, and in a few instances early buboes may develop shortly before death.

In this form, the nervous and cerebral symptoms often develop with great rapidity and intensity, and the course of the disease is very rapid, the bacilli appearing in the blood almost at the onset of severe symptoms. The attack usually begins with trembling and rigors, intense headache, vomiting, and high fever. The countenance usually depicts intense anxiety. Extreme nervous prostration, restlessness, rapid shallow respirations, and delirium are common symptoms. In some cases the cardiac symptoms are the most prominent. The patients soon pass into a comatose condition, and die sometimes within 24 hours of the onset of the attack, but sometimes not until the third day.

Cases of primary septicemic plague are always fatal. Hemorrhages from the intestine sometimes occur in this form of plague as well as in bubonic plague. There is no distinct evidence that such cases are of primary intestinal origin. Hemorrhages from the nose and kidneys are also not uncommon.

The plague bacillus produces a powerful endotoxin which often causes a dilatation of the arteries, lowering of the blood pressure, and alterations in the functional activity of the heart, as well as degenerative changes in the heart muscle. It also acts particularly upon the endothelial cells of the blood vessels and lymphatics, the inflammatory reaction frequently causing circulatory obstruction. One of the most characteristic features of the pathology of plague is the tendency to produce general dilatation and engorgement of the vessels, with cutaneous, subserous, submucous, parenchymatous, and interstitial hemorrhages. In patients who have died of plague, the most common of the latter are in the epicardium, the pleura, peritoneal surfaces, the stomach and intestines, and the mucosa of the stomach and small intestine. Sometimes extensive hemorrhages are found in the peritoneal, mediastinal or pleura cavities. In the kidneys there are frequently subcapsular and renal hemorrhages, and blood extravasation into the pelves of the kidneys and ureters, as well as in the bladder and generative organs.

Sometimes there are considerable extravasations of blood into the substance of the brain. In bubonic plague, numerous hemorrhages are almost always present in the bubo. The tissues are characterized by vascular dilatation and engorgement. followed by edematous infiltration, the effect of the toxin being evident on the vessel walls. The endothelial cells become swollen, proliferated, and degenerated. Later hyaline degeneration of the walls may occur.

During the clinical course of the disease, hemorrhages are frequent. The bleeding may take place from the nose, mouth, lungs, stomach, or kidney, and sometimes from the uterus and bladder. These hemorrhages generally occur in severe cases of the disease. On examining the skin small punctifonn hemorrhages from about 1 to 2 millimeters in diameter are sometimes observed scattered over the skin in greater or less profusion. The petechie may occur on the face, neck. chest, abdomen or extremities. Sometimes larger patches of ecchymosis, in the neighborhood of 1 centimeter in diameter, are observed in the skin. Larger cutaneous effusions of blood are rarely seen, except at autopsy. The purpuric hemorrhages in bubonic plague usually do not appear before the third day of the disease. However, in septicemic plague they may be seen earlier.

At autopsy, the right side of the heart and the great veins are usually distended with fluid or only partially coagulated blood. During the disease, the patient frequently experiences a feeling of oppression over the precardial region. The heart sounds at first are clear, and the second pulmonic sound may be accentuated, but as the disease progresses they become feebler, or embryocardiac, in character and die first sound may be no longer heard. Sometimes heart failure may occur without any other sign of collapse. It may occur following exertion. such as sitting up. but it sometimes takes place while the patient is lying in bed. In primary septicemic plague, the course of which is very rapid, the cardiac symptoms are frequently the most prominent ones. In pneumonic plague, the limits of dullness of the heart are sometimes increased to the right of the sternum. At onset, the second pulmonic may be accentuated, but it soon becomes indistinct. As the disease progresses, gallop rhythm may occur. Death takes place usually from cardiac paralysis and exhaustion.


After penetration into the organism plague bacillus fill up the lymphatic nodes, blood and sputum. Their presence in the urine is very inconstant, but their detection during the bacteriological examination is very valuable for diagnostic. All the materials from the patients are to be received before the antibiotic treatment.

The materials for the bacteriological diagnostics are taken from the inflamed lymphatic node or bubo with the help of the sterile syringe. After the skin. which is over it, is cleansed, the node is fixed by the left hand and the needle attached to the syringe is slicked into it. It is better to take the punctate from the peripheral dense part of the bubo. With the slight movement of the needle several times up and down in the node the aspiration is made. The received liquid is poured into a small test-tube and when with all the required precautions it is to be send to the special laboratory, where one drop is used for the inoculation into of ligue agar, and another one for the smears, and the rest is injected under the skin of the guinea-pig.



Patients, who suffer from plague necessarily, hospitalize in appropriate hospitals where they are transported by ambulance.

Treatment should be started already on place of revealing of the patient. Early prescription of antibiotics (during the beginning of disease), as a rule, salvages it life. Efficiency of therapy by antibiotics in later terms is considerably lowest.

The most effective is Streptomycinum. At the bubonic form immediately infuse 1 gm of preparation into muscle, and then in hospital indicate 0.5-1.0 gm 3 times per day during one week. At a pulmonary and septic plague a dose of Streptomycinum enlarge to 5-6 gm. Antibiotics of tetracyclines (oxytetracycline, chlortetracycline), 0.25-1.0 gm 4-6 times are recommended. From other antibiotics it is possible to indicate monomicin, morphocyclin, ampicilin. After clinical indications it will be carried out pathogenic and symptomatic treatment.

After normalization of a body temperature and reception of negative datas of bacteriological researching from nasopharynx, sputum, punctate of bubones- patients leave hospital after 4-6 week.

Dispensary observation during 3 months its necessary for reconvalescense with obligatory bacteriological researching from mucosa of pharynx and sputum.

It is necessary to protect people from expansion of plague diseases. This work is carried out by workers of sanitation center, ambulatory - polyclinic network and antiplague establishments. Plague is the quarantine diseases, so on it the international medico-sanitary rules (WHO, 1969) are distributed on it.

Workers of the general medical network observe health of the population with the purpose of early revealing the patients on plague. Each medical worker should know the basic attributes of disease, the rules of personal prophylaxis, be able to carry out initial antiepidemic actions.

At presence of epizootia among rats and diseases of camels vaccination of the population by local services under the control of antiplague establishment will be carried out. As active immunization use living plague vaccine (dose for epicutaneous indication for children till 7 years 1 billion, 7-10 years - 2 billion, adults 3 billion microbes bodies, at a hypodermic immunization 1/10 of epicutaneous doses). Immunity is kept during 6 months, then if it necessary will spend revaccination in one year.

