Granulocytic anaplasmosis is an infectious disease with a transmissible transmission pathway. The main symptoms are prolonged fever with pronounced general intoxication manifestations. Disorders of the gastrointestinal tract, cough, myalgia and skin rashes are much less common. Diagnosis of anaplasmosis is carried out by PCR and dark-field microscopy of stained blood smears to identify the pathogen, with the help of ELISA, antibodies are determined. Treatment includes etiotropic antibacterial drugs, pathogenetic, symptomatic agents.
A79.9 Rickettsiosis, unspecified
Human granulocytic anaplasmosis is a disease transmitted by ticks. Anaplasmas were discovered by the English veterinarian Tayler in 1910, the disease was first described by the doctor Bakken in 1991 (USA). The infection is common in the UK, Sweden, USA, Canada. More often affected are men over 45 years of age, residents of rural areas, suburbs. The seasonality of the disease – summer-autumn with peaks in June, July and November, has a connection with the activity of vectors.
The causative agent of the disease is the bacterium Anaplasma, species A. phagocytophilum, A. marginale. The source and reservoir of infection are white-footed mice, roe deer, forest rats, cattle. Carriers of granulocytic anaplasmosis are ixodes mites, mainly of the species I. scapularis, I. pacificus, I. ricinus, I. persulcatus.
The main risk factors are old age, taking immunosuppressants, diabetes mellitus, collagenosis, HIV infection, symptoms of drug, oncogenic immune deficiency. Of interest for modern clinical infectology is the studied possibility of the connection of the severe course of granulocytic anaplasmosis with mutations of genes specifically affecting the exocytosis of cytotoxic effector molecules during macrophage activation.
After suction of the carrier, the pathogen with saliva enters the thickness of the skin. Anaplasmas are able to penetrate mature neutrophils. Colonies (morules) are formed inside the cytosol. Infected leukocytes activate the secretion of chemokines that attract lymphocytes and macrophages to reproduction. These immune cells further produce pro-inflammatory gamma interferons, thereby enhancing the inflammatory component of the body’s response.
With the blood flow, anaplasmas are transferred to the spleen, liver, lymph nodes and bone marrow, where hematopoiesis is disrupted due to induced chemokines, which are strong inhibitors of stem cell proliferation. Monocytes and natural T-killers responsible for the regulation of activated macrophages become dysfunctional, which leads to pronounced inflammatory damage in tissues due to increased secretion of IFN-γ, IL-12, IL-1β and IL-10.
The incubation period is 14 days, can be shortened to 3 days or lengthened to 3 weeks. The onset of granulocytic anaplasmosis is acute, with symptoms of general intoxication: weakness, fatigue, moderate headaches. Fever is characterized by duration, tremendous chills, reaches 38.5 ° C or more. Nausea, abdominal discomfort, a feeling of pressure and swelling in the right hypochondrium, vomiting and stool disorders may occur.
Some patients complain of muscle and joint pain, dry cough (19%), sore throat, nasal congestion. Much less often there are such dangerous symptoms as disturbances of consciousness, hallucinations, delirium, paralysis, photophobia, gingival and nasal bleeding, the appearance of blood in urine and feces, a feeling of lack of air, fainting when getting up abruptly. If these signs appear, an urgent consultation with a doctor is necessary.
Complications of granulocytic anaplasmosis are considered rare conditions, more characteristic of patients with a burdened premorbid background. The most common symptoms are toxic shock, sepsis, acute respiratory failure, pneumonia (1%), myocarditis, rhabdomyolysis and neurological disorders (about 1%) – demyelinating polyneuritis, meningoencephalitis.
Cases of such complications of granulocytic anaplasmosis as arrhythmias, respiratory distress syndrome of adults, intestinal and gastric bleeding, hemophagocytic lymphohistiocytosis are described. Against the background of weakened immunity in the presence of anaplasmas, symptoms of pulmonary aspergillosis, disseminated candidiasis, cryptococcosis, necrotizing herpetic pharyngitis may manifest.
Verification of the diagnosis and the appointment of treatment are carried out by an infectious disease specialist. Other medical specialists are involved according to indications. It is important to carefully collect an epidemiological history with clarification of being in an endemic region, the fact and duration of tick suction, and taking preventive medications. The basic clinical, laboratory and instrumental signs of human granulocytic anaplasmosis are:
- Physical data. An objective examination reveals lymphadenopathy, hyperemia of the pharynx, sometimes single wheezing in the lungs during auscultation, rumbling, diffuse abdominal pain, moderate hepatomegaly, less often splenomegaly. A rash on the body occurs in less than 10% of cases, spotty-papular. Meningeal symptoms are necessarily investigated.
