Janet E. Foley

Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses.

Abstract Feline infectious peritonitis virus (FIPV) strains from six cats and three different geographic areas were compared genetically with feline enteric coronavirus (FECV) isolates obtained from cats inhabiting the same environments. Sequence comparisons were made from 1.2- to 8.9-kb segments on the 3′ end of the genome. FECV/FIPV pairs from the same catteries or shelters were 97.3–99.5% related but were genetically distinct from FIPV and FECV strains obtained from cats living in geographically distinct environments. The high genetic similarity between FECVs and FIPVs from the same environment strongly suggested a common ancestry. Based on the presence of deletion mutations in the FIPVs and not in the FECVs, it was concluded that FIPVs evolved as mutants of FECVs. The mutations are deletions in the FIPVs and not insertions in the FECVs since similar sequences are present in other strains that have segregated earlier from a common ancestor. Therefore, the order of descent is from FECV to FIPV. Mutations unique to FIPVs were found in open reading frames (ORFs) 3c in 4 of 6 isolates and/or 7b in 3 of 6 isolates. When the study was extended to include 7 additional FIPV isolates, 11/13 of the FIPVs sequenced were found to have mutated 3c ORFs.

Causal inference in disease ecology: investigating ecological drivers of disease emergence

Despite awareness that disease emergence may be related to ecological change, few studies have rigorously analyzed the underlying environmental drivers of the dynamics of disease emergence. This may be due to the fact that ecological change and disease emergence are often mediated through complex and large-scale processes that are not amenable to traditional reductionist approaches to causal inference. Here, we suggest strategies assembled from diverse disciplines, including ecology, epidemiology, and the social sciences, to analyze complex relationships, promote cooperation, increase efficiency, and minimize bias when investigating the ecological drivers of disease emergence. These techniques, which complement traditional hypothesis testing, include epidemiologic causal criteria, strong inference, causal diagrams, model selection, and triangulation. We also present several examples from recent emerging infectious disease investigations, including Hendra virus, Nipah virus, coral diseases, and avian influenza, where these techniques were successfully applied. Here, we outline some of the barriers to advancing our understanding of causation in disease ecology and offer some solutions for investigating large-scale ecological drivers, such as global warming, pollution, and land-use change.

Reproduction and nutritional stress are risk factors for Hendra virus infection in little red flying foxes (Pteropus scapulatus)

Hendra virus (HeV) is a lethal paramyxovirus which emerged in humans in 1994. Poor understanding of HeV dynamics in Pteropus spp. (flying fox or fruit bat) reservoir hosts has limited our ability to determine factors driving its emergence. We initiated a longitudinal field study of HeV in little red flying foxes (LRFF; Pteropus scapulatus) and examined individual and population risk factors for infection, to determine probable modes of intraspecific transmission. We also investigated whether seasonal changes in host behaviour, physiology and demography affect host–pathogen dynamics. Data showed that pregnant and lactating females had significantly higher risk of infection, which may explain previously observed temporal associations between HeV outbreaks and flying fox birthing periods. Age-specific seroprevalence curves generated from field data imply that HeV is transmitted horizontally via faeces, urine or saliva. Rapidly declining seroprevalence between two field seasons suggests that immunity wanes faster in LRFF than in other flying fox species, and highlights the potentially critical role of this species in interspecific viral persistence. The highest seroprevalence was observed when animals showed evidence of nutritional stress, suggesting that environmental processes that alter flying fox food sources, such as habitat loss and climate change, may increase HeV infection and transmission. These insights into the ecology of HeV in flying fox populations suggest causal links between anthropogenic environmental change and HeV emergence.

Epidemiologic evaluation of multiple respiratory pathogens in cats in animal shelters

Upper respiratory tract infection (URI) propagates readily within cats in shelters and often results in euthanasia of affected cats. In a case-control evaluation of 573 cats in eight shelters in California in 2001 and 2002, the prevalence of feline calicivirus (FCV) was from 13 to 36%, feline herpesvirus (FHV) was from 3 to 38%, and prevalence of Bordetella bronchiseptica, Chlamydophila felis, and Mycoplasma species was from 2 to 14%. Cats with URI tended to be housed in isolation, dehydrated, and younger than cats without URI, and infected with FHV, Mycoplasma species, FCV, or C felis. Shelters differed in the prevalence of pathogens and many cats appeared positive for infection after about 1 week of sheltering. It is helpful for shelters to understand the risk factors associated with URI in order to evaluate the costs and benefits of treatment and improve their procedures to decrease the incidence of URI within their facilities. Antiherpetics and antimycoplasmal drugs may be beneficial for individual animal care. Results document the utility of comprehensive URI surveillance and herd management for specific pathogens typical in that shelter.

Canine granulocytic anaplasmosis: a review.

