FIV and Upper Respiratory Disease
1. Introduction
2. Pathogens
3. Treatment
1. Introduction
All cats are liable to upper respiratory infections. In immune-competent adult cats, most are viral in origin. Upper respiratory infections can be a particular problem for immune-suppressed FIV+ cats, however, because of their recurrence and unusual severity. About 30% of FIV+ cats experience chronic upper respiratory infections [1]. Symptoms may include nasal congestion, discharge, watering eyes, and coughing. Secondary manifestations include loss of interest in food and general depression. Feline URI is passed from cat to cat by fluid discharged from the mouths and noses of infected cats, just as flu virus is passed between
humans. The pathogen can be spread through the air with sneezing, coughing, or breathing; or by
direct physical contact with almost anything in the environment.
2. Pathogens
Viral Pathogens
The most common causes of upper respiratory disease in all cats are viral: feline herpesvirus (FHV) and feline calici virus (FCV). If oral ulcers are present, calicivirus is most likely. If
corneal ulcers are present, herpesvirus 1 is most likely [2]. How common are these viral
diseases? A recent (2005) study by the University of Bristol of 1748 cats at 218 shelters,
catteries, breeders, and households with five or more cats found that both were more common
than other opportunistic pathogens and that calici virus (FCV) was considerably more common
than herpesvirus (FHV), about three times more common [3], probably because of shedding
characteristics. Other sources have characterized herpesvirus as the most common cause of
URTIs. Neither virus is normally life-threatening to an immune-competent cat, although a virulent strain of calici has appeared in recent years. Both tend to be chronic infections. After the initial
acute infection, a chronic carrier state sets in. Herpes is particularly notable for “flares” during
periods of stress or taxed immunity
Almost from the time of discovery of the feline immunodeficiency virus, the question of its relation to viruses such as FHV and FCV has been a subject of research and of clinical concern.
Does FIV-induced immunosuppression make these viral infections worse in FIV+ cats than in
FIV- cats? Do these viral infections cause problems in FIV+ cats that they do not necessarily
cause in FIV- cats? Does having these viruses actually advance FIV disease by taxing the
immune system? The answers to all of these questions are more probable than definite: Yes, yes,
and no.
There is a strong suspicion that FIV+ cats are actually predisposed to infection with chronic
respiratory virus carriers [4]. There is strong evidence that cats with FIV suffer more from the
effects of these viruses than do those without FIV. A 1992 Cal Davis study of FIV + cats found
that FHV-1 made them sicker and in greater need of supportive care than their FIV-negative
counterparts. Their lymphocytes (the object of FIV infection) showed greater and more sustained
proliferative response, indicating that they were less efficient in coping with the FHV. Their
initial antibody response (IgM) was also weaker, although their long-term response (IgG) was
unaffected [5]. Similarly, a 1994 Cal Davis study found that calici virus (FCV) caused more
severe disease in FIV+ cats with higher amounts of FCV being produced [6]. However, the news
was not all bad. Both studies found that neither duration of illness nor length of time in shedding
of viruses was affected by FIV infection. There is some contradictory evidence about calici virus.
A 1991 study at the University of Liverpool found that FIV+ cats were more likely to become
chronic carriers of the disease [7]; the Cal Davis study found that none of the experimentally
infected cats became chronic carriers.
Yes, it is probably true that infection with these viruses causes a particular set of problems in FIV+ cats. In the Bristol study, 47% of the cats in places where upper respiratory disease was
active showed calici virus, 16% herpesvirus [3]. Therefore, the already cited liability of FIV+
cats to more severe infection is going to play a role. Herpesvirus, in addition to causing upper
respiratory disease, has a particular role in recurrent eye infections. Both viruses–most
particularly calici virus–have been strongly implicated in chronic oral disease. (See
Gingivostomatitis.)
No, the available evidence does not seem to support the notion that infection with FHV and FCV
has a role in FIV disease advancement. A 1994 Cal Davis study exposed FIV+ cats to a wide
variety of pathogens, including FHV and FCV. FIV+ cats did not show a short or long-term
pattern of higher viral loads, or fewer CD4+ lymphocytes or lower CD4+/CD8+ ratios
(barometers of FIV immune-suppression), when compared to FIV- cats. It was concluded that
"repeated immune stimulation did not have a deleterious effect on the course of FIV-induced
immunodeficiency" [8]. The 1994 Cal Davis report on calici virus alone reported the same
conclusion [6] A 1995 Japanese study found that herpesvirus had the ability to transactivate (and
therefore increase) FIV virus embedded in the host genes in some circumstances, while in others
transactivation of viral replication was actually inhibited by FHV [9].
