Human granulocytic anaplasmosis

Anaplasmosis infectious disease refers to transmissible pathologies - that is, to those that are transmitted from blood-sucking insects. In this case, the disease is spread by ixodid ticks - the very arthropods that can also tolerate tick-borne encephalitis and borreliosis.

Anaplasmosis has polymorphic symptoms and characteristic seasonality (mainly spring-summer time), associated with periods of natural tick-borne activity. A sick person does not spread the infection, so contact with him is not dangerous to others. [1]

Epidemiology

Anaplasmosis was first reported in 1994 by Chen et al. (J Clin Micro 1994; 32 (3): 589-595). Anaplasmosis has been reported all over the world; in the United States, it is most commonly reported in the upper Midwest and Northeast. Disease activity has also been reported in Northern Europe and Southeast Asia. [2],  [3],  [4], [5]

In Russia, anaplasma infection through ticks occurs in 5-20% (the overwhelming number of cases occurs in the Baikal region and the Perm Territory). In Belarus, the infection rate ranges from 4 to 25% (the highest prevalence is recorded in the forests of Belovezhskaya Pushcha). In Ukraine and Poland, the percentage of distribution is approximately the same - 23%. The number of cases of anaplasmosis in the United States reported to the CDC has grown steadily since the disease was first reported, from 348 cases in 2000 to a peak of 5,762 in 2017. The cases reported in 2018 were significantly lower but increased around 2017 in 2019 from 5655 cases. [6]

Anaplasmosis is distinguished by its seasonality, which corresponds to the active period of ixodid ticks. Bursts of infections are noted from mid-spring to late summer, or more precisely, from April to early September. As a rule, anaplasmas are found in the same zoning as other types of infections transmitted by ticks - in particular, pathogenic borrelia. It has been determined that one ixodid tick can simultaneously carry up to seven pathogens of viral and microbial diseases. That is why more than half of the cases of the disease are mixed infections - lesions by several infectious pathogens at the same time, which significantly worsens the outcome of the pathology. In most patients, anaplasmosis is found in combination with tick-borne borreliosis or encephalitis, or with monocytic ehrlichiosis. In more than 80% of cases, there is a joint infection with anaplasmosis and borreliosis .

Causes of the anaplasmosis

The causative agent of infectious pathology is anaplasma (full name Anaplasma phagocytophilum, Anaplasma Phagocytophilum) - the smallest intracellular bacterium. When it enters the human bloodstream, it seeps into granulocytes and spreads to all points of the body.

Under natural conditions, anaplasma often settles in the organisms of mice and rats, and in habitable zones, dogs, cats, horses and other animals can become infected. At the same time, they do not pose a danger to people: even if an infected animal bites a person, infection does not occur. [7]

The danger for people in terms of the development of anaplasmosis is the attack of the ixodid tick, since during the bite it secretes saliva into the wound, which contains anaplasma.

The bacterium that causes the development of anaplasmosis has a diameter of less than 1 micron. It enters the systemic circulation along with the insect's salivary fluid. Getting into the tissue of internal organs, the pathogen activates the inflammatory process. Bacteria begin to multiply vigorously, which entails suppression of immunity and, as a result, the addition of secondary infectious diseases - microbial, viral or fungal.

The main reservoir is the white-footed mouse  Peromyscus leucopus; however, a wide variety of wild and domestic mammals have been identified as reservoirs. [8],  [9] Ticks can spread infection between wild and farm animals - in particular, cloven-hoofed, dogs, rodents and even birds that regularly migrate and thereby promote greater transfer of the pathogen. Anaplasma lives in animal organisms for several weeks, and during this time, previously uninfected insects become distributors.

Risk factors

Blood-sucking ticks are capable of transmitting various infections. The most famous are tick-borne encephalitis and borreliosis, and such a pathogen as anaplasma was isolated only a few decades ago.

The risk of anaplasma infection depends on the total number of ticks in the area, on the percentage of infected insects and on human behavior. In areas of increased likelihood of the spread of anaplasmosis, the danger threatens primarily those who rest or work in forest, forest plantation and park areas - for example, hunters, fishermen, mushroom pickers, foresters, tourists, farmers, military men, etc.are special risk categories. NS.

