Haemoplasmosis

Haemoplasmosis, formerly called haemobartonellosis, is a vector-suspected infection of the red blood cells that affects both, cats (Clark, 1942; Flint and Moss, 1953; Foley et al., 1998; Willi et al., 2005) and dogs (Benjamin and Lumb, 1959; Donovan and Loeb, 1960). Besides these two affected species, closely related haemoplasmas have also been detected in several other mammals (see e.g., Messick, 2004 for detailed listing). In cats, the corresponding disease is also named feline infectious anaemia or feline haemotrophic mycoplasmosis.

Regarding humans, organisms resembling haemoplasmas have been reported in blood smears from human patients. Mycoplasma suis (Yuan et al., 2007, 2009), Mycoplasma ovis (Sykes et al., 2010), but also Mycoplasma haemofelis in an HIV patient with concurrent Bartonella henselae infection (dos Santos et al., 2008) have been reported. Furthermore haemoplasma-like bacteria with an intra- and extra-erythrocytic position and found inside megakaryocytes have been reported to be associated with systemic lupus erythematosus in human patients (Kallick et al., 1972; Kallick et al. 2007). Thus, a zoonotic potential of haemoplasmas cannot be excluded and should be further addressed (Sykes, 2010; Willi et al., 2007).

Pathogens

Haemoptrophic (hemotropic) mycoplasmas, formerly known as Haemobartonella and Eperythrozoon, are small (<1 mm), pleomorphic bacteria that attach to red blood cells of various mammalian species (Willi et al., 2007). Until recently, they were classified as rickettsial organisms, based on their small size, Gram-negative staining properties, red blood cell parasitism and proposed transmission by blood-sucking arthropods (Kreier and Ristic, 1984). Meanwhile, based on molecular characterization, a closer relationship to members of the class Mollicutes has been described (Neimark et al., 2001; Rikihisa et al., 1997). This molecular relationship and some further phenotypic characteristics led to a reclassification of the genera Haemobartonella and Eperythrozoon within the genus Mycoplasma (family Mycoplasmataceae) as haemoptrophic/hemotropic mycoplasmas (Neimark et al., 2001), also denominated haemoplasmas (hemoplasmas) as trivial name (Neimark et al., 2001).

These haemoplasmas are characterized as small (0.3–0.8 mm), unculturable, epierythrocytic bacteria that are capable of causing severe haemolytic anaemia (Sykes, 2010).

Relevant species described in cats are Mycoplasma haemofelis (Mhf) (formerly designated the “large form” or Ohio strain/isolate), Candidatus Mycoplasma haemominutum (CMhm) (formerly designated the “small form” or California strain/isolate) (Foley and Pedersen, 2001; Neimark et al., 2001; Tasker and Lappin, 2002) and Candidatus Mycoplasma turicensis (CMt) identified in a Swiss pet cat for the first time (Willi et al., 2005, 2006).

Microscopical image of red blood cells infected with Mycoplasma haemofelis.

Microscopical image of red blood cells infected with Mycoplasma haemofelis (Wright stain). Arrows indicate individual haemoplasmas.1

  • 1. By courtesy of S. Tasker, University of Bristol, UK.

In dogs, two species have been described. Mycoplasma haemocanis (Mhc), formerly known as Haemobartonella canis, has been described in 1959/1960 (Benjamin and Lumb, 1959; Donovan and Loeb, 1960), but early reports of sporadic cases of haemobartonellosis in dogs in the United States even date back to 1935 (Knutti and Hawkins, 1935; McNaught et al., 1935). As with the feline species, the pathogen has been reclassified to Mycoplasma haemocanis (Messick et al., 2002). In 2004, a second haemotrophic mycoplasma was identified in a splenectomized immunocompromised dog named Candidatus Mycoplasma haematoparvum (CMhp) (Sykes et al., 2004, 2005).

Recently, the two feline species CMhm and CMt were also detected in dogs (Obara et al., 2011; Soto et al., 2017), and Candidatus Mycoplasma haematoparvum-like was found in cats (Sykes et al., 2007; Martínez-Díaz et al., 2013; Vergara et al., 2016).