Vaccines are available for these viruses, although the effectiveness of vaccine for calici (of which
there are multiple strains) has been called into question [18]. They do not prevent disease, but do
lessen its severity and lessen the risk of transmission to other cats. Vaccines are given by
injection or intranasal drops. However, vaccinating FIV+ cats is a controversial proposition,
since vaccinations activate the immune response and stress the immune system. The
effectiveness of vaccines in FIV+ cats is a likewise unsettled subject. The AAFP currently
recommends vaccinations up to two years post-infection [10] But few owners of FIV+ cats
probably know when their cat was infected, and the two-year figure may be a shot in the dark in
any case.
Diagnostic testing for calici and herpes is not a simple matter. In both cases, viral shedding is
intermittent, so repeat testing is necessary when a negative result exists in order to insure that the
test was not done at a time when virus was not being shed. PCR testing for herpes is reliable;
PCR testing for calici is not, and the more laborious viral isolation test may be necessary[18]. Idexx has recently introduced a relatively inexpensive real-time PCR panel for the five most common upper respiratory pathogens, including herpes and calici. It is unclear whether the assay for calici has improved in reliability.
Bacterial Pathogens
Primary bacterial infection as a cause of upper respiratory disease in adult cats is not usual.
Chlamydia, the most common bacterial pathogen, is most often seen in kittens or young cats,
producing symptoms, such as sneezing, runny nose, runny eyes, and conjunctivitis. “The
conjunctivitis may or may not become chronic, and the conjunctivitis may also involve the
herpes virus, which sometimes manifests in the same manner” [11 ] PCR is the preferred method
of diagnostic testing. Vaccines are available for chlamydia, but are generally not recommended
because of potentially serious side effects.
Bordetella infection is largely limited to kittens and to cattery and rescue situations. The
distinguishing feature is cough. A vaccine is available.
Mycoplasma bacteria (notable for lack of a cell wall) are part of normal flora in the oral mucosae
of 70-80% of cats. For reasons not entirely clear, some species, particularly M. Felis, can cause
upper respiratory disease and conjunctivitis, occasionally pneumonia. Systemic illness has been
reported in immunosuppressed cats [24].
Fungal Pathogens
Cryptococcus neoformans is the most common fungus causing upper respiratory disease in
cats.[11]. Testing can confirm the diagnosis. Noticeable deformity to external features is one
characteristic that frequently separates fungal from viral or bacterial infection because fungal
infection causes more damage to the turbinate bones and associated tissue of the nose. Co-infection with FeLV or FIV can worsen the prognosis. In one 1997 study, FIV+ cats had a higher
likelihood of treatment failure than FIV- cat [12 ]. However, another study found that FIV+ cats
apparently had no greater likelihood of contracting this fungal infection[13].
Rhinitis
Chronic rhinitis signifies an ongoing inflammatory condition of the nasal passage. “The
pathogenesis of chronic rhinitis is unknown,” according to authority Lynelle Johnson, speaking
to an American College of Internal Veterinary Medicine forum in 2003. Primary bacterial
rhinitis is uncommon; chronic rhinitis almost always involves bacterial infection, but these
bacteria are usually secondary manifestations of another underlying cause, such as viral or fungal
infection. However, immunosuppression associated with FIV and FeLV can predispose to
bacterial rhinitis [11]. Fungal infections can cause a particularly destructive chronic rhinitis. For
the most part, however, the following alternative scenarios for chronic rhinitis involving virus are
most likely to be operative: “ It is possible that FHV-1 is an initiating pathogen in chronic rhinitis
with affected cats undergoing chronic or recurrent bacterial colonization secondary to anatomic
or physiologic alterations. An exuberant inflammatory response to the presence of virus or
bacteria might worsen disease. Alternatively, clinical signs might be related to permanent
destruction of nasal structures following acute viral cytolysis during a bout of acute severe
rhinitis. Finally, virus may chronically reactivate from the trigeminal ganglia into nasal tissues
and cause cumulative cytolytic destruction of nasal epithelium and bony turbinates” [14].
Whichever the case, the result is a disease state that is difficult, often impossible, to permanently
eliminate.
3. Treatment
Agents and dosages reflect individual research sources and do not carry the force of a veterinary recommendation.
Symptomatic
--Nose drops: Neo-Synephrine pediatric nose drops for congestion. (Couple drops per nostril).
--Chlor-Trimiton antihistamine (1/4 tablet/6 hrs, pure chlorpheniramine formula only)
--Steam (as in a bathroom with the cat shut in).
