Erlihiozı

Ehrlichiosis (Ehrlichiosis) is a group of acute zoonotic, mainly transmissible, infectious diseases characterized by polymorphism of clinical manifestations.

Epidemiology of erlihiasis

The maintenance and propagation in nature of pathogens of monocytic and granulocyte erlichiosis are associated with ixodid mites, and the causative agent of erlichiosis is sennet - presumably with fish mollusks.

In the United States, the causative agent of monocytic erlichiosis is transmitted by A. Americanum, D. Variabilis, I. Pacificus, in a significant part of Eurasia - I. Persulcatus. The main carrier of granulocytic anaplasmosis in the United States is I. Scapularis, I. Ricinus in Europe , I. Persulcatus in the West Siberian region . The infestation of various ixodid ticks by Ehrlichia can range from 4.7 to 50%. In addition, several different microorganisms (for example, Ehrlichia, Borrelia and tick-borne encephalitis virus) can coexist in the body of a tick, and it is possible to infect humans with these pathogens simultaneously.

The main reservoir hosts of E. Canis are considered to be dogs, the masters of E. Chaffeensis are deer. Potential E. Chaffeensis can also be dogs and horses. Antibodies to E. Phagocytophila have been found in several species of wild rodents, but apparently in the USA the main host of these erlichia is the white-legged hamster, as well as forest rats, and in the UK - roe deer. In Russia and Ukraine - the main host Anaplasma phagocytophilum - red vole.

Ehrlichia enter the human body with the saliva of the sucking infected tick. With a sennet fever, infection is associated with eating raw fish.

The disease affects people of any age; among the sick, men predominate. In the United States, it has been established that monocyte erlichiosis occurs among the permanent residents of some states of the South of the country at the same frequency as the spotted fever of the Rocky Mountains endemic for these areas. Hunters, residents of rural areas, people who often visit forests and taiga are more often ill. Group diseases are also possible.

Erlichiosis is currently registered in many countries. In the United States for serological testing, the disease with monocytic erlichiosis has been confirmed virtually throughout the country. Single cases of monocytic erlichiosis are serologically recorded in Europe (Spain, Belgium Portugal), and also in Africa (Mali). Granulocyte anaplasmosis, in addition to the United States, is registered among people who have been attacked by ixodids in England, Italy, Denmark, Norway, Sweden.

Monocytic and granulocytic erlichiosis are also found in Russia. When using the PCR method of ticks collected in the Perm Krai, the infection of I. Persulcatus with monocytic erlichia was identified, which is attributed to E. Muris. This species of erlichia was described in Japan, but nothing was known about its pathogenicity to humans. Starting from 1999-2002. Antibodies to E. Muris and E. Phagocytophila, as well as to A. phagocytophilum, are found in patients to which the tick sucked. In the Perm region of Russia, the share of granulocyte anaplasmosis in the structure of tick-borne infections is 23% and is second only to tick-borne borreliosis; more than 84% of cases, these diseases occur as a mixed infection.

Mortality in the US is 3-5% for monocytic erlichiosis and 7-10% for granulocyte anaplasmosis.

Activation of ticks in a warmer season determines the seasonality of monocytic erlichiosis: April-September with a peak in May-July. Granulocytic anaplasmosis is characterized by a two-peak incidence: the most significant peak in May-June is related to the activity of the nymphal stage of the transporter, and the second peak by October (until December) is associated with the predominance of adult tick-ticks at this time.

Emergency specific prophylaxis should be performed in endemic areas when a tick is detected (a single dose of 0.1 g of doxycycline). Nonspecific prophylaxis consists in carrying out anti-maltreatment measures before going out to the terrain, endemic for ixodid mites (special closed clothing, sekaricide treatment). After visiting the endemic area, mutual and self-examination is necessary to identify sucking ticks.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

What causes erlichiosis?

The generic name Ehrlichia was proposed in 1945. Moshkovsky in honor of Paul Ehrlich. Ehrlichia are immobile gram-negative, rickettsiose-like organisms, obligate intracellular parasites, reproducing binary fission, not forming a spore. According to the modern classification, the tribe Ehrlichia belongs to the family Rickettsiaceae of the order Rickettsiales tribe a-proteobacteria. In the tribe, in addition to unclassified genera and the genus Ehrlichia itself, there are three more bacterial species (Anaplasma, Cowdria, Neorickettsia) that cause diseases in mammals. The genus Ehrlichia is divided into three genogroups. The genotype of canis unites erlichia of four species: E. Canis. E. Chaffeensis, E. Ewingii, E. Muris. The phagocytophila gene group combines E. Bovis, E. Equi, E. Phagocytophila, E. Platus. several genovidov Ehrlichia spp. To the genomic group risticii belong two species - E. Risticii and E. Sennetsu. Part of the Ehrlichia is not yet classified and is grouped into the group Ehrlichia spp.

