Effects of Nasal-spraying LiveSpo Navax in Treatment of Acute Respiratory Infections in Children

Summary

Rationals: Infection with the Respiratory Syncytial Virus (RSV) is one of the most common causes of respiratory tract diseases. However, treatment for pediatric RSV infection remains supportive to prevent co-infection bacteria and respiratory failure. In recent years, preventive and supportive probiotic therapies for respiratory tract infections (RTIs) have been increasingly strengthened, however, the use of oral administrative probiotics as functional foods is effective only for mild symptoms and not applicable for Acute RTIs (ARTIs). Here, we propose that direct spraying of probiotics into the nose can be a fast and effective symptomatic treatment for ARTIs. Objectives: Investigate symptomatic treatment effects of probiotic product LiveSpo Navax, as liquid-suspension form containing Bacillus spores of safe B. subtilis ANA4 and B. clausii ANA39 strains, in children having acute respiratory diseases caused by RSV: * Primary Objective: Evaluation of improved efficacy and reduced treatment time of LiveSpo Navax in children infected with RSV. * Secondary Objectives: Measurement of changes in RSV viral load, co-infectious bacterial concentrations, and major cytokine indicators in the nasopharyngeal mucosa before and after 3 days using LiveSpo Navax. Endpoints: Primary endpoint: LiveSpo Navax alleviates RSV-infection symptoms about 25% more effectively, as indicated by 90% of patients using LiveSpo Navax (Navax group) are symptom-free at day 3-6 of intervention depending on symptoms, compared to 65% of patients in Control group. Secondary endpoint: Patients in Navax group had more significant reductions in RSV load (\>10 fold) than patients in Control group at day 3 of intervention. Study Population: Sample size is 100. Description of Sites: The study is carried out at Vietnam National Children's Hospital. Description of Study Intervention: Totally 100 eligible patients are divided randomly into 2 groups (n = 50/group each): Patients in Control group received the routine treatment and three times per day 0.9% NaCl physiological saline while the and patients in Navax group received three times per day LiveSpo Navax in addition to the same standard of care treatment. The standard treatment regimen is 3-6 days but can be extended further depending on the severity of the patients' respiratory failure. Study Duration: 12 months

