Test 2- Parvoviridae

Question 1

Family Parvoviridae

 General Properties:

Answer 1

 General Properties:
 Nonenveloped icosahedral virion, small size, 18-25 nm in diameter.
 Virion capsid is composed of 60 protein subunits, T=1
 Single- stranded DNA genomes which are linear, approximately 4–6 kb in size  Most viruses hemagglutinate red blood cells

 Viruses are very stable, resisting 60°C for 60 minutes and pH 3 to pH 9. Disinfection of contaminated premises is difficult.

Question 2

Family Parvoviridae

 Replication:

Answer 2

 Replication:
 Replication occurs in the nucleus of rapidly dividing cells.
 Infection leads to large intranuclear inclusion bodies.

primary in nucleus with inclusion bodies

Question 3

Family Parvoviridae

 Genus Parvovirus:

Answer 3

 Virus replication occurs only in cells that pass through mitotic S phase (actively dividing cells).

 Cannot replicate in stationary cells, as rely on enzymes of actively dividing cells (mitosis).

 Feline panleukopenia

 Canine parvovirus
 Porcine parvovirus

Question 4

Family Parvoviridae

 Genus: Erythrovirus (Fifth Disease, Slap Cheek Rash):

Answer 4

 Genus: Erythrovirus (Fifth Disease, Slap Cheek Rash):

 Replicate autonomously.
 Includes human parvovirus B19.

 In children, B19 causes:

 Mild rash illness, also called erythema infectiosum.  Aplastic anemia in children
 Painful joints

 Different from the parvovirus seen in dogs and cats. No evidence of transmission of B19 to humans from dogs or cats, or vice versa (source: CDC)

Question 5

Answer 5

Family Parvoviridae  Genus: Erythrovirus (Fifth Disease, Slap Cheek Rash):

Question 6

Family Parvoviridae

 Genus: Dependovirus

Answer 6

 Viruses are themselves replication defective and do not cause disease as they are unable to replicate except in the presence of a helper virus, usually an adenovirus.

 Includes goose and duck parvoviruses and, provisionally, bovine parvovirus 2.

Question 7

 Genus: Bocavirus

Answer 7

 Bocaviruses are unique among parvoviruses, as they contain a third ORF (Open Reading Frame) between non-structural and structural coding regions

 These viruses generally infect the gastrointestinal and respiratory tracts.

 Found in human, dogs, cattle.

Question 8

Answer 8

Human bocavirus

Question 9

Family Parvoviridae

Answer 9

Family Parvoviridae Feline parvovirus

Disease: Feline panleukopenia (FPV)

Question 10

Feline panleukopenia

Etiology, Host, distribution

Answer 10

Feline panleukopenia (FPV)
 Synonyms: Feline distemper; feline infectious enteritis

 Etiology: Feline parvovirus. Antigenically related to canine parvovirus 2 and mink parvovirus

 Host:
 All members of the family Felidae are probably susceptible to infection.
 Highly contagious, often fatal disease of cats. Severe in kittens.

 Also in related families, such as raccoon, mink, etc.

 Distribution: Worldwide

Question 11

Feline panleukopenia (FPV)

 Epidemiology:

Answer 11

 Epidemiology:

 The virus is ubiquitous because of its contagious nature and capacity for persistence in the environment.

 Virtually all cats are exposed and infected within first year of life.

 Unvaccinated kittens that acquire maternal antibodies are protected up to 3 months of age.

 Most infections are subclinical, as much as 75% of unvaccinated healthy cats have demonstrable antibody titers by 1 year of age.

 Cats can shed the virus in their urine or feces for a maximum of 6 weeks after recovery.

 FPV is maintained in population by environmental persistence rather than by prolonged viral shedding.

 Owners losing a kitten to feline panleukopenia should not introduce a new kitten into the household without having it vaccinated.

Question 12

Feline panleukopenia

Transmission:

Answer 12

 Transmission:

 Cats are infected oro-nasally by exposure to infected animals, their feces,secretions, or contaminated fomites.

 In-utero transmission occurs.

 Mechanical transmission by flies.

Question 13

Feline panleukopenia Pathogenesis

Answer 13

Question 14

Feline panleukopenia Pathogenesis

Answer 14

 After virus entry in the oropharynx, initial virus replication occurs in pharyngeal lymphoid tissue.