The causative agents of the disease in humans can be at least four types of these bacteria. The etiological agents of monocytic erlichiosis are considered to be two species of erlichia - E. Chaffeensis and E. Muris. Anaplasma phagocytophilum - the causative agent of human granulocyte erlichiosis (which since 2004 is called granulocyte anaplasmosis) is also referred to as tribe Ehrlichia (genus Anaplasma). E. Sennetsu is the causative agent of sennet fever, highly endemic for a limited area of the south of Japan.

Morphologically, all Ehrlichia species are small pleomorphic coccoid or ovoid microorganisms that have a dark blue or purple hue when painted according to Romanovsky-Giemsa. They are found in vacuoles - phagosomes of the cytoplasm of affected eukaryotic cells (mainly leukocyte series) in the form of compact clusters of separate parasite particles, due to the external appearance called morulae. Cytoplasmic occlusions usually contain 1-5 erlichia, and the number of such vacuoles can reach 400 or more in one cell. With Ehrlichiae electron microscopy, the ultrastructure is similar to the rickettsia, and the same method of reproduction is a simple binary division. The peculiarity of the cell wall of an individual Ehrlichia is the lag of the outer membrane from the cytoplasmic one and its wavy appearance. The inner membrane retains a smoothly contoured profile.

The distribution of ribosomes and fibrils of Ehrlichia DNA, in particular monocytic erlichiosis, are represented by two types of cells morphologically different.

• With a uniform distribution over the cytoplasm, cells of the reticular type; they have dimensions of 0.4-0.6x0.7-2.0 μm.
• With the concentration and compaction of these components in the center of the cell. This type of cells has dimensions of 0.4-0.8 x 0.6 microns.

It is assumed that cells of the reticular type are the early stage of the development of the microbe, and cells of the second type reflect the stationary phase of the life cycle. Ehrlichia is released by rupturing the membrane of the morula-vacuole and then the cell wall of the target cell or by exocytosis (extrusion) of erlichia from the morula or exocytosis of morula entirely from the cell.

According to the antigenic composition of Ehrlichia, they do not share common properties with rickettsia of the tick-and-typhus-typhoid group, as well as with Borrelia. Within the group itself, erlichia has cross antigens.

Ehrlichia do not grow on artificial nutrient media. The only available substrate for accumulation of Ehrlichia is to study them and prepare specific antigens - macrophage-like (line of canine macrophages DN 82) or epithelio-like (human endothelial cell line, VERO, HeLa cells, LEC) transplantable eukaryotic cells. This process is laborious and takes a long time; the accumulation of erlichia in these cells is insignificant. For the reproduction of E. Sennetsu, in addition, white mice can be used in which erlichia cause a generalized process with accumulation of the pathogen in the macrophages of the peritoneal fluid and in the spleen.

Pathogenesis of erlichiosis

Pathogenesis and pathomorphology of erlichiosis have not been studied enough due to the limited availability of data on the results of autopsy, however, experimental studies on macaques allowed a more detailed study of this disease at the histomorphological level.

The pathogenesis of monocytic and granulocyte erlichiosis in the initial stage is due to the introduction of the pathogen through the skin and is identical to that of rickettsiosis. There are no traces at the site of suction of the tick. The causative agent enters the underlying tissues and spreads hematogenously throughout the body. Just as with rickettsiosis, the pathogen is introduced into the cells, multiplies in the cytoplasmic vacuole, and then leaves it. Macrophages of the spleen, liver, lymph nodes, bone marrow are mainly affected. It is possible to develop focal necrosis and perivascular lymphohistiocyte infiltrates in many organs and skin. In the spleen, liver, lymph nodes and bone marrow, megakaryocytosis and hemophagocytosis develop, in response to this myeloid hypoplasia is formed. Polyorganic perivascular infiltration of lymphohystocytes, hemophagocytosis in organs and bone marrow, impaired vascular permeability and development of hemorrhage in internal organs and skin are especially pronounced in severe disease. With the fatal outcome of monocytic erlichiosis, a total defeat of vital organs occurs with an irreversible violation of their function. E. Chaffeensis can penetrate the cerebrospinal fluid and cause meningitis. Changes in the cellular composition of the blood are described as "hemophagocytosis syndrome". The mechanism of suppression of immune defense in erlichiosis is still unknown, but the lethal outcome develops more often in patients with clinical signs of secondary lesions of a fungal or viral nature. There are experimental data, suggesting that erlichia can be characterized by the process of L-transformation.

