Fatal Pandemic (H1N1) 2009 Influenza A Virus Infection in a Pennsylvania Domestic Cat

ORIGINAL ARTICLE

Fatal Pandemic (H1N1) 2009 Influenza A Virus Infection in aPennsylvania Domestic CatE. R. Campagnolo1,2, J. T. Rankin2, S. A. Daverio3, E. A. Hunt4, J. R. Lute5, D. Tewari6, H. M. Acland6,S. R. Ostrowski1, M. E. Moll2, V. V. Urdaneta2 and S. M. Ostroff2

1 Centers for Disease Control and Prevention, Office of Public Health Preparedness and Response, Office of Science and Public Health Practice,

Atlanta, GA, USA2 Pennsylvania Department of Health, Bureau of Epidemiology, Harrisburg, PA, USA3 Williamsport West Veterinary Hospital, Williamsport, PA, USA4 Pennsylvania Department of Health, Bureau of Community Health Systems, Williamsport, PA, USA5 Pennsylvania Department of Health, Bureau of Laboratories, Exton, PA, USA6 Pennsylvania Department of Agriculture, Pennsylvania Veterinary Laboratory, Harrisburg, PA, USA

Impacts

• Report of the earliest laboratory-confirmed pandemic pH1N1 fatality in a

domestic cat associated with influenza-like illness in a Pennsylvania family.

• Risk of exposure of domestic cats to pet owners ill with influenza-like illness

(ILI) during the peak period of the fall wave of 2009 pH1N1 in

Pennsylvania.

• Information presented will assist veterinary care providers and pet owners

in understanding the clinical features of this disease in domestic cats and

the potential for transmission of infection to pets from infected humans.

Introduction

Influenza A virus is an important respiratory pathogen

known to affect both humans and animals. Although aqua-

tic birds are considered to be the natural reservoir for most

influenza A viruses, many subtypes are relatively species-

specific and non-pathogenic to humans. Pigs can become

simultaneously infected with multiple influenza A sub-

types, including those found in humans, providing oppor-

tunities to recombine viral genetic segments and producing

new strain variants. This occurred in early 2009, when a

newly recognized recombinant influenza A/H1N1 variant,

composed of genetic segments from humans, pigs and

birds, was detected in two children in southern California

(Garten et al., 2009). This virus quickly spread throughout

North America and the rest of the world, and by June 2009

was termed a pandemic virus by the World Health Organi-

zation and is now referred to as pandemic H1N1 (pH1N1).

Although pH1N1 is thought to have originated in

mammalian (swine) viruses, once it had adapted to pro-

Keywords:

Pandemic; pH1N1; zoonoses; cat; fatal;

influenza A virus; veterinary public health;

pneumonia; influenza-like illness;

cardiomyopathy; Pennsylvania

Correspondence:

Dr. Enzo R. Campagnolo. Career

Epidemiology Field Officer, Pennsylvania

Department of Health, Northwest District

Office, 19 McQuiston Drive, Jackson Center,

PA 16133, USA. Tel.: 724 662 6081;

Fax: 724 662 6086; E-mail: [email protected]

Received for publication August 03, 2010

doi: 10.1111/j.1863-2378.2011.01390.x

Summary

We report the earliest recognized fatality associated with laboratory-confirmed

pandemic H1N1 (pH1N1) influenza in a domestic cat in the United States.

The 12-year old, indoor cat died on 6 November 2009 after exposure to multi-

ple family members who had been ill with influenza-like illness during the peak

period of the fall wave of pH1N1 in Pennsylvania during late October 2009.

The clinical presentation, history, radiographic, laboratory and necropsy find-

ings are presented to assist veterinary care providers in understanding the fea-

tures of this disease in cats and the potential for transmission of infection to

pets from infected humans.

Zoonoses and Public Health

500 Published 2011. This article is a US Government work and is in the public domain in the USA. • Zoonoses Public Health. 58 (2011) 500–507

duce human infection the virus caused sporadic infections

in other animal species. Starting in August 2009, labora-

tory-confirmed pH1N1 infection began to be reported in

swine (Pereda et al., 2010; ProMED, 2009a), in several

domestic species (cats, ferrets, dogs, turkeys), and in a

cheetah (USDA, 2009, 2010; AVMA, 2010; USDA-APHIS,

2010, ProMED, 2009b,c). These reports demonstrate that

pH1N1 can be anthroponotic (i.e. carried by humans and

transmitted to animals). In these cases, there was close

interaction between the infected animals and their human

owners, some of whom were reported to have influenza-

like illness (ILI). Although it has become apparent that

humans can transmit pH1N1 to animals, it has yet to be

established whether or not the spread of pH1N1 can be

bidirectional.

