In host–pathogen arms races, increases in host resistance prompt counteradaptation by pathogens, but the nature of that counteradaptation is seldom directly observed outside of laboratory models. The best-documented field example is the coevolution of myxoma virus (MYXV) in European rabbits. To understand how MYXV in Australia has continued to evolve in wild rabbits under intense selection for genetic resistance to myxomatosis, we compared the phenotypes of the progenitor MYXV and viral isolates from the 1950s and the 1990s in laboratory rabbits with no resistance. Strikingly, and unlike their 1950s counterparts, most virus isolates from the 1990s induced a highly lethal immune collapse syndrome similar to septic shock. Thus, the next step in this canonical case of coevolution after a species jump has been further escalation by the virus in the face of widespread host resistance.

ABSTRACT:Iridoviruses of the genus Ranavirus are well known for causing mass mortality events of fish and amphibians with sporadic reports of infection in reptiles. This article describes five instances of Ranavirus infection in chelonians between 2003 and 2005 in Georgia, Florida, New York, and Pennsylvania, USA. Affected species included captive Burmese star tortoises (Geochelone platynota), a free-ranging gopher tortoise (Gopherus polyphemus), free-ranging eastern box turtles (Terrapene carolina carolina), and a Florida box turtle (Terrepene carolina bauri). Evidence for Ranavirus infection was also found in archived material from previously unexplained mass mortality events of eastern box turtles from Georgia in 1991 and from Texas in 1998. Consistent lesions in affected animals included necrotizing stomatitis and/or esophagitis, fibrinous and necrotizing splenitis, and multicentric fibrinoid vasculitis. Intracytoplasmic inclusion bodies were rarely observed in affected tissues. A portion of the major capsid protein (MCP) gene was sequenced from each case in 2003-2005 and found to be identical to each other and to Frog virus 3 (FV3) across 420 base pairs. Ranavirus infections were also documented in sympatric species of amphibians at two locations with infected chelonians. The fragment profiles of HindIIIdigested whole genomic DNA of Ranavirus, isolated from a dead Burmese star tortoise and a southern leopard frog (Rana utricularia) found nearby, were similar. The box turtle isolate had a low molecular weight fragment that was not seen in the digestion profiles for the other isolates. These results suggest that certain amphibians and chelonians are infected with a similar virus and that different viruses exist among different chelonians. Amphibians may serve as a reservoir host for susceptible chelonians. This report also demonstrated that significant disease associated with Ranavirus infections are likely more widespread in chelonians than previously suspected.

A thorough understanding of the physical and chemical changes that occur in the body after death is critical for accurate interpretation of gross and microscopic pathology at autopsy. Furthermore, knowledge of the postmortem processes and the factors that affect them will aid in the estimation of the postmortem interval (PMI). The estimation of the PMI is important in many human and animal death investigations. Despite many decades of research, accuracy in estimation of the time of death has not significantly improved, and no single method can be reliably used to accurately estimate the time of death. Great care should be taken when formulating such an estimate, for it is dependent on multiple circumstantial and environmental factors, and the accuracy and precision of the estimate decrease as the PMI increases. The majority of the research in the field has been conducted on human bodies, but many relevant conclusions may be drawn regarding the expected postmortem changes in animals and the estimation of the PMI. The veterinary pathologist must use great caution when attempting to extrapolate data and apply formulas designed for use in humans. Methods reviewed include gross changes, microscopic changes, temperature-based methods, postmortem chemistry, molecular methods, microbial assay, ocular changes, radiography, entomology, and others. Although only several of these methods are currently practical for use in the workup of cases, it is expected that future research will result in improved techniques with enhanced accuracy in the estimation of the PMI, which will benefit both human and veterinary forensic investigations.

Comparison of patient mortality rates in cystic fibrosis (CF) obtained from different institutions requires the use of case-mix adjustment methods to account for baseline differences in patient and disease characteristics. There is no current professional consensus on the use of case-mix adjustment methods for use in comparing mortality rates in CF. Characteristics used for this case-mix adjustment should include those that are different across institutions and are associated with patient survival. They should not include characteristics of disease severity that may be a consequence of effectiveness of treatment. The goal of these analyses was to identify a set of these characteristics of patients or disease that would be useful for case-mix adjustment of CF mortality rates. Data from the Cystic Fibrosis Foundation Patient Registry and from the United States Census of the Population (1990) were used in these analyses. Kaplan-Meier techniques, the log-rank test, and Cox proportional hazards regression were used to estimate survivorship, calculate hazard ratios (HR), 95% confidence intervals (CI(95%)), and to conduct tests of statistical significance. The data set included all 30,469 CF patients seen at CF Care Centers from 1982-1998. There were 5,906 deaths during 508,721 person-years of follow-up. In multivariate analyses, female gender (HR 1.30, CI(95%) (1.16, 1,47), P < 0.001), nonwhite race (HR 1.48, CI(95%) (1.07, 2.04), P = 0.018), Hispanic ethnicity (HR 1.85, CI(95%) (1.42, 2.43), P < 0.001), and symptomatic presentation (respiratory, gastrointestinal, respiratory and gastrointestinal, meconium ileus, and other symptomatic presentations; HRs 1.38-1.83; P values, 0.028 to < 0.001) were associated with higher risk of death. The homozygous Delta F508 genotype (HR 1.36, CI(95%) (1.19, 1.55), P < 0.001) and neither mutation being Delta F508 (HR 1.40, CI(95%) (1.15, 1.71), P = 0.001) were also associated with higher risk of death. Patients diagnosed after 36 months of age had almost 50% reduction in risk of death compared to those diagnosed before 6 months of age (HR 0.52 CI(95%) (0.44, 0.61), P < 0.001). When patients living in zip codes with a median household income > $50,000/year (corrected for the 1999 consumer price index) were compared with those living in areas with a median household income < $20,000/year, it was apparent that those in the wealthier areas had a 40% reduced risk of death (HR 0.60, CI(95%) (0.44, 0.82), P = 0.001). All of these characteristics were independently significant predictors of death, and all of these characteristics differed significantly across the CF Care Centers. This case-mix adjustment model uses patient and disease characteristics available at the time of diagnosis of CF, and is not believed to be influenced by subsequent treatment to predict the risk of death. If these case-mix adjustment methods are adopted broadly, they will make it possible to study treatment effects and differences in mortality outcomes, while adjusting for baseline differences in patient and disease ...

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