Feline Panleukopenia

A Re-emergent Disease

Vanessa R. Barrs, BVSc(hons), PhD, MVetClinStud, FANZCVS

KEYWORDS
 Parvovirus  Canine  Feline  Panleukopenia  Enteritis  Shelter medicine
 Carnivore protoparvovirus

KEY POINTS
 Feline panleukopenia (FPL) is caused by Carnivore protoparvovirus 1. Feline parvovirus
(FPV) causes 95% of cases, whereas 5% are caused by Canine parvovirus (CPV) variants,
specifically CPV-2a, b, and c.
 Outbreaks of FPL occur in shelters from summer to autumn (median age at diagnosis 2–
4 months) associated with a seasonal influx of kittens with waning or absent maternally
derived antibodies.
 In Australia FPL has re-emerged to cause large-scale outbreaks among unvaccinated
shelter cats with spill over to the owned cat population.
 In contrast to CPV enteritis of dogs, hemorrhagic diarrhea occurs in only 3% to 15% of
cases of FPL. Lethargy, anorexia, and fever, the most prominent signs in some cats, pre-
cede vomiting and diarrhea.
 Even with treatment FPL has a high mortality rate of 50% to 80%. Poor prognostic indi-
cators include low leukocyte or platelet counts or hypoalbuminaemia or hypokalemia at
presentation.

INTRODUCTION

Feline panleukopenia (FPL) is the clinical disease syndrome caused by infection

with Carnivore protoparvovirus 1. Both feline parvovirus (FPV; formerly FPL virus)
and canine parvovirus (CPV) can cause FPL, although CPV infections in cats are
uncommon.
The detection of endogenous parvovirus-like DNA sequences in the genomes of
numerous carnivore species provides evidence that parvoviruses have likely
been circulating in carnivores for millions of years.1 Feline panleukopenia is the oldest
known viral disease of cats. Several epizootics that decimated domestic cat

Disclosure Statement: The author has nothing to disclose.

Sydney School of Veterinary Science, Faculty of Science, and Marie Bashir Institute of Infectious
Diseases & Biosecurity, University of Sydney, New South Wales 2006, Australia
E-mail address: [email protected]

Vet Clin Small Anim 49 (2019) 651–670

https://doi.org/10.1016/j.cvsm.2019.02.006 vetsmall.theclinics.com
0195-5616/19/ª 2019 Elsevier Inc. All rights reserved.
652 Barrs

populations in the 1800s could have been caused by FPV.2,3 In the first decade of the
1900s, multiple reports of an infectious enteritis in cats, with high mortality and sea-
sonal incidence were published, and subsequently reviewed in 1934.4 Feline panleu-
kopenia was first identified to have a viral cause in 1928,5 and cats were successfully
vaccinated against FPV in 1934 using formalin-inactivated tissue extracts from
infected cats.4 A breakthrough in 1964 led to successful isolation of FPV in tissue cul-
ture,6 which paved the way for the development of inactivated tissue culture vaccines
and modified live virus (MLV) vaccines. With progressively increased uptake of primary
kitten vaccinations by pet owners from w18% in the UK in 1973 to w82% in 2016,7,8
FPL became an uncommon disease diagnosis in companion animal veterinary prac-
tice in several countries including the UK, Australia, New Zealand, and United States,
except for sporadic outbreaks in shelters.
In some countries, such as Australia, there were no outbreaks of FPL reported even
in shelters for over 30 years. In 2014, FPL re-emerged in Australia, in Victoria, primarily
among shelter-housed cats. Since then, large-scale outbreaks have occurred in mul-
tiple shelters in Eastern Australia in New South Wales and Queensland, with spillover
to the owned cat population. A “perfect storm” of events surrounds the re-emergence
including the failure of many municipal and privately owned shelters to routinely vacci-
nate cats, wide geographic dissemination of kittens to shelters and foster-care net-
works aided by social media, and poor infection control practices and training.9 In
addition, trap-neuter-return schemes are uncommon in Australia, and increasing
lengths of stay associated with the introduction of “no kill” policies or higher rehoming
targets, has resulted in crowding and longer duration of stay for individual cats in some
shelters, increasing the risk of exposure to pathogens.
Here, the causes, epidemiology, diagnosis, treatment, prognostic indicators, and
management of FPL outbreaks in shelters are reviewed.

VIRAL CAUSES OF FELINE PANLEUKOPENIA

The virus family Parvoviridae, contains vertebrate parvoviruses (subfamily Parvoviri-

nae), and invertebrate parvoviruses (subfamily Densovirinae).10 Carnivore protoparvo-
virus 1 is a viral species in genus Protoparvovirus. Feline panleukopenia is the clinical
disease syndrome caused by infection with Carnivore protoparvovirus 1 strains,
including FPV (90%–95% of cases) and current circulating strains of CPV (<10% of
cases) (Table 1).
Carnivore protoparvovirus 1 is a small, nonenveloped, linear, single-stranded DNA
virus with a 5.1-kb genome encoding 2 major genes, the nonstructural (NS) and struc-
tural protein genes. The NS gene encodes the NS1 and NS2 proteins involved in DNA
replication, capsid assembly, and intracellular transport, whereas the structural gene
encodes capsid virus protein 1 (VP1) and VP2. The viral capsid is comprised of 60
protein subunit molecules (w10% VP1 and 90% VP2) arranged in an icosahedral
symmetry.
The host range of FPV includes domestic and wild felids (suborder Feliformia) and
some wild canids (suborder Caniformia), for example, raccoons and foxes, but not do-
mestic dogs.11,12 Although FPV can replicate in lymphoid tissues of dogs (thymus and
bone marrow) after experimental inoculation, it cannot bind to the canine transferrin
receptor (TfR), which is critical for efficient infection, and onward transmission of infec-
tion does not occur.13–15
Canine parvovirus emerged as a new pathogen in domestic dogs in the mid-
1970s and caused a global panzootic in 1978.16,17 The virus was initially named
CPV-2 to distinguish it from an unrelated canine parvovirus, Canine minute virus,
 Feline Panleukopenia 653