The first recognized case of laboratory-confirmed

pH1N1 illness in a domestic cat occurred in Iowa on 30

October 2009 (Sponseller et al., 2010; ProMED, 2009d);

this cat survived the infection and recovered. The earliest

fatal case of pH1N1 in a domestic cat occurred 1 week

later in Pennsylvania on 6 November 2009. The infection

was confirmed by the United States Department of Agri-

culture (USDA), National Veterinary Services Laborato-

ries (NVSL) in Ames, Iowa.

In this report, we describe the clinical features of the

illness observed in this cat, including necropsy findings,

to enhance awareness among veterinary clinicians about

this disease and to increase their index of suspicion about

the diagnosis in pets presenting with cardio-respiratory

illness, especially during periods of high influenza activity

in the community.

Case Report

On 5 November 2009, a previously healthy 12-year-old

domestic short-haired (DSH), orange tabby neutered

male cat, was brought to a veterinary clinic in north

central Pennsylvania with a respiratory illness (tachyp-

noea with dyspnoea), anorexia and lethargy. The pet

owner reported to the attending veterinarian that the ill-

ness was first noticed on 3 November 2009; the owner

expressed concern about the possibility of the cat having

pH1N1 infection because all human household members

had flu symptoms in the 2–3 weeks preceding the cat’s

illness. The cat was kept indoors 100% of the time, with

no opportunities for exposure to people or animals out-

side the home environment. The cat was reportedly a

very sociable and affectionate animal, inclined to sit

close to its owners, and often seeking face-to-face con-

tact with humans. Two dogs and a tortoise living in the

same home as the cat were reported as healthy. The pet

owners provided no history of coughing, sneezing, rhin-

orrhea, or conjunctivitis in the cat, nor were any of

these clinical signs observed by the attending veterinar-

ian.

There were four human household members living in

the home with the sick cat (Table 1). All four were

reported to have respiratory illness typical of influenza

with dates of onset between 19 October 2009 and 4

November 2009. On 1 November 2009, the 18-year-old

male household member was seen in the local hospital

emergency department and was clinically diagnosed with

pH1N1 infection. During this period, human pH1N1 ill-

ness was widespread in all regions of Pennsylvania, and

therefore no specimens were collected by the attending

physician to confirm this diagnosis. Of the 3697 speci-

mens submitted to the Pennsylvania state public health

laboratory for testing between 1 October 2009 and 26

November 2009, a total of 2542 (69%) were positive for

influenza virus, and 99% of the positive specimens were

characterized as pH1N1 (Pennsylvania Department of

Health Bureau of Laboratories BOL, 2009). The other

household members did not seek health care for their ill-

ness.

Clinical examination

Upon examination of the cat, the veterinary practitioner

noted difficulty in breathing, described as rapid, shallow

breathing, along with expiratory wheezing and slightly

harsh broncho-vesicular sounds on auscultation. The oral

mucous membranes were described as medium pink. The

cat was tachycardic with a heart rate of 200 beats/minute

(normal: 120–140), which was described as regular and

without murmur. The resting respiratory rate was signifi-

cantly elevated at 100 breaths per minute (normal: 16–

40). The rectal temperature was 102 �F at the time of the

examination (normal: 98.5–101.5 ± 1�F).

Table 1. Onset of respiratory illness in human household members

and pet cat, October 2009 to November 2009

Onset of respiratory

illness

Age

(years) Gender Clinical signs

19 October 2009 1.5 Female Fever, cough, congestion,

diarrhoea

23 October 2009 18 Female Congestion, cough,

malaise

28 October 2009 18 Male Fever, cough, congestion,

vomiting, arthralgia

3 November 2009 12 Male

(cat)

Tachypnoea, dyspnoea,

anorexia, lethargy

4 November 2009 49 Male Fever, cough, congestion,

nausea, arthralgia

E. R. Campagnolo et al. Fatal Pandemic (H1N1) 2009 Influenza A in a Domestic Cat

Published 2011. This article is a US Government work and is in the public domain in the USA. • Zoonoses Public Health. 58 (2011) 500–507 501

Clinical laboratory findings

A venous blood sample was collected from the cat and

analyzed in-house for a blood profile which included a

complete blood count (CBC) and blood chemistry

(Table 2). The only abnormalities noted were a slightly

low blood phosphorus of 2.8 mg/dL (normal: 3.1–7.5),

and a slightly elevated blood glucose of 161.0 mg/dL

(normal: 71–159).

Radiology

Dorsal and lateral thoracic radiographs were obtained.

The thoracic radiographs (Fig. 1) showed bilateral mot-

tled, mixed bronchial–interstitial and alveolar patterns

throughout the majority of the dorsal lung fields, consis-

tent with the clinical signs of compromised respiratory

function. The heart silhouette was distinct, and did not

appear to be enlarged or misshapen. A more consolidated

appearing area of soft-tissue/fluid density was evident cra-

nial to the heart and mediastinum. There was no appar-

ent deviation of the trachea or of the heart.

The cat was clinically diagnosed as having a respiratory

infection, and was administered 0.5 mL of procaine peni-

cillin-G subcutaneous by the veterinarian and dispensed

an oral antibiotic (Clavamox 125 mg tablets) to be taken

twice a day, according to standard hospital protocols. The

cat was then discharged from the veterinary hospital and

taken home by its owner.

