Is Zithromax Good For Upper Respiratory Infections

Overview of FIV and Upper Respiratory Infection

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  • FIV and Upper Respiratory Infection

  • 1. Introduction

  • 2. Pathogens

  • 3. Treatment

  • Click here to open a Glossary of Terms in a separate window.
  • 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 eye infections 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. Clinical illness may persist up to three weeks, and pneumonia or sepsis due to secondary bacterial infection is always possible. However, neither virus is normally life-threatening to an immune-competent adult cat, although a virulent strain of calici has appeared in recent years. Both tend to be chronic infections with a chronic carrier state setting in after the initial acute infection. The calici carrier cat sheds virus continuously. It has been estimated that approximately 10% of healthy household cats are FCV carriers [19]. Chronic calici infections are particularly associated with periodontal disease and gingivostomatitis. In herpes carriers viral shedding is not continuous. Herpes is particularly notable for “flares” during periods of stress or taxed immunity. Recrudescent herpes infections are associated with keratitis and corneal ulceration, chronic snuffling and nasal discharge.

  • 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.

  • Suspicion has been expressed that FIV+ cats are actually predisposed to infection by chronic respiratory virus carriers [4a], although a recent study found no statistical association between FIV status and co-infection with FHV and FCV. 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, and calici - FIV coinfection is a probable risk factor for its development [19]. (See “FIV and 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 the case of herpes, 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. Shedding of calici is much more likely to be continuous. However, whereas PCR testing for herpes has been reliable, PCR testing for calici historically has not been, and the more laborious viral isolation test was 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]. One study of infection with chlamydia found that FIV infection prolonged the duration of clinical symptoms, that development of chronic conjunctivitis was more likely, and that clearance of the organism following standard therapy took nearly four times as long [31]. 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]. Sources differ on whether infection is or is not more common in cats with FIV. One source says it is [29]. However, another study found that it wasn't [13]. Serum antigen testing can usually 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- cats [12]. CNS disease a complication in 25% of cats [29].

  • 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.) Echinacea can be used alternatively or in combination with Goldenseal. Dosage recommendations vary, but 1 or 2 drops of glycerine-based tincture 3-4 times daily or 1 drop per pound per day are common. Both are immune stimulating herbs and should be used for short periods only (
  • --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.

  • *Note: 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.

  • Antiviral

  • Antibiotics are not effective against viruses. They can, however, both prevent and address secondary bacterial infections that are frequently associated with viral infections.

  • --L-Lysine 500 mg bid for acute herpes outbreaks, 125 - 250 mg sid/bid as maintenance [20]. Ineffective for nonherpes URTIs.
  • --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.
  • --Cranberry extract, 250 mg divided twice daily, inhibits acute or chronic calici [27]. Avoid long-term use in cats prone to oxalate (not struvite) stone formation in urinary tract. Black currant extract is a urine alkalyzer with known (human) anti-herpetic activity that might be used to neutralize the acidifying effect of the cranberry extract.
  • --Bovine Lactoferrin, 250 - 350 mg divided twice daily for acute herpes [21] or calici [22] outbreak, 125-175 mg sid for maintenance; lactoferrin has antiretroviral properties, as well.
  • --Famciclovir (62.5 mg sid/bid, 125 mg tid in varying protocols), effectiveness demonstrated against both herpetic upper respiratory/ destructive rhinosinusitis and ocular symptoms of herpes. [28]
  • --Low-Dose Oral Interferon-Alpha (human) 30 IU sid for acute or chronic herpes [15]; unlikely to help with calici. High-Dose Interferon-α (10, 000-20, 000 U/kg SC sid) for acute herpes or calici, esp. if pneumonia is suspected [30].
  • --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-ω (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 and Supplements” .) FIV is treated by a protocol different from herpes or calici. (See “Bud's Medications and Supplements”)
  • --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” [4].
  • --Thymus-derived products may be helpful, particularly for immune-suppressed cats. A human study of a partially refined preparation of thymus peptides (Thymostimulin) found that chronic purulent rhinosinusitis showed improvement at a 1mg/kg dosage in adults with clinical signs of immunodeficiency [26]. Product was delivered by injection, however, as another thymic derivative, Lymphocyte T Cell Immunomodulator (LTCI), is.

  • __________________________________________________________________________________________

  • References

  • [1] Nash H. Feline Immunodeficiency Virus (FIV). Peteducation.Com.

  • [2] Lappin M. Infectious Diseases of the Feline Upper Respiratory Tract. World Small Animal Veterinary Association Congress. Vancouver, 2003.

  • [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.

  • [4a] Ford RB. Feline Viral Upper Respiratory Disease: Herpesvirus and Calicivirus. 30th World Congress of the World Small Animal Veterinary Association. Mexico city, 2005.

  • [4b] Hellard E, Pontier D, Sauvage F, Poulet H, Fouchet D. True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses. PLoS One. 2012;7(1):e29618. Epub 2012 Jan 3.

  • [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.

  • [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.

  • [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.

  • [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.

  • [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.

  • [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.

  • [11] Lappin M. Infectious Diseases of the Feline Upper Respiratory Tract. World Small Animal Veterinary Association Congress. Vancouver, 2001.

  • [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.

  • [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.

  • [14] McKiernan B. Sneezing and Snorting—What Should I Do? World Small Animal Veterinary Congress. Vancouver, 2001.

  • [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.

  • [16] Truyen U, 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.
  • Uchino T et al. Full-Scale Study in the Field of Feline Interferon in Feline Calici Virus Infection. SAC Journal (Japan), 1997.

  • [18] Addie D. Feline Infectious Upper Respiratory Disease: A Book for Veterinary Surgeons. Melchizedek Publications.

  • [19] Ford R. Feline viral upper respiratory disease: why it persists! CVC in San Diego Proceedings. Oct 1, 2008; updated October 2009.

  • [20] Maggs DJ, 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.

  • [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.

  • [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.

  • [23] Boothe DM. Small Animal Clinical Pharmacology and Therapeutics: Introduction to Drug Use in Small Animals. Google Books.

  • [24] Mycoplasma.
  • https://

  • [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.

  • [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): 304313.

  • [27] Su X, Howell AB, D'Souza DH. The effect of cranberry juice and cranberry proanthocyanidins on the infectivity of human enteric viral surrogates. Food Microbiol. 2010 Jun;27(4):535-40.

  • [28] Malik R, Lessels NS, Webb S, Meek M, Graham PG, Vitale C, Norris JM, Power H. Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. J Feline Med Surg. 2009 Jan;11(1):40-8.

  • [29] Dullard SJ. "Fungal Infection" in Feline Internal Medicine Secrets. Hanley and Belfus, Inc., 2001. Google Books.

  • [30] Lappin MR. "Viral Diseases" in Feline Internal Medicine Secrets. Hanley and Belfus, Inc., 2001. Google Books.

  • [31]O'Dair HA, CD Hopper, TJ Gruffydd-Jones, DA Harbour and L Waters. Clinical aspects of Chlamydia psittaci infection in cats infected with feline immunodeficiency virus. Veterinary Record 1994;134:365-368.

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