Table 1
CPV isolates detected among fecal samples testing positive for FPV or CPV from clinically
unwell cats

No. of CPV-Positive Isolates/

Year Country No. of Isolates Examined (%) CPV Variants Detected
1985–1990104 United States 2/20 (10) CPV-2b
1989–199124 Japan 3/48 (6) unknown
1993–199430 Japan 1/34 (3) CPV-2a
1993–1995104 Germany 3/39 (8) CPV-2a (2)
CPV-2b (1)
2000–200933 Italy 2/25 (8) CPV-2a
CPV-2c
2001–2007105 Italy/UK 0/39 (0)
2004–2014106 Bulgaria 1/18 (6) CPV-2a
2011–201426 India 1/4 (25) CPV-2a
2010–2013107 China 2/16 (13) CPV-2a
All years and countries. 15/243 (6)

which has since been reclassified as a Bocaparvovirus (Canine bocavirus 1).10 The
new CPV differed from FPV by only 6 amino acid residues in the VP2 region that are
critical for virus binding to the canine TfR, and for efficient infection of canine cells
through clathrin-mediated endocytosis.15 Thus, CPV-2 was unable to replicate in
any tissues of cats in vivo,18 although it was able to grow in feline cell cultures
in vitro.13
Frequent cross-transmission of FPV-like and CPV-like viruses between wild carni-
vore species suggests that FPV and CPV may have evolved independently from an
ancestral sylvatic parvovirus.11,12 Previously, it was thought that CPV evolved from
an FPV of domestic cats after cross-species transmission to wild carnivores, because
viruses intermediate between FPV and CPV have been detected in wild red foxes.19
However, the directionality of mutations was not considered. It has since been shown
that the VP2 mutations present in these viral intermediates can be induced by
passaging CPV-2 in fox cells in vitro.12
In 1979, shortly after the emergence of CPV-2, a new antigenic CPV variant
emerged (CPV2-a) with 4 amino acid mutations (L87M, I101T, A300G, and D305Y),
which could bind to canine and feline TfRs and cause disease in both host spe-
cies.20,21 It soon replaced CPV-2 in the wild and 2 other antigenic variants subse-
quently evolved with nonsynonymous mutations involving amino acids 426 and 555,
being first detected in 1984 in the United States22 (N426D, I555V termed CPV-2b)
and then in 2000 in Italy (D426E, termed CPV-2c).23 These variants cocirculate in vary-
ing proportions in different geographic regions around the world. All 3 antigenic vari-
ants have retained the feline host range.

CANINE PARVOVIRUS CAUSES CLINICAL AND SUBCLINICAL INFECTIONS IN CATS

Active Subclinical Infections
Canine parvovirus-2 antigenic variant strains have been detected by polymerase chain
reaction (PCR) and virus isolation in the feces of healthy cats.24–26 In the UK, fecal
shedding of CPV was detected in more than a third of fecal samples collected from
healthy cats from 2 mixed canine and feline shelters.25 None of the cats were found
654 Barrs

to be shedding FPV. Weekly fecal testing was performed in 1 of the shelters, in which
46% of cats, but no dogs, shed CPV on at least 1 occasion over an 8-week period.
Fecal samples were screened using conventional PCR to detect the VP2 region of
FPV/CPV, and sequencing and virus isolation was performed on positive samples.
The diversity of isolates detected, the time association of shedding with arrival to
the shelter, and the lack of fecal shedding by any dogs in the shelter, suggested
that cats were infected with CPV before their arrival. Around half of the feline CPV
sequence types were identical to those obtained from sick dogs with CPV-associated
diarrhea in a previous study.27
The high prevalence of CPV shedding in healthy shelter-housed cats raised con-
cerns about the role of cats as reservoirs of infection for dogs, and has important im-
plications for biosecurity, especially in mixed animal shelters housing both cats and
dogs. More recently, healthy shelter-housed cats were tested for fecal shedding of
CPV in 3 shelters in 2 states of Australia, using conventional PCR. Canine parvovirus
was not detected in any sample, while 4% of samples were FPV positive.28 Ongoing
surveillance and quantitation of fecal viral loads is required to further understand the
significance of CPV shedding by cats in different geographic regions.