Timeline

Start

2020-08-29

Primary completion

2021-06-16

Completion

2021-08-29

Publications

• Results Lima SF, Teixeira AG, Higgins CH, Lima FS, Bicalho RC. The upper respiratory tract microbiome and its potential role in bovine respiratory disease and otitis media. Sci Rep. 2016 Jul 1;6:29050. doi: 10.1038/srep29050.
• Results Chotirmall SH, Gellatly SL, Budden KF, Mac Aogain M, Shukla SD, Wood DL, Hugenholtz P, Pethe K, Hansbro PM. Microbiomes in respiratory health and disease: An Asia-Pacific perspective. Respirology. 2017 Feb;22(2):240-250. doi: 10.1111/resp.12971.
• Results Principi N, Cozzali R, Farinelli E, Brusaferro A, Esposito S. Gut dysbiosis and irritable bowel syndrome: The potential role of probiotics. J Infect. 2018 Feb;76(2):111-120. doi: 10.1016/j.jinf.2017.12.013. Epub 2017 Dec 29.
• Results Sonawane AR, Tian L, Chu CY, Qiu X, Wang L, Holden-Wiltse J, Grier A, Gill SR, Caserta MT, Falsey AR, Topham DJ, Walsh EE, Mariani TJ, Weiss ST, Silverman EK, Glass K, Liu YY. Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection. Sci Rep. 2019 Sep 25;9(1):13824. doi: 10.1038/s41598-019-50217-w.
• Results Li KJ, Chen ZL, Huang Y, Zhang R, Luan XQ, Lei TT, Chen L. Dysbiosis of lower respiratory tract microbiome are associated with inflammation and microbial function variety. Respir Res. 2019 Dec 3;20(1):272. doi: 10.1186/s12931-019-1246-0.
• Results Valdivieso-Ugarte M, Gomez-Llorente C, Plaza-Diaz J, Gil A. Antimicrobial, Antioxidant, and Immunomodulatory Properties of Essential Oils: A Systematic Review. Nutrients. 2019 Nov 15;11(11):2786. doi: 10.3390/nu11112786.
• Results Elshaghabee FMF, Rokana N, Gulhane RD, Sharma C, Panwar H. Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives. Front Microbiol. 2017 Aug 10;8:1490. doi: 10.3389/fmicb.2017.01490. eCollection 2017.
• Results Raveendran S, Parameswaran B, Ummalyma SB, Abraham A, Mathew AK, Madhavan A, Rebello S, Pandey A. Applications of Microbial Enzymes in Food Industry. Food Technol Biotechnol. 2018 Mar;56(1):16-30. doi: 10.17113/ftb.56.01.18.5491.
• Results Yang L, Zeng X, Qiao S. Advances in research on solid-state fermented feed and its utilization: The pioneer of private customization for intestinal microorganisms. Anim Nutr. 2021 Dec;7(4):905-916. doi: 10.1016/j.aninu.2021.06.002. Epub 2021 Sep 16.
• Results Oggioni MR, Pozzi G, Valensin PE, Galieni P, Bigazzi C. Recurrent septicemia in an immunocompromised patient due to probiotic strains of Bacillus subtilis. J Clin Microbiol. 1998 Jan;36(1):325-6. doi: 10.1128/JCM.36.1.325-326.1998. No abstract available.
• Results Cukovic-Cavka S, Likic R, Francetic I, Rustemovic N, Opacic M, Vucelic B. Lactobacillus acidophilus as a cause of liver abscess in a NOD2/CARD15-positive patient with Crohn's disease. Digestion. 2006;73(2-3):107-10. doi: 10.1159/000094041. Epub 2006 Jun 20.
• Results Borriello SP, Hammes WP, Holzapfel W, Marteau P, Schrezenmeir J, Vaara M, Valtonen V. Safety of probiotics that contain lactobacilli or bifidobacteria. Clin Infect Dis. 2003 Mar 15;36(6):775-80. doi: 10.1086/368080. Epub 2003 Mar 5.
• Results Song M, Hong HA, Huang JM, Colenutt C, Khang DD, Nguyen TV, Park SM, Shim BS, Song HH, Cheon IS, Jang JE, Choi JA, Choi YK, Stadler K, Cutting SM. Killed Bacillus subtilis spores as a mucosal adjuvant for an H5N1 vaccine. Vaccine. 2012 May 9;30(22):3266-77. doi: 10.1016/j.vaccine.2012.03.016. Epub 2012 Mar 22.
