PLAGUE
TULAREMIA
ANTRAX
ERYSIPELAS
Plague is nan acute infectious disease caused by Yersinia npestis with an severe intoxication, fever, affection of lymphatic system nand lungs. It belongs to the group of the extremely dangerous infections n(quarantines).
Historic reference
Apparently, the word “plague” comes nfrom the ancient Arabic word “jumma” which means “bean”.
During the last 2000 years, Y. pestis has caused social and economic ndevastation on a scale unmatched by other infectious diseases or by armed nconflicts. It is generally considered that there have been three world npandemics of plague and credible estimates indicate that together these nresulted in 200 million deaths. During these pandemics, the disease occurred iboth the bubonic and pneumonic forms.
The first, the Justinian plague, occurred nduring the period AD 542 to AD 750. This pandemic is thought to have originated nin
Eight epidemic breakouts of plague nhave been registered in
World Health Organization (WHO) nindicated plague, cholera, hemorrhagic fevers and small pox as internationally quarantinable ninfectious disease (most dangerous). As a class 1 notifiable disease, all suspected cases nmust be reported to, and investigated by, public health authorities and nconfirmed cases must be reported to the WHO in Geneva, Switzerland. During the nperiod 1967-1993, the average worldwide incidence of plague was 1,666 cases. Although the nincidence trend was downwards until 1981, there has been an apparent increase nin the incidence of disease over the last decade, possibly because of more nefficient diagnosis and reporting of cases. Even today, many cases of plague nare not diagnosed and it is likely that the true incidence of disease is nseveral times the WHO figures.
The Indian outbreak of plague in 1994. Despite the high incidence of plague in
At the peak of the epidemic, over n6300 suspected cases were recorded. However, official figures released later nindicated that only 876 presumptive cases of plague were identified (by nserological testing for antibodies to Fl antigen of Y.pestis) and there were 54 fatalities. The cases were confined to nsix states in central and western India; none of the suspected cases in other nstates, such as Bihar, Punjab, Rajasthan and West Bengal, had positive nserological markers for presumptive plague.
Etiology
Yersinia pestis (bacillus pestis) Fig.1, the netiological agent of plague was first described by A. Yersen in 1894 iHong-Hong, the International committee of systematization of bacteria (1982) nreferred it to Yersinia genus together nwith bacillus pseudotuberculosis and yersiniosis.
Fig.1. Yersinia pestis (bacillus npestis)
It is a short, oval bacillus with nrounded ends occurring singly and in pairs. In the tissues a typical capsule may nbe observed, in cultures grown at 37 °C material can be demonstrated by means nof India ink preparations, but it no well-defined.
The organism is Gram-negative, nand when stained with a weak stain (methylene blue) shows characteristic nbipolar staining which is an important feature in identification.
In culture the plague bacillus is less typical. Longer forms nare frequent and polar staining is less obvious. Pleomorphism is marked nespecially in old cultures, and involution or degeneration forms are particularly nnoticeable. These are markedlly enlarged, stain faintly and include globular, npear-shaped, elongated or irregular forms. In fact the microscopic picture of nan old culture often suggested that of a yeast or mould. Involution in culture ncan be hastened by the presence of 3% sodium chloride and this has sometimes nbeen utilized in identifying the organism.
In fluid culture the bacilli tend to nbe arranged in chains. The organism is non-motile and non-sporing.
Rodents are natural reservoir for nplague infection. Yersen was the first who noticed the connection between a rats plague epizootic and a human epidemic. Bacillus pestis carriage was proved for nblack and gray rats and for such steppe rodents as gophers, marmots, sandworts, nsmall mousekind rodents and others. There are almost 300 species and subspecies nof basic sources and keepers of plague infection. Besides, during an epizootic namong rodents, there can be found other mammals contaminated with plague – npolecats, shrews, foxes, monkeys (makaky genus), domestic cats, one- and ntwo-humped camels. Epizootics among rodents are kept by different species of nfleas – carriers of plague infection.
It is now known that plague is nnot communicable from animal to animal by simple contact, but is readily ncommunicated by fleas (Fig.2), which bite man, dogs and other animals. nConglomerate of Y. pestis block nesophagus and pre-stomach of the flea. During the bite and sucking of blood nbacilli regurgitate into the wound of object.
Fig.2. Flea
Especially convincing are the experiments nof the Indian Plague Commission, which clearly showed that, if fleas are nexcluded, healthy rats will not contract the disease, even if kept in intimate nassociation with plague-infected rats. Young rats may even be suckled by their nplague-stricken mothers and remain healthy. It suffices to transfer fleas from na plague-infected to a healthy animal, or to place the latter in a room iwhich plague rats had died recently and had been subsequently removed. The nfleas that have left the body of the dead rats, try to found another host for nliving.
In ordinary circumstances the nrat-flea completes its developmental cycle in from 14 days to 3 weeks, but iwarm damp weather this may be shortened to 10 days. It requires ideal tropical nconditions for propagation. The average life of a flea, separated from its nhost, is about ten days, but it is capable of remaining alive without food for ntwo months, should the temperature of the air be low.
Human infection, however, is not nalways transmitted by fleas. In a small percentage of the bubonic cases, ninfection occurs after direct contact of skin with Bacillus pestis. Instances of such infection have occurred ibarefooted individuals with small wounds of the feet from walking on floors or nstepping on material infected with plague bacilli, or through abrasions on the nhands of those who have performed autopsies on or handled the bodies of those nwho have died of plague, or who have shot and skinned rodents infected with nplague.
Infection in primary human septicemic nplague is usually acquired through the mucous membranes, particularly of the nmouth and throat and the conjunctivae. Particles of infected sputum which have nbeen accidentally coughed into the eye have produced human septicemic plague. nAnimals such as monkeys may be given primary septicemic plague by instilling a nfew drops of a culture of Bacillus pestis nin the eye, or by rubbing a small amount of the culture on the mucous nmembranes of the gums without producing visible erosions. Infection of the nmucous membranes of the mouth may occur also in man through the hands conveying ninfection, as might occur in individuals who have shot or skinned infected nrodents.
Pathogenesis
Penetratioof Yersinia pestis through skin (respiratory or gastrointestinal tract).
Involving nof the lymph node (primary bubo).
Penetration into blood n(bacteremia, generalization of the process, formation of methastases) also nspreading through lymphatic system (secondary buboes).
Destructive neffect of the toxin (general congestion of all organs of the body).
Morbid pathology
The main points noted in a plague autopsy nare:
1) The nmarked involvement of the lymphatic system as shown by intense congestion and nhemorrhagic edema of the lymphatic glands. Not only are the glands involved ntributary to the site of inoculation, thus forming the primary bubo, but there nis secondarily more or less inflammatory change in many of the lymphatic glands nof body. There is also a marked periglandular edema, with hemorrhagic nextravasations of the connective tissue surrounding the primary bubo, this mass nbeing made up of a group of glands matted together by this periglandular nexudate.
2) The marked destructive neffect of the toxin of the plague bacillus, upon the endothelial cell lining of nblood vessels as well as of lymphatic ones. This causes nthe extensive blood extravasations are characteristic of plague and shown by npetechial spots, not only of the skin, but of the serous and mucous membranes nas well throughout the body.
Microscopically there is a distensioof the alveoli and bronchial passages with a hemorrhagic exudate. There is npractically no fibrin in the alveolar exudate. The process seems to extend by ncontinuity along the bronchi and bronchioles. Plague bacilli pack the exudate nfound in the bronchi and bronchioles. In a report on the autopsy findings of nsepticemic plague in
Clinical manifestations
Incubation period of humaplague varies usually from to n10 days, but is generally from to n4 days. In primary pneumonic plague it may not be over 2 or 3 days.
In bubonic plague premonitory symptoms are not usually observed, nthough occasionally there may be 1 or 2 days of malaise and headache. The nonset, except in mild cases, is usually abrupt, with fever commonly accompanied nby a moderate rigor or repeated shivering. The temperature rises rapidly to n39,4 °C or 40 ˚C. sometimes even reaching 41,7 °C. The pulse becomes rapid and the nrespirations increased. There is headache which is usually severe and mental ndullness, and this condition is generally followed by mental anxiety or excitement. nThe patient may become maniacal. The skin is hot and dry, the face bloated, the neyes injected, and the hearing dulled. The tongue is usually swollen and coated nwith a creamv fur, or later with a brown or black layer. The symptoms usually ncomplained of within the first 24 hours are very severe headache and backache. nBurning in the throat or stomach, and nausea and vomiting may occur. nConstipation is present as a rule. The pulse is either very small and nthread-like or full and bounding. At times there may be acute delirium; at nothers, lethargy and coma. In children, convulsions usually occur. The urine is nscanty and generally does not contain more than a trace of albumin and no ncasts. Later in the disease the albumin may increase somewhat, The high febrile nstage lasts from 2 to 5 days or longer. The decline in temperature may be nsudden or gradual. Cases that do well usually show a gradual fall of ntemperature, and after 14 days the temperature may be subnormal. Buboes, ninflammatory enlargements of the lymph glands are sometimes the first sign to nattract attention by their pain. They more often make their appearance from the nsecond to the fifth day after the onset of the fever. The temperature nfrequently shows a decline when they appear.