At occurrence of a plague among the population the antiepidemic actions carry out wich is directed on localization and liquidation of epidemic pesthole. They include: revealing of patients and their hospitalization in special hospitals in isolation wards with severe antiepidemic regime; and establishment of territorial quarantine: revealing and isolation of all persons which was in contact with patients they must be isolated for 6 days and will carry out emergency prophylaxis by antibiotics - Streptomycinum 0.5 gm 2 times per day in muscle or Tetracyclinum on 0,5 gm 3 times per day inside during 6 days); revealing the patients with fever and their hospitalization in special departaments; final disinfection, and also disinfestation and deratization at territory of settlement and around it. Invaluable things are liable to destruction. The personnel should be work in antiplague costumes. For persons who need to leave zone of quarantine, will carry out an observation.





Tularemia is an acute infectious disease of a septicemic character that is manifested by intoxication, fever and the affection of the lymph nodes; it belongs to the zoonosis group with natural foci.

Historic reference

In 1910 the American bacteriologist named Mc Coy who studied plague in the shot of ground squirrels in California discovered in them anatomic pathologic changes similar to plague, but the plague pathogen was not isolated. In 1911 having used a special dense medium cultivated by himself Mc Coy together with Chapin isolated the pathogen of this disease from ground squirrels in the clean medium.

After the name of the district Tulare, the word tule means large cane in aztec, the pathogen was named Bacterium tularense in 1912. During the work Chapin had a feverish disease for 28 days, it was not accompanied by an enlargement of the lymph nodes, after the recovery he discovered complement bound antigens and agglutinins to B. tularense in his own blood serum. In 1912 Vail observed a patient with conjunctivitis and an enlargement of the regional lymph nodes. Wherry and Lamb isolated the B. tularense culture from an eye of the pathologic material taken from this patient for the first time in the medical practice. Some time later they reported on the isolation of the same microbe from two hares that had been found dead. In 1919 and 1920 having examined seven patients (one of them died on the 28th day of his disease) Francis isolated the B.tularese from the blood and pus taken from them. In 1921 this gave him a ground to suggest the name tularemia for the disease, it became part of the international nomenclature.


The tularemia bacteria have very small dimensions - 0,3-0,5, but there are the smallest ones with a diameter of 0,1-0,2, they have an ability to pass the bacterial filter of Zeits (Fig.3).

Fig.3. F. tularensis in the hystologic smear

In case of cultivation on the small coccus, and in the animals organs it can be more often found in the form of coccobacteria. In the cultures on the nutrient medium tularemia bacteria are polymorphic, it is especially expressed in the American variety. The microbe is immobile, it does not make spores, and it has a small capsule. It is characteristic of the bacteria to produce mucous in the cultures, it can be easily detected during the preparation of smears on the glass. The tularemia bacteria can be tinctured with all kinds of stains, which are usually used in the laboratory practice. They are Gram-negative. In the smears-impression from the organs of the animals, which had died from tularemia the bacteria are well tinctured by Romanowsky-Giemsa obtaining the lilac color. The tularemia microbes, being obviously expressed pathogenic microorganisms, which are adapted to a strictly parasitic life style, are noted to be capricious in case of the cultivation on the artificial mediums - plain agar and broth.

The microbe is not very sensitive to low temperatures, it survives in the frost of 30 ; it can be preserved in the frozen meat up to 93 days. The tularemia bacteria are not stable to the temperature increase. The higher the temperature is the quicker the microbes die. Thus, the pathogen remains in the animal skins at a temperature of 8-12 for more than a month, and at a temperature of 32-33 - only during a week. The microbe dies at a temperature of 60 in 20 minutes, and boiling kills them immediately. The tularemia bacteria die under the influence of the sun rays in 20-30 minutes, their vital capacity remains in the diffused light up to 3 days. The tularemia bacteria are not stable to common disinfectants and are destroyed by an ultrasound.


Tularemia is epidemically defined as zoonosis which has natural foci mainly supported by wild rodents and blood sucking insects. The adherence of the people who live in the rural areas to this disease is one of the main peculiarities of the tularemia epidemiology, it is connected with the natural foci of this infection and the absence of the conditions for spreading among the home rodents in the big cities. The cases of the people infection in the cities are infrequent and connected with bringing infected food or animals from the rural areas. More often the city-dwellers get infected when they go to the country where there are natural foci.

The main sources of the tularemia infection are rodents, especially, common field voles, water-rats, house mice. sometimes muskrats and hamsters as well as hares. The infection of humans occurs either as a result of the contact with sick or dead rodents and hares or the bites of the infected blood-sucking arthropoda or due to water, food, straw and other substrata contaminated by the discharge of the animals sick with tularemia. A typical feather of the tularemia microbe is its ability to penetrate the organism of the humans and animals through small scratches on the skin. unaffected mucous membranes of the eye, throat, pharynx, the respiratory tract, and in case of a considerable dose the infection may penetrate through the unaffected skin. One of the typical epidemiological peculiarities of tularemia is almost 100% susceptibility of the humans to it irrespective of age and also the fact that the sick people are not contagious for the healthy ones.

The mentioned above peculiarities of the tularemia infection e. i. a great adaptation of the pathogen in nature, its possible ability to be transmitted by the animals or different objects of the environment (water, food. etc.) and a high susceptibility of the human to this infection resulted in the tularemia outbreaks, which involved great numbers of people under certain conditions. The tularemia outbreaks often reminded the epidemics of grippe or malaria in their character, and earlier they were diagnosed like this.

The concrete ways (mechanisms) of the tularemia infection of the humans are the following: contagious, alimentary, aspirational, transmissional. The infection often occurs by means of a contact with sick animals, a contact with the objects contaminated by them (hay, straw, corn, etc.), swimming in the reservoirs. The diseases belonging to this group are mainly typical of hunters-producers and in some cases of the members of their families who helped them to skin the shot animals. Besides this, there have been described some sporadic cases and even separate outbreaks occurring as a result of hunting hares. Not only did the hunters fell ill, but also the housewives who were infected while cutting carcasses.

The aspirational way of infection often occurred during the belated agricultural work while inhaling the dust rising into the air from the infected straw, corn and other substrates during their machinery or manual processing, cleaning, transportation, etc. In some cases the infection was accompanied by a contagious way.

The alimentary way of infection occurs while using the water and food containing the tularemia pathogen. The water way of the microbe transmission is due to the fact that it is considerably stable in water, especially, at a low temperature. The reservoir infection is due to the sick with the t infection water rats that live on their banks. The infection of the humans usually occurs in the summer, the morbidity increase is connected with hay mowing and other field work during which the population widely uses the water from the open reservoirs for drinking and washing.

The disease of the alimentary type is often connected with house mice penetrating the human's house or food stores, warehouses and other facilities and contaminating the food with their discharge. Bread, milk, cookies, crackers can be among such kinds of food.