In the case of sennet fever, the entrance gates are located in the area of the mucosa of the mouth or pharynx. Then the infection spreads through the lymphatic and blood vessels and is accompanied by generalized lymphadenopathy, bone marrow damage and leukocytopenia. Sometimes the endothelium of the capillaries is involved in the infectious process, as evidenced by the appearance of a petechial or erythematous rash.

Ehrlichiosis reduces the production of cytokines - immune response regulators of various families (TNF-a, IL-6, granulocyte-macrophage cholinostimulating factor) and IL-1, IL-8 and IL-10 production, which contributes to the death of phagocytosed bacteria and indicates participation immunocompetent cells in local inflammatory reactions.

Symptoms of Ehrlichiosis

Ehrlichiosis have an incubation period, which lasts 1-21 days, and a clinically pronounced disease - 2-3 weeks, but can sometimes be delayed up to 6 weeks. Symptoms of erlichiosis are diverse - from asymptomatic to severe clinical picture with a severe, life-threatening course. Common to all symptoms of ehrlichiosis: sudden onset of fever, the appearance of fever, fatigue, headache, muscle pain, anorexia, nausea and vomiting, and other nonspecific symptoms of intoxication observed in the rickettsial infections. With erlichiosis sennet, fatal outcomes are not described, and rashes are rare, while in monocytic and granulocyte erlichiosis lethality reaches 3-10%, and erythematous or petechial rash is recorded in 2-11 (up to 36%) cases, respectively. The main symptoms of senetus fever are a rise in body temperature to 38-39 ° C, generalized lymphadenopathy and an elevated monocyte content in the peripheral blood.

The duration of the febrile period with sennet fever does not exceed 2 weeks, with monocytic erlichiosis - 23 days, with granulocyte anaplasmosis - 3-11 weeks. Since erlichiosis does not have clinical pathognomonic features, patients are most often suspected of different types of rickettsiosis, sepsis, influenza, upper respiratory tract infections, infectious mononucleosis, etc.

In patients with granulocytic anaplasmosis, the disease began acutely, with a rise in temperature during the first day to 39-40 ° C, which was accompanied by chills. At the same time, there is a severe headache, painful pain in the muscles and large joints. As the disease progressed, patients complained of persistent insomnia, anxiety sleep, sleepiness during the day. None of the patients had neurological disorders. They noted tachycardia, hypotension, deafness of heart sounds; half of the patients had nausea and vomiting in the first two days of the disease. According to the literature, erythematous, papular or petechial rash is detected at an earlier time in 10% of patients, in the first week of the disease - in 23%, and throughout the period of the disease - in 36.2%. The rash spreads throughout the body, excluding the palms and soles. In the Khabarovsk Territory, the rash is recorded in 87% of cases; she appeared on the 1 st-8 th, more often - on the 3rd day of the disease. The rash was predominantly spotted, pale pink, the elements did not merge, the dimensions did not exceed 10 mm. The phenomenon of falling asleep was not observed. The reverse development of the rash occurred without residual effects, usually on the 8th-9th day. In some patients, the presence of a dense infiltrate up to 20 mm, covered in the center with a dark brown crust (this local reaction was only in a patient with a prolonged, more than a day, tick sucking) was noted at the site of suction of the tick. None of the patients had lymphadenopathy. Against the background of high fever, dry mouth, anorexia, stool retention for several days were noted. In 20% of patients, darkening of the urine, icteric sclera; in 33% of patients - enlargement of the liver. The most constant laboratory test in most patients with monocytic and granulocyte erlichiosis was an increase in the activity of hepatic transferases in the blood serum (ALT 3-4 times, ACT 1.5-2.5 times). In the hemogram, leukopenia, neutropenia (not more than 2.0 × ^{10 9} / L), pronounced shift of the formula to the left. In 71% of patients, moderate thrombocytopenia was recorded, and ESR was more often increased (an average of 23 mm / h). In 40% of patients, changes in urine were observed, which were characterized by proteinuria (0.033-0.33 g / l) to moderate leukocyturia (up to 30-40 in the field of vision).