Active Clinical Infections

All antigenic variants of CPV-2 have been detected among samples testing positive for
parvoviruses from clinically unwell cats in many countries (see Table 1). In general,
CPV is an uncommon cause of FPL, although only small numbers of isolates have
been tested (see Table 1). Samples testing positive for CPV were from individual feline
submissions to veterinary virology testing laboratories, and to date no large-scale out-
breaks of FPL, for example, in shelter-housed cats, have been confirmed to be caused
by CPV.
Naturally occurring CPV infections with clinical signs indistinguishable to
those caused by FPV, have been described in several cats.29–31 In 1 case of a fatal
CPV-2a infection in a 3-month-old Persian kitten, the source of infection was consid-
ered likely to be from 2 puppies with parvoviral enteritis that were infected with the
same strain and cohoused with the cat in a pet shop.31 Coinfections of CPV and
FPV have also been detected in cats with clinical disease.32,33 All CPV antigenic var-
iants have been shown to cause clinical disease in experimental infections of cats.34,35

Latent Infections
Carnivore protoparvovirus 1 DNA persists for long periods in the tissues of animals that
have recovered from infection, leaving behind a convenient molecular footprint of pre-
vious infection.11,12 The virus can remain latent in peripheral blood mononuclear cells,
as demonstrated by successful culture of FPV and CPV from the peripheral blood
mononuclear cells of healthy cats with high virus-neutralizing titers.36–38 Latency has
been demonstrated for other parvoviruses, including B19 parvovirus of humans. The
lifelong tissue persistence of B19 viral genomes, which are not re-shed, is termed the
“bioportfolio.”39 Whether certain conditions such as immune-suppression could induce
re-shedding of FPV or CPV in cats has not been investigated.

EPIDEMIOLOGY OF FELINE PANLEUKOPENIA

Age Susceptibility and Seasonality
Epidemiologic data from cases or outbreaks of FPL have been reported over many de-
cades (Table 2).40–43 Younger median age was apparent in reports involving shelter-
housed cats compared with reports from veterinary hospitals.
 Feline Panleukopenia 655

Table 2
Epidemiologic data from FPV outbreaks in the United States, Europe, and Australia

% of Cases
No. of Occurring in Cats Median Age at Age Range
Year Country Cases <1 y of Age Diagnosis (mo) of Affected Cats
1946–194840 United States 574 66 7 –
1964–197141 United States 185 70 5 –
1990–200742 Germany 244 72 4 2 wk–15 y
2010 United States 79 83% <6 mo of age 2–3 2 wk–7 y
2011–201371 Italy 133 71 3 2 mo–3 y
2014–2018 Australia 326 89 2.5 3 wk–8 y

Males were affected more commonly than females in 3 studies (57%–

59.5%),40–42 although in 2 of these studies from 1949 to 1976, males outnumbered
females in hospital admissions overall, partially reflecting a tendency for male cats
to be kept preferentially as pets at a time when desexing was not routinely
practiced.40
Feline panleukopenia occurs most frequently in unvaccinated and incompletely
vaccinated kittens. Age susceptibility is correlated with waning titers of maternally
derived antibodies (MDAs) as well as “the immunity gap” in incompletely
vaccinated kittens, when MDAs have waned below protective titers but are
adequate to neutralize vaccine antigen (see vaccination below). After being
ingested in colostrum, MDAs have a biological half-life of 10 to 11 days,44 and
generally remain at protective titers until 6 to 8 weeks of age.45 In 2 studies,
50% and 67%, respectively, of kittens born to FPV-immune queens became sus-
ceptible to FPV challenge at 10 weeks of age, whereas 75% and 100% were sus-
ceptible by 12 weeks of age, and all were susceptible by 16 weeks of age.46,47 In a
retrospective case series of FPL, of affected kittens that been vaccinated at least
once, none had received a vaccination in the primary kitten series after 12 weeks of
age.42
Importantly, almost 50% of kittens sourced from healthy queens in rescue shelters
and breeding catteries to investigate the effects of MDA on serologic responses to
vaccination had no MDAs at 6 weeks of age, highlighting the susceptibility of kittens
to infection among population groups in which queens are unlikely to be vaccinated
or exposed to FPV.48
The likelihood of an unvaccinated cat developing immunity to FPV from exposure
to field virus increases with age.49 Overall, seroprevalence among adult cats
varies widely among different populations tested (Table 3). The extent to
which exposure to CPV provides cross-reacting protective serum neutralizing anti-
body titers in cats is not fully known. Oral inoculation of 3 cats with CPV-2c
resulted in high serum neutralizing antibody titers against a commonly studied
FPV strain (TU-1), whereas inoculation of 2 cats with CPV-2a resulted in a low
anti-TU-1 antibody titer in 1 cat and a high titer in another.50 In vitro testing of
FPV and CPV against a panel of monoclonal antibodies produced against these vi-
ruses also demonstrated cross-reactivity because many antigenic epitopes are
shared.21,51,52
Feline panleukopenia generally occurs from summer to early autumn coinciding
with the onset of seasonal polyestrus and the corresponding influx of large numbers
of kittens with progressively waning MDA levels into shelters.41
656 Barrs

Table 3
Seroprevalence of FPV among populations adult cats that were unvaccinated or of unknown
vaccination status

Year of No. of Cats FPV Seroprevalence

Sampling Country Origin of Cats Tested (%)
1968108 New Zealand Commercial suppliers 50 78
1981109 Australia Unowned stray and feral cats 92 79
199836–38 Vietnam Animal markets 119 50
1998–2000110 Saudi Arabia Feral cats 10 10
1998–2001111 Costa Rica Owned cats 52a 93
2001112 Guatemala Owned cats 24 38
2005113 United States Feral cats 61a 33
2007114 France Owned and unowned stray 469a 25
cats
201049 United States New shelter admissions 111 55
2011–2012115 Germany Owned cats 28a 29
2013116 Russian Owned cats 60 45
a
Some cats <1 year old were included in these data.