The transmission outbreaks depend on the infection transmission by mosquitoes and gadflies, less often - by ixodes ticks. The insects are infected while sucking the blood of the sick animals but there are indications that the gadflies can be infected by the carcasses of the water rats as well as the water infected with tularemia. The infection of the humans at the transmission outbreaks occurs exclusively in the warm season and, as a rule, not far from the reservoirs, on the flood lands, during hay mowing and haymaking.


The tularemia pathogen can be brought into the human organism by different ways: through the skin, mucous membrane of the eye, respiratory tract, the gastroenteric tract and by a combined way. The localization of the infection gate undoubtedly influence the tularemia clinical manifestations. But it would be a mistake to consider this fact to be the only one and a decisive one. The ways of the human infection combined with immunobiologic reactions of the microorganism and the pathologic peculiarities of the pathogen determine the development of one or another clinical form of tularemia, one or another clinical course of the disease.

The tularemia pathogen is not known to have ability for an independent movement. That is why it is clear that from the entrance gate where its primary adaptation may take place, the following movement of the infect can be only in the direction of the liquid substrate. As a rule, it actually takes place with the lymph flow and very seldom with the blood flow.

The tularemia pathogen often gets into blood some time later, this causes bacteremia and may result in the generalized process. Hence in the pathogenesis of the tularemia infection in the humans the phase of the lymphatic mole precedes the pathogen penetration into blood. It is by the phases of the lymphatic mole and corresponding reactions of the microorganism that the formation and presence of the tularemia local clinical manifestations, that are so important for the diagnostics, are determined. Among such clinically expressed symptoms tularemia lymphadenitis, which is more often called a bubo, is sure to take the first place.

Pathogenically a sum of the reactive local changes in response to the influence of the tularemia bacteria is the basis for the development of such buboes. They remain in the lymph node during the lymph filtration and due to phagocytosis. The tularemia bacilli brought with the lymph flow reproduce in the lymph node and partly dying influence the node and the surrounding tissues by the secreted endotoxins, it results in adenitis and later periadenitis, the tularemia bubo development. Pathogenically the buboes can be divided into primary and secondary. The primary ones are often connected with the location of the entrance gate and are divided into the buboes of the first, second degree, etc. In contrast to the primary tularemia buboes the secondary ones do not have a territorial connection with the localization of the infection gate. Pathogenically they develop as a result of the hematogenic metastases. According to the terms of the development they are delayed and less expressed clinically. The secondary buboes do not usually produce any purifonn softening. It is clear that it is not only the reproduction of the tularemia microbes that takes place in the foci of their concentration, but also their death with the excretion of endotoxins, which stipulate the symptoms of the general intoxication.

Thus every clinical form of tularemia has the symptoms of the general intoxication though the intensity and character of the local changes are different and retain their diagnostic value. Hence, the general intoxication of the patient's organism with specific endotoxins is the basis of the general manifestations of the disease.

The tularemia pathogen penetrates the organism through the mucous membranes of the eyes, respiratory tract, gastroenteric tract and the localization of the entrance gate influences the development one or another clinical form of tularemia. However theoretically the ways of the tularemia pathogen movement remain the same e. i. the lymphatic and then the hematogenic one.

The bacteremia breaks of the tularemia bacilli followed by metastases in the lungs, liver, spleen, marrow, etc. is the basis of the specific pathomorphologic changes and the development of the multiple foci, which is the basis for the possible development of the tularemia process as a septic one. In some patients such metastases stipulate the presence of such specific complications of the secondary character (secondary tularemia pneumonia, tularemia meningitis, etc). In the most severe cases with the increasing symptoms of intoxication the lethal outcomes are possible (severe secondary tularemia sepsis).

Anatomic pathology

The anatomic pathologic changes in human tularemia have not been studied very well partly because of the low mortality. The formation of the tularemia granulomas in the form of whitish or whitish-yellow nodes is very typical. The granulomas are characterized by a zonal structure: there are epithelioid cells in the center, then - lymphoid. plasmatic and neutrophilic erythrocytes. then fibroblasts and often eosinophils. The central necrotic disintegration is crumb-like, acidophilic with a great number of chromatin clods in the fresher granulomas. The granulomas gradually enrich themselves with fibroblasts, argyrophil and collagenic fibrae that result in the granulomas scarring. There are no capillaries in the granulomas and they desolate soon. There are focal hemorrhages on the periphery of the granulomas. The granulomas in tularemia are similar to those in tuberculosis.

Catarrhal laryngotracheobronchitis often develops in the primary pulmonic forms. The inflammatory changes of the lungs are macrofocal. can be similar to croupous pneumonia but tularemia pneumonia develops as serous or serous-fibrinous with a conversion to necrotic one. The abscess formation is usually observed. Pneumonia is usually complicated by serous-fibrinous or purulent pleuritis, later by similar pericarditis. There are changes typical of tularemia (necrosis, granulomas, suppuration) in the peribronchial and mediastinal lymph nodes.

In the anginous-glandular form one tonsil is affected. The process can only be limited by plethora and hyperplasia. However, more often focal necrosis develops in the beginning, then it is followed by extended necrosis and ulceration with purulent melting or diphtheritic patches. The transformation of the submaxillary, superior cervical lymph nodes into buboes occurs simultaneously.

The eye disease can be in the form of the primary eye-glandular form and in the form of the secondary affections. At first there develop papules mainly in the lower eyelid mucous membrane, they suppurate and ulcerate with the discharge of purulent exudate. The eyelids are sharply swollen. The cornea is not often affected. The buboes typical of tularemia are localized in the parotid lymph nodes but the superior cervical lymph nodes also be affected.

Clinical manifestations

The incubation period in tularemia often lasts from 3 to 7 days. The cases of the incubation period in humans within the limits of the first 24 hours are practically very rare exceptions, and the cases of the incubation period exceeding two weeks are very doubtful.

There are three periods in the clinical course of the disease: 1) primary, 2) high point of the disease, 3) a period of convalescence. It is extremely important to pay special attention to the first period for the sake of both clinical and epidemiological diagnostics.

The onset is always acute without prodromal phenomena, which are accompanied by chills or expressed shivering and abrupt temperature increase up to 39 C and higher. Most patients name not only the day but also the hour of the disease onset without any difficulties. The patients complain of a headache, malaise, various muscle aches, which are often in the sural and waist areas. Besides this there is dizziness and appetite worsening, which develops into complete anorexia. The sleeping disorders as well as increased sweating, especially at night, are quite typical. In more severe cases there is vomiting, nose bleeding and later there can develop the conscious darkening and delirium. The headaches are the most persistent and prolonged. The hyperemia of the face and sometimes of the fauces is objectively observed. On the part of the upper respiratory tract there are usually no catarrhal symptoms, rhinitis and sneezing are very rare. Conjunctivitis and watery eyes are the most clearly expressed in the primary eye affection.

