Case study: Canine non‐epitheliotropic CD4‐positive cutaneous T‐cell lymphoma: a case report
Case study: Canine non‐epitheliotropic CD4‐positive cutaneous T‐cell lymphoma: a case report Robert Lo, Ph.D, D.V.M A 5‐year‐old, spayed female French Bulldog presented with multiple papules on the skin of the scapular area. Histopathological examination of skin biopsy specimens showed proliferated small lymphoid cells in the superficial dermis and in the area around the hair follicle. Immunohistochemical examination revealed that these cells were positive for CD3, CD4 and TCRαβ antibodies, but negative for CD1c, CD8α, CD8β, CD11c, CD20, CD45RA, CD90, MHC-II and TCRγδ antibodies. In addition, CD45 is highly expressed, and proliferation is very low. The genetic recombination test of the T cell receptor G chain detects the proliferation of recombinant clones. Skin lesions were removed by surgery because of progressing to the outside of the forelegs. The postoperative clinical course was good, and no recurrence was observed until the dog died in a traffic accident about a year later. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498901/ Figure 1 Clinical features of the dog. Multiple papules are present on the right scapular area. Figure 2 Histopathological features of the lesion. Small lymphoid cells are proliferative at the superficial dermis and the perifollicular areas. Figure 3 Immunohistochemical analysis via the avidin‐biotin‐peroxidase complex method. Dense infiltration of CD4‐positive small lymphoid cells is evident at the superficial dermis. Bar = 200 μm.
Case study: Coinfection with Tritrichomonas foetus and Giardia duodenalis in Two Cats with Chronic Diarrhea
Case study: Coinfection with Tritrichomonas foetus and Giardia duodenalis in Two Cats with Chronic Diarrhea Robert Lo, Ph.D, D.V.M A mixed infection of Tritrichomonas foetus and Giardia duodenalis was confirmed in two 6-year-old Maine Coon cats. One of the cats had a history of chronic liquid diarrhea and several treatment failures. Both cats observed G. duodenalis and trichomonas from the fecal smears, and the infection of T. foetus was also confirmed by RT-PCR. The cat recovered completely after taking ronidazole treatment. In refrigerated stool specimens collected from cats with chronic diarrhea, drop-shaped trichomonad pseudocysts, which are smaller than the cysts of G. duodenalis, were detected. When the pseudocysts are stained with Lugol’s solution or Giemsa, they appear brown or light blue, respectively, and their morphological characteristics are similar to those of bovine T. foetus in vitro. It is worth noting that the pseudocysts in feline trichomonads may be a way for the protozoa to fight against unfavorable environments. Clinicians detected pseudocysts in refrigerated stool, which may be a useful clues to the diagnosis of this disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005279/ Figure 1 Fecal smears of a 6-month-old female Maine Coon cat with chronic liquid diarrhea, stained with Lugol’s solution (a–c) and Giemsa stain (d–f); showed (a) and (d) Giardia duodenalis trophozoites ; (B) and (e) a Giardia duodenalis cyst; (c) and (f) drop-shaped trichomonads (630x). Fecal smears from a 6-month-old female Maine Coon cat with chronic liquid diarrhea stained with Lugol’s solution (a–c) and Giemsa stain (d–f); (a) and (d) showed Giardia duodenalis trophozoite; (b) and (e) showed a Giardia duodenalis cyst; (c) and (f) showed drop-shaped trichomonads (630x). Figure 2 Trichomonads in fecal smear from the cat with diarrhea. Arrow heads in (a) indicate anterior flagella emerging from the trophozoite, while arrow heads in (b) indicate undulating membrane (1000x). Figure 3 Typical morphology of trichomonads observed in saline solution-diluted fresh fecal smear from the cat with diarrhea. Arrow heads in (a) and in (b) indicate anterior flagella and undulating membrane, respectively (630x). Figure 4 Drop-shaped unidentified elements in fecal smears stained with Lugol’s solution (a) and Giemsa stain (b-c). Arrow heads in (a) indicate an internal oval structure (400x). Arrow heads in (b) indicate a curved linear structure (1000x). Arrow heads in (c) indicate an undulated portion of the surface (1000x).
