MD918Z - Method for treating enteroviral meningitis in children - Google Patents

Abstract

The invention relates to medicine, in particular to infectious diseases and may be used for the treatment of enteroviral meningitis in children. According to the invention, the claimed method consists in performing the basic therapy which includes observing the hygienic, dietary, bed rest during the period. Acute pathogenetic, symptomatic, detoxification and improvement of cerebral blood flow, as well as bone supplementation, 5α-furostan-3β, 22,26-triol-3- [O-β-D-glucopyranosyl- (1 → 2 ) -β-D-glucopyranosyl (1 → 4) -β-D-galactopyranosyl] -26-O-β-D-glucopyranoside), 100 mg 2 times daily, 30 min before meal, for 30 minutes days.

Description

The invention relates to medicine, in particular to infectious diseases and can be used for the treatment of enteroviral meningitis in children.

The method of treatment of enteroviral meningitis in children is known, which includes hospitalization of the patient with observance of the hygienic and dietary regime, bed rest during the acute period of the disease, oral cavity hygiene (rinsing with 2% sodium bicarbonate solution), diet adapted to tolerance, natural feeding (breastfeeding) of infants, fluid intake (still mineral water, juices, compote, tea, milk), pathogenetic, symptomatic and detoxification treatment. Detoxification therapy may include oral rehydration (tea, juices), intravenous infusions of 10% glucose solutions, Ringer's and colloids (dextran - 40, albumin sol. 10%), the colloid/crystalloid ratio is 1:3, with hourly diuresis monitoring, dehydration therapy, improvement of cerebral blood circulation (Pentoxifylline 5…10 mg/kg/day i/v, Vinpocetine (Cavinton) - 0.5…1.0 mg/kg/day), the treatment series is 3…4 weeks. Corticosteroid therapy (in meningoencephalitis) includes administration of the drug Dexamethasone 0.5…1 mg/kg/24 hours i/v or i/m for 2…3 days or/and Prednisolone 2…3 mg/kg/24 hours i/v, or i/m for 2…3 days. Antiviral therapy includes immunomodulators such as Viferon-3 (1 million U), 1 suppository 2 times a day, for 5 days for school-age children or Viferon-2 (500,000 U), 1 suppository 2 times a day, for 5 days for preschool children. In case of bacterial superinfection (presence of purulent tonsillitis, bronchitis, pyelonephritis), antibiotic therapy is indicated. However, some of these remedies are very expensive and cause the development of side effects, which limits their application in medical practice for most patients, especially young ones [1].

The disadvantages of this method are the low efficacy of the preparations that do not allow to obtain the expected results and the fact that they are contraindicated in some children, at the same time the therapeutic problems facing the doctor are only partially solved. On the other hand, children with enteroviral meningitis who have contraindications to the administration of the basic therapy recommended by national and international protocols are deprived of the possibility of performing another alternative treatment. It is not always achieved a faster reduction of the manifestations of the general toxic syndrome, fever, headache, persistence of meningeal signs and the normalization of paraclinical indicators such as the number of leukocytes, ESR, etc.

The problem solved by the proposed invention is to increase the effectiveness of the treatment of enteroviral meningitis in children, manifested by a more rapid reduction in time of the signs of general toxic syndrome, fever, headache, persistence of meningeal signs and the normalization of paraclinical indicators such as leukocytes, ESR, etc., normalization of the general condition and improvement of the child's quality of life.

According to the invention, the claimed method consists in performing basic therapy which includes compliance with the hygienic, dietary regime, bed rest in the acute period, pathogenetic, symptomatic, detoxification and improvement of cerebral blood circulation treatment, while additionally administering 5α-furostane-3β,22,26-triol-3-[O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl(1→4)-β-D-galactopyranosyl]-26-O-β-D-glucopyranoside), 100 mg 2 times a day, 30 min before meals, for 30 days.

The result obtained consists in the improvement of clinical and paraclinical indices with the reduction of the duration of hospitalization which is obtained due to the supplementation of classical therapy with the preparation Pacovirin (5α-furostane-3β,22,26-triol-3-[O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl(1→4)-β-D-galactopyranosyl]-26-O-β-D-glucopyranoside). This treatment method can be applied to children with enteroviral meningitis, including children with contraindications to the administration of classical therapy.

To approve the proposed treatment method for enteroviral meningitis, children hospitalized in the IMSP Municipal Clinical Hospital for Infectious Diseases for Children, Chisinau (SCMBCC) were investigated in June - September 2013 and May - June 2014.

The study subjects were 48 patients (the experimental group consisting of 28 patients who benefited from treatment with the local preparation Pacovirin and the control group - of 20 patients who received basic treatment) and their observation sheets (form 003/e), with the clinical diagnosis of enteroviral meningitis, hospitalized in the IMSP Municipal Clinical Hospital for Children's Infectious Diseases, during the nominated period.