As the primary period of tularemia does not have any pathognomonic symptoms, the epidemiological anamnesis, which should be distinctly reliable and exhaustive, is of great importance. The total duration of the primary period is 2-3 days. Later the clinical symptoms of the disease develop in different ways depending on the development of tularemia in one or another clinical form.

The forms of tularemia which are distinguished according to the clinic-pathogenic and epidemiological data are as follows. The bubonic, ulcer-bubonic, eye-bubonic forms develop when the infection penetrates through the skin and eye mucous membrane. In the anginous-bubonic and abdominal forms the infection penetrates through the mouth. In the pulmonic (bronchial and pneumonic variants) the infection penetrates through the respiratory tract. Besides there is a generalized or primary septic form (it is observed in any way of infection, especially, in weakened people).

The bubonic form of tularemia is characterized by the development of the inflammatory process in the regional lymphatic node (Fig.4). A bubo (lymphadenitis) is an obligatory and fundamental symptom of the disease here. There are primary and secondary buboes. The primary buboes develop in a lyphogenous way and are connected with the area of the pathogen penetration. The secondary buboes develop as a result of the hematogenic spreading and are not connected with the localization of the entrance gate. The size of the tularemia buboes varies from the size of a small nut to a chicken egg and larger. It is usually not a separate regional node that gets involved in the process, but several nodes in a particular area. The buboes are dense, slightly painful, there is no expressed periadenitis. There can be several main variants of the tularemia bubo outcome: complete dissolving, suppuration, ulceration with the following scarring and sclerotization. If there is no suppuration, the reverse development or dissolving is slow and undulating with changing of improvement and an acute condition. The process lasts up to 2 and more months. The softening of the bubo begins in 2-3 weeks from the disease onset, but sometimes even later. The suppurating softening develops approximately in half of the cases. At first there is no distinct reaction on the part of the surrounding cellular and skin but soon there develops swelling and skin reddening gradually increasing in intensity and extensity and, finally, there is a breakage with buboes draining. The puss of the tularemia buboes is thick, white, without any smell, it looks like cream or sour cream.

Fig.4. Neck lymphadenitis

The bubonic form of tularemia with the primary affection on the part of the sight organ - an eye-bubonic form develops if the pathogen penetrates the eye mucous membrane. In this case there is expressed conjunctivitis, sometimes the presence of papules and ulcers besides regional (parotid, front cervical, submaxillary) lymphadenitis on the part of an eye. The eyelids are swollen and dense, the patients complain of their tenderness at moving, the amount of the mucopurulent discharge is moderate. On the eyelid mucous membrane there are inflammatory small foci in the form of the cone, they are yellowish and have a whitish top with the size of a pin's head up to 3-10 millet grains. There is a considerable number of separate groups of yellow dots on the lower eyelid on the background of a big number of scattered formations, a smaller number of them is observed on the upper eyelid.

There are inflammatory small foci with a bunch of the superficial widened vessels on the sclera conjunctivas, the foci are almost always located near the limbus. No changes on the part of the cornea or other refracting media of the eye have been found. In a number of cases the eye-bubonic form is accompanied by dacryocystitis. the lachrymal sack phlegmons have been described. Almost all the patients have an affection of the parotid and submaxillary lymph nodes, in some patients their increase is observed on the 3-10th day of the disease. The clinical course of the eye tularemia affection is within the limits of 20 days to 3 months. The eye affection may be secondary, in this case the eye changes as well as the eyelid skin ones take a course similar to that of metastatic granulomatosis and is observed in different clinical forms of tularemia.

The anginous-bubonic form of tularemia is first accompanied by the development of angina with characteristic local changes on the part of the tonsils: hyperemia, hyperplasia, grayish-whitish patch, which is often on one side. There are local pains and swallowing difficulties. The degree and quality of the local affections in the anginous-bubonic form as well as the dynamics of the process are diverse. According to the clinical peculiarities there are three types of tularemia angina: catarrhal, patch-diphtheritic and infiltrative-ulcerative.

There is hyperemia of the fauces, pain at swallowing, high temperature, enlargement of the cervical lymph nodes - the formation of buboes in the catarrhal variant of tularemia angina. A white patch firmly sticking to the mucous membrane develops on the tonsils and airfoils in the second form. There is hyperemia with a cyanotic tint in the circumference of the grayish-greenish covers. The covers usually remain for a long time and begin to tear away only two weeks later. A massive, quite dense infiltrate, which has no inclination to abscess forming and which goes up till the hard palate, develops from the very beginning in case of infiltrative-ulcer variety. Its reverse development lasts 2-3 weeks and in some cases ulcers develop in the area of the infiltrate.

Expressed catarrhal pharyngitis, cyanosis of the mucous membrane with a crimson tint that looks like venous congestion are observed in all cases. The congestion phenomena in the fauces remain for a long time, even after the end of the ulcerative-necrotic processes. The insignificant subjective feelings during a severe ulcerative-necrotic destructive process in the fauces are typical of tularemia angina. In some cases the enlargement and tenderness of the cervical lymph nodes coincide with the changes in the throat, sometimes buboes are formed only by the moment of the angina disappearance. A bubo remains for 2-8 months, less often shorter. Tularemia angina is characterized by a strict localization in most cases the changes are limited by one tonsil irrespective of the severity of the changes.

The abdominal form of tularemia has not been studied well so far, so it is supposed to occur more often than it is diagnosed. Severe pains in the stomach are typical of the abdominal form. The process is characterized by a deep localization of the affected, mainly mesenteric lymph nodes, in contrary to other variants of the bubonic form with the peripheral buboes localization. This variant cannot be united with the generalized form as in this case the affection of the lymph nodes of a certain (abdominal) area prevails. Epidemiologically it is most often observed at the outbreaks, which are characterized by the massive doses of infection that penetrate through the throat (water outbreaks).

The pulmonary (thoracal) form of tularemia occurs in case of the aspiration way of infection and is characterized by the development of the primary inflammatory process in the lungs. Epidemiologically this pneumonia is connected with certain conditions of infection. Thus, during threshing when the stacks are infected with the discharge of the mouse-like rodents, the infection is airborne and several people fall ill. The airborne infection in the laboratories is less frequent, with separate cases.

In case of the primary pulmonary form the inflammatory process develops in the lungs from the very beginning. There can be two main variants in this case: bronchial, when the process occupies only the large respiratory tracts, and bronchial pneumonic when the deeper parts are affected - bronchioles, alveoles. The clinical picture is diverse and depends on the localization of the intensity process and the combination of the inflammatory changes. Only tracheitis, bronchitis and their combinations are possible, this confirms their aspirational way of infection. Hence in some cases the pulmonary tissue does not get involved in the pathological process. But the process is localized in the chest and spreads on the mediastinal lymph nodes, that is why these forms of tularemia are named thoracal.

