RU2519143C1 - Method for prevention of ixodic tick-borne borreliosis in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method for prevention of ixodic tick-borne borreliosis in children by an antibacterial therapy consists in the fact that after establishing the fact of Borrelia infected tick suction, ceftriaxone 50 mg/kg a day is injected intramuscularly for 3 days in a combination with a single intramuscular injection of bicillin 5 in a dose of 50 thousand IU/kg; anaferone is also prescribed in a dose of 1 tablet 3 times a day for 30 days.

EFFECT: method provides efficacy and safety that promotes reducing the incidence of ixodic borreliosis.

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Description

This invention relates to medicine, more specifically to infectology, and is intended to prevent the development of tick-borne tick-borne borreliosis in children.

Tick-borne tick-borne borreliosis (IKB) belongs to the group of infectious transmissible natural focal diseases caused by Borrelia of the Boreelia burgdorferi sensu lato group and transmitted by ixodid ticks. Tick-borne tick-borne borreliosis (IKB) or Lyme disease (BL) is the most common tick-borne vector-borne disease and is present almost everywhere in the world. In Russia, spontaneous infection of ixodid ticks with borrelia can reach 70-90%. Currently, in the Russian Federation IKB is registered in 68 subjects. The incidence of this infection tends to increase annually. So, in 2010, 7063 cases were registered in the Russian Federation, the incidence rate per 100 thousand population was 4.98. In 2011, the incidence increased by 41%, the incidence rate was 7.02 per 100 thousand of the population. The territory of the North-West region, including St. Petersburg, is endemic according to the ICD, where the incidence is 2-4 times higher than the all-Russian indicators, including among children. So, in 2011, the incidence rate of ICD among children under 14 years old in St. Petersburg doubled compared to 2010 and amounted to 10.78 per 100 thousand of the population.

IKB is distinguished by polymorphism of the clinical picture, staged development of the disease. In most cases, the disease is acute. The most common clinical manifestation of the acute period of ICD is erythema migrans (up to 90%), followed by neuroborreliosis (15-48%), arthritis (12-33%), anicteric hepatitis (15-27%), carditis (0.3- 10%), ophthalmoborreliosis (up to 10%). In some cases, the disease takes a chronic course, which is also characterized by damage to organs that are tropic for Borrelia: skin (benign lymphocytoma, chronic atrophic acrodermatitis, scleroderma), the nervous system (disseminated encephalomyelitis, cerebral infarction, chronic polyneuroradiculopathy, encephalopathy with psychopathic disorders) apparatus (chronic arthritis, fibromyalgia), heart (pancreatitis).

The acute period of the disease proceeds, as a rule, favorably and in most cases ends with recovery. However, Lyme disease is characterized by a high frequency of chronicity. The chronic stage of the disease poses the greatest danger to the patient’s life, is characterized by low treatment efficacy, recurrent course, progressive inflammatory process in the skin, joints, nervous system, less often in other organs, leading to atrophic and degenerative changes in the affected tissues, which can lead to further disability of patients, as well as death. Follow-up observation of children who have undergone ICD has shown that chronic infection can occur after a course of etiotropic antibiotic therapy in 33% of cases.

Specific immunoprophylaxis of BL does not currently exist. Currently, if there are sufficient prerequisites for the infection, the use of antibiotics is usually considered. Specific prophylaxis of Lyme disease has not yet been developed. Most sources of information reflect the treatment of ICD, while the prevention of ICD in children is practically unknown.

The use of antibacterial drugs in adult patients is known after suction of ixodid ticks in which Borrelia were detected, and tick-borne encephalitis virus was absent. Antibiotics of the penicillin (retarpen, amoxiclav) and tetracycline (doxycycline) groups according to the schemes were prescribed as treatment and partially preventive. Retarpen was injected intramuscularly once at a dose of 2.4 million ME at a time (1.2 million units in each buttock) after staging a test for penicillin tolerance by a standard technique. Doxycycline was prescribed in capsules of 0.1 g 2 times a day by mouth after meals for 10 days. Amoxiclav was used in tablets of 0.375 g 4 times a day by mouth for 5 days. [Krumgolts V.F. Etiotropic therapy and emergency antibiotic prophylaxis of tick-borne tick-borne borreliosis: author. dis ... candidate of medical sciences / V.F.Krumgolts. -SPb .: VMEDA, 1999. - 27]. The disadvantage of this method of prevention is the standard dosage of drugs, regardless of the age of the patient. Given the duration of the use of antibiotics, this method can be considered as a method of treatment of ICD and only in adults.