• Results Hong JE, Kye YC, Park SM, Cheon IS, Chu H, Park BC, Park YM, Chang J, Cho JH, Song MK, Han SH, Yun CH. Alveolar Macrophages Treated With Bacillus subtilis Spore Protect Mice Infected With Respiratory Syncytial Virus A2. Front Microbiol. 2019 Mar 12;10:447. doi: 10.3389/fmicb.2019.00447. eCollection 2019.
• Results Lefevre M, Racedo SM, Ripert G, Housez B, Cazaubiel M, Maudet C, Justen P, Marteau P, Urdaci MC. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immun Ageing. 2015 Dec 3;12:24. doi: 10.1186/s12979-015-0051-y. eCollection 2015.
• Results Tavares Batista M, Souza RD, Paccez JD, Luiz WB, Ferreira EL, Cavalcante RC, Ferreira RC, Ferreira LC. Gut adhesive Bacillus subtilis spores as a platform for mucosal delivery of antigens. Infect Immun. 2014 Apr;82(4):1414-23. doi: 10.1128/IAI.01255-13. Epub 2014 Jan 13.
• Results Fazle Rabbee M, Baek KH. Antimicrobial Activities of Lipopeptides and Polyketides of Bacillus velezensis for Agricultural Applications. Molecules. 2020 Oct 27;25(21):4973. doi: 10.3390/molecules25214973.
• Results Marseglia GL, Tosca M, Cirillo I, Licari A, Leone M, Marseglia A, Castellazzi AM, Ciprandi G. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study. Ther Clin Risk Manag. 2007 Mar;3(1):13-7. doi: 10.2147/tcrm.2007.3.1.13.
• Results Piewngam P, Zheng Y, Nguyen TH, Dickey SW, Joo HS, Villaruz AE, Glose KA, Fisher EL, Hunt RL, Li B, Chiou J, Pharkjaksu S, Khongthong S, Cheung GYC, Kiratisin P, Otto M. Pathogen elimination by probiotic Bacillus via signalling interference. Nature. 2018 Oct;562(7728):532-537. doi: 10.1038/s41586-018-0616-y. Epub 2018 Oct 10.
• Results Collins PL, Murphy BR. Respiratory syncytial virus: reverse genetics and vaccine strategies. Virology. 2002 May 10;296(2):204-11. doi: 10.1006/viro.2002.1437. No abstract available.
• Results Nguyen SN, Nguyen TNT, Vu LT, Nguyen TD. Clinical Epidemiological Characteristics and Risk Factors for Severe Bronchiolitis Caused by Respiratory Syncytial Virus in Vietnamese Children. Int J Pediatr. 2021 Nov 15;2021:9704666. doi: 10.1155/2021/9704666. eCollection 2021.
• Results Wang X, Li Y, Deloria-Knoll M, Madhi SA, Cohen C, Ali A, Basnet S, Bassat Q, Brooks WA, Chittaganpitch M, Echavarria M, Fasce RA, Goswami D, Hirve S, Homaira N, Howie SRC, Kotloff KL, Khuri-Bulos N, Krishnan A, Lucero MG, Lupisan S, Mira-Iglesias A, Moore DP, Moraleda C, Nunes M, Oshitani H, Owor BE, Polack FP, O'Brien KL, Rasmussen ZA, Rath BA, Salimi V, Scott JAG, Simoes EAF, Strand TA, Thea DM, Treurnicht FK, Vaccari LC, Yoshida LM, Zar HJ, Campbell H, Nair H; Respiratory Virus Global Epidemiology Network. Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study. Lancet Glob Health. 2021 Jan;9(1):e33-e43. doi: 10.1016/S2214-109X(20)30393-4. Epub 2020 Nov 26.
• Results Griffiths C, Drews SJ, Marchant DJ. Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment. Clin Microbiol Rev. 2017 Jan;30(1):277-319. doi: 10.1128/CMR.00010-16.
• Results Kakimoto Y, Seto Y, Ochiai E, Satoh F, Osawa M. Cytokine Elevation in Sudden Death With Respiratory Syncytial Virus: A Case Report of 2 Children. Pediatrics. 2016 Dec;138(6):e20161293. doi: 10.1542/peds.2016-1293. Epub 2016 Nov 10.
• Results Caly L, Ghildyal R, Jans DA. Respiratory virus modulation of host nucleocytoplasmic transport; target for therapeutic intervention? Front Microbiol. 2015 Aug 14;6:848. doi: 10.3389/fmicb.2015.00848. eCollection 2015.
