Mycoplasma haemofelis (previously known as Haemobartonella felis) is an epierythrocytic haemoplasma (to which Ehrlichia spp and Anasplasma spp belong) responsible for Feline Infectious Anemia (FIA)^[1].

Four different species of feline mycoplasma have been characterised. Theses species were previously classified as rickettsial organisms due to their obligate parasitism, small size, erythrocyte tropism and suspected arthropod transmission. However, recent molecular sequencing and phylogeny data have shown these species to be more closely related to the family Mycoplasmaceae, supported by their small size and genomes, fastidious growth requirements and lack of a cell wall^[2].

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Haemoplasma species	Reported prevalence
Candidatus M. haemominutum[3]	10 – 32.1 %
M. haemofelis	0.4 – 46.6 %
Candidatus M. turicensis[4]	0.4 – 26 %
Candidatus M. haematoparvum-like	0 – 0.7 %[5]

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The inability to culture these pathogens in vitro has limited the possibilities of investigating the epidemiology and pathogenesis of these agents. However, the development of conventional PCR (cPCR) and real-time PCR have enabled the ascertainment of prevalence of some hemoplasmas worldwide^[6].

Prevalence rates vary from country to country; Switzerland 1% to 26% in South Africa. In Brazil, it has been shown that mycoplasmas are present in 57% of anaemic cats, and in FIV-positive cats, the prevalence of M. haemominutum was approximately 36% and M. haemofelis 37%. There is however, no direct relationship between FIV/FeLV status and mycoplasma infection^[7].

Cats infected with Mycoplasma spp typically develop regenerative anaemia. The related species Mycoplasma haemominutum (a less pathogenic strain) may also cause anaemia. A third species, M. turicensis has also been isolated from wild felids in Brazilian zoos^[8][9].M. haemofelis (formerly Hemobartonella felis) is a gram-negative, non-acid-fast mycoplasma that lives on the surface of the red blood cell. Measuring between 0.5 and 1.5 µm in diameter or length, this blood parasite exists as paired cocci, short rods, or small rings on the red blood cell plasma membrane. M. haemofelis infections are relatively common in cats in North America and produce extravascular haemolytic anaemia. M. haemofelis is also commonly recognised as a pathogen in conjunction with retroviruses, including FIV ( Feline Immunodeficiency virus), FeLV ( Feline leukaemia) and other debilitating diseases. FeLV-positive cats with compromised immunity seem most susceptible to disease. It has been suggested that cats having a pre-existing retroviral infection may be at a greater risk for becoming infected with feline haemoplasmas. Further, cats that were experimentally infected with retroviruses and M. haemominutum developed more severe anaemia than cats infected with the parasite alone. Studies also suggest that M. haemofelis and M. haemominutum may act as cofactors, accelerating the rate of progression of feline retrovirus-related diseases. Thus, cats that are co-infected with haemoplasmas and retroviruses may be at greater risk for the development of lymphoma, leukaemia and immunodeficiency syndrome^[10].

Transmission of the parasite is thought to occur by blood-sucking arthropods such as fleas or by bite wounds. Nevertheless, attempts to experimentally transmit the infections by feeding cats infected fleas failed, while transmission via haematophagus activity of fleas was not conclusive. Queens can transmit the parasite to their offspring, although it is unknown if the transmission occurs transplacentally, at birth, or transmammary. Experimental transmission via intravenous, intraperitoneal and oral routes have been reported.

Clinical signs

A cat infected with M. haemofelis may show mild anaemia without clinical signs or may exhibit severe anaemia with marked depression or subsequent death. Parasitemic episodes correlate with a decline in the packed cell volume (PCV). The erythrocyte life span also shortens with each bout of parasitemia. The primary method of red blood cell destruction is Immune-mediated haemolytic anaemia, although some direct damage may result from the presence of the parasite. Presumably, the host makes antibodies against exposed erythrocyte antigens or altered erythrocyte antigens that result from attached organisms. Due to the immune-mediated destruction of the red cell, these cats are Coombs’ positive or may occasionally demonstrate autoagglutination. At necropsy, infected cats usually appear pale and emaciated. Splenomegaly and moderate icterus commonly are observed. Histologically, both erythroid hyperplasia of the bone marrow and extramedullary hematopoiesis are present. Erythrophagocytosis and splenic hemosiderosis also are observed^[11].

FeLV/FIV and Mycoplasma co-infection

The prevalence of FeLV and FIV has been shown to be much higher in cats with clinical hemotropic mycoplasmosis than in the general population. Cats infected with FIV, FeLV or both, were at greater risk of being hemoplasma infected than retroviral negative cats. M. haemominutum infection is more likely to occur in association to FIV infection. For many years it was known that cats infected with FeLV and M. haemofelis develop more severe anemia than cats infected with M. haemofelis alone. Beside this, there are evidences that infection with M. haemofelis may induce myeloproliferative disease in FeLV infected cats. In the other hand, M. haemominutum, the small variant of Haemobartonella felis may lose its pathogenicity by passage through FeLV-free cats^[12].