Toxoplasmosis In Cats: A Review
Toxoplasmosis In Cats: A Review. Maigan Espinili Maruquin Structure and Replication Fig. 01 Structure of Toxoplasma gondii (https://www.123rf.com/photo_81668845_stock-vector-toxoplasma-gondii-structure-.html) The family Felidae is the only animal species that hosts infective oocysts of Toxoplasma gondii and passes through their feces, however, this parasite infects most species of birds and mammals (Elmore, Jones et al. 2010). This pathogen is an obligate intracellular coccidian parasite an can infect warm-blooded animals, including people (Hartmann, Addie et al. 2013) (Dubey JP, 2005; Dubey JP and Lappin MR, 2006). The complex life cycle of T. gondii undergoes three distinguished stages. The tachyzoites, formerly called the trophozoite or endozoite, is the active multiplying stage and most likely to cause clinical disease and spread to almost all organs. The next stage is the bradyzoite stage where multiplication is slow and usually within a tissue cyst, leading to a life-long chronic infection. This stage penetrates the small intestine epithelial cells. Finally, the oocysts, which are excreted and shed in feces of infected felid, are the result of sexual reproduction within the intestine and constitute the environmentally resistant stage. (Dubey JP, 2005; Dubey JP and Lappin MR, 2006) (Dabritz, Gardner et al. 2007, Dabritz, Miller et al. 2007, Hartmann, Addie et al. 2013, Wyrosdick and Schaefer 2015, Calero-Bernal and Gennari 2019). Oocysts are non- infectious when excreted in feces but begin to become sporulate after 1-5 days of exposure to air and moisture. These are round to oval in shape and around 10 x 12 μm in size. Most naïve cats who get infected take 3–10 days of ingestion of tissue cysts to complete the cycle (Hartmann, Addie et al. 2013) (Dubey JP, 2005; Dubey JP and Lappin MR, 2006). Infection/ Pathogenesis The very first case of toxoplasmosis in cats was diagnosed from a domestic cat in Middletown, NY, in 1942 (Olafson and Monlux, 1942; Dubey, 2008)(Wyrosdick and Schaefer 2015). Generally, most cats at 6 to 10 weeks were detected to have antibodies to T. gondii while maternally transferred antibodies (MTAs) disappear by 12 weeks of age. Seropositivity increases with the age and varies according to the cat’s lifestyle (like hunting food) (Dubey, J.P., 2010)(Dubey, Cerqueira-Cézar et al. 2020). The oocysts were noted to remain infectious in the environment for at least 12 months (Hutchison 1965, Wyrosdick and Schaefer 2015). Generally, transmissions of the parasite are congenital infection, ingestion of the infected tissue, and ingestion of oocyst-contaminated food or water (Dubey JP and Lappin MR., 2006) (Hartmann, Addie et al. 2013). Most likely, congenitally infected kittens show clinical signs while post-natal infections are usually through ingestion of infected tissue cysts and in some cases, oocysts (Dubey and Jones 2008, Elmore, Jones et al. 2010). Queens giving birthe to infected kittens during gestation can become infected transplacentally or via suckling (Dubey JP, et al., 1996) (Calero-Bernal and Gennari 2019) The most common method of feline infection due to predation of intermediate hosts is tissue cyst ingestion where shedding occurs in 3 to 5 days, while ingestion of tachyzoites takes 8- 10 days, and 21-24 days after ingestion of oocysts (Dubey, J.P., 2010) (Schares, Vrhovec et al. 2008, Wyrosdick and Schaefer 2015). Clinical Signs Feline toxoplasmosis develops clinical signs rarely but causes inflammation and tissue necrosis from intracellular growth of tachyzoites (Dubey JP and Lappin MR, 2006)(Hartmann, Addie et al. 2013). It frequently results to hepatitis, pneumonia, and encephalitis with signs of ascites, lethargy, and dyspnea while infected adults do not show specific clinical signs (Brennan A, et al, 2016) (Dubey and Carpenter 1993, Calero-Bernal and Gennari 2019). Moreover, observations also showed extra- intestinal enteritis (Cohen, Blois et al. 2016) and inflammatory intestinal disease (Peterson, Willard et al. 1991). Tissues that are most commonly affected are the central nervous system, the muscles, the lungs, and the eyes. Infected cats show neurological signs, muscle hyperesthesia, jaundice, diarrhea, fever, depression, anorexia, vomiting, paresis, dermatitis and weight loss (Dubey JP and Lappin MR, 2006) (Hartmann, Addie et al. 2013, Dubey, Cerqueira-Cézar et al. 2020). When severe respiratory and neurological signs were observed, it’s usually fatal (Dubey and Carpenter 1993). Diagnosis Diagnosis in cats for toxoplasmosis include ante-mortem fecal examination for oocysts and serologic testing (Johnson, Tinker et al. 2009, Elmore, Jones et al. 2010). However, geographical location may influence differential diagnosis (Calero-Bernal and Gennari 2019). The shedding of the oocysts of an infected cats may only be once in their lifetime (Elmore, Jones et al. 2010) which can be diagnosed in their fecal samples via microscopy (Hartmann, Addie et al. 2013). However, there is low probability of finding oocysts in the fecal samples of infected cats and there is a confusing morphological resemblance of the T. godii oocysts to other coccidian like Hammondia hammondi and Besnoitia spp (Elmore, Jones et al. 2010). Therefore, molecular and bioassay techniques can be used to distinguish them while only mouse bioassay is the definitive confirmation method (Dubey 2009, Elmore, Jones et al. 2010). In diagnosing T. gondii, confirmation is when the organism is found in body fluids or tissue (Hartmann, Addie et al. 2013). For tachyzoites detection, ante- mortem diagnosis in tissues and body fluids during acute illness may use cytology or polymerase chain reaction (PCR). A definitive diagnosis is when tachyzoites were detected rarely in blood but aqueous humour, lymph nodes, and transtracheal or bronchoalveolar lavage fluid can be used (Hartmann, Addie et al. 2013). On the other hand, antibodies of the IgM, IgG and IgA isotypes can be detected by immunofluorescence assay (IFA). For antibody- negative, cats are likely to shed oocysts while antibody- positive cats don’t shed oocysts wherein antibodies need 2–3 weeks to develop (Dubey JP, 2005)(Hartmann, Addie et al. 2013). Despite the development of immunofluorescence and ELISA tests, requirement for species-specific protein conjugate makes it limitedly used in veterinary diagnostics (Wyrosdick and Schaefer 2015). After comparing indirect hemagglutination test, latex agglutination test, Feldman dye test and modified agglutination tests, the aqueous humour resulted to be the most sensitive of