The following day (6 November 2009), the cat was

brought back to the veterinary clinic with progressive ill-

ness, including increased anorexia and worsening respira-

tory symptoms, which included rapid shallow abdominal

breathing, suggestive of pneumonia or acute congestive

heart failure, although no cyanosis was observed. In

response, the veterinarian administered a fluoroquinolone

antibiotic (Baytril 22.7 mg/mL), 1 mL intramuscular and

subcutaneous fluid treatment with 100 mL of sterile 0.9%

NaCl saline and admitted the cat to the clinic for obser-

vation.

Because of the pet owner’s concerns about possible

pH1N1 illness in the household, the attending veterinar-

ian contacted the Pennsylvania Department of Agriculture

(PDA) for guidance. Although there was no apparent

nasal discharge, based on advice from PDA, nasal swabs

were collected from the ill cat and submitted to the Penn-

sylvania Department of Health Bureau of Laboratories

(BOL) for pH1N1 testing. To accomplish this, several

attempts at nasal and nasopharyngeal swabbing were per-

formed due to lack of nasal discharge.

While under observation, the cat died unexpectedly

later on the day of 6 November 2009. When first admit-

ted, kennel staff reported the cat as alert and sitting in his

cage, which appeared clean. The cat had used its litter

box, and had eaten a small portion of the canned food

provided. About 30 min later, the cat was noted to be

agonal and was lying on its side with the contents of the

cage having been disturbed as if there had been a seizure

or excessive thrashing. The cat vomited the recently eaten

food and expired a few minutes later.

Necropsy findings

On 7 November 2009, a necropsy was performed on the

cat by the attending veterinarian. There was no evidence

of cyanosis, and the oral mucus membranes were

observed to be pink. However, the cat’s heart and lungs

appeared grossly abnormal. The ventricular walls were

thickened with a corresponding decrease in heart chamber

size, compatible with the common pathologic condition

of feline hypertrophic cardiomyopathy (fHCM). The

lungs appeared mottled, but there was no evidence of

pulmonary oedema, nor was there presence of pulmonary

or pleural fluid. The entire bronchial tree (i.e. trachea,

bronchi and lungs) and heart were submitted, along with

the nasal swabs collected on November 6, to the BOL for

pH1N1 testing. Frozen lung tissue from the cat was also

submitted for histopathologic and microbiologic analysis

to the Pennsylvania Veterinary Laboratory.

Table 2. Blood profile for cat with respiratory illness, 5 November

2009

Complete blood count Blood chemistry

RBC 8.41 M/lL BUN 16.0 mg/dL

HCT 42.7% CREA 1.4 mg/dL

HGB 12.8 g/dL PHOS 2.8 mg/dL*

MCV 50.8 fL CA 8.8 mg/dL

MCH 15.28 pg TP 7.0 g/dL

MCHC 30.1 g/dL ALB 3.3 g/dL

RDW 19.7% GLOB 3.7 g/dL

%RETIC 0.3 ALT 62.0 U/L

RETIC 29.2 K/lL ALKP 52.0 U/L

WBC 8.09 K/lL TBIL 0.1 mg/dL

%NEU 76.5 CHOL 160.0 mg/dL

%LYM 11.6 AMYL 861.0 U/L

%MONO 8.9 GLU 161.0 mg/dL*

%EOS 2.4

%BASO 0.6

NEU 6.19 K/lL

LYM 0.94 K/lL

MONO 0.72 K/lL

EOS 0.19 K/lL

BASO 0.05 K/lL

PLT 302.0 K/lL

MPV 10.2 fL

PDW 17.9%

PCT 0.3%

*Denotes an abnormal value.

Fatal Pandemic (H1N1) 2009 Influenza A in a Domestic Cat E. R. Campagnolo et al.


Diagnostic laboratory testing

Influenza virology

The nasal swabs collected on 6 November 2009 were

transferred to individual sterile Universal Transport

Media (UTM) tubes (3 mL, Diagnostic Hybrids, Athens,

OH, cat #) and shipped overnight on frozen cold packs

to the BOL. On receipt, the swabs in UTM were mixed

vigorously for 30 s then manually extracted for viral RNA

using QIAamp Viral RNA Mini kit (QIAGen Sciences,

Maryland) following the manufacturer’s protocol. The

extract from each specimen was then tested by real time

RT-PCR (rRT-PCR) for influenza virus using the CDC

Swine Influenza Protocol (CDC, 2010). These specimens

were found to be below the detection limit used to iden-

tify 2009 influenza pH1N1 viral RNA and were read as

negative.