PATHOGENESIS

Carnivore protoparvovirus 1 is a highly contagious, resilient virus capable of persisting

in infected premises such as shelters for at least 1 year.53,54 It is also resistant to heat-
ing (80 C for 30 min) and low pH (3.0).55 In infected cats, virus is shed in large quan-
tities in all excretions including saliva, urine, feces, and vomitus.56
The major portals of infection are the gastrointestinal (GI) tract via orofecal transmis-
sion and, less commonly, the respiratory tract through inhalation of aerosolized virus.
The latter route was confirmed by transmission experiments in the 1930s through
intranasal inoculation of FPV.4,57 In the field, transmission is predominantly indirect
by fomites.56 In 1 retrospective review of naturally occurring FPV infections, 62% of
affected cats were housed exclusively indoors, and 15% had no contact with other
cats.42
After infection, Carnivore protoparvovirus 1 binds to its cellular receptor, the TfR, a
transmembrane protein that is expressed in many tissues.15,58,59 Virions enter cells by
clathrin-mediated endocytosis and colocalize with transferrin in endosomes before
entering the cytoplasm to allow viral DNA to gain access to the nucleus.60 Viral DNA
is released from the capsid and replicates through double-stranded RNA intermedi-
ates in the nucleus of the cell. The virus does not possess its own DNA polymerase
and must “hijack” that of the host for replication to occur. Since the virus can only
replicate in actively diving S-phase cells, it has tropism for lymphoid tissue, bone
marrow, intestinal crypt epithelium, and the tissues of neonates still undergoing active
replication-FPV can replicate in the Purkinje cells of the cerebellum in neonates less
than 10 days old.56,61
Viral replication in oropharyngeal lymphoid tissue occurs 18 to 24 h postinfection,
and viremia can be detected within 2 to 7 days postinfection (DPI).56 Clinical disease
occurs in cats after 2 to 10 days incubation.56 Shedding of virus in feces may occur in
the absence of clinical signs (subclinical infections), or before clinical signs of disease
are detected. In experimental infections, virus shedding, detected by virus isolation,
occurred in urine for as long as 21 DPI and in feces for up to 6 weeks, although
 Feline Panleukopenia 657

most cats stopped shedding virus in feces after 3 weeks.56,62 Low-level shedding of
virus, as detected by sensitive methodologies such as quantitative PCR may persist
for greater than 6 weeks.
Transplacental infection can also occur, resulting in abortion, mummified fetuses or
stillborn kittens (early gestation), or kittens born with central nervous system deficits
(late gestation) (see clinical signs).63

CLINICAL PRESENTATION

Infection by FPV or CPV can be clinical or subclinical. High seroprevalence rates in

some populations of unvaccinated adult cats (see Table 3) suggest that subclinical in-
fections are common in young adult cats. Determinants of clinical disease include age,
immune status, and coinfections with intestinal parasites, viruses, and bacteria.64
Disease can be peracute, resulting in sudden death from septic shock with no pre-
monitory signs, especially in kittens less than 2 month old. The most common presen-
tation is characterized by an acute course of disease over several days with high fever
104 F to 106 F (40 C –41 C),4 lethargy, anorexia, vomiting, diarrhea, and severe dehy-
dration. Only some of these signs may be present, vomiting usually precedes diarrhea,
and, in contrast to dogs with CPV enteritis, hemorrhagic diarrhea is much less com-
mon, ranging from 3% to 15% of cats with FPL in 3 studies.40,43,65 Hypersalivation
from nausea may be present (Fig. 1), and was observed in 20% of cats with FPL in
1 shelter.43 Abdominal palpation may be painful and reveal thickened intestinal loops
and/or mesenteric lymph node enlargement (Fig. 2).
Myocarditis is a recognized complication of CPV infection in puppies, but
convincing evidence to support a role for parvoviral infection in cats with myocarditis
is lacking. Although parvoviral DNA has been amplified from the myocardium of kit-
tens66 and cats with myocarditis,67 this could be reflect previous active infection,
because in situ hybridization did not show any association with inflammatory foci.66
Depending on the stage of pregnancy at which infection occurs, infected queens
can abort (early pregnancy) or give birth to kittens with central nervous system and
ocular defects (late pregnancy), including cerebellar hypoplasia, hydrocephalus,
hydranencephaly, retinal dysplasia, and optic nerve hypoplasia.63,68,69 Clinical signs
of parvovirus infection in queens range from absent (subclinical infection) to severe.

Fig. 1. FPV-infected cat with nausea-associated hypersalivation.

658 Barrs

Fig. 2. (A) FPL causes severe enteritis, which is often segmental, affecting the jejunum, as
shown here. Clinical signs on palpation may include thickened, painful intestinal loops or
an abdominal mass associated with (B) mesenteric lymph node enlargement.

