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Nipah virus is a relatively newly discovered emerging virus on the WHO list of priority pathogens which has the potential to cause outbreaks with high fatality rates. Whilst progress is being made in the development of animal models for evaluating vaccines and therapies, some of the more fundamental data on Nipah virus are lacking. We performed studies to generate novel information on the aerosol survival of Nipah virus and to look at the efficacy of two common disinfectants. We also performed studies to evaluate the inactivation of Nipah virus by using neutral buffered formalin. Nipah virus was relatively stable in a small particle (1–5 µm) aerosol in the dark, with it having a decay rate of 1.46%min−1. Sodium hypochlorite (at 10%) and ethanol (at 80%) reduced the titre of Nipah virus to undetectable levels. Nipah virus that was in tissue culture medium was also inactivated after 24 h in the presence of 10% formalin. [ABSTRACT FROM AUTHOR]

During outbreaks of virus diseases, many variants may appear, some of which may be of concern. Stability in an aerosol of several Ebola virus and Marburg virus variants was investigated. Studies were performed measuring aerosol survival using the Goldberg drum but no significant difference in biological decay rates between variants was observed. In addition, historic data on virulence in a murine model of different Ebola virus variants were compared to newly presented data for Ebola virus Kikwit in the A129 Interferon alpha/beta receptor-deficient mouse model. Ebola virus Kikwit was less virulent than Ebola virus Ecran in our mouse model. The mouse model may be a useful tool for studying differences in virulence associated with different variants whereas aerosol stability studies may not need to be conducted beyond the species level. [ABSTRACT FROM AUTHOR]

Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route with a dose range of high-virulence WEEV strain Fleming to establish the median lethal dose (MLD). The disease course was acute, culminating in severe clinical signs, neuroinvasion, and dose-dependent mortality. Further groups of mice were exposed by the aerosol route, periodically sacrificed, and tissues excised for histopathological examination and virology. Viral titres peaked four days post-challenge in the brain and lungs, corresponding with severe bilateral lesions in rostroventral regions of the encephalon, especially in the olfactory bulb and piriform cortex. Recapitulation of the most serious clinical presentations of human WEEV disease in mice may prove a useful tool in the evaluation of medical countermeasures. [ABSTRACT FROM AUTHOR]

Porton Down houses two separate sites capable of conducting high containment research on ACDP (Advisory Committee on Dangerous Pathogens) Hazard Group 4 agents: the Defence Science and Technology Laboratory (Dstl) and the Health Protection Agency (HPA), and filovirus research has been performed at Porton Down since the first Marburg virus disease outbreak in 1967. All work is conducted within primary containment either within cabinet lines (for in vitro work) or large rigid half-suit isolators (for in vivo work). There are extensive aerobiological facilities at high containment and the use of these facilities will be reported. Research at Dstl is primarily focused on assessing and quantifying the hazard, and testing the efficacy of medical countermeasures against filoviruses. Fundamental research directed to the study and understanding of the infectious and pathogenic nature of the filoviruses, particularly in aerosols, will be reported. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is the causative agent of melioidosis, which is considered a potential deliberate release agent. The objective of this study was to establish and characterise a relevant, acute respiratory Burkholderia pseudomallei infection in BALB/c mice. Mice were infected with 100 B. pseudomallei strain BRI bacteria by the aerosol route (approximately 20 median lethal doses). Bacterial counts within lung, liver, spleen, brain, kidney and blood over 5 days were determined and histopathological and immunocytochemical profiles were assessed. Bacterial numbers in the lungs reached approximately 108 cfu/ml at day 5 post-infection. Bacterial numbers in other tissues were lower, reaching between 103 and 105 cfu/ml at day 4. Blood counts remained relatively constant at approximately 1.0 × 102 cfu/ml. Foci of acute inflammation and necrosis were seen within lungs, liver and spleen. These results suggest that the BALB/c mouse is highly susceptible to B. pseudomallei by the aerosol route and represents a relevant model system of acute human melioidosis. [ABSTRACT FROM AUTHOR]

Knowledge of the survival and stability of a pathogen is important for understanding its risk, reducing its transmission, and establishing control measures. Lassa virus is endemic in West Africa, causes severe disease, and is an emerging pathogen of concern. Our study examined the survival of Lassa virus in blood and tissue culture media at two different temperatures. The stability of Lassa virus held within a small particle aerosol was also measured. In liquids, Lassa virus was found to decay more quickly at 30 °C compared to room temperature. Sealed samples protected from environmental desiccation were more stable than samples open to the environment. In a small particle aerosol, the decay rate of Lassa virus was determined at 2.69% per minute. This information can contribute to risk assessments and inform mitigation strategies in the event of an outbreak of Lassa virus. [ABSTRACT FROM AUTHOR]

Background: Eastern equine encephalitis virus is an alphavirus that naturally cycles between mosquitoes and birds or rodents in Eastern States of the US. Equine infection occurs by being bitten by cross-feeding mosquitoes, with a case fatality rate of up to 75% in humans during epizootic outbreaks. There are no licensed medical countermeasures, and with an anticipated increase in mortality when exposed by the aerosol route based on anecdotal human data and experimental animal data, it is important to understand the pathogenesis of this disease in pursuit of treatment options. This report details the clinical and pathological findings of mice infected with EEEV by the aerosol route, and use as a model for EEEV infection in humans. Methods: Mice were exposed by the aerosol route to a dose range of EEEV to establish the median lethal dose. A pathogenesis study followed whereby mice were exposed to a defined dose of virus and sacrificed at time-points thereafter for histopathological analysis and virology. Results: Clinical signs of disease appeared within 2 days post challenge, culminating in severe clinical signs within 24 h, neuro-invasion and dose dependent lethality. EEEV was first detected in the lung 1 day post challenge, and by day 3 peak viral titres were observed in the brain, spleen and blood, corresponding with severe meningoencephalitis, indicative of encephalitic disease. Lethality follows severe neurological signs, and may be linked to a threshold level of virus replication in the brain. Effective medical countermeasures for EEEV may necessitate early inoculation to inhibit infection of the brain in zoonotic incidents, and be able to traverse the blood-brain barrier to sufficiently interrupt replication in the brain in cases of aerosol infection. Conclusions: There is little human data on the hazard posed by aerosol infection with encephalitic alphaviruses, and use of EEEV as a bioweapon may be by the aerosol route. A well characterized model of aerosol exposure that recapitulates some of the most severe human clinical features is necessary to evaluate the efficacy of putative medical countermeasures, and to increase our understanding about how this route of infection induces such rapid neuro-invasion and resulting disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] RNA polymerase inhibitor T-705 is undergoing clinical trials against influenza viruses. [•] T-705 given orally gave complete protection against Ebola virus, a high priority threat agent. [•] Protection was achieved after aerosol infection in an immune deficient mouse model. [•] T-705 was also shown to inhibit Ebola virus infection in vitro. [•] T-705 could become the first licensed therapy for Ebola virus infection. [Copyright &y& Elsevier]