Ixodid ticks are climatic sensitive: they choose to live in areas with moderate or abundant humidity, frequent precipitation, or covered with abundant thickets, where a humidity level of about 80% can be maintained. Insects priority - deciduous and mixed forests, felling, forest-steppe, parks, squares and gardens. Over the past few years, blood-sucking arthropods have spread quite widely to the highlands and northern regions. [10]

Pathogenesis

Anaplasmosis is transmitted by a tick attack at the time of bloodsucking. In the environment of ticks, the infection is transmitted from the female to the offspring, which causes the constant circulation of pathogens. The contact route of transmission of anaplasma (through skin lesions), as well as the digestive tract (when consuming milk, meat) has not been proven.

Most of all, people are exposed to tick attacks in the spring-summer period, which is the peak of insect activity. The start time of the tick season varies depending on the weather conditions. If the spring is warm and early, then the arthropods begin to "hunt" by the end of March, significantly increasing their activity by the second half of summer due to the accumulation of large volumes of bacteria.

Insects are active almost around the clock, but in warm sunny weather, their highest aggressiveness is observed from eight to eleven in the morning, then gradually decreases and again increases from five to eight in the evening. In cloudy weather, the daily activity of ticks is approximately the same. A slowdown in activity is noted in hot conditions and during heavy rains.

Blood-sucking insects live mainly in massive, less often in small forests, forest belts and forest-steppe. There are more mites in humid places, in forest ravines, thickets, near streams and paths. They also live in cities: on the banks of rivers, in nature reserves, as well as parks and squares, and they sense the approach of a living object by smell already from a distance of 10 meters.

A tick goes through several stages of development: an egg, a larva, a nymph, an adult. To ensure the normal course of all stages, the blood of a warm-blooded animal is required, so the tick is diligently looking for a “breadwinner”: it can be either a small forest animal or bird, as well as large animals or livestock. In the process of sucking blood, the mite "shares" the bacterium with the animal, as a result of which it becomes an additional infectious reservoir. It turns out a kind of bacterial circulation: from a tick - to a living being, and - again to a tick. In addition, bacterial cells can spread from the insect to its offspring. [11]

Infection of people occurs in a transmissible way through tick bites. The pathogen enters the human body through the bitten skin and enters the bloodstream, and then into various internal organs, including distant ones, which determines the clinical picture of anaplasmosis.

Anaplasma "infects" granulocytes, especially mature neutrophils. Inside the leukocyte cytosol, whole bacterial colonies of morula are formed. After infection, the pathogen enters the cell, begins to multiply in the cytoplasmic vacuole, and then leaves the cell. The pathological mechanism of the development of the disease is accompanied by damage to splenic macrophages, as well as liver and bone marrow cells, lymph nodes and other structures, within which an inflammatory reaction begins to develop. Against the background of leukocyte damage and the development of an inflammatory process, the body's immune system is suppressed, which not only aggravates the situation, but also contributes to the appearance of a secondary infection of any origin. [12]

Symptoms of the anaplasmosis

With anaplasmosis, you can observe extensive symptoms of varying degrees of severity, which depends on the characteristics of the course of the disease. The first signs appear at the end of the latent incubation period, which lasts from several days to several weeks (more often, about two weeks), if counted from the moment the bacteria entered the human bloodstream. [13]

In mild cases, the clinical picture is similar to the usual ARVI - acute respiratory viral infection. The following symptoms are characteristic:

• a sharp deterioration in health;
• increase in temperature indicators up to 38.5 ° C;
• fever;
• a strong feeling of weakness;
• loss of appetite, dyspepsia;
• pain in the head, muscles, joints;
• sometimes - a feeling of pain and dryness in the throat, coughing, discomfort in the liver.

In moderately severe cases, the severity of the symptoms is more obvious. To the above symptoms are added the following:

• dizziness and other signs of neurology;
• frequent vomiting;
• labored breathing;
• decrease in daily urine output (anuria may develop);
• swelling of soft tissues;
• slowing heartbeat, lowering blood pressure indicators;
• discomfort in the liver.