The necropsy tissues were received at the BOL for fur-

ther testing on 10 November 2009. The heart had already

been cut open but the tongue, trachea, bronchi and lungs

were intact. Using aseptic technique, four specimens were

collected for rRT-PCR analysis: a swab specimen from the

interior surface of the trachea; a tissue specimen (approx-

imately 5-mm square by 1- to 2-mm thick) from the

heart interior spanning a portion of the ventricles and

atria; a swab specimen from the interior of both branches

of bronchi; and a combined tissue specimen from both

lungs. Remaining tissue was frozen at )20�C, and then

subsequently transferred to )70�C freezer 24 h later.

All four specimens were transferred aseptically to indi-

vidual sterile tubes of UTM. The two tissue specimens in

UTM were processed using sterile 15 mL conical tissue

grinders (VWR International). The two swab specimens

were processed as described previously. Aliquots of the

tissue or swab supernatant solution were then manually

extracted and tested for 2009 influenza pH1N1 as

described above. All four necropsy specimens tested posi-

tive for the 2009 pH1N1 virus. Confirmatory tests were

repeated using fresh extracts.

On 18 November 2009, the remaining frozen cat tissue

samples were shipped from the BOL to the United States

Department of Agriculture (USDA), National Veterinary

Services Laboratories (NVSL) in Ames, Iowa. The clinical

specimens were tested by rRT-PCR for the presence of

the influenza matrix gene and for the pandemic neur-

aminidase gene (NVSL-SOP-BPA-9024, 2009; NVSL-SOP-

BPA-9034, 2010; NVSL-SOP-BPA-9035, 2010).

Samples were also inoculated onto Madin–Darby

Canine Kidney cells for virus isolation. Isolated viruses

were tested by both PCRs. The hemagglutinin, neuramini-

dase, and matrix genes were sequenced and found to be

the 2009 pandemic H1N1 virus. On 20 November 2009,

positive Matrix PCR, positive N1 PCR, positive virus iso-

lation, and genetic sequencing results were reported out

by NVSL for all tissue samples, including heart, tongue,

trachea, bronchi and lungs.

The lung tissue submitted to the Pennsylvania Veteri-

nary Laboratory (PVL) was also examined for bacterial

infection by culture, and for mycoplasma spp. infection

by PCR (Harasawa et al., 1986) with negative findings.

Immunohistochemistry

Immunohistochemistry was performed by the PVL using

a polyclonal swine influenza antibody purchased from

Iowa State University, a Dako LSAB2 HRP staining sys-

tem, and NovaRED� chromagen. Histopathology of the

lung section showed moderately severe diffuse acute fibr-

inous pneumonia showing strands of fibrin in alveolar

spaces, bronchi and bronchioles. A few inflammatory cells

including neutrophils and macrophages were also located

(b)

(a)

Fig. 1. Left lateral (a) and ventrodorsal (b) radiographic views of a

12-year-old neutered domestic cat with pH1N1 virus infection, 5

November 2009 (2 days after the onset of first clinical signs).



in the alveolar spaces, bronchi and bronchioles. Both

macrophages and bronchiolar epithelial cells in the lung

tissue section showed staining of influenza antigen further

confirming the lung infection with H1N1 influenza virus.

Contacts

At the time the ill cat was seen and hospitalized at the

veterinary clinic, six staff members were present in the

hospital. There were also three dogs that were caged in

the same observation room as the sick cat. Neither the

veterinary hospital staff, nor the hospitalized animals, at

any time developed ILI.

Discussion

This case report suggests that infection with pandemic

H1N1 influenza virus may be associated with severe and

fatal illness in domesticated cats. The Pennsylvania cat

became ill near the peak of pH1N1 activity during the fall

2009 wave, and most likely was infected by ill humans in

the household.

The gross necroscopy findings suggested to the attend-

ing veterinarian that the cat had underlying cardiac dis-

ease. Because heart tissue was not submitted for

histopathologic evaluation, it is not clear whether the

cat’s sudden death resulted from pH1N1 influenza-associ-

ated myocarditis or from pH1N1 influenza exacerbating

the underlying cardiac disease. The former is a well

known and fatal complication of influenza infections in

humans (Nolte et al., 2000; Greaves et al., 2003; Kitaura

et al., 2003; Kuiken and Taubenberger, 2008; Bratincsak

et al., 2010; Gross et al., 2010), and should be considered

in mammals kept as family pets and exposed to humans

with ILI.

Sudden death has been reported in both humans and

animals infected with influenza A virus. During the resur-

gence and spread of Highly Pathogenic Avian Influenza

H5N1 in Asia in 2004, this occurred in big cats at a zoo

in Thailand (FAO, 2010; WHO, 2010), when two tigers

and two leopards fed fresh chicken carcasses died unex-

pectedly, and H5N1 virus was identified in tissue samples

collected at necropsy (AVMA, 2009; WHO, 2010). In

humans, there have also been reports of sudden pH1N1

paediatric deaths in the absence of ILI, primarily linked

to fulminant viral myocarditis (Nolte et al., 2000; Gross

et al., 2010). The possibility that pH1N1-infected domes-

tic cats can also experience sudden death from viral

myocarditis should be further assessed if more tissue

specimens are made available from suspected cases.