The bronchial pneumonic variant, or tularemia pneumonia, is characterized by a dull and exhausting course, it lasts up to a month, less often 2 months and longer. Anatomically these are small foci, which have a tendency to confluence and cause lobar pneumonia.

Pneumonia has a severe course but it does not have a cyclic course. it has a tendency to relapses and the formation of different specific complications: bronchiectasia, abscesses, the lungs gangrene, dry and moist pleuritis. Necrosis in the affected parts of the lung can result in the cavity formation - tularemia caverns. Sometimes the changes in the lung tissue have a dull prolonged character with clinically expressed intoxication. The patient with tularemia pneumonia is not contagious for the surrounding people.

It is necessary to distinguish this primary tularemia form from the secondary one, which can join any other clinical form as a complication. It develops in a metastatic way later and deteriorates the course of the disease. The terms of the end of such pneumonia are quite various - from 2 weeks to 2 months and longer.

In case of the generalized form of tularemia the fundamental sign is the development of the general symptoms of the disease without previous local symptoms, which are absent in the future, as a rule. It is the only form of tularemia, which does not have a primary and a regional reaction. Clinically the generalized form is distinguished by more severe manifestations of intoxication, sometimes even fainting and delirium.

The headaches are intense and persistent, adynamia and muscle aches are very expressed. The fever lasts about 3 and more weeks, and the temperature curve is often oscillatory. A rash similar to exudative polymorph erythema often develops during the second half of the disease. The rash on the upper and lower extremities is usually symmetric, pink-red, later has a crimson-coppery tint and at the end it has a cyanotic shimmer in the form of the tularemia "gloves", "gaiters", "socks". The rash remains for 8-12 days. there is peeling and prolonged pigmentation after the rash disappears.

In the generalized form of tularemia the capacity to work is recovered especially slow, the relapses are not excluded.


There are several methods of the tularemia pathogen isolation in the laboratory. These are direct bacterioscopia, bacteriology with the microbes identification and a biological method. However the immunologic methods are more often used to diagnose the disease in people than the bacteriological ones. It depends on the fact that the tularemia pathogen belongs to the first group of microorganisms, that is why its isolation and identification can be done only in the specially equipped laboratories of the departments for the especially dangerous infections.

The agglutination reaction is the most popular method of the serologic diagnostics. The reaction is considered positive when serum is diluted 1:100 and higher and becomes positive from the second week of the disease. It is necessary to take into account the fact that there is antigenic closeness between the tularemia and brucellosis pathogens, that is why the serum of the tularemia patients can give a positive reaction of agglutination with brucellas and. vice versa, the brucellous patient can give a positive reaction with the tularemia pathogen. As a result of this the agglutination reaction has a diagnostic value only when the antibodies titers increase in the dynamics of the disease.

The sanguinous-dropping agglutination reaction is an accelerated method of the approximate serologic diagnostics of tularemia. However it does not relied the dynamics of the increase of the antibodies titers and cannot he an early method of diagnostics. For this purpose a thick drop of a patient's blood, a drop of the distilled water, which is used for the lysis of erythrocytes and easy reading of the reaction, and a drop of diagnosticum are put on the glass. The agglutination begins immediately if there are agglutinins in the diagnostic titer 1:100 and higher in the patient's blood. The later agglutination on the glass during 2-3 minutes is doubtful for the diagnostics.

For the purpose of the accelerated preliminary orientation in the diagnostics it is possible to use microseroreaction. For this puqiose it is not a drop of blood but a drop of blood serum of a patient that is put on the glass, and a drop of undiluted tularemia diagnosticum containing 5 billion microbic cells in 1 ml is added to it. The serologic reaction becomes positive from the 9-10th day of the disease, sometimes earlier, if the titer of antibodies at volume agglutination is 1:10 - 1:20.

The compliment binding reaction (CBR), hemagglutination reaction, precipitation reaction and others can also be used.

An intracutaneous allergic reaction on the injection of allergen - tularin, 1 ml of which contains 100 million microbic bodies killed by heating at a temperature of 70 C during an hour, is highly specific. The suspension of the tularemia microbes (antigen) is prepared in the physiological salt solution with the addition of the 3 % glycerin. The preparation is injected strictly intracutaneously. sterile in the amount of 0.1 ml in the middle third of the forearm, on the palm side. The intracutaneous test is valid in all the clinical forms of tularemia. The result of the reaction should be considered dynamically in 24-36-48 hours after its beginning. An expressed edema or infiltrate is considered to be a positive allergic reaction. Hyperemia without edema, which disappears in 24 hours is considered to be a negative result (a nonspecific reaction). In some cases the positive reaction is accompanied by the formation of a pustule and sometimes necrosis or lymphangitis and slight regional lymphadenitis with the body temperature increase up to 37,5-38,0 C during 1-2 days.

The test is quite specific (it is necessary to take into account the possibility of inoculative or anamnestic reaction) and usually allows to diagnose the disease from the fifth day after its onset.



The patients are treated in the infectious hospital. Antibiotics are the main in complex therapy. Streptomycin is the most effective: 0,5 gm 2 times per day in a muscle. At pulmonary and generalized forms daily dose of Streptomycin enlarge till 2 gm. Course of treatment lasts all period of fever and the next 5 days with normal body temperature. Streptomycini sulfas has bactericidal effect, after its introduction reaction of Yarish-Hercscheimer may be observed. Therefore in serious cases antibiotic therapy is combined with Prednisolon or its analogues.

Tetracyclin, Doxycyclin, Levomycetin, Kanamycin, Gentamicin, rendering bacteriostatic action are less effective. At pulmonary and generalized forms daily dose of the specified antibiotics is enlarged in 1,5 times. Preparations of Tetracyclin are expedient for combining with Aminoglycosides.

At lingering current and relapses of tularemia provide combined treatment with antibiotics and inactivated vaccine which infuse parenteraly in a single dose 1,5 - 15 million microbic bodies with interval 5 - 6 days. Course of treatment consists of 6 - 12 infusions.

As desintoxication therapy it is expedient to use Reopoliglycin, standard saline solutions with glucose. Widely use vitamin preparations desensitizing agents. Using of bandage with Unguenti of Streptomicin in bubo form.

At anginous-bubonic form of tularemia the inhalation of Chlorophilyptus are recomended. At procces of eyes indicate 20 - 30 % a solution of Sulfacyl-natrii.

The treatment is complex, the antibacterial therapy plays the main role in it. Streptomycin, tetracycline, chloromycetin are the most effective medicines. A day's dose of streptomycin 1-2 gm, tetracycline - 1,5-2 gm, chloromycetin - 2 gm. At the highest point of the disease detoxication therapy is prescribed (an intravenous injection of the salt solutions, haemodesum, polyglucinum, 5 % solution of glucose, ascorbic acid). The detoxication therapy is done by taking enterodesum and other preparations of this group. Calcium gluconate, diphenylhydramine, pipolphen, diazolinum are used to decrease the allergic manifestations.

