Feline respiratory Mycoplasma infections

Edited May 2020

These Guidelines were drafted by Fulvio Marsilio et al.

 

Introduction

 

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).

 

Aetiology

 

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).

 

Epidemiology

 

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.

 

Pathogenesis

 

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).

 

Clinical signs

 

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).

 

Diagnosis

 

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).

 

Fig 1: X-ray from a cat with asthma that had a secondary mycoplasmal infection diagnosed by PCR. Courtesy of Prof. Séverine Tasker

Fig 2: X-ray from the same cat of fig. 1 after 6 weeks of doxycycline treatment. Courtesy of Prof. Séverine Tasker

 

 

 

 

 

 

 

 

 

 

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).

 

Fig 3: BAL sample in a vial from the same cat above. Courtesy of Prof. Séverine Tasker

 

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.

 

Treatment

 

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).

 

DrugDose
Doxycycline10 mg/kg every 24 h
5 mg/kg every 12 h
Azithromycin5-10 mg/kg, every 24 h for 5 days, then every 48 h
Clindamycin10-15 mg/kg, every 12 h
Marbofloxacin2 mg/kg every 24 h
Pradofloxacin5-10 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).

 

Disease control

 

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).

 

Acknowledgement

 

ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD) and Virbac.

 

References

 

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