The naffected gland is often hard and painful to the touch. In fatal cases, it may nretain these characteristics; in others it suppurates. The average size of the nbubo is from a walnut to an egg. Generally the plague bubo at the onset is hard to the ntouch and very painful. Often at the time of onset of the bubo, pain in it is nthe symptom of all others of the disease most complained of. In rare instances, nhowever, the pain may not be marked. Usually if the bubo is in the groin the npain is sufficient so that the patient lies in bed with the thigh flexed and nthe leg drawn up to relieve any pressure on the inflamed glands while if the nbubo is in me axillary region the affected arm is held away from the side. The nbubo may terminate by resolution, suppuration, or induration n(Fig.3).
Fig.3. Ruptured plague bubo
If the bubo suppurates, the ngland becomes at first more swollen and the overlying skin gradually more ninflamed and tense during the first week. Later the gland begins to soften and nnecrosis then occurs more quickly. Frequently the whole center of the gland nbreaks down into an abscess cavity and perforation then occurs, revealing a ncavity with dark scarlet or bright red walls. Later the walls become reddish nyellow in appearance and emit whitish-yellow pus. On microscopical examinatioof the pus normal and degenerating plague bacilli are found and many npolymorphonuclear leucocytes and degenerating endothelial cells. The bacilli nare often seen engulfed in phagocytic cells. In the later stages the buboes noften become secondarily infected with other microorganisms, particularly the npus cocci. Rarely the bubo does not perforate for several weeks. Sometimes its nsuppuration is accompanied by much sloughing of the skin in the vicinity whefairly large ulcers result with indurated infiltrated margins. In some ninstances the lesions may heal in from a week to ten days, but with larger nbuboes sometimes complete cicatrization does not occur for a month or two. Imany other cases the bubo terminates by resolution. The tenderness, nand periglandular infiltration then gradually decrease, the overlying and nadjacent skin becomes softer, and the glands may eventually return almost to ntheir normal size with but moderate induration about them. In other instances nan enlarged cicatricial node remains at the site of the bubo.
Buboes nappear in 75 % of the cases. In the cases in which buboes are present, they noccur in the inguinal glands in approximately 65 to 70 %, nin the axillary. 15 to 20 %, and the cervical, 5 to 10 %. Carbuncles appear in about 2 %, in which there are reddened nindurated patches of skin, which subsequently necrose. The spleen is frequently nmoderately enlarged, but often cannot be palpated. Hemorrhages from the stomach nand intestine are not uncommon, and when the disease is complicated with the npneumonic form they may occur from the lung. Epistaxis is also not infrequent. nThe blood usually shows a leucocytosis of forty thousand or more the increase nbeing in the polymorphonuclear leucocytes. The plague organism can be isolated nfront the blood in about forty-five per cent of the bubonic cases.
The attack of high fever lasts generally three to nfive days or longer, but the patient may die earlier. If however, he lives for nfive days there is greater chance of recovery. If the bubo suppurates recovery nmay be delayed from two or three weeks to a month.
The onset of pneumonic plague is usually somewhat abrupt; nprodromal symptoms are rare. The disease usually begins with chilly sensations, nbut a distinct rigor is unusual. Epistaxis is also rare. There is headache, nloss of appetite, an increase in the pulse rate, and fever. Within from ntwenty-four to thirty-six hour after the onset, the temperature usually has nreached 39,4 °C or 40 °C, and the pulse 110 to 130 or more beats per minute. Cough nand dyspnoe appear within twenty-four hours after the onset of the first nsymptoms. The cough is usually not painful. The expectoration is at first nscanty, but soon becomes more abundant. The sputum at first consists of mucus nwhich shortly becomes blood-tinged. Later the sputum becomes much thinner and nof a bright red color; it then contains enormous numbers of plague bacilli ialmost pure culture. The typical rusty sputum of croupous pneumonia was not nobserved. The conjunctiva become injected, and the tongue coated with either a nwhite or brownish layer. The expression is usually anxious, and the face nfrequently assumes a dusky hue. Labial herpes is very uncommon. The patients nsometimes complain of pain in the chest, but usually this is not severe. Apart nfrom the disturbances due to the dyspnoe and their anxiety for their condition, nthey usually appear to suffer but little and usually do not complain of pain. nIn the later stages of the disease, the respirations become greatly increased nand the dyspnoe usually very marked, the patients frequently gasping for air nfor several hours before death. Cyanosis is then common.
The signs of cardiac involvement are always marked in the advanced ncases, the pulse becoming gradually more rapid, feeble, and running; finally it ncaot be felt.
Septicemic plague occur during the course of bubonic plague, always occurs in pneumonic plague, nand may occur as a form of primary infection. When primary septicemic plague nresults, the infection has usually occurred through the mucous membrane of the nmouth and throat, death resulting from septicemia before macroscopic lesions nare visible in the lymphatic glands or lungs. Nevertheless, at autopsy, at nleast some of the lymphatics are usually found to be enlarged, congested, and neven hemorrhagic, and in a few instances early buboes may develop shortly nbefore death.
In this form, the nervous and ncerebral symptoms often develop with great rapidity and intensity, and the ncourse of the disease is very rapid, the bacilli appearing in the blood almost nat the onset of severe symptoms. The attack usually begins with trembling and nrigors, intense headache, vomiting, and high fever. The countenance usually ndepicts intense anxiety. Extreme nervous prostration, restlessness, rapid nshallow respirations, and delirium are common symptoms. In some cases the ncardiac symptoms are the most prominent. The patients soon pass into a comatose ncondition, and die sometimes within 24 hours of the onset of the attack, but nsometimes not until the third day.
Cases of primary septicemic nplague are always fatal. Hemorrhages from the intestine sometimes occur in this nform of plague as well as in bubonic plague. There is no distinct evidence that nsuch cases are of primary intestinal origin. Hemorrhages from the nose and nkidneys are also not uncommon.
The plague bacillus produces a npowerful endotoxin which often causes a dilatation of the arteries, lowering of nthe blood pressure, and alterations in the functional activity of the heart, as nwell as degenerative changes in the heart muscle. It also acts particularly nupon the endothelial cells of the blood vessels and lymphatics, the ninflammatory reaction frequently causing circulatory obstruction. One of the nmost characteristic features of the pathology of plague is the tendency to nproduce general dilatation and engorgement of the vessels, with cutaneous, nsubserous, submucous, parenchymatous, and interstitial hemorrhages. In patients nwho have died of plague, the most common of the latter are in the epicardium, nthe pleura, peritoneal surfaces, the stomach and intestines, and the mucosa of nthe stomach and small intestine. Sometimes extensive hemorrhages are found ithe peritoneal, mediastinal or pleura cavities. In the kidneys there are nfrequently subcapsular and renal hemorrhages, and blood extravasation into the npelves of the kidneys and ureters, as well as in the bladder and generative norgans.
Sometimes there are considerable nextravasations of blood into the substance of the brain. In bubonic plague, nnumerous hemorrhages are almost always present in the bubo. The tissues are ncharacterized by vascular dilatation and engorgement. followed by edematous ninfiltration, the effect of the toxin being evident on the vessel walls. The nendothelial cells become swollen, proliferated, and degenerated. Later hyaline ndegeneration of the walls may occur.
During the nclinical course of the disease, hemorrhages are frequent. The bleeding may take nplace from the nose, mouth, lungs, stomach, or kidney, and sometimes from the nuterus and bladder. These hemorrhages generally occur in severe cases of the ndisease. On examining the skin small punctifonn hemorrhages from about 1 to 2 nmillimeters in diameter are sometimes observed scattered over the skin igreater or less profusion. The petechie may occur on the face, neck. chest, nabdomen or extremities. Sometimes larger patches of ecchymosis, in the nneighborhood of 1 centimeter in diameter, are observed in the skin. Larger ncutaneous effusions of blood are rarely seen, except at autopsy. The purpuric nhemorrhages in bubonic plague usually do not appear before the third day of the ndisease. However, in septicemic plague they may be seen earlier.