Epidemiology

Haemotrophic mycoplasmas (haemoplasmas) have been described as pathogens in dogs and cats, causing feline and canine haemplasmosis. The reported feline species Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm) and Candidatus Mycoplasma turicensis (CMt), as well as the two described canine species Mycoplasma haemocanis (Mhc) and Candidatus Mycoplasma haematoparvum (CMhp) possess worldwide geographical variation in prevalence (Aquino et al., 2014; Barker et al., 2009; Bauer et al., 2008; Gentilini et al., 2009; Kenny et al., 2004; Roura et al., 2010; Sasaki et al., 2008; Sykes et al., 2008; Weingart et al., 2016; Wengi et al., 2008; Willi et al., 2006a, 2006b, 2007b). Apart from the feline and canine species found in the corresponding pet species, two of the feline species (CMhm and CMt) were also detected in dogs (Obara et al., 2011; Soto et al., 2017) and Candidatus Mycoplasma haematoparvum-like has been reported in cats vice versa (Martínez-Díaz et al., 2013; Sykes et al., 2007; Vergara et al., 2016).

Haemoplasma infections have been documented as well in different captive and free-ranging wild felid species from Europe, Africa and South America (Willi et al., 2007c), but a final conclusion on the pathogenic potential of feline haemoplasmas in wild felids cannot yet be drawn (Willi et al., 2007b). Nevertheless, their potential role as reservoirs and asymptomatic carriers should be further addressed (Willi et al, 2007b). Accordingly, canine haemoplasmas have also been reported in wild canids (Di Cataldo et al., 2021; Millán et al., 2019).

The mode of transmission of feline and canine haemoplasmas is still under discussion. Arthropods, especially fleas and ticks have been suggested as vectors, but confirmation of transmission e.g. by fleas is still controversial (Woods et al., 2006). Infection is also prevalent in some regions where e.g. flea infestation is uncommon (Jensen et al., 2001) or where specific tick species of dogs are not encountered (Cabello et al., 2013; Millán et al., 2019). Nevertheless, the clustered geographical distribution of infection in some studies strongly supports the role of an arthropod vector in haemoplasma transmission, and so haemoplasmas are often considered as vector-borne infections (Persichetti et al., 2018; Sykes et al., 2007). For more details on potential arthropod transmission see under Transmission.

In most recent studies, feline haemoplasma infection has been strongly associated with male sex, non-pedigree status, and access to the outdoors (Grindem et al., 1990; Luria et al., 2004; Sykes et al., 2007; Sykes et al., 2008; Tasker et al., 2003; Willi et al., 2006a, 2006b). Transmission has been reported via infected blood, as through blood transfusion (Ravagnan et al., 2017). Transplacental spread has also been hypothesized (Harvey and Gaskin, 1977). DNA of the haemoplasmas was also amplified from saliva, which likely explains the evidence for direct transmission (Dean et al., 2008). Thus, the agents should be on the differential list for cats with a history of fighting (Lappin, 2018). Additionally, haemoplasmas have been detected among others in faeces of experimentally infected cats early in the course of infection, as well as in the saliva, gingival, and claw beds of naturally infected cats, although organism levels in these secretions have been low (Dean et al., 2008; Lappin et al., 2008; Willi et al., 2007a). Since the haemoplasma DNA loads in saliva and faeces samples of CMt-infected cats e.g. were rather low, it was hypothesized that aggressive interactions, rather than oronasal exposure through mutual grooming or sharing of food dishes are necessary for successful transmission of haemoplasmas (Willi et al., 2007a).

Accordingly, higher incidences have in parts also been reported in male dogs (Barker et al., 2010; Di Cataldo et al., 2021), thus suggesting that aggressive interactions may be involved in the transmission in dogs as well (Barker et al., 2010; Di Cataldo et al., 2021).

As a consequence of these suggested, but still discussed modes of transmission, ectoparasite control and avoiding fights or aggressive behaviour should lessen the risk of acquiring haemoplasmosis.

The bacteria can persist for years in latently infected animals without causing clinical disease, but subjecting latently infected animals to splenectomy, stress or other predisposing factors often results in the appearance of large numbers of infected erythrocytes in the circulation; overt disease may result (Neimark et al. 2001).

