Aims: Filoviruses are associated with high morbidity and lethality rates in humans, are capable of human‐to‐human transmission, via infected material such as blood, and are believed to have low infectious doses for humans. Filoviruses are able to infect via the respiratory route and are lethal at very low doses in experimental animal models, but there is minimal information on how well the filoviruses survive within aerosol particles. There is also little known about how well filoviruses survive in liquids or on solid surfaces which is important in management of patients or samples that have been exposed to filoviruses.
Methods and Results: Filoviruses were tested for their ability to survive in different liquids and on different solid substrates at different temperatures. The decay rates of filoviruses in a dynamic aerosol were also determined.
Conclusions: Our study has shown that Lake Victoria marburgvirus (MARV) and Zaire ebolavirus (ZEBOV) can survive for long periods in different liquid media and can also be recovered from plastic and glass surfaces at low temperatures for over 3 weeks. The decay rates of ZEBOV and Reston ebolavirus (REBOV) plus MARV within a dynamic aerosol were calculated. ZEBOV and MARV had similar decay rates, whilst REBOV showed significantly better survival within an aerosol.
Significance and Impact of the Study: Data on the survival of two ebolaviruses are presented for the first time. Extended data on the survival of MARV are presented. Data from this study extend the knowledge on the survival of filoviruses under different conditions and provide a basis with which to inform risk assessments and manage exposure to filoviruses.
Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 α/β -/- interferon receptor-deficient KO mice, strain A129 IFN-α/β -/-, were used to determine the lethality of a range of filoviruses, including Lake Victoria marburgvirus (MARV), Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV) and Côte d'Ivoire ebolavirus (CIEBOV), administered by using intraperitoneal (IP) or aerosol routes of infection. One hundred percent mortality was observed in all groups of KO mice that were administered with a range of challenge doses of MARV and ZEBOV by either IP or aerosol routes. Mean time to death for both routes was dose-dependent and ranged from 5.4 to 7.4 days in the IP injection challenge, and from 10.2 to 13 days in the aerosol challenge. The lethal dose (50 % tissue culture infective dose, TCID(50)) of ZEBOV for KO mice was <1 TCID(50) ml(-1) when administered by either the IP or aerosol route of infection; for MARV the lethal dose was <1 TCID(50) ml(-1) by the IP route of infection and <10 TCID(50) ml(-1) by the aerosol route. In contrast, there was no mortality after infection with SEBOV or REBOV by either IP or aerosol routes of infection; all the mice lost weight (~15 % loss of group mean body weight with SEBOV and ~7 % with REBOV) but recovered to their original weights by day 14 post-challenge. There was no mortality in mice administered with CIEBOV via the IP route of infection and no clinical signs of infection were observed. The progression of disease was faster following infection with ZEBOV than with MARV but ultimately both viruses caused widespread infection with high titres of the infectious viruses in multiple organs. Histopathological observations were consistent with other animal models and showed widespread organ damage. This study suggests that MARV and ZEBOV are more virulent when administered via the IP route rather than by aerosol infection, although both are highly virulent by either route. The KO mouse may provide a useful model to test potential antiviral therapeutics against wild-type filoviruses.
Both gatifloxacin and moxifloxacin were more effective at preventing mortality than ciprofloxacin and could be considered as alternative antibiotics in the treatment of systemic F. tularensis infection.
Fluoroquinolones do not provide good post-exposure protection against infection with B. pseudomallei. The newer agents moxifloxacin and gatifloxacin are not significantly better than ciprofloxacin for this purpose.
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