At autopsy, the right side of the heart nand the great veins are usually distended with fluid or only partially ncoagulated blood. During the disease, the patient frequently experiences a nfeeling of oppression over the precardial region. The heart sounds at first are nclear, and the second pulmonic sound may be accentuated, but as the disease nprogresses they become feebler, or embryocardiac, in character and die first nsound may be no longer heard. Sometimes heart failure may occur without any nother sign of collapse. It may occur following exertion. such nas sitting up. but it sometimes takes place while the npatient is lying in bed. In primary septicemic plague, the course of which is nvery rapid, the cardiac symptoms are frequently the most prominent ones. Ipneumonic plague, the limits of dullness of the heart are sometimes increased nto the right of the sternum. At onset, the second pulmonic may be accentuated, nbut it soon becomes indistinct. As the disease progresses, gallop rhythm may noccur. Death takes place usually from cardiac paralysis and exhaustion.
Diagnosis
After penetration into the norganism plague bacillus fill up the lymphatic nodes, blood and sputum. Their npresence in the urine is very inconstant, but their detection during the nbacteriological examination is very valuable for diagnostic. All the materials nfrom the patients are to be received before the antibiotic treatment.
The materials for the nbacteriological diagnostics are taken from the inflamed lymphatic node or bubo nwith the help of the sterile syringe. After the skin. which is over it, is cleansed, the node is fixed by the left nhand and the needle attached to the syringe is slicked into it. It is better to ntake the punctate from the peripheral dense part of the bubo. With the slight nmovement of the needle several times up and down in the node the aspiration is nmade. The received liquid is poured into a small test-tube and when with all nthe required precautions it is to be send to the special laboratory, where one ndrop is used for the inoculation into of ligue agar, and another one for the nsmears, and the rest is injected under the skin of the guinea-pig.
Treatment
Patients, who suffer from nplague necessarily, hospitalize in appropriate nhospitals where they are transported nby ambulance.
Treatment should be started already oplace of revealing of the patient. Early prescription of antibiotics (during nthe beginning of disease), as a rule, salvages it life. Efficiency of therapy nby antibiotics in later terms is considerably lowest.
The most effective is Streptomycinum. At the bubonic nform immediately infuse 1 gm of preparation into muscle, and then in hospital nindicate 0.5-1.0 gm 3 times per day during one week. At a pulmonary and septic nplague a dose of Streptomycinum enlarge to 5-6 gm. Antibiotics of tetracyclines n(oxytetracycline, chlortetracycline), 0.25-1.0 gm 4-6 times are recommended. nFrom other antibiotics it is possible to indicate monomicin, morphocyclin, nampicilin. After clinical indications it will be carried out pathogenic and nsymptomatic treatment.
After nnormalization of a body temperature and reception of negative datas of nbacteriological researching from nasopharynx, sputum, punctate of bubones- patients leave hospital nafter 4-6 week.
Dispensary nobservation during 3 months it’s necessary for reconvalescense nwith obligatory bacteriological researching from mucosa of pharynx and sputum.
It is necessary to protect people from nexpansion of plague diseases. This work is carried out by workers of sanitatiocenter, ambulatory – polyclinic network and antiplague establishments. Plague nis the quarantine diseases, so on it the international medico-sanitary rules n(WHO, 1969) are distributed on it.
Workers nof the general medical network observe health of the population with the npurpose of early revealing the patients on plague. Each medical worker should nknow the basic attributes of disease, the rules of personal prophylaxis, be nable to carry out initial antiepidemic actions.
At npresence of epizootia among rats and diseases of camels vaccination of the populatioby local services under the control of antiplague establishment will be carried nout. As active immunization use living plague vaccine (dose for epicutaneous nindication for children till 7 years 1 billion, 7-10 years – 2 billion, adults n3 billion microbes bodies, at a hypodermic immunization 1/10 of epicutaneous ndoses). Immunity is kept during 6 months, then if it necessary will spend revaccination nin one year.
At noccurrence of a plague among the population the antiepidemic actions carry out wich is directed non localization and liquidation of nepidemic pesthole. They include: revealing of patients and their nhospitalization in special hospitals in isolation wards with severe nantiepidemic regime; and establishment of territorial quarantine: revealing and nisolation of all persons which was in contact with patients they must be nisolated for 6 days and will carry out emergency prophylaxis by antibiotics – nStreptomycinum 0.5 gm 2 times per day in muscle or Tetracyclinum on 0,5 gm 3 ntimes per day inside during 6 days); revealing the patients with fever and their hospitalization in special ndepartaments; final disinfection, and also ndisinfestation and deratization at territory of settlement and around nit. Invaluable things are liable to destruction. The personnel should be nwork in antiplague costumes. For persons who need to leave nzone of quarantine, will carry out an observation.
.
TULAREMIA
Definition
Tularemia is an acute ninfectious disease of a septicemic character that is manifested by nintoxication, fever and the affection of the lymph nodes; it belongs to the nzoonosis group with natural foci.
Historic reference
In 1910 the Americabacteriologist named Mc Coy who studied plague in the shot of ground squirrels nin
After the name of the district
Etiology
The tularemia bacteria have very nsmall dimensions – 0,3-0,5, but there are the smallest nones with a diameter of 0,1-0,2, they have an ability to pass the bacterial nfilter 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 cabe more often found in the form of coccobacteria. nIn the cultures on the nutrient medium tularemia bacteria are polymorphic, it is especially expressed in the American variety. nThe microbe is immobile, it does not make spores, and it has a small capsule. nIt is characteristic of the bacteria to produce mucous in the cultures, it cabe easily detected during the preparation of smears on the glass. The tularemia nbacteria can be tinctured with all kinds of stains, which are usually used ithe laboratory practice. They are Gram-negative. In the smears-impression from nthe organs of the animals, which had died from tularemia the bacteria are well ntinctured by Romanowsky-Giemsa obtaining the lilac color. The tularemia nmicrobes, being obviously expressed pathogenic microorganisms, which are nadapted to a strictly parasitic life style, are noted to be capricious in case nof the cultivation on the artificial mediums – plain agar and broth.
The microbe is not very sensitive to low ntemperatures, it survives in the frost of 30 °; it can be preserved in the nfrozen meat up to 93 days. The tularemia bacteria are not stable to the ntemperature increase. The higher the temperature is the quicker the microbes ndie. Thus, the pathogen remains in the animal skins at a temperature of 8-12 ° nfor more than a month, and at a temperature of 32-33 ° n- only during a week. The microbe dies at a temperature of 60 ° in 20 minutes, nand boiling kills them immediately. The tularemia bacteria die under the ninfluence of the sun rays in 20-30 minutes, their vital capacity remains in the ndiffused light up to 3 days. The tularemia bacteria are not stable to commodisinfectants and are destroyed by an ultrasound.
Epidemiology
Tularemia is nepidemically defined as zoonosis which has natural foci mainly supported by nwild rodents and blood sucking insects. nThe adherence of the people who live in the rural areas to this disease is one nof the main peculiarities of the tularemia epidemiology, nit is connected with the natural foci of this infection and the absence of the nconditions for spreading among the home rodents in the big cities. The cases of nthe people infection in the cities are infrequent and connected with bringing ninfected food or animals from the rural areas. More often the city-dwellers get ninfected when they go to the country where there are natural foci.
The maisources of the tularemia infection are rodents, especially, common field voles, nwater-rats, house mice. sometimes muskrats and nhamsters as well as hares. The infection of humans occurs either as a result of nthe contact with sick or dead rodents and hares or the bites of the infected nblood-sucking arthropoda or due to water, nfood, straw and other substrata contaminated by the discharge of the animals nsick with tularemia. A typical feather of the tularemia microbe is its ability nto penetrate the organism of the humans and animals through small scratches othe skin. unaffected mucous membranes of the eye, nthroat, pharynx, the respiratory tract, and in case of a considerable dose the ninfection may penetrate through the unaffected skin. One of the typical nepidemiological peculiarities of tularemia is almost 100% susceptibility of the nhumans to it irrespective of age and also the fact that the sick people are not ncontagious for the healthy ones.
