Suchergebnisse

Rickettsia rickettsii is the causative agent of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae, which is found in North, Central, and South America. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through tick bites; however, some cases of aerosol transmission also have been reported. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment, it can be fatal. This article develops dose‐response models of different routes of exposure for RMSF in primates and humans. The beta‐Poisson model provided the best fit to the dose‐response data of aerosol‐exposed rhesus monkeys, and intradermally inoculated humans (morbidity as end point of response). The average 50% infectious dose among (ID50) exposed human population, N50, is 23 organisms with 95% confidence limits of 1 to 89 organisms. Similarly, ID10 and ID20 are 2.2 and 5.0, respectively. Moreover, the data of aerosol‐exposed rhesus monkeys and intradermally inoculated humans could be pooled. This indicates that the dose‐response models fitted to different data sets are not significantly different and can be described by the same relationship.

Q fever is a zoonotic disease caused by the intracellular gram‐negative bacterium Coxiella burnetii (C. burnetii), which only multiplies within the phagolysosomal vacuoles. Q fever may manifest as acute or chronic disease. The acute form is generally not fatal and manifestes as self‐controlled febrile illness. Chronic Q fever is usually characterized by endocarditis. Many animal models, including humans, have been studied for Q fever infection through various exposure routes. The studies considered different endpoints including death for animal models and clinical signs for human infection. In this article, animal experimental data available in the open literature were fit to suitable dose‐response models using maximum likelihood estimation. Research results for tests of severe combined immunodeficient mice inoculated intraperitoneally (i.p.) with C. burnetii were best estimated with the Beta‐Poisson dose‐response model. Similar inoculation (i.p.) trial outcomes conducted on C57BL/6J mice were best fit by an exponential model, whereas those tests run on C57BL/10ScN mice were optimally represented by a Beta‐Poisson dose‐response model.

The effect of bioaerosol size was incorporated into predictive dose‐response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol‐size‐dependent models were formulated as modification of the exponential and β‐Poisson dose‐response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose‐response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose‐response data was best fit by an exponential dose‐response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol‐size‐dependence equation and models that better represent the observed dose‐response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.

Human Brucellosis is one of the most common zoonotic diseases worldwide. Disease transmission often occurs through the handling of domestic livestock, as well as ingestion of unpasteurized milk and cheese, but can have enhanced infectivity if aerosolized. Because there is no human vaccine available, rising concerns about the threat of Brucellosis to human health and its inclusion in the Center for Disease Control's Category B Bioterrorism/Select Agent List make a better understanding of the dose‐response relationship of this microbe necessary.Through an extensive peer‐reviewed literature search, candidate dose‐response data were appraised so as to surpass certain standards for quality. The statistical programming language, "R," was used to compute the maximum likelihood estimation to fit two models, the exponential and the approximate beta‐Poisson (widely used for quantitative risk assessment) to dose‐response data. Dose‐response models were generated for prevalent species of Brucella: Br. suis, Br. melitensis, and Br. abortus. Dose‐response models were created for aerosolized Br. suis exposure to guinea pigs from pooled studies. A parallel model for guinea pigs inoculated through both aerosol and subcutaneous routes with Br. melitensis showed that the median infectious dose corresponded to a 30 colony‐forming units (CFU) dose of Br. suis, much less than the N50 dose of about 94 CFU for Br. melitensis organisms. When Br. melitensis was tested subcutaneously on mice, the N50 dose was higher, 1,840 CFU. A dose‐response model was constructed from pooled data for mice, rhesus macaques, and humans inoculated through three routes (subcutaneously/aerosol/intradermally) with Br. melitensis.