Diagnosis

The best method of diagnosis is observation of M. haemofelis-infected erythrocytes in the Romanowsky-stained blood film. In addition, organisms may detach from erythrocytes where they can be observed scattered singly or in small aggregates in the background of the smear. The presence of stain precipitate may interfere with the identification of parasitemia, especially if few organisms are present. If stain precipitate is present, the ring form of M. haemofelis is the most reliable morphologic evidence of parasitemia. Parasitised erythrocytes also may be seen in splenic and bone marrow aspirates. In addition, macrophages may contain the organisms within phagocytic vacuoles^[13].

M. haemofelis infection usually is accompanied by a markedly regenerative anaemia characterized by polychromasia and macrocytosis. Metarubricytes (nucleated erythrocytes) and Howell Jolly bodies are commonly seen in circulation during acute parasitemia. As the disease progresses, bone marrow myeloid-to-erythroid ratio generally decreases.

Since the parasitemia is cyclic in nature, M. haemofelis organisms may be absent from the blood smear at various time periods. A positive Coombs’ test with regenerative anaemia, autoagglutination, or erythrophagocytosis is suggestive of Hemobartonellosis; however, other diseases such as primary autoimmune haemolytic anaemia and FeLV-induced haemolytic anaemia also should be considered in the differential diagnosis. Carriers of M. haemofelis exist and may incidentally have organisms in the stained blood smear. If infected with FeLV, these cats may relapse and develop clinical signs of disease^[14].

When examining the blood smear for M. haemofelis, one must take care to differentiate the parasite from other artefacts, organisms, and morphologic abnormalities. Stain precipitate may mimic or obscure M. haemofelis, especially if few organisms are present in the stained blood film. Stain precipitate is more variable in appearance, lies in a different plane of focus than the parasite, and also may be observed in the background of the smear. If stain precipitate is present, the ring form of M. haemofelis is the most reliable morphologic evidence of parasitemia. The signet-ring appearance of Cytauxzoon felismay look somewhat similar to the smaller, ring-form of M. haemofelis^[15]. Howell-Jolly bodies are small, round, purple, nuclear remnants that are generally larger than M. haemofelis. Basophilic stippling, a dusting of the cytoplasm with fine grey granules, can also mimic M. haemofelis. Basophilic stippling, especially in lead toxicosis, may be accompanied by metarubricytosis, anisocytosis, and hypochromia. The basophilic inclusions in punctate reticulocytes of new methylene blue-stained blood films may also resemble the blood parasite. Therefore, Romanowsky-stained blood films are preferred to document parasitemia^[16].

Treatment

In cats, blood transfusions may be necessary if a rapid haemolytic crisis occurs (PCV declines to 12-15%). Transmission of haemoplasmas via transfusions has been reported^[17].

Oral tetracyclines such as doxycycline (10 mg/kg orally once daily for up to 8 weeks) has shown efficacy at improving clinical signs, although proof of total elimination has not been shown in any studies^[18]. Doxycycline appears effective against all three species of haemoplasma, although controlled studies have only been reported in M. haemofelis^[19].

Fluoroquinolones are also effective against haemoplasma infections. Enrofloxacin (5 mg/kg orally once daily) has been successful in treating M. haemofelis, although diffuse retinal degeneration and acute blindness have been reported (Dowers et al, 2002). Marbofloxacin (2.75 mg/kg daily) has also been used effectively against M. haemofelis and Candidatus M. haemominutum. Ocular pathology has not been reported with use of this drug^[20]. Similarly, pradofloxacin (5 mg/kg orally once daily) has been effective at imrpvng clinical signs and haematological values and lowering M. haemofelis numbers in the blood^[21].

Although imidocarb (5 mg/kg intramuscularly every 2 weeks for 2 – 4 injections) has been effective in clinical trials of haemoplasma infections, controlled studies fail to show any beneficial effects on clinical signs and haematological values in M. haemofelis-infected cats^[22]. It may have some use in refractory cases of feline haemobartonellosis unresponsive to tetracycline or fluoroquinolone therapy. The injectable nature of this drug may be an advantage for some owners.

During oral antibiotic treatment, cats should be monitored for fever, anorexia, and liver toxicity. To diminish the immune-mediated component of the disease process, an oral glucocorticoid such as prednisolone, have been recommended, however, the value of corticosteroids has not been proven and anaemic, Coombs’-positive cats with M. haemofelis infection respond to antibiotic treatment alone^[23]. It has also been shown that a Candidatus M. turicensis infected cat that received methylprednisolone acetate prior to infection developed a more severe anaemia than an immunocompetent cat^[24].

