Dual-subtype vaccine (Fel-O-Vax FIV) protects cats against contact challenge with heterologous subtype B FIV infected cats

Fel-O-Vax FIV is a dual-subtype vaccine consisting of inactivated whole viruses of subtype A (Petaluma strain) and subtype D (Shizuoka strain). The efficacy of this vaccine against heterologous subtype A strain challenge was demonstrated, but it is unclear whether the result reflects efficacy in the field. In this study, we evaluated the efficacy of this vaccine against contact challenge by exposing both vaccinated and unvaccinated control animals with cats infected with Aomori-2 strain belonging to subtype B, a subtype prevalent in many regions of the world. Nineteen specific-pathogen-free (SPF) cats were divided into a vaccinated group (six cats), an unvaccinated control group (eight cats), and a challenge group (five cats), and maintained in the same room. Cats were monitored for FIV proviral DNA by nested PCR and for FIV-specific antibody levels by ELISA. After 1 year of commingling, each cat in the vaccinated group was given a booster dose. In addition, the original challenge group was removed and replaced with another challenge group of SPF cats, which were inoculated with the Aomori-2 strain. FIV infection was confirmed in four of the eight animals in the unvaccinated control group by the 29th week in the second year of commingling. In contrast, all of the animals were negative in the vaccinated group. These findings confirmed the efficacy of this vaccine against heterologous stains classified as subtype B, and suggested that the vaccine exhibits broad efficacy against genetically diverse FIV.     

Investigation of chlamydophilosis from naturally infected cats

Background Chlamydophila felis, formerly known as Chlamydia psittaci var. felis, is frequently associated with ocular, respiratory, and occasionally reproduction tract infections. Even though the infection is sometimes asymptomatic, it potentially results in a latent immunosuppressive infection.ObjectiveThis study aimed to identify occurrences of feline chlamydophilosis, rarely reported in cats in Indonesia.MethodsThe observation was conducted in three cats with clinical signs of Cp. felis infection, particularly relapsing conjunctivitis. The cats'' histories were recorded based on owners'' information. Conjunctival swabs were sampled for cytology examination and molecular assay detection. A phylogenetic tree was generated using MEGA-X software to reveal group clustering. A post-mortem examination was performed on the cat that died during an examination.ResultsCp. felis was detected in both cytological examination and polymerase chain reaction assay. The phylogenetic tree demonstrated that the Cp. felis isolated in this study clustered with several other isolates from the other countries. Cp. felis can be isolated from cats with different clinical manifestations and levels of severity. The chronic fatal infection demonstrated interstitial broncho-pneumonia under histopathological examination.ConclusionsMolecular assay of Cp. felis is always recommended to obtain a definitive diagnosis of feline chlamydophilosis since the disease can have various clinical manifestations. Even though it may be subclinical and is often not fatal, an infected cat may be a carrier that could spread the pathogen in the surrounding environment. Serious disease management is suggested to avoid high costs associated with regularly relapsing disease.     

Alteration in blood gases in cats naturally infected with Aelurostrongylus abstrusus

Four cats were presented with respiratory signs and first-stage larvae of Aelurostrongylus abstrusus were found in faecal samples. Anthelmintic treatment was given to the infected cats and venous blood gases were analysed during the treatment period. Blood gas analysis suggested hypoventilation and respiratory acidosis in infected cats. Hypoventilation may be the result of airway obstruction by adults and larvae in respiratory bronchioles and the alveolar canals. The blood gas values had returned close to the physiological range by two months after treatment. Assessment of respiratory acidosis may aid development of additional treatment methods in cats infected with A. abstrusus.     

Genetic complexity and multiple infections with more Parvovirus species in naturally infected cats

ABSTRACT: Parvoviruses of carnivores include three closely related autonomous parvoviruses: canine parvovirus (CPV), feline panleukopenia virus (FPV) and mink enteritis virus (MEV). These viruses cause a variety of serious diseases, especially in young patients, since they have a remarkable predilection for replication in rapidly dividing cells. FPV is not the only parvovirus species which infects cats; in addition to MEV, the new variants of canine parvovirus, CPV-2a, 2b and 2c have also penetrated the feline host-range, and they are able to infect and replicate in cats, causing diseases indistinguishable from feline panleukopenia. Furthermore, as cats are susceptible to both CPV-2 and FPV viruses, superinfection and co-infection with multiple parvovirus strains may occur, potentially facilitating recombination and high genetic heterogeneity. In the light of the importance of cats as a potential source of genetic diversity for parvoviruses and, since feline panleukopenia virus has re-emerged as a major cause of mortality in felines, the present study has explored the molecular characteristics of parvovirus strains circulating in cat populations. The most significant findings reported in this study were (a) the detection of mixed infection FPV/CPV with the presence of one parvovirus variant which is a true intermediate between FPV/CPV and (b) the quasispecies cloud size of one CPV sample variant 2c. In conclusion, this study provides new important results about the evolutionary dynamics of CPV infections in cats, showing that CPV has presumably started a new process of readaptation in feline hosts.     