As part of the differential diagnosis, a co-infection with

Feline Calicivirus (FVC) and/or Feline Herpesvirus I

(FHV-I) was also considered. Together, these pathogens

are responsible for approximately 80–90% of all feline

respiratory disease complex, and could have exacerbated a

co-infection with pH1N1, possibly leading to the cat’s

demise. Histopathology ruled out infection with FHV-I

because of the absence of intra-nuclear inclusion bodies

or syncitia in the lung tissue samples; these findings are a

hallmark of herpesvirus infection. FCV infection was also

ruled out because of the absence of clinical signs com-

monly observed with this disease, such as lameness and

ulceration of the tongue, mouth and palate.

Regardless of the cause of death in this cat, veterinari-

ans should remain alert to the possibility of pandemic

influenza virus infection in animals during periods of

community influenza activity. The index of suspicion

should be especially high when concomitant ILI is

reported in their human contacts.

Until recently, domestic cats had been considered rela-

tively resistant to influenza virus infections (Hinshaw

et al., 1981; Lohr et al., 2010). Current reports indicate

that cats, naturally or experimentally infected with Highly

Pathogenic Avian Influenza Virus H5N1, exhibit clinical

signs indicating both a respiratory and systemic involve-

ment (Kuiken et al., 2004; Rimmelzwaan et al., 2006;

Klopfleisch et al., 2007; Lohr et al., 2010). To date, there

have been too few documented cases of laboratory-con-

firmed pH1N1 infection in domestic cats to describe a

‘typical’ clinical presentation of pH1N1 infection. Table 3

represents a compilation of clinical signs in laboratory-

Table 3. Clinical signs reported in domestic cats with laboratory-confirmed 2009 pH1N1 influenza, USA, October 2009 to January 2010

State

Human

ILI Anorexia Cough Cyanosis Death Dehydration Dyspnoea Fever Lethargy Rhinorrhea Sneezing Wheezing

OR 4 4 4 4 4 4 4 4

OR 4 4 4 4 4 4 4

PA 4 4 4 4 4 4 4

IA 4 4 4 4

CA 4 4 4 4

CO 4 4 4

CO 4 4 4

UT 4 4

Total 8 (100%) 2 (25%) 1 (12.5% 1 (12.5%) 3 (37.5%) 4 (50%) 4 (50%) 0 (0%) 3 (37.5%) 5 (62.5%) 5 (62.5%) 2 (25%)



confirmed pH1N1 infections reported from October

2009 through January 2010 in domestic cats by the

AVMA (2009) and by the Pennsylvania cat’s attending

veterinarian.

All pet cats (100%) in Table 3 had contact with

humans with reported ILI, and three (37.5%) died. The

most common clinical signs were dyspnoea (50%), rhin-

orrhea (nasal discharge) (62.5%) and sneezing (62.5%);

100% of cats had at least one respiratory symptom, simi-

lar to what is seen with pH1N1 infection in other animal

species, particularly swine. Histopathology conducted on

the lung tissues samples obtained from the two feline

fatalities in Oregon indicated that both domestic cats had

necrotizing bronchointerstitial pneumonia (Lohr et al.,

2010).

The two large dogs living in the same household as the

sick Pennsylvania cat were reported as healthy. Although

also susceptible to pH1N1 infection, and exposed to the

same ill humans, the dogs did not develop any clinical

signs of illness. The varying degree of contact with house-

hold members could explain this difference, as could dif-

ferential susceptibility of dogs and cats to the 2009

pH1N1 virus. As the two dogs never exhibited clinical

signs of illness, veterinary clinical follow up and serologi-

cal testing to search for evidence of pH1N1 infection were

not pursued.

Antiviral drugs were not administered to the sick cat

despite concerns of pH1N1 infection. Oseltamivir has

not been approved by the Food and Drug Administra-

tion (FDA) for use in pets; however, extra-label use by

veterinarians is allowed on a case-by-case basis, under

the provisions of the Animal Medicinal Drug Use Clarifi-

cation Act (AMDUCA) of 1994 (FDA, 1994; AVMA,

2007). The AVMA guidelines indicate that decisions

regarding the use of oseltamivir in animals should be

based on both the severity of the animal’s illness and the

veterinarian’s clinical judgment. Many veterinary practi-

tioners did not prescribe antiviral drugs during the

H1N1 pandemic out of concern about the potential for

the development of antiviral drug resistance due to inap-

propriate or excessive use. Another concern was that

oseltamivir is the only influenza antiviral drug with wide

applicable use in humans, for whom use of oseltamivir is

associated with reduced mortality in severely ill persons.

However, based on documented fatalities associated with

pH1N1 infection in companion animals that were not

administered antivirals, consideration should be given to

defining situations better where antiviral administration

may be appropriate.