Anaplasma phagocytophilum is an emerging pathogen of humans, horses, and dogs worldwide that is transmitted by Ixodid ticks and maintained in a variety of small wild mammal species. Recent studies suggest that multiple strains of A. phagocytophilum may be circulating in wild and domestic animal populations, and these strains may have differential host tropisms and pathogenicity. The organism infects and survives within neutrophils by disabling key neutrophil functions, including neutrophil motility, phagocytosis, the oxidative burst mechanism, and neutrophil-endothelial cell interactions, as well as interfering with neutrophil apoptosis. Coinfections with other tick-borne pathogens may occur, especially Borrelia burgdorferi. A. phagocytophilum causes an acute febrile illness in dogs with lethargy and inappetence. Less frequent signs include lameness, coughing, polydipsia, intermittent vomiting, and hemorrhages. Diagnosis is based on finding morulae within granulocytes in the peripheral blood, the combination of acute and convalescent serology using immunofluorescent antibody techniques, and detection of the DNA of A. phagocytophilum using specific polymerase chain reaction assays. Whether persistent infection or reinfection with A. phagocytophilum occurs after natural infection requires additional study, with most reports suggesting that anaplasmosis is a self-limiting disease in dogs that responds well to a 2-week course of doxycycline therapy.

Common virus infections in cats, before and after being placed in shelters, with emphasis on feline enteric coronavirus

The purpose of this study was to determine the origin and subsequent spread of feline calicivirus (FCV), feline herpesvirus (FHV), and feline enteric coronavirus (FECV) in cats relinquished to shelters. FCV was isolated from the oral fauces of 11% of healthy cats upon entry, and isolation rates were highest for kittens (33%). FHV shedding was very low (4%) at the time of entry and occurred mainly in juveniles. FECV shedding was also common among newly relinquished cats (33%), especially older kittens and juveniles (90%). The subsequent spread of all three viruses was rapid and efficient in the shelter environment. Fifteen percent of cats were shedding FCV, 52% FHV, and 60% FECV after 1 week. More detailed studies were done with FECV shedding, which could be accurately quantitated. The amounts of FECV shed by infected cats ranged from 102 to 1016particles/swab of feces. FECV shedding was several logs higher in young kittens with primary infection than adult cats with primary infections. The mean levels of FECV shedding among adults were the same for primary and chronic infections. Although shelters were not the primary source of these viruses for many relinquished cats, factors intrinsic to the shelter environment were critical in amplifying shedding and spread to susceptible individuals. Extrinsic factors were especially important for the spread of FHV and FECV. FHV shedding rates increased from 4% to 50% in 1 weeks time. The speed and magnitude of the increase in FHV shedding suggested that there was reactivation of latent infections as well as acquisition of new infections. FECV shedding increased 10 to 1,000,000 fold in 1 week among cats that were already infected at entry, and more than one-half of initially negative cats were shedding FECV a week later. Feline calicivirus infection was the least likely to spread in the shelter. The infection rate only increased from 11 to 15% in 1 week.

Tick-Borne Rickettsial Pathogens in Ticks and Small Mammals in Korea

ABSTRACT In order to investigate the prevalence of tick-borne infectious agents among ticks, ticks comprising five species from two genera (Hemaphysalis spp. and Ixodes spp.) were screened using molecular techniques. Ticks (3,135) were collected from small wild-caught mammals or by dragging/flagging in the Republic of Korea (ROK) and were pooled into a total of 1,638 samples (1 to 27 ticks per pool). From the 1,638 tick samples, species-specific fragments of Anaplasma phagocytophilum (1 sample), Anaplasma platys (52 samples), Ehrlichia chaffeensis (29 samples), Ehrlichia ewingii (2 samples), Ehrlichia canis (18 samples), and Rickettsia rickettsii (28 samples) were amplified by PCR assay. Twenty-one pooled and individual tick samples had mixed infections of two (15 samples) or three (6 samples) pathogens. In addition, 424 spleen samples from small captured mammals (389 rodents, 33 insectivores, and 2 weasels) were screened for selected zoonotic pathogens. Species-specific DNA fragments of A. phagocytophilum (110 samples), A. platys (68 samples), E. chaffeensis (8 samples), E. ewingii (26 samples), E. canis (51 samples), and Rickettsia sp. (22 samples) were amplified by PCR assay. One hundred thirty small mammals had single infections, while 4, 14, and 21 striped field mice (Apodemus agrarius) had mixed infections of four, three, and two pathogens, respectively. Phylogenetic analysis based on nucleotide sequence comparison also revealed that Korean strains of E. chaffeensis clustered closely with those from China and the United States, while the Rickettsia (rOmpA) sequences clustered within a clade together with a Chinese strain. These results suggest that these agents should be considered in differential diagnosis while examining cases of acute febrile illnesses in humans as well as animals in the ROK.