The mentioned above peculiarities of nthe tularemia infection e. i. a great adaptation of the pathogen iature, its npossible ability to be transmitted by the animals or different objects of the nenvironment (water, food. etc.) and a high susceptibility of the human to this ninfection resulted in the tularemia outbreaks, which involved great numbers of npeople under certain conditions. The tularemia outbreaks often reminded the nepidemics of grippe or malaria in their character, and earlier they were ndiagnosed like this.
The concrete ways (mechanisms) nof the tularemia infection of the humans are the following: contagious, nalimentary, aspirational, transmissional. The infectiooften occurs by means of a contact with sick animals, a contact with the nobjects contaminated by them (hay, straw, corn, etc.), swimming nin the reservoirs. The diseases belonging to this group are mainly typical of nhunters-producers and in some cases of the members of their families who helped nthem to skin the shot animals. Besides this, there have been described some nsporadic cases and even separate outbreaks occurring as a result of hunting nhares. Not only did the hunters fell ill, but also the housewives who were ninfected while cutting carcasses.
The aspirational way of infectiooften occurred during the belated agricultural work while inhaling the dust nrising into the air from the infected straw, corn and other substrates during ntheir machinery or manual processing, cleaning, transportation, etc. In some ncases the infection was accompanied by a contagious way.
The alimentary way of infectiooccurs while using the water and food containing the tularemia pathogen. The nwater way of the microbe transmission is due to the fact that it is nconsiderably stable in water, especially, at a low temperature. The reservoir ninfection is due to the sick with the t infection water rats that live on their nbanks. The infection of the humans usually occurs in the summer, the morbidity nincrease is connected with hay mowing and other field work during which the npopulation widely uses the water from the open reservoirs for drinking and nwashing.
The disease of the alimentary type is noften connected with house mice penetrating the human’s house or food stores, nwarehouses and other facilities and contaminating the food with their ndischarge. Bread, milk, cookies, crackers can be among such kinds of food.
The transmission outbreaks depend othe infection transmission by mosquitoes and gadflies, less often – by ixodes nticks. The insects are infected while sucking the blood of the sick animals but nthere are indications that the gadflies can be infected by the carcasses of the nwater rats as well as the water infected with tularemia. The infection of the nhumans at the transmission outbreaks occurs exclusively in the warm season and, nas a rule, not far from the reservoirs, on the flood lands, during hay mowing nand haymaking.
Pathogenesis
The ntularemia pathogen can be brought into the human organism by different ways: nthrough the skin, mucous membrane of the eye, respiratory tract, the ngastroenteric tract and by a combined way. The localization of the infectiogate undoubtedly influence the tularemia clinical nmanifestations. But it would be a mistake to consider this fact to be the only none and a decisive one. The ways of the human infection combined with nimmunobiologic reactions of the microorganism and the pathologic peculiarities nof the pathogen determine the development of one or another clinical form of ntularemia, one or another clinical course of the disease.
The tularemia pathogen is not knowto have ability for an independent movement. That is why it is clear that from nthe entrance gate where its primary adaptation may take place, the following nmovement of the infect can be only in the direction of nthe liquid substrate. As a rule, it actually takes place with the lymph flow nand very seldom with the blood flow.
The tularemia pathogen often gets ninto blood some time later, this causes bacteremia and nmay result in the generalized process. Hence in the pathogenesis of the ntularemia infection in the humans the phase of the lymphatic mole precedes the npathogen penetration into blood. It is by the phases of the lymphatic mole and ncorresponding reactions of the microorganism that the formation and presence of nthe tularemia local clinical manifestations, that are so important for the ndiagnostics, are determined. Among such clinically expressed symptoms tularemia nlymphadenitis, which is more often called a bubo, is sure to take the first nplace.
Pathogenically na sum of the reactive local changes in response to the influence of the ntularemia bacteria is the basis for the development of such buboes. They remaiin the lymph node during the lymph filtration and due to phagocytosis. The ntularemia bacilli brought with the lymph flow reproduce in the lymph node and npartly dying influence the node and the surrounding tissues by the secreted endotoxins, it results in adenitis and later periadenitis, the ntularemia bubo development. Pathogenically the buboes can be divided into nprimary and secondary. The primary ones are often connected with the locatioof the entrance gate and are divided into the buboes of the first, second ndegree, etc. In contrast to the primary tularemia buboes the secondary ones do nnot have a territorial connection with the localization of the infection gate. nPathogenically they develop as a result of the hematogenic metastases. nAccording to the terms of the development they are delayed and less expressed nclinically. The secondary buboes do not usually produce any purifonn softening. nIt is clear that it is not only the nreproduction of the tularemia microbes that takes place in the foci of their nconcentration, but also their death with the excretion of endotoxins, which nstipulate the symptoms of the general intoxication.
Thus every clinical form of ntularemia has the symptoms of the general intoxication though the intensity and ncharacter of the local changes are different and retain their diagnostic value. nHence, the general intoxication of the patient’s organism with specific nendotoxins is the basis of the general manifestations of the disease.
The tularemia pathogen penetrates the norganism through the mucous membranes of the eyes, respiratory tract, ngastroenteric tract and the localization of the entrance gate influences the ndevelopment one or another clinical form of tularemia. However ntheoretically the ways of the tularemia pathogen movement remain the same e. i. nthe lymphatic and then the hematogenic one.
The bacteremia breaks of the tularemia bacilli nfollowed by metastases in the lungs, liver, spleen, marrow, etc. is the basis nof the specific pathomorphologic changes and the development of the multiple nfoci, which is the basis for the possible development of the tularemia process nas a septic one. In some patients such metastases stipulate the presence of nsuch specific complications of the secondary character (secondary tularemia npneumonia, tularemia meningitis, etc). In the most severe cases with the nincreasing symptoms of intoxication the lethal outcomes are possible (severe nsecondary tularemia sepsis).
Anatomic pathology
The anatomic pathologic nchanges in human tularemia have not been studied very well partly because of nthe low mortality. The formation of the tularemia granulomas in the form of nwhitish or whitish-yellow nodes is very typical. The granulomas are ncharacterized by a zonal structure: there are epithelioid cells in the center, nthen – lymphoid. plasmatic and neutrophilic erythrocytes. nthen fibroblasts and often eosinophils. The central nnecrotic disintegration is crumb-like, acidophilic with a great number of nchromatin clods in the fresher granulomas. The granulomas gradually enrich nthemselves with fibroblasts, argyrophil and collagenic fibrae that result ithe granulomas scarring. There are no capillaries in the granulomas and they ndesolate soon. There are focal hemorrhages on the periphery of the granulomas. nThe granulomas in tularemia are similar to those in tuberculosis.
Catarrhal laryngotracheobronchitis noften develops in the primary pulmonic forms. The inflammatory changes of the nlungs are macrofocal. can be similar to croupous npneumonia but tularemia pneumonia develops as serous or serous-fibrinous with a nconversion to necrotic one. The abscess formation is usually observed. nPneumonia is usually complicated by serous-fibrinous or purulent pleuritis, nlater by similar pericarditis. There are changes typical of tularemia n(necrosis, granulomas, suppuration) in the peribronchial and mediastinal lymph nnodes.
In the anginous-glandular form one ntonsil is affected. The process can only be limited by plethora and nhyperplasia. However, more often focal necrosis develops in the beginning, theit is followed by extended necrosis and ulceration with purulent melting or ndiphtheritic patches. The transformation of the submaxillary, superior cervical nlymph nodes into buboes occurs simultaneously.
The eye disease can be in the form of nthe primary eye-glandular form and in the form of the secondary affections. At nfirst there develop papules mainly in the lower eyelid mucous membrane, they nsuppurate and ulcerate with the discharge of purulent exudate. The eyelids are nsharply swollen. The cornea is not often affected. The buboes typical of ntularemia are localized in the parotid lymph nodes but the superior cervical nlymph nodes also be affected.
Clinical manifestations
The incubation period itularemia often lasts from to n7 days. The cases of the incubation period in humans within the limits of the nfirst 24 hours are practically very rare exceptions, and the cases of the nincubation period exceeding two weeks are very doubtful.
There are three periods in the clinical course of the disease: 1) primary, 2)
The onset is always acute nwithout prodromal phenomena, which are accompanied by chills or expressed nshivering and abrupt temperature increase up to 39° C and higher. Most patients nname not only the day but also the hour of the disease onset without any ndifficulties. The patients complain of a headache, malaise, various muscle naches, which are often in the sural and waist areas. Besides this there is ndizziness and appetite worsening, which develops into complete anorexia. The nsleeping disorders as well as increased sweating, especially at night, are quite ntypical. In more severe cases there is vomiting, nose nbleeding and later there can develop the conscious darkening and delirium. The nheadaches are the most persistent and prolonged. The hyperemia of the face and nsometimes of the fauces is objectively observed. On the part of the upper nrespiratory tract there are usually no catarrhal symptoms, nrhinitis and sneezing are very rare. Conjunctivitis and watery eyes are the nmost clearly expressed in the primary eye affection.
