CRIMEAN HEMORRHAGIC FEVER

From Big Medical Encyclopedia

CRIMEAN HEMORRHAGIC FEVER (synonym acute infectious capillary toxicosis) — the acute infectious disease with a natural ochagovost which is transmitted by ixodic mites and characterized by the general intoxication, the expressed hemorrhagic syndrome, a leukopenia and thrombocytopenia.

History

For the first time To. of l. it is described as an independent disease of the person by M. P. Chumakov, A. E. Sokolov, A. A. Kalachev, I. R. Drobinsky, etc. in 1945 — 1947 on materials of studying of epidemic flash in the Crimea by M. P. Chumakov (1944). However the first mentioning of clinically similar disease in Central Asia occurs in 12 century at the Tajik doctor and the philosopher Dzhurdzhoni («Horezmshakh's Treasure»). In 1945 — 1969 many authors described under various names cases of a hemorrhagic disease of the specified type in the Krasnodar and Stavropol regions, the Astrakhan and Rostov regions, in the territory of the Central Asian republics and Kazakhstan. During this period the centers are revealed To. of l. also in the territory of Bulgaria, Yugoslavia, Hungary, some countries of Asia (Iran, India, Pakistan) and Africa (Zaire, Nigeria, Uganda, Kenya, Senegal), etc.

Since 1967 — 1969 it became known of existence of the so-called Congo virus which on antigenic properties was related to a virus K. of l. Unlike To. of l., the disease connected with the Congo virus seldom was observed at people (less than 20 cases), but the virus often was found in animals. Since 1964 it is known of existence of a so-called virus of the Khazar allocated in Pakistan from mites of Ixodes redikorzevi which is also close to a virus K. of l. However the diseases caused by this virus among people and animals are not registered.

Geographical distribution

Incidence of people To. of l. in the Soviet Union it is registered in the Crimea, the Krasnodar and Stavropol regions, the Astrakhan, Rostov, Donetsk and Kherson regions, in the Uzbek, Turkmen, Kyrgyz, Kazakh, Armenian Soviet Socialist Republic, etc., and also in Bulgaria, Yugoslavia, Iran, India, Pakistan, etc. Besides, serol, and virusol. researches established existence of the natural centers To. of l. without the registered incidence among people (the so-called potential local centers To. of l.) in many districts in the mentioned territories, and also in the Azerbaijani and Moldavian SSR, Dagestan and Kalmyk the ASSR. Serol, researches allow to assume existence of the natural centers To. of l. in Turkey, Afghanistan, France (on border with Spain). The weight of evidence suggests an area To. of l. in yuzh. the countries of Europe and Asia wider as there are identical species of ixodic mites — carriers of activators K. of l.

The incomplete accounting of diseases To. of l. is defined by insufficient acquaintance of doctors to this disease and the fact that the attention of doctors is drawn by hl. obr. severe forms To. of l., especially at emergence of group infections of medics in-tsakh or members of families of the patients who got sick owing to contact with blood and the allocations containing blood in the acute period of a disease.

Similar (if not identical) with To. of l. the hemorrhagic disease in Africa caused by the Congo virus is registered in a small number of cases in Zaire (1956, 1958), Uganda (1959 — 1960) and the Central African Republic (1976). In the same territories, and also in Nigeria, Kenya, Senegal quite often found the Congo virus in arthropod several types, at house and wildings.

Etiology

Fig. 1. The diffraction pattern of negatively painted virions of the Crimean hemorrhagic fever from drug of the infected cellular culture; X 220 000.
Fig. 2. Diffraction pattern of virion of the Crimean hemorrhagic fever: spiral laying of a tyazh of a ribonucleoprotein is visible; x 250 000.

For the first time an etiology To. of l. it is established in 1945 — 1946 by M. P. Chumakov in the Crimea when several virus strains from carriers — ixodic mites of Hyalomma plumbeum plumbeum Panz were allocated. and from blood of sick people in an acute stage of a disease, and immunol, reactions proved specificity of a virus as a disease-producing factor. Virus K. of l. is a part this. Bunyaviridae, a prototype to-rogo the virus In unyam were, about the Crimea, however, at viruses K is considered. of l. — There is no Congo — the Khazar of group serol, communication. The activator concerns to ecological group arbovirus (see). Virions (a particle of a virus) To. l. a spherical or ellipsoidal shape of 90 in size — 100 nanometers, have external a lipid the containing cover with ledges on a surface in the form of thorns. The central part of virion — almost spherical nucleoid, in Krom is spiralno laid tyazh a ribonucleoprotein (fig. 1 and 2).

