Bacteriophage Therapy in Tonsillitis

Study Overview
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Brief Summary
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The patients received bacteriophage therapy with a liquid piobacteriophage complex (liquid pyobacteriophage complex - PCL). PСL was administered via nebulizer inhalation to irrigate the tonsil mucosa. A total of 5 ml of PCL was inhaled for 10 minutes every 5 days. The drug causes the lysis of certain bacteria, including staphylococcus, enterococcus, streptococcus, enteropathogenic E. coli, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Klebsiella oxytoca. The choice of this drug was based on bacteriological studies.

Detailed Description
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Comprehensive outpatient treatment was based on standard clinical guidelines, and symptomatic treatment was performed. On the first day of diagnosis, patients were prescribed complex antibacterial therapy on the basis of possible causative agents. Subsequently, antibiotic therapy was adjusted based on the results of the bacteriological examinations. A total of 67 patients received bacteriophage therapy using a liquid complex of pyobacteriophages (pyobacteriophage complex liquid - PСL). PСL was administered via nebulizer inhalation to irrigate the mucous membranes of the tonsils. In total, 5 ml of PCL was inhaled for up to 10 minutes once every 5 days. The drug causes lysis of specific bacteria including Staphylococcus, Enterococcus, Streptococcus, enteropathogenic Escherichia coli, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Klebsiella oxytoca. The drug is recommended for use for diseases of the ear, throat, nose, respiratory tract and lungs; inflammation of the sinuses and middle ear; tonsillitis; pharyngitis; laryngitis; tracheitis; bronchitis; pneumonia, pleurisy; and other inflammatory diseases. The choice of this drug was based on bacteriological studies.

Official Title
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Bacteriophage Therapy in Acute Tonsillitis

Conditions
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Acute Tonsillitis

Intervention / Treatment
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* Drug: Nebulizer inhalation irrigation of the mucous membranes of the tonsils with a bacteriophage.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: children from 3 to 14 years old. children with sore throat. children diagnosed with acute tonsillitis. children diagnosed with acute respiratory infection (rhinitis, sinusitis, nasopharyngitis). children with the opportunity to visit the outpatient clinic. children with the ability to receive inhalation therapy. children from parents (or guardians) who have given written permission to conduct clinical and laboratory research. Exclusion Criteria: children under 3 years old and over 14 years old. children receiving hospital treatment. children with acute respiratory tract diseases (bronchitis, pneumonia, pleurisy). children with сhronic respiratory tract diseases (bronchitis, pneumonia). children who are allergic to antibiotics. children with cancer, immunological and hematological diseases. children with severe psychological illnesses (schizophrenia, mental retardation, etc.) children with cancer, immunological and hematological diseases. children with tuberculosis.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Children aged 3 to 14 years with clinically diagnosed acute tonsillitis will receive bacteriophage therapy using a liquid pyobacteriophage complex (liquid pyobacteriophage complex - PCL).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nebulizer inhalation bacteriophage therapy<br>To study the effects of bacteriophage therapy on acute tonsillitis in children and adolescents in an outpatient setting. | Drug: Nebulizer inhalation irrigation of the mucous membranes of the tonsils with a bacteriophage.<br>* Bacteriophage therapy using a liquid complex of pyobacteriophages (pyobacteriophage complex liquid - PСL). PСL was administered via nebulizer inhalation to irrigate the mucous membranes of the tonsils. In total, 5 ml of PCL was inhaled for up to 10 minutes once every 5 days.<br>* Other names: Bacteriophage therapy.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical observation of sick children. | Children with clinically diagnosed acute tonsillitis are examined. The clinical study will be carried out on an outpatient basis in cooperation with the clinic of the Tashkent Pediatric Medical Institute. Prior to the study, written permission will be obtained from the parents or guardians of the children to participate in the study. Investigated: anamnesis of the child, the course of the disease, complaints of parents about the child's condition, body temperature in dynamics, visually - the state of the nasopharynx, the manifestation of clinical symptoms (sore throat, headaches, difficulty swallowing food, aphonia, and other signs) in dynamics, the functional state of internal organs (percussion, palpation and auscultation). | study of one patient - 4 weeks | 
| Laboratory research methods. | All examined children will undergo general clinical examination and pharyngoscopy. Additionally, all patients will have tonsil swabs for bacteriological examination (bacteriological culture, n x 10⁴/mL ) according to the standard technique. Also, swabs from the nasopharynx will be taken for viral lesions by the standard method - PCR (polymerase chain reaction). The research will be carried out in specialized laboratories. | study of one patient - 2 weeks | 
| Experimental clinical stage. Bacteriophage therapy. | Comprehensive outpatient treatment will be based on standard clinical guidelines. Patients will be prescribed antibiotic therapy based on possible pathogens. Patients will receive bacteriophage therapy using a liquid pyobacteriophage complex (liquid pyobacteriophage complex - PCL), through nebulizer inhalation to irrigate the mucous membranes of the tonsils. Just 5 ml PCL for 10 minutes once every 5 days. Efficacy will be studied based on immunological studies.A study of cellular (class of T-lymphocytes, Inflammatory cytokines (e.g., IL-1,2,4,5,6,11,13 - U/ml) and TNF-α) and humoral ( IgA / IgM / IgG -IU/mL) immunity in children will be carried out, using (Enzyme Linked Immunosorbent Assay) ELISA which is an immunoassay, suited to the determination of antibodies in the field of infectious serology. | study of one patient - 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The second stage of the study (statistical). | The results will be analyzed using a statistical program based on Excel 2017 (Microsoft Office 2017). Clinical signs will be calculated as a percentage (%) incidence. We will calculate the chi-square (χ2) test or Fisher's exact test (for expected values <5) to assess if certain pairs of microbes are more common than expected by chance in bacteriological examination. In addition, we will use the Kruskal-Wallis test to compare the average delay between disease onset and sample collection between samples containing one or more organisms. When evaluating immunological analyzes, characterizing the statistical significance of differences, the Student's t-test will be used with the definition of the confidence interval. The X-square test will be used to assess the frequency of identifying qualitative features. In all analyzes, P ≤ 0.05 was considered significant. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute tonsillitis, children, bacteriophage, immunity, ambulatory treatment