As the primary period of ntularemia does not have any pathognomonic symptoms, the epidemiological nanamnesis, which should be distinctly reliable and exhaustive, is of great nimportance. The total duration of the primary period is 2-3 days. Later the nclinical symptoms of the disease develop in different ways depending on the ndevelopment of tularemia in one or another clinical form.
The forms of tularemia which nare distinguished according to the clinic-pathogenic and epidemiological data nare as follows. The bubonic, ulcer-bubonic, eye-bubonic forms develop when the ninfection penetrates through the skin and eye mucous membrane. In the nanginous-bubonic and abdominal forms the infection penetrates through the nmouth. In the pulmonic (bronchial and pneumonic variants) the infectiopenetrates through the respiratory tract. Besides there is a generalized or nprimary septic form (it is observed in any way of infection, especially, iweakened people).
The bubonic nform of tularemia is characterized by the development of the inflammatory nprocess in the regional lymphatic node (Fig.4). A bubo (lymphadenitis) is aobligatory and fundamental symptom of the disease here. There are primary and nsecondary buboes. The primary buboes develop in a lyphogenous way and are nconnected with the area of the pathogen penetration. The secondary buboes ndevelop as a result of the hematogenic spreading and are not connected with the nlocalization of the entrance gate. The size of the tularemia buboes varies from nthe size of a small nut to a chicken egg and larger. It is usually not a nseparate regional node that gets involved in the process, but several nodes ia particular area. The buboes are dense, slightly painful, there is no nexpressed periadenitis. There can be several main variants of the tularemia nbubo outcome: complete dissolving, suppuration, ulceration with the following nscarring and sclerotization. If there is no suppuration, the reverse ndevelopment or dissolving is slow and undulating with changing of improvement nand an acute condition. The process lasts up to 2 and more months. The nsoftening of the bubo begins in 2-3 weeks from the disease onset, but sometimes neven later. The suppurating softening develops approximately in half of the ncases. At first there is no distinct reaction on the part of the surrounding ncellular and skin but soon there develops swelling and skin reddening gradually nincreasing in intensity and extensity and, finally, there is a breakage with nbuboes draining. The puss of the tularemia buboes is thick, white, without any nsmell, it looks like cream or sour cream.
Fig.4. Neck lymphadenitis
The bubonic form of tularemia with nthe primary affection on the part of the sight organ – an eye-bubonic form ndevelops if the pathogen penetrates the eye mucous membrane. In this case there nis expressed conjunctivitis, sometimes the presence of papules and ulcers nbesides regional (parotid, front cervical, submaxillary) lymphadenitis on the npart of an eye. The eyelids are swollen and dense, the patients complain of ntheir tenderness at moving, the amount of the mucopurulent discharge is nmoderate. On the eyelid mucous membrane there are inflammatory small foci ithe form of the cone, they are yellowish and have a whitish top with the size nof a pin’s head up to 3-10 millet grains. There is a considerable nnumber of separate groups of yellow dots on the lower eyelid on the nbackground of a big number of scattered formations, a smaller number of them is nobserved on the upper eyelid.
There are inflammatory small nfoci with a bunch of the superficial widened vessels on the sclera conjunctivas, the foci are almost always located near the nlimbus. No changes on the part of the cornea or other refracting media of the neye have been found. In a number of cases the eye-bubonic form is accompanied nby dacryocystitis. the lachrymal sack phlegmons have nbeen described. Almost all the patients have an affection of the parotid and nsubmaxillary lymph nodes, in some patients their increase is observed on the 3-10th day nof the disease. The clinical course of the eye tularemia affection is withithe limits of 20 days to 3 months. The eye affection may be secondary, in this ncase the eye changes as well as the eyelid skin ones take a course similar to nthat of metastatic granulomatosis and is observed in different clinical forms nof tularemia.
The anginous-bubonic form of ntularemia is first accompanied by the development of angina with characteristic nlocal changes on the part of the tonsils: hyperemia, hyperplasia, ngrayish-whitish patch, which is often on one side. There are local pains and nswallowing difficulties. The degree and quality of the local affections in the nanginous-bubonic form as well as the dynamics of the process are diverse. nAccording to the clinical peculiarities there are three types of tularemia nangina: catarrhal, patch-diphtheritic and infiltrative-ulcerative.
There is hyperemia of the nfauces, pain at swallowing, high temperature, enlargement nof the cervical lymph nodes – the formation of buboes in the catarrhal variant nof tularemia angina. A white patch firmly sticking to the mucous membrane ndevelops on the tonsils and airfoils in the second form. There is hyperemia nwith a cyanotic tint in the circumference of the grayish-greenish covers. The ncovers usually remain for a long time and begin to tear away only two weeks nlater. A massive, quite dense infiltrate, which has no inclination to abscess nforming and which goes up till the hard palate, develops from the very nbeginning in case of infiltrative-ulcer variety. Its reverse development lasts n2-3 weeks and in some cases ulcers develop in the area of the infiltrate.
Expressed catarrhal npharyngitis, cyanosis of the mucous membrane with a crimson tint that looks nlike venous congestion are observed in all cases. The ncongestion phenomena in the fauces remain for a long time, even after the end nof the ulcerative-necrotic processes. The insignificant subjective feelings nduring a severe ulcerative-necrotic destructive process in the fauces are ntypical of tularemia angina. In some cases the enlargement and tenderness of the ncervical lymph nodes coincide with the changes in the throat, sometimes buboes nare formed only by the moment of the angina disappearance. A bubo remains for n2-8 months, less often shorter. Tularemia angina is characterized by a strict nlocalization in most cases the changes are limited by one tonsil irrespective nof the severity of the changes.
The nabdominal form of tularemia has not been studied well so far, so it is supposed nto occur more often than it is diagnosed. Severe pains in the stomach are ntypical of the abdominal form. The process is characterized by a deep nlocalization of the affected, mainly mesenteric lymph nodes, in contrary to nother variants of the bubonic form with the peripheral buboes localization. nThis variant cannot be united with the generalized form as in this case the naffection of the lymph nodes of a certain (abdominal) area prevails. nEpidemiologically it is most often observed at the outbreaks, which are ncharacterized by the massive doses of infection that penetrate through the throat n(water outbreaks).
The pulmonary (thoracal) form nof tularemia occurs in case of the aspiration way of infection and is ncharacterized by the development of the primary inflammatory process in the nlungs. Epidemiologically this pneumonia is connected with certain conditions of ninfection. Thus, during threshing when the stacks are infected with the ndischarge of the mouse-like rodents, the infection is airborne and several npeople fall ill. The airborne infection in the laboratories is less frequent, nwith separate cases.
In case of the primary npulmonary form the inflammatory process develops in the lungs from the very nbeginning. There can be two main variants in this case: bronchial, when the nprocess occupies only the large respiratory tracts, and bronchial pneumonic nwhen the deeper parts are affected – bronchioles, alveoles. The clinical npicture is diverse and depends on the localization of the intensity process and nthe combination of the inflammatory changes. Only tracheitis, bronchitis and ntheir combinations are possible, this confirms their aspirational way of ninfection. Hence in some cases the pulmonary tissue does not get involved ithe pathological process. But the process is localized in the chest and spreads non the mediastinal lymph nodes, that is why these nforms of tularemia are named thoracal.
The bronchial pneumonic nvariant, or tularemia pneumonia, is characterized by a dull and exhausting course, it lasts up to a month, less often 2 months and nlonger. Anatomically these are small foci, which have a tendency to confluence and cause lobar pneumonia.
Pneumonia has a severe course nbut it does not have a cyclic course. it has a ntendency to relapses and the formation of different specific complications: nbronchiectasia, abscesses, the lungs gangrene, dry and moist pleuritis. nNecrosis in the affected parts of the lung can result in the cavity formation – ntularemia caverns. Sometimes the changes in the lung tissue have a dull nprolonged character with clinically expressed intoxication. The patient with ntularemia pneumonia is not contagious for the surrounding people.