If the patient suffers from an immune deficiency, then against his background, anaplasmosis is especially difficult. The following symptoms are present:

• persistently elevated temperature, without normalization for several weeks;
• pronounced neurological signs, often with a picture of cerebral lesions (disorders of consciousness - from lethargy to coma), seizures of a generalized nature;
• increased bleeding, the development of internal bleeding (there is blood in the feces and urinary fluid, bloody vomiting);
• heart rhythm disturbances.

Symptoms of peripheral nervous system involvement include brachial plexopathy, cranial nerve palsy, demyelinating polyneuropathy, and bilateral facial nerve palsy. Recovery of neurological function can take several months. [14],  [15], [16]

First signs

Immediately after the expiration of the incubation term, which on average lasts 5-22 days, the first symptoms appear:

• a sudden increase in temperature indicators (febrile temperature);
• headache;
• severe fatigue, weakness;
• various manifestations of dyspepsia: from pain in the abdomen and liver area to severe vomiting;
• decrease in blood pressure indicators, dizziness;
• increased sweating.

Signs such as pain and burning in the throat, coughing, are not found in all patients, but are not excluded. As you can see, the clinical picture is nonspecific and rather resembles any viral respiratory infection, including influenza. Therefore, there is a high probability of misdiagnosis. Anaplasmosis can be suspected if the patient indicates a recent tick bite. [17]

Anaplasmosis in a child

If in adults anaplasmosis is transmitted by a tick bite, then in children there is another way of transmission of the infection - from mother to fetus. The disease is characterized by high fever, pain in the head and muscles, a slow heart rate and a decrease in blood pressure.

The clinical picture with anaplasmosis is most often presented by a moderate and severe form, however, these types of course are characteristic mainly in adult patients. Children suffer from an infectious disease mainly in a mild form. Only in some cases, children develop anicteric hepatitis with increased transaminase activity. Even less often, kidney damage is observed with the development of hypoisostenuria, proteinuria and erythrocyturia, as well as an increase in the level of creatinine and urea in the blood. In isolated cases, the pathology is complicated by infectious toxic shock, acute failure of renal function, acute respiratory distress syndrome, meningoencephalitis. [18]

Treatment of the disease in childhood, as well as in adults, is based on taking Doxycycline. It is generally accepted that this drug is prescribed to children from the age of 12. However, there were cases of earlier treatment with Doxycycline - in particular, from the age of 3-4 years. The dosage is selected individually.

Stages

There are three stages of anaplasmosis development: acute, subclinical and chronic.

The acute stage is characterized by temperature drops to high rates (40-41 ° C), severe emaciation and weakness, shortness of breath like dyspnea, enlarged lymph nodes, the appearance of purulent rhinitis and conjunctivitis, an enlarged spleen. Some patients have hypersensitivity provoked by irritation of the meninges, as well as seizures, muscle twitching, polyarthritis, and cranial nerve palsies. [19]

The acute stage is gradually transformed into subclinical, in which there is anemia, thrombocytopenia, leukopenia (in some cases, leukocytosis). Further, after about 1.5 to 4 months (even in the absence of treatment), either recovery or the next, chronic stage of the disease may occur. It is characterized by anemia, thrombocytopenia, edema, accession of secondary infectious pathologies. [20]

Forms

Depending on the intensity of symptoms, the following types of anaplasmosis are distinguished:

• hidden, asymptomatic (subclinical);
• manifest (explicit).

Taking into account the severity of the infectious disease, a mild, moderate and severe course is distinguished.

In addition, platelet and granulocytic anaplasmosis are distinguished, however, platelet damage is characteristic only in relation to veterinary medicine, since it is found mainly in cats and dogs. [21]

Anaplasma is the causative agent of the disease not only in humans, but also in dogs, cows, horses and other animal species. Tick-borne anaplasmosis in humans can occur almost all over the world, since the carriers of the disease - ticks - live in both European and Asian countries.

