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470Project InsightsIt appears that chlorine dioxide aqueous solution can be applied in hospital settings for the prevention of a wide range of nosocomial infectionschlorine dioxide holds a lot of potential,’ highlights Obinata.The team of researchers have identified the potential success of chlorine dioxide as a countermeasure against nosocomial infections. ‘In nosocomial infections, contact infections such as drug resistant bacteria and viruses become a problem. Furthermore, measures such as ventilation of air-conditioning and prevention of aerosol spread by shielding are being taken as measures against aerosol infection and air infection, which are also the problems we are seeing with the new COVID-19 virus,’ observes Obinata. ‘However, standard infection prevention measures alone leave viruses and bacteria in the environment. Secondary infections also occur in actual medical settings, making it difficult for clusters to occur.’ He says they believe that it is possible to further reduce the risk of nosocomial infections by adding a more reliable infection countermeasure in spatial disinfection and virus removal using chlorine dioxide gas to the conventional infection countermeasures.IMPROVING EXISTING MEASURESOf course, measures already exist within hospitals to prevent or counteract air and droplet infections. One of the chief methods is the use of high-efficiency particulate air (HEPA) filters, but even if the pathogenic microorganisms are captured by the filter, they are not sterilised or killed - meaning that the problems are not really solved in any meaningful way. There are also problems with the associated costs of HEPA filters, as well as the issues they cause regarding the need for secure spaces in hospitals - something difficult to achieve when HEPA filters are installed.On the other hand, chlorine dioxide exists as a gas at room temperature and dissolves in water to form an aqueous solution. Chlorine dioxide gas and aqueous solution are known to have a sufficient effect on aerosol infection of the causative microorganism for nosocomial pneumonia and an improvement of its efficacy can be expected by using it in combination with the conventionally used HEPA filter. ‘The infection route for nosocomial pneumonia is associated with aerosol infection when performing endotracheal suction operation in cases of respiratory management,’ points out Obinata. He explains that as a preventive measure, the use of negative pressure and positive pressure chambers to prevent the diffusion and inflow of microorganisms are being carried out, in addition to the use of a closed suction system, the disinfection of hospital rooms, cleaning of the environment, ventilation and the use of HEPA filters. ‘However, the installation of a negative pressure chamber is expensive and the HEPA filter cannot sterilise or kill the pathogenic organisms even if it can capture them. Alcohol is not effective for the disinfection of objects against norovirus and adenovirus while sodium hypochlorite has a problem in terms of producing carcinogens such as trihalomethane,’ he outlines. The low concentration of chlorine dioxide gas and aqueous solution are considered to be sufficiently effective against aerosol infection for the causative microorganism of nosocomial infection, and it is expected that when it is used in combination with a HEPA filter, it will be highly safe with good prevention effect and cost effectiveness.FINDINGS TRANSLATEDSo far, the team’s investigations have shown that chlorine dioxide aqueous solution is effective against various bacteria, viruses and fungi at a lower concentration than sodium hypochlorite solution. However, it has also been found that low-concentration of chlorine dioxide gas is effective against airborne bacteria and viruses, as well as adherent bacteria and viruses. In mouse models, the team has shown that it is effective against aerosol infection for the influenza virus and against influenza-like illness in humans.Chlorine dioxide aqueous solution has been proven to be effective against MRSA and MDRPA too - which seems to support its use against other nosocomial infections. ‘Interestingly, the team’s research has also found that it is effective against the new coronavirus (SARS-CoV-2) and the mechanisms of action that inhibits the binding of the spike protein of the SARS-CoV-2 on ACE2 through the action of chlorine dioxide has been verified,’ confirms Obinata. ‘Based on these results, it appears that chlorine dioxide aqueous solution can be applied in hospital settings for the prevention of a wide range of nosocomial infections.’The next stage is for the researcher to find a means of ensuring that the concentration of chlorine dioxide can be kept to safe and constant levels so that the effects are beneficial and not harmful. Thus, they are working to clarify the installation location of the chlorine dioxide generating gel in hospital rooms, as well as the time at which the mechanism should be replaced. If these final pieces of the puzzle can be put together, there is a genuine chance that the findings can be translated into real-world settings, thereby saving the lives of patients around the world. lFUNDING JSPS, KAKENHI, Grants-in-Aid for Scientific Research, Grant number JP18K10012COLLABORATORS • Dr Takashi Shibata (Taiko Pharmaceutical) • Japan Chlorine Dioxide Industry Association TEAM MEMBERS MSc Takanori Miura (Juntendo University), Dr Takahiro Niizuma (Juntendo University Urayasu Hospital), Dr Kyoko Suzuki (Juntendo University Nerima Hospital), Professor Toshiaki Shimizu (Juntendo University Faculty of Medicine)CONTACT Professor Kaoru ObinataT: +81 47 353 3111E: obinata@juntendo-urayasu.jpE: kobinata@juntendo.ac.jpW: https://www.hosp-urayasu.juntendo.ac.jp/medicalcare/pediatrics/BIO Professor Kaoru Obinata is currently based in the Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan, where he has worked since 2009. He previously worked at the Karolinska Institute, Department of Pediatrics, Huddinge Hospital, Sweden. Obinata has a special interest in pediatric infectious diseases.www.impact.pub 39

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