- Laboratory tests. In general clinical blood test – leukopenia, neutropenia, lymphopenia, thrombocytopenia, anemia, acceleration of ESR, in severe cases pancytopenia. The activity of ALT, AST, urea, CRP, LDH, creatinine increases. In the general analysis of urine – proteinuria, erythrocyturia. In the cerebrospinal fluid – lymphocytic pleocytosis, an increase in protein content.
- Identification of infectious agents. Dark-field microscopy of thin blood smears makes it possible to detect morules (vacuoles with anaplasmas) in the first week of the disease; the method is uninformative. The appointment of PCR is recommended before the start of etiotropic treatment. ELISA becomes diagnostically significant, starting from the second week of the disease, is performed twice with an interval of 2-3 weeks.
- Instrumental methods. During chest radiography, enlarged lymph nodes of the lung roots, infiltrates, and an increase in the pulmonary pattern are visualized. During ultrasound examination, the symptoms of enlargement of the liver and spleen are determined. Transient myocardial conduction disturbances, bradycardia are noted on the ECG.
Differential diagnosis is carried out with human monocytic ehrlichiosis and pyroplasmosis (laboratory verification is needed). With ku fever, there is a lesion of the respiratory tract, jaundice, muscle pain, hemorrhagic component is characteristic of leptospirosis, the Rocky Mountain spotted fever clinic includes a profuse rash with a hemorrhagic component, involvement of the central nervous system. Ixodic tick-borne borreliosis is manifested by erythema, a lesion of the musculoskeletal system.
Empirical therapy is prescribed to feverish patients, upon the fact of sucking a tick for more than 4-24 hours without taking chemoprophylaxis. In the presence of symptoms of granulocytic anaplasmosis, treatment is carried out on an outpatient basis with a mild and moderate course of infection, the absence of a burdened premorbid background. Hospitalization is required in 30% of cases of the disease, more often – pregnant women, young children. Bed rest is observed for up to 2-3 days without fever.
The complicated course of the disease in 3% of cases is an indication for staying in the intensive care unit, sometimes artificial ventilation. Dietary recommendations include a gentle fortified diet, the exclusion of animal fats, sugar, spices, marinades, alcohol and coffee. In the absence of contraindications, it is recommended to take an increased amount of boiled water, oral polyionic solutions.
Standards for the medical management of granulocytic anaplasmosis have not been developed. The average duration of therapy is about 6-14 days. In patients without complications, normalization of body temperature is noted after about four days, laboratory parameters usually stabilize within a week. Most often , the treatment of infectious pathology is carried out with the following drugs:
- Etiotropic. Anaplasmas are sensitive to tetracycline, doxycycline, rifampicin, chloramphenicol. The latter should be used with caution due to the risk of additional inhibition of hematopoiesis, it is considered ineffective. Clinical improvement is assessed after 48 hours of antibacterial monotherapy; it is necessary to remember about co-infection with other tick-borne diseases.
- Pathogenetic. Detoxification is carried out by infusion methods using glucose-salt, succinate-containing solutions, chlosol, acesol. NSAIDs are prescribed to reduce body temperature, pain relief and relief of symptoms of inflammation; acetylsalicylic acid and analogues are used with caution. Sometimes a transfusion of platelets, erythrocyte mass is required.
- Symptomatic. In case of catarrhal manifestations, local anti-inflammatory treatment, antitussive medications are recommended. To relieve the symptoms of dyspepsia, patients receive enzymes, antispasmodics, antiemetics, sorbing agents. Damage to the nervous system may require the appointment of glucocorticosteroids, anticholinesterase drugs, lipoic acid.
People with HIV infection can tolerate granulocytic anaplasmosis in both asymptomatic and generalized forms, more often in the form of pneumonia, DIC syndrome or symptoms of manifestation of opportunistic infections. If this tick-borne nosology is suspected, it is necessary to immediately start taking etiotropic drugs for 2 or more weeks. Tetracycline preparations are contraindicated for children under 8 years of age and pregnant women.
The available in vitro data indicate the ineffectiveness of the treatment of human granulocytic anaplasmosis with such antibacterial pharmaceuticals as penicillins, cephalosporins, macrolides and aminoglycosides – there are very few results of evaluating the effectiveness of drugs in the body, and they are inconclusive. However, there are few reports of efficacy against anaplasmas of fluoroquinolones (levofloxacin, ofloxacin).
Prognosis and prevention
The prognosis is favorable for cases of timely detection of symptoms and treatment. The duration of the fever period may be more than 3 weeks. Mortality in granulocytic anaplasmosis reaches 0.2-1%; predictors are old age, high creatinine levels, AST, LDH, symptoms of various disorders of consciousness, systemic inflammatory response.
There are no specific vaccine preparations for the prevention of infection. Non–specific measures – acaricidal treatment of fields, parks, rural areas, suburban settlements and cemeteries, appropriate equipment for being in endemic zones. It is necessary to use repellents, seek medical help in a timely manner in case of tick suction, and receive timely full-fledged antibacterial prophylaxis.