COMPLICATIONS OF FELINE PANLEUKOPENIA

Common complications that usually result in death include circulatory shock, septi-
cemia, and disseminated intravascular coagulation (DIC). Cats with FPL are also sus-
ceptible to coinfections as a result of severe immunosuppression. In previous reports
of disseminated fungal infections of cats, including aspergillosis and mucormycosis,
17% to 59% of cases had concurrent FPL.70

DIAGNOSIS
Hematology and Biochemistry
The onset of GI signs usually coincides with severe leukopenia (leukocyte counts
50–3000 cells/mL in severe cases; 3000–7000 cells/mL in less severe cases). Leuko-
penia is diagnosed in 65% to 75% of cases,42,71 and is characterized by neutrope-
nia and lymphopenia.42 In 1 study 5 to 6 days after experimental inoculation, white
blood cell counts were 350 to 500 cells/mL, but recovery was rapid and a rebound
leukocytosis occurred within 2 to 3 days of the nadir.72
Thrombocytopenia, diagnosed in approximately 55% of cases,42,71 results from
megakaryocyte destruction or DIC. Anemia occurs in 50% of cases and is usually
mild unless there is severe GI blood loss. The most common serum biochemical ab-
normalities are hypoalbuminemia (45%–52%), hypochloridemia (36%), hyponatre-
mia (32%), hypoproteinemia (30%), and elevations of aspartate aminotransferase
(27%).42,71
Neutralizing antibodies bind to the 3-fold spike regions of the viral capsid, the major
antigenic site of FPV/CPV, and can be detected within 6 to 8 DPI.56 Serologic detec-
tion of antibody is not used for diagnosis, because it does not distinguish between
presence of MDAs or acquired humoral immunity to field or vaccine strains of virus.

Confirmatory Tests: Fecal Antigen Tests, Polymerase Chain Reaction, Virus Isolation
Cage-side fecal antigen enzyme-linked immunosorbent assay test kits designed to
detect CPV in dogs can be used for diagnosis of FPL in cats, as they detect both
CPV-2a-c and FPV antigen in feline feces. The sensitivity of these tests in 1 small study
of 200 feline fecal samples, including 52 from cats with diarrhea, of which 10 were
confirmed to have parvovirus infection on electron microscopy, ranged from 50% to
80% in 5 different commercial kits. Test specificity was high (94%–100%).73 A
 Feline Panleukopenia 659

diagnosis of FPL should never be ruled out based on a negative fecal antigen enzyme-
linked immunosorbent assay test result; intermittent viral shedding or prevention of
binding of monoclonal antibodies to viral epitopes by endogenous antibodies can
negatively affect test sensitivity.
Vaccination against FPV using MLV vaccines can result in false-positive test fecal
antigen results for at least 14 days after vaccination.74 The specificity of CPV fecal
antigen tests in recently vaccinated kittens was shown to vary widely depending
on the brand of kit used (79.8%–98.4%).75
Polymerase chain reaction assays can be used to confirm the diagnosis of FPL in
cases that test negative on point-of-care fecal antigen tests, but in which clinical
presentation is suggestive of disease. Commercial PCR assays are usually quanti-
tative PCR assays that will amplify and detect the DNA of carnivore protoparvovirus
1, but may not distinguish between feline (FPV) and canine (CPV) strains. False-
positives can occur in recently vaccinated cats. Copy numbers of vaccine strains
of CPV in dogs are generally 4- to 5-fold lower than those of dogs infected with field
strains.76,77 Whether the same is true in cats has not been determined.
Other confirmatory tests for diagnosis that have largely been superseded by the
ready availability of fecal antigen tests and PCR include virus isolation, hemagluttina-
tion assays or detection of parvovirus particles using immuno-electron microscopy.

Necropsy
Gross postmortem findings range from minimal to extensive segmental enteritis with
dilation, hyperemia, hemorrhage, and necrosis, and/or serosal petechial or ecchy-
motic hemorrhages (see Fig. 2). Lesions are most severe in the jejunum and ileum.
Thickening of intestinal walls secondary to edema is also common. Mesenteric lymph
nodes are often enlarged, hemorrhagic, and edematous.4,57,61 On histology, intestinal
crypts are dilated and distended, with mucus and sloughed necrotic cell debris.78
Intranuclear inclusion bodies may be present in crypt enterocytes. Destruction of in-
testinal crypt epithelium results in mucosal collapse, with contraction and fusion of in-
testinal villi. In severe, acute disease, crypt epithelium can slough completely, leaving
only the basement membrane. In addition to edema and hemorrhage, there is marked
lymphocyte destruction in mesenteric lymph nodes. Lymphocytic infiltrates are absent
from all tissues, and intestinal mucosal infiltration by inflammatory cells is mild, owing
to the absence of leukocytes.

SEROLOGIC TESTING

Serology can be performed to identify cats at low risk of developing FPL after expo-
sure to FPV. A point-of-care test (ImmunoComb Feline VacciCheck, Biogal), which re-
quires minimal whole blood (10 mL), and tests up to 12 samples in parallel, was recently
evaluated after modification by the manufacturers to increase its sensitivity.79 Sera
from 347 cats were tested and a hemagglutination inhibition assay was used as the
reference method. Using a cutoff of 1:40 in the hemagglutination inhibition assay
to define a protective titer, test sensitivity was 83%, specificity was 86%, and, given
the overall antibody prevalence of 71%, the positive predictive value was 94% and the
negative predictive value was 68%. Therefore, in the study population, a positive test
result was very likely (94%) to indicate that the cat was protected against FPL,
whereas a negative test result was much less likely (68%) to indicate lack of protec-
tion. For managing FPL in a shelter, the specificity of this serologic test is more critical
than sensitivity, because the most likely consequence of a false-negative result is an
unnecessary primary or booster vaccination. However, failure to identify a susceptible
660 Barrs

animal (false-positive result) confers a risk of fatal disease if the result is used to inform
the decision whether to vaccinate the cat.

TREATMENT

Because of the high risk of contagion, any cat diagnosed with FPL and treated as an
in-patient should be quarantined in isolation, and barrier-nursed using strict hygiene to
prevent fomite transmission.