Heartworm in Cats
Heartworm in Cats Andy Pachikerl, Ph.D Introduction of Feline Heartworm Heartworm disease is a serious and potentially fatal disease in pets worldwide and it is caused by foot-long worms (heartworms) that dwells in the heart, lungs, and associated blood vessels of affected pets. This in turn cause severe lung disease, heart failure and damage to other organs in the body. Heartworm disease affects dogs, cats, and ferrets, but heartworms also live in other mammal species, including wolves, coyotes, foxes, sea lions and—in rare instances—humans. Because wild species such as foxes and coyotes live in proximity to many urban areas, they are considered important carriers of the disease (Ettinger, et al., 2010). Among mammalian definitive hosts, they are best adapted to domesticated and wild dogs. If untreated, their numbers can increase, and dogs have been known to harbour several hundred worms in their bodies. Heartworm disease causes lasting damage to the heart, lungs, and arteries, and can affect the dog’s health and quality of life long after the parasites are gone (2019). For this reason, prevention is by far the best option, and treatment—when needed—should be administered as early in the course of the disease as possible. Heartworm disease in cats is quite distinctive from heartworm disease in dogs. Since cat is an atypical host for heartworms, most worms in cats do not survive to the adult stage. Cats with adult heartworms usually have just one to three worms, and many cats affected by heartworms have no adult worms. Even if feline host of heartworm rarely occurs, cat heartworm disease often goes undiagnosed. Therefore, it is important to understand that even immature worms cause real damage in the form of a condition known as heartworm associated respiratory disease (HARD). Moreover, the medication used to treat heartworm infections in dogs cannot be used in cats, so prevention is the only means of protecting cats from the effects of heartworm disease (Society, 2007). Transmission Figure 1. Diagram from American Heartworm Society showing how the heartworm is spread and inter-transmission can occur via different host pets. The mosquito plays an essential role in the heartworm life cycle. Adult female heartworms living in an infected dog, fox, coyote, or wolf produce microscopic baby worms called microfilaria that circulate in the bloodstream. When a mosquito bites and takes a blood meal from an infected animal, it picks up these baby worms, which develop and mature into “infective stage” larvae over a period of 10 to 14 days (Johnstone, 1998). Then, when the infected mosquito bites another dog, cat, or susceptible wild animal, the infective larvae are deposited onto the surface of the animal’s skin and enter the new host through the mosquito’s bite wound. Once inside a new host, it takes approximately 6 months for the larvae to mature into adult heartworms. Once mature, heartworms can live for 5 to 7 years in dogs and up to 2 or 3 years in cats. Because of the longevity of these worms, each mosquito season can lead to an increasing number of worms in an infected pet (Knight, et al., 1998). Symptoms and signs of heartworm in cats Signs of heartworm disease in cats can be of two extremes: very subtle or plain out dramatic. Symptoms may include coughing, asthma-like attacks, periodic vomiting, lack of appetite, or weight loss. Occasionally an affected cat may have difficulty walking, experience fainting or seizures, or suffer from fluid accumulation in the abdomen. Unfortunately, the first sign in some cases is collapse of the cat, or sudden death (Society, 2007). How significant is my cat’s risk for heartworm infection? Figure 2. Diagram showing the severity of heartworms in the USA as shown by the American Heartworm Society Many factors must be considered, even if heartworms do not seem to be a problem in your local area. Your community may have a greater incidence of heartworm disease than you realize—or you may unknowingly travel with your pet to an area where heartworms are more common. Heartworm disease is also spreading to new regions of the country each year. Stray and neglected dogs and certain wildlife such as coyotes, wolves, and foxes can be carriers of heartworms. Mosquitoes blown great distances by the wind and the relocation of infected pets to previously uninfected areas also contribute to the spread of heartworm disease (this happened following Hurricane Katrina when 250,000 pets, many of them infected with heartworms, were “adopted” and shipped throughout the country). The fact is that heartworm disease has been diagnosed in all 50 states, and risk factors are impossible to predict. Multiple variables, from climate variations to the presence of wildlife carriers, cause rates of infections to vary dramatically from year to year—even within communities. And because infected mosquitoes can come inside, both outdoor and indoor pets are at risk. For that reason, the American Heartworm Society recommends that you “think 12:” (1) get your pet tested every 12 months for heartworm and (2) give your pet heartworm preventive 12 months a year. Diagnosis Heartworm disease is a serious, progressive disease. The earlier it is detected, the better the chances the pet will recover. There are few, if any, early signs of disease when a dog or cat is infected with heartworms, so detecting their presence with a heartworm test administered by a veterinarian is important. The test requires just a small blood sample from your pet, and it works by detecting the presence of heartworm proteins. Some veterinarians process heartworm tests right in their hospitals while others send the samples to a diagnostic laboratory. In either case, results are obtained quickly. If your pet tests positive, further tests may be ordered (Yin, 2007). Diagnosis period Heartworm infection in cats is harder to detect than in dogs, because cats are much less likely than dogs to have adult heartworms. The preferred method for screening cats includes the use of both an antigen and an antibody test (the “antibody”
