Feline respiratory Mycoplasma infections
Edited May 2020
These Guidelines were drafted by Fulvio Marsilio et al.
Mycoplasmas are widely distributed in nature. Various species of these small prokaryotic organisms cause economically important infections in domestic animals (like mammals and birds), and infect also reptiles, as well as man. In addition, mycoplasmas represent a significant problem in diagnostic and in research laboratories, as well as in the vaccine industry, working with various cultures of mammalian cells. Mycoplasma infection of in vivo maintained cell cultures can cause disastrous effects, by altering cellular parameters and leading to unreliable diagnostic or experimental results and jeopardizing the safe production of vaccines or other biotechnological products (Wehbe et al., 2018).
The mycoplasmas that are of importance in human and veterinary medicine belong to the genus Mycoplasma (family Mycoplasmataceae, order Mycoplasmatales). In cats, several species of mycoplasmas have been described and they are currently divided into haemotropic and non-haemotropic types, on the basis of their ability to infect or to not infect erythrocytes, respectively. The mycoplasmas involved in the respiratory infections are of the non-haemotropic type, and the most important species isolated from cats with respiratory clinical signs is Mycoplasma felis (Greene and Chalker, 2012).
Mycoplasmas are the smallest prokaryotic organisms with the smallest genomes (a total of about 500 to 1000 genes) that can grow in cell-free culture medium (fried-egg-shaped colonies are seen on agar).
The dependence of mycoplasmas of their hosts for many nutrients may explain the great difficulty in cultivating many of these infectious agents in the laboratory. For example, they require cholesterol, a unique property among prokaryotes, for their growth in vitro.
The term mycoplasma (from Greek: mykes, fungus; plasma, formed) refers to the filamentous (fungus-like) nature of the organisms of some species and to the plasticity of the outer membrane resulting in pleomorphism (from spherical to filamentous). Mycoplasmas have surface antigens such as membrane proteins, lipoproteins, glycolipids, and lipoglycans. Some of the membrane proteins undergo spontaneous antigenic variation (Razin, 1996). As they lack cell walls, mycoplasma cells are easily damaged outside of the host (Maglaras and Koenig, 2015).
In cat several species of non-haemotropic mycoplasmas have been described: M. arginini, M. arthriditis, M. canadense, M. canis, M. cynotis, M. feliminutum, M. felis, M. gallisepticum, M. gatae, M. hyopharyngis, M. lipophilum., M. pulmonic and M. spumans.
Although Mycoplasma spp. may be part of the normal flora of the upper respiratory tract of cats (Tan et al., 1977), M. felis may be identified in cats with clinical signs or in healthy cats living with infected animals (Holst et al., 2010). Nowadays it is considered a primary pathogen of upper respiratory tract disease (URTD) (Chandler and Lappin, 2002; Holst et al., 2010; Le Boedec, 2017).
As a normal inhabitant of the respiratory mucosae, M. felis is transmitted directly from the infected cat to the in-contact one by aerosol. Indirect transmission is not important, because mycoplasmas are not able to survive for a long time outside the host (Maglaras and Koenig, 2015).
Stressors, such as overcrowding, concurrent respiratory viral infections and poor hygienic situations, may promote proliferation of mycoplasmas and their transmission between cats (Sykes, 2014).
In US shelter cats, Bannasch and Foley (2005) found a high prevalence (50%) of M. felis DNA, whereas McManus et al. (2014) found M. felis in 58% of cats showing clinical signs of URTD (ocular or nasal discharge, sneezing, coughing, conjunctivitis, or blepharospasm) and in 38% of healthy cats.
In Switzerland, Berger et al. (2015) found that 48% of Feline Calicivirus-suspect cats but also 31% of clinically healthy cats were positive for M. felis. Co-infection with M. felis was identified as one of the risk factors for FCV infection.
In Spain, Fernandez et al. (2017) reported that the prevalence of M. felis in cats with upper respiratory clinical signs was 46.5%, with conjunctivitis 38.3%, with gingivostomatitis 37.7% and 20.4% in healthy cats.
In Australia, Nguyen et al. (2018) found that out of 3126 samples from cats with upper respiratory clinical signs, 673 (21.5%) were positive for M. felis (21.5%) alone and 418 (13.4%) for M. felis associated with FCV.
