Mycoplasmosis

Mycoplasmosis is a broad term encompassing infections caused by bacteria of the genus Mycoplasma, which are the smallest self-replicating prokaryotes lacking a cell wall. In veterinary medicine, mycoplasmas are significant pathogens in companion animals, particularly in cats and dogs, causing respiratory, urogenital, ocular, and joint diseases. Mycoplasma species are characterized by their small genome, fastidious growth requirements, and ability to evade the host immune system through antigenic variation and intracellular survival. In cats, Mycoplasma felis and Mycoplasma gatae are common commensals of the upper respiratory tract and conjunctiva, but can become pathogenic under stress or immunosuppression. Mycoplasma haemofelis (formerly Haemobartonella felis) is an epicellular erythrocytic parasite causing infectious anemia. In dogs, Mycoplasma cynos is associated with infectious tracheobronchitis and pneumonia, while Mycoplasma haemocanis causes hemolytic anemia. Mycoplasmosis can manifest as acute, chronic, or subclinical infections, with clinical signs varying by species and organ system involved. The disease is often secondary to primary viral or bacterial infections, immunosuppression, or stress, and can complicate the clinical course of other respiratory diseases.

The primary causative agents of mycoplasmosis in companion animals include: Mycoplasma felis (cats: conjunctivitis, upper respiratory disease, pneumonia, arthritis), Mycoplasma gatae (cats: conjunctivitis, respiratory disease), Mycoplasma haemofelis (cats: hemotropic mycoplasmosis, infectious anemia), Mycoplasma cynos (dogs: infectious tracheobronchitis, pneumonia), Mycoplasma haemocanis (dogs: hemotropic mycoplasmosis, anemia), and Mycoplasma canis (dogs: urogenital infections, pneumonia). Mycoplasmas are pleomorphic, cell-wall-deficient bacteria that are among the smallest free-living organisms. They possess a trilaminar membrane and lack peptidoglycan, making them inherently resistant to beta-lactam antibiotics. Virulence factors include adhesins (e.g., P1-like proteins) that facilitate attachment to host epithelial cells, and variable surface lipoproteins that undergo phase and antigenic variation to evade immune responses. Some species produce hydrogen peroxide and superoxide radicals, causing oxidative damage to host tissues. Mycoplasma haemofelis and M. haemocanis are epicellular parasites that adhere to erythrocytes, leading to extravascular hemolysis and anemia. Transmission occurs via direct contact with respiratory secretions, fomites, or arthropod vectors (fleas, ticks) for hemotropic species. Vertical transmission has been reported. In cats, M. felis is often secondary to feline herpesvirus-1 or calicivirus infections, while in dogs, M. cynos is frequently associated with canine infectious respiratory disease complex (CIRDC).

Mycoplasmosis is distributed worldwide, with prevalence varying by species, geographic region, and management practices. In cats, Mycoplasma felis is commonly isolated from the upper respiratory tract of healthy cats, with colonization rates up to 90% in multi-cat environments. Clinical disease is more frequent in young kittens, stressed animals, and those with concurrent viral infections. Mycoplasma haemofelis infection is more prevalent in cats with outdoor access, a history of flea infestation, and in regions with high flea populations. The prevalence of hemotropic mycoplasmosis in cats ranges from 1% to 30% depending on the population studied. In dogs, Mycoplasma cynos is a common cause of infectious tracheobronchitis, particularly in kennels and shelters, with outbreaks occurring in high-density populations. Mycoplasma haemocanis is less common and often associated with immunosuppression or splenectomy. Breed predispositions are not well-defined, but certain breeds may have increased susceptibility to hemotropic mycoplasmosis due to genetic factors affecting erythrocyte membrane antigens. Age predilection is seen in young animals for respiratory mycoplasmosis, while hemotropic infections can occur at any age. Sex predilection is not significant. Seasonal patterns may reflect vector activity for hemotropic species, with higher incidence in warmer months.

