{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:04:59Z","timestamp":1793257499449,"version":"4.5.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Influenza viruses are known to be infected through epithelial cells of the upper respiratory tract. The oral cavity is in close anatomical proximity to the upper respiratory tract, and it is conceivable that the viruses could pass through the oral cavity and infect to the upper respiratory tract. Several researchers have suggested that colonization of certain pathogenic bacteria such as Staphylococcus aureus or Streptococcus pneumoniae might affect the risk of influenza viral disease, indicating that oral hygiene and\/or condition might play an important role in respiratory viral infection. Therefore, the purpose of this study was to investigate whether an oral hygiene\/condition might impact influenza infection. We conducted a retrospective observational study of Japanese citizens\u2019 regional cohort (N = 2,904) consisting of National Health Insurance beneficiaries who underwent annual health\/dental examination with data entries in the Kokuho database (KDB). Trained dentists checked the oral hygiene\/condition, and saliva specimens were examined using the LION dental saliva multi-test (SMT) kit. Influenza infection was identified from the diagnosis recorded in the KDB. The correlations between influenza infection and oral hygiene, dryness of the mouth, or various salivary test results were examined by a multivariate analysis adjusting for confounding factors such as gender, age, recent smoking, alcohol drinking, BMI, HbA1c, RBC for influenza infection. The logistic regression model showed that age significantly correlated with influenza infection. In addition, oral hygiene status had a nearly significant impact on influenza infection (p = 0.061), whereby, the subjects with poor oral hygiene had a higher risk of influenza infection than those with good oral hygiene (odds ratio: 1.63, 95% confidence interval: 0.89\u20132.95). Further, the prevalence of influenza infection was lower in the subjects with saliva weakly acidic and\/or containing higher protein level. The results of this study suggested that the maintenance of oral health conditions might be one of the pivotal factors for preventing and reducing influenza infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0254981","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T17:53:58Z","timestamp":1629309238000},"page":"e0254981","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exploration of correlation of oral hygiene and condition with influenza infection"],"prefix":"10.1371","volume":"16","author":[{"given":"Makiko","family":"Kawamoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3719-3144","authenticated-orcid":true,"given":"Hirokazu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinari","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Otagiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imahito","family":"Karasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kurita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"issue":"1","key":"pone.0254981.ref001","doi-asserted-by":"crossref","DOI":"10.1186\/s13054-019-2566-7","article-title":"Host susceptibility to severe influenza A virus infection","volume":"23","author":"S Clohisey","year":"2019","journal-title":"Crit Care"},{"issue":"3","key":"pone.0254981.ref002","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1136\/jech-2014-204678","article-title":"Causal analysis of H1N1pdm09 influenza infection risk in a household cohort","volume":"69","author":"Y Mansiaux","year":"2015","journal-title":"J Epidemiol Community Health"},{"issue":"2","key":"pone.0254981.ref003","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4049\/jimmunol.1801010","article-title":"Influenza Pathogenesis: The Effect of Host Factors on Severity of Disease","volume":"202","author":"AP Gounder","year":"2019","journal-title":"J Immunol"},{"issue":"5","key":"pone.0254981.ref004","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1750-2659.2008.00051.x","article-title":"Sialic acid tissue distribution and influenza virus tropism","volume":"2","author":"U Kumlin","year":"2008","journal-title":"Influenza Other Respi Viruses"},{"issue":"4","key":"pone.0254981.ref005","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1600-0765.1990.tb00912.x","article-title":"Accessible sialic acid content of oral epithelial cells from healthy and gingivitis subjects","volume":"25","author":"G Davis","year":"1990","journal-title":"J Periodontal Res"},{"issue":"2","key":"pone.0254981.ref006","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.archger.2005.10.004","article-title":"Professional oral care reduces influenza infection in elderly","volume":"43","author":"S Abe","year":"2006","journal-title":"Arch Gerontol Geriatr."