Fig. 3. The diffraction pattern of the particles of a virus of the Crimean hemorrhagic fever forming on membranes of tanks of a lamellar complex: 1 — particles of a virus; 2 — a membrane of the tank; x 120 000.
Fig. 4. The diffraction pattern of the kristallopodobny structures (are specified by shooters) found in cellular cultures at late stages after infection with a virus of the Crimean hemorrhagic fever; X 45 000.

Virus K. of l. has coefficient of sedimentation 425 + 25 S, the floating density of 1,17 g/ml, a pier. weight apprx. 300•10 6 dalton. The ribonucleoprotein of a virus has floating density of 1,34 g/ml, the genome is presented by three fragments of one-filamentous RNA which have a pier. weight apprx. 0,8•10 6  ; 2,0•10 6 and 3,0•10 6 dalton. Virions get into a sensory cell by a viropeksis. Maturing of again formed virions happens budding on intracellular plasma membranes of a lamellar complex (Golgi's complex — fig. 3) and an endoplasmic reticulum. Usually virions accumulate in cytoplasmatic vacuoles. Sometimes in the cells affected with a virus, at late stages of an infection, accumulations of kristallopodobny structures (fig. 4) are found. Escaping of a cell of virions usually happens an exocytosis, in rare instances — as a result of a lysis of a cell.

Viruses K. of l. are sensitive to zhirorastvoritel (ether, chloroform) or a dezoksikholat of sodium and to detergents (see), destroying a cover; are not steady in a suspension of tissue of brain at t ° 37 °, 45 °, 56 °, completely losing infectious respectively in 20 hours, 2 hours, 5 — 10 min. and almost instantly at boiling. Viruses well remain in the frozen substrate and is satisfactory in the material which is dried up in the cold containing proteins; they are infektsiozna in the limited range of pH values 6,0 — 9,0 (an optimum of pH 7,0 — 8,0), have no resistance to usually used concentration of desinfectants. The majority of virus strains To. of l. are almost deprived of hemagglutinins, do not give destruction of cells in the infected cultures of fabric.

For isolation, reproduction and identification of virus strains To. of l. it is the most convenient to use infection in a brain and in an abdominal cavity of newborn white mice. Accumulation of a passazhny virus K. of l. (after several subinoculations) it is possible also in a brain of the infected newborn white rats and in cultures of the intertwined lines of renal cells of pigs. In the infected cultures of fabrics under a layer of an agar plaques — colonies of a virus appear. The Passazhny virus in a brain suspension or in cultural liquid can be concentrated, e.g., polyethyleneglycol and to clear for use as antigens in serol, reactions: fixation of the complement or diffusion precipitation in an agar (RDPA). Virus K. of l. it can be allocated from blood of patients in the feverish period of a disease, from section materials, and also from a suspension of the pounded mites carriers. Adult mice, rats, other animals do not give a wedge, pictures of a disease after inoculation of a virus K. of l., but develop specific antibodies. The virus is without loss filtered via the membrane filter with a diameter of time of 220 nanometers and almost completely lingers on filters with a diameter of time less than 100 nanometers.

The epidemiology

Is supposed that sources of activators K. of l. there can be mammals (cows, goats, hares, the African hedgehogs, etc.). The intrahospital and family flashes connected with infection at contact of medical staff or family members with a bloody emetic masses, blood (are frequent at bleedings from a nose) sick people. Also accidental infection of people at contact with blood of sick animals is possible. Cases of laboratory infection of personnel are noted during accidents during the centrifuging of virussoderzhashchy materials and in other conditions of infection of the air environment with a virus K. of l. At the same time serve as a carrier and a tank of an infection Ixodic mites (see) many types in which the virus K is found. of l. — H. plumbeum plumbeum, H. anatolicum, H. asiaticum, H. detritum; Rhipicephalus rossicus, Rh. bursa, Rh. sanguineus, Rh. pumilio; Dermacentor marginatus, D. daghestanicus; Boophilus calcaratus and an argasovy tick — Argas persicus. Mites of some types during a lineage keep a virus K. of l. also transfer him to an animal at a krovososaniye. The virus breeds, transferred to posterity on the course in a body of a tick of H. plumbeum plumbeum a metamorphosis of a tick and transovarialno. The related Congo virus was allocated in Africa and in Asia (Pakistan) from mites of the sort Hyalomma, Boophilus and Amblyomma, and also from mokrets of Culicoides sp. and from blood of cows, goats (during parasitizing of mites on them).

Incidence To. of l. has characteristic seasonality (warm season) that is defined by the period of activity of the different types of mites carriers attacking people depending on climatic factors.