In case of relapses and acute forms it is necessary to prescribe antibiotics courses, but it is necessary to remember about dysbacteriosis.

Compresses, ointment bandages and wanning treatment are used at the area of buboes at the stage of dissolving. If the buboes suppurate. they are widely opened and treated as a purulent wound together with treating the main disease. In case of the timely and valuable treatment the prognosis is usually favorable. The lethality is up to 0,5% and occurs in the complicated pulmonary and abdominal forms of tularemia. The ability to work is recovered slowly.


The prophylaxis includes the control over the natural foci, the interruption of the mechanism of the disease transmission, as well as the vaccination of the population in the epidemic foci. The planning and the fulfillment of this work in the tularemia foci are done by the sanitary-antiepidemic service with the participation of the medical workers of the medical institutions who perform the rounds in the houses and the vaccination of the population.










Acute infection in both animals and humans in three forms: cutaneous, respiratory, and gastrointestinal. The incidence of anthrax has decreased in developed countries but it remains a considerable health problem in developing countries.

Historic reference


There are descriptions of anthrax involving both animals and humans in the early literature of Hindus, Greeks, and Romans. In the seventeenth century, a pandemic referred to as the black bane swept through Europe, causing many human and animal deaths. Later the disease in humans was described as the malignant pustule.

Several distinguished microbiologists in the nineteenth century characterized the pathology of the disease and attempted to develop a vaccine because of serious problems with anthrax in the livestock industry. Pasteur developed and field tested in sheep his attenuated spore vaccine in 1881. In 1939, Sterne reported his development of an animal vaccine that is a spore suspension of an avirulent, noncapsulated live strain. This is the animal vaccine currently recommended for use.

From the beginning of this century the annual number of cases reported in developed countries has steadily decreased. This decrease is the result of the use of a cell-free anthrax vaccine in humans who are in high-risk industrial groups, decreased use of imported potentially contaminated animal products, improved hygiene in industry, and improved animal husbandry.



Pus or tissue from patients suspected to have anthrax should be stained by both Gram stain, to reveal gram-positive bacilli, and polychrome methylene blue, to show the polypeptide capsule. Bacilli are usually abundant in the specimen and easy to culture on standard blood or nutrient agar (Fig.5).

Fig.5. Bacillus antracis


In heavily contaminated specimens such as stool it may be necessary to use selective agar or decontamination methods that rely on the resistance of the anthrax spores to heat or ethanol. The colonies are gray-white to white and nonhemolytic. Identification of the isolate depends on biochemical tests, presence of a capsule, lack of motility, catalase positivity, lysis by γ-bacteriophage, penicillin susceptibility, and aerobic endospore production. Commercially available test strips (API Products, Plainview, NY) and fluorescent antibody staining can be used to aid identification.


Anthrax is usually a disease of herbivores and only incidentally infects humans who come into contact with infected animals or their products. Because anthrax remains a problem in developing countries, animal products imported from these areas continue to pose a risk.

Human cases may occur in an industrial or in an agricultural environment. Industrial cases result from contact with anthrax spores that contaminate raw materials that are used in manufacturing processes. In the United States, occasional epidemics occurred in industrial settings, probably related to the processing of batches of highly contaminated imported animal fibers, particularly goat hair. These epidemics were primarily of cutaneous anthrax.

One epidemic was recently reported in Switzerland. Within less than 3 years, 25 workers in one textile factory contracted the disease; 24 cases had cutaneous and 1 inhalation anthrax. The infection was imported in goat hair from Pakistan. The rarity of the illness contributed to a general lack of experience and therefore hindered recognition of the clinical symptoms. In addition, repeated attempts failed to identify the pathogenic agent conclusively.

Human cases of anthrax in an agricultural environment result from direct contact with animals that are sick or have died from anthrax.

In Africa there have been multiple epidemics of human disease associated with epizootics of anthrax in cattle. The largest reported agricultural outbreak occurred in Zimbabwe, with more than 10,000 cases reported between 1979 and 1985. Endemic cases continue to occur in the involved area. The majority of patients had cutaneous infections located primarily on the exposed parts of the body; some gastrointestinal cases were also reported. Domestic cattle deaths were noted. A similar large outbreak of human and animal anthrax occurred in Chad, mainly in the Department of Chari Baguirmi, from September to December 1988, infecting more than 50 % of donkeys and horses. There were 716 human cases reported, with 88 deaths.

In African wildlife, which cannot easily be vaccinated and in which the other aspects of control are not relevant, the disease remains a major cause of uncontrolled mortality in herbivores.

Organisms can also be transmitted by a common vehicle such as food (meat), although this is more rare. Large outbreaks have been reported in Thailand and Russia. This last outbreak of human anthrax occurred in north central Russia in 1979, in which the government health authorities of the former U.S.S.R. reported that the source of infection was contaminated meat. Officially there were 96 cases: 79 of gastrointestinal anthrax and 17 of cutaneous anthrax. However, there is novel evidence concerning the real nature of this anthrax outbreak. Intelligence authorities in the United States had initially reported hundreds of fatalities, including military personnel, and had suspected that an explosion at a secret germ warfare facility in Sverdlovsk had sent deadly anthrax spores airborne. The United States has repeated this allegation, but it never formally accused the former U.S.S.R. of violating the germ warfare treaty or substantiated its charge. The hospital records of the patients affected by this outbreak including the autopsy reports have been unavailable.

Recently two Russian pathologists published hidden secret information describing the necropsy of 42 cases, which consistently revealed pathologic lesions diagnostic of inhalation anthrax. Main features include hemorrhagic necrosis of the thoracic lymph nodes in the lymphatic drainage of the lungs and hemorrhagic mediastinitis. This information underscores the potential use of B. anthracis in biological warfare.


The virulence of B. anthracis is determined by the presence of three components: edema toxin, lethal toxin, and capsular material. To exert their effect within cells, both edema and lethal toxin require participation of a common transport protein called protective antigen. The capsule material contains poly-D-glutamic acid, which helps protect the bacillus from ingestion by phagocytes. Production of the toxic factors is regulated by one plasmid and that of the capsular material by a second plasmid.

The effects of anthrax toxin components on human neutrophils have been studied in detail. Phagocytosis of opsonized and radiation killed B. anthracis was not affected by the individual anthrax toxin components. However, a combination of lethal toxin and edema toxin inhibited bacterial phagocytosis and blocked the oxidative burst of polymorphonuclear neutrophils. The two-toxin combination also increased intracellular cyclic AMP levels. These studies suggest that two of the protein components of anthrax toxin increase host susceptibility to infection by suppressing polymorphonuclear neutrophil function and impairing host resistance.