The prognosis is good, although many cats remain carriers as the parasite is incompletely eliminated from the blood.

References

1. ↑ Maher, IE et al (2010) Polymerase chain reaction survey of fleine haemoplasma infections in Greece. JFMS 12:601-605
2. ↑ Tasker, S et al (2009) Description of outcomes of experimental infection with feline haemoplasmas: copy numbers, haematology, Coombs’ testing and blood glucose concentrations. Vet Microbiol 139:323-332
3. ↑ Tasker S et al (2006) Effect of chronic feline immunodeficiency infection, and efficacy of marbofloxacin treatment, on ‘Candidatus Mycoplasma haemominutum’ infection. Microbes Infect 8(3):653-661
4. ↑ Hagiwara, M.K., Reche Junior, A. & Lucas, S.R. (2997) Estudo clínico da infecção de felinos pelo virus da leucemia felina em São Paulo. Revista Brasileira de Ciência Veterinaria 4(1):35-38
5. ↑ Sykes, JE et al (2007) Use of conventional and real-time polymerase chain reaction to determine the epidemiology of haemoplasma infections in anemic and nonanemic cats. J Vet Intern Med 21:685-693
6. ↑ Carney HC & England JJ (1993) Feline hemobartonellosis. Vet Clin North Am Small Anim Pract 23:79-90
7. ↑ Messick, J.B. (2003) New perspectives about Hemotropic mycoplasmas (formerly, Haemobartonella and Eperythrozoon species) infections in dogs and cats. Veterinary Clinics Small Animal Practice 33:1453-1465
8. ↑ Simpson CF, Gaskin JM, Harvey JW (1978) Ultrastructure of erythrocytes parasitized by Hemobartonella felis. J Parasitol 64:504-511
9. ↑ Vet.uga.edu
10. ↑ Macieira, D.B. et al (2008) Prevalence and risk factors for hemoplasmas in domestic cats naturally infected with feline immunodeficiency virus and/or feline leukemia virus in Rio de Janeiro, Brazil. JFMS 10(2):120-129
11. ↑ Cowell RL, Tyler RD, Meinkoth JH (1999) Diagnostic Cytology and Hematology of the Dog and Cat. Mosby, St. Louis, pp:271-272
12. ↑ Gentilini, FG et al (2009) Use of combined conventional and real-time PCR to determine the epidemiology of feline hemoplasma infections in northern Italy. JFMS 11:277-285
13. ↑ Willi, B. et al (2008) From Haemobartonella to hemoplasma: molecular methods provide new insights. Veterinary Microbiology 125:197-209
14. ↑ Simpson CF, Gaskin JM, & Harvey JW (1978) Ultrastructure of erythrocytes parasitized by Hemobartonella felis. J Parasitol 64:504-11
15. ↑ Harvey JW (2001) Atlas of Veterinary Hematology. WB Saunders Company, Philadelphia, p. 41
16. ↑ Greene CE (1998) Infectious Diseases of the Dog and Cat. WB Saunders Company, Philadelphia, pp:166-171
17. ↑ Willi, B et al (2006) Prevalence, risk factor analysis and follow-up of infections caused by three feline haemoplasma species in cats in Zwitzerland. J Clin Microbiol 44:961-969
18. ↑ Tasker, S et al (2006) Effect of chronic FIV infection, and efficacy of marbofloxacin treatment on Candidatus Mycoplasma haemominutum infection. Microbes Infect 8:653-661
19. ↑ Dowers, KL et al (2002) Use of enrofloxacin for treatment of large-form Haemobartonella felis in experimentally-infected cats. J Am Vet Med Assoc 221:250-253
20. ↑ Ishak, AM et al (2008) Marbofloxacin for the treatment of experimentally induced Mycoplasma haemofelis infection in cats. J Vet Intern Med 22:288-292
21. ↑ Dowers, KL et al (2009) Use of pradofloxacin to treat experimentally induced Mycoplasma haemofelis infection in cats. Am J Vet Res 70:105-111
22. ↑ Lappin, MR, Brewer, M & Radecki, S (2002) Effects of imidocarb diproprionate in cats with chronic haemobartonellosis. Vet Therapeutics 2:144-149
23. ↑ Tasker, S (2002) Feline haemoplasmas – detection, infection, dynamics and distribution. PhD thesis, University of Bristol
24. ↑ Willi, B et al (2005) identification, molecular characterization and experimental transmission of a new haemoplasma isolate from a cat with haemolytic anaemia in Switzerland. J Clin Microbiol 43:2581-2585