Local pulmonary immune responses in domestic cats naturally infected with Cytauxzoon felis

Cytauxzoonosis is a hemoprotozoal disease of cats and wild felids in the South and Southeastern United States caused by Cytauxzoon felis. Although the causative agent has been recognized since the seventies, no study has examined the local immune response in affected organs, such as the lung, and compared them to the lungs of uninfected domestic cats. Previous studies have suggested that the histopathologic findings in the lungs of C. felis-infected cats are caused by the release of pro-inflammatory mediators, such as cytokines and increased production of inducible nitric oxide synthase (iNOS), by the infected macrophages. Our laboratory had previously found an upregulation of the adhesion molecule CD18, which can stimulate the release of these pro-inflammatory mediators. The objective of this study was to characterize local pulmonary immune responses in cats naturally infected with C. felis. Immunohistochemistry was performed to detect tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and major histocompatibility complex (MHC) II in 19 lungs from affected cats that died between 2005 and 2013. Results showed increased expression of all of these molecules when compared to lungs from uninfected, healthy cats. Furthermore, MHC II is expressed in the endothelium of C. felis naturally infected cats. These results support that there is a marked, local, pro-inflammatory immune response that can contribute to the pathogenesis of cytauxzoonosis in the lungs.     

Distribution of immune cells in the female reproductive tract in uninfected and FIV infected cats

Cell-free and cell-associated FIV effectively cross the mucosa of the feline female reproductive tract. To identify possible cellular targets of FIV and to characterize changes in mucosal immunity after infection, we examined the types and numbers of immune cells residing in the reproductive tracts of control and intravaginally FIV-infected cats. Sections of the vestibule, vagina, cervix, uterus, and ovaries, were examined by immunohistochemistry for CD4+ and CD8+ T lymphocytes, CD22+ B lymphocytes, CD1a+ dendritic cells, and CD14+ macrophages. The reproductive tract of uninfected cats contained substantial numbers of CD8+ T lymphocytes, CD4+ T lymphocytes and macrophages, as well as moderate numbers of CD1a+ dendritic cells, and few B lymphocytes. The most prominent change between FIV- and FIV+ cats was a marked decrease in the concentration of CD4+ T lymphocytes resulting in inverted CD4+:CD8+ ratios throughout the reproductive tract of infected cats. There was also a trend towards increasing numbers of CD1a+ dendritic cells in the intravaginally-infected FIV+ cats, and decreasing numbers of macrophages and CD22+ B lymphocytes. This study indicates that similar to the peripheral immune system, FIV infection is associated with CD4+ cell loss and reduced CD4+:CD8+ ratios in the female reproductive mucosal tissue.     

Renal effects of Dirofilaria immitis in experimentally and naturally infected cats

Canine heartworm infection has been associated with glomerular disease and proteinuria. We hypothesized that proteinuria, likely due to glomerular damage, would also be found in cats experimentally and naturally infected with Dirofilaria immitis. Two populations of cats were evaluated, including 80 that were each experimentally infected with 60 infective heartworm larvae as part of a drug safety study, and 31 that were naturally infected with D. immitis. Each had a control population with which to be compared. In the experimentally infected group, we evaluated urine from 64 cats. Ten of these cats were shown to have microalbuminuria 8 months post infection. No cat refractory to infection with larvae and no cats from the control group demonstrated microalbuminuria. All 10 microalbuminuric cats were shown to have significant proteinuria, as measured by the urine protein:creatinine ratio. There was a subtle, but significant, association between worm burden and proteinuria, and although the presence of adult heartworms was required for the development of proteinuria, both microfilaremic and amicrofilaremic cats were affected. Neither the presence of circulating heartworm antibodies and antigen nor the presence of antigenuria predicted the development of proteinuria. Both heavily infected cats (5-25 adult heartworms) and cats with worm burdens compatible with natural infections (1-4 adult heartworms) developed proteinuria, and the relative numbers of cats so affected were similar between heavily and more lightly infected cats. Naturally infected cats, for which only dipstick protein determinations were available, were shown to have a significantly greater incidence of proteinuria (90% vs 35%) than did those in an age- and gender-matched control population. Additionally, the proteinuria in heartworm-infected cats was 3- to 5-fold greater in severity. We conclude that cats infected with mature adult heartworms are at risk for developing proteinuria and that this is recognized relatively soon after infection. While heavier infections may predispose cats to developing proteinuria, this complication is seen in naturally infected cats and experimental cats with worm burdens similar to those seen in natural infections (i.e., "clinically appropriate" worm burdens). The clinical relevance of heartworm-associated proteinuria is yet to be determined.     