Experiments performed in animals suggest that spores deposited beneath the skin or in the respiratory or intestinal mucosa germinate and the resulting vegetative forms multiply and produce a toxin. The local lesion results from the action of the toxin on the surrounding tissue, which causes tissue necrosis. The toxin or organisms or both may disseminate by the vascular system, causing systemic symptoms and signs of toxicity or bacteremia. Organisms are also often picked up by the lymphatic system, resulting in lymphangitis and lymphadenopathy.

Morbid anatomy


The most significant findings at autopsy are those seen in patients who have died of inhalation anthrax. The classic finding is that of hemorrhagic mediastinitis with enlarged, hemorrhagic lymphadenitis. There may be inflammation of the pleura and some pleural effusion. Some patients may have hemorrhagic meningitis, and hemorrhages may be seen in the gastrointestinal tract.

In deaths due to gastrointestinal anthrax there is typically hemorrhagic enteritis, with congestion, thickening, and edema of the intestinal walls. Mucosal ulcers with necrosis may be seen in the terminal ileum and cecum. The regional lymph nodes are enlarged, edematous, and hemorrhagic with some necrosis. There may be acute splenitis. Peritonitis with ascitic fluid is often present.


Clinical manifestations

Approximately 95 % of anthrax cases in developed counties are cutaneous and 5 % are respiratory: confirmed epidemic cases of gastrointestinal anthrax have often been reported in Third World countries.

The clinical presentation of cutaneous anthrax is so characteristic that the diagnosis is not often missed by physicians familiar with the disease. Most of the cases occur in exposed skin areas mostly on the arms and hands followed by the face and neck. The infection begins as a pruritic papule that resembles an insect bite. The papule enlarges and within 1 or 2 days develops into an ulcer surrounded by vesicles. The lesion is usually 1-3 cm in diameter and usually remains round and regular (Fig.6, 7). A characteristic black necrotic central eschar develops later with associated edema (Fig.8, 9). The lesion is most often painless and may first be noticed because of pruritus. After 1-2 weeks the lesion dries, and the eschar begins to loosen and shortly thereafter separates, revealing a permanent scar. There may be regional lymphangitis and lymphadenopathy and some systemic symptoms such as fever, malaise, and headache. Antibiotic therapy does not appear to change the natural progression of the lesion itself: however, it will decrease or inhibit development of edema and systemic symptoms. Differential diagnosis include conditions due to potential contact with infected animals such as plague and tularemia.


Fig.6. Anthrax carbuncle

Fig.7. Anthrax carbuncle


Fig.8. Edema of skin


Fig.8. Edema of skin


Respiratory anthrax shows a biphasic clinical pattern with a benign initial phase followed by an acute, severe second phase that is almost always fatal. The initial phase begins as a nonspecific illness consisting of malaise, fatigue, myalgia, mild fever, nonproductive cough, and, occasionally, a sensation of precordial oppression.

The illness may cause disorder of a mild upper respiratory tract infection such as a cold or viral influenza. After 2-4 days, the patient may show signs of improvement. However, there is then the sudden onset of severe respiratory distress characterized by severe hypoxia and dyspnea. In several cases, subcutaneous edema of the chest and neck has been described. The pulse, respiratory rate. and temperature become elevated. Physical examination reveals moist, crepitant rales over the lungs and possibly evidence of pleural effusion. Radiographic examination of the chest may reveal widening of the mediastinum and pleural effusion. Patients soon become hypotensive and septicemia and meningitis may develop. Death occurs in most persons with inhalation anthrax within 24 hours after the onset of the acute phase. Inhalation anthrax is very difficult to diagnose early.

The incubation period of gastrointestinal anthrax is commonly 3-7 days. There are two clinical presentations following ingestion of B. antracis-contaminated food: abdominal and oropharyngeal.

The symptoms of abdominal anthrax are initially nonspecific and include nausea, vomiting, anorexia, and fever. Lesions are frequently described in the cecum and adjacent areas of the bowel. Some reports have described lesions in the large bowel, and rarely in the duodenum. With progression of the disease abdominal pain, hematemesis and bloody diarrhea develop. With further progression toxemia develops, with shock, cyanosis, and death. The time from onset of symptoms to death has most frequently varied from 2 to 5 days.

In the oropharyngeal form edema and tissue necrosis occur in the cervical area. There are several reports describing the development of an inflammatory lesion resembling a cutaneous lesion in the oral cavity involving the posterior wall. the hard palate, or the tonsils. The main clinical features are sore throat, dysphagia, fever, regional lymphadenopathy in the neck and toxemia. Most of these patients die with toxemia and sepsis.


It is estimated that approximately 20 % of untreated cases of cutaneous anthrax will result in death, whereas inhalation anthrax is almost always fatal. Deaths are, however, rare after antimicrobial treatment in the cutaneous form.

Intravenous penicillin is the drug of choice, with a dose of 4 million units every 4-6 hours. Lesions become culture negative in a few hours but therapy should be continued for 7-10 days. For the penicillin allergic patient, erythromycin, a tetracycline or chloramphenicol is satisfactory. Antibiotic therapy is designed to ameliorate systemic symptoms, although progression to eschar is not prevented. Excision of the lesion is contraindicated. Topical therapy is not effective. Systemic corticosteroids have been used for patients with extensive or cervical edema and in those with meningitis but indications are not well established. Tracheotomy may be needed when cervical edema compromises the airway.

Dressings with drainage from the lesions should be incinerated, autoclaved, or otherwise disposed of as biohazardous waste. Patients with draining lesions should be placed in "contact isolation." although this is superfluous is hospitals using "universal precautions." Person-to-person transmission has not been documented, including from patients with inhalation anthrax.



For the detection of anthrax bacillus, sterile swabs should be soaked in the fluid of the vesicles, Vesicular fluid should reveal B. anthacis organisms microscopically and on culture. Anthrax bacilli are easily seen on Gram stain smears and cultures from vesicular fluid. The differential diagnosis includes staphylococcal disease, plague, and tularemia.

An enzyme-lined immunosorbent assay (EL1SA) has been developed that measures antibodies to the lethal and edema toxins. The diagnosis may be confirmed serologically by demonstrating a fourfold change in liter in acute and convalescent-phase serum specimens collected 4 weeks apart or by a single titer of greater than 1:32.

Although extensive serologic studies have not been conducted, antibody liters in some surveys of exposed individuals suggest some degree of previous subclinical infection.

Control and prevention

The resistance of the spore form of B. anthracis to physical and chemical agents is reflected in the persistence of the organism in the inanimate environment. Organisms have been demonstrated to persist for years in factories in which the environment became contaminated during the processing of contaminated imported materials of animal origin. Accordingly, they may serve as the source of infection for people who work in the area. Special efforts are required to decontaminate this environment; one method is to use paraformaldehyde vapor, which is successful in killing B. anthracis spores. In the laboratory, surfaces may be decontaminated with either 5% hypochlorite or 5% phenol (carbolic acid); instruments and other equipment may be autoclaved.