It is necessary to distinguish this nprimary tularemia form from the secondary one, which can join any other nclinical form as a complication. It develops in a metastatic way later and deteriorates nthe course of the disease. The terms of the end of such pneumonia are quite nvarious – from 2 weeks to 2 months and longer.
In case of the generalized nform of tularemia the fundamental sign is the development of the general nsymptoms of the disease without previous local symptoms, which are absent ithe future, as a rule. It is the only form of tularemia, which does not have a nprimary and a regional reaction. Clinically the generalized form is ndistinguished by more severe manifestations of intoxication, sometimes evefainting and delirium.
The headaches are intense and npersistent, adynamia and muscle aches are very nexpressed. The fever lasts about 3 and more weeks, and the temperature curve is noften oscillatory. A rash similar to exudative polymorph erythema oftedevelops during the second half of the disease. The rash on the upper and lower nextremities is usually symmetric, pink-red, later has a crimson-coppery tint nand at the end it has a cyanotic shimmer in the form of the tularemia “gloves”, n”gaiters”, “socks”. The rash remains for 8-12 days. there is peeling and prolonged pigmentation after the rash ndisappears.
In the generalized form of ntularemia the capacity to work is recovered especially slow, the relapses are nnot excluded.
Diagnosis
There are several methods of nthe tularemia pathogen isolation in the laboratory. These are direct nbacterioscopia, bacteriology with the microbes nidentification and a biological method. However the immunologic methods are nmore often used to diagnose the disease in people than the bacteriological nones. It depends on the fact that the tularemia pathogen belongs to the first ngroup of microorganisms, that is why its isolation and nidentification can be done only in the specially equipped laboratories of the ndepartments for the especially dangerous infections.
The agglutination reaction is the nmost popular method of the serologic diagnostics. The reaction is considered npositive when serum is diluted 1:100 and higher and becomes positive from the nsecond week of the disease. It is necessary to take into account the fact that nthere is antigenic closeness between the tularemia and brucellosis pathogens, that is why the serum of the tularemia patients ncan give a positive reaction of agglutination with brucellas and. vice versa, nthe brucellous patient can give a positive reaction with the tularemia npathogen. As a result of this the agglutination reaction has a diagnostic value nonly when the antibodies titers increase in the dynamics of the disease.
The sanguinous-dropping agglutinatioreaction is an accelerated method of the approximate serologic diagnostics of ntularemia. However it does not relied the dynamics of nthe increase of the antibodies titers and cannot he an early method of ndiagnostics. For this purpose a thick drop of a patient’s blood, a drop of the ndistilled water, which is used for the lysis of erythrocytes and easy reading nof the reaction, and a drop of diagnosticum are put on the glass. The nagglutination begins immediately if there are agglutinins in the diagnostic ntiter 1:100 and higher in the patient’s blood. The later agglutination on the nglass during 2-3 minutes is doubtful for the diagnostics.
For the purpose of the accelerated npreliminary orientation in the diagnostics it is possible to use nmicroseroreaction. For this puqiose it is not a drop of blood but a drop of nblood serum of a patient that is put on the glass, and a drop of undiluted ntularemia diagnosticum containing 5 billion microbic cells in 1 ml is added to nit. The serologic reaction becomes positive from the 9-10th day of nthe disease, sometimes earlier, if the titer of antibodies at volume nagglutination is .
The compliment binding reactio(CBR), hemagglutination reaction, precipitation reaction and others can also be nused.
An intracutaneous allergic reactioon the injection of allergen – tularin, 1 ml of which contains 100 milliomicrobic bodies killed by heating at a temperature of 70 °C during an hour, is nhighly specific. The suspension of the tularemia microbes (antigen) is prepared nin the physiological salt solution with the addition of the 3 % glycerin. The npreparation is injected strictly intracutaneously. sterile nin the amount of 0.1 ml in the middle third of the forearm, on the palm side. nThe intracutaneous test is valid in all the clinical forms of tularemia. The nresult of the reaction should be considered dynamically in 24-36-48 hours after nits beginning. An expressed edema or infiltrate is considered to be a positive nallergic reaction. Hyperemia without edema, which disappears in 24 hours is considered to be a negative result (a nonspecific nreaction). In some cases the positive reaction is accompanied by the formatioof a pustule and sometimes necrosis or lymphangitis and slight regional nlymphadenitis with the body temperature increase up to 37,5-38,0° nC during 1-2 days.
The test is quite specific (it is nnecessary to take into account the possibility of inoculative or anamnestic nreaction) and usually allows to diagnose the disease nfrom the fifth day after its onset.
Treatment
The patients are treated ithe infectious hospital. nAntibiotics are the main in complex therapy. Streptomycin is the most neffective: 0,5 gm 2 times per day in a muscle. At npulmonary and generalized forms daily dose of Streptomycin enlarge till 2 gm. nCourse of treatment lasts all period of fever and the next 5 days with normal nbody temperature. Streptomycini sulfas has bactericidal effect, after its nintroduction reaction of Yarish-Hercscheimer may be observed. Therefore iserious cases antibiotic therapy is combined with Prednisolon or its analogues.
Tetracyclin, Doxycyclin, Levomycetin, Kanamycin, nGentamicin, rendering bacteriostatic action are less effective. At pulmonary nand generalized forms daily dose of the specified antibiotics is enlarged in 1,5 times. Preparations of Tetracyclin are expedient for ncombining with Aminoglycosides.
At lingering current and relapses of tularemia nprovide combined treatment with antibiotics and inactivated vaccine which ninfuse parenteraly in a single dose 1,5 – 15 million microbic nbodies with interval 5 – 6 days. Course of treatment consists of 6 – 12 ninfusions.
As desintoxication therapy it is nexpedient to use Reopoliglycin, standard saline solutions with glucose. Widely nuse vitamin preparations desensitizing agents. nUsing of bandage with Unguenti of Streptomicin in bubo form.
At anginous-bubonic form of tularemia nthe inhalation of Chlorophilyptus are recomended. At procces of eyes indicate n20 – 30 % a solution of Sulfacyl-natrii.
The treatment is complex, nthe antibacterial therapy plays the main role in it. Streptomycin, ntetracycline, chloromycetin are the most effective nmedicines. A day’s dose of streptomycin 1-2 gm, tetracycline – 1,5-2 gm, chloromycetin – 2 gm. At the highest point of the ndisease detoxication therapy is prescribed (an intravenous injection of the nsalt solutions, haemodesum, polyglucinum, 5 % solution of glucose, ascorbic nacid). The detoxication therapy is done by taking enterodesum and other npreparations of this group. Calcium gluconate, diphenylhydramine, pipolphen, ndiazolinum are used to decrease the allergic manifestations.
In case of relapses and acute nforms it is necessary to prescribe antibiotics courses, but it is necessary to nremember about dysbacteriosis.
Compresses, ointment bandages nand wanning treatment are used at the area of buboes at the stage of ndissolving. If the buboes suppurate. they are widely opened and treated as a purulent wound ntogether with treating the main disease. In case of the timely and valuable ntreatment the prognosis is usually favorable. The lethality is up to 0,5% and occurs in the complicated pulmonary and abdominal nforms of tularemia. The ability to work is recovered slowly.
Prophylaxis
The prophylaxis includes the ncontrol over the natural foci, the interruption of the mechanism of the disease ntransmission, as well as the vaccination of the population in the epidemic nfoci. The planning and the fulfillment of this work in the tularemia foci are ndone by the sanitary-antiepidemic service with the participation of the medical nworkers of the medical institutions who perform the rounds in the houses and nthe vaccination of the population.
ANTHRAX
Definition
Acute infection in both animals and humans in three forms: cutaneous, nrespiratory, and gastrointestinal. The incidence of anthrax has decreased ideveloped countries but it remains a considerable health problem in developing ncountries.
Historic reference
There are descriptions of anthrax involving both animals and humans in the nearly literature of Hindus, Greeks, and Romans. In the seventeenth century, a npandemic referred to as “the black bane” swept through
Several distinguished microbiologists in the nineteenth century ncharacterized the pathology of the disease and attempted to develop a vaccine nbecause of serious problems with anthrax in the livestock industry. Pasteur ndeveloped and field tested in sheep his attenuated spore vaccine in 1881. I1939, Sterne reported his development of an animal vaccine that is a spore nsuspension of an avirulent, noncapsulated live strain. This is the animal nvaccine currently recommended for use.
From the beginning of this century the annual nnumber of cases reported in developed countries has steadily decreased. This ndecrease is the result of the use of a cell-free anthrax vaccine in humans who nare in high-risk industrial groups, decreased use of imported potentially ncontaminated animal products, improved hygiene in industry, and improved animal nhusbandry.