Kopecny et al. (2019), in US cats with spontaneous acute URTD, found M. felis only associated with other respiratory agents such as Chlamydia felis, Bordetella bronchiseptica, Feline Calicivirus and Feline Herpesvirus.
The primary habitat of mycoplasma in general and, in particular, of M. felis, is the mucous surface of the upper respiratory tract where it adheres to the epithelial lining. The intimate association between the adhering mycoplasmas and their host cells provide an environment in which local concentration of toxic metabolites (i.e. H2O2) excreted by the bacteria build up and cause tissue damage. Furthermore, as mycoplasmas lack cell walls, fusion between the membrane of the bacteria and host cells may occur causing changes in cell membrane composition and increased permeability to the mycoplasma’s hydrolytic enzymes. These events are able to exacerbate the damage to the host tissues. Finally, the spontaneous genetic mutations are responsible for rapid changes at major surface protein antigenic levels helping the bacteria to escape the recognition by the immune system of the host (Razin, 1996).
Mycoplasmas may invade the lower respiratory tract as secondary opportunistic pathogens in animals with impaired mucociliary functions as consequence of primary bacterial or viral infection and of ciliary dyskinesia (Bernis, 1992).
M. felis is typically associated with URTD but sometimes it may be associated with lower respiratory tract infefctions (LRTIs).
The upper respiratory tract includes the nasal passages, sinuses, pharynx, and the larynx. Signs of upper respiratory tract infections include clear or coloured discharge from the eyes or nose, coughing, sneezing, conjunctivitis with swelling of the conjunctival mucous membranes (chemosis), lethargy, and anorexia. Rarely, cats may have trouble breathing. Very young, very old and immunosuppressed cats are more likely to develop severe disease and possibly die as a result of their URTD, usually due to secondary infections (e.g. causing pneumonia), consequence of anorexia (hepatic lipidosis) and dehydration (Cohn, 2011).
LRTIs may cause coughing, lethargy, anorexia, tachypnoea or dyspnoea, nasal discharge and pyrexia in the lower respiratory tract, which includes the portion of the larynx below the vocal folds, the trachea, bronchi, and bronchioles (MacDonald et al., 2003; Foster et al., 2004). Cats showing coughing, dyspnoea or tachypnoea should be investigated for LRTI (Foster and Martin, 2011).
After the first isolation and identification of M. felis by Cole et al. (1967) from cat saliva and ocular discharges, several authors described in detail, in which syndromes M. felis may be involved.
Switzer (1967) and Pedersen (1988) reported mycoplasmal pneumonia in kittens and Tan (1974) described subclinical pneumonitis developed in young cats experimentally infected with M. felis.
Glucocorticoid immunosuppressed cats may also develop mycoplasma pneumonia (Pedersen, 1988) and a mycoplasma species has been isolated from a pulmonary abscess in a mature cat (Crisp et al., 1987).
Mycoplasma purulent pleurisy (pyothorax) was described for the first time by Malik et al. (1991) and Trow et al. (2008) reported a clinical case of an adult cat with primary mycoplasma pneumonia associated with reversible respiratory failure.
M. felis may be associated with chronic rhinosinusitis in cats (Johnson et al., 2005) and Schulz et al. (2014) described Mycoplasma spp. in cats with lower respiratory disease (asthma and chronic bronchitis).
Hofmann-Lehmann reported an association between M. felis infection and nasal discharge and conjunctivitis in an epidemiological study (personal communication) and recently Pazzini et al. (2018) described a clinical case of upper respiratory disease in a cat showing chronic purulent nasal discharge and co-infection with M. felis and Tritrichomonas foetus.
Lastly, M. felis was identified in cats with ulcerative keratitis (Gray et al., 2005; Ledbetter and Scarlett, 2008), with conjunctivitis (Hartmann et al., 2010) and with polyarthritis (Hooper et al., 1985) or monoarthritis (Liehmann et al., 2006).
Mycoplasma infection may be clinically suspected in cats with URTD and has to be evaluated in cats with chronic respiratory disease, such as asthma (Fig. 1, 2) and chronic bronchitis, as well as in unresponsive patients being treated with antimicrobial drugs targeting cell wall synthesis (which are not effective against mycoplasmas as they do not have cell walls).