There is also known a method for the treatment and partial prevention of ICD in adults affected by attacks of ticks infected with borrelia, according to an epidemiological study. In case of detection of borrelia in a tick, the authors prescribed a short-term course of antibiotics according to the following schemes: bicillin “3” or retarpen intramuscularly once at a dose of 1.2 and 2.4 million units, respectively, once intramuscularly, and with penicillin intolerance - doxycycline 0.1 g each 2 times a day for 3 days [Kozlov S.S. Lyme borreliosis in the North-West region of Russia: author. Dis ... Dr. med.science / S.S. Kozlov. - SPb .: VMEDA, 1999. - 39 p.]. According to the author, in persons who were attacked by tick-borrelia ticks but did not receive antibiotics, the incidence rate was 14.8%, while in the group of people taking antibiotics it did not exceed 2.2%. However, as before, the prescription of drugs was carried out mainly in the treatment of ICD and without taking into account age-related aspects. A clear way to prevent ICD in this source is not presented.

A known method for the treatment and prevention of ICD has been proposed for children and adults affected by attacks of ticks infected with borrelia. This method of prevention included the appointment of Suprax (cefixime) in a dose of 8 mg / kg per day for children from 6 months to 12 years old, and for children over 12 years old and adults 400 mg once a day. The course of chemoprophylaxis was 5 days. [Tick-borne tick-borne borreliosis (ecology, epidemiology, clinic, diagnosis, treatment and prevention): guidelines for doctors / Yu.V. Lobzin, A.N. Uskov, Yu.D. Yushchuk [et al.]. - M., 2007. -46 p.] The disadvantage of this method of prevention can be considered the lack of use of another alternative antibiotic, especially taking into account the possibility of intolerance to the drug or its components, especially in children.

Closest to the proposed method is a method of using parenteral cephalosporins as monotherapy or in combination with prolonged penicillins. The authors suggest that no later than the 5th day after the suction of the tick infected with borrelia, III generation cephalosporins (ceftriaxone) are prescribed at a dose of 20-80 mg / kg per day in 2 intramuscular injections for 3 days. When carrying out prophylaxis later than 5 days after the suction of the ixodic tick, the three-day course of cephalosporins is supplemented by a single administration of retarpen of 2.4 million ME (for children - 50 thousand IU / kg). [Tick-borne tick-borne borreliosis in children and adults: guidelines for doctors / Yu.V. Lobzin [et al.].-SPb, 2010.-64 p.] The disadvantage of this method is the appointment of cephalosporins as monotherapy with a short course for 3 days in the first 5 days from the time of the tick attack. Since it is known that the risk of transmission of B.burgdorferi s.l. from Ixodes ticks to humans (Ixodes scapularis ticks) reaches 25% after 72 hours after sucking the tick. Therefore, at least a quarter of affected people may develop a disease - tick-borne borreliosis. Given the features of BL in the form of a late humoral (antibody) response and the absence of Borrelia in the patient’s blood in the early stages of the disease, laboratory diagnosis of this infection in the incubation period is ineffective using standard research methods, including molecular genetic (PCR - polymerase chain reaction) and serological (ELISA - enzyme-linked immunosorbent assay) methods. Thus, in the absence of the development of clinical symptoms of the disease and laboratory confirmation of infection, the diagnosis of ixodic tick-borne borreliosis in the early stages of the disease is impossible, especially with the development of the non-erythema form of ICD. Thus, the use of ceftriaxone in a short course at low doses (<30 mg / kg per day) as monotherapy after suctioning the tick, especially after 3 days, is insufficient to prevent the disease or further development of the infectious process due to the rapid removal of the drug from the body ( the elimination half-life of ceftriaxone is 5.8–8.7 hours). An additional administration of retarpen in a therapeutic dose (50 thousand units / kg / day) after a course of ceftriaxone is able to ensure the prolongation of the antibacterial effect only for 3 weeks, which corresponds to the average incubation period of Lyme disease.

In order to eliminate these shortcomings of the previously described schemes, the authors offer a fundamentally new method of complex chemoprophylaxis of UTI in children, taking into account regional epidemiological features.