The pathophysiology of mycoplasmosis involves several mechanisms depending on the species and site of infection. For respiratory mycoplasmosis, Mycoplasma organisms adhere to ciliated epithelial cells of the respiratory tract via specialized adhesins, leading to ciliostasis, loss of cilia, and epithelial cell damage. This impairs mucociliary clearance, predisposing to secondary bacterial infections. The organisms produce hydrogen peroxide and other toxic metabolites that cause oxidative stress and inflammation. The host immune response, including neutrophil infiltration and cytokine release, contributes to tissue damage. In hemotropic mycoplasmosis, Mycoplasma haemofelis and M. haemocanis attach to erythrocyte membranes, causing structural damage and immune-mediated hemolysis. The attachment alters erythrocyte membrane antigens, leading to opsonization and phagocytosis by macrophages in the spleen and liver. This results in extravascular hemolysis, anemia, and potentially icterus. The severity of anemia correlates with the degree of parasitemia. Chronic infection may lead to immune-mediated destruction of uninfected erythrocytes, exacerbating anemia. In urogenital mycoplasmosis, organisms can cause inflammation of the reproductive tract, leading to infertility, abortion, or urethritis. Mycoplasmas can also induce arthritis by localizing in joints, causing synovitis and effusion. The lack of a cell wall allows mycoplasmas to evade immune recognition and resist antibiotics targeting cell wall synthesis, leading to persistent infections.

Predisposing factors for mycoplasmosis include: 1) Immunosuppression: FIV, FeLV, or chronic corticosteroid use increase susceptibility to clinical disease. 2) Concurrent viral infections: Feline herpesvirus-1, calicivirus, canine distemper virus, or canine adenovirus-2 can damage respiratory epithelium, facilitating mycoplasma colonization. 3) Stress: overcrowding, transportation, weaning, or environmental changes can trigger clinical disease in carrier animals. 4) Age: Young animals are more susceptible due to immature immune systems. 5) Poor ventilation and hygiene in shelters or kennels increase respiratory transmission. 6) Ectoparasite infestation: Fleas and ticks are vectors for hemotropic mycoplasmas. 7) Splenectomy or splenic dysfunction increases the severity of hemotropic mycoplasmosis. 8) Genetic factors: Certain breeds may have altered immune responses or erythrocyte membrane characteristics. 9) Nutritional deficiencies: Malnutrition can impair immune function. 10) Concurrent bacterial or parasitic infections can synergistically worsen disease.

Clinical signs of mycoplasmosis vary by species and organ system. Respiratory mycoplasmosis in cats: serous to mucopurulent nasal discharge, sneezing, conjunctivitis, ocular discharge, and in severe cases, pneumonia with coughing, dyspnea, and fever. In dogs, Mycoplasma cynos causes acute onset of cough, nasal discharge, and in severe cases, bronchopneumonia with fever, lethargy, and anorexia. Hemotropic mycoplasmosis (feline infectious anemia): acute onset of lethargy, pale mucous membranes, tachycardia, tachypnea, and fever. Icterus may be present in severe cases. Chronic infection may cause weight loss and intermittent fever. Urogenital mycoplasmosis: vaginal discharge, urethritis, cystitis, and reproductive failure. Arthritis: lameness, joint swelling, and pain. Ocular mycoplasmosis: conjunctivitis with chemosis, hyperemia, and ocular discharge. Systemic signs include fever, depression, and anorexia. In peracute cases, especially with hemotropic mycoplasmosis, sudden death may occur due to severe anemia. Subclinical infections are common, with carriers showing no clinical signs but capable of shedding organisms.