Anaplasmosis of cattle and other farm animals is a long-known disease that was first described back in the 18th century: then it was called tick-borne fever, it mainly affected goats, calves and sheep. Granulocytic anaplasmosis was officially confirmed in horses in 1969 and in dogs in 1982. [22] In addition to ticks, horseflies, fly flies, midges, sheep suckers, biting beetles can become carriers of the infection.

Anaplasmosis of sheep and other farm animals is manifested by the following first signs:

• sudden rise in temperature;
• yellowing of mucous tissues due to excess bilirubin in the bloodstream;
• shortness of breath, signs of hypoxia;
• fast heartbeat;
• rapid weight loss;
• loss of appetite;
• apathy, lethargy;
• digestive disorders;
• decrease in milk yield;
• swelling (dewlap and limbs);
• coughing.

Infection in animals is often identified as an eating disorder. So, sick individuals due to impaired metabolism try to taste and chew inedible objects. Failure in metabolism, inhibition of redox processes lead to a violation of hematopoiesis, a drop in the level of hemoglobin in the blood, the development of hypoxia. Intoxication entails the development of inflammatory reactions, edema and hemorrhage are noted. The decisive role in the prognosis of pathology is decided by the correct diagnosis and timely prescription of treatment. [23]

A considerable number of not only domestic, but also wild animals can act as a reservoir for the causative agent of anaplasmosis. At the same time, dogs, cats, and the person himself are random owners that do not play the role of a transmitter of infection to other living beings.

Anaplasmosis in cats is the most rare - only in isolated cases. Animals become easily tired, tend to avoid any activity, mostly rest, practically do not eat. The development of jaundice is often noted.

Anaplasmosis in dogs also does not differ in specific signs. There is depression, fever, enlargement of the liver and spleen, lameness. There are descriptions of cough, vomiting and diarrhea in animals. It is noteworthy that in North America, the pathology has a predominantly mild course, while in European countries, deaths are often noted.

For most animals, the prognosis for anaplasmosis is favorable - subject to timely antibiotic therapy. The blood picture stabilizes within 2 weeks from the start of therapy. Fatalities in dogs and cats have not been reported. A more complex course of pathology is noted with a combined infection, when anaplasma is combined with other pathogens transmitted during a tick bite. [24]

Complications and consequences

If a patient with anaplasmosis does not go to the doctor, or the treatment is initially prescribed incorrectly, then the risk of complications increases significantly. Unfortunately, this happens quite often, and instead of rickettsial infection, the patient is treated with ARVI, flu or acute bronchitis. [25]

It is necessary to understand that complications of an infectious disease can indeed be dangerous, since they often lead to aggravated consequences, and even to the death of the patient. Among the most common complications are the following:

• monoinfection;
• failure of renal activity;
• damage to the central nervous system;
• cardiac insufficiency, myocarditis;
• pulmonary aspergillosis, respiratory failure;
• infectious toxic shock;
• atypical pneumonia;
• coagulopathy, internal bleeding;
• meningoencephalitis.

These are the most common, but not all known consequences that can develop as a result of anaplasmosis. Of course, there are cases of spontaneous cure of the disease, which is typical for people with good and strong immunity. However, if the immune defense is impaired - for example, if a person has recently been ill or is suffering from chronic diseases, or has taken immunosuppressive therapy, or had an operation, then the development of complications in such a patient is more than likely. [26]

The most unfavorable outcome may be the death of the patient as a result of multiple organ failure.

Diagnostics of the anaplasmosis

An important role in the diagnosis of anaplasmosis is played by the collection of epidemiological anamnesis. The doctor needs to pay attention to such moments as tick bites, the patient's stay in an infectious-endemic region, his visits to forests and forest parks over the past month. The received epidemiological information in combination with the existing symptoms help to orient and lead the diagnosis in the right direction. Additional help is provided by changes in the blood picture, however, laboratory research becomes the main diagnostic moment.