Beta cell and insulin antibodies in treated and untreated diabetic cats

Beta cell and insulin antibodies are involved in the pathogenesis of diabetes in human patients. Beta cell antibodies have also been found in about 50% of newly diagnosed diabetic dogs. This study's objective was to examine these antibodies' role in feline diabetes. The serum of 26 newly diagnosed untreated diabetic cats, 29 cats on insulin therapy, 30 cats with diseases other than diabetes, and 30 healthy cats was examined for beta cell and insulin antibodies. For beta cell antibody testing, purified beta cells from a radiation-induced transplantable rat insulinoma were used. Serum from cats in which anti-beta cell antibodies were induced by injecting a purified beta cell suspension subcutaneously was used as a positive control. Following incubation with test sera, fluorescein-labeled anti-cat immunoglobulins were used to visualize binding between the beta cells and cat gamma globulins. Each serum was tested on two different tumor preparations. For the detection of insulin antibodies, a charcoal separation method was used. It was found that none of the healthy cats, none of the newly diagnosed, untreated diabetic cats and none of the cats with diseases other than diabetes had antibodies against beta cells or against endogenous insulin. Four diabetic cats (14%) that had been treated with different insulin preparations had insulin antibodies.It is concluded that immune-mediated processes are not causing diabetes in the cat. Further studies are needed to evaluate if antibodies directed against exogenous insulin alter the response of diabetic cats to insulin.     

Changes in the levels of eicosanoids in cats naturally and experimentally infected with Dirofilaria immitis

Feline heartworm (Dirofilaria immitis) infection is a severe, life-threatening disease. The eicosanoids are lipid mediators derived from the metabolism of the arachidonic acid, involved in the regulation of the immune response and of inflammatory reactions. In this study, naturally infected cats showed significant higher levels of prostaglandin E(2) (PGE2), thromboxane B(2) (TXB(2)) and leukotriene B(4) (LTB4) than uninfected cats. Changes in the levels of eicosanoids during the infection were observed in experimentally infected cats. PGE2 increased significantly during the first 60 days post-infection, then progressively decreased until day 180 post-infection. At this time, PGE2 values are still significantly higher than those observed before the infection. TxB2 and LTB4 increased progressively from the beginning of infection and reached their maximum levels 180 days post-infection. In experimentally infected, ivermectin-treated cats, 15 days after treatment (45 days after infection) both PGE2 and LTB4 levels were similar to those observed in experimentally infected, untreated cats. No significant differences of PGE2 levels were found before the infection and at the end of the experiment (165 days post-treatment, 195 days post-infection). Increased levels of LTB4 were found 15 days post-treatment, afterward they progressively decreased. These data show that D. immitis infection influences the production of intravascular eicosanoids in cats. The high levels of PGE2 observed in the early phase of infection could be related to the survival of the worms, while those of TxB2 and LTB4 detected at the end of the study could mediate the inflammatory reactions and thrombi formation during the feline dirofilariosis.     

Acute phase proteins response in cats naturally infected by hemotropic mycoplasmas

Information about the acute phase proteins (APP) response in cats naturally infected with hemoplasmas and in cats co-infected with different species of hemoplasmas is lacking.This study evaluated serum amyloid A (SAA), haptoglobin (Hp) and albumin in 48 cats naturally infected with hemoplasmas, including 25 with Candidatus Mycoplasma haemominutum and 23 co-infected with different hemoplasmas agents; and in 10 healthy control cats.Infected cats had significantly higher Hp and lower albumin than controls. Symptomatic cats had significantly higher SAA and Hp, and lower albumin than asymptomatic animals, and also than controls. Asymptomatic cats had significantly higher Hp than controls. Concentrations of APP were not significantly different between single infected and co-infected cats.According with these results, hemoplasmosis should be considered when alterations in APP are detected in diseased cats with compatible clinical signs. Furthermore, a subclinical infection should be considered in apparently healthy cats from endemic areas with increased Hp.     

Clonality analysis of various hematopoietic disorders in cats naturally infected with feline leukemia virus

The clonality analysis of the bone marrow cells was carried out by detecting the integrated proviruses of feline leukemia virus (FeLV) to understand the pathogenesis of FeLV-associated hematopoietic disorders in cats. Bone marrow cells from 4 cases with acute myeloid leukemia (AML), 9 cases with myelodysplastic syndromes (MDS), 2 cases with pure red cell aplasia (PRCA) and 3 healthy carriers infected with FeLV were subjected to Southern blot analyses using an exogenous FeLV probe. Clonal hematopoiesis was found in all the cases with AML and in 6 of the 9 cases with MDS, but not in the cases with both PRCA and healthy carriers infected with FeLV. In the 2 cases with MDS, it was thought that the same clones of the hematopoietic cells might proliferate before and after the progression of the disease irrespective of the changes of the hematological diagnoses by cytological examination. This study indicates that MDS in cats is a disease manifestation as a result of clonal proliferation of hematopoietic cells and can be recognized as a pre-leukemic state of AML.     