--Eucalyptus oil in a diffuser or on a wet cloth
--Vicks Vaporub smeared on the chin
--Stinging nettle has a natural antihistamine effect (200-500 mg added to meals)
--Goldenseal extract can be given PO or as nosedrops. Oregon grape is an alternative source of berberine, a contact antinflammatory and antimicrobial. (Goldenseal is often combined with
echinacea, but both are immune stimulants and should be used carefully and for short periods only (< 2 weeks) in FIV+ cats,
since immune activation increases infectivity and the hyperimmune activity associated with the disease.)
--Sucralfate [Carafate] used off-label for oral or esophageal ulceration from calicivirus infection. Binds to and forms a protective coating on ulcerated sites [23]. Prescription item. Mix with water to make a slurry. Slippery elm syrup may also be helpful
Antibiotic
For chlamydiosis, doxycycline at 5–10 mg/kg q24h PO for seven to 10 days is usually effective [11], although one source recommends treatment for 4 weeks, or for two weeks after
disappearance of clinical signs [18]. Bordetella responds to a five-day course of doxycycline (20-40 mg/kg sid) [18]. Mycoplasma likewise respond to doxycycline [24].
For cryptococcosis, “Ketoconazole, itraconazole, and fluconazole are effective treatments. Of the
published cases, fluconazole has the highest success rate. Due to increased toxicity, ketoconazole
should not be used in cats. Current ocular disease, CNS disease, or coinfection with FeLV or FIV
can worsen the prognosis. However, all FIV-infected cats in one study responded to fluconazole.
Serum antigen tests often do not return to negative following treatment even though measurable
disease has resolved. Itraconazole administered at 5.0 mg/kg q24h PO is recommended for
uncomplicated nasal cryptococcosus. Fluconazole administered at 50 mg/cat q24h PO is
recommended if ocular or CNS disease is occurring” [11].
For bacterial infections secondary to chronic viral disease or for primary bacterial rhinitis,
various approaches have been recommended. Some veterinarians will culture nasal secretion and
use an antibiotic recommended on the pathologist’s report. However, many internists take the
view that the cultured pathogen often does not reflect conditions deep within the nasal passages
or sinus cavity. Cultures taken by rhinoscopy often turn up different pathogens. In cases of long-standing or recurrent URTI, some veterinarians, therefore, routinely choose an antibiotic with a
broad spectrum against gram positive bacteria (ampicillin, amoxicillin, clavamox, clindamycin,
doxycycline) [14 ] and/or good action in penetrating bony and cartilaginous tissue (e.g.,
clindamycin), activity against anaerobes (clindamycin, metronidazole), and antinflammatory
properties(doxycycline, metronidazole) [11]. With convenience, as well as effectiveness, in
view, “Azithromycin (Zithromax) has been recommended in cases of chronic rhinitis in cats
(e.g., viral induced secondary bacterial infections). Doses recommended are 5 mg/kg daily
initially and then every 48 hr for chronic cases (there is a long t½ in cats: 35 hours!)” [14]. Keeping an FIV+ cat on antibiotics (for almost any infection) for a little longer than an FIV- counterpart is often a good idea. Some
veterinarians believe, however, that when a chronic upper respiratory infection has proved itself refractory, antibiotic therapy should cease. In the case of an FIV+ cat this is a difficult call, with much depending on immune
status.
*Some veterinarians and some pet owners on their own initiative prefer to deliver antibiotics for
URTIs, particularly stubborn ones, with a nebulizer. The cat is confined in a chamber once or
twice daily while a fine mist of antibiotic is sprayed into the air in the chamber, where it is
inhaled by the cat. If nothing else, the GI effects that some cats experience with antibiotics are
side-stepped. Here is a link describing building and use of a nebulizer.
http://catnipkids.homestead.com/nebulizer.html.
Antiviral
--L-lysine 500 mg bid for acute herpes outbreaks, 125 - 250 mg sid/bid as maintenance [20]. Ineffective for nonherpes URTIs.
--Bovine Lactoferrin, 250 - 350 mg divided twice daily for acute herpes [21]or calici [22] outbreak, 125-175 mg sid for maintenance. Has antiretroviral properties, as well.
--Prunella Vulgaris (a.k.a. All Heal, Self Heal) for acute herpes [25], 5-8 drops of tincture bid, 100-200mg dry extract bid; sid for maintenance (unverified dosages). Has antiretroviral
properties, as well.
--Low-Dose Oral interferon (human) 30 IU sid for acute or chronic herpes [15]; unlikely to help with calici.