Although there was no evidence that the cat transmit-

ted the virus back to people or to the other animals in

the household, this potential exists. Therefore, veterinary

hospital staff should always make use of good infection-

control practices when handling animals potentially har-

bouring a zoonotic or animal-to-animal transmissible dis-

ease. These practices include the use of exam gloves and

other personal protective equipment, as appropriate, a

dedicated Infectious disease exam room that is sanitized

between animals, and careful hand Hygiene when

handling animals or when cleaning up after pets (CDC,

2009a,b, AVMA, 2010). Pet owners and veterinary hospi-

tal staff diagnosed with pH1N1 infection, or exhibiting

clinical signs of ILI, should limit their close contact expo-

sure to pets, and should practice appropriate respiratory

protection, and hand sanitation.

During an influenza pandemic, it would be advisable

for veterinary public health staff to establish a standard

series of influenza-related health questions for veterinary

clinical staff to ask if pets or pet owners are exhibiting

ILI. This would provide the opportunity for trained veter-

inary staff to discuss with pet owners ways of reducing

spread of infection. In order to limit exposure to other

animals, co-workers, or other clients, appointments for

pets with ILI could be scheduled towards the time of the

work day, when such exposure would be minimal.

Although not generally feasible in most practice settings,

a separate entrance and respiratory isolation area could

be made available for animals with respiratory illness.

Nasopharyngeal swabs are generally considered to be

the optimal specimens for animals with suspected influ-

enza. However, nasopharyngeal swabbing was difficult in

the Pennsylvania cat as there was no nasal discharge and

the swabs turned out to be negative. In circumstances

where the index of suspicion for influenza is high and

nasal discharge is minimal, consideration should be given

to obtaining specimens by means of nasal washes, and

collecting specimens from other sites, including the oro-

pharynx, for influenza testing.

Conclusion

We report the earliest laboratory-confirmed feline fatality

from the pH1N1 virus in the United States and postulate

that the abrupt death of this previously healthy in-door

domestic cat from Pennsylvania, presented to a veterinary

clinic with mild respiratory signs, suggests a cardiac com-

ponent to this pH1N1 infection, similar to what has been

document in big cats and humans as the gross appearance

of the heart during the necropsy/autopsy. Veterinary

practitioners may want to consider the findings presented

in this report while formulating a differential diagnosis

when confronted with a domestic cat with similar clinical

signs during a period of human pH1N1 illness.

Furthermore, the ‘One Health’ concept (Marano and

Pappiaoanou, 2004; AVMA, 2008; One Health Initiative,

2008; Hristovski et al., 2010), which includes the merging



of perspectives from the human and the veterinary medi-

cal disciplines, was exemplified by this investigation. This

particular case underlined the importance of the coopera-

tion, collaboration, and interactions between human pub-

lic health, veterinary public health, medical and veterinary

diagnostic laboratories, and the veterinary medical

practice, when dealing with cases of an emerging zoonotic

disease.

Acknowledgements

We thank the following for their contributions to this inves-

tigation: Dr. David V. Daverio, Dr. Sabrina L. Swenson, Dr.

Andre‘ C. Weltman, Dr. Kumar Nalluswami, Dr. Amy J.

Nesselrodt, Dr. Kirsten Waller, Dr. Virginia M. Dato, Mr.

Owen Simwale, Ms. Jamie Orres and Mr. Jerry Grabigel.

References

AVMA, 2007: Extralabel Drug Use (ELDU). An Information

Outline of the Animal Medicinal Drug Use Clarification Act

(AMDUCA). Brochure, Schaumburg, IL.

AVMA, 2008: One Health: A New Professional Imperative.

One Health Initiative Task Force: Final Report. July 15.

Schaumburg, IL.

AVMA, 2009: Public Health: Frequently Asked Questions

About 2009 H1N1 Flu Virus. Available at: http://www.

avma.org/public_health/influenza/new_virus/default.asp

(accessed on 15 April 2010).

AVMA, 2010: Public Health: Frequently Asked Questions

About 2009 H1N1 Flu Virus. Available at: http://www.

avma.org/public_health/influenza/new_virus/new_flu_

virus_faq_pet_owners.asp (accessed on 15 April 2010).

Bratincsak, A., H. G. El-Said, J. S. Bradley, K. Shayan, P. D.

Grossfeld, and C. R. Cannavino, 2010: Fulminant myocardi-

tis associated with pandemic H1N1 influenza A virus in

children. J. Am. Coll. Cardiol. 55, 928–929.

CDC, 2009a: H1N1 Flu (Swine Flu). Available at: http://

www.cdc.gov/h1n1flu/ (accessed on 14 January 2010).

CDC, 2009b: Compendium of Measures to Prevent Disease

Associated with Animals in Public Settings, 2009.

MMWR.National Association of State Public Health Veteri-

narians, Inc. (NASPHV), Atlanta, GA, USA. May1/Vol.58/

No.RR-5.

CDC, 2010: H1N1 Flu (Swine Flu): Resources for Laboratories.