The most effective way to diagnose anaplasmosis is direct dark-field microscopy, the essence of which is to visualize embryonic structures - morula - inside neutrophils, during light microscopy of a thin blood smear with Romanovsky-Giemsa stain. The visible morula forms from about the third to the seventh day after the introduction of the bacterium. The relatively simple research method also has a certain drawback, since it shows insufficient efficiency with a low level of anaplasma in the blood. [27]

General clinical studies and, in particular, a general blood test demonstrates leukopenia with a shift of the leukocyte formula to the left, a moderate increase in ESR. Many patients have anemia and pancytopenia.

The general analysis of urine is characterized by hypoisostenuria, hematuria, proteinuria.

Blood biochemistry indicates increased activity of liver function tests (AST, ALT), LDH, increased levels of urea, creatinine and C-reactive protein.

Antibodies to anaplasmosis are determined by the serological test (ELISA). Diagnostics is based on determining the dynamics of titers of specific antibodies to bacterial antigens. Initial IgM antibodies appear from the eleventh day of the disease, reaching a peak amount from 12 to 17 days. Further, their number decreases. IgG antibodies can be detected already on the first day of the infectious process: their concentration gradually increases, and the peak level falls on 37-39 days. [28]

PCR for anaplasmosis is the second most common direct diagnostic method that detects anaplasma DNA. The biomaterial for PCR analysis is blood plasma, leukocyte fraction, cerebrospinal fluid. It is also possible to examine the tick, if any.

Instrumental diagnostics consists in carrying out the following procedures:

• X-ray examination of the lungs (picture of bronchitis or pneumonia, enlarged lymph nodes);
• electrocardiography (picture of impaired conduction);
• ultrasound examination of the abdominal organs (enlarged liver, diffusely altered liver tissue).

Differential diagnosis

Differentiation of various endemic rickettsial diseases is performed taking into account clinical and epidemiological signs. It is important to pay attention to the epidemiological data typical for most of the endemic rickettsioses (a trip to the endemic focus, seasonality, tick attacks, etc.), as well as symptoms such as the absence of primary affect, regional enlargement of lymph nodes, absence of rash.

In some cases, anaplasmosis may resemble mild epidemic typhus and mild Bril's disease. With typhus, neurological symptoms are more pronounced, there is a roseolous-petechial rash, there are symptoms of Chiari-Avtsyn and Govorov-Godelier, tachycardia, Rosenberg's enanthem, etc. [29]

It is important to timely distinguish anaplasmosis from influenza and SARS. With flu, the febrile period is short (3-4 days), the headache is concentrated in the superciliary and temporal regions. There are catarrhal symptoms (coughing, runny nose), there is no enlargement of the liver.

Another disease requiring differentiation is leptospirosis . The pathology is characterized by severe pain in the calf muscles, scleritis, palpitations, neutrophilic leukocytosis. The severe course of leptospirosis is characterized by yellowness of the sclera and skin, meningeal syndrome, cerebrospinal fluid changes like serous meningitis. The diagnosis is established by the determination of leptospira in the bloodstream and urinary fluid, as well as a positive reaction of agglutination and lysis.

For dengue is characterized by two-wave curve of temperature, severe joint pain, typical changes of gait, the original tachycardia. With the second wave, an itchy rash appears, followed by scaling. Diagnostics is based on virus isolation.

Brucellosis is characterized by wave-like fever, profuse sweating, migrating arthralgias and myalgias, micropolyadenitis with further damage to the musculoskeletal system, nervous and genitourinary apparatus. [30]

Ehrlichiosis and anaplasmosis are two rickettsial infections that have many similarities in the clinical course. Diseases often begin acutely, like an acute viral infection. There are such nonspecific signs as a strong increase in temperature indicators with chills, weakness, muscle pain, nausea and vomiting, coughing, pain in the head. But rashes on the skin for anaplasmosis are uncharacteristic, in contrast to ehrlichiosis, in which papular or petechial elements are found in the region of the limbs and trunk.

Both anaplasmosis and ehrlichiosis can be complicated by disseminated intravascular coagulation , multiple organ deficiency, convulsive syndrome, and the development of a coma. Both diseases are infections with a complex course associated with an increased risk of death in people with immunodeficiency. The development of the infectious process is especially dangerous in patients who have previously taken immunosuppressive treatment, have undergone surgery to remove the spleen, or in HIV-infected patients.