A Review on Feline Calicivirus
Maigan Espinili Maruquin Structure and Replication The Caliciviruses are small, non-enveloped, positive strand RNA viruses which infects a wide range of hosts (Sosnovtsev and Green 2003), which, in cats, feline calicivirus- (FCV) is associated with upper respiratory tract infections (Gaskell, R. M., 1985). The FCV is a naked and icosaedral virus, 30–40 nm in diameter (Carter MJ, Madeley CR, 1987). The single protein capsid is 65- 66 kDa (Neill, Reardon et al. 1991, Carter, Milton et al. 1992), having a single-stranded positive- sense RNA genome of 7.7 kb (Carter, Milton et al. 1992). Having 3 ORFs, the ORF1 encodes a 200 kDa polyprotein to be processed into six mature non-structural proteins (Di Martino, Marsilio et al. 2007). Whereas, the ORF2, which is divided into six regions (A, B, C, D, E, and F), encodes a 73 kDa capsid precursor (preVP1) which undergoes rapid proteolytic cleavage during the maturation process, yielding a mature 60 kDa capsid protein (VP1) (Carter 1989, Carter, Milton et al. 1992, Sosnovtsev, Sosnovtseva et al. 1998, Sosnovtsev and Green 2003, Di Martino, Marsilio et al. 2007, Prikhodko, Sandoval-Jaime et al. 2014). The E-region is responsible for antigenic properties of the FCV virion (Guiver, Littler et al. 1992, Milton, Turner et al. 1992, Seal, Ridpath et al. 1993, Tohya, Yokoyama et al. 1997, Prikhodko, Sandoval-Jaime et al. 2014) and is also responsible to the protruding (P) subdomain P2 on the virion surface (Chen, Neill et al. 2006, Ossiboff, Zhou et al. 2010, Prikhodko, Sandoval-Jaime et al. 2014). Finally, the ORF3, encodes a small minor structural protein, 12 kDa, with 106 amino acids, VP2, and is essential for the production of infectious virions (Sosnovtsev, Belliot et al. 2005, Di Martino, Marsilio et al. 2007). The replication of FCV includes a plus-sense genomic RNA of approximately 7.7 kb, and a subgenomic RNA of 2.4 kb (Herbert, Brierley et al. 1996, Sosnovtsev and Green 2003) Fig. 01. The Feline Calicivirus Source: https://www.123rf.com/photo_29482486_feline-calicivirus-capsid-causes-a-viral-disease-in-cats-a-vaccine-exists-atomic-level-structure-.html Epidemiology The FCV has originally been isolated from the gastrointestinal tract of cats in New Zealand (Fastier 1957, Pesavento, Chang et al. 2008). High viral prevalence in a population has been explained by long-term shedders (Hurley, Pesavento et al. 2004), sequential infections and episodes of reinfection (Coyne, Gaskell et al. 2007, Pesavento, Chang et al. 2008). With the features of FCV: high genetic variability, a capacity to persist in infected individuals, stability in the environment, and ubiquity in feline populations worldwide are causing the severity of the disease (Pesavento, Chang et al. 2008). Humans are not susceptible to FCV (Radford, Addie et al. 2009). Cats may also shed from 30 days to years even after recovery (Wardley 1976). The FCV infection is widespread among cat populations, having a report of 25–40% from colonies and shelters (Wardley, Gaskell et al. 1974, Bannasch and Foley 2005, Helps, Lait et al. 2005, Radford, Addie et al. 2009). Pathogenesis / Clinical Signs The FCV enters via nasal, oral or conjunctival routes wherein oropharynx is the primary site of replication. At 3 to 4 days of post infection, transient viraemia occurs and can be detected in many other tissues. Epithelial necrosis occurs while vesicles develop into ulcers, which is usually in the margin of the tongue. Neutrophils infiltrate the dermis of other tissues; and it takes 2 to 3 weeks to start healing (Gaskell RM, 2006) (Radford, Coyne et al. 2007, Radford, Addie et al. 2009). a. Oral and Upper Respiratory Tract Disease Mostly in kittens, incubation period takes 2–10 days. oral ulceration, sneezing and serous nasal discharge start to appear (Gaskell RM, 2006) (Radford, Addie et al. 2009). In some severe cases, pneumonia occurs, pulmonary lesions occur more rarely, dyspnoea, coughing, fever and depression, can occur, particularly in young kittens (Radford, Coyne et al. 2007, Radford, Addie et al. 2009). b. FCV-associated Lameness There could be lesions in the joints of cats with acute synovitis, consists with thickening of the synovial membrane and an increase in quantity of synovial fluid (Dawson, Bennett et al. 1994, Radford, Coyne et al. 2007). Fever could be observed following FCV infection and vaccination, usually a few days or weeks after the acute oral or respiratory signs (Pedersen NC, 1983) (Radford, Addie et al. 2009). c. Virulent systemic FCV disease (VSD) The virulent systemic FCV disease is manifested by systemic inflammatory response syndrome, disseminated intra – vascular coagulation, multi- organ failure and death, with mortality rates of up to 67% (Foley, Hurley et al. 2006, Radford, Addie et al. 2009). During VSD, virus infiltrates cellular compartments not normally associated with FCV; lesions are widespread with ulceration of the skin, broncho-interstitial pneumonia and necrosis in the liver, spleen and pancreas (Pedersen, Elliott et al. 2000, Pesavento, Maclachlan et al. 2004, Radford, Coyne et al. 2007). The FCV evolves to be efficiently transmitted among the cat