The technical result of the present invention is to prevent the development of ICD disease in children affected by tick attacks, and, as a result, reduce the incidence of ICD, disability of patients.

This is achieved by the fact that in the method of preventing ixodic tick-borne borreliosis in children, by conducting antibacterial therapy with ceftriaxone, characterized in that from the first day from the moment of suction of the tick infected with borrelia, bicillin “5” is administered intramuscularly at a dose of 50 thousand IU / kg, Anaferon is prescribed 1 tablet 3 times a day for 30 days.

2. The method according to claim 1, characterized in that ceftriaxone is administered at a dose of 30-50 mg / kg per day parenterally intramuscularly for 3 days.

Fundamentally new is the fact that the authors found and proved the feasibility and effectiveness of the simultaneous sequential use of antibacterial drugs in combination with an immunomodulating drug as a complex chemoprophylaxis of ICD. The authors established the dose, duration and sequence of the combined use of drugs taking into account children's characteristics.

The authors established the need for comprehensive chemoprophylaxis of BL from the first day of establishing the fact of suctioning a tick infected with borrelia. The authors recommend that in the incubation period, without waiting for the first symptoms of the disease, to appoint III generation cephalosporins, namely ceftriaxone. 3rd generation cephalosporins are the drugs of choice for Borrelia burgdorferi sensu lato. Ceftriaxone, as a representative of this group of antibiotics, is most preferable, according to the authors, since it has 100% bioavailability, is rapidly absorbed from the injection site and reaches high concentrations in the blood serum. Moreover, the short courses of ceftriaxone are comparable in effectiveness with long courses. Ceftriaxone is administered parenterally, which is especially important when used in childhood, as in this way the authors of the proposal proved the fact of ensuring accurate targeted delivery of the drug in the required dosage. Ceftriaxone is administered once a day, which is preferred for the prophylactic course and is convenient for use in children.

The sequential administration of (for the first time) prolonged penicillin - bicillin “5” (benzylpenicillin + benzathine benzylpenicillin) in the scheme developed by the authors is new, since this drug was not previously used to prevent the development of borreliosis and was not used in such a complex. We have proved the necessity of using this drug for the additional prolongation of antibacterial chemoprophylaxis due to the long incubation period of the ICD, as well as the possibility of the initial latent persistence of borrelia in the human body. Bicillin "5" belongs to the group of natural penicillins and is a highly active drug against spirochetes, including Borrelia burgdorferi sensu lato. In combination with another bactericidal antibiotic of the cephalosporin group (ceftriaxone), bicillin "5" has a synergistic antibacterial effect on spirochetes of the genus Borrelia. Prolonged penicillins do not create high concentrations in the blood and, therefore, should not be used as a starting prevention of borreliosis infection. The authors proved that bicillin "5" can be used as a support agent, the action of which is aimed at preventing the development of the disease throughout the incubation period of ICD. The optimal antimicrobial effect of Bicillin “5” was proved experimentally, namely for 30 days, which corresponds to the duration of the incubation period of Lyme disease.

The authors first obtained the best result when using anaferon in combination with antibiotics. The authors showed that the effect of anaferon is aimed at stimulating the type 1 T-cell immune response during the initial contact of the human body with borrelia, which ensures the synthesis of early endogenous interferons - α, β, γ. Subsequently, anaferon modulates the cellular immune response, switching it from the 1st to the 2nd type, which is very important in this method, since it promotes the irradiation of Borrelia from the host and thus prevents the development of infection. This fact is not obvious, was not found by us in the previously described analogues and prototype.

The authors proved that this combination and the sequence of the complex chemoprophylaxis with the used dosages provide the effect that leads to the prevention of the disease in children with a high risk of developing ICD, namely, those affected by sucking ticks infected with borrelia. In the literature available to us, there are no such methods for the prevention of tick-borne tick-borne borreliosis in children attacked by infected ticks.

Thus, the claimed method, in the opinion of the authors, can claim non-obviousness, novelty, efficiency and inventive step.

This method is as follows. When ascertaining the fact of suctioning a tick infected with borrelia, as well as tick-borne endemic regions when it is impossible to test a tick, parenteral administration of ceftriaxone at a dose of 50 mg / kg per day for 3 days, followed by a single administration of bicillin “5” at a dose of 50 thousand .ed / kg. Simultaneously with the use of an antibiotic from the first day, anaferon is prescribed for children in a dose of 1 tablet. 3 times a day for 30 days.