The main differential role in the diagnosis of anaplasmosis or ehrlichiosis is played by serological tests and PCR. Cytoplasmic inclusions are found in monocytes (with ehrlichiosis) or in granulocytes (with anaplasmosis).

Borreliosis and anaplasmosis have a general endemic prevalence, develop after a tick bite, but the clinical picture of these infections is different. With borreliosis at the site of the bite, there is a local skin inflammatory reaction called erythema tick-borne migrans, although a non-erythema course of the disease is also possible. With the spread of borrelia throughout the body, the musculoskeletal system, the nervous and cardiovascular systems, and the skin are affected. Lameness, lethargy, and cardiac dysfunctions are characteristic. About six months after infection, severe articular lesions occur, and the nervous system suffers. Diagnostics is reduced to the use of ELISA, PCR and immunoblotting methods. [31]

Treatment of the anaplasmosis

The main treatment for anaplasmosis is antibiotic therapy. The bacterium is sensitive to antibacterial drugs of the tetracycline series, so the choice often falls on Doxycycline, which patients take orally 100 mg twice a day. Duration of admission is from 10 days to three weeks. [32]

In addition to tetracycline drugs, anaplasma is also sensitive to amphenicol, in particular to Levomycetin. But the use of this antibiotic by specialists is not welcomed, which is associated with pronounced side effects of the drug: during treatment, patients develop granulocytopenia, leukopenia, thrombocytopenia. [33]

For female patients during pregnancy and lactation, the appointment of Amoxicillin or protected penicillins in individual dosages is indicated.

If antibiotics are prescribed within three days after tick suction, then a shortened course of therapy is carried out - within a week. With a later visit to the doctor, the full therapy regimen is practiced.

Additionally, symptomatic therapy is carried out, during which the following groups of drugs can be prescribed:

• non-steroidal anti-inflammatory drugs;
• hepatoprotectors;
• multivitamins;
• antipyretic drugs;
• pain relievers;
• medicines for the correction of concomitant disorders of the respiratory, cardiovascular, nervous system.

The clinical effectiveness of the therapy is assessed by its results: a decrease in the severity and disappearance of symptoms, normalizing the dynamics of disorders in laboratory and instrumental studies, a change in the titers of specific antibodies to anaplasma are considered positive signs. If necessary, drugs are replaced and a second course of treatment is prescribed.

Medicines

Most often, the following treatment regimen is used for anaplasmosis:

• Doxycycline, or its soluble analogue Unidox solutab - 100 mg twice a day;
• Amoxicillin (according to indications, or if it is impossible to use Doxycycline) - 500 mg three times a day;
• in severe anaplasmosis, the optimal drug is Ceftriaxone in the amount of 2 g intravenously 1 time per day.

Penicillin drugs, II-III generation cephalosporins, macrolides can also be considered as alternative antibiotics.

Since the use of antibiotics for anaplasmosis is usually long-term, the consequences of such therapy can be very different: most often side effects are expressed in digestive disorders, skin rashes. After the completion of the treatment course, a set of measures is necessarily prescribed to eliminate such consequences and restore the adequate functioning of the digestive system.

The most common consequence of antibiotic therapy is intestinal dysbiosis, which develops as a result of the inhibitory effect of antibacterial drugs, both on pathogens and on the natural microflora in the body. To restore such microflora, the doctor prescribes probiotics, eubiotics.

In addition to dysbiosis, prolonged antibiotic therapy can contribute to the development of fungal infections. For example, candidiasis of the oral cavity and vagina often develop.

Another possible side effect is allergies, which can be limited (rash, rhinitis) or complex (anaphylactic shock, Quincke's edema). Such conditions require urgent cancellation (replacement) of the drug and emergency antiallergic measures, using antihistamines and glucocorticoid drugs.