Antibody responses to Toxoplasma gondii antigens in aqueous and cerebrospinal fluids of cats infected with T. gondii and FIV.

Antibodies to antigens of Toxoplasma gondii were measured in the aqueous and cerebrospinal fluid (CSF) of 16 specific-pathogen free kittens experimentally infected with feline immunodeficiency virus (FIV), T. gondii, or both pathogens. The results indicated that all cats infected with T. gondii had antibody responses to antigens of T. gondii in both aqueous fluids and CSF. Co-infection with FIV did not affect antibody levels. Aqueous fluids from eyes of cats with toxoplasmic retinochoroiditis did not necessarily have higher antibody levels than those from eyes without lesions. Antibodies to T. gondii were also detected in the CSF of two cats from whose brains no parasites were isolated by in vivo mouse inoculation. Total IgG did not increase significantly in the aqueous fluids and CSF of cats infected with T. gondii whether or not they were also infected with FIV.     

Peripheral and intracerebral T cell immune response in cats naturally infected with Borna disease virus.

Borna disease virus (BDV) is a neurotropic agent with capacity to cause encephalomyelitis in a wide range of animal species, including horses and cats. Recent studies also point to a link between BDV and human neuropsychiatric disorders. The pathogenesis of Borna disease (BD) has been proposed to be immune-mediated, mainly through the effects of cytotoxic T cells. We used flow cytometric analysis in order to characterize the peripheral and intracerebral T cell immune response in cats naturally infected with BDV. Our results show the presence of two different CD8+ cell populations (CD8+low and CD8+high) in the blood, spleen and brain of these cats. In the brain, CD8+low cells predominated over CD8+high cells. Since CD8+low cells have been suggested to represent a non-MHC-restricted T cell population, the recruitment of such cells to the brains of BDV-infected cats could possibly be of importance for the clearance of virus from neurones.     

Quantification of viral ribonucleic acid in plasma of cats naturally infected with feline immunodeficiency virus

OBJECTIVE: To assess plasma viral RNA concentration in cats naturally infected with feline immunodeficiency virus (FIV). ANIMALS: 28 FIV-infected cats. PROCEDURE: Cats were categorized into 1 of the 3 following stages on the basis of clinical signs: asymptomatic (nonclinical) carrier (AC; n = 11), acquired immunodeficiency syndrome-related complex (ARC; 9), or acquired immunodeficiency syndrome (AIDS; 8). Concentration of viral RNA in plasma (copies per ml) was determined by use of a quantitative competitive polymerase chain reaction (QC-PCR) assay. Total lymphocyte count, CD4+ cell and CD8+ cell counts, and the CD4+ cell count-to-CD8+ cell count ratio were determined by use of flow cytometry. RESULTS: Plasma viral RNA concentration was significantly higher in cats in the AIDS stage, compared with cats in AC and ARC stages. Most (5/7) cats in the AIDS stage had low total lymphocyte, CD4+ cell, and CD8+ cell counts. CONCLUSIONS AND CLINICAL RELEVANCE: Concentration of plasma viral RNA is a good indicator of disease progression in FIV-infected cats, particularly as cats progress from the ARC to the AIDS stage. Determination of CD4+ and CD8+ cell counts can be used as supportive indicators of disease progression.     

Genomic variations among Bartonella henselae isolates derived from naturally infected cats

The purpose of this study was to understand the mechanisms of persistent infection with Bartonella henselae in cats. Blood samples were collected from three naturally infected cats for 24 months. These cats were confirmed to be persistently infected with B. henselae by serological and bacteriological examination. Relapsing bacteremia was found in all three cats with intervals of 3-19 months. Following the peaks of bacteremia, increases of specific antibody titer were observed in these cats. To examine the genetic differences among the isolates derived from the first and following bacteremia, the genome DNA patterns of the restriction enzyme fragment length polymorphism (RFLP) of the isolates were examined by pulsed field gel electrophoresis. The isolates derived from the first bacteremia showed an identical RFLP pattern in each of the three cats. The isolates derived from the following peaks, however, showed 1-3 of different RFLP patterns in these cats. Furthermore, the isolates showing different RFLP patterns from those of the first bacteremia were also detected at the following bacteremic peaks in all three cats examined. The 16S ribosomal RNA (rRNA) gene type of all isolates was found to be 16S rRNA type I. The emergence of genetically distinct organisms at various peaks of bacteremia may contribute to the establishment of persistent infection in the naturally infected cats.