Fluid, Electrolyte, and Glucose Supplementation

Dehydration is often profound, and is a major contributor to mortality. Fluid, acid-base,
and electrolyte imbalances should be monitored and restored. Blood glucose should
be monitored in kittens. Parenteral glucose supplementation may be required in addi-
tion to intravenous crystalloid therapy. Hypoalbuminemic cats (albumin <20 g/L)
require plasma, synthetic colloids (eg, hetastarch), or typed whole-blood transfusion
if there is concurrent anemia. Plasma and heparin therapy are appropriate for treat-
ment of DIC.

Antimicrobial Therapy and Anthelminthics

Antimicrobial therapy is essential, because overwhelming sepsis associated with
translocation of GI tract bacteria and profound immunosuppression are a leading
cause of death. Antimicrobials with efficacy against Gram-negative, Gram-positive
and anaerobic bacteria should be chosen and given intravenously where possible.
Other important considerations include patient factors such as age, hydration
status, and renal function, as well as jurisdictional regulatory requirements for
antimicrobial use. For example, amoxycillin-clavulanate, ampicillin-sulbactam,
amoxicillin, or ampicillin could be combined with marbofloxacin, or, if the patient
is rehydrated and there is no evidence of acute renal injury, with gentamicin.
Others have recommended the combination of a potentiated penicillin with a
third-generation cephalosporin.80
The use of anthelminthics (eg, milbemycin oxime-praziquantel, imidacloprid-moxi-
dectin, or fenbendazole) is another important consideration, because intestinal
parasitism is a common comorbidity, especially in shelter-housed cats. Oral anthel-
minthics should not be administered to vomiting cats.

Antiemetic and Gastroprotectants Therapy

Antiemetic therapy should be prescribed for vomiting cats. Early enteral nutrition
with highly digestible diets is indicated as soon as emesis is controlled. Maropitant,
a 5-HT3 receptor antagonist, is the antiemetic of choice,71 and, when vomiting
is intractable, it can be combined with ondansetron, another 5-HT3 receptor antag-
onist.81 Mirtazapine, an antidepressant drug with serotonergic effects that is
commonly used for appetite stimulation in cats, also has antinausea and antiemetic
properties, mediated through 5-HT3 receptor antagonism.82 However, caution
should be exercised when using combinations of 5-HT3 receptor antagonists
because serotonin syndrome is a possible adverse effect.83 In addition, the safety
of mirtazapine in kittens has not been evaluated. In cats with hematemesis or with
severe intractable vomiting, and in which secondary reflux and esophagitis are of
concern, parenteral GI protectants, such as proton pump inhibitors (eg, esomepra-
zole or pantoprazole) or H2 receptor antagonists (eg, ranitidine or famotidine) may
be indicated.
 Feline Panleukopenia 661

Recombinant Feline or Human Granulocyte Colony-Stimulating Factor Therapy

Prospective studies evaluating the efficacy of recombinant feline or human granulo-
cyte colony-stimulating factor (rHuG-CSF) in cats with FPL are warranted. Bone
marrow cultures derived from healthy cats were inoculated with FPV, resulting in
loss of 80% to 90% of cells of myeloid lineage by 6 to 7 DPI.84 Treatment of uninfected
bone marrow cultures with rHuG-CSF, granulocyte macrophage-CSF, or
macrophage-CSF stimulated growth of myeloid progenitor cells. However, myeloid
progenitor cell proliferation was inhibited after inoculation of these cell cultures with
FPV.84 Treatment of clinical cases of FPL with rHuG-CSF did not increase leukocyte
count.85
In dogs with parvoviral enteritis, 2 of 3 studies showed no effect of rHuG-CSF on
neutrophil counts of CPV-infected dogs compared with controls.85–87 Treatment of
naturally occurring CPV infections in dogs using recombinant canine G-CSF was
associated with a significant increase in neutrophil and white blood cell counts
compared with controls, and with decreased hospitalization times.88 However, mortal-
ity was significant higher in the treatment group, and 2 of the 4 dogs that died had DIC,
raising questions about a possible adverse treatment effect.

Passive Immunotherapy
In some European countries, immune-serum raised in horses containing FPV anti-
bodies is commercially available for treatment and prevention of infection in suscepti-
ble animals (Feliserin Plus, IDT Biologika GmbH, Germany). Treatment efficacy has not
been evaluated in any prospective trials in cats. In 1 small retrospective study, the sur-
vival rate among 19 treated cats (68%), was significantly higher than in untreated cats
(51%).89 A prospective, randomized, placebo-controlled, double-masked study to
evaluate its efficacy for treatment of CPV enteritis was performed in dogs, after estab-
lishing that the sera fully neutralized all antigenic variants of CPV in vitro.90 No treatment
benefit was demonstrated—there were no significant differences between treatment
and placebo groups for clinical signs, laboratory parameters, survival, recovery time,
or fecal viral loads. For information on passive immunization in shelter cats using ho-
mologous serum see “Shelter management of an FPL outbreak, newly admitted cats.”

