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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.

Symptoms and course of pneumonic plague. The onset of the disease 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 °Ñ or 40 °Ñ, and the pulse 110 to 130 or more beats

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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.

Symptoms and course of septicemia plague. 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,

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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 punctiform 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.

The pulse in bubonic plague varies greatly. More commonly, at the onset of the disease it is full and bounding, 100 to 120 per minute, becoming later still

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more rapid, 120 to 140 per minute, small, thready, irregular, and often dicrotic. However, in some cases it is small and thread-like, and very rapid from the onset of symptoms. In cases likely to prove fatal, the pulse becomes so rapid and thready that it is impossible to count it. In such cases, however, the larger arteries can often be observed to pulsate forcibly. In mild cases of plague, the pulse may only show slight acceleration.

The temperature curve in plague is often very irregular and not characteristic. In the severe cases, the initial rise is usually rapid and may be anywhere from 39.4 °Ñ to 41.1 °Ñ. The temperature may reach its highest point on the evening of the first day of fever, but usually the height of the curve is not readied till the close of the second or third day. From the third to the firth day, there is usually a remission of several degrees. Later the temperature may again rise, and in fatal cases it may reach 41.7 °Ñ before death. A sudden fall of temperature during the height of the disease, with a collapsed condition, sometimes occurs and usually also indicates a fatal issue. In more favorable cases, after the secondary rise the temperature often falls slowly and gradually, with more marked remissions each morning, until the normal or even subnormal point is reached. The course of the fever often lasts in uncomplicated cases from 6 to 12 days. Suppuration of the buboes, however, may cause great irregularity of temperature, and the occurrence of complications may considerably prolong the period of fever. As a rule, the higher and more continuous the temperature, the severer the other symptoms. In mild cases of bubonic plague, the temperature may fall to normal as early as the second or third day, and it may not reach over 37.7 °Ñ during the attack. In primary septicemic plague, the temperature usually rises suddenly and remains high until death supervenes. Occasionally, however, if the patient lives from forty-eight to seventy-two hours after the onset, the temperature may fall suddenly, reaching normal or becoming subnormal just before the fatal outcome. In primary pneumonic plague the onset of the temperature is rapid and reaches the maximum point usually within twenty-four to thirty-six hours. In this form of the disease the temperature also often declines to below normal before death.

Early in the disease there is no reduction in the number of red blood corpuscles or in the percentage of the hemoglobin. In fact, both Rogers and Castellani have observed that the red cells and hemoglobin are not infrequently increased above normal. In the late stages of bubonic plague, particularly in the cases with complications, a moderate secondary anemia may occur. A leucocytosis is almost invariable in bubonic plague except in the mildest cases, during the first three days of the disease. Usually the count is in the neighborhood of from twenty to twenty-five thousand. In about 5 % of the cases it may be higher, the leucocytes occasionally numbering forty thousand or even more. A differential count will show that the polymorphonuclear leucocytes are found to be increased and the large mononuclear cells usually diminished. In some of the very rapidly fatal septicemic and primary pneumonic cases in which collapse and death appear

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early, there may be no leucocytosis. In such cases plague bacilli may sometimes be present in the blood in such numbers that a simple microscopical examination of a hardened and stained specimen suffices for their detection. The plague bacillus can be cultivated from the blood in the primary septicemic and primary pneumonic cases, as well as in about one-half of the bubonic cases of plague. The plague bacilli after they appear in the blood in bubonic plague increase up to the time of death and they can always be cultivated from the blood at autopsy. Over 90 % of the cases of bubonic plague in which the bacilli appear in the blood terminate fatally.

Buboes or inflammatory swellings of the lymphatic glands, which develop in about three-fourths of the cases of plague, may become noticeable any time from the onset of the attack to the fifth day. More often they develop within forty-eight hours of the onset of the fever. Usually they increase rapidly in size.

At first a single gland may be felt enlarged, but more commonly several adjacent glands are involved. Sometimes groups of glands become successively infected, in which case there is always more or less periglandular infiltration. Thus a bubo in the inguinal region not infrequently extends into the iliac region affecting the lymphatic glands of the abdominal cavity, and forming secondary buboes which can sometimes be felt as a mass through the abdominal wall. This condition has been mistaken for an appendicular abscess. The buboes vary greatly in size, more commonly they are about the size of a walnut, but they may be as large as an egg or even^n orange. They are usually single, but in about 10-12 % of the cases they may be multiple and form on both sides of the body. As has been emphasized,the buboes form in the inguinal region in from about 60-70 %, one or more of the inguinal or femoral glands being involved. In about fifteen to twenty per cent they occur in the axillary region where the bubo often occludes the axillary space and obliterates the outline of the margin of the pectoralis major. In this region there is usually extensive inflammatory exudation which extends over the side of the chest and sometimes upwards to the shoulders and even to the side of the neck. Such cases frequently result fatally,and cases with axillary buboes often become septicemic early in the disease. In about five to ten per cent of the cases the bubo forms under the jaw or at its angle; more rarely elsewhere in the neck or in the tonsils. In these situations there is often much edema and exudation especially in the vicinity of the bubo and the patient may die from suffocation, the trachea and glottis first becoming very edematous. In some instances in which the buboes have occurred in the tonsils,cases have been mistaken for diphtheria and even scarlet fever. More rarely buboes form in the epitrochlear region or popliteal space, the mammary gland, testicle, or in isolated glands in other parts of the body.