population (Radford, Coyne et al. 2007). Clinical signs initially appear as a severe acute upper respiratory tract disease. Lesions, ulcers and alopecia are observed on the nose, lips and ears, around the eyes and on the footpads (Radford, Addie et al. 2009). d. Molecular pathogenesis Cytopathic effect is observed in infected cells, with cell rounding and membrane blebbing (Knowles J.O, 1988), which leads to inhibition of cellular protein synthesis (shut-off) (Willcocks, Carter et al. 2004) and may stop translation of cellular mRNAs to focus on the viral VpG-bound RNA (Radford, Coyne et al. 2007). It has been identified that the junctional adhesion molecule-1 (JAM-1) serves as a cellular receptor for FCV in cell culture (Makino, Shimojima et al. 2006). Diagnosis Nucleic acid can be detected in conjunctival and oral swabs, blood, skin scrapings and lung tissue using conventional, nested and real-time reverse-transcriptase PCR (RT-PCR) assays. Molecular assays are validated in a large panel of strains to minimize false-negative results. The use of reverse transcriptase PCR allows unique virus strains detection (Abd-Eldaim, Potgieter et al. 2005, Radford, Addie et al. 2009). The presence of replicating virus can be isolated from nasal, conjunctival and oropharyngeal swabs, depending
Canine blood-typing
Canine blood-typing Andy Pachikerl, Ph.D Introduction: Dog erythrocyte antigens are responsible for initiating approximately 70% to 80% of immune-mediated transfusion reactions in the dog. As with other species, the red blood cell antigens found in the dog have various immunogenicities. In health, these antigens are participants in cell recognition-self versus nonself. In disease, they may serve as antigens for antibody or markers in disease occurrence. Little is known about their biochemical properties. Currently their description is reliant on polyclonal antibody serology. This reliance has limited the progress of transfusion practice in the dog. Historically, the study of canine blood groups and their importance in transfusion began in the 1600s through a physician, Richard Lower. He is credited with the first canine-to-canine transfusion. The efforts of doctors Lower and Denis in heterologous transfusion using lamb, dog, and human subjects introduced the basic transfusion premise “like transfuses like.” In 1910, Von Dungem and Hirszfeld documented the presence of four hemolysins and agglutinins based on canine alloimmunization (Swisher & Young, 1961). Further work by Ottenburg, Kaliski, and Friedman in 1913 confirmed these findings. From 1937 to 1949, Wright, Whipple, and Eyquem further defined the presence of six canine blood groups (Colling & Saison, 1980). However, not until 1961 was the importance of these antigens in transfusion and disease investigated by Swisher, Young, and Trabold (Swisher, et al., 1962). To date, the work submitted by Swisher and Young remains the most current published information of the importance of canine blood groups in transfusion (Swisher, 1954; Swisher, et al., 1962; Young, et al., 1951). Additional blood groups have been identified by Rubenstein (1968), Suzuki/5 Colling and Saison (Colling & Saison, 1980; Colling & Saison, 1980), and Symons and BelLl9 (Symons & Bell, 1992). Of this latter group, only the antigen first noted by Rubenstein (Colling & Saison, 1980) was evaluated in regard to transfusion significance by Bull (Bull, 1976). The importance of canine blood groups in veterinary transfusion medicine is based on three factors: the incidence of the antigen in the dog population, the incidence of naturally occurring antibody within the population, and the effect of the antibody against the antigen in vivo. Current blood typing schemes identify six erythrocyte antigens with possible importance. The dog erythrocyte system Blood groups are defined by glycolipids and glycoproteins on the surface of the red blood cell membrane. Current blood typing schemes identify six dog erythrocyte antigens (DEAs): 1.1, 1.2, 3, 4, 5, and 7 (Table 1). Blood groups are independently inherited. Simple Mendelian laws of dominance govern their inheritance. These antigens are defined by using polyclonal antibodies generated through canine alloimmunization. Polyclonal antibody recognition may be dependent on multiple recognition sites to define the “antigens” currently accepted. Biochemically, little is known about the DEA system. Table 1. Dog erythrocyte antigens established as international standards: classification, occurrence, and significance This blood group system has been defined with multiple alleles. They include the antigens 1.1, 1.2, 1.3, and a null type. An individual dog may show only one of the four phenotypes. Family studies suggest a Mendelian type of autosomal dominance. Table 2 describes the current phenotypic and genotypic information on this blood group system. 1.1- and 1.2-positive dogs have been studied for transfusion significance. Naturally occurring antibody to these alleles has not yet been found. Therefore, first-time transfusion reactions do not occur. However, if a negative dog is exposed to 1.1- positive erythrocytes, a strong hemolysin can result. On second exposure, an immune-mediated hemolytic transfusion reaction results causing removal of transfused cells in less than 12 hours. Hemoglobinuria and hyperbilirubinemia frequently occur. In addition to uncross matched, untyped transfusion, pregnancy can cause production of antibody against DEA 1.1 25% of the time. For these reasons 1.1-positive dogs are excluded as transfusion donors. 1.2-positive dogs can cause a problem as both the transfusion donor and recipient. A previously sensitized negative type dog undergoes permanent red blood cell removal and loss 12 to 24 hours after the administration of 1.2-positive red blood cells. Thus, 1.2-positive dogs are poor erythrocyte donors. If a 1.2-positive dog is sensitized with DEA 1.1 red blood cells, it will produce a potent anti-DEA 1.1 antibody. Administration of DEA 1.1 red blood cells to a sensitized 1.2 dog results in an immediate hemolytic transfusion reaction. Therefore, 1.2-positive dogs are at risk after sensitization for immediate transfusion. 