Update on Feline Haemoplasmas

The haemotropic mycoplasmas (haemoplasmas) are small bacteria that parasitise red blood cells (RBCs) and can induce haemolysis, causing anaemia. A recent review has been published, focusing on feline haemoplasma species 1. A resumé of currently recognised feline haemoplasma species is shown below.

Feline haemoplasma species, their prevalence and pathogenicity

In most studies, feline haemoplasma infections are more common in male, non-pedigree cats with outdoor access. Infection with ‘Ca. M. haemominutum’ is usually more prevalent in older cats, presumably because the chance of acquiring chronic subclinical infection increases with time. Some studies have shown an association between haemoplasma infection and feline immunodeficiency virus (FIV) infection^2,3 whereas others have not⁴. Most studies have failed to show an association between haemoplasma infection and feline leukaemia virus (FeLV) infection,^2-4 but variable results are seen in different reports.

Prevalence studies have been performed worldwide with very varied results. ‘Ca. M. haemominutum’ is usually the most common species found in prevalence studies. M. haemofelis and ‘Ca. M. turicensis’ infections generally are less common, although occasionally high prevalences are reported. Interestingly, some Canadian studies have reported very high prevalence of haemoplasma infection in cats, with one study documenting that 46.6% of stray cats were M. haemofelis infected.⁵

Outcome of Haemoplasma Infection

Mycoplasma haemofelis is the most pathogenic of the feline haemoplasma species. Acute infection often results in severe haemolytic anaemia although in some cases only mild anaemia results. Chronic infection is not usually associated with significant anaemia. Cats do not need to be immunocompromised or splenectomised to succumb to clinical disease with M. haemofelis, unlike dogs for the canine haemoplasmas. Persistent autoagglutination or positive Coombs’ testing, indicating the presence of RBC-bound antibodies, have been demonstrated in anaemic cats with acute M. haemofelis infection. Although ‘Ca. M. haemominutum’ infection can cause a drop in RBC parameters, anaemia is not usually induced except in cats with concurrent problems (e.g., FeLV infection). However, cases of so-called primary ‘Ca. M. haemominutum’ anaemia, without any apparent concurrent disease or infection present, have also been reported.^6,7 ‘Candidatus M. turicensis’ infection has resulted in anaemia or a small drop in RBC parameters in some experimental studies, but generally anaemia is uncommon following infection. Concurrent disease and immunosuppression are both thought to be involved in the pathogenesis of ‘Ca. M. turicensis’ disease, in a similar way to ‘Ca. M. haemominutum’.⁸ Long-term asymptomatic carrier status can occur, especially with ‘Ca. M. haemominutum’ and M. haemofelis infection.⁴ Clinical disease associated with reactivation has been reported.^7,9,10

Transmission

The natural route of transmission of hemoplasma infection between cats in the field has not yet been determined. Vectors have been implicated, as have biting and fighting, but neither have been proven. Vertical transmission has not been definitively shown for feline haemoplasma infections but has been strongly suggested for other haemoplasma species.^11,12 Blood transfusion can result in transmission, and blood donors should be screened for haemoplasma infection.^13,14

Clinical Signs

These include lethargy, weakness, reduced appetite, dehydration, weight loss and intermittent pyrexia (which can be high). Pallor, associated with anaemia, is also reported. Splenomegaly may be evident in some cats. Severe anaemia may result in tachycardia, tachypnoea and weak or bounding femoral pulses with haemic cardiac murmurs. Icterus is uncommon despite the haemolytic nature of the anaemia.

Diagnosis

Pathogenic haemoplasma infections typically cause a regenerative macrocytic hypochromic anaemia although pronounced reticulocytosis is not always evident.¹⁵ Positive Coombs’ test results can occur. Hyperbilirubinaemia is seen occasionally, due to haemolysis, and hypoxic liver damage may result in increased activities of alanine aminotransferase.

Haemoplasmas are currently unculturable in vitro. Cytology of blood smears may show haemoplasmas on the surface of RBCs but this is known to be very insensitive and non-specific for diagnosis. PCR assays are now the diagnostic method of choice for haemoplasma infection, being far more sensitive and specific than cytology. Real-time quantitative PCR (qPCR) assays allow quantification of haemoplasma DNA in the sample being analysed. Some M. haemofelis-infected cats show very large fluctuations in M. haemofelis copy number over time; this should be considered when interpreting qPCR results. In contrast, ‘Ca. M. haemominutum’ and ‘Ca. M. turicensis’-infected cats show little fluctuation in copy number over time. The reasons for the marked fluctuations in blood M. haemofelis copy number over time is not known but may be due to antigenic variation.