Distribution

All three reported feline (Mycoplasma haemofelis [Mhf], Candidatus Mycoplasma haemominutum [CMhm] and Candidatus Mycoplasma turicensis [CMt]) as well as the two canine species (Mycoplasma haemocanis [Mhc] and Candidatus Mycoplasma haematoparvum [CMhp]) can be encountered worldwide, but with geographical variation in prevalence. The geographical prevalence variations might be influenced by the type of pets sampled in the different studies, e.g. in some studies only ill anaemic pets were screened, whereas others sample healthy pets only; some test stray feral animals whereas others focus on owned ones etc.

Countries with reported occurrence of feline haemoplasma infections are e.g. Australia (Willi et al., 2006b), Brazil (Munhoz et al., 2018; Santos et al., 2014), Canada (Stojanovic and Foley, 2011; Kamrani et al., 2008), Chile (Vergara et al., 2016), Cyprus (Attipa et al., 2017), Denmark (Rosenqvist et al., 2016), Germany (Bauer et al., 2008), Iran (Ghazisaeedi et al., 2014), Ireland (Juvet et al., 2010), Italy (Latrofa et al., 2020; Ravagnan et al., 2017), Japan (Tanahara et al., 2010), Malta (Mifsud et al., 2020), Portugal (Martinez-Diaz et al., 2013; Mesa-Sanchez et al., 2021), Romania (Imre et al., 2020), Serbia (Sarvani et al., 2018), South Africa (Willi et al., 2006b), South Korea (Hwang et al., 2017), Spain (Roura et al., 2010; Mesa-Sanchez et al., 2021), Switzerland (Willi et al., 2006a), Thailand (Assarasakorn et al., 2012), Turkey (Ural et al., 2009), the UK (Tasker et al., 2003), and the USA (Sykes et al., 2008).

Of the feline haemoplasmas, CMhm seems usually more prevalent than Mhf and CMt.

In dogs, positive haemoplasma samples have been documented e.g. in Brazil (Constantino et al., 2017), Chile (Di Cataldo et al., 2021; Soto et al., 2017), France (Kenny et al., 2004), Italy (Ravagnan et al., 2017), Japan (Sasaki et al., 2008), Spain (Roura et al., 2010), Switzerland (Wengi et al., 2008), northern Tanzania (Barker et al., 2010), Thailand (Kaewmongkol et al., 2017), Trinidad (Barker et al., 2010), Turkey (Aktas and Ozubek, 2018), and the USA (Compton et al., 2012).

Regarding canine haemoplasmas, kennel raised dogs seem to possess higher prevalence than pet dogs (Kemming et al., 2004).

Transmission

The mode of transmission of feline and canine haemoplasmas is still under discussion. Arthropods, here especially fleas and ticks, have been suggested as vectors, but confirmation of the transmission e.g. by fleas is still controversial (Woods et al., 2006). Feline haemoplasma DNA has been amplified from fleas and ticks (Assaraskorn et al., 2012; Barrs et al., 2010; Duplan et al., 2018; Lappin et al., 2006; Shaw et al., 2004; Taroura et al., 2005; Willi et al., 2007b). However, this does not equate with vector-mediated transmission, as the presence of haemoplasma DNA could merely reflect the haematophagous activity of the arthropods on infected hosts (Lappin et al., 2020). As an example, in an experimental flea transmission study, only very transient Mycoplasma haemofelis (Mhf) infection transmission in cats and no clinical and haematological signs of Mhf infection in the recipient cat could be recorded (Woods et al., 2005). Further studies have shown that infection is also prevalent in some regions where e.g. flea infestation is uncommon (Jensen et al., 2001). Regarding ticks, Mhf and Mhm have been detected in some Ixodes ricinus ticks from Europe (Schabereiter-Gurtner et al., 2003) or unfed Ixodes ovatus ticks from Japan (Taroura et al., 2005), suggesting a transstadial transmission of haemotrophic mycoplasmas in the latter tick species (Willi et al., 2007b). But other studies did not yield evidence of haemoplasma DNA in a larger number of unfed Ixodes spp. (Willi et al., 2007a). Thus, different Ixodes species might vary in their capability to harbour haemoplasmas (Willi et al., 2007b). Additionally, infections have been described in suburban areas where there is minimal tick exposure (Sykes et al., 2007). Nevertheless, the clustered geographical distribution of infection in some studies supports the role of an arthropod vector in haemoplasma transmission, and so haemoplasmas are often considered as vector-borne infections (Persichetti et al., 2018; Sykes et al., 2007).