 Cell-associated viremia(virus in blood) to other organs and tissues via the blood stream.

 Cells that have appropriate receptors and are in the S phase of the cell cycle are infected and killed or prevented from entering mitosis.

Question 15

Feline panleukopenia Pathogenesis

 Panleukopenia:

Answer 15

 Hallmark of the disease- The more severe the leukopenia, the poorer the prognosis

 The characteristic profound leukopenia involves destruction of all white blood cell elements, including lymphocytes, neutrophils, monocytes, and platelets.

 Cells present in the circulation [consequence of virus adsorption and cytotoxic lysis] as well as those in lymphoid organs, including the thymus, bone marrow, lymph nodes, spleen, and Peyer’s patches are destroyed.

 Thrombocytopenia (due to damage to bone marrow) may accompany leukopenia.

Question 16

Answer 16

Feline hemorrhagic ileocecal lymph node

Question 17

Panleukopenia

WBC counts

Answer 17

• TotalWBCcountsof five cats infected with feline parvovirus

Question 18

Feline panleukopenia Pathogenesis

 Enteritis:

Answer 18

 Virus selectively damages replicating cells deep in the crypts of the intestinal mucosa.

 Differentiating adsorptive cells on the surface of the villi are non-dividing and are not affected.

 Normally, the epithelial cells at the tips of the intestinal villi are continuously lost into lumen of the gut.

 These are replaced by dividing cells from the crypts.

Question 19

Feline panleukopenia Pathogenesis

 Enteritis:

Answer 19

Question 20

Feline panleukopenia Pathogenesis

 During FPV infection

Answer 20

 During FPV infection, loss of cells from tip of villus continues as a normal process. However, since virus replicates and destroys cells of crypts, there is no replacement of the lost absorptive cells at tips of the villi with cells from the crypts.

 This results in shortening of intestinal villi, marked villus blunting and fusion, malabsorption and diarrhea.

Question 21

Answer 21

Feline panleukopenia

Enteritis

Hemorrhagic Spleen, Intestines and Mesenteric Lymph Node

Question 22

Answer 22

Feline panleukopenia

Dark , Hemorrhagic Jejunum and a Ileum

Question 23

Answer 23

Feline panleukopenia

Enteritis

Intestine opened to Show Fibrinous Cast

Question 24

Answer 24

Feline panleukopenia

Enteritis

Basophilic Intranuclear Inclusion Bodies [Arrows]

Question 25

Answer 25

Feline panleukopenia ENTERITIS Feline small intestine dilatation

Question 26

Answer 26

Feline panleukopenia ENTERITIS Feline small intestine epithelial necrosis, **hypereplasia**

Question 27

Answer 27

Feline panleukopenia ENTERITIS Feline ileocecal junction necrotic enteritis

Question 28

Answer 28

Feline panleukopenia ENTERITIS Feline GI tract dilated, congested jejunum

Question 29

Feline panleukopenia  In-Utero infection

Answer 29

_ Early in-utero infection in pregnant queen can result in_ :  Early fetal death and resorption with infertility of the queen  Abortions  Birth of mummified fetuses. _ Infection closer to end of gestation:_  Birth of live kittens with varying degree of damage to the late-developing neural tissues.- **You will see ataxia in the kittens**  Variable effects on kittens from the same litter.

Question 30

Feline panleukopenia  Central Nervous System infection:

Answer 30

 Central Nervous System infection:  The CNS, optic nerve and retina are susceptible to damage by FPV during prenatal or early neonatal development.  Of neurological lesions, cerebellar damage has been most commonly reported.  Cerebellar hypoplasia is usually observed in fetuses infected during the last 2 weeks of pregnancy and the first two weeks of life.

Question 31

Answer 31

Dark foci in retina from a kitten with optic nerve hypoplasia as a result of in-utero FPV infection

Question 32

Feline panleukopenia

Answer 32

Fetal cerebellum consists of external germinal layer, cells of which undergo rapid cell division and migrate to form internal germinal and Purkinje cell layers. Normal postnatal cerebellar cortex, outer germinal layer with stellate cells; middle Purkinje cell layer and a deeper granular layer.