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

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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.

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.

Cellulo-cutaneous plague. The occurrence of petechiae and of larger ecchymoses in the skin have already been referred to. Plague carbuncles have also been reported. They occur most commonly on the buttocks or back, sometimes on the flanks or abdomen, the shoulders or posterior surface of the legs and arms. They generally make their appearance in the later stages of the disease and usually originate about ecchymotic patches. Subsequently a vesicle is formed, which soon ruptures and reveals a well circumscribed patch which may measure 1 centimeter or more in diameter. The base of the lesion is usually moist and either brownish red or bluish in color, while the margins are indurated and infiltrated. The necrosis in some instances becomes deeper, and large indolent ulcers are formed. Sometimes there is considerable edema about the ulcers, and plague bacilli may be found in the edematous fluid which exudes. However in indolent ulcers, degenerating plague bacilli and pus cocci are often found,and not infrequently other bacilli. In a small proportion of bubonic plague cases, what probably constitutes the primary lesion may be observed. This consists usually of a small vesicle or papule which may become pustular, and which is situated on the skin drained by the inflamed lymphatics in the region of the bubo. It perhaps sometimes indicates the original point of the infected flea bite.

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Microscopical examination of the contents of these lesions frequently shows large numbers of plague bacilli.

In severe cases of bubonic plague, oppression of the chest is often complained of. As the disease progresses, the breathing becomes labored and the respirations increase in frequency,sometimes numbering from 30 to 60 per minute. Cough is frequently present. The sputum may be viscid at first, but often becomes purulent and sometimes blood-stained. Auscultation and percussion frequently reveal signs of congestion and edema at the bases of the lungs. Bronchitis is also not uncommon. Pneumonia occurs in plague, first as primary plague pneumonia in which the alveoli and sputum contain plague bacilli in enormous numbers. This form has already been thoroughly discussed elsewhere in this article. Secondary bronchial pneumonia also due to the plague bacillus may result metastatically and emboli and abscesses may be formed in the lungs. In addition, pneumonia in bubonic plague may occur as a result of infection with Diplococcus pneumonias, and in some of these lesions both the diplococcus and the plague bacillus may be encountered. In the metastatic form of pneumonia, it is frequently very difficult to recognize the condition clinically. Occasional crepitant rale may be heard over small areas. In such cases the rapid decline in the general condition of the patient may suggest the condition. However, if the lesions are sufficiently extensive in the lungs, plague bacilli may sometimes be found in the sputum.

The kidneys are usually markedly affected in plague. Congestion and parenchyniatous degeneration are almost always present. Extensive hemorrhages may occur in the pelves of the kidneys, ureters, or bladder. Microscopically, profound cloudy swelling of the epithelium of the uriniferous tubules, with the presence of granular or hyaline material in the latter, is almost always present in fatal cases. A very characteristic change in the kidneys in plague sometimes observed is the presence of hyaline fibrin thrombosis of the glomerular capillaries. A lesion which was first emphasized in Manila by Herzog (1909). These lesions explain in a general way the urinary disturbances which may be observed clinically. The urine is usually diminished in quantity,of a high color, sometimes smoky, and of high specific gravity. It usually contains a moderate amount of albumin, but albumin is not always present in the less severe cases. The urea, uric acid, and chlorides are often decreased. Microscopically, epithehal cells, pus cells, and sometimes red blood corpuscles and even plague bacilli may be observed. The plague bacillus does not usually occur in kidney tissue in particularly large numbers, and it is probable that only when this organism is present in considerable numbers in the capsular space of the glomeruli, or where there has occurred hemorrhage in the urinary system, will the plague bacillus be found in the urine. In grave cases of plague, hematuria is not uncommon, and suppression or retention of urine occasionally occurs. Severe uterine hemorrhages may develop, and in pregnant women abortion always occurs, which is usually fatal to both mother and child.