The paraclinical investigation program included:

1. Complete blood count.

2. Biochemical examination with assessment of aminotransferase levels (ALAT, ASAT), serum bilirubin and its fractions, and amylase.

3. Lumbar puncture with cytological and biochemical examination of cerebrospinal fluid (CSF) in all patients.

4. Virus isolation in RD (rhabdomyosarcoma) cell cultures from CSF and feces with identification of isolates in the neutralization reaction in cell cultures using standardized enteroviral specific immune sera Bilthoven, Netherlands.

5. All patients were consulted by a neurologist and ENT doctor.

6. Instrumental methods - if necessary (ultrasonography of abdominal organs).

7. Statistical methods.

Criteria for inclusion in the batch:

patients with a diagnosis of enteroviral meningitis, confirmed by epidemiological, clinical data, cytological and biochemical examination of CSF, as well as by virological methods (isolation and identification of enteroviruses);

age criteria - 0…18 years.

Criteria according to which patients were excluded from the group:

does not fall within the age range of 0…18 years;

the epidemiological, clinical, paraclinical (cytological and biochemical examination of CSF, RIF) and virological criteria for establishing the diagnosis of enteroviral meningitis were not present.

The experimental group consisted of 19 boys and 9 girls, compared to the control group: 12 boys and 8 girls (Fig. 1).

The obtained data show the maximum incidence in the first study group of children aged 4…7 years (12…42.8%) and over 7 years (13…46.5%), compared to children up to 4 years (3…10.7%). The same data were recorded in the control group (children aged 4…7 years - 12 (60.0%) and over 7 years - 6 (30.0%), and up to 4 years - 2 (10.0%)). The majority of patients, both from the first group (89.3%) and from the second group (70.0%) attended community centers. The maximum incidence and hospitalization rate in the experimental group falls on the months of June-July (June - 6 patients, July - 19, August - 2, September - 1), with the same data in the control group. About 1/3 (35.7%) of the patients in the first group were consulted before hospitalization by specialist doctors, who initiated treatment with an antibiotic (Ampicillin, Amoxicillin, Augmentin - in 5 cases, cephalosporins - in 4, macrolides - in one case). Most of the children in the first study group were hospitalized by the emergency team doctor (39.3%), less often by the family doctor (14.3%) and by self-referral (17.8%). 28.6% were transferred from other hospitals, a fact that can be explained by the variation in clinical symptoms at the onset of the disease, which required the hospitalization of these children in other hospitals. The same patterns were found in the control group. The majority (71.4%) of patients in group I were hospitalized in the first four days of illness (1st day - 3 patients, 2nd day - 6, 3rd day - 4, 4th...7), and in 8 cases there was a late hospitalization.

The classic triad present in the clinical picture of meningitis in children: fever and headache were detected in all (100%) patients from both groups, and single vomiting - in 24 (85.7%) patients from group I and in 16 (80.0%) - from group II. Among other clinical signs were found: vertigo (group I - in 46.5% patients, group II - in 40.0%), pain in the eyeballs (group I - in 28.6% patients, group II - in 25.0%), abdominal pain (group I - in 14.3% patients, group II - in 15.0%), myalgia (group I - in 14.3% patients, group II - in 20.0%), general weakness and fatigue in all patients in the study (table 1).

Fever values up to 38.0°C were recorded in 4 (14.3%) patients from group I, between 38.1... 39.0°C - in 15 (53.6%) and above 39.0°C - in 9 (32.1%). In group II, the most frequent (15...75.0%) was fever with values between 38.1... 39.0°C, less often up to 38.0°C (2...10.0%) and above 39.0°C (3...15.0%). In more than 1/2 (60.7%) of patients from group I, single vomiting (1...3 times) was recorded, and in 25.0% - more than 4 vomitings per day (tab. 1).

Table 1

Clinical signs present at the time of hospitalization in patients with enteroviral meningitis

Clinical signs Experimental group Control group Abs. % Abs. % Fever 28 100 20 100 Headache 28 100 20 100 Vomiting 24 85.7 16 80 Dizziness 13 46.5 8 40 Eye pain 8 28.6 5 25 Abdominal pain 4 14.3 3 15 Myalgia 4 14.3 4 20 General weakness 28 100 20 100

