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Susan Smith

Publications and source records attributed to Susan Smith.

8 recordsLinked to original sources

Moderate susceptibility to subcutaneous plague (Yersinia pestis) challenge in vaccine-treated and untreated Sonoran deer mice (Peromyscus maniculatus sonoriensis) and northern grasshopper mice (Onychomys leucogaster)

The variable response of wild mice to Yersinia pestis infection, the causative agent of plague, has generated much speculation concerning their role in the ecology of this potentially lethal disease. Researchers have questioned the means by which Y. pestis is maintained in nature and also sought methods for managing the disease. Here we assessed the efficacy of a new tool, the sylvatic plague vaccine (SPV), in wild-caught northern grasshopper mice ( Onychomys leucogaster ) and commercially acquired Sonoran deer mice ( Peromyscus maniculatus sonoriensis ). More than 40% of the animals survived a subcutaneous Y. pestis challenge of 175,000 colony forming units (over 30,000 times the white mouse 50% lethal dose) in both vaccine-treated and control groups. Our results indicate that SPV distribution is unlikely to protect adult mice from plague infection in field settings and corroborate the heterogeneous response to Y. pestis infection in mice reported by others.

Journal of Wildlife Diseases

VNTR diversity in Yersinia pestis isolates from an animal challenge study reveals the potential for in vitro mutations during laboratory cultivation

Underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. Although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. Here, we investigated tissue samples and Yersinia pestis isolates from a rodent laboratory challenge with strain CO92 using whole genome sequencing and multi-locus variable-number tandem repeat (VNTR) analysis (MLVA). We identified six VNTR mutations that were found to have occurred in vitro during laboratory cultivation rather than in vivo during the rodent challenge. In contrast, no single nucleotide polymorphism (SNP) mutations were observed, either in vivo or in vitro . These results were consistent with previously published mutation rates and the calculated number of Y. pestis generations that occurred during the in vitro versus the in vivo portions of the experiment. When genotyping disease outbreaks, the potential for in vitro mutations should be considered, particularly when highly variable genetic markers such as VNTRs are used.

Infection, Genetics and Evolution

Age at vaccination may influence response to sylvatic plague vaccine (SPV) in Gunnison’s prairie dogs ( Cynomys gunnisoni )

Gunnison&rsquo;s prairie dogs ( Cynomys gunnisoni ) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or &ldquo;montane&rdquo; population and a C. g. zuniensis or &ldquo;prairie&rdquo; population for vaccine efficacy and challenge studies. No differences ( P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates ( P < 0.01) than those from the montane population. Upon further analysis, we determined that response to immunization was most likely associated with differences in age, as the prairie group was much younger on average than the montane group. Vaccinates that were juveniles or young adults survived plague challenge at a much higher rate than adults ( P < 0.01 and P = 0.02, respectively), but no difference ( P = 0.83) was detected in survival rates between control animals of different ages. These results suggest that host susceptibility is probably not related to the assumed greater risk from plague in the C. g. gunnisoni or &ldquo;montane&rdquo; populations of Gunnison&rsquo;s prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

Colorado

The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs

Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with &ge;99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

Arizona

Consumption of baits containing raccoon pox-based plague vaccines protects black-tailed prairie dogs (Cynomys ludovicianus)

Baits containing recombinant raccoon poxvirus (RCN) expressing plague antigens (fraction 1 [F1] and a truncated form of the V protein-V307) were offered for voluntary consumption several times over the course of several months to a group of 16 black-tailed prairie dogs ( Cynomys ludovicianus ). For comparison, another group of prairie dogs ( n = 12) was injected subcutaneously (SC) (prime and boost) with 40 μg of F1-V fusion protein absorbed to alum, a vaccine-adjuvant combination demonstrated to elicit immunity to plague in mice and other mammals. Control animals received baits containing RCN without the inserted antigen ( n = 8) or injected diluent ( n = 7), and as there was no difference in their survival rates by Kaplan–Meier analysis, all of them were combined into one group in the final analysis. Mean antibody titers to Yersinia pestis F1 and V antigen increased ( p < 0.05) in the vaccinated groups compared to controls, but titers were significantly higher ( p < 0.0001) in those receiving injections of F1-V fusion protein than in those orally vaccinated with RCN-based vaccine. Interestingly, upon challenge with approximately 70,000 cfu of virulent Y. pestis , oral vaccination resulted in survival rates that were significantly higher ( p = 0.025) than the group vaccinated by injection with F1-V fusion protein and substantially higher ( p < 0.0001) than the control group. These results demonstrate that oral vaccination of prairie dogs using RCN-based plague vaccines provides significant protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous flea bites.

Vector-Borne and Zoonotic Diseases

Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis

Previous studies have established that vaccination of black-footed ferrets ( Mustela nigripes ) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis . This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis -infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis -infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period.

Journal of Wildlife Diseases

Toxicoinfectious botulism in commercial caponized chickens

During the summer of 2003, two flocks of commercial broiler chickens experienced unusually high death losses following caponizing at 3 wk of age and again between 8 and 14 wk of age. In September, fifteen 11-wk-old live capons were submitted to the Iowa State University Veterinary Diagnostic Laboratory for assistance. In both flocks, the second episode of elevated mortality was associated with incoordination, flaccid paralysis of leg, wing, and neck muscles, a recumbent body posture characterized by neck extension, and diarrhea. No macroscopic or microscopic lesions were detected in affected chickens. Hearts containing clotted blood and ceca were submitted to the National Wildlife Health Center in Madison, WI. Type C botulinum toxin was identified in heart blood and ceca by mouse bioassay tests. Enzyme-linked immunosorbent assay tests on heart blood samples were also positive for type C botulinum toxin. Clostridium botulinum was isolated from the ceca and genes encoding type C botulinum toxin were detected in cecal contents by a polymerase chain reaction test. Chickens are less susceptible to botulism as they age, and this disease has not previously been documented in broilers as old as 14 wk of age. Wound contamination by spores of C. botulinum may have contributed to the unusually high death losses following caponizing.

Avian Diseases

Preliminary evaluation of a simple in vitro test for the diagnosis of type C botulism in wild birds

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of type C botulinum toxin ( Clostridium botulinum ) in wild birds. This simple, antigen-capture ELISA utilizes polystyrene immunosticks as the solid substrate, chicken antitoxin (IgY) as the coating antibody, rabbit antitoxin as the primary antibody, and peroxidase-labeled goat-anti-rabbit as the secondary antibody. To evaluate the immunostick ELISA as a diagnostic test for avian botulism, known concentrations of toxin were added to heparinized blood collected from healthy birds and tested by both the ELISA and mouse bioassay. Also, blood samples from 236 bird carcasses submitted to the National Wildlife Health Center (NWHC) for cause of death determinations were tested by both procedures. Using ≤ 0.5 ml as the test volume for both procedures, the ELISA was less sensitive, detecting 0.25 ng/ml of toxin compared to 0.12 ng/ml for the mouse bioassay. Using the same volume of test sample for diagnostic submissions (≤ 0.5 ml), the ELISA was positive for 60% of the 149 clinically-diagnosed cases of botulism, whereas the mouse bioassay was positive for 79%. However, we demonstrated that with larger sample volumes (≥ 1.0 ml), the sensitivity of the ELISA may be equivalent or better than the mouse test due to the concentrating effect of the ELISA procedure. These preliminary results suggest that when adequate sample volumes are available, the immunostick ELISA can replace the mouse test for the diagnosis of botulism in wild birds.

Journal of Wildlife Diseases