--Feline omega interferon (Virbagen Omega) has significant action against both herpes [16]and calici [17]. 2006 Manufacturer’s protocol calls for three injections (2.5 MU/kg) on alternate days to treat acute infection, but Virbac representatives advise additional symptomatic treatment in the case of chronic URTI to
control acute symptoms. High-Dose Oral interferon (feline omega) 50,000 IU daily recommended by one source [18]. Calici associated with chronic gingivostomatitis is treated by a separate protocol. (See Gingivostomatitis: Medications . . . .) FIV is treated by a protocol different from herpes or calici. (See Bud's Medications . . . .)
--Intranasal vaccination with the bivalent FHV-1 and FCV vaccine may help to control active viral infection. “Prior to administering vaccine, 2-3 days of pretreatment with an antimicrobial
may be necessary to reduce the amount of nasal discharge. A single dose of intranasal vaccine is
administered in accordance with manufacturers' recommendations: 1 drop in each eye and the
remaining volume onto the nose-web. A response is expected within 10 to 14 days as the volume
of discharge and associated sneezing diminishes significantly. If there is no initial response, some
cats may respond to a second dose administered 30 days following the first dose” [19].
--Thymus-derived products may be helpful, particularly for immune-suppressed cats A human study of a partially refined thymus peptide (Thymostimulin) found that chronic purulent rhinosinusitis showed improvement at a 1mg/kg dosage in adults with clinical signs of immunodeficiency. Product was delivered by injection, however, as Lymphocyte T Cell Immunomodulator (LTCI) is.
__________________________________________________________________________________________
References
[1] Holly Nash. Feline Immunodeficiency Virus (FIV). Peteducation.Com.
http://www.peteducation.com/article.cfm?cls=1&cat=1316&articleid=213
[2] Michael Lappin. Infectious Diseases of the Feline Upper Respiratory Tract. World Small Animal Veterinary Association Congress. Vancouver, 2003.
http://www.vin.com/VINDBPub/SearchPB/Proceedings/Pr05000/pr00110.htm
[3] Helps CR, Lait P, Damhuis A, Bjornehammar U, Bolta D, Brovida C, Chabanne L, Egberink H, Ferrand G, Fontbonne A, Pennisi MG, Gruffydd-Jones T, Gunn-Moore D, Hartmann K, Lutz H, Malandain E, Mostl K, Stengel C, Harbour DA, Graat EA. Factors associated with upper respiratory tract disease caused by feline herpesvirus, feline calicivirus, Chlamydophila felis and Bordetella bronchiseptica in cats: experience from 218 European catteries. Vet Rec. 2005 May 21;156(21):669-73.
http://www.ncbi.nlm.nih.gov/pubmed/15908495?
[4] Richard B. Ford. Feline Viral Upper Respiratory Disease: Herpesvirus and Calicivirus. 30th World Congress of the World Small Animal Veterinary Association. Mexico city, 2005.
http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=10952&O=Generic
[5] Reubel GH, George JW, Barlough JE, Higgins J, Grant CK, Pedersen NC. Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in
experimentally infected specific pathogen free cats. Vet Immunol Immunopathol. 1992
Dec;35(1-2):95-119.
http://www.ncbi.nlm.nih.gov/pubmed/1363011?
[6] Reubel GH, George JW, Higgins J, Pedersen NC. Effect of chronic feline immunodeficiency virus infection on experimental feline calicivirus-induced disease. Vet Microbiol. 1994
Apr;39(3-4):335-51.
http://www.ncbi.nlm.nih.gov/pubmed/8042279?
[7] Dawson S, Smyth NR, Bennett M, Gaskell RM, McCracken CM, Brown A, Gaskell CJ.
Effect of primary-stage feline immunodeficiency virus infection on subsequent feline calicivirus
vaccination and challenge in cats. AIDS. 1991 Jun;5(6):747-50.
http://www.ncbi.nlm.nih.gov/pubmed/8042279?
[8] Reubel GH, Dean GA, George JW, Barlough JE, Pedersen NC. Effects of incidental
infections and immune activation on disease progression in experimentally feline
immunodeficiency virus-infected cats. J Acquir Immune Defic Syndr. 1994 Oct;7(10):1003-15.
http://www.ncbi.nlm.nih.gov/pubmed/7916048?
[9] Kawaguchi Y, Maeda K, Pecoraro MR, Inoshima Y, Jang HK, Kohmoto M, Iwatsuki K,
Ikeda Y, Shimojima M, Tohya Y, et al. The feline herpesvirus type 1 ICP4 down-regulates feline
immunodeficiency virus long terminal repeat (LTR)-directed gene expression via the C/EBP site
in the LTR. J Vet Med Sci. 1995 Dec;57(6):1129-31.
http://www.ncbi.nlm.nih.gov/pubmed/8720064?