Differential diagnoses for respiratory mycoplasmosis include: 1) Feline herpesvirus-1 (FHV-1) infection: causes severe conjunctivitis and upper respiratory signs, but often with corneal ulcers; PCR can differentiate. 2) Feline calicivirus (FCV): causes oral ulcers and pneumonia; PCR differentiates. 3) Bordetella bronchiseptica: causes similar respiratory signs; culture or PCR. 4) Chlamydia felis: primarily causes conjunctivitis; PCR. 5) Canine infectious respiratory disease complex (CIRDC) agents: canine adenovirus-2, parainfluenza virus, Bordetella; PCR panels. 6) Primary bacterial pneumonia (e.g., Streptococcus, E. coli): culture and cytology. For hemotropic mycoplasmosis, differentials include: 1) Immune-mediated hemolytic anemia (IMHA): Coombs test positive, spherocytosis. 2) Feline leukemia virus (FeLV) or FIV-associated anemia: serology. 3) Cytauxzoonosis: intraerythrocytic piroplasms on blood smear. 4) Babesiosis: larger intraerythrocytic organisms. 5) Heinz body anemia: oxidative damage, eccentrocytes. 6) Blood loss anemia: history of trauma or bleeding. 7) Nutritional deficiencies (iron, B12). 8) Chronic disease anemia. For arthritis: immune-mediated polyarthritis, septic arthritis (other bacteria), trauma. For conjunctivitis: eosinophilic keratoconjunctivitis, foreign body, trauma.

The diagnostic approach to mycoplasmosis should be systematic: 1) History and physical examination: assess signalment, vaccination status, environment, and clinical signs. 2) Complete blood count (CBC): look for anemia, leukocytosis, or thrombocytopenia. In hemotropic mycoplasmosis, blood smear may show epicellular organisms on erythrocytes (especially with Wright-Giemsa stain). 3) Serum biochemistry: evaluate for hyperbilirubinemia, elevated liver enzymes, and globulins. 4) Serology: ELISA or IFA for antibodies to Mycoplasma spp., but may cross-react with other species. 5) PCR: highly sensitive and specific for detection of Mycoplasma DNA in blood, respiratory swabs, or joint fluid. Real-time PCR is the gold standard for hemotropic mycoplasmosis. 6) Culture: requires specialized media (e.g., SP4 broth) and is slow; not routinely performed. 7) Imaging: thoracic radiographs for pneumonia; joint radiographs for arthritis. 8) Cytology: joint fluid analysis for inflammatory arthritis; tracheal wash or bronchoalveolar lavage for respiratory disease. 9) Rule out other causes: FeLV/FIV testing, Coombs test, and PCR for other respiratory pathogens. 10) Response to therapy: clinical improvement with appropriate antibiotics (e.g., doxycycline) supports the diagnosis.

Hematology: In hemotropic mycoplasmosis, regenerative anemia (reticulocytosis, polychromasia) is common; non-regenerative anemia may occur in chronic cases. Blood smear may show basophilic coccobacilli on erythrocyte surface (M. haemofelis) or chains (M. haemocanis). Leukocytosis with neutrophilia may be present. Thrombocytopenia may occur due to immune-mediated destruction. Serum biochemistry: Hyperbilirubinemia and elevated liver enzymes (ALT, AST) due to hemolysis. Hyperglobulinemia may be present. Hypoalbuminemia may occur in chronic disease. Urinalysis: Bilirubinuria and hemoglobinuria in severe hemolysis. Blood gas analysis: Metabolic acidosis may occur in severe anemia. Specific biomarkers: Serum amyloid A (SAA) may be elevated in inflammatory mycoplasmosis. PCR: Positive for Mycoplasma DNA in blood (hemotropic) or respiratory samples. Serology: Antibody titers may be elevated but are not reliable for acute infection. Coombs test may be positive in immune-mediated hemolysis secondary to mycoplasmosis.