A comparable situation has been described in dogs. Rhipicephalus sanguineus was believed to be involved in the transmission of canine haemoplasmas (Aktas and Ozubek, 2018; Novacco et al., 2010; Seneviratna et al., 1973), but other studies could neither confirm this association (Cabello et al., 2013; Millán et al., 2019), nor an association with other tick species (Millán et al., 2019) or ectoparasite occurrence in a wider range (e.g., Constantino et al., 2017; Di Cataldo et al., 2021). Whereas, on the contrary, other authors again described an association of canine haemoplasma infection with general vector presence (Valle et al., 2014), with vector-borne pathogens (Roura et al., 2010) or suggested other vectors such as fleas to play a potential role in transmission (Millán et al., 2019; for Pulex irritans).

The fact that feline haemoplasmas have also been detected in wild felids, also suggests that these animals may act as reservoirs of infection for arthropod transmission (Willi et al., 2007c). Similar, canine haemoplasmas have been reported in wild carnivores, which might also be natural hosts (Di Cataldo et al., 2021; Millán et al., 2018).

Recently, Aedes aegypti were shown to ingest Mhf or CMhm, but transmission to naïve cats was not documented, suggesting this mosquito is not a biological vector (Reagan et al., 2017). A role for mites in mechanical transmission of infection has been proposed for dogs (Willi et al., 2010).

Apart from suggested arthropod transmission, direct transmission has also been discussed in haemoplasmas. Transplacental spread has been hypothesized in feline (Harvey and Gaskin, 1977) as well as in canine haemoplasmas (here Mhc) (Lashnits et al., 2019). Direct transmission through biting and fighting is suggested as a possible mode of transmission, based on the strong male sex predeliction and association with FIV infection in some feline studies (Sykes, 2010). Higher incidences in male dogs in some studies (Barker et al., 2010; Di Cataldo et al., 2021) led to similar suggestions in dogs with aggressive interactions potentially being involved in canine haemoplasma transmission (Barker et al., 2010; Di Cataldo et al., 2021), but could not be confirmed via gender association in other studies (Kenny et al., 2004; Wengi et al., 2008; Novacco et al., 2010). Haemoplasmas have also been detected in saliva and faeces of experimentally infected cats, as well as in the saliva, gingival, and claw beds of naturally infected cats, although organism levels in these secretions have been low (Dean et al., 2008; Lappin et al., 2008; Willi et al., 2007a). Finally, transmission has been reported via infected blood, as through blood transfusion (Ravagnan et al., 2017).

As a consequence of all these suggested, but still discussed modes of transmission, ectoparasite control and avoiding fights and aggressions should lessen the risk of acquiring haemoplasmosis and thus are recommended until the modes of haemoplasma transmission are better understood.

Pathogenesis

Haemotrophic Mycoplasma species share some characters (listed by Neimark et al., 2001): They parasitize erythrocytes of their hosts and adhere to the erythrocyte surface, often in an indentation or deformation of the erythrocyte membrane, they have been shown by electron microscopy to lack a cell wall and to be coccoidal in shape, usually with a diameter of less than 0.9 µm, and they are uncultivated in vitro.

Infections with canine and feline haemoplasmas can have a wide clinical spectrum from asymptomatic to life-threatening haemolytic crises. The spectrum of clinical signs is dependent on haemoplasma species, host susceptibility, presence of acute or chronic infections etc. (Willi et al., 2007; here for feline species). For the induction of anaemia and haemolysis by haemotrophic mycoplasmas, several mechanisms have been proposed (Messick, 2004). The attachment of the organism leads to an indentation of the red blood cell surface (Jain and Keeton, 1973), indicative of a direct damage of the red blood cell membrane. Alternatively, cold agglutinins observed in cats infected with haemoplasmas (Zulty and Kociba, 1990) suggest the involvement of immunological mechanisms in red blood cell destruction. These antibodies could be directed against the attached organisms and destroy the red blood cells as ‘innocent bystanders’. Alternatively, they could represent autoantibodies that had been produced against red blood cell antigens exposed by or modified due to the organisms’ attachment (Willi et al., 2007). Apart from autoantibodies that trigger an immune response (Denman, 1991), the production of free radicals by the organism that induce oxidative damage of host cell membranes (Almagor et al., 1986; Somerson et al., 1965), the secretion of mycoplasmal enzymes leading to localized tissue disruption (Bhandari and Asnani, 1989; Rottem et al., 1973) and chromosomal aberrations (Paton et al., 1965), the depletion of nutrients or biosynthetic precursors by mycoplasmas leading to host cell damage (Russel, 1966), and the capability of active cellular penetration as a mechanism of cell damage (Lo et al., 1992) have been discussed as explanation of the pathogenicity of mycoplasmas (Messick, 2004).