EXPOSURE TO FELINE AND CANINE PATHOGENS IN BOBCATS AND GRAY FOXES IN URBAN AND RURAL ZONES OF A NATIONAL PARK IN CALIFORNIA

Exposure of bobcats (Lynx rufus) and gray foxes (Urocyon cinereoargenteus) to a range of common canine and feline pathogens was assessed in urban and rural zones of Golden Gate National Recreation Area, a National Park in the San Francisco Bay Area, (California, USA) from 1992 to 1995. Testing included serology for canine distemper virus, canine parvovirus (CPV), canine adenovirus, Leptospira interrogans, feline calicivirus (FCV), feline panleukopenia virus, feline herpesvirus, feline enteric coronavirus (FECV), feline immunodeficiency virus, feline leukemia virus, Toxoplasma gondii, and Bartonella henselae. Testing was also performed for Dirofilaria immitis. Significantly more gray foxes were seropositive for CPV in the urban zone than in the rural zone. In addition, radio-tracking of gray foxes in the rural zone indicated that all three of the rural CPV-seropositive foxes had traveled into adjoining small towns, whereas only one of the 11 seronegative animals had done so. Significantly more bobcats were seropositive for FCV in the rural zone than in the urban zone. Individual bobcats with positive FCV antibody titers had patterns of movement that intercepted park inholdings where domestic cats lived. Bobcat samples were seronegative for all five of the other viral feline pathogens, with the exception of a FECV-seropositive bobcat. High seroprevalence was detected for B. henselae and T. gondii in both zones. Variation in the seroprevalence for different pathogens might be related to differences in the exposure of bobcats and foxes to domestic animals: in the urban zone, gray foxes were located in residential areas outside the park, whereas bobcats were not. Although for most of the pathogens examined there was no relationship between urbanization and exposure, our results for CPV in foxes and FCV in bobcats indicated that proximity to urban areas or contact with humans can increase the risk of disease exposure for wild carnivore populations. Combining behavioral information from radio-tracking with data on pathogen exposure or disease incidence can provide valuable insights into the ecology of wildlife disease that might be missed with broadscale, population-level comparisons alone.

Investigating and managing the rapid emergence of white-nose syndrome, a novel, fatal, infectious disease of hibernating bats

White-nose syndrome (WNS) is a fatal disease of bats that hibernate. The etiologic agent of WNS is the fungus Geomyces destructans, which infects the skin and wing membranes. Over 1 million bats in six species in eastern North America have died from WNS since 2006, and as a result several species of bats may become endangered or extinct. Information is lacking on the pathogenesis of G. destructans and WNS, WNS transmission and maintenance, individual and site factors that contribute to the probability of an outbreak of WNS, and spatial dynamics of WNS spread in North America. We considered how descriptive and analytical epidemiology could be used to fill these information gaps, including a four-step (modified) outbreak investigation, application of a set of criteria (Hills) for assessing causation, compartment models of disease dynamics, and spatial modeling. We cataloged and critiqued adaptive-management options that have been either previously proposed for WNS or were helpful in addressing other emerging diseases of wild animals. These include an ongoing program of prospective surveillance of bats and hibernacula for WNS, treatment of individual bats, increasing population resistance to WNS (through vaccines, immunomodulators, or other methods), improving probability of survival from starvation and dehydration associated with WNS, modifying hibernacula environments to eliminate G. destructans, culling individuals or populations, controlling anthropogenic spread of WNS, conserving genetic diversity of bats, and educating the public about bats and bat conservation issues associated with WNS.

Aortic Valve Endocarditis in a Dog Due to Bartonella clarridgeiae

ABSTRACT We report the first documented case of endocarditis associated withBartonella clarridgeiae in any species. B. clarridgeiae was identified as a possible etiological agent of human cat scratch disease. Infective vegetative valvular aortic endocarditis was diagnosed in a 2.5-year-old male neutered boxer. Historically, the dog had been diagnosed with a systolic murmur at 16 months of age and underwent balloon valvuloplasty for severe valvular aortic stenosis. Six months later, the dog was brought to a veterinary hospital with an acute third-degree atrioventricular block and was diagnosed with infective endocarditis. The dog died of cardiopulmonary arrest prior to pacemaker implantation. Necropsy confirmed severe aortic vegetative endocarditis. Blood culture grew a fastidious, gram-negative organism 8 days after being plated. Phenotypic and genotypic characterization of the isolate, including partial sequencing of the citrate synthase (gltA) and 16S rRNA genes indicated that this organism was B. clarridgeiae. DNA extraction from the deformed aortic valve and the healthy pulmonic valve revealed the presence of B. clarridgeiae DNA only from the diseased valve. No Borrelia burgdorferi orEhrlichia sp. DNA could be identified. Using indirect immunofluorescence tests, the dog was seropositive for B. clarridgeiae and had antibodies against Ehrlichia phagocytophila but not against Ehrlichia canis, Ehrlichia ewingii, B. burgdorferi, orCoxiella burnetii.