Radiography: Thoracic radiographs in respiratory mycoplasmosis may show interstitial to alveolar patterns, especially in the cranioventral lung lobes, consistent with bronchopneumonia. In chronic cases, bronchiectasis may be evident. Abdominal radiographs may show hepatosplenomegaly in hemotropic mycoplasmosis. Ultrasonography: Splenomegaly and hepatomegaly may be seen. Echocardiography: Not typically indicated unless cardiac complications arise. CT: High-resolution CT may reveal bronchiectasis or pulmonary nodules in chronic respiratory mycoplasmosis. MRI: Not routinely used. Endoscopy: Tracheobronchoscopy may reveal mucosal erythema, edema, and excessive mucus; samples can be collected for cytology and PCR.

Cytology: Tracheal wash or bronchoalveolar lavage fluid may show neutrophilic inflammation with intracellular and extracellular bacteria. Joint fluid analysis in mycoplasmal arthritis shows inflammatory synovial fluid with increased neutrophils. Blood smear for hemotropic mycoplasmosis: organisms appear as small basophilic cocci or rings on erythrocytes. Histopathology: Lung biopsy may show bronchointerstitial pneumonia with neutrophilic infiltration and epithelial necrosis. In hemotropic mycoplasmosis, spleen and liver may show hemosiderosis and erythrophagocytosis. Special stains: Giemsa or Wright stain for blood smears; silver stains may highlight organisms in tissues.

Treatment of mycoplasmosis involves antimicrobial therapy, supportive care, and management of underlying conditions. The drug of choice for most mycoplasmal infections is doxycycline (5-10 mg/kg PO q12h or 10 mg/kg PO q24h) for 2-3 weeks. For hemotropic mycoplasmosis, doxycycline is also first-line, but in severe anemia, blood transfusion may be necessary. Alternative antibiotics include fluoroquinolones (e.g., enrofloxacin 5-10 mg/kg PO q24h) or macrolides (e.g., azithromycin 5-10 mg/kg PO q24h). In cats, doxycycline should be administered with food or water to prevent esophagitis; use of doxycycline hyclate is preferred. For respiratory mycoplasmosis, treatment may include doxycycline for 7-14 days, along with supportive care such as nebulization, bronchodilators (e.g., terbutaline 0.01 mg/kg SC or PO q8h), and anti-inflammatory doses of corticosteroids if severe inflammation. For arthritis, doxycycline for 4-6 weeks may be needed. In cases of immune-mediated hemolytic anemia secondary to mycoplasmosis, immunosuppressive doses of corticosteroids (e.g., prednisolone 2-4 mg/kg PO q24h) may be added. Supportive care includes fluid therapy, nutritional support, and oxygen therapy if dyspneic. In severe anemia (PCV < 15%), blood transfusion is indicated. Prevention of flea and tick infestation is crucial for hemotropic mycoplasmosis.

The prognosis for mycoplasmosis is generally good with appropriate antimicrobial therapy, especially in immunocompetent animals. For respiratory mycoplasmosis, clinical signs typically resolve within 1-2 weeks of treatment, but chronic carriers may persist. For hemotropic mycoplasmosis, the prognosis is guarded to good; with prompt treatment, most cats recover, but mortality can be high in severe anemia or concurrent infections. Negative prognostic indicators include severe anemia (PCV < 10%), icterus, concurrent FeLV/FIV infection, and lack of response to therapy within 48-72 hours. Chronic infection may lead to persistent parasitemia and recurrence. In dogs with Mycoplasma cynos pneumonia, prognosis is good with treatment, but severe cases may require hospitalization. Overall, the recurrence rate is low if underlying predisposing factors are addressed.

Follow-up for mycoplasmosis should include: 1) Recheck examination 7-14 days after initiation of therapy to assess clinical response. 2) Repeat CBC and blood smear for hemotropic mycoplasmosis to monitor parasitemia and anemia resolution. 3) PCR testing 4-6 weeks after treatment to confirm clearance of infection, especially in hemotropic cases. 4) For respiratory mycoplasmosis, repeat thoracic radiographs if clinical signs persist. 5) Monitor for adverse effects of doxycycline, such as esophagitis in cats. 6) Long-term management includes minimizing stress, providing good nutrition, and controlling ectoparasites. 7) In cats with FIV/FeLV, regular monitoring for recurrence is recommended. 8) For breeding animals, consider screening for urogenital mycoplasmosis before breeding.