Anaemia, as one of the most significant clinical signs, primarily results from extravascular haemolysis (Sykes, 2010), although intravascular haemolysis has been described in a Candidatus Mycoplasma turicensis (CMt)-infected cat (Willi et al., 2005). Positive direct Coombs, increased osmotic fragility, and decreased erythocyte lifespan have also been noted in cats with haemoplasmosis (Maede, 1975; Maede and Hata, 1975; Willi et al., 2005; Zulty and Kociba, 1990).

The different feline haemoplasma species possess different pathogenic potential. Mycoplasma haemofelis (Mhf) was found to be more pathogenic than Candidatus Mycoplasma haemominutum (CMhm) (Foley et al., 1998; Westfall et al., 2001), while CMt could induce mild to moderate anaemia (Museux et al., 2009; Tasker et al., 2009; Willi et al., 2005). Dual infection with haemoplasmas may potentiate pathogenesis of the disease (in cats) (Lappin, 2018).

Clinical cases of haemoplasmosis in dogs have occasionally been reported, but cofactors such as splenectomy, immunosuppression, or concurrent infections seem to play a role in the pathogenesis of the disease (Kemming et al., 2004; Sykes et al., 2004).

Recovered cats have been suggested to remain potential carriers for years with the organism evading the host immune system and a possible reactivation of the disease induced by stress, pregnancy, intercurrent infection, or neoplasia (Berent et al., 1998; Harvey and Gaskin, 1977, 1978). During the persistence of the pathogens in latently infected animals without clinical disease, the bacteria are apparently cleared from the circulation by sequestration in the spleen (Maede, 1979). Subjecting latently infected animals to splenectomy, stress or other predisposing factors often result in the appearance of large numbers of infected erythrocytes in the circulation; overt disease may also result (Neimark et al., 2001). But in contrast to haemoplasma infections of other host species, as e.g. in dogs, splenectomy has a variable effect on the course of feline haemoplasmosis. Recrudescence of anaemia and bacteraemia has been documented in some chronically infected cats, although other studies suggest splenectomy increases the number of visible organisms in blood smears without causing significant anaemia (Alleman et al., 1999; Harvey and Gaskin, 1978).

Diagnosis

Diagnosis of haemoplasmosis can be based on demonstration of the organism on the surface of erythrocytes on examination of a thin blood film or, as a far more reliable technique, on PCR assay results (Lappin et al., 2020). Organism numbers fluctuate and so blood film examination can be very insensitive for diagnosis (0-37.5%) (Ghazisaeedi et al., 2014; Jensen et al., 2001; Tasker et al., 2003a; Westfall et al., 2001). Particularly in the chronic phase the organism may be difficult to find on cytology (Lappin, 2018). Specificity is also an issue with blood film examination, especially when performed by someone inexperienced in clinical pathology (Lappin et al., 2020). When properly designed and executed, PCR is far more sensitive and specific than cytology, and species-specific assays are now routinely used (Peters et al., 2008). However, healthy animals can also be positive for haemoplasma DNA in blood and so PCR assay results do not always correlate with clinical illness, as is the case with the interpretation of many PCR assays (Willi et al., 2006, 2007; Roura et al., 2010). On the other side, it is important to recognize that animals receiving antibiotics may become PCR-negative within a few days of treatment. However, after treatment the animal may revert to a positive PCR test without having overt clinical signs of infection (Berent et al., 1998; here for cats). Thus, a negative PCR test obtained during or shortly after antibiotic treatment does not rule out the possibility of a chronic infection (Messick, 2003). A real-time PCR assay has further been developed that may provide additional information about the significance of a positive PCR result and be a useful method for assessing the response to treatment with antibiotics (Tasker et al., 2003b).