In order to collect the right diagnostic samples (depending on the location of the infection), contacting the diagnostic laboratory is useful to ensure the appropriate collection, handling and transportation of specimens (Maglaras and Koenig, 2015). Veir et al. (2008) suggested collection of both samples from nasal and pharyngeal sites from cats with URTD, while Lee-Fowler and Reinero (2012) recommended the endotracheal wash or the Broncho-Alveolar Lavage (BAL) for sampling the lower feline airways. Samples should be collected and placed into a solid transport medium for isolation (Amies is the best choice) or a sterile tube for biomolecular tests (Fig. 3). They have to be kept cool (not frozen) during the transportation (Chandler and Lappin, 2002).
At the laboratory, the samples are tested for mycoplasmal DNA by the Polymerase Chain Reaction (PCR). PCR, mainly real time-PCR, is widely used for its rapidity, sensitivity and ability to identify non-viable bacteria (Söderlund et al., 2011; Litster et al., 2015), as well as allowing identification of non-culturable species. The isolation is not used as routine diagnostic test because the mycoplasmas do not survive outside the host and then the culture may be negative as result of improper handling, prolonged transport time or collection errors.
As reported by Reed et al. (2012), if the organism is not cultured and only DNA is detected, the possibility of commensal contamination has to be considered, due to the higher sensitivity of PCR over culture. However, quantitative PCR is very useful to interpret positive results in the clinical scenario, mainly when conjunctival cells from cats with conjunctivitis or BALs from cats with LRTIs or lung samples from dead cats are collected. In cats with no clinical signs M. felis may be detected in oropharyngeal cells, less often in conjunctival cells.
Antimicrobial therapy is commonly used to treat mycoplasma respiratory infections. Doxycycline is a good first choice because it is well tolerated by cats. The recommended dose is 5 mg/kg, PO, q12h or 10 mg/kg, PO, q24 (Lappin et al., 2017).
Macrolides (azithromycin), lincosamides (clindamycin) and fluoroquinolones (marbofloxacin or pradofloxacin) could be used as second line drugs (Hartmann et al., 2008; Maglaras and Koenig, 2015).
The duration of treatment required is not clear. Clinical signs disappear within one week, but chronic intracellular infections may prevent the complete elimination (Reed, 2016). Greene and Chalker (2012) suggested a treatment period longer than one week. Hartmann et al. (2008) recommended a treatment period of 42 days with doxycycline or pradofloxacin, to achieve PCR negative results (Table 1).
|Doxycycline||10 mg/kg every 24 h
5 mg/kg every 12 h
|Azithromycin||5-10 mg/kg, every 24 h for 5 days, then every 48 h|
|Clindamycin||10-15 mg/kg, every 12 h|
|Marbofloxacin||2 mg/kg every 24 h|
|Pradofloxacin||5-10 mg/kg every 24 h|
As mycoplasmas lack of a cell wall, ß-lactam antibiotics (i.e. penicillin) are not effective (Lee-Fowler, 2014).
The antimicrobial susceptibility test results from nasal discharges are difficult to interpret because mycoplasmas cannot be cultured on standard laboratory media and sometimes positive cultures might not be associated with bacterial infection due to growth of commensal organisms (Lappin et al., 2017).
As no vaccine is currently available, the prevention of mycoplasma infections is based on the control of concurrent infections and the right management of the cat communities. For example, in shelters, efforts have to be made to avoid overcrowding, to reduce stressors and concurrent infections (Lappin et al., 2017). Washing hands and wearing gloves when handling a cat with respiratory clinical signs, may reduce the spreading of the pathogens among the animals (Lee-Fowler, 2014). Furthermore, it is good practice to isolate cats with respiratory signs and the routine use of effective disinfectants (Addie et al., 2015).
ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD) and Virbac.
Addie DD, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hartmann K, Horzinek MC, Hosie MJ, Lloret A, Lutz H, Marsilio F, Pennisi MG, Radford AD, Thiry E, Truyen U, Möstl K (2015): European Advisory Board on Cat Diseases. Disinfectant choices in veterinary practices, shelters and households: ABCD guidelines on safe and effective disinfection for feline environments. J Feline Med Surg 17, 594-605.
Bannasch MJ, Foley JE (2005): Epidemiologic evaluation of multiple respiratory pathogens in cats in animal shelters. J Feline Med Surg 7, 109-119.
Berger A, Willi B, Meli ML, Boretti FS, Hartnack S, Dreyfus A, Lutz H, Hofmann-Lehmann R (2015): Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland. BMC Vet Res 11, 282.