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The mucous membranes of the mouth and throat are more or less hyperemic and occasional hemorrhagic patches are present. The tonsils may be swollen and hyperemic and in instances in which infection has occurred through the mucous membrane of the mouth or throat, a bubo may form in the tonsil and edema of the glottis may occur. In these instances, as well as in pneumonic plague, the sputum contains the plague bacillus. Apart from the hemorrhages which may occur in the mucous membrane of the stomach or intestine, the other lesions of the alimentary tract are not of special clinical significance. Vomiting, preceded by nausea, is a common early symptom of plague; sometimes the vomiting persists and then the vomits is likely to contain blood. Constipation is usual in plague, but diarrhea sometimes occurs, and in some cases the stools are dysenteric in character and contain much blood. During the epidemic of primary pneumonic plague in Manchuria several cases of primary intestinal plague were reported in which bloody diarrhea appeared to be the most prominent symptom. However, none of these cases was studied at necropsy and it appears that no definite evidence of the occurrence of primary intestinal infection during the epidemic was produced. In the few instances in which plague bacilli were reported in the feces, infection had evidently occurred secondarily from the blood. Albrecht and Ghon, in the report of the Austrian Commission, have mentioned the only suggestive case of primary intestinal plague occurring during a bubonic epidemic of plague, and even in this case the evidence of such infection is not conclusive. However, it seems established that primary intestinal plague has been produced in rats by feeding large quantities of virulent plague bacilli. In many instances during the Manchurian epidemic, the patients with pneumonic plague must have swallowed enormous numbers of plague bacilli in the saliva and sputum. Nevertheless, in none of the necropsies performed during the epidemic were evidences of primary intestinal infection present, nor was serious involvement of the intestine encountered. This fact certainly speaks strongly against the existence of primary intestinal plague in man, and would seem to show that even if the intestines are sometimes secondarily involved, this condition in human beings must be very rare. It has not been possible to isolate the plague bacillus from the feces in cases of bubonic plague, probably sometimes largely on account of its association with so many other microorganisms, though it seems very probable that in those cases in which the plague bacillus is present in the blood during life, and extensive intestinal hemorrhage has occurred, that it may be present in the bloody evacuations also.

Pathological anatomical conditions in the nervous system are unusual. Meningitis occurs only occasionally, as does hemorrhage of any degree in the brain substance. A few punctate hemorrhages may be more commonly observed at autopsy in the meninges, mesencephalon, and medulla oblongata. The nervous symptoms, which are often marked, are largely dependent upon the toxaemia and congestion, and hence are functional.

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Complications

One of the feared complications of bubonic plague is secondary pneumonia, which in addition to high mortality is highly contagious by airborne transmission. Plague meningitis is a rarer complication and typically ocurrs more then 1 week following inadequately treated bubonic plague.

Diagnosis

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.

For the bacteriological examination the blood is taken from the vein cubitas at the amount of five to ten milliliters. The smears are prepared immediacy near the patients bed, one or two milliliters of the received blood are mixed with the melted agar, 5 mL are poured into the small bottle with a hundred milliliters of the bouillon, which is used for further examinations in the laboratory. The residual 1-2 milliliters are injected under the skin of the guinea-pigs.

The sputum is gathered into the broad-mouth jar with the ground in taps. At the pneumonic form of the plague the sputum is to be examined by the direct microscopy and by the inoculation on the medium for the isolation of the pure culture. Usually the pneumonic form of the plague contains a big amount of plague bacillus, but sometimes at the bubonic form, which is complicated with the pneumonic plague, a small amount of bacillus is discharged or there are no bacillus at all. In such cases when the pathogen is not detected at microscopy the inoculation on the medium for the isolation of the pure culture and infection of the animals are used.

All the glassware is warped up into the serviettes wetted with disinfecting solution, placed into a box and sent to the laboratory.

Differential diagnosis

Mild or moderately severe cases of bubonic plague with adenitis may be confused sometimes with climatic bubo, venereal bubo, febrile adenitis, filarial infection, or certain other diseases. Since the bacteriological examination is a simple procedure and gives reliable information, the final diagnosis should always depend upon it and in bubonic plague the bacillus should be sought for in the bubo or swollen lymphatics and in the blood.

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The bacteriological diagnosis is the only certain one for excluding pneumonic infection due to microorganisms other than Bacillus pestis, but from the general condition of the patient, in connection with the absence of marked physical signs in the lungs, the diagnosis of pneumonic plague infection is often particularly suggested. Labial herpes has not been observed in primary pneumonic plague. The presence of numerous coarse, pi ping or sibilant bronchial rales in the lungs is an argument against pneumonic plague infection. The sputum in pneumonic plague is not purulent as it frequently is in catarrhal bronchitis or in bronchial pneumonia, and it is not so tenacious and has not the rusty appearance of the sputum so often seen in croupous pneumonia. The cough is usually not so painful as in croupous pneumonia. The duration of the disease is usually less than two days, though many cases do not have longer than sixteen hours after the onset of symptoms. Cases sometimes survive for three and, more rarely, for four days, but not ever one week without antibiotic treatment. Nowadays the early use of the large doses of antibiotics results in recovery.

Treatment

Patients, which 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 the life. Efficiency of antibioticoterapy in later terms is considerably lowest.

From etiotropic agents the most effective is streptomycinum. At the bubonic form immediately 1 gm of preparation is infused into muscle, and then in hospital is indicated 0.5-1.0 gm 3 times per day during one week. At a pulmonary and septic plague a dose of streptomycinum is enlarged 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, ampicilini. After clinical indications it will be carried out pathogenic and symptomatic treatments.

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

Prophylaxis

Dispensary observation during 3 months is 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 disease, so 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

Date: 2014-12-21; view: 973