PROGNOSIS

Feline panleukopenia has a high mortality rate; survival rates in 3 retrospective studies,
in which all affected cats were given supportive treatment, were 20%, 34%, and
51%.43,65,71 In 1 study, the risk of death was greater in cats with (vs without) lethargy,
hypothermia (rectal temperature <100.2 F [37.9 C]), or low body weight at admis-
sion.71 Treatment with any of the following—antibiotics (amoxicillin-clavulanic acid),
antiparasiticides, or antiemetics (maropitant)—was associated with a lower risk of
nonsurvival. Administration of a glucose infusion was statistically associated with
death, and likely reflects the poor prognosis of cats with advanced sepsis. The admin-
istration of recombinant feline omega interferon (rFeIFN) at 1 MU/kg subcutaneously
(SC) q24 h for 3 days was not associated with survival. The finding that treatment
with rFeIFN did not confer an increased chance of survival contrasts with results of
a report in which treatment of dogs experimentally infected with CPV was associated
with improved clinical signs and reduced mortality.91 In cats, further prospective in-
vestigations are warranted, because, in the retrospective feline study, the mortality
rate was high (80%) and cats that died before completion of the 3-day course of ther-
apy were included in the analyses.71 In an in vitro study, treatment of feline cell cultures
with rFeIFN before FPV infection had a strong antiviral effect.92
662 Barrs

Other poor prognostic indicators for FPL include low leukocyte or platelet counts at
presentation,42 low leukocyte counts during hospitalization (days 3, 4, and 7),71 or
hypoalbuminaemia (albumin <30 g/L) or hypokalemia (<4 mmol/L) at presentation42

VACCINATION AGAINST FELINE PARVOVIRUS

In most kittens, MDAs have waned below concentrations that will cause vaccine inter-
ference by 8 to 12 weeks of age.45 However, in some kittens MDAs may persist at
interfering titers until 16 to 20 weeks of age,48,93 especially if the queen has high anti-
body titers against FPV. The World Small Animal Veterinary Association (WSAVA)
vaccination guidelines and the American Association of Feline Practitioners (AAFP) fe-
line vaccination advisory panel report recommend a schedule of feline core vaccina-
tions against FPV, feline calicivirus, and feline herpesvirus 1 commencing at 6 to
8 weeks of age, and then repeating vaccination every 2 to 4 weeks until 16 weeks
of age.45,94 The WSAVA guidelines also recommend consideration of bringing forward
the “booster” vaccine, which aims to capture nonresponders to the primary series of
kitten vaccines, from 12 to 6 months of age, to decrease the risk of exposure to field
virus in unprotected individuals.45
For adult cats receiving their first vaccination, an initial series of 2 doses of an inac-
tivated or MLV core vaccine, administered 2 to 4 weeks apart, is recommended to
establish a protective immune-response to feline calicivirus and feline herpesvirus 1,
although only a single dose of an MLV vaccine is required to establish a protective
immune-response to FPV.45 Modified live virus vaccines should be avoided in preg-
nant queens to prevent severe neurologic sequelae in developing fetuses.69
Vaccination against FPV induces a long-lasting humoral immunity in responders
(approximately 7 years), and a triannual revaccination interval is recommended. How-
ever, for cats entering potentially high-stress, high-exposure environments such as
boarding facilities, the AAFP guidelines recommend considering a booster 7 to
10 days before admission, particularly if the cat has not received a vaccination in
the last 12 months.
In shelter environments the core vaccine schedule is as above, except that the
first dose is recommended to be given as early as 4 weeks of age, but not later
than 6 weeks of age.45,94 Administration of MLV vaccines against FPV in kittens
younger than 4 weeks of age is not recommended because of the risk of cerebellar
hypoplasia.94 Because of faster onset of action,95 greater efficacy at overcoming
MDAs,48 and greater likelihood of a protective antibody titer occurring, MLV paren-
teral vaccines are recommended over inactivated vaccines.45,94 Intranasal FPV
vaccination is not recommended in shelters because it is inferior to FPV parenteral
vaccines, and its use was associated with re-emergent outbreaks of FPV in shelters
in the United States in the late 1990s and early 2000s.96 In shelters where FPV
exposure is likely to occur, vaccination of pregnant queens or queens of unknown
pregnancy status, with MLV vaccines, with an inherent risk of fetal death or malfor-
mation, may be preferable to not vaccinating against FPV, which risks loss of both
the queen and her offspring from FPL.94

SHELTER MANAGEMENT OF A FELINE PANLEUKOPENIA OUTBREAK

Diagnosis and Isolation
After confirmation of a suspected outbreak of FPL in a shelter (see confirmatory tests
above), diagnosis of FPL in subsequent cases is often based on 1 or more of the
following: consistent clinical signs in exposed cats, positive fecal antigen test results,
and/or low white blood cell count on a peripheral blood smear. It is imperative that all
 Feline Panleukopenia 663

sick cats with confirmed or suspected FPL are moved to an isolation area for treat-
ment that is, ideally, physically separated from the rest of the shelter. Staff working
in the isolation area should not enter other areas of the shelter.

Identification and Quarantine of Exposed Cats

In the face of an outbreak, all clinically healthy exposed and at-risk cats and kittens
more than 4 weeks old should be vaccinated with MLV vaccines immediately and
held in a separate quarantine area for 2 weeks. The quarantine area should only
contain nonporous surfaces that are easy to clean and disinfect. Handling of cats
should be kept to a minimum, to reduce stress and the risk of fomite transmission.
Serologic testing can be used to identify adult cats at low risk of infection and to
reduce the number of cats requiring quarantine during an outbreak. Seropositive
exposed cats are unlikely to develop FPL and can be adopted out of the shelter imme-
diately, bypassing the need for quarantine during the incubation period, even if they
have not been vaccinated or vaccination status is unknown. All kittens should be
vaccinated regardless, since serologic tests do not differentiate MDAs from acquired
humoral immunity. All seronegative animals are susceptible and should be vaccinated
and subsequently retested to confirm seroconversion.