In local rural districts To. of l. cattle breeders, shepherds, shearers, milkmaids, veterinarians and other persons who are attacked by ixodic mites catch preferential.

The pathogeny

the Pathogeny is studied insufficiently. The activator gets into a human body at a krovososaniye the infected tick. He is fixed and breeds in an endothelium of vessels, epithelial cells of a liver, kidneys (that is proved by means of specific reactions of an immunofluorescence) and in other elements of reticuloendothelial system. Develops vasculitis (see) with preferential edematous and destructive defeat of a microcirculator bed up to a fibrinoid necrosis and a loosening of membrane structures, with the early and sharply expressed alterativno-necrotic processes in bodies. Substantially necroses connect with the fabric allergic reaction developing in the course of a disease. Damages of a brain, kidneys and other bodies, most likely, are connected with circulator frustration, and hemorrhagic manifestations — with the hyperpermeability of vessels which is especially expressed at severe forms To. of l.

Pathological anatomy

At the dead from To. of l. there are multiple hemorrhages (see) in skin, on visible mucous membranes; on section they come to light in friable connecting fabric, in various bodies, on mucous membranes of a trachea, a stomach, intestines, in a pleura, a peritoneum. In a gleam of a stomach and intestines find liquid blood or liquid in the form of a coffee thick, in a large intestine — tar-like or brown color contents. In a gleam of a throat and trachea there can be clots, and in pleural cavities — bloody liquid. Lungs of crimson color because of a krovenapolneniye; the pneumonic centers have hemorrhagic character. Hemorrhages find in a myocardium and in a brain. The soft meninx is moderately edematous. The liver is sometimes increased, kidneys and almost always a spleen of the usual sizes. Vessels of all parenchymatous bodies are full-blooded, interfabric layers are impregnated with blood.

In the acute period gistol, the picture is characterized by generalized serous and hemorrhagic inflammation (see), caused by a hyperpermeability of vessels. In kidneys, a liver, a myocardium and endocrine glands dystrophic changes and the centers of necroses are observed. The brain is edematous, with the centers of defeat of nervous cells and ischemic changes. The edematous loosening of a wall of blood vessels, preferential microcirculator bed, desquamation of a vascular endothelium, perivascular hypostasis and hemorrhages by emigration in fabric of various bodies are typical. In bodies of a hemopoiesis hypoplastic reaction with a delay of maturing of leukocytes is found.

Immunity

Postponed To. of l. leads to development of strong and long immunity that comes to light serol, reactions nearby.

Clinic

the Incubation interval To. of l. from 2 to 14, 3 — 5 days are more often. The disease proceeds in an easy, medium-weight and severe form with a hemorrhagic syndrome or without it. At To. allocate to of h.p. with a hemorrhagic syndrome 3 periods: initial, or all-toxic, period of a heat, or hemorrhagic manifestations, and period of reconvalescence.

To. of h.p. and without it begins a hemorrhagic syndrome equally sharply, without the prodromal phenomena: from a tremendous fever or chilling, bystry temperature increase to 38 — 40 °, a severe headache and weakness, an ache in all body, weakness, sometimes nausea and vomitings, abdominal pains, in joints and muscles, in a waist, sometimes with a positive symptom of Pasternatsky. Face skin, necks and breasts is often hyperemic, the xeroderma and mucous membranes is noted. Sometimes there is herpes that, apparently, is a consequence of an aggravation latentno of the proceeding herpes infection. Pulse corresponds to temperature. In blood a leukopenia, a neutropenia, a lymphocytosis, shift of neutrophils to the left, thrombocytopenia, and in urine an albuminuria and a microhematuria, sometimes a cylindruria. Duration of an initial stage of 3 — 6 days then quite often temperature falls on 1 — 2 day and then ate its increases there comes the period of a heat of a disease with development of a hemorrhagic syndrome in the form of hemorrhagic rash on skin, mucous membranes of an oral cavity, a pharynx, nasal bleedings (see), hematomas (see) on places of injections, metrorrhagias (see. Uterine bleedings ), bleeding of gums, sometimes bleedings from ears, blood spitting (see). In the presence of only hemorrhagic rash or its combination to short-term bleedings from a nose and gums To. of l. proceeds rather easily. Existence of massive hemorrhagic manifestations — plentiful hemorrhagic rash, gastrointestinal bleeding (see) — burdens disease. Hemorrhagic manifestations can last from several hours to 2 — 7 days. The face of patients during this period becomes pale and a little bloated, there can be a Crocq's disease. Hemorrhagic rash from dot petechias of dark cherry color to blue-crimson spots of various sizes on various body parts is observed (almost at all patients). Pulse labile to 120 — 130 in 1 min., the ABP decreases, even the collapse is possible. Cardiac sounds are muffled. In lungs there can be dry rattles, seldom melkoochagovy pneumonia. Appetite is absent, at most of patients language is laid over, gingivas are loosened and bleed, nausea and vomiting, quite often unrestrained, plentiful, blood almost entirely can be various intensity of an abdominal pain (see. Hematemesis ). Micro impurity of blood to Calais, a tar-like chair are frequent (see. Melena ), sometimes pure blood. Often the liver increases, the hepatargy is possible; less often the spleen increases. Changes of urinogenital system are moderately expressed and decreases in specific weight of urine are shown in the form of a non-constant symptom of Pasternatsky, an oliguria, an insignificant albuminuria, identification in an urocheras of single leukocytes and fresh erythrocytes. Severe headaches, drowsiness, block, slackness, apathy are usually noted. At a heavy current consciousness is darkened, the nonsense, an involuntary urination and seldom involuntary defecation is possible. Muscle tension of a nape, Kernig's signs and Brudzinsky is found in certain patients. In blood sharp or moderate hypochromia anemia, thrombocytopenia, a leukopenia is noted.

