Optimization of the treatment of acute tonsillopharyngitis in childhood
DOI:
https://doi.org/10.15574/SP.2022.128.105Keywords:
children, acute tonsillopharyngitis, Umckalor, Tonsilotren, IL-8, C-reactive protein, γ-IFN, tumor necrosis factor αAbstract
Acute tonsillopharyngitis (ATP) in children is an actual and not fully solved problem, which has interdisciplinary importance and requires optimization of diagnosis and treatment to improve the prognosis of the disease and the quality of life of children.
Purpose - to optimize the tactics of treatment of children with ATP by supplementing the complex of therapy with drugs of anti-inflammatory and immunomodulatory action with the evaluation of clinical and immunological markers of the effectiveness of the proposed treatment.
Materials and methods. We monitored 51 hospitalized children with a clinical diagnosis of ATP. All children underwent a complex clinical and paraclinical examination with the determination of C-reactive protein (CRP) in the blood serum upon admission to the hospital, and on the 7th day of treatment, the serum concentration of interleukin (IL) -4, -6, -8, tumor necrosis factor α (TNFα), and interferon-γ (γ-IFN) as markers of therapy effectiveness.
The patients were randomly divided into 2 clinical groups: the Group 1 was formed by 28 patients (average age - 8.0±0.9 years, the share of boys - 53.5±6.1%) with ATP, who received standard treatment and standardized extract of Pelargonium sidoides EPs® 7630 (Umckalor) and the complex homeopathic drug Tonsilotren in age-related doses according to the instructions. The remaining 23 children formed the clinical Group 2 (average age - 8.7±1.0 years (p>0.05), the share of boys - 56.5±8.3% (p>0.05), and received the same standard treatment for ATP and served as a comparison group. The groups were matched for the main clinical characteristics.
Results. We obtained significantly better results of treatment of children with ATP when using the combination of the drugs Umckalor and Tonsilotren in complex therapy, which are proven by the presence of statistically reliable chances of a milder clinical course of the disease on the 3rd day of treatment (assessment of the severity of ATP - <26 points): attribute risk - 59.8%, relative risk - 2.8 (95% CI: 1.1-7.2), odds ratio - 25.6 (9.0-72.6).
The effectiveness of the proposed therapy was confirmed on the 7th day of treatment by the probably lower content of pro-inflammatory markers IL-8 (15.2±5.4 pg/ml vs 37.6±7.6 pg/ml) and γ-IFN (21.8±2.3 pg/ml vs. 30.0±1.2 pg/ml) compared to standard treatment, as well as twice lower TNF-α concentration (2.1±0.5 pg/ml vs. 4.5±2.5 pg/ml). The use of the combination of the drugs Umckalor and Tonsilotren was accompanied by a statistically significant reduction in the risk of maintaining a high serum concentration of pro-inflammatory cytokines (CRP - >10.0 mg/l, γ-IFN and IL-8>10.0 pg/ml) in relation to the standard treatment: absolute risk reduction - 20.8%, relative risk reduction - 32.3% with the minimum required number of patients to treat - 3.1.
Conclusions. In the complex treatment of children with ATP, the use of a combination of the standardized extract of Pelargonium sidoides EPs® 7630 (Umckalor) and the complex homeopathic drug Tonsilotren demonstrated better effectiveness compared to the same standard treatment.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
References
Anderson J, Paterek E. (2022). Tonsillitis. StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/31335062/.
Arvind B, Ramakrishnan S. (2020). Rheumatic Fever and Rheumatic Heart Disease in Children. Indian J Pediatr. 87 (4): 305-311. https://doi.org/10.1007/s12098-019-03128-7; PMid:31925717
Bartlett A, Bola S, Williams R. (2015). Acute tonsillitis and its complications: an overview. J R Nav Med Serv. 101 (1): 69-73. https://doi.org/10.1136/jrnms-101-69; PMid:26292396
Berger A, Meinel DM, Schaffer A, Ziegler R, Pitteroff J, Konrad R, Sing A. (2016). A case of pharyngeal diphtheria in Germany. Infection. 44 (5): 673-675. https://doi.org/10.1007/s15010-016-0882-2; PMid:26883545
Brouwer S, Jespersen MG, Ong CY, De Oliveira DMP, Keller B, Cork AJ, Djoko KY, Davies MR, Walker MJ. (2022). Streptococcus pyogenes Hijacks Host Glutathione for Growth and Innate Immune Evasion. mBio. 13 (3): 676-682. https://doi.org/10.1128/mbio.00676-22; PMid:35467425 PMCid:PMC9239160
Carapetis JR, Beaton A, Cunningham MW, Guilherme L, Karthikeyan G, Mayosi BM, Sable C, Steer A, Wilson N, Wyber R. (2016). Acute rheumatic fever and rheumatic heart disease. Nat. Rev. Dis. Primers. 2: 1-24. https://doi.org/10.1038/nrdp.2015.84; PMid:27188830 PMCid:PMC5810582
Carapetis JR, Steer AC, Mulholland EK, Weber M. (2005). The global burden of group A streptococcal diseases. Lancet Infect. Dis. 5: 685-694. https://doi.org/10.1016/S1473-3099(05)70267-X; PMid:16253886
Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ. (2019). Feigin and Cherry's Textbook of Pediatric Infectious Diseases. Group A, Group C, and Group B beta-hemolytic streptococcal infections. The Netherlands: 813-822.