Biosecurity
Infection control practices including signage (eg, infectious disease hazard signs,
handwashing, and disinfection posters), personal protective equipment (disposable
gloves, gown, boots/shoe covers), and equipment, as well as infection control training
procedures for shelter staff and volunteers, should be reviewed, to minimize the po-
tential for fomite spread. Restriction of access of nonessential personnel to the shelter
and closure to new intake should occur until the outbreak is controlled. Infection con-
trol training for all staff and volunteers (eg, workshops, on-line modules) is highly
recommended.
Effective disinfectants against Carnivore protoparvovirus 1 include sodium hypo-
chlorite (5%–6% household bleach diluted 1:30), accelerated hydrogen peroxide
(eg, Accel or Rescue, Virox Technologies Inc.), and potassium peroxymonosulfate
(eg, Trifectant, Virkon). Parvoviruses are resistant to quaternary ammonium com-
pounds (QAC). Some disinfectants containing QAC/biguanide combinations (eg,
F10, Trigene II) carry label claims of efficacy against parvoviruses in Europe, although
independent, peer-reviewed, published efficacy trials are lacking. Since most disin-
fectants are inactivated by the presence of organic matter, cleaning with detergent
before application of disinfection is essential. Disinfection of porous surfaces, such
as carpets, is problematic because residual organic matter is likely to persist after
cleaning. Also, using wet heat (eg, steam cleaning), a temperature of 90 C and min-
imum application time of 10 minutes, is required to inactivate parvoviruses.97
Alcohol-based hand sanitizers are ineffective against parvoviruses. Handwashing us-
ing liquid-soap or foaming handwash from dispensers is required to physically remove
fomites.98 Manufacturer guidelines for disinfectant dilutions, shelf-life once diluted, and
contact times should be strictly observed. For example, diluted bleach solutions must
be made-up fresh monthly and stored in light-proof containers to retain efficacy.99 Rinse
steps are also essential after contact times have been observed, because some disin-
fectants are corrosive (eg, bleach and potassium peroxymonosulfate) and/or cause
caustic injury to cats after direct exposure to footpads, conjunctiva, and skin, as well
as oral ulceration and esophagitis from inadvertent ingestion during grooming.100
Isolation and quarantine areas should each have their own dedicated equipment for
cleaning and disinfection to prevent inadvertent fomite transmission to other parts of
664 Barrs

the shelter. Work flow, based on infection risk, is critical during an outbreak. Separate
staff should care for each different cohort and, if possible, their movements to other
parts of the shelter should be restricted. If staff numbers are limited, new admissions
should be cleaned and fed first, followed by quarantined incumbent cats, then sick
affected cats in isolation.

Protection of Newly Admitted Cats

All cats and kittens 4 weeks of age should be vaccinated against FPV using MLV
vaccines and kittens should be revaccinated every 2 weeks, while they remain in
the shelter, until 20 weeks of age.45
For exposed cats and kittens that are known to be unvaccinated or colostrum
deprived, passive immunization using homologous serum from a recently immunized
cat, or nonhomologous serum (eg, Feliserin Plus), can be used to confer rapid protec-
tion. Passive immunization of kittens using sera from cats recovered from recent FPV
infection was practiced as early as 1949, and was found to confer protection against
infection for 2 to 3 weeks.40 A study in 2001 found that administration of 150 mL/kg of
adult cat serum given SC or intraperitoneally (IP) to colostrum-deprived kittens
achieved comparable concentrations with those ingested in colostrum.101 For passive
immunization against FPV, a dose of homologous serum from a recently vaccinated
cat, of 2 mL/kitten SC or IP, has also been recommended.102 Alternatively, plasma
can be given intravenously. Because immunoglobulins can persist for up to 4 weeks,
vaccination of passively immunized kittens must be delayed by 2 to 4 weeks.103

Documentation and Communication

Comprehensive daily records should be maintained, documenting all aspects of an FPL
outbreak including case numbers, clinical presentation and disease course, mortality,
methods of diagnosis, biosecurity and vaccination protocols, and husbandry practices
before and after the outbreak, so that progress can be tracked. A communication strat-
egy is essential to limit disease spread, and all stakeholders should be informed of the
outbreak, including other shelters and veterinary hospitals in the same region, foster
carers, shelter-volunteers, as well as shelter and veterinary associations.

SUMMARY

Feline panleukopenia, the oldest known viral disease of cats, is highly contagious.
Despite the availability of highly effective vaccines against FPV, which also confer a
long duration of immunity, the prevalence of exposure to FPV remains high worldwide.
In some countries, such as Australia, FPL is a re-emerging disease. In addition, all cur-
rent circulating canine parvoviruses can infect and cause disease in cats. Group-
housed cats are highly susceptible to FPL outbreaks, which are most likely to occur
from summer to autumn, in association with an influx of kittens with waning maternally
derived immunity into shelters. To effectively combat outbreaks of FPL, knowledge of
the characteristics of parvoviruses, disease epidemiology, diagnostics, optimal treat-
ment, and infection control practices, as well as WSAVA- and AAFP-recommended
vaccination strategies, is essential.

ACKNOWLEDGEMENTS

The author’s research on FPL is generously funded by the Cat Protection Society of
New South Wales, the Morris Animal Foundation (D18FE-001) and the Winn Feline
Foundation (W18-006).
 Feline Panleukopenia 665

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