Pearls: 1) Mycoplasma infections are often secondary; always investigate for underlying viral infections or immunosuppression. 2) Doxycycline is the drug of choice; always administer with food or water in cats to prevent esophagitis. 3) Blood smear examination is quick and can be diagnostic for hemotropic mycoplasmosis, but PCR is more sensitive. 4) In cats with conjunctivitis, consider Mycoplasma felis as a cause, especially if no corneal ulcers. 5) Mycoplasma cynos is a common cause of kennel cough; include it in the differential for dogs with persistent cough. Pitfalls: 1) Do not use beta-lactam antibiotics (penicillins, cephalosporins) as they are ineffective due to lack of cell wall. 2) Avoid using enrofloxacin in young cats due to risk of retinal toxicity. 3) Do not rely solely on serology for diagnosis; PCR is preferred. 4) In hemotropic mycoplasmosis, do not confuse with other hemoparasites; confirm with PCR. 5) Do not discontinue antibiotics prematurely; complete the full course to prevent recurrence.

Antimicrobials: Doxycycline (5-10 mg/kg PO q12h or 10 mg/kg PO q24h) for 14-21 days; for hemotropic mycoplasmosis, treat for at least 28 days. Enrofloxacin (5-10 mg/kg PO q24h) as an alternative, but avoid in young cats (< 6 months) due to retinal toxicity. Azithromycin (5-10 mg/kg PO q24h) for 3-5 days, then every other day. Clindamycin (10-20 mg/kg PO q12h) may be effective but less preferred. Supportive care: Fluid therapy with balanced crystalloids (e.g., LRS) at maintenance rates (60-80 ml/kg/day) adjusted for dehydration. Blood transfusion: For PCV < 15% or clinical signs of anemia; use fresh whole blood or packed RBCs. Anti-inflammatory: Prednisolone (0.5-1 mg/kg PO q12h) for severe inflammation, but use cautiously in infectious cases. Bronchodilators: Terbutaline (0.01 mg/kg SC or PO q8h) for respiratory distress. Antiemetics: Maropitant (1 mg/kg SC q24h) if vomiting. Nutritional support: Appetite stimulants (e.g., mirtazapine 3.75 mg/cat PO q48h) if anorexic. Note: Adjust dosages for renal/hepatic impairment; doxycycline should be used with caution in animals with hepatic disease. Drug interactions: Doxycycline may chelate with antacids; separate administration by 2 hours.

Key studies and guidelines: 1) ACVIM consensus statement on the diagnosis and treatment of hemotropic mycoplasmosis (2016) recommends PCR as the diagnostic test of choice and doxycycline as first-line therapy. 2) A study by Tasker et al. (2003) demonstrated that doxycycline is effective in clearing Mycoplasma haemofelis infection in experimentally infected cats. 3) ISCAID guidelines for the management of canine infectious respiratory disease complex (2017) include Mycoplasma cynos as a primary pathogen and recommend doxycycline for treatment. 4) A study by Lappin et al. (2006) showed that Mycoplasma felis is a common cause of conjunctivitis in cats and responds to doxycycline. 5) Research by Sykes et al. (2010) evaluated the prevalence of hemotropic mycoplasmas in cats and found that co-infection with FIV/FeLV increases disease severity. 6) A meta-analysis by Barker et al. (2010) concluded that doxycycline is superior to enrofloxacin for treating hemotropic mycoplasmosis. 7) Expert consensus recommends treating all cats with hemotropic mycoplasmosis with doxycycline for at least 28 days, and monitoring with PCR to confirm clearance.