1.3-positive dogs have not been evaluated for transfusion significance. Future study is limited because of the unavailability of typing sera for DEA 1.3. DEA 7 This red blood cell antigen is the most controversial among the six antigens discussed. Published reports of naturally occurring antibody to this antigen suggest that this antibody has a natural prevalence as high as 50% in DEA 7-negative dogs. Recent reports by Giger fail to support the presence of naturally occurring anti-DEA 7. Observations by the author suggest that naturally occurring antibody does exist in 20% to 50% of all DEA 7-negative dogs. However, the naturally occurring antibody is quite weak, rarely producing a titter greater than 1:8. In the presence of naturally occurring antibody, as in the cat, immunemediated transfusion reaction can occur during a first transfusion. Sensitized DEA 7-negative dogs, when transfused with DEA 7-positive erythrocytes show a delayed transfusion reaction. Hemolysis does not occur; however, an irreversible sequestration and loss of red blood cells occurs in 72 hours. This type of delayed transfusion reaction is only significant if the regenerative ability of the transfusion recipient is compromised. Because of the presence of naturally occurring antibody in the DEA 7-negative population and because of the delayed loss of erythrocytes in sensitized dogs, DEA 7-positive dogs are not recommended as donors. DEA3 This antigen has not been considered significant because of its low incidence in the dog population of the United States. However, recent evaluation of DEA type by breed suggests that it may be more important. Only 6% of the general population has DEA 3-positive cells. Yet 23% of the Greyhounds typed from 1990 to
Case study: Cerebral toxoplasmosis in a cat with feline leukemia and feline infectious peritonitis viral infections
Case study: Cerebral toxoplasmosis in a cat with feline leukemia and feline infectious peritonitis viral infections Robert Lo, Ph.D, D.V.M A diarrheic young cat died because of severe multifocal meningoencephalitis caused by Toxoplasma gondii. Protozoan cysts and tachyzoites in the brain were confirmed by immunohistochemical staining. Coinfection of feline leukemia virus (FeLV) and feline infectious peritonitis (FIP) might be the possible contributors to the clinical, fatal outcome. Original paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049326/ Histological lesions and immunohistochemistry (IHC) of the brain and kidney of a 6-month-old cat that was diagnosed with cerebral toxoplasmosis following postmortem examination. a — Kidney showing chronic pyogranulomatous nephritis. Hematoxylin and eosin (H&E), 40×. b — Brain showing perivascular cuffing of lymphocytes and plasma cells with multifocal vasculitis. Many oval protozoan cysts having a thin wall and containing basophilic bradyzoites were seen near to the vascular structures. H&E, 20×. c — Kidney stained by IHC with feline coronavirus antibodies showing multifocal positive reaction in the cytoplasm of macrophages, 40×. d — Brain stained by IHC with anti-Toxoplasma gondii antibodies and showing several positively stained protozoan cysts and tachyzoites, 20×.
The Feline Herpesvirus: An Overview
The Feline Herpesvirus: An Overview Maigan Espinili Maruquin The feline herpesvirus infection is common and recurring ocular disease is common (Stiles 2000). It is the most studied infectious cause of ocular surface disease in cats (Andrew 2001). Developing latent infections may recrudesce at later points in life of an infected cat (Stiles 2000). I. Structure and Replication Fig. 01. Structure of Herpes Virus. https://www.slideteam.net/0814-herpes-virus-medical-images-for-powerpoint.html The feline herpesvirus (FHV 1) causes feline viral rhinotracheitis (FVR) (Gaskell and Wardley 1978, Gaskell, Dawson et al. 2007, Henzel, Brum et al. 2012). This virus is double-stranded DNA with a glycoprotein-lipid envelope and is a member of the Varicellovirus genus in the Alphaherpesvirinae subfamily (Gaskell, Dawson et al. 2007). This virus was also found out to be relatively fragile in the external environment and is highly susceptible to the effects of common disinfectants (Scott 1980, Eleraky, Potgieter et al. 2002, Gaskell, Dawson et al. 2007). The FHV- 1 has short replication cycle, rapid cell-to-cell spread, has tendency to induce cell lysis, and displays persistence in sensory ganglia of their host (Gould 2011). It replicates in epithelial cells of both the conjunctiva and upper respiratory tract, and in neurons. The neuronal infection can lead to a lifelong latency after the primary infection (Thiry, Addie et al. 2009). For 18 hours, it can survive in damp environment, less in dry conditions and is also recorded to be relatively unstable as an aerosol (Povey and Johnson 1970, Donaldson and Ferris 1976, Stiles 2000, Gaskell, Dawson et al. 2007, Gould 2011). II. Infection and Epidemiology There are only three main genotype groups recognized for FHV-1 strains with very little genomic variations (Gould 2011). The virus sheds in ocular, nasal, and oral secretions with large transmission by direct contact with an infected cat. Although one of the most important sources of virus are the acutely infected cats, susceptible cats may also be infected by latently infected carrier cats (Gaskell and Povey 1982, Gaskell, Dawson et al. 2007). On the other hand, the environment may not be a primary source of transmission but catteries may cause indirect transmission through contaminated housing, feeding and cleaning utensils, and personnel (Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009). Latently infected cats may also transmit FHV to their kittens due to the parturition and