},{"key":"pone.0254981.ref007","first-page":"61","volume-title":"Kokumin Eisei no Doko. 2014\/2015","author":"Association H and WS","year":"2015"},{"issue":"2","key":"pone.0254981.ref008","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/01.aoa.0000482594.11253.a7","article-title":"Influenza Virus Infection in Pregnancy: A Review","volume":"36","author":"WJ Meijer","year":"2016","journal-title":"Obstet Anesth Dig."},{"key":"pone.0254981.ref009","unstructured":"Ministry of Health L and W. Specific Healthcheckup and Specific Health Guidance. [Internet]. [cited 2020 Jan 14]. Available from: https:\/\/www.mhlw.go.jp\/english\/wp\/wp-hw3\/dl\/2-007.pdf."},{"issue":"11","key":"pone.0254981.ref010","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3928\/0098-9134-20041101-06","article-title":"Evidence-based protocol: oral hygiene care for functionally dependent and cognitively impaired older adults","volume":"30","author":"J Chalmers","year":"2004","journal-title":"J Gerontol Nurs"},{"key":"pone.0254981.ref011","first-page":"30","article-title":"Guideline for diagnosis of dry mouth in the disabled","volume":"27","author":"Y Kakinoki","year":"2008","journal-title":"J Jpn Assoc Dent Sci"},{"key":"pone.0254981.ref012","first-page":"0","year":"2012","journal-title":"Correlation Data From Salivary Multi Test Using SillHa [Internet]"},{"issue":"2","key":"pone.0254981.ref013","first-page":"93","article-title":"An Oral Cleanliness Test Based on Ammonia Concentration and\/or Turbidity of Mouth Rinse Solution","volume":"59","author":"H Sakamoto","year":"2009","journal-title":"J Dent Heal"},{"issue":"1","key":"pone.0254981.ref014","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2329\/perio.40.111","article-title":"Evaluation of a Screening Test for Periodontal Disease Using Anti-human Hemoglobin Monoclonal Antibody to Detect Occult Blood in Saliva. Comparison with the Clinical Parameters","volume":"40","author":"M Ohshima","year":"1998","journal-title":"Nihon Shishubyo Gakkai Kaishi (Journal Japanese Soc Periodontol"},{"issue":"3","key":"pone.0254981.ref015","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.bdj.4806930","article-title":"Identification of caries risk in schoolchildren: Salivary buffering capacity and bacterial counts, sugar intake and caries experience as predictors of 2-year and 3-year caries increment","volume":"167","author":"RF Wilson","year":"1989","journal-title":"Br Dent J"},{"issue":"4","key":"pone.0254981.ref016","first-page":"321","article-title":"Development of Comprehensive Salivary Test System","volume":"58","author":"E Nishinaga","year":"2015","journal-title":"Japanese J Conserv Dent"},{"issue":"6104","key":"pone.0254981.ref017","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/325536a0","article-title":"Role of Staphylococcus protease in the development of influenza pneumonia","volume":"325","author":"M Tashiro","year":"1987","journal-title":"Nature"},{"issue":"2","key":"pone.0254981.ref018","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0042-6822(87)90284-4","article-title":"Synergistic role of staphylococcal proteases in the induction of influenza virus pathogenicity","volume":"157","author":"M Tashiro","year":"1987","journal-title":"Virology"},{"issue":"4","key":"pone.0254981.ref019","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/infdis\/166.4.783","article-title":"Interactions between Bacteria and Influenza A Virus in the Development of Influenza Pneumonia","volume":"166","author":"H Scheiblauer","year":"1992","journal-title":"J Infect Dis"},{"issue":"12","key":"pone.0254981.ref020","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.cmi.2016.07.007","article-title":"Functional balance between neuraminidase and haemagglutinin in influenza viruses","volume":"22","author":"A Gaymard","year":"2016","journal-title":"Clin Microbiol Infect"},{"issue":"7","key":"pone.0254981.ref021","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3382\/ps.2008-00549","article-title":"Proteolytic bacteria in the lower