Cheung AY, Kan KY, Jang S, Cohen MB, Levi JR. (2020). Socioeconomic variables as a predictor of indication for pediatric adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 136: 1101-1108. https://doi.org/10.1016/j.ijporl.2020.110181; PMid:32563841
Derzhavnyi ekspertnyi tsentr MOZ Ukrainy. (2021). Adaptovana klinichna nastanova, zasnovana na dokazakh. Vedennia naibilsh poshyrenykh staniv u ditei vikom do 5-ty rokiv u konteksti intehrovanoho vedennia khvorob dytiachoho viku: 64. URL: https://www.dec.gov.ua/wp-content/uploads/2021/09/2021_1945_kn_ivhdv.pdf.
Di Mario S, Gagliotti C, Buttazzi R, Marchetti F, Dodi I, Barbieri L, Moro ML. (2021). Reducing antibiotic prescriptions in children is not associated with higher rate of complications. Eur. J. Pediatr. 180: 1185-1192. https://doi.org/10.1007/s00431-020-03861-8; PMid:33145703
ESCMID Sore Throat Guideline Group. Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, Verheij T. (2012). Guideline for the management of acute sore throat. Clin Microbiol Infect. 18 (1): 1-28. https://doi.org/10.1111/j.1469-0691.2012.03766.x; PMid:22432746
González-Abad MJ, Alonso Sanz M. (2020). Invasive Streptococcus pyogenes infections (2011-2018): EMM-type and clinical presentation. An Pediatr (Engl Ed). 92 (6): 351-358. https://doi.org/10.1016/j.anpede.2019.10.006; PMid:31879253
Gottlieb M, Long B, Koyfman A. (2018). Clinical Mimics: An Emergency Medicine-Focused Review of Streptococcal Pharyngitis Mimics. J Emerg Med. 54 (5): 619-629. https://doi.org/10.1016/j.jemermed.2018.01.031; PMid:29523424
Hansen NS, Leth S, Nielsen LT. (2020). Toxic shock syndrome. Ugeskr Laeger. 182 (20): 111-119.
Henriquez KM, Hayney MS, Xie Y, Zhang Z, Barrett B. (2015). Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection. J Med Virol. 87 (2): 330-337. https://doi.org/10.1002/jmv.24042; PMid:25132248 PMCid:PMC4348013
Horbatiuk IB. (2019). Optymizatsiia diahnostyky ta likuvannia hostrykh nestreptokokovykh tonzylofarynhitiv u ditei. Avtoref.dys.kand.med.n. Chernivtsi: 22.
Ijaz M, Ameen F, Alfoteih YA, Shamim S, Alshehri WA, Murtaza G. (2020). Dissecting Streptococcus pyogenes interaction with human. Arch Microbiol. 202 (8): 2023-2032. https://doi.org/10.1007/s00203-020-01932-w; PMid:32504132
Kachroo P, Eraso JM, Olsen RJ, Zhu L, Kubiak SL, Pruitt L et al. (2020). New Pathogenesis Mechanisms and Translational Leads Identified by Multidimensional Analysis of Necrotizing Myositis in Primates. mBio. 11 (1): 3303-3319. https://doi.org/10.1128/mBio.03363-19; PMid:32071274 PMCid:PMC7029145
Kanda N. (2021). Psoriasis: Pathogenesis, Comorbidities, and Therapy Updated. Int J Mol Sci. 22 (6): 2979-2984. https://doi.org/10.3390/ijms22062979; PMid:33804147 PMCid:PMC8000092
Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P et al. (2021). Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 184 (1): 149-168. https://doi.org/10.1016/j.cell.2020.11.025; PMid:33278357 PMCid:PMC7674074
Kozlov RS, Veselov AV. (2015). Vnebolnychnыe ynfektsyy dыkhatelnыkh putei. Hlava 10. Tonzyllyt/farynhyt. Zdorovia Ukrainy. URL: https://health-ua.com/article/16227-vnebolnichnye-infektcii-dyhatelnyh-putejglava-10-tonzillitfaringit.