Question 33

Answer 33

**Feline panleukopenia** **Cerebellar Hypoplasia**  Lysis of mitotic cells of the external germinal layer  Impaired cerebellar development DESTROY GERMINAL LAYER- which causes no developement of the cerebellum

Question 34

Answer 34

Feline panleukopenia Cerebellar Hypoplasia

Question 35

Answer 35

Feline panleukopenia Cerebellar Hypoplasia Normal Cerebellum [Right] and Cerebellar Hypoplasia [Left]

Question 36

Answer 36

Feline panleukopenia Kitten with Marked Ataxia

Question 37

Answer 37

Feline panleukopenia Hydranencephaly- no development of brain and fluid in the brain because a part has not developed

Question 38

Feline panleukopenia  Disseminated Intravascular Coagulation

Answer 38

 Disseminated Intravascular Coagulation  Kittens with FPV infection are also susceptible to secondary bacterial infection.  Gram-negative endotoxemia, with or without bacteremia, is a common sequelae of systemic FPV infection.  **Endotoxin (LPS)** induces expression of tissue factor [factor III] on endothelial cells.  Tissue factor is a potent activator of coagulation, resulting in DIC, followed by hemorrhages.

Question 39

Feline panleukopenia  Clinical signs:

Answer 39

 Most common in kittens 3 to 5 months of age.  Incubation period ranges from 2-10 days [5 days]  Fever, depression, anorexia, rough coat, repeated vomiting, profuse, persistent and frequently bloody diarrhea.  Severe dehydration, hypothermia, sudden death from complications with secondary bacterial infections, dehydration and DIC.  Queens infected or vaccinated during pregnancy may show infertility or abortion of dead or mummified fetuses.  Cerebellar hypoplasia: kittens are ataxic, usually not apparent until kitten begins to walk at 3-4 weeks of age.  Retinal degeneration in infected kittens.

Question 40

Answer 40

Feline panleukopenia in a young kitten

Question 41

Answer 41

A moribund kitten infected by FPV

Question 42

Feline panleukopenia Diagnosis  Clinical signs, postmortem findings.

Answer 42

 Hematology: **Leukopenia_, neutropenia_ more consistent than lymphopenia. Total WBC counts \<2,000 cells/μL are associated with a poorer prognosis.**  **Virus isolation in cell culture:** Swabs from pharynx or rectum, spleen, ileum, or mesenteric lymph nodes.  **Fecal viral antigen testing using immunochromatographic test kit or ELISA.** Results may remain positive up to 2 weeks following MLV vaccination.  **PCR for detection of viral DNA in tissues**  **Direct hemagglutination** of pig or rhesus RBCs.

Question 43

Feline panleukopenia  Diagnosis:  Serologic testing:

Answer 43

 Serologic testing:  Single sample antibody titers do not distinguish between active infection or past exposure to virulent or vaccine strains.  Paired serum samples, the 1st one as soon as possible during illness, and second one 2 weeks after.  _A fourfold rise in titer is considered indicative of acute infection._  Virus neutralization test is commonly used.  Also, Complement fixation, hemagglutination, hemagglutination inhibition.

Question 44

Feline panleukopenia Treatment :

Answer 44

 Good nursing care, fluid therapy, withholding in early stages to lessen vomition and slow down mitotic activity of cells.  Broad spectrum antibiotics to prevent secondary bacterial infection.

Question 45

Feline panleukopenia Control

Answer 45

Control:  Large catteries: strict hygiene and quarantine of incoming cats.  Disinfection: Inactivated by bleach [6% sodium hypochlorite], 4% formaldehyde and 1% glutaraldehyde in 10 minutes at room temperature.

Question 46

Feline panleukopenia Vaccination

Answer 46

 Attenuated (modified) live vaccines (MLV)  Inactivated vaccines

Question 47

 MLV should not be administered to:

Answer 47

 Pregnant cats  Immunosuppressed cats  Sick cats  Kittens less than 4 weeks old.