digestive tract of poultry may affect avian influenza virus pathogenicity","volume":"88","author":"MD King","year":"2009","journal-title":"Poult Sci"},{"issue":"2","key":"pone.0254981.ref022","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/0042-6822(75)90284-6","article-title":"Activation of influenza A viruses by trypsin treatment","volume":"68","author":"HD Klenk","year":"1975","journal-title":"Virology"},{"issue":"10","key":"pone.0254981.ref023","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1128\/JVI.00079-08","article-title":"Influenza A Virus Neuraminidase Limits Viral Superinfection","volume":"82","author":"I-C Huang","year":"2008","journal-title":"J Virol"},{"key":"pone.0254981.ref024","first-page":"18","article-title":"The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09","author":"CR MacIntyre","year":"2018","journal-title":"BMC Infect Dis."},{"issue":"7","key":"pone.0254981.ref025","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJMra1714562","article-title":"Aspiration Pneumonia","volume":"380","author":"LA Mandell","year":"2019","journal-title":"N Engl J Med [Internet]"},{"issue":"1","key":"pone.0254981.ref026","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/prd.12301","article-title":"Oral-lung microbiome interactions in lung diseases","volume":"83","author":"MJ Mammen","year":"2000","journal-title":"Periodontol"},{"issue":"8","key":"pone.0254981.ref027","first-page":"1211","article-title":"The oral-lung axis: The impact of oral health on lung health","volume":"65","author":"NT Gaeckle","journal-title":"Respir Care. 2020"},{"issue":"7","key":"pone.0254981.ref028","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1902\/jop.1999.70.7.793","article-title":"Role of Oral Bacteria in Respiratory Infection","volume":"70","author":"FA Scannapieco","year":"1999","journal-title":"J Periodontol."},{"issue":"3","key":"pone.0254981.ref029","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1046\/j.1532-5415.2002.50106.x","article-title":"Oral care reduces pneumonia in older patients in nursing homes","volume":"50","author":"T Yoneyama","year":"2002","journal-title":"J Am Geriatr Soc"},{"issue":"2","key":"pone.0254981.ref030","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1067\/moe.2002.123493","article-title":"Effect of professional oral health care on the elderly living in nursing homes","volume":"94","author":"M Adachi","year":"2002","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"issue":"8","key":"pone.0254981.ref031","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1017\/ice.2015.77","article-title":"Prevention of Healthcare-Associated Pneumonia with Oral Care in Individuals Without Mechanical Ventilation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"36","author":"A Kaneoka","year":"2015","journal-title":"Infect Control Hosp Epidemiol."},{"issue":"3\u20134","key":"pone.0254981.ref032","first-page":"253","article-title":"Efficacy of a New Post-Mouthwash Intervention (Wiping Plus Oral Nutritional Supplements) for Preventing Aspiration Pneumonia in Elderly People: A Multicenter, Randomized, Comparative Trial","volume":"71","author":"T Higashiguchi","year":"2018","journal-title":"Ann Nutr Metab."},{"issue":"15_suppl","key":"pone.0254981.ref033","doi-asserted-by":"crossref","first-page":"e16017","DOI":"10.1200\/JCO.2018.36.15_suppl.e16017","article-title":"Effect of perioperative oral care on prevention of postoperative pneumonia associated with esophageal cancer surgery: A multicenter case-control study with propensity score matching analysis","volume":"36","author":"S Soutome","year":"2018","journal-title":"J Clin Oncol."},{"issue":"2","key":"pone.0254981.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003151","article-title":"Influenza HA Subtypes Demonstrate Divergent Phenotypes for Cleavage Activation and pH of Fusion: Implications for Host Range and Adaptation","volume":"9","author":"SE Galloway","year":"2013","journal-title":"PLoS Pathog."