Bernis DA (1992): Bordetella and mycoplasma respiratory infections in dogs and cats. Vet Clinics North America: Small Anim Pract 22, 1173-1186.
Chandler JC, Lappin MR (2002): Mycoplasmal respiratory infections in small animals: 17 cases (1988-1999). J Amer Anim Hosp Assoc 38, 111-119.
Cohn L (2011): Feline respiratory disease complex. Veterinary Clinics: The Small Animal Practice 41, 1273-1289.
Cole BC, Golightly I, War JR (1967): Characterization of mycoplasma strains from cats. J Bacteriology 94, 1451-1458.
Crisp MS, Birchards J, Lawrence E, Fingeroth J (1987): Pulmonary abscess caused by a Mycoplasma species in a cat. J Amer Vet Medical Assoc 191, 340-341.
Fernandez M, Manzanilla EG, Lloret A, León M, Thibault JC (2017): Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydophila felis and Mycoplasma felis DNA and associated risk factors in cats in Spain with upper respiratory tract disease, conjunctivitis and/or gingivostomatitis. J Feline Med Sur 19, 461-469.
Foster SF, Martin P, Allan GS, Barrs VR, Malik R (2004): Lower respiratory tract infections in cats: 21 cases (1995–2000). J Feline Med Surg 6, 167-180.
Foster S, Martin P (2011): Lower respiratory tract infections in cats. Reaching beyond empirical therapy. J Feline Med Surg 13, 313-332.
Gray LD, Ketring KL, Tang Y-W (2005): Clinical use of 16S rRNA gene sequencing to identify Mycoplasma felis and M. gatae associated with feline ulcerative keratitis. J Clin Microbiol 43, 3431-3434.
Greene CE, Chalker VJ (2012): Nonhemotropic Mycoplasmal, Ureaplasmal and L-Form Infections. In: Infectious Diseases of the Dog and Cat. 4th ed, Sykes J and Greene CE (Eds), Saunders Company, 319-325.
Hartmann AD, Hawley J, Werckenthin C, Lappin MR, Hartmann K (2010): Detection of bacterial and viral organisms from the conjunctiva of cats with conjunctivitis and upper respiratory tract disease. J Feline Med Surg 12, 775-782.
Hartmann AD, Helps CR, Lappin MR, Werckenthin C, Hartmann K (2008): Efficacy of pradofloxacin in cats with feline upper respiratory tract disease due to Chlamydophila felis or Mycoplasma infections. J Vet Intern Med 22, 44–52.
Holst BS, Hanås S, Berndtsson LT, Hansson I, Söderlund R, Aspán A, Sjödahl-Essén T, Bölske G, Greko C (2010): Infectious causes for feline upper respiratory tract disease – a case–control study. J Feline Med Surg 12, 783–789.
Hooper PT, Ireland LA, Carter A (1985): Mycoplasma polyarthritis in a cat with probable severe immune deficiency. Australian Vet J 62, 352.
Johnson LR, Foley JE, De Cock HEV, Clarke HE, Maggs DJ (2005): Assessment of infectious organisms associated with chronic rhinosinusitis in cats. J Vet Med Assoc 227, 579-585.
Kopecny L, Maggs DJ, Leutenegger CM, Johnson LR (2019): Effects of famciclovir in cats with spontaneous acute upper respiratory tract disease. J Feline Med Surg 1–8, doi.org/10.1177/1098612X19857587.
Lappin MR, Blondeau J, Boothe D, Breitschwerdt EB, Guardabassi L, Lloyd DH, Papich MG, Rankin SC, Sykes JE, Turnidge J, Weese JS (2017): Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med 31, 279-294.
Le Boedec K (2017): A systematic review and meta-analysis of the association between Mycoplasma spp and upper and lower respiratory tract disease. J Amer Vet Med Assoc 250, 397-407.
Ledbetter EC, Scarlett JM (2008): Isolation of obligate anaerobic bacteria from ulcerative keratitis in domestic animals. Vet Ophthalmology 11, 114-122.
Lee-Fowler T (2014): Feline respiratory disease: what is the role of Mycoplasma species? J Feline Med Surg 16, 563-571.
Lee-Fowler T, Reinero C (2012): Bacterial respiratory infections. In: Infectious Diseases of the Dog and Cat. 4th ed, Sykes J and Greene CE (Eds), Saunders Company, 936–950.