Along with antibiotic therapy, symptomatic drugs are prescribed. So, at elevated temperatures, severe intoxication, detoxification solutions are used, with edema - dehydration, with neuritis, arthritis and joint pain - nonsteroidal anti-inflammatory drugs and physiotherapy. Patients with a picture of damage to the cardiovascular system are prescribed Asparkam or Panangin 500 mg three times a day, Riboxin 200 mg 4 times a day.

If an immunodeficiency state is detected, Timalin is shown at 10-30 mg daily for two weeks. For patients with autoimmune manifestations - for example, with recurrent arthritis - it is recommended to take Delagil 250 mg daily in combination with non-steroidal anti-inflammatory drugs.

Vitamin therapy involves the use of preparations containing vitamins C and E.

Additionally, the treatment regimen includes vascular agents (Nicotinic acid, Complamin). To facilitate the ingress of antibacterial drugs into the central nervous system, patients are injected with Euphyllin, a glucose solution, as well as drugs to optimize cerebral circulation and nootropics (Piracetam, Cinnarizin).

In the chronic course of the disease, immunocorrective treatment is indicated.

Prevention

The carriers of anaplasmosis live on the ground, but they can climb high grass and shrubs up to 0.7 m high and wait for a potential carrier there. A tick attack is practically not felt by a person, therefore, people often do not pay attention to the bite.

As a preventive measure, it is recommended to wear clothing that can protect against insect attacks, and, if necessary, use special repellents. After each walk (especially in the forest), the whole body should be checked: if a tick is found, it must be removed immediately. The removal procedure is carried out using tweezers or pointed forceps, grabbing the arthropod as close as possible to the area of contact with the skin surface. It must be pulled out very carefully, with loosening and twisting movements, trying to prevent parts of the tick's body from coming off and remaining in the wound. To prevent infection, at the end of the procedure, it is important to treat the bitten area with an antiseptic.

After any, even a short stay in the forest belt, it is necessary to check the skin, and not only in visible places: it is imperative to check the skin folds, since insects often tend to areas with high moisture on the body - for example, in the armpits and groin, under the milk glands, on the bends of the arms and legs. In children, among other things, it is important to carefully examine the head and neck, behind the ear. [34]

Before entering the apartment, it is advisable to also inspect things and clothes, because insects can be brought even in a bag or on shoes.

To prevent infection with anaplasmosis, it is recommended:

• avoid walking in places where blood-sucking insects can live;
• have an idea of the correct removal of ticks and the first signs of anaplasmosis infection;
• if necessary, be sure to use insect repellents;
• for forest and park walks, wear appropriate clothing (with long sleeves, covered with ankles and feet).

Forecast

For the vast majority of patients with anaplasmosis, the prognosis is assessed as positive. As a rule, about 50% of patients need inpatient treatment. In some infected people, the disease heals on its own, but some painful symptoms disappear only after a while - within a few months.

A worsening prognosis is observed with the development of hematological and neurological complications, which is typical for patients with immunodeficiency states, chronic liver and kidney diseases. Mortality is relatively low. [35]

In general, the course and outcome of the pathology depend on the correct diagnosis, timely prescription of antibacterial and symptomatic drugs. In moderate and severe cases, patients are placed in an infectious hospital. It is important for the patient to ensure peace, good hygiene and nutrition. During the period of increasing temperature and fever, the diet of a sick person should be extremely gentle, both mechanically and chemically and thermally, with minimization of products that cause fermentation and putrefaction in the intestine. At the same time, meals should be high in calories. Bed rest should be observed until the temperature returns to normal, plus a few more days. It is important to use effective etiotropic drugs that increase the specific and nonspecific reactivity of the body.

If the patient began to be treated with a delay, or were treated incorrectly, then the disease can acquire a chronic course. Persons who have undergone anaplasmosis are subject to medical observation of the dynamics for 12 months. Observation involves regular examination by an infectious disease specialist, a therapist, and, if necessary, a neurologist. [36]

Cattle that have undergone anaplasmosis become temporarily immune to infection. But this immunity does not last long: about four months. If a pregnant female has suffered the disease, then her offspring will have a longer immunity to infection due to the presence of antibodies in the blood. If infection of the offspring does occur, then the disease will be characterized by a milder course.