Kronman MP, Gerber JS, Grundmeier RW, Zhou C, Robinson JD, Heritage J, Stout J, Burges D, Hedrick B, Warren L. (2020). Reducing Antibiotic Prescribing in Primary Care for Respiratory Illness. Pediatrics. 146: 202-208. https://doi.org/10.1542/peds.2020-0038; PMid:32747473 PMCid:PMC7461202
Krüger K, Töpfner N, Berner R, Windfuhr J, Oltrogge JH. (2021). Clinical Practice Guideline: Sore Throat. Dtsch Arztebl Int. 118 (11): 188-194. https://doi.org/10.3238/arztebl.m2021.0121; PMid:33602392 PMCid:PMC8245861
Little P, Stuart B, Hobbs FDR. (2014). Antibiotic prescription strategies for acute sore throat: a prospective observational cohort study. Lancet Infect Dis. 14: 213-219. https://doi.org/10.1016/S1473-3099(13)70294-9; PMid:24440616
Matsubara K, Fukaya T. (2007). The role of superantigens of group A Streptococcus and Staphylococcus aureus in Kawasaki disease. Curr Opin Infect Dis. 20 (3): 298-303. https://doi.org/10.1097/QCO.0b013e3280964d8c; PMid:17471041
Meng M, Zhou Q, Lei W, Tian M, Wang P, Liu Y, Sun Y, Chen Y, Li Q. (2022). Recommendations on Off-Label Drug Use in Pediatric Guidelines. Front Pharmacol. 13: 89-97. https://doi.org/10.3389/fphar.2022.892574; PMid:35754484 PMCid:PMC9218488
Mitchell RB, Archer SM, Ishman SL, Rosenfeld RM, Coles S, Finestone SA et al. (2019). Clinical Practice Guideline: Tonsillectomy in Children (Update). Otolaryngol Head Neck Surg. 160 (1): 1-42. https://doi.org/10.1177/0194599818801757; PMid:30798778
Palm J, Kishchuk VV, Ulied A, Fernandez JP, De Jaegere S, Jong MC et al. (2017). Effectiveness of an add-on treatment with the homeopathic medication SilAtro-5-90 in recurrent tonsillitis: An international, pragmatic, randomized, controlled clinical trial. Complementary Therapies in Clinical Practice. 28: 181-191. https://doi.org/10.1016/j.ctcp.2017.05.005; PMid:28779928
Ralph AP, Noonan S, Wade V, Currie BJ. (2021). The 2020 Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease. Med J Aust. 214 (5): 220-227. https://doi.org/10.5694/mja2.50851; PMid:33190309
Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM et al. (2020). Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J. Am. Coll. Cardiol. 76: 2982-3021.
Rwebembera J, Nascimento BR, Minja NW, de Loizaga S, Aliku T, Dos Santos LPA et al. (2022). Recent Advances in the Rheumatic Fever and Rheumatic Heart Disease Continuum. Pathogens. 11 (2):179-187. https://doi.org/10.3390/pathogens11020179; PMid:35215123 PMCid:PMC8878614
Stelter K. (2014). Tonsillitis and sore throat in children. GMS Curr Top Otorhinolaryngol Head Neck Surg. 13: 1-24.
Ticinesi A, Lauretani F, Nouvenne A. (2017). C-reactive protein (crp) measurement in geriatric patients hospitalized for acute infection. European Journal of Internal Medicine. 37: 7-12. https://doi.org/10.1016/j.ejim.2016.08.026; PMid:27594414
Todorović MM, Zvrko EZ. (2013). Immunoregulatory cytokines and chronic tonsillitis. Bosn J Basic Med Sci. 13 (4): 230-236. https://doi.org/10.17305/bjbms.2013.2330; PMid:24289758 PMCid:PMC4334011
Van Driel ML, De Sutter AI, Thorning S, Christiaens T. (2021). Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst Rev. 3 (3): 44-56. https://doi.org/10.1002/14651858.CD004406.pub5; PMid:33728634 PMCid:PMC8130996
Wang Q, Du J, Jie C, Ouyang H, Luo R, Li W. (2017). Bacteriology and antibiotic sensitivity of tonsillar diseases in Chinese children. Eur Arch Otorhinolaryngol. 274 (8): 3153-3159. https://doi.org/10.1007/s00405-017-4603-y; PMid:28551703
Wessels MR. (2011). Clinical practice. Streptococcal pharyngitis. N. Engl. J. Med. 364: 648-655. https://doi.org/10.1056/NEJMcp1009126; PMid:21323542
Wessels MR. (2016). Pharyngitis and Scarlet Fever. URL: https://pubmed.ncbi.nlm.nih.gov/26866221/.
Wi D, Choi SH. (2021). Positive Rate of Tests for Group a Streptococcus and Viral Features in Children with Acute Pharyngitis. Children (Basel). 8 (7): 599-607. https://doi.org/10.3390/children8070599; PMid:34356578 PMCid:PMC8304790
Yang X, Zhang Y, Lin H, Zhong H, Wu Z. (2022). Diagnostic Value of the Triple Combination of Serum Heparin-Binding Protein, Procalcitonin, and C-Reactive Protein in Children with Acute Bacterial Upper Respiratory Tract Infection. J Healthc Eng: 187-196. https://doi.org/10.1155/2022/1877960; PMid:35310200 PMCid:PMC8930251
Zhu L, Charbonneau ARL, Waller AS, Olsen RJ, Beres SB, Musser JM. (2017). Novel Genes Required for the Fitness of Streptococcus pyogenes in Human Saliva. mSphere. 2 (6): 6-17. https://doi.org/10.1128/mSphereDirect.00460-17; PMid:29104937 PMCid:PMC5663985
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