• Results Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C, Alassani I, Ali A, Antonio M, Awasthi S, Awori JO, Azziz-Baumgartner E, Baggett HC, Baillie VL, Balmaseda A, Barahona A, Basnet S, Bassat Q, Basualdo W, Bigogo G, Bont L, Breiman RF, Brooks WA, Broor S, Bruce N, Bruden D, Buchy P, Campbell S, Carosone-Link P, Chadha M, Chipeta J, Chou M, Clara W, Cohen C, de Cuellar E, Dang DA, Dash-Yandag B, Deloria-Knoll M, Dherani M, Eap T, Ebruke BE, Echavarria M, de Freitas Lazaro Emediato CC, Fasce RA, Feikin DR, Feng L, Gentile A, Gordon A, Goswami D, Goyet S, Groome M, Halasa N, Hirve S, Homaira N, Howie SRC, Jara J, Jroundi I, Kartasasmita CB, Khuri-Bulos N, Kotloff KL, Krishnan A, Libster R, Lopez O, Lucero MG, Lucion F, Lupisan SP, Marcone DN, McCracken JP, Mejia M, Moisi JC, Montgomery JM, Moore DP, Moraleda C, Moyes J, Munywoki P, Mutyara K, Nicol MP, Nokes DJ, Nymadawa P, da Costa Oliveira MT, Oshitani H, Pandey N, Paranhos-Baccala G, Phillips LN, Picot VS, Rahman M, Rakoto-Andrianarivelo M, Rasmussen ZA, Rath BA, Robinson A, Romero C, Russomando G, Salimi V, Sawatwong P, Scheltema N, Schweiger B, Scott JAG, Seidenberg P, Shen K, Singleton R, Sotomayor V, Strand TA, Sutanto A, Sylla M, Tapia MD, Thamthitiwat S, Thomas ED, Tokarz R, Turner C, Venter M, Waicharoen S, Wang J, Watthanaworawit W, Yoshida LM, Yu H, Zar HJ, Campbell H, Nair H; RSV Global Epidemiology Network. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017 Sep 2;390(10098):946-958. doi: 10.1016/S0140-6736(17)30938-8. Epub 2017 Jul 7.
• Results Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Ismail N, Matar C. Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders. Molecules. 2020 Oct 22;25(21):4891. doi: 10.3390/molecules25214891.
• Results Lehtoranta L, Pitkaranta A, Korpela R. Probiotics in respiratory virus infections. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1289-302. doi: 10.1007/s10096-014-2086-y. Epub 2014 Mar 18.
• Results Starosila D, Rybalko S, Varbanetz L, Ivanskaya N, Sorokulova I. Anti-influenza Activity of a Bacillus subtilis Probiotic Strain. Antimicrob Agents Chemother. 2017 Jun 27;61(7):e00539-17. doi: 10.1128/AAC.00539-17. Print 2017 Jul.
• Results Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, Sanders ME, Shamir R, Swann JR, Szajewska H, Vinderola G. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021 Sep;18(9):649-667. doi: 10.1038/s41575-021-00440-6. Epub 2021 May 4.
• Results Anderson LJ, Dormitzer PR, Nokes DJ, Rappuoli R, Roca A, Graham BS. Strategic priorities for respiratory syncytial virus (RSV) vaccine development. Vaccine. 2013 Apr 18;31 Suppl 2(Suppl 2):B209-15. doi: 10.1016/j.vaccine.2012.11.106.
• Results Domachowske JB, Anderson EJ, Goldstein M. The Future of Respiratory Syncytial Virus Disease Prevention and Treatment. Infect Dis Ther. 2021 Mar;10(Suppl 1):47-60. doi: 10.1007/s40121-020-00383-6. Epub 2021 Mar 3.
• Results Arnold R, Humbert B, Werchau H, Gallati H, Konig W. Interleukin-8, interleukin-6, and soluble tumour necrosis factor receptor type I release from a human pulmonary epithelial cell line (A549) exposed to respiratory syncytial virus. Immunology. 1994 May;82(1):126-33.
• Results Ugonna K, Douros K, Bingle CD, Everard ML. Cytokine responses in primary and secondary respiratory syncytial virus infections. Pediatr Res. 2016 Jun;79(6):946-50. doi: 10.1038/pr.2016.29. Epub 2016 Feb 16.

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