Etiology
Pus or tissue from patients suspected to have nanthrax should be stained by both Gram stain, to reveal gram-positive bacilli, and polychrome methylene blue, nto show the polypeptide capsule. Bacilli nare usually abundant in the specimen and easy to culture on standard blood or nnutrient agar (Fig.5).
Fig.5. Bacillus nantracis
In heavily contaminated specimens nsuch as stool it may be necessary to use selective agar or decontaminatiomethods that rely on the і resistance of the anthrax spores to heat or ethanol. nThe colonies are ngray-white to white and nonhemolytic. Identification of the isolate depends obiochemical tests, presence of a capsule, і lack of motility, catalase npositivity, lysis by γ-bacteriophage, penicillisusceptibility, and aerobic endospore production. Commercially available test nstrips (API Products,
Epidemiology
Anthrax is usually a disease of herbivores and nonly incidentally infects humans who come into contact with infected animals or ntheir products. Because anthrax remains a problem in developing countries, nanimal products imported from these areas continue to pose a risk.
Human cases may occur in an industrial or in aagricultural environment. Industrial cases result from contact with anthrax nspores that contaminate raw materials that are used in manufacturing processes. nIn the
One epidemic was recently reported in
Human cases of anthrax in an agricultural nenvironment result from direct contact with animals that are sick or have died nfrom anthrax.
In
In African wildlife, which cannot easily be vaccinated and in which the nother aspects of control are not relevant, the disease remains a major cause of nuncontrolled mortality in herbivores.
Organisms can also be transmitted by a common vehicle such as food n(meat), although this is more rare. Large outbreaks nhave been reported in
Recently two Russian pathologists published hidden secret informatiodescribing the necropsy of 42 cases, which consistently revealed pathologic nlesions diagnostic of inhalation anthrax. Main features include hemorrhagic nnecrosis of the thoracic lymph nodes in the lymphatic drainage of the lungs nand hemorrhagic mediastinitis. This information underscores the potential nuse of B. anthracis in biological warfare.
Pathogenesis
The virulence of B. anthracis is ndetermined by the presence of three components: edema toxin, lethal toxin, and capsular nmaterial. To exert their effect within cells, both edema and lethal toxirequire participation of a common transport protein called protective antigen. nThe capsule material contains poly-D-glutamic acid, which helps protect the nbacillus from ingestion by phagocytes. Production of the toxic factors is nregulated by one plasmid and that of the capsular material by a second plasmid.
The effects of anthrax toxin components on humaeutrophils have been studied nin detail. Phagocytosis of opsonized and radiation killed B. anthracis nwas not affected by the individual anthrax toxin components. However, a ncombination of lethal toxin and edema toxin inhibited bacterial phagocytosis nand blocked the oxidative burst of polymorphonuclear neutrophils. The two-toxicombination also increased intracellular cyclic AMP levels. These studies nsuggest that two of the protein components of anthrax toxin increase host nsusceptibility to infection by suppressing polymorphonuclear neutrophil nfunction and impairing host resistance.
Experiments performed in animals suggest that nspores deposited beneath the skin or in the respiratory or intestinal mucosa ngerminate and the resulting vegetative forms multiply and produce a toxin. The nlocal lesion results from the action of the toxin on the surrounding tissue, nwhich causes tissue necrosis. The toxin or organisms or both may disseminate by nthe vascular system, causing systemic symptoms and signs of toxicity or nbacteremia. Organisms are also often picked up by the lymphatic system, nresulting in lymphangitis and lymphadenopathy.
Morbid anatomy
The most significant findings at autopsy are nthose seen in patients who have died of inhalation anthrax. The classic finding nis that of hemorrhagic mediastinitis with enlarged, hemorrhagic lymphadenitis. nThere may be inflammation of the pleura and some pleural effusion. Some npatients may have hemorrhagic meningitis, and hemorrhages may be seen in the ngastrointestinal tract.
In deaths due to gastrointestinal anthrax there nis typically hemorrhagic enteritis, with congestion, thickening, and edema of nthe intestinal walls. Mucosal ulcers with necrosis may be seen in the terminal nileum and cecum. The regional lymph nodes are enlarged, edematous, and hemorrhagic nwith some necrosis. There may be acute splenitis. Peritonitis with ascitic nfluid is often present.
Clinical manifestations
Approximately 95 % of anthrax cases in developed ncounties are cutaneous and 5 % are respiratory: nconfirmed epidemic cases of gastrointestinal anthrax have often been reported nin “
The clinical presentation of cutaneous anthrax is so characteristic that the diagnosis is not noften missed by physicians familiar with the disease. Most of the cases occur nin exposed skin areas mostly on the arms and hands followed by the face and nneck. The infection begins as a pruritic papule that resembles an insect bite. nThe papule enlarges and within 1 or 2 days develops into an ulcer surrounded by nvesicles. The lesion is usually 1-3 cm in diameter and usually remains round nand regular (Fig.6, 7). A characteristic black necrotic central eschar develops nlater with associated edema (Fig.8, 9). The lesion is most often painless and nmay first be noticed because of pruritus. After 1-2 weeks the lesion dries, and nthe eschar begins to loosen and shortly thereafter separates, revealing a npermanent scar. There may be regional lymphangitis and lymphadenopathy and some nsystemic symptoms such as fever, malaise, and headache. Antibiotic therapy does nnot appear to change the natural progression of the lesion itself: however, it nwill decrease or inhibit development of edema and systemic symptoms. nDifferential diagnosis include conditions due to npotential 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 nanthrax shows a biphasic clinical pattern with a benign initial nphase followed by an acute, severe second phase that is almost always fatal. nThe initial phase begins as a nonspecific illness consisting of malaise, nfatigue, myalgia, mild fever, nonproductive cough, and, occasionally, a nsensation of precordial oppression.
The illness may cause disorder of a mild upper nrespiratory tract infection such as a cold or viral influenza. After 2-4 days, nthe patient may show signs of improvement. However, there is then the suddeonset of severe respiratory distress characterized by severe hypoxia and ndyspnea. In several cases, subcutaneous edema of the chest and neck has beedescribed. The pulse, respiratory rate. and temperature become elevated. Physical examinatioreveals moist, crepitant rales over the lungs and possibly evidence of pleural neffusion. Radiographic examination of the chest may reveal widening of the nmediastinum and pleural effusion. Patients soon become hypotensive and nsepticemia and meningitis may develop. Death occurs in most persons with ninhalation anthrax within 24 hours after the onset of the acute phase. nInhalation anthrax is very difficult to diagnose early.
The incubation period of gastrointestinal anthrax is commonly 3-7 days. There are two nclinical presentations following ingestion of B. antracis-contaminated nfood: abdominal and oropharyngeal.
The symptoms of abdominal anthrax are initially nnonspecific and include nausea, vomiting, anorexia, and fever. Lesions are nfrequently described in the cecum and adjacent areas of the bowel. Some reports nhave described lesions in the large bowel, and rarely in the duodenum. With nprogression of the disease abdominal pain, hematemesis and bloody diarrhea ndevelop. With further progression toxemia develops, with shock, cyanosis, and ndeath. The time from onset of symptoms to death has most frequently varied from n to 5 days.
In the oropharyngeal form edema and tissue necrosis occur in the ncervical area. There are several reports describing the development of ainflammatory lesion resembling a cutaneous lesion in the oral cavity involving nthe posterior wall. the hard palate, or the tonsils. nThe main clinical features are sore throat, dysphagia, fever, regional nlymphadenopathy in the neck and toxemia. Most of these patients die with ntoxemia and sepsis.
Treatment
It is estimated that approximately 20 % of nuntreated cases of cutaneous anthrax will result in death, whereas inhalatioanthrax is almost always fatal. Deaths are, however, rare after antimicrobial ntreatment in the cutaneous form.
Intravenous penicillin is the drug of choice, nwith a dose of 4 million units every 4-6 hours. Lesions become culture negative nin a few hours but therapy should be continued for 7-10 days. For the npenicillin allergic patient, erythromycin, a tetracycline or chloramphenicol is nsatisfactory. Antibiotic therapy is designed to ameliorate systemic symptoms, nalthough progression to eschar is not prevented. Excision of the lesion is ncontraindicated. Topical therapy is not effective. Systemic corticosteroids nhave been used for patients with extensive or cervical edema and in those with nmeningitis but indications are not well established. Tracheotomy may be needed nwhen cervical edema compromises the airway.