Clinical Signs

Haemoplasmas can cause acute haemolytic anaemia and various chronic diseases in vertebrate hosts. The clinical spectrum of infection ranges from asymptomatic to life threatening (Messick, 2004). The acute haemolysis can be associated with anorexia, lethargy, dehydration, weight loss and sudden death of infected animals (Willi et al., 2010).

The clinical signs of haemoplasmosis depend on the degree of anaemia, the stage of infection, and the immune status of the infected animals (Lappin, 2018; here for cats). There is strong evidence that host immune reactions play an important role in the development of clinical signs associated with both acute and chronic mycoplasma infections. Animals may be predisposed to acute infection by age, concurrent disease, immunosuppression, or splenectomy (Messick, 2004).

In cats, three relevant haemoplasma species have been described: Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm), and Candidatus Mycoplasma turicensis (CMt). In multiple studies of experimentally infected cats, Mhf is apparently the most pathogenic species (Tasker et al., 2009; Westfall et al., 2001). Dual infection with haemoplasmas may furthermore potentiate pathogenesis of the disease (Westfall et al., 2001).

After inoculation of experimental cats with Mhf, there is a delay of 2-34 days before the acute onset of clinical signs. In the acute phase, which lasts 3-4 weeks in the absence of treatment, severe anaemia and bacteraemia occur. During this phase, sharp declines in the haematocrit may correlate with the appearance of large numbers of organisms in blood smears (Foley et al., 1998; Harvey and Gaskin, 1977). This may be due to direct erythrocyte damage or through immune-mediated mechanisms (Zulty and Kociba, 1990). Anaemia results primarily from extravascular haemolysis (Sykes, 2010), although intravascular haemolysis has been described in a CMt-infected cat (Willi et al., 2005). Additionally, sequestration of infected erythrocytes in the spleen may also be accountable to a lower packed cell volume (Maede, 1979). Anaemia in cats can result in signs of lethargy, inappetence, pallor, and weakness (Sykes and Tasker, 2016). Some studies did not find an association of Mhf infection and anaemia.

Without therapy, up to one third of the cats with uncomplicated acute Mhf infection die as a result of severe anaemia. Cats that mount a sufficient immune response to the organism and a regenerative bone marrow response that compensates for the erythrocyte destruction recover from the disease (Messick and Harvey, 2016). In these surviving cats, the immune system intervenes, with a corresponding increase in the haematocrit, and a disappearance of organisms from blood smears. Despite this organism disappearance, positive PCR results persist (Berent et al., 1998).

Besides causing primary disease in cats, Mhf is also commonly recognized as a pathogen in conjunction with retroviruses, including feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV), and with other debilitating diseases (George et al., 2002; Grindem et al., 1990; Harrus et al., 2002; Lappin, 1995).

The two further feline species CMhm and CMt are less pathogenic, but can induce anaemia under some circumstances. Anaemia has been seen following CMhm infection in some studies involving cats infected with retroviruses. Furthermore, CMhm-associated anaemia has been reported in immunosuppressed cats and occasionally in cats without any evidence of immunosuppression (Tasker, 2016). Similar CMt infection has shown variable clinical results from slight red blood cell reduction to moderate or severe anaemia, especially in case of immunosuppression (Tasker, 2016). Aggravating in the assessment of CMt infections is the often-occurring coinfection with other feline hameoplasmas or further concurrent disease (Tasker, 2016).

In contrast to haemoplasma infections of other host species, splenectomy has a variable effect on the course of feline haemoplasmosis. Recrudescence of anaemia and bacteraemia has been documented in some chronically infected cats, although other studies suggest splenectomy increases the number of visible organisms in blood smears without causing significant anaemia (Alleman et al., 1999; Harvey and Gaskin, 1978). Infection of splenectomized cats with Mhm does not seem to enhance the pathogenicity of this organism (Sykes et al., 2007).

In dogs, two haemoplasma species are in the focus: Mycoplasma haemocanis (Mhc) and Candidatus Mycoplasma haematoparvum (CMhp). Mhc causes anaemia primarily in splenectomized or immunocompromised dogs (Messick et al., 2002), but infection in non-splenectomized dogs can also occur (Austerman, 1979). CMhp was first described in association with anaemia in a splenectomized dog undergoing chemotherapy for leukaemia (Sykes et al., 2004). Clinical signs in dogs further include weakness, lethargy, and pallor, and some dogs are inappetent (Sykes and Tasker, 2016).