Accompanying hron, diseases, especially cardiovascular system, kidneys, a liver, blood, burden To. of l. Clinic To. of l. at adults and children it is almost identical. At pregnant women To. of l. proceeds extremely adversely.

Complications are not frequent and are shown as bronchitis (see), focal pneumonia (see), fluid lungs (see) at the increasing cardiovascular insufficiency and hepatargy (see) at persons with a cirrhotic liver (alcoholism), about stry renal failure (see), thrombophlebitises (see).

The diagnosis

the Diagnosis during an initial stage of a disease is very difficult, and usually To. of l. regard as flu. In the period of a heat of a disease establishment of the correct diagnosis is helped by hemorrhagic manifestations against the background of the general toxicosis, the nature of changes of blood, epidemiol, the anamnesis. For confirmation of the diagnosis use a lab. researches: detection of a virus K. of l. infection in a brain of newborn white mice blood of the patient in the acute period or a suspension of fabric of bodies of a corpse of a mouse with the subsequent passages on newborn white rats (a brain from sick mice); identification of a virus in reactions of binding complement (see), reactions of diffusion precipitation in an agar — RDPA (see. Immunodiffusion ) and in reaction immunofluorescence (see); identification of antigen of a virus K. of l. in prints or in cryostately cuts of a liver of a corpse of a mouse by means of a method of fluorescent antibodies, definition of changes of antiserum capacities in early and late tests of blood serum of patients in RSK, RDPA and by a method of an immunofluorescence with cultural antigen on glasses. Reaction of indirect hemagglutination (RNGA) with antigen of a virus is applicable. Identification of the allocated virus is possible also in reaction of an interference in culture of fabric (see. Interference of viruses ) against a cytopathic virus of vesicular stomatitis.

Identification in late tests of blood serum of sick antibodies to a virus K. of h.p. the help of RSK even at rather low credits (cultivation of serum 1: 4) with definiteness confirms the diagnosis.

The differential diagnosis

the Disease needs to be differentiated with flu (see), hay fever (see), an epidemic sapropyra (see. Sapropyra epidemic ), Shenleyn's disease — Genokh (see. Shenleyna — Genokh a disease ), Verlgof's disease (see. Werlhof's disease ), acute leukosis (see), an alimentarnotoksichesky aleukia (see. Aleukia alimentary and toxic ), aplastic anemia (see. Hypoplastic anemia ), yellow fever (see); in Africa — with Lass's fevers and Ebola (see. Lassa-likhoradka , Ebola hemorrhagic fever ).

Treatment

Treatment of patients is carried out in a hospital. For fight against intoxication, bleedings and complications pathogenetic therapy is appointed. For desintoxication plentiful drink and parenteral administration fiziol, solution, Hydrolysinum, Amincrovinum and other drugs in the general dose to 1,5 — 2 l a day is recommended. At bleedings enter a whole blood, dry plasma, eritrotsitny, trombotsitny, leukocyte masses, fibrinogen, aminocaproic to - that. As koagulyantny means use ascorbic to - that, Calcium chloratum, citrin, Vikasolum, Gelatinolum. At development of a picture of a hepatargy appoint corticosteroids. In need of dehydration use sulfate magnesia, hypothiazid, furosemide, urea. Cardiovascular means, analgetics, antiemetic and other symptomatic drugs are appointed according to indications. Specific gamma-globulin and serum of convalescents as drugs for an immunotherapy are in a stage of studying.