[10] Vaccinations. The Cornell Feline Health Center College of Veterinary Medicine, Cornell University & The American Association of Feline Practitioners and the Academy of Feline
Medicine Advisory Panel on Feline Vaccines.
http://maxshouse.com/vaccine_protocols.htm.
[11] Michael Lappin. Infectious Diseases of the Feline Upper Respiratory Tract. World Small Animal Veterinary Association Congress. Vancouver, 2001.
http://www.vin.com/VINDBPub/SearchPB/Proceedings/Pr05000/pr00110.htm
[12] Jacobs GJ, Medleau L, Calvert C, Brown J. Cryptococcal infection in cats: factors influencing treatment outcome, and results of sequential serum antigen titers in 35 cats. Vet Intern Med. 1997 Jan-Feb;11(1):1-4.
http://www.ncbi.nlm.nih.gov/pubmed/9132477?
[13] Sierra P, Guillot J, Jacob H, Bussieras S, Chermette R. Fungal flora on cutaneous andmucosal surfaces of cats infected with feline immunodeficiency virus or feline leukemia. Am J
Vet Res. 2000 Feb;61(2):158-61.
http://www.ncbi.nlm.nih.gov/pubmed/10685687?
[14] Brendan McKiernan. Sneezing and Snorting—What Should I Do? World Small Animal Veterinary Congress. Vancouver, 2001.
http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00197.htm
[15] Hargis AM, Ginn PE. Feline herpesvirus 1-associated facial and nasal dermatitis and stomatitis in domestic cats. Vet Clin North Am Small Anim Pract. 1999 Nov;29(6):1281-90.
http://www.ncbi.nlm.nih.gov/pubmed/10562999?
[16] Uwe Truyen, Animal Health Service Bavaria . Antiviral Effects of Interferon Omega on In-Vitro Replication of Relevant Canine and Feline Viruses (German). Lecture 47. Annual
Convention of the Specialized Small Animals Group of the German Veterinary Medicine
Society and Lecture 7 of Conference of the Federation of the European Companion Animal
Veterinary Association, 25 October 2001 in Berlin.
www.tgd-bayern.de
[17] Uchino T et al. Full-Scale Study in the Field of Feline Interferon in Feline Calici Virus Infection. SAC Journal (Japan), 1997.
http://vetinterferon.nexenservices.com/aff_abstract.php?id=156&lang=eng
[18] Addie Diane. Feline Infectious Upper Respiratory Disease: A Book for Veterinary Surgeons. Melchizedek Publications.
[19] Ford RB. Feline Viral Upper Respiratory Disease: Herpesvirus and Calicivirus. 30th World Congress of the WSAVA, May 11-14, 2005. Mexico City.
http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=10952&O=Generic
[20] David J. Maggs , Nasisse MP, Kass PH. Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus. American Journal of Veterinary Research, January
2003, 64.1, 37-42.
http://avmajournals.avma.org/doi/abs/10.2460/ajvr.2003.64.37
[21] Beaumont SL, Maggs DJ, Clarke HE. Effects of bovine lactoferrin on in vitro replication of feline herpesvirus. Vet Ophthalmol. 2003 Sep;6(3):245-50.
http://www.ncbi.nlm.nih.gov/pubmed/12950656?
[22] Addie DD, Radford A, Yam PS, Taylor DJ. Cessation of feline calicivirus shedding coincident with resolution of chronic gingivostomatitis in a cat. J Small Anim Pract. 2003
Apr;44(4):172-6.
http://www.ncbi.nlm.nih.gov/pubmed/12703869?
[23] Boothe DM. Small Animal Clinical Pharmacology and Therapeutics: Introduction to Drug Use in Small Animals. Google Books.
[24] Mycoplasma.
https://www.vetconnect.com.au/5min/data/08400841.htm
[25] Zhang Y, But PP, Ooi VE, Xu HX, Delaney GD, Lee SH, Lee SF.. Chemical properties, mode of action, and in vivo anti-herpes activities of a lignin-carbohydrate complex from Prunella
vulgaris. Antiviral Res. 2007 Sep;75(3):242-9.
http://www.ncbi.nlm.nih.gov/pubmed/17475343
[26] Tas M, Leezenberg JA, and Drexhage HA. Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects. Clin Exp Immunol. 1990 June; 80(3): 304–313.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535186/?
[Page Top]