Question 48

Feline panleukopenia  Time of Vaccination:

Answer 48

 Kittens receive two or three modified live vaccine doses SC, 3–4 wk apart.  The first vaccination is usually given at 6–9 wk of age.  The last dose of the initial vaccination series should not be administered before the kitten is 1_6 wk old, to ensure that interfering maternal antibodies do not inactivate the modified live virus._

Question 49

Canine Parvovirus (CPV)

Answer 49

Considered a _canine-specific variant of the feline panleukopenia virus_ that emerged in 1978 as a consequence of an interspecies jump from other carnivores to dogs.  Canine parvovirus 1 (CPV-1): Mild to inapparent illness (diarrhea) in dogs, especially in young pups less than 8 weeks old. **Not important.** ** Canine parvovirus 2 (CPV-2): One of most common infectious diseases of dogs.  Three antigenic variants: CPV-2a, CPV-2b and CPV-2c.**

Question 50

Canine parvovirus 2(CPV-2) Host, Distribution, Transmission, Epidemiology

Answer 50

 Host: Domestic and wild Canidae. Self limiting-infection in experimentally infected cats.  Distribution: Worldwide. **In north America, CPV-2b and CPV-2c are more common.** _ Epidemiology:_  Virus is highly contagious and very stable in the environment.  Resistant to many common detergents and disinfectants.  Infectious CPV can persist indoors at room temperature for at least 2 months. _ Transmission:_  Oro-nasal exposure to contaminated feces.  In-utero infection  Contact with virus-contaminated fomites (environment, personnel, equipment).

Question 51

Pathogenesis & Clinical Findings:

Answer 51

Pathogenesis & Clinical Findings: Similar to FPV ** Enteritis  Myocarditis  Panleukopenia**  Neurologic disease:  Cerebellar hypoplasia  Hemorrhage in CNS, DIC, Hypoglycemia  Cutaneous Disease: Ulceration, vesicles **_Clinically, three age –related syndromes have been recognized:_** ** 2-12 days: Generalized neonatal disease. _Uncommon._  3-8 weeks: Myocarditis.  2-4 months: Enteritis & Panleukopenia. _Most common._**

Question 52

Canine parvovirus 2(CPV-2)  Enteritis:

Answer 52

CPV-2 **infects the germinal epithelium of the intestinal crypts,** causing destruction and collapse of the epithelium. No replacement of cells lost from tip of villus. Villi shortened.

Question 53

Answer 53

Immunoperoxidase Stain CPV antigens in crypt epithelium CPV-2 Enteritis

Question 54

Answer 54

CPV-2 Enteritis Crypt Necrosis

Question 55

Answer 55

Dog with severe bloody diarrhea CPV-2 Enteritis

Question 56

Answer 56

Three month old dog infected with CVP-2, exhibiting watery stool. CPV-2 Enteritis

Question 57

Answer 57

Hemorrhagic Enteritis Enteritis

Question 58

Answer 58

Acute Parvovirus Infection Enteritis

Question 59

Answer 59

Collapse and Necrosis of Intestinal Villi Enterisitis

Question 60

Answer 60

Canine Parvovirus Infection (Courtesy: Dr. Richard Miller) Hemorrhagic Intestine Ballooned Small Intestine

Question 61

Answer 61

Canine Parvovirus Infection Ingesta visible through Small Intestinal Wall

Question 62

Canine Parvovirus 2 (CPV-2)  Myocarditis:

Answer 62

 _Develops from infection in-utero or from pups \< 6 weeks of age._  **Myocardial necrosis** with acute cardiopulmonary failure.  Sudden death, or die after short period of clinical signs (dyspnea, crying & retching).

Question 63

Answer 63

Necrotizing Myocarditis Necrotizing Myocarditis with Eosinophilic Inclusions

Question 64

Canine Parvovirus  Diagnosis:

Answer 64

** Clinical signs**- Primary  Fecal viral antigen testing using immunochromatographic test kit or ELISA.  Nucleic acid detection using PCR  Virus isolation  _Serology (antibody detection) is not best method to test CPV,_ because most dogs are vaccinated, or have been previously exposed to CPV

Question 65

Canine Parvovirus  Control:

Answer 65

Same as FPV

Question 66

 Vaccination: Canine Parvovirus

Answer 66

 _Vaccination with a modified-live vaccine is recommended at 6–8, 10–12, and 14–16 wk of age, followed by a booster administered 1 yr later and then every 3 yr._  Because of _potential damage by CPV to myocardial or cerebellar cells, **inactivated** rather than modified-live vaccines are indicated in pregnant dogs or colostrum- deprived puppies vaccinated before 6–8 wk of age._