},{"issue":"4","key":"pone.0254981.ref035","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.bbamem.2013.10.004","article-title":"Receptor binding and pH stability\u2014How influenza A virus hemagglutinin affects host-specific virus infection","volume":"1838","author":"CM Mair","year":"2014","journal-title":"Biochim Biophys Acta\u2014Biomembr"},{"issue":"36","key":"pone.0254981.ref036","doi-asserted-by":"crossref","first-page":"17744","DOI":"10.1016\/S0021-9258(18)45442-7","article-title":"Effects of low pH on influenza virus. Activation and inactivation of the membrane fusion capacity of the hemagglutinin","volume":"262","author":"T Stegmann","year":"1987","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0254981.ref037","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1128\/JVI.01927-14","article-title":"Variations in pH Sensitivity, Acid Stability, and Fusogenicity of Three Influenza Virus H3 Subtypes","volume":"89","author":"DA Costello","year":"2015","journal-title":"J Virol"},{"issue":"6","key":"pone.0254981.ref038","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1248\/bpb.b15-00120","article-title":"Low-pH stability of influenza A virus sialidase contributing to virus replication and pandemic","volume":"38","author":"T Takahashi","year":"2015","journal-title":"Biol Pharm Bull"},{"issue":"9","key":"pone.0254981.ref039","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.joms.2020.06.029","article-title":"Hypochlorous Acid: A Review","volume":"78","author":"MS Block","year":"2020","journal-title":"J Oral Maxillofac Surg."},{"issue":"2","key":"pone.0254981.ref040","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1292\/jvms.14-0413","article-title":"Evaluation of sprayed hypochlorous acid solutions for their virucidal activity against avian influenza virus through in vitro experiments","volume":"77","author":"H Hakim","year":"2015","journal-title":"J Vet Med Sci"},{"issue":"4","key":"pone.0254981.ref041","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.cell.2008.09.024","article-title":"Bleach Activates a Redox-Regulated Chaperone by Oxidative Protein Unfolding","volume":"135","author":"J Winter","year":"2008","journal-title":"Cell"},{"key":"pone.0254981.ref042","first-page":"159","author":"DM Desiderio","year":"2010"},{"key":"pone.0254981.ref043","author":"Incorporated GSM","year":"1998","journal-title":"Essentials of Human Physiology"},{"issue":"2","key":"pone.0254981.ref044","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1067\/mpr.2001.113778","article-title":"A review of saliva: Normal composition, flow, and function","volume":"85","author":"SP Humphrey","year":"2001","journal-title":"J Prosthet Dent"},{"issue":"5","key":"pone.0254981.ref045","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jsps.2015.02.015","article-title":"Oral antimicrobial peptides: Types and role in the oral cavity","volume":"24","author":"Z Khurshid","year":"2016","journal-title":"Saudi Pharm J"},{"issue":"4","key":"pone.0254981.ref046","article-title":"Innate antimicrobial defense of skin and oral mucosa.","volume":"9","author":"PW Wertz","year":"2020","journal-title":"Antibiotics [Internet]"},{"issue":"1","key":"pone.0254981.ref047","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/irv.12294","article-title":"Risk factors of pandemic influenza A\/H1N1 in a prospective household cohort in the general population: Results from the CoPanFlu-France cohort","volume":"9","author":"RM Delabre","year":"2015","journal-title":"Influenza Other Respi Viruses"},{"issue":"46","key":"pone.0254981.ref048","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2019.24.46.1900585","article-title":"Paradoxical clade- And age-specific vaccine effectiveness during the 2018\/19 influenza A(H3N2) epidemic in Canada: Potential imprint-regulated effect of vaccine (I-REV)","volume":"24","author":"DM Skowronski","year":"2019","journal-title":"Eurosurveillance"},{"issue":"2","key":"pone.0254981.ref049","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1089\/vim.2017.0141","article-title":"Influenza Virus: Dealing with a Drifting and Shifting Pathogen","volume":"31","author":"H Kim","year":"2018","journal-title":"Viral Immunol"},{"key":"pone.0254981.ref050","volume-title":"Influenza Medical Guide 2019\u201320","author":"S Y","year":"2019"},{"key":"pone.0254981.ref051","first-page":"12","article-title":"High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa","author":"H Xu","year":"2020","journal-title":"Int J Oral Sci."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0254981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T17:54:37Z","timestamp":1629309277000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0254981"}},"subtitle":[],"editor":[{"given":"Agnieszka","family":"Rynda-Apple","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0254981","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]}}}