lactation inducing stress that may lead to viral reactivation and shedding, making kittens susceptible to the virus, depending on the level of maternally derived antibodies (MDA) they possess. High levels of MDA protects kittens against the disease and may develop subclinical infection leading to latency while insufficient MDA may lead to clinical signs (Gaskell and Povey 1982, Thiry, Addie et al. 2009). Recovered cats become latently infected carriers and reactivation happens particularly after periods of stress (Gaskell, Dawson et al. 2007). However, it doesn’t shed immediately after the stress. It undergoes lag phase of 4–11 days, precedes the shedding from 1–13 days (Gaskell and Povey 1973, Gaskell and Povey 1977, Gaskell, Dawson et al. 2007). Further, risk factors associated with FeHV-1 shedding includes contact with other cats, the presence of upper respiratory disease, younger cats, poor hygiene, and larger households (Sykes, Anderson et al. 1999, Binns, Dawson et al. 2000, Helps, Lait et al. 2005, Gaskell, Dawson et al. 2007). III. Pathogenesis Infection routes include nasal, oral, and conjunctival mucous membranes and is primarily shed in secretions for 1–3 weeks following infection (Andrew 2001, Gaskell, Dawson et al. 2007). In pregnant queens, vaginitis was caused by intravaginal instillation virus and causes congenitally infected kittens while intravenous inoculation leads to transplacental infection and abortion (Bittle and Peckham 1971, Hoover and Griesemer 1971, Gaskell, Dawson et al. 2007). After 1 to 2 exposure of naive animals to FHV-1, the viral replication happens and epithelial cell necrosis occur in the nasal turbinates, nasopharynx and conjunctival mucosa (Gaskell & Dawson 1998). Lytic infection of the nasal epithelium with spread to the conjunctivas, pharynx, trachea, bronchi and bronchioles occurs and lesions characterized by multifocal epithelial necrosis with neutrophil infiltration and inflammation are also observed. Moreover, neonates or hypothermic kittens display transient viraemia associated with mononuclear cells (Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009). It has been recorded that almost all infected cats become lifelong carriers. During the latency period, virus was spread along the sensory nerves and neurons with viral genome doesn’t replicate. Whereas, reactivating stressors include lactation and moving into a new environment (Gaskell and Povey 1977, Gaskell and Povey 1982, Pedersen, Sato et al. 2004, Thiry, Addie et al. 2009). Lesions may be developed upon viral reactivation in adult cats and ‘recrudescence’ disease may also be a consequence (Thiry, Addie et al. 2009). As high as 70% mortality rates was reported for infected kittens (Povey 1990). Although MDA may persist for 2 to 10 weeks, this may not protect cats from subclinical infection (Gaskell & Dawson 1998)(Andrew 2001). IV. Clinical Signs Generally, FHV- infected cats display acute upper respiratory and ocular disease with usually 2 to 6 days incubation period, or may be longer (Gaskell and Povey 1979, Stiles 2000, Gaskell, Dawson et al. 2007) with depression, fever, lethargy, inappetence, pyrexia, sneezing, coughing, nasal discharge, and conjunctivitis with ocular discharge depending on the viral exposure and individual susceptibility (Hoover, Rohovsky et al. 1970, Crandell 1973, Stiles 2000, Gaskell, Dawson et al. 2007, Thiry, Addie et al. 2009) (Gaskell R.M., Dawson S, 1994). Also, excessive salivation with drooling may also be observed during the initial clinical signs of the disease (Gaskell, Dawson et al. 2007).Once the virus reaches the lungs, pneumonia may kill the infected kittens (Stiles 2000, Thiry, Addie et al. 2009) (Gaskell R, et al. 2006). The primary FHV- 1 infection with secondary bacterial infection leads in conjunctivitis sometimes with severe hyperemia and chemosis. The conjunctivitis is manifested as hyperaemia or redness with serous discharge, progressing to mucopurulent ocular discharge whereas, chemosis is swelling or oedema of the conjunctiva which may occur to
Symmetric dimethylarginine (SDMA)
Symmetric dimethylarginine (SDMA) Andy Pachikerl, Ph.D Introduction For over a millennium and a few centuries, urinalysis has given leads to medical diagnoses. It was until the repetitive use of clinical chemistry approximately 50 – 60 years that these data of renal biomarkers became commonplace in human and veterinary medicine. From here onwards, both an improved understanding of the renal system and ability to diagnose renal disease was updated. In the past, renal biomarkers have focused on kidney function testing, and this is the basis for current conventional test in blood (serum creatine [sCr], urea or urea nitrogen [UN] as endogenous indicators of glomerular filtration rate [GFR]). Recently, we are becoming more aware of the need to identify renal disease at an early stage when therapeutic options are most effective. Both sCr and UN both play vital role in diagnosis of kidney disease, their limitations create poor confidence for their use as early indicators for disease. New markers of renal function try to overcome these limitations. Additionally, there are now many urinary markers that can detect kidney damage and help localize that damage to the compartment of the kidney that is affected. Endogenous markers of GFR Creatine The most common endogenous marker for estimating GFR is serum creatinine and its metabolism. Measurement and diagnostic significance in dogs have previously been reviewed (Braun, et al., 2003). Recent reviews, however, suggested factors that can either enhance or limit the clinical use of sCr to optimize diagnostician and clinical pathologist to interpret the data of this conventional test. Particularly, accurate interpretation of published data, population-specific reference intervals, trending of sCr and consideration of muscle mass influence and analytic variability are all needed to best interpret sCr in