Question 67

Canine Parvovirus Use of oseltamivir (Tamiflu) in the treatment of canine parvoviral enteritis

Answer 67

 **MOA (Mechanism of Action) not clear, as parvovirus does not use neuraminidase in its replication.**  Speculation is that neuraminidase is an _important enzyme used by pathogenic bacteria_ invading through the protective mucous barrier of the GI tract, and by this process indirectly facilitate CPV infection. Tamiflu may act on these bacterial neuraminidase. **STUDIES HAVE SHOWN THAT IT HELPS WITH A BACTERIA**

Question 68

Porcine Parvovirus General + Transmission

Answer 68

Porcine parvovirus disease is an infectious cause of reproductive failure in swine throughout the world.  Some manifestations of the disease are described by the acronym, **SMEDI** (stillbirth, mummification, embryonic death, infertility).  In most herds, a large proportion of gilts are infected naturally before they conceive, and hence are immune. _ Transmission:_  Oronasal in the non-immune pregnant Sow followed by transplacental transmission.  Venereal transmission is possible, as Boars shed virus in semen for protracted periods.

Question 69

Porcine Parvovirus  Pathogenesis:

Answer 69

Oronasal infection of the nonimmune pregnant dam followed by viremia. It takes about 15 days after maternal infection for the virus to reach the fetus.

Question 70

Porcine Parvovirus  Transplacental infection:

Answer 70

 Transplacental infection:  Each fetus or embryo has a separate placenta. **Therefore, not all embryos or fetuses are infected at same time.**  However, infection of a fetus or embryo is followed by virus spread through the uterus and infection of some or all remaining fetuses or embryos. **_ Hence, death at different stages of pregnancy is typical of PPV infections_**

Question 71

 Sites of Viral replication: Porcine Parvovirus

Answer 71

 Predilection for mitotically active cells in fetal tissues.  Virus replicates in blood lymphocytes , monocytes , macrophages, lymph nodes, tonsils, thymus, spleen, lungs, salivary glands, and other organs.  **Extensive endothelial cell damage may be reflected in damage to many organs.**

Question 72

Porcine Parvovirus  Clinical signs:

Answer 72

**_ The increase in mummified fetuses after a normal gestation period is the hallmark of PPV._**  Abortions are uncommon.

Question 73

 Time of infection of Porcine Parvovirus is critical:

Answer 73

 _Embryo/Fetus (\<30 days)_: Dies and reabsorbed. Dams may return to estrus.  _Early fetus (30-70 days):_ Fetuses die and become relatively dehydrated (mummified)-expelled at the end of normal gestation period  _Late fetus (\>70 days to term):_ Frequently develop lesions, but also mount an immune response and usually survival in-utero.

Question 74

Immunotolerant pigs

Answer 74

 Immunotolerant pigs: some piglets are born immunotolerant and can shed the virus continuously or intermittently.  Boars, Sows and Gilts( THUS IN ADULTS): Mostly inapparent or subclinical infection.

Question 75

Porcine Parvovirus • Major cause of

Answer 75

• Major cause of SMEDI Stillbirth, mummification, embryonic death, and infertility • Less common Respiratory tract infections; vesicular diseases; and systemic neonatal disease • Long-term infection in swine herds

Question 76

Answer 76

PPV-SMEDI Mummies and Stillborn

Question 77

Porcine Parvovirus  Diagnosis:

Answer 77

 FA staining of frozen sections of fetal tissues.  PCR for nucleic acid detection in fetus  ELISA, HA, or HI.  _Serologic tests are of limited value_, because the virus is so widespread in swine, and vaccination may interfere.

Question 78

Porcine Parvovirus  Immunity:

Answer 78

 Passively acquired maternal antibody can persist for up to 6 months.  Some gilts can become seronegative at time of conceiving and are susceptible to infection.  _Unlike most parvoviruses, porcine parvoviruses can cause persistent infection with periodical shedding of virus._

Question 79

Parvo in pigs- vaccination/immunization

Answer 79

 Vaccination/Immunization:  A number of inactivated and live vaccines are available to prevent PPV infection.  **Best way:** Vaccinate all susceptible breeding stock twice, 2 weeks apart, several weeks before breeding.  Alternatively, gilts can be naturally infected several weeks before breeding, by mingling with older breeding stock that may be shedding the virus.