Dressings with drainage from the lesions should nbe incinerated, autoclaved, or otherwise disposed of as biohazardous waste. nPatients with draining lesions should be placed in “contact nisolation.” although this is superfluous is hospitals nusing “universal precautions.” Person-to-person transmission has not nbeen documented, including from patients with inhalation anthrax.
Diagnosis
For the detection of anthrax bacillus, sterile swabs should be soaked in the fluid of nthe vesicles, Vesicular fluid should reveal B. nanthacis organisms microscopically and on culture. Anthrax bacilli are neasily seen on Gram stain smears and cultures from vesicular fluid. The ndifferential diagnosis includes staphylococcal disease, plague, and tularemia.
An enzyme-lined immunosorbent assay (EL1SA) has nbeen developed that measures antibodies to the lethal and edema toxins. The ndiagnosis may be confirmed serologically by demonstrating a fourfold change iliter in acute and convalescent-phase serum specimens collected 4 weeks apart nor by a single titer of greater than .
Although extensive serologic studies have not beeconducted, antibody liters in some surveys of exposed individuals suggest some ndegree of previous subclinical infection.
Control and prevention
The resistance of the spore form of B. anthracis to physical and nchemical agents is reflected in the persistence of the organism in the ninanimate environment. Organisms have been demonstrated to persist for years ifactories in which the environment became contaminated during the processing of ncontaminated imported materials of animal origin. Accordingly, they may serve nas the source of infection for people who work in the area. Special efforts are nrequired to decontaminate this environment; one method is to use nparaformaldehyde vapor, which is successful in killing B. anthracis nspores. In the laboratory, surfaces may be decontaminated with either 5% nhypochlorite or 5% phenol (carbolic acid); instruments and other equipment may nbe autoclaved.
Employees should be educated about the disease nand the recommendations for working in a contaminated environment and for reducing nthe risk of developing the disease. Medical consultation services should be navailable to the employees. Adequate cleanup facilities and clothes-changing nareas should be available so that workers do not wear contaminated clothes nhome.
It should be noted that the risk of industrial infection has beereduced significantly as the use of imported animal products decreased because nof changing business conditions, the increased use of synthetic materials, and nthe use of human vaccine.
Gastrointestinal anthrax can be prevented by forbidding the sale for nconsumption of meat from sick animals or animals that have died from disease. nDepending on the circumstances, it may be important to alert individuals who nmay come in contact with contaminated meat about the disease and about the need nto cook all meats thoroughly. Prophylactic penicillin may be used if ncontaminated food has been ingested.
Animals that graze in areas known as anthrax districts should be nvaccinated annually with the animal vaccine. All animals suspected of dying nfrom anthrax should be examined microbiologically: blood or tissue smears cabe examined microscopically, and cultures can be set up from these same nmaterials. Necropsies with spillage of contaminated blood with resultant nsporulation of organisms should be avoided. All animals that have died with a nconfirmed diagnosis of anthrax should be thoroughly burned and the remaining nbones and other materials buried deeply.
Control of the disease in humans ultimately ndepends on control of the disease in animals. Effective animal vaccines are navailable, and all cases should be reported to state veterinary authorities.
Both an attenuated live vaccine and a killed nvaccine have been developed. However, the only human vaccine in current use ithe United States is the killed vaccine derived from a component of the nexotoxin. This vaccine was field tested in employees of four different textile nmills in the
The ability to prepare purified components of anthrax toxin by nrecombinant technology has opened the possibility of new anthrax vaccines. For nexample, immunization with protective antigen (PA) toxoid vaccines or nPA-producing live vaccines elicits partial or complete protection against nanthrax infection and these new vaccines deserve careful field testing.
Erysipelas
Definition
Erysipelas nis a distinctive type of superficial border serous or serous-hemorrhagic ninflammation of the skin with prominent lymphatic involvement with acute or nchronic course of disease.
Etiology
It is almost always due to group A b–hemolytic streptococci (uncommonly, group С or G). Group В streptococci have nproduced erysipelas in the newborns.
Epidemiology
Erysipelas is more common in infants, nyoung children, and older adults. Evidence of streptococcal infections (groups A, G, and C) was found in 26 of 27 npatients with clinical erysipelas, utilizing the combination of direct nimmunofluorescence and cultures of punch biopsy specimens along with serologic ntiters. Very rarely, a similar skin lesion is caused by S. aureus.
Formerly, nthe face was most commonly involved, and an antecedent streptococcal nrespiratory tract infection preceded cutaneous involvement in about one-third nof patients even though streptococci might not be found on culture at the time nthe skin lesion became evident.
Source of disease is sick nperson with erysipelas and other streptococcal ninfections (tonsillitis, pneumonia, scarlet fever, streptodermia) and nhealthy carriers.
Contact mechanism of ntransmission. Increasing of morbidity in summer-autumperiod.
Pathogenesis
Most ninterest has focused on streptococcal npyrogenic exotoxins (SPEs). In edition to mediating the nscarlatinal rush, SPE exibit a variety of adverse biologic effects, including nthe multiorgan damage and lethal shock. There is an amino acid homology nof 50 % and immunologic reactivity between SPE A and staphylococcal nenterotoxins B and C. SPE of ngroup A streptococcus nis a superantigen and it is a potent inducer of tumor necrosis factor.
The nantistreptolysin O response after cutaneous streptococcal infection is wea. nThere is experimental evidence to suggest that this may be due to local ninactivation of streptolysin O by skin lipids. The immune response to antiDNase B is brisk, and antihyaluronidase reactivity is nalso a useful test in the serodiagnosis of erysipelas.
Clinical manifestations
Usual localization of erysipelas: n70-80 % of the lesions on the lower extremities and 5-20 % on the face. Portals nof entry are commonly skin ulcers, local trauma or abrasions, psoriatic or neczematous lesions, or fungal infections; in the neonate, erysipelas may ndevelop from an infection of the umbilical stump. Predisposing factors include nvenous stasis, paraparesis, diabetes mellitus, and alcohol abuse. Patients with nthe nephrotic syndrome are particularly susceptible. Erysipelas tends to occur nin areas of preexisting lymphatic obstruction or edema (after a radical nmastectomy). Also, because erysipelas itself produces lymphatic obstruction, it ntends to recur in an area of earlier infection. Over a 3-year period, the nrecurrence rate is about 30 %, predominantly in individuals with venous ninsufficiency or lymphedema.
Streptococcal bacteremia occurs in about 5 % of patients with erysipelas; group A, C, nor G streptococci can be isolated othroat culture from about 20 % of cases.
The face (often bilaterally)(Fig.9), nan arm or a leg (Fig.10) is most often involved. The lesion is well demarcated, nshiny, red, edematous and tender; vesicles and bullas often develop. Patches of nperipheral redness and regional lymphadenopathy are seen occasionally; high nfever, chills and malaise are common. Erysipelas may be recurrent and may nresult in chronic lymph edema. A cause of infection may be an interdigital nfungal infection of the foot that may require long-term therapy to prevent nrecurrent erysipelas.
Uncomplicated erysipelas nremains confined primarily to the lymphatics and the dermis. Occasionally, the ninfection extends more deeply, producing cellulitis, subcutaneous abscess, and nnecrotizing fasciitis.
Leukocytosis is common with nerysipelas. Group A streptococci nusually cannot be cultured from the surface of the skin lesion, and only rarely ncan they be isolated from tissue fluid aspirated from the advancing edge of the nlesion. In cases of erysipelas complicating infected ulcers, group A streptococci nhave been isolated from the ulcerated area in 30 % of patients.
Fig.9. Erysipelas nof face
Fig.10. Erysipelas of leg
Diagnosis
Diagnosis from the characteristic appearance is nusually easy. The causative organism is difficult to culture from the lesion, nbut it may occasionally be cultured from the blood.
Therapy
Mild early cases of erysipelas in the adult nmay be treated with intramuscular procaine penicillin (600,000 units once or ntwice daily) or with oral penicillin V (250-500 mg every 6 hours). Erythromyci(250-500 mg orally every 6 hours) is a suitable alternative. For more extensive nerysipelas, patients should be hospitalized and receive pare) aqueous npenicillin G (600,000-2 millions units every 6 hours).
Prophylaxis
Adherense nto good regimens of personal hygiene, with special attention to frequent nscrubbing with soap and water, is the most effective preventive measure ncurrently available. The in time treatment of streptococcal pharyngitis is of nmuch importance.
