Background Primary pneumonic plague is rare among humans, but treatment efficacy may be tested in appropriate animal models under the FDA ‘Animal Rule’.
Methods Ten African Green monkeys (AGMs) ...inhaled 44–255 LD50 doses of aerosolized Yersinia pestis strain CO92. Continuous telemetry, arterial blood gases, chest radiography, blood culture, and clinical pathology monitored disease progression.
Results Onset of fever, >39°C detected by continuous telemetry, 52–80 hours post‐exposure was the first sign of systemic disease and provides a distinct signal for treatment initiation. Secondary endpoints of disease severity include tachypnea measured by telemetry, bacteremia, extent of pneumonia imaged by chest x‐ray, and serum lactate dehydrogenase enzyme levels.
Conclusions Inhaled Y. pestis in the AGM results in a rapidly progressive and uniformly fatal disease with fever and multifocal pneumonia, serving as a rigorous test model for antibiotic efficacy studies.
Background Junín virus (JUNV), the etiologic agent of Argentine hemorrhagic fever (AHF), is classified by the NIAID and CDC as a Category A priority pathogen. Presently, antiviral therapy for AHF is ...limited to immune plasma, which is readily available only in the endemic regions of Argentina. T-705 (favipiravir) is a broadly active small molecule RNA-dependent RNA polymerase inhibitor presently in clinical evaluation for the treatment of influenza. We have previously reported on the in vitro activity of favipiravir against several strains of JUNV and other pathogenic New World arenaviruses. Methodology/Principal Findings To evaluate the efficacy of favipiravir in vivo, guinea pigs were challenged with the pathogenic Romero strain of JUNV, and then treated twice daily for two weeks with oral or intraperitoneal (i.p.) favipiravir (300 mg/kg/day) starting 1-2 days post-infection. Although only 20% of animals treated orally with favipiravir survived the lethal challenge dose, those that succumbed survived considerably longer than guinea pigs treated with placebo. Consistent with pharmacokinetic analysis that showed greater plasma levels of favipiravir in animals dosed by i.p. injection, i.p. treatment resulted in a substantially higher level of protection (78% survival). Survival in guinea pigs treated with ribavirin was in the range of 33-40%. Favipiravir treatment resulted in undetectable levels of serum and tissue viral titers and prevented the prominent thrombocytopenia and leucopenia observed in placebo-treated animals during the acute phase of infection. Conclusions/Significance The remarkable protection afforded by i.p. favipiravir intervention beginning 2 days after challenge is the highest ever reported for a small molecule antiviral in the difficult to treat guinea pig JUNV challenge model. These findings support the continued development of favipiravir as a promising antiviral against JUNV and other related arenaviruses.
This article describes the development of a novel, high-performance personal aerosol sampler intended to monitor occupational air pollution, specifically, microbial constituents. This prototype ...sampler has a horizontally positioned conical cyclone with recirculating liquid film and an ejection supply of adsorptive liquid into the inlet nozzle. Airborne pollutants were collected in the adsorptive liquid, thus improving the survivability of microbiological aerosol samples. Experimental modules of different dimensions were first evaluated. Based on the test results, a prototype sampler was fabricated and tested. Evaluation of the collection efficiency of the prototype unit indicated a higher than 90% collection efficiency for particles > 1.0 μ m. The 50% cutoff diameter was between 0.70-0.75 μ m. For assessment of the sampling process effect on the collected microorganisms, Bacillus thuringiensis was tested at a concentration of about 1.0 × 10
6
cells per cm
3
. The viability in the prototype sampler decreased to 78% after 60 min of operation.
Letters to the Editor Fogle, Matthew R.; Brasel, Trevor L.; Wilson, Stephen C. ...
Journal of applied toxicology,
03/2007, Volume:
27, Issue:
2
Journal Article
Letters to the Editor Fogle, Matthew R.; Brasel, Trevor L.; Wilson, Stephen C. ...
Journal of applied toxicology,
March/April 2007, Volume:
27, Issue:
2
Journal Article
Letters to the Editor Fogle, Matthew R.; Brasel, Trevor L.; Wilson, Stephen C. ...
Journal of applied toxicology,
03/2007, Volume:
27, Issue:
2
Journal Article
Previous evidence by our laboratory has shown that mice inoculated with viable Penicillium Chrysogenum conidia or spores at levels comparable to those found in contaminated buildings induced spore ...antigen-specific allergic responses. We proposed that mice exposed to low levels of viable P. Chrysogenum conidia would not develop allergic symptoms. We also hypothesized that the symptoms induced by high numbers of conidia were the result of sensitization to allergens released by the conidia.
C57BL/6 and BALB/c mice were exposed to 1 x 10(2) viable P. Chrysogenum conidia by intranasal instillation weekly for a period of 11 weeks. C57BL/6 mice were also sensitized to a viable P. Chrysogenum conidia protease extract by intraperitoneal injections for a period of 6 weeks followed by intranasal challenge with protease extract, viable, or nonviable P. Chrysogenum conidia for 2 weeks.
C57BL/6 mice inoculated with low numbers of conidia developed no significant lung inflammation or increased serum immunoglobulins. Mice sensitized to the protease extract and challenged with both protease extract and viable conidia produced significant increases in serum IgE and IgG1. Mice sensitized to and challenged with the protease extract developed significant eosinophilia and mucus hyperproduction as determined by bronchoalveolar lavage and histopathological examination of lung tissue.
Mice did not develop allergic symptoms in response to challenge with low levels of P. Chrysogenum conidia. Protease allergens from viable conidia induced specific allergic responses in mice, indicating the importance of P. Chrysogenum conidia in allergic sensitization to the organism.
The growth and propagation of fungi in water-damaged buildings has long been recognized as a potential health risk to occupants of such environments. Reported symptoms from inhabitants of these ..."sick" buildings range from allergic rhinitis, headaches and watering of the eyes to more severe symptoms that warrant considerable concern such as hemorrhaging, nausea/vomiting/diarrhea, dizziness, and loss of mental capacity. Of the fungi capable of contaminating indoor environments, Stachybotrys chartarum is thought to pose the most significant human health risk. S. chartarum is a known producer of many compounds that have the potential to adversely effect occupant health, the most noteworthy being the highly toxic macrocyclic trichothecene mycotoxins. Currently, the relationship between the presence of trichothecene-producing strains of S. chartarum in water-damaged buildings and adverse human health effects is unclear. This is primarily due to the lack of data showing the co-presence of this organism and its mycotoxins (in an airborne state) in such environments. In this study, we present evidence that S. chartarum trichothecene mycotoxins become airborne and exist in buildings contaminated with this organism. Under controlled situations, we were repeatedly able to separate and collect airborne particulates originating from Stachybotrys growth. Our results demonstrated that airborne trichothecene mycotoxins were present on large, poorly respirable particles such as intact conidia, as well as highly respirable particulate matter such as fungal fragments. Furthermore, we were able to collect airborne trichothecene mycotoxins in natural indoor environments contaminated with S. chartarum, one in which separation and collection of particles was done as in our controlled setups. Concentrations ranged from less than 10 to greater than 1000 pg/m 3 of sampled air. In addition, we present data demonstrating that these compounds can be detected in sera from individuals with known mold (specifically S. chartarum) exposure. Overall concentrations were low with the exception of two samples that demonstrated uniquely high values (43 and 84 ng/ml) indicating a definitive exposure. When looked at in total, our data show that airborne trichothecene mycotoxins can be isolated in Stachybotrys chartarum -contaminated buildings and, based on their detection in human serum samples, may represent a significant occupant health risk.
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