Liehmann L, Degasperi B, Spergser J, Niebauer GW (2006): Mycoplasma felis arthritis in two cats. J Small Anim Practice 47, 476-479.
Litster A, Wu CC, Leutenegger CM (2015): Detection of feline upper respiratory tract disease pathogens using a commercially available real-time PCR test. The Vet J 206, 149-153.
MacDonald ES, Norris CR, Berghaus RB, Griffey SM (2003): Clinicopathologic and radiographic features and etiologic agents in cats with histologically confirmed infectious pneumonia: 39 cases (1991–2000). JAVMA 223, 1142-1150.
Maglaras C, Koenig A (2015): Mycoplasma, Actinomyces, and Nocardia. In: Small animal critical care. 2nd ed, Silversten DC and Hopper K (Eds), Elsevier Inc, 481-487.
Malik R, Love DN, Hunt GB, Canfield PJ, Taylor V (1991): Pyothorax associated with a Mycoplasma species in a kitten. J Small Anim Practice 32, 31-34.
McManus CM, Levy JK, Andersen LA, McGorray SP, Leutenegger CM, Gray LK, Hilligas J, Tucker SJ (2014): Prevalence of upper respiratory pathogens in four management models for unowned cats in the Southeast United States. The Vet J 201, 196-201.
Nguyen D, Barrs VR, Kelman M, Ward MP (2018): Feline upper respiratory tract infection and disease in Australia. J Feline Med Surg 21, 973-978.
Pazzini L, Mugnaini L, Mancianti F, Ressel L (2018): Tritrichomonas foetus and Mycoplasma felis coinfection in the upper respiratory tract of a cat with chronic purulent nasal discharge. Vet Clinical Pathol 47, 294–296.
Pedersen NC (1988): Mycoplasmosis. In: Feline Infectious Diseases. American Veterinary Publications, Goleta, 251-220.
Razin S (1996): Mycoplasmas. In: Baron S (ed). Medical Microbiology. 4th ed, Galveston (TX): University of Texas Medical Branch at Galveston; Chapter 37. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7637/
Reed N (2016): Respiratory and ocular mycoplasmal infections: significance, diagnosis, and management. In: August's Consultations in Feline Internal Medicine, Volume 7, Saunders Ed, 23-33.
Reed N, Simpson K, Ayling R, Nicholas R, Gunn-Moore D (2012): Mycoplasma species in cats with lower airway disease: improved detection and species identification using a polymerase chain reaction assay. J Feline Med Surg 14, 833-840.
Schulz BS, Richter P, Weber K, Mueller RS, Wess G, Zenker I, Hartmann K (2014): Detection of feline Mycoplasma species in cats with feline asthma and chronic bronchitis. J Feline Med Surg 16, 943-949.
Söderlund R, Bölske G, Holst BS, Aspán A (2011): Development and evaluation of a real-time polymerase chain reaction method for the detection of Mycoplasma felis. J Vet Diagnost Invest 23, 890–893.
Switzer P (1967): The genus Mycoplasma. In: Merchant and Packer: Veterinary Bacteriology and Virology. 7th ed, Iowa State University Press, Ames, 531-548.
Sykes JE (2014): Pediatric feline upper respiratory disease. Vet Clinics North America: Small Anim Pract 44, 331-342.
Tan RJS (1974): Susceptibility of kittens to Mycoplasma felis infection. Jpn J Exp Med 41, 235–240. Cited by Foster and Martin (2011): J Feline Med Surg 13, 313-332.
Tan RJS, Lim EW, Ishak B (1977): Ecology of mycoplasmas in clinically healthy cats. Australian Vet J 53, 515-518.
Trow AV, Rozanski EA, Tidwell AS (2008): Primary mycoplasma pneumonia associated with reversible respiratory failure in a cat. J Feline Med Surg 10, 398-402.
Veir JK, Ruch-Gallie R, Spindel ME, Lappin MR (2008): Prevalence of selected infectious organisms and comparison of two anatomic sampling sites in shelter cats with upper respiratory tract disease. J Feline Med Surg 10, 551-557.
Wehbe K, Vezzalini M, Cinque G (2018): Detection of mycoplasma in contaminated mammalian cell culture using FTIR microspectroscopy. Analytical and Bioanalytical Chemistry 410, 3003–3016.