Patients with monocytic erlichiosis from the Perm Krai (1999-2000) reported almost the same symptomatology, with the exception of catarrhal phenomena in 1/4 patients, enlarged to 1.5 cm of submandibular lymph nodes and development of a number of meningitis patients. Some of them showed lesion of the facial nerve according to the central type. Unlike patients with granulocyte anaplasmosis, patients with monocytic erlichiosis did not have a rash. 42% of patients reported injecting vessels with sclera and conjunctiva. Possible hepatomegaly, subcritic sclera and darkening of urine with an increase in the level of bilirubin and aminotransferase activity. Part of the patients detected a two-wave course of the disease: the second wave had a more severe course, which was manifested by a high and prolonged fever, marked by intoxication: in some patients serous meningitis developed at that time. There was also an increase in the level of creatinine, but there were no clinical manifestations of renal failure. Half of patients had thrombocytopenia, an increase in ESR (16-46 mm / h): leukocytopenia (2.9-4.0x10 ⁹ / l).

Clinical symptoms disappear on the 3-5th day after the onset of antibiotic therapy. In convalescents, asthenia persists for 4-6 weeks after discharge. With severe course of monocytic and granulocyte erlichiosis and absence of etiotropic therapy, renal dysfunction was most often noted. Up to renal failure (9%), development of DIC syndrome with gastrointestinal, pulmonary or multiple bleeding. In 10% of patients with granulocyte anaplasmosis, the development of pulmonary infiltrates was observed. Some patients had convulsions at the beginning of the disease, a coma was developing.

Diagnosis of erlichiosis

The main signs that make it possible to diagnose "erlichiosis" are clinical and laboratory data in combination with an epidemiological anamnesis: the patient's stay in an area endemic to erlichiosis, a tick attack.

The study of blood smears stained by Romanovsky-Giemsa gives positive findings (vacuoles in the cytoplasm of neutrophils or monocytes containing Ehrlichia accumulations) are rare, and only in the acute phase of the disease.

Serologic Diagnosis of erlichiosis is carried out with the help of RNIF, ELISA, less often immunoblotting. Seroconversion occurs during the first week of the disease, and antibodies detected in the sick may persist for 2 years. The minimum diagnostic titer is 1: 64-1: 80 for a single serum sample taken during the febrile period or during the early convalescence, and also within a period not exceeding one year after the onset of the disease. The maximum antibody titers in monocytic erlichiosis at 3-10 weeks of the disease were 1: 640-1: 1280. With unconvincing results of serological research, the use of PCR is promising.

[11], [12], [13], [14], [15], [16]

Differential diagnosis of erlichiosis

Since there are no pathognomonic symptoms of erlichiosis and possibly the course of the disease as a mixed infection, differential diagnosis is difficult. To presume a clinical diagnosis, even taking into account changes in the blood picture, is quite difficult. Information about the attack of a tick for 1-3 weeks before the illness gives grounds to suspect systemic tick-borne borreliosis (lime-borreliosis), and in endemic areas - other tick fever (Colorado, spotted fever of the Rocky Mountains). Differential diagnosis is also carried out with infectious mononucleosis, typhus and typhoid fever, leptospirosis. Frequently occurring mixed infection (erlichiosis with classical tick-borne borreliosis and tick-borne encephalitis) leaves a mark on the picture of the disease and often does not have clear differential signs necessary for clinical diagnosis, however, with granulocyte anaplasmosis, acute jaundice hepatitis, as well as severe leukopenia , lymphopenia and an increase in the number of stab elements at the onset of the disease.

[17], [18], [19], [20], [21], [22], [23]

Indications for consultation of other specialists

Life-threatening complications (severe renal failure, massive bleeding, etc.) require the advice of the resuscitator with subsequent treatment of the patient in the intensive care unit.

Indications for hospitalization

Indications for hospitalization include a severe course of the disease, the development of complications. Hospitalization needs 50-60%, and about 7% of patients require intensive care.

Treatment of erlichiosis

Ehrlichia are sensitive to tetracycline drugs (tetracycline, doxycycline), to a lesser extent to chloramphenicol.

The most effective tetracycline (0.3-0.4 g four times a day for 5-10 days) or doxycycline (0.1 g twice in the first day, then once: levomitsetin can be used.The treatment of erlichiosis must be combined with pathogenetic and symptomatic means (detoxification, combating complications, etc.).

Clinical examination

Examination is not regulated. It is recommended that medical supervision be performed before the restoration of disability.

[24], [25], [26], [27]

What prognosis are erlichiosis?

Ehrlichiosis have a serous prognosis for the development of severe complications in the absence of timely complex treatment.