Employees should be educated about the disease and the recommendations for working in a contaminated environment and for reducing the risk of developing the disease. Medical consultation services should be available to the employees. Adequate cleanup facilities and clothes-changing areas should be available so that workers do not wear contaminated clothes home.

It should be noted that the risk of industrial infection has been reduced significantly as the use of imported animal products decreased because of changing business conditions, the increased use of synthetic materials, and the use of human vaccine.

Gastrointestinal anthrax can be prevented by forbidding the sale for consumption of meat from sick animals or animals that have died from disease. Depending on the circumstances, it may be important to alert individuals who may come in contact with contaminated meat about the disease and about the need to cook all meats thoroughly. Prophylactic penicillin may be used if contaminated food has been ingested.

Animals that graze in areas known as anthrax districts should be vaccinated annually with the animal vaccine. All animals suspected of dying from anthrax should be examined microbiologically: blood or tissue smears can be examined microscopically, and cultures can be set up from these same materials. Necropsies with spillage of contaminated blood with resultant sporulation of organisms should be avoided. All animals that have died with a confirmed diagnosis of anthrax should be thoroughly burned and the remaining bones and other materials buried deeply.

Control of the disease in humans ultimately depends on control of the disease in animals. Effective animal vaccines are available, and all cases should be reported to state veterinary authorities.



Both an attenuated live vaccine and a killed vaccine have been developed. However, the only human vaccine in current use in the United States is the killed vaccine derived from a component of the exotoxin. This vaccine was field tested in employees of four different textile mills in the United States, and an effectiveness of 92,5 percent was demonstrated. This vaccine should be used for all employees who may be exposed to contaminated materials or environment. Additionally, anyone who comes into a mill processing B.antracis-contaminated materials should also be vaccinated. Currently, the vaccine is given parenterally with three doses given at 2-week intervals followed by three booster inoculations at 6-month intervals and the annual booster inoculations. Veterinarians and other persons who, because of their occupation, have potential contact with anthrax should also be immunized with the human anthrax vaccine.

The ability to prepare purified components of anthrax toxin by recombinant technology has opened the possibility of new anthrax vaccines. For example, immunization with protective antigen (PA) toxoid vaccines or PA-producing live vaccines elicits partial or complete protection against anthrax infection and these new vaccines deserve careful field testing.




Erysipelas is a distinctive type of superficial border serous or serous-hemorrhagic inflammation of the skin with prominent lymphatic involvement with acute or chronic course of disease.



It is almost always due to group A bhemolytic streptococci (uncommonly, group or G). Group streptococci have produced erysipelas in the newborns.



Erysipelas is more common in infants, young children, and older adults. Evidence of streptococcal infections (groups A, G, and C) was found in 26 of 27 patients with clinical erysipelas, utilizing the combination of direct immunofluorescence and cultures of punch biopsy specimens along with serologic titers. Very rarely, a similar skin lesion is caused by S. aureus.

Formerly, the face was most commonly involved, and an antecedent streptococcal respiratory tract infection preceded cutaneous involvement in about one-third of patients even though streptococci might not be found on culture at the time the skin lesion became evident.

Source of disease is sick person with erysipelas and other streptococcal infections (tonsillitis, pneumonia, scarlet fever, streptodermia) and healthy carriers.

Contact mechanism of transmission. Increasing of morbidity in summer-autumn period.



Most interest has focused on streptococcal pyrogenic exotoxins (SPEs). In edition to mediating the scarlatinal rush, SPE exibit a variety of adverse biologic effects, including the multiorgan damage and lethal shock. There is an amino acid homology of 50 % and immunologic reactivity between SPE A and staphylococcal enterotoxins B and C. SPE of group A streptococcus is a superantigen and it is a potent inducer of tumor necrosis factor.

The antistreptolysin O response after cutaneous streptococcal infection is wea. There is experimental evidence to suggest that this may be due to local inactivation of streptolysin O by skin lipids. The immune response to antiDNase B is brisk, and antihyaluronidase reactivity is also a useful test in the serodiagnosis of erysipelas.




Clinical manifestations

Usual localization of erysipelas: 70-80 % of the lesions on the lower extremities and 5-20 % on the face. Portals of entry are commonly skin ulcers, local trauma or abrasions, psoriatic or eczematous lesions, or fungal infections; in the neonate, erysipelas may develop from an infection of the umbilical stump. Predisposing factors include venous stasis, paraparesis, diabetes mellitus, and alcohol abuse. Patients with the nephrotic syndrome are particularly susceptible. Erysipelas tends to occur in areas of preexisting lymphatic obstruction or edema (after a radical mastectomy). Also, because erysipelas itself produces lymphatic obstruction, it tends to recur in an area of earlier infection. Over a 3-year period, the recurrence rate is about 30 %, predominantly in individuals with venous insufficiency or lymphedema.

Streptococcal bacteremia occurs in about 5 % of patients with erysipelas; group A, C, or G streptococci can be isolated on throat culture from about 20 % of cases.

The face (often bilaterally)(Fig.9), an arm or a leg (Fig.10) is most often involved. The lesion is well demarcated, shiny, red, edematous and tender; vesicles and bullas often develop. Patches of peripheral redness and regional lymphadenopathy are seen occasionally; high fever, chills and malaise are common. Erysipelas may be recurrent and may result in chronic lymph edema. A cause of infection may be an interdigital fungal infection of the foot that may require long-term therapy to prevent recurrent erysipelas.

Uncomplicated erysipelas remains confined primarily to the lymphatics and the dermis. Occasionally, the infection extends more deeply, producing cellulitis, subcutaneous abscess, and necrotizing fasciitis.

Leukocytosis is common with erysipelas. Group A streptococci usually cannot be cultured from the surface of the skin lesion, and only rarely can they be isolated from tissue fluid aspirated from the advancing edge of the lesion. In cases of erysipelas complicating infected ulcers, group A streptococci have been isolated from the ulcerated area in 30 % of patients.

Fig.9. Erysipelas of face

Fig.10. Erysipelas of leg



Diagnosis from the characteristic appearance is usually easy. The causative organism is difficult to culture from the lesion, but it may occasionally be cultured from the blood.



Mild early cases of erysipelas in the adult may be treated with intramuscular procaine penicillin (600,000 units once or twice daily) or with oral penicillin V (250-500 mg every 6 hours). Erythromycin (250-500 mg orally every 6 hours) is a suitable alternative. For more extensive erysipelas, patients should be hospitalized and receive pare) aqueous penicillin G (600,000-2 millions units every 6 hours).



Adherense to good regimens of personal hygiene, with special attention to frequent scrubbing with soap and water, is the most effective preventive measure currently available. The in time treatment of streptococcal pharyngitis is of much importance.