dogs and cats. Of note, although creatinine is referred to as sCr throughout this manuscript, creatinine is also commonly measured in plasma. Nephron mass vs nephron function. It is generally accepted that 75% of nephron mass must be lost before sCr increases above the reference limit (Braun, et al., 2003). The original source for this statement likely originates from partial nephrectomy studies in dogs. However, it is often mistaken for 75% loss of renal function vs mass. In partial nephrectomy studies, ¾ loss of renal mass related to about 50–60% or 35–45% reduction in renal function based on inulin clearance one month or 13 months post-surgery, respectively (Brown, et al., 1990; Bovee, et al., 1979). The much lower decrease in function as compared with the percentage of nephron loss is due to compensatory changes in remaining nephrons (ie, compensatory renal hypertrophy) (Brown, et al., 1990; Bricker, et al., 1964). Furthermore, using an age- and breed-specific reference limit (sCr ≥ 106 mmol/L or 1.2 mg/dL) along with frequent monitoring, adolescent dogs with rapidly progressive kidney disease due to X-linked hereditary nephropathy (XLHN) demonstrated increased sCr after GFR had decreased an average of 48% (range 39–68%).8 Based on these studies, sCr can be more sensitive for detecting decreased renal function than has been historically assumed. Value of population-specific reference intervals. While sCr is not as poorly sensitive as generally believed, its inability to regularly detect < 50% decline in kidney function at least partly stems from reference intervals that are overly wide for patients with low baseline sCr. Since current methodologies are highly specific for creatinine, the wide reference intervals largely stem from biologic differences in sCr among individuals. Serum creatinine has relatively high individuality in dogs and cats (Baral, et al., 2014; Ruaux, et al., 2011), meaning that variability between individuals is much higher than the variability observed within a single animal. Serum creatinine is influenced by age (Rosset, et al., 2012; Rørtveit, et al., 2015) and particularly by breed in dogs (Misbach, et al., 2014; Zaldívar-López, et al., 2011) and, to a lesser extent, in cats.20 It might also be influenced by sex and the veterinary clinic evaluating the patient.21 Therefore, sCr would benefit from age- and breed-specific reference intervals, ideally (although not practically) for every individual instrument and laboratory. Trending of serum creatinine. Small increases in sCr even within the reference interval can reflect significant decreases in GFR in an individual patient8, particularly since variation in sCr within an individual healthy dog or cat is minimal over weeks to months and even years (Braun, et al., 2003; Baral, et al., 2014; Ruaux, et al., 2011). In fact, the critical difference or reference change value for detecting a significant increase or decrease in sCr is only 23–27 lM/L (0.3 mg/dL) in clinically healthy dogs10, and 17% (corresponding to similar absolute values as in dogs) in clinically healthy cats (Braun, et al., 2003). Thus, the sensitivity of sCr for detecting early kidney disease can be improved by evaluating serial fasted sCr measurements in an individual animal (trending) to look for increases that likely reflect worsening renal function. This concept of detecting small but clinically relevant increases in sCr is actively being adopted in cases of acute kidney injury (AKI), illustrated by the International Renal Interest Society (IRIS) Grading of AKI. In this grading scheme, an increase in sCr ≥ 26 lmol/L (0.3 mg/dL) within a 48- hour period is a criterion for identifying Grade I and Grade II AKI (www.IRIS-Kidney.com). Furthermore, in adolescent dogs with XLHN, trending of sCr detected an average of 27% (range 5–49%) decrease in GFR (Nabity, et al., 2015). Despite heightened awareness of small, but clinically relevant increases in sCr over a short time frame, more recognition is needed with slowly progressive CKD, in which small increases might occur over many months or years. Analytic challenges. Finally, sCr is plagued by inconsistencies in its measurement between instruments and laboratories, which can result in markedly different results. While most reference laboratory instruments have excellent precision and provide results of similar magnitude among instruments (Ulleberg, et al., 2011), recent studies illustrate the high imprecision and bias possible with some instruments and among different laboratories (Ulleberg, et al., 2011; Braun, et al., 2008). In normal to mildly azotaemia samples,
Case study: Report of the first clinical case of intestinal trichomoniasis caused by Tritrichomonas foetus in a cat with chronic diarrhoea in Brazil
Case study: Report of the first clinical case of intestinal trichomoniasis caused by Tritrichomonas foetus in a cat with chronic diarrhoea in Brazil Robert Lo, Ph.D, D.V.M A seven-month-old, entire male domestic shorthair kitten was presented to the Veterinary Hospital of the School of Veterinary Medicine – University of São Paulo, Brazil. The cat showed a six-month history of persistent large intestinal diarrhoea, faecal incontinence, prostration, apathy and weight loss. P Protozoan parasites were observed under microscope using fresh fecal sample obtained via colon flush. Infection of Tritrichomonas foetus was confirmed by PCR and DNA sequencing. After treatment with ronidazole (30 mg/kg, PO q24h for 14 days), the cat showed resolution of clinical signs. This is the first clinical case of T. foetus infection in a chronic diarrheic cat in Brazil and South America. Original paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392982/ Fig. 1 Tritrichomonas foetus in cat feces. a Numerous pyriform trophozoites. b The three free anterior flagella (large arrow) and the undulating membrane (small arrows) can be visualised in some trophozoites. Fresh preparation in saline 0.85%.