The method developed by the authors for the prevention of tick-borne tick-borne borreliosis in children has passed clinical trials. In order to carry out emergency chemoprophylaxis of ICD, a clinical follow-up observation was conducted for 105 children admitted to the department of neuroinfection and organic pathology of the nervous system in the early stages of sucking a tick infected with borrelia. All children were assigned prevention of ICD according to various schemes.

The first group consisted of patients taking cefixime (suprax) at a dose of 8 mg / kg per day in 1 ingestion for 5 days. The second group included patients taking azithromycin (sumamed) at a dose of 10 mg / kg per day in 1 ingestion for 3 days. The third group of patients took amoxicillin / clavulanate (augmentin, amoxiclav) at a dose of 20 mg / kg per day in 3 divided doses for 5 days. The fourth group included children who received a course of ceftriaxone at a dose of 50 mg / kg per day intramuscularly for 3 days, after which bicillin “5” was administered once to all patients at a dose of 50 thousand units / kg intramuscularly, and all patients received anaferon inside children from the first day of prevention for 30 days. The timing of the onset of chemoprophylaxis ranged from 1 to 6 days from the moment of establishing the fact of suction of the tick infected with borrelia. Upon admission to chemoprophylaxis, all children underwent a comprehensive clinical and laboratory diagnosis of BL, including an examination by an infectious disease specialist, a blood test using the molecular genetic method (polymerase chain reaction) aimed at detecting B.burgdorferi sl DNA, and the immunological serological method enzyme analysis), which allows to determine antibodies of classes M and G to Borrelia. In all patients, the data of molecular genetic and serological examination for tick-borne borreliosis were negative. Subsequently, follow-up monitoring of patients was carried out during the year, including clinical and laboratory monitoring at maternal times. All children were monitored for antibodies to borrelia by ELISA with the determination of immunoglobulins of classes M and G in the blood 1, 3, 6 months after a course of chemoprophylaxis.

According to the study, it was found that in 40% of children in the first group, chemoprophylaxis of IKB with cefixime was ineffective: 10 people developed the erythema form of Lyme borreliosis, 2 patients were diagnosed with an erythema form of borreliosis. The diagnosis was confirmed clinically and laboratory based on the detection of IgM for blood borrelia 1 month after the course of cefixime. In the second group, the disease developed in 33% of cases: 5 people were clinically diagnosed with migratory erythema after a course of azithromycin. Among the patients of the third group receiving amokiscillin / clavulanate, only 3 patients showed an erythema form of the disease, which accounted for 15% of cases. The patients who made up the fourth group who received complex chemoprophylaxis of ICD using ceftriaxone, bicillin 5 and anaferon did not develop the disease.

All children who developed a clinic of ixodic tick-borne borreliosis after conducting a course of chemoprophylaxis were hospitalized in the Department of Neuroinfection NIIDI, where they received a course of etiotropic and pathogenetic therapy of IKB lasting 10 to 28 days.

According to the study, it was found that the method of complex chemoprophylaxis of ICD in children, proposed by the authors, is the most effective.

The proposed method for the prevention of tick-borne tick-borne borreliosis in children can be confirmed by the following specific examples.

Example 1. Mikhail A., 4 years old, weight = 14 kg, medical history No. 1676. Suction of a tick in the scalp 05/14/12 in the Vyborg district of the Leningrad region. The tick was removed on the second day. Borrelia was found in a removed tick. He entered the day hospital of the Department of Neuroinfection 05/17/2012 for the prevention of infectious diseases. He received ceftriaxone 700 mg once a day, intramuscularly for 3 days. On the fourth day, bicillin “5” was administered intramuscularly at a dose of 700 thousand units. From the first day I took anaferon for children, 1 tab. 3 times a day for 30 days. The child did not get sick with tick-borne tick-borne borreliosis.

Example 2. Artyom A., 5 years old, weight = 20 kg, medical history No. 2262. Suction tick on 05.21.2012 in the parietal region of the head occurred in the village of Tosno, Leningrad region. The tick was removed on the fourth day and submitted for research, according to which the infection of the tick with borrelia was confirmed. In this regard, I asked for help at the NIIDI 04/28/2012. For prophylactic purposes, he received ceftriaxone at a dose of 1 g per day intramuscularly for 3 days, after which bicillin "5" was administered intramuscularly at a dose of 1 million units. From the first day of admission to NIIDI, anaferon was prescribed for children, 1 tab. 3 times a day for 30 days. The patient did not get sick with tick-borne tick-borne borreliosis.