Differential Diagnoses

Haemoplasmosis should be considered as a differential diagnosis in cats presenting with regenerative (although occasionally non-regenerative) anaemia and possibly associated pyrexia. Other diagnoses to consider are primary immune-mediated haemolytic anaemia, secondary immune-mediated haemolytic anaemia (e.g., secondary to drugs, neoplasia, infections), cytauxzoonosis, retroviral infection, babesiosis, Heinz body associated haemolysis, hypophosphataemia and inherited RBC disorders such as pyruvate kinase deficiency.

Treament for Haemoplasmosis

1. Antibiotics

Antibiotic treatment is indicated for cats with clinical signs and clinicopathological abnormalities consistent with haemoplasmosis. Treatment should also be considered for cats that test positive for M. haemofelis in certain situations in view of the potential for recrudescence of anaemia with this haemoplasma species, which is the most pathogenic.

Antibiotics are typically given for 2–4 weeks. Doxycycline is often used as 1st line treatment and is adequate to induce a clinical response in M. haemofelis cases, but it does not consistently eliminate infection.^16,17 Unfortunately, controlled doxycycline treatment studies have not been performed for either ‘Ca. M. haemominutum’ or ‘Ca. M. turicensis’ infection. Fluoroquinolones are usually used as 2nd line treatments for haemoplasmosis; marbofloxacin treatment for 4 weeks significantly lowered ‘Ca. M. haemominutum’¹⁸ and M. haemofelis copy numbers,¹⁹ but the ‘Ca. M. haemominutum’ copy numbers only plateaued at a relatively high level during treatment, with no negative PCR results seen, and copy numbers rose back to near pre-treatment levels (very high) within 7–10 days of finishing marbofloxacin treatment. Conversely the fall in M. haemofelis copy numbers during marbofloxacin treatment was progressive with intermittent negative PCR results obtained at the end of the marbofloxacin treatment period and thereafter. Pradofloxacin has also been effective for haemoplasmosis in cats,²⁰ with one study suggesting that 2 weeks of pradofloxacin treatment may be more effective at clearing M. haemofelis than doxycycline. The author has found pradofloxacin to be effective in the treatment of ‘Ca. M. haemominutum’ infection in clinical observational cases but again no controlled studies have yet been performed.

A goal of treatment should be to eliminate infection, although proving infection has been eliminated is difficult without performing PCR on the whole cat! Repeatedly negative PCR results on blood samples are probably most reliable to indicate elimination. If negative PCR results do not result from treatment, control of clinical signs and a reduction of copy numbers in the blood indicates efficacy of treatment even if elimination is not possible. However, recrudescence of disease remains possible in cats that remain haemoplasma positive. A recent study²¹ reported that to facilitate clearance of M. haemofelis, when this is required, doxycycline treatment is given for 28 days followed by monitoring of copy numbers in the blood by quantitative PCR. If the cat remains PCR positive and clearance is needed, treatment should be switched to a fluoroquinolone (marbofloxacin was used in the published study) for 14 days, as this was associated with apparent clearance of infection in the study. So, although no antibiotic treatment regime that predictably eliminates haemoplasma infection with any species has yet been described, this study suggests that the use of doxycycline followed by marbofloxacin may be useful for clearance of M. haemofelis.

2. Corticosteroids

Corticosteroids have been recommended as adjunct treatment for haemoplasmosis, to treat any immune-mediated component of anaemia, although their efficacy has not yet been proven. In our experience, clinically ill cats, including those that are Coombs’ positive, respond to antibiotic treatment and supportive care alone without the need for corticosteroids. Indeed, immunosuppressive doses of corticosteroids have been used experimentally to exacerbate haemoplasma infection, so their routine use is not advised.

3. Supportive Care

Supportive care is also required for acute haemoplasmosis treatment. This should include correction of dehydration with fluid therapy, and blood transfusion if the anaemia is severe.

Prevention

Blood donors should be screened for haemoplasma infected by PCR to help prevent inadvertent transmission by blood transfusion from asymptomatic carrier cats. Keeping cats indoors is also likely to prevent infection, as outdoor status has been identified as a risk factor, but this will often be unpractical. In view of the potential for vector transmission, preventative flea and tick treatment is recommended. Recent work suggests that protective immunity develops following M. haemofelis infection,²² opening the way for future haemoplasma vaccination.

References

References are available on request.