CDC Protocol of Realtime RTPCR for Swine Influenza

A(H1N1). Available at: http://www.cdc.gov/h1n1flu/lab/

(accessed on 5 May 2010).

FAO, 2010: H5N1 in Cats. Available at: http://www.fao.org/

avianflu/en/wildlife/wild_animals.htm (accessed on 23 April

2010).

FDA, 1994: Animal Medicinal Drug Use Clarification Act

(AMDUCA) of 1994. Federal Food, Drug, and Cosmetic Act

(FD&C Act). January 25. Washington, DC.

Garten, R. J., C. T. Davis, C. A. Russell, B. Shu, S. Lindstrom,

A. Balish, W. M. Sessions, X. Xu, E. Skepner, V. Deyde, M.

Okomo-Adhiambo, L. Gubareva, J. Barnes, C. B. Smith, S.

L. Emery, M. J. Hillman, P. Rivailler, J. Smagala, M. de

Graaf, D. F. Burke, R. A. M. Fouchier, C. Pappas, C. M.

Alpuche-Aranda, H. Lopez-Gatell, H. Olivera, I. Lopez, C.

A. Myers, D. Faix, P.J. Blair, C. Yu, K. M. Keene, P. D.

Dotson Jr., D. Boxrud, A. R. Sambol, S. H. Abid, K. St.

George, T. Bannerman, A. L. Moore, D. J. Stringer, P.

Blevins, G. J. Demmler-Harrison, M. Ginsberg, P. Kriner, S.

Waterman, S. Smole, H. F. Guevara, E. A. Belongia, P. A.

Clark, S. T. Beatrice, R. Donis, J. Katz, L. Finelli, C. B.

Bridges, M. Shaw, D. B. Jernigan, T. M. Uyeki, D. J. Smith,

A. I. Klimov, and N. J. Cox, 2009: Antigenic and genetic

characteristics of swine-origin 2009 A(H1N1) influenza

viruses circulating in humans. Science 325, 197–201.

Greaves, K., J. S. Oxford, C. P. Price, G. H. Clarke, and T.

Crake, 2003: The prevalence of myocarditis and skeletal

muscle injury during acute viral infection in adults: mea-

surement of cardiac troponins I and T in 152 patients with

acute influenza infection. Arch. Intern. Med. 163, 165–168.

Gross, E. R., J. W. Gander, A. Reichstein, R. A. Cowles, C. J.

Stolar, and W. Middlesworth, 2010: Fulminant pH1N1-09

influenza-associated myocarditis in pediatric patients.

Pediatr. Crit. Care Med. 12, 1–3.

Harasawa, R., H. Mizusawa, and K. Koshimizu, 1986: A reli-

able and sensitive method for detecting mycoplasmas in cell

cultures. Microbiol. Immunol. 30, 919–921.

Hinshaw, V. S., R. G. Webster, B. C. Easterday, and W. J.

Bean, 1981: Replication of avian influenza A viruses in

mammals. Infect. Immun. 34, 354–361.

Hristovski, M., A. Cvetkovik, I. Cvetkovik, and V. Dukoska,

2010: Concept of one health – a new professional impera-

tive. Maced. J. Med. Sci. 3, 229–232.

Kitaura, Y., H. Deguchi, F. Terasaki, A. Ukimura, H. Morita,

and T. Tatsumi, 2003: Influenza myocarditis–pathophysio-

logy and developmental mechanism of myocarditis. Nippon

Rinsho. 61, 1945–1952.

Klopfleisch, R., P. U. Wilf, W. Uhl, S. Gerst, T. Harder, E. Sta-

rick, T. W. Vahlenkamp, T. C. Mettenleiter, and J. P. Teifke,

2007: Distribution of lesions and antigen of highly patho-

genic avian influenza virus A/Swan/Germany/R65/06

(H5N1) infection in domestic cats after presumptive infec-

tion by wild birds. Vet. Pathol. 44, 261–268.

Kuiken, T., and J. K. Taubenberger, 2008: Pathology of human

influenza revisited. Vaccine 26 (Suppl 4), D59–D66. Review.

Kuiken, T., G. Rimmelzwaan, D. van Riel, G. van Amerongen,

M. Baars, R. Fouchier, and A. Osterhaus, 2004: Avian H5N1

influenza in cats. Science 306, 241.

Lohr, C. V., E. E. DeBess, R. J. Baker, S. L. Hiett, K. A. Hoff-

man, V. J. Murdoch, K. A. Fischer, D. M. Mulrooney, R. L.

Selman, and W. M. Hammill-Black, 2010: Pathology and

viral antigen distribution of lethal pneumonia in domestic

cats due to pandemic (H1N1) 2009 influenza A virus. Vet.

Pathol. 47, 378–386.



Marano, N., and M. Pappiaoanou, 2004: Historical, new, and

reemerging links between human and animal health. Emerg.

Infect. Dis. 10, 2065–2066.