Example 3. Igor P., 4 years old, weight = 14 kg, medical history No. 1584. He entered a day hospital in the Department of Neuroinfection NIIDI 05/12/2012 in connection with the suction of a tick in the behind-the-ear area 05/08/2012. The tick was removed on 05/09/2012 and submitted to the laboratory for research. The tick was infected with borrelia. From 05/12/12 received ceftriaxone at 700 mg once a day intramuscularly for 3 days, then bicillin “5” was prescribed once intramuscularly at a dose of 700 thousand units. From 05/12/2012 to 06/10/12 took anaferon for children, 1 tab. 3 times a day. The child did not get sick with tick-borne tick-borne borreliosis.

Tick-borne infections (Ixodes tick-borne borreliosis and tick-borne encephalitis) were excluded for all children by molecular genetic method (PCR), aimed at determining tick-borne encephalitis virus RNA and Borrelia DNA, and serological method (ELISA), aimed at determining IgM and IgG to the virus tick-borne encephalitis and borrelia. Clinical and laboratory monitoring was carried out for all patients in the follow-up, including an examination by an infectious disease doctor, as well as a re-determination of IgM and IgG for Borrelia at maternal intervals after 1, 3, 6 months.

According to the proposed method, 50 children who suffered from sucking ticks infected with Borrelia got prophylaxis. The result was the absence of the disease in all children, and the drugs used by the children were well tolerated, no adverse reactions were noted.

To compare the effectiveness of the scheme developed by the authors with other previously described methods for preventing ICD, we present clinical examples.

Example 1. Patient Lyuba G., 9 years old, medical history No. 28446. I was treated at the Department of Neuroinfections and Organic Pathology of the Nervous System of NIIDI from 05/11/2011 to 05/23/2011 with a diagnosis of tick-borne tick-borne borreliosis, erythema form, moderate course. From the anamnesis: 05/02/2011, the suction of a tick in the forest-park zone of the village of Vyritsa, Leningrad Region, in the right auricle. The tick was removed on the same day in Vyritska Central District Hospital and submitted for research. Borrelia was found in the tick. In connection with this, a polyclinic doctor was prescribed suprax in a dose of 200 mg per day from 05/03/2011 to 05/08/2011. The girl fell ill on 05/10/2011, when the rise in body temperature to 37.0-37.2 ° C was first recorded. The patient was examined by a local pediatrician and sent for hospitalization with a suspected tick-borne infection. Upon admission to the hospital NIIDI 05/11/2011 state of moderate severity, temperature 37.0 ° C. There are no catarrhal phenomena. On the lobe of the right ear, a trace from the suction of a tick, there is no erythema. Identified behind the ear lymphadenitis on both sides more on the right. By internal organs without features. On examination, May 12, 2011, the department was feverish up to 37.2 ° C, ring-shaped erythema up to 6 cm appeared on the right in the behind-the-ear area, regional posterior cervical and occipital lymph nodes on both sides increased. In the clinical analysis of blood from 05/11/2011 leukocytosis 12.6 * 10 ⁹ / l, the leukocyte formula by age, ESR within normal limits. In the general analysis of urine without inflammatory changes. In a blood test using the NDP method, Borrelia and tick-borne encephalitis virus were not detected. Antibodies (IgM and IgG) to Borrelia and tick-borne encephalitis virus in the blood were not detected. The department received ceftriaxone in a daily dose of 800 mg for 10 days, after which bicillin “5” was administered at a dose of 800 thousand units intramuscularly. Against the background of the treatment, body temperature returned to 05/21/2011, erythema completely died out on 05/22/2011. Was discharged with clinical recovery under the clinical supervision of an infectious disease specialist.

Conclusion: in this case, an example of ineffective chemoprophylaxis of ICD with the antibacterial drug Suprax (cefixime) is described, as a result of which the child develops a disease. This required hospitalization of the patient in a hospital for a long course of therapy.