In most patients in group I, following the objective examination performed at the time of hospitalization, positive meningeal signs were detected: neck stiffness - in 96.4%, upper and lower Brudzinski sign - in 57.1% and Kernig - in 50.0%, and abolished abdominal reflexes were in 57.1%. In group II, positive neck stiffness was detected in 85.0% patients, upper and lower Brudzinski sign - in 75.0%, Kernig - in 45.0%. Hemoleukograms performed at the time of hospitalization were characterized by the presence of anemia in 3 (10.7%) patients in group I, leukocytosis - in 9 (32.1%), accelerated ESR - in 27 (60.7%). ALT and AST values were within normal limits in both study groups. In all cases, to confirm the definitive clinical diagnosis, lumbar puncture was performed. In most patients in group I (27…96.4%) colorless, transparent CSF was obtained, with a negative Pandy reaction and normal protein levels. In 75% of cases, cytological examination of CSF revealed a cytosis of up to 500 cells/mm3 and in 25% - over 500 cells/mm3, with a predominance of lymphocytes (tab. 2). In 6 cases, when lumbar puncture was performed in the first two days from the onset of the disease, neutrophils predominated in the CSF. In group II, the cytological and biochemical examination of CSF revealed the same regularities (except for the cytosis indices up to 500 cells/mm3 - at 40.0% and over 500 cells/mm3 - at 60.0% compared to the experimental group 75.0% up to 500 cells/mm3 and 25.0% over 500 cells/mm3, which demonstrates a significant reduction in the inflammatory process, p=0.01).

Table 2

Cytological examination of CSF in patients with enteroviral meningitis from study group I

Cytosis level Experimental group n=28 Control group n=28 Abs. % Abs. % up to 50/mm3 5 17.8±7.2 3 15.0±8.0 51-100/mm3 5 17.8±7.2 3 15.0±8.0 101-500/mm3 11 39.4±9.2 2 10.0±6.7 501-1000/mm3 3 10.7±5.8 5 25.0±9.7 over 1000/mm3 4 14.3±6.6 7 35.0±10.7

From the cerebrospinal fluid of 11 (39.3%) patients, enteroviruses were isolated in cell cultures (including COXSACKIE B1-6 virus in 9, ECHO11 in 2), from feces - COXSACKIE B1-6 virus was isolated in 2 patients. A detailed survey was completed for each patient, which included passport data and necessary information related to the history of the disease, epidemiological data, objective data, results of clinical, biochemical, serological and instrumental investigations, dynamics of clinical and laboratory data, treatment performed, possible adverse reactions, follow-up data.

All children included in the study (both from the experimental group and those from the control group) benefited from pathogenetic, symptomatic and detoxification treatment. In the acute phase of the disease, bed rest and a balanced diet were indicated. In the case of bacterial superinfection (presence of purulent tonsillitis, bronchitis, pyelonephritis) in 19 patients, antibiotic therapy was indicated.

The Pacovirin preparation was administered to patients in group I (experimental), one pill twice a day, 30 min before the morning and evening meals for a period of 30 days. All patients were monitored daily by the attending physician, with the assessment of all clinical and paraclinical parameters characteristic of the preparation and possible adverse reactions to the administration of the preparation. The results of the monitoring were entered into the observation sheet. All 28 patients selected for the experimental group tolerated the treatment well in inpatient conditions and continued the administration of the Pacovirin preparation on an outpatient basis, for up to 30 days. Towards the end of the inpatient therapy, the assessment of clinical changes (duration of fever and headache, persistence of positive meningeal signs) and laboratory data was performed. The evolution of the disease in all patients was benign. In patients in the experimental group, the intensity and duration of fever and headache were significantly reduced compared to those in the control group. The dynamics of the general toxic syndrome (manifested by loss of appetite, drowsiness, general weakness and dizziness) during the observation period in patients from group I had a more pronounced and favorable character compared to group II. The duration of fever up to 7 days was in the majority (71.4%) of patients from group I and in 13 (65.0%) - from group II, and over 7 days - in 8 (28.6%) and 7 (35.0%) patients, respectively. In the experimental group, headache persisted up to 7 days in 18 (64.3%) patients, in the control group - in 11 (55.0%), and over 7 days - in 10 (35.7%) and 9 (45.0%), respectively (Fig. 2).

At the time of discharge from the hospital, anemia was not present in any patient in the experimental group, but it persisted in 2 of the control group. The elevated leukocyte level persisted only in 2 patients in group I, compared to 3 in group II, and the accelerated ESR - in 12 patients in group I, with the maximum level up to 25 mm/hour.

The evaluation of clinical data and paraclinical results in patients who received treatment with Pacovirin demonstrates increased efficacy of the treatment with faster regression of the basic symptoms of enteroviral meningitis.

The preparation Pacovirin administered one pill twice a day for a period of 30 days in children with enteroviral meningitis contributed to: a more rapid reduction of the manifestations of general toxic syndrome, fever, headache, persistence of meningeal signs with the normalization of paraclinical indices such as leukocytes, ESR, etc.).

1. National clinical protocol. Enteroviral infection in children. Ministry of Health of the Republic of Moldova, Chisinau, 2012, p.

Claims (1)

Method of treatment of enteroviral meningitis in children, which consists in performing basic therapy that includes compliance with the hygienic, dietary regimen, bed rest in the acute period, pathogenetic, symptomatic treatment, detoxification and improvement of cerebral blood circulation, while additionally administering 5α-furostane-3β,22,26-triol-3-[O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl(1→4)-β-D-galactopyranosyl]-26-O-β-D-glucopyranoside), 100 mg 2 times a day, 30 min before meals, for 30 days.