Nolte, K. B., P. Alakija, G. Oty, M. W. Shaw, K. Subbarao, J.

Guarner, W. J. Shieh, J. E. Dawson, T. Morken, N. J. Cox,

and S. R. Zaki, 2000: Influenza A virus infection compli-

cated by fatal myocarditis. Am. J. Forensic Med. Pathol. 21,

375–379.

NVSL-SOP-BPA-9024, 2009: 2009 H1N1 Influenza Virus Isola-

tion. Ames, Iowa.

NVSL-SOP-BPA-9034, 2010: Real-Time Rt-Pcr for the Detec-

tion of Swine Influenza Virus and Identification of Novel

N1 Subtypes in Clinical Samples. Ames, Iowa.

NVSL-SOP-BPA-9035, 2010: Amplification and Purification of

PCR Products for Direct Sequencing of Hemagglutinin,

Neuraminidase and Matrix Genes of Swine Influenza Virus.

Ames, Iowa.

One Health Initiative, 2008: One Health Initiative will Unite

Human and Veterinary Medicine. Available at: http://

www.onehealthinitiative.com/index.php (accessed on 2

February 2010).

Pennsylvania Department of Health Bureau of Laboratories

BOL, 2009: 2008/09 Influenza Virology Surveillance Data.

Pennsylvania Laboratory Information Management System

(LIMS) Available at: http://www.portal.state.pa.us/portal/

server.pt/community/laboratories/14158. (accessed 9 Apr

2010).

Pereda, A., J. Cappuccio, M. A. Quiroga, E. Baumeister, L.

Insarralde, M. Ibar, R. Sanguinetti, M. L. Cannilla, D.

Franzese, O. E. Escobar Cabrera, M. I. Craig, A. Rimondi,

M. Machuca, R. T. Debenedetti, C. Zenobi, L. Barral, R.

Balzano, S. Capalbo, A. Risso, and C. J. Perfumo, 2010:

Pandemic (H1N1) 2009 outbreak on a pig farm, Argentina.

Emerg. Infect. Dis. 16, 304–307.

ProMED, 2009a: Archive Number 20091020.3600. Available at:

http://www.promedmail.org/pls/apex/f?p = 2400:1001:2922

133396374024::::F2400_P1001_BACK_PAGE,F2400_P1001_

ARCHIVE_NUMBER,F2400_P1001_USE_ARCHIVE:1001,

20091020.3600,Y.

ProMED, 2009b: Archive Number 20091128.4079. Available at:

http://www.promedmail.org/pls/apex/f?p = 2400:1001:2922

133396374024::::F2400_P1001_BACK_PAGE,F2400_P1001_

ARCHIVE_NUMBER,F2400_P1001_USE_ARCHIVE:1001,

20091128.4079,Y.

ProMED, 2009c: Archive Number 20091115.3947. Available at:

http://www.promedmail.org/pls/apex/

f?p = 2400:1001:2922133396374024::::F2400_P1001_BACK_

PAGE,F2400_P1001_ARCHIVE_NUMBER,F2400_P1001_

USE_ARCHIVE:1001,20091115.3947,Y.

ProMED, 2009d: Archive Number 20091105.3816. Available at:

http://www.promedmail.org/pls/apex/

f?p = 2400:1001:::NO::F2400_

P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,

79947.

Rimmelzwaan, G., D. van Riel, M. Baars, T. M. Bestebroer, G.

van Amerongen, R. Fouchier, A. Osterhaus, and T. Kuiken,

2006: Influenza A (H5N1) infection in cats causes systemic

disease with potential novel routes of virus spread within

and between hosts. Am. J. Pathol. 168, 176–183.

Sponseller, B. A., E. Strait, A. Jergens, J. Trujillo, K. Harmon,

L. Koster et al., 2010: Influenza pandemic (H1N1) 2009

virus infection in domestic cat. Emerg. Infect. Dis. 16, 534–

537.

USDA, 2009: Final results 2009 Pandemic H1N1 Influenza.

Available at: http://www.usda.gov/documents/

FINAL_RESULTS_2009_PANDEMIC_H1N1_INFLUENZA_

CHT.pdf (accessed on 8 April 2010).

USDA, 2010: Final Results 2010 Pandemic H1N1 Influenza.

Available at: http://www.usda.gov/documents/H1N1_INFLU-

ENZA_CHART_SAMPLES_FOR_CY2010_032210.pdf

(accessed on 8 April 2010).

USDA-APHIS, 2010: H1N1 Influenza. Available at: http://

www.aphis.usda.gov/newsroom/hot_issues/h1n1/ (accessed

on 2 February 2010).

WHO, 2010: H5N1 Avian Influenza: Timeline. Available at:

http://www.who.int/csr/disease/avian_influenza/timeline.pdf

(accessed on 23 April, 2010).



Documents

Fatal Pandemic (H1N1) 2009 Influenza A Virus Infection in a Pennsylvania Domestic Cat