Example 2. Patient Vika B., 5 years old, medical history No. 31057. She was treated at the Department of Neuroinfections and Organic Pathology of the Nervous System of NIIDI from 08/11/2011 to 08/30/2011 with a diagnosis of Ixodes tick-borne borreliosis, erythema form, Banvart's syndrome (sensory-motor polyneuropathy, left facial neuropathy, serous meningitis), severe course. From the anamnesis: 07/11/2011 there was a fact that the tick was sucked into the temporal region on the right in the Novgorod region. The tick was removed on the same day, not examined. Anti-tick-borne immunoglobulin was not administered. From 07.16. On July 19, 2011, for 3 days, Sumamed took 250 mg of 1 r per day. She became ill on August 5, 2011, sharply from a rise in body temperature to 37.7 ° C, on August 6, she continued to have a low-grade fever, and a runny nose joined. 07.08 - rise in temperature to 38 ° С, face asymmetry appeared. 8, 9, 10.08 - complained of sore throat against a background of low-grade fever, face asymmetry persisted. 11.08. - examined by a local pediatrician, neurologist and hospitalized. Upon admission to NIIDI, the state of moderate severity, was febrile up to 38.3 ° C, catarrhal syndrome is not expressed. In the region of the left half of the face, an extensive annular erythema is 15 cm in diameter, swelling of the left half of the face. Regional cervical lymph nodes are enlarged to 1.2 cm on both sides. In the throat - moderate hyperemia without raids. By internal organs without features. In the neurological status of the cranial nerves, pronounced facial asymmetry was determined due to weakness of the facial muscles of the left half of the face. Eye slots S> D, pupils S = D. The reaction of the pupils to the light is alive.

Accommodation and convergence are not disturbed. Lagophthalmus to the left up to 2 mm. Lacrimation from the left eye. Muscle tone in the extremities satisfactory S = D. Tendon reflexes from arms and legs alive, S = D. Sensitive disturbances are not revealed. Meningeal symptoms are negative. In the clinical analysis of blood, leukocytosis (11.1 × 10%) with neutrophilia 68%, ESR acceleration to 18 mm / h. Biochemical blood parameters within the age limits. In the general analysis of urine without inflammatory changes. On ENMG, there are signs of mild neuropathy of the sensory and motor fibers of the upper and lower extremities of a demyelinating nature of the type of polyneuropathy in combination with moderate facial neuropathy on the left with a complete block of nerve conduction with the type of lesion - neuropraxia. In the blood, including the dynamics after 3 weeks, IgM and IgG to Borrelia were detected, which determined the etiology of the disease. Given the persisting subfebrile condition, despite the ongoing etiotropic therapy, as well as the existing neurological symptoms, a lumbar puncture was performed for diagnostic purposes, and a mononuclear cytosis of 117/3 was obtained. Thus, serous meningitis was diagnosed. Received therapy: ceftriaxone intramuscularly 1.5 g * 2 r per day from 12.08 to 08.25.2011, bicillin 1 million units. once on August 25, 2011, 5 mg neuromidine intramuscularly from August 18 to August 24, 2011, diacarb, aspartame, picamilon, nurofen, lorahexal, elkar. In parallel, she received FTL and facial massage. Against the background of treatment, a clear positive trend. The patient was discharged from the hospital with improvement, with residual effects of facial neuropathy in the form of a symptom of eyelashes, smoothness of the left nasolabial fold.

Conclusion: in this case, an example of the inefficiency of the use of sumamed (azithromycin) is given to prevent tick-borne tick-borne borreliosis, which entailed the development of the disease with damage to the skin, central and peripheral nervous system and required hospitalization for a long course of etiopathogenetic therapy and rehabilitation.

Thus, the above data indicate the effectiveness and safety of the method proposed by the authors to prevent the development of tick-borne tick-borne borreliosis in children, which allows us to recommend the proposed method of chemoprophylaxis for use in practical health care, which will reduce the incidence of ixodic borreliosis.

Claims (1)

A method for the prevention of tick-borne tick-borne borreliosis in children by antibacterial therapy with ceftriaxone, characterized in that when ascertaining the fact of sucking the tick infected with borrelia, intramuscularly ceftriaxone is prescribed at a dose of 50 mg / kg per day for 3 days, followed by a single intramuscular injection of bicillin “5” at a dose 50 thousand IU / kg, at the same time anaferon is prescribed 1 tablet 3 times a day for 30 days.