The forecast

At most of patients in 2 — 3 weeks from an onset of the illness comes recovery, a cut goes slowly. Many patients after an extract a long time remain disabled. Shock as a result of intoxication, massive bleeding in internals, especially in a stomach and intestines is the reason of lethal outcomes, is more rare — a fluid lungs, wet brain, an acute renal failure, chronic cardiovascular pathology.

Prevention

the Main measure of the prevention To. of l. protection of the person against attack of mites is. Apply protective (antitick-borne) clothes to individual protection of the people working in endemic areas — overalls on a zipper, edges of sleeves and trousers to-rogo tighten rubber tapes; in the presence of boots trousers fill in tops, a shirt in trousers; the head is closed a hood. If there are no overalls, then the usual clothes are densely buttoned, sleeves are tied tapes. The clothes are processed by the frightening-off means (see. Repellents ). The hood can be replaced with Pavlovsky's grid (see. Protecting screens ). During the working day it is necessary to make each 1,5 — 2 hours most and mutually surveys and to delete the found ticks; in a lunch break and upon termination of the working day people shall undress and examine each other for possible detection of the stuck ticks. Removal of the stuck ticks is made tweezers, carefully shaking it not to tear off an oral part; the removed ticks are burned or thrown into kerosene (gasoline).

Domestic animals are regularly examined and exempted from the stuck ticks, define species composition of ixodic mites, reveal antibodies in blood at the cattle. Among the population it is necessary to carry out daily a dignity. - a gleam, work to train people in individual protection from mites.

As infection is possible To. of l. at hit of blood of the sick person on skin or mucous membranes, hospitalization of patients To. of l. it is obligatory. In a hospital it is observed strict protivoepidemich. the mode for the prevention of intrahospital infections through blood of the patient (protection of hands rubber gloves, respiratory tracts a gauze bandage).

In the center it is carried out epidemiologich. inspection for receiving reliable information about the place, time and circumstances of infection (about possible contact with sick people, about attack of a tick in recent times and so forth), and also disinfection of allocations of the patient, his bedding, linen, ware.



Bibliography: Arbovirus, under the editorship of M. P. Chumakov, century 2, page 152, M., 1969; Viral hemorrhagic fevers, under the editorship of M. P. Chumakov, M., 1971; Galperin E. A. Clinic of infectious hemorrhagic diseases and fevers, page 122, M., 1960; Hemorrhagic fevers, under the editorship of Yu. A. Perov, Volgograd, 1977, bibliogr.; Donets M. A., Korolev M. B. of M. P's ichumak. Studying of physical and chemical properties, morphology and a morphogenesis of an arbovirus of the KGL-Congo group for the purpose of definition of taxonomical position of these agents in system of modern classification, Vestn. USSR Academy of Medical Sciences, No. 5, page 28, 1977; Medical virology, under the editorship of M. P. Chumakov, page 5, 25, M., 1974; The Guide to infectious diseases, under the editorship of V. I. Pokrovsky and K. M. Loban, page 233, M., 1977; Smorodintsev A. A., Kazbin-tsev L. I. and Chudakov V. G. Viral hemorrhagic fevers, page 172, M., 1963; Chumakov M. P. To the 30 anniversary of studying of the Crimean hemorrhagic fever. Works Ying-that poliomyelitis and viral encephalitis, t. 22, century 2, page 5, M., 1974, bibliogr.; Local viral infections (hemorrhagic fevers), under the editorship of M. P. Chumakov, page 226, M., 1965; Casals J. Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus, Proc. Soc. exp. Biol. (N. Y.), v. 131, p. 233, 1969; Causey O. R. a. o. Congo virus from domestic livestock, African hedgehog and arthropods in Nigeria, J. trop. Med. Hyg., v. 19, p. 846, 1970; Donets M. A. a. o. Physicochemical characteristics, morphology and morphogenesis of virions of the causative agent of Crimean hemorrhagic fever, Intervirology, v. 8, p. 294, 1977, bibliogr.; Porterfield J. S. a. o. Bunyaviruses and bunyaviridae, ibid., v. 6, p. 13, 1975 —1976; Simpson D. I. a. o. Congo virus, hit-hertoundescribed virus occuring in Afrika, Part 1, E. Afr. med. J., v. 44, p. 86, 1967; Woodall J. P., Williams M. C. a. Simpson D. I. Congo virus, hit-hertoundescribed virus occuring in Africa, Part 2, ibid., p. 93.


M. P. Chumakov; K. M. Loban (patol., stalemate. An., clinic, treatment).

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