 

Regarding pathogen elimination, it has been suggested that recovered cats may remain pathogen carriers for years, the organism evading the host immune system, with possible reactivation of disease with stress, pregnancy, intercurrent infection, or neoplasia (Berent et al., 1998; Harvey and Gaskin, 1977, 1978).

Generally, if latently infected animals without clinical signs are subjected to splenectomy, stress or other predisposing factors, the appearance of large numbers of infected erythrocytes in the circulation often results; overt disease may also result (Neimark et al., 2001). Finally, treatment is unlikely to completely eliminate feline as well as canine haemoplasma infections (Willi et al., 2010).

Treatment & Prevention

Treatment

Treatment of haemoplasmosis is indicated in cats with clinical signs and laboratory abnormalities consistent with haemoplasma infection (Sykes, 2010). Treatment of PCR-positive asymptomatic cats is not recommended according to Sykes (2010).

Successful management of clinical haemoplasmosis can be achieved with appropriate antibiotic treatment in combination with basic supportive care. Before the start of an antimicrobial treatment in cats with haemolytic anaemia and associated clinical signs, diagnostic tests such as fresh blood smear evaluation, slide agglutination test, complete blood count, Coombs test, cross-match and blood typing, serological tests for feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV), chemistry panel, as well as PCR testing for Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm) and Candidatus Mycoplasma turicensis (CMtc) should be initiated (Sykes, 2010).

Based on the characteristics of haemoplasmas lacking a cell wall and possessing a parasitic nature, the antibiotic spectrum for treatment is restricted. Tetracyclines and fluoroquinolones have been shown to be effective for the treatment of clinical haemoplasmosis in cats (Berent et al., 1998; Dowers et al., 2002, 2009; Foley et al., 1998; Harvey and Gaskin, 1977, 1978; Rikihisa et al., 1997; Tasker et al., 2004, 2006a, 2006b). The European Advisory Board on Cat Diseases (ABCD) currently recommends doxycycline as first-line drug for clinical haemoplasmosis (Tasker et al., 2018). Fluoroquinolones could be considered as alternative (Barker, 2019). Diverse protocols have been tested in experimentally infected Mhf cats using tetracyclines and fluoroquinolones reporting a rapid resolution of clinical signs (Dowers et al., 2002, 2009; Ishak et al., 2008; Tasker et al., 2006b). But in the majority of Mhf cases treated with doxycycline, enrofloxacin or marbofloxacin, clearance of the infection was not achieved during and after treatment (Dowers et al., 2002; Ishak et al., 2008; Tasker et al., 2006b), whereas pradofloxacin treatment (Dowers et al., 2009) or a prolonged treatment of doxycycline eventually combined with marbofloxacin (Novacco et al., 2018) may be more effective at long-term Mhf organism clearance. For detailed information on different treatment protocols of Mhf and considerations on treatments of CMhm and CMt infections see Barker (2019).

Besides antibiotic treatment transfusion with packed red cells or whole blood might be necessary as well as eventually fluid therapy, depending on the clinical situation (see also Barker, 2019; Sykes, 2010). Corticosteroids are controversial as they as well may cause reactivation of latent haemoplasma infection (Sykes, 2010).

The consequences of the chronic haemoplasma infection (‘carrier state’) are poorly understood (Barker, 2019), especially regarding an influence on myeloproliferative disease, severity of anaemia and viraemia during retrovirus infection (see Barker, 2019, for summarized study results).

Situations in which clearance of infection may be desirable in addition to clinical cure are in cats which are immunocompromised by concurrent infection, by treatment or following splenectomy (Barker, 2019). Clearance might also be considered in case of cats representing a risk to other cats or an immunocompromised owner (Barker, 2019; see Zoonotic Potential for more details). Finally, clearance of infection may be a requirement of re-homing (Barker, 2019).

Cats testing positive for Mhf using PCR should be excluded as blood donors. The significance of positive test results for the other two haemoplasma species is less clear (Sykes, 2010). Excluding cats testing positive for CMhm is problematic because of the high infection prevalence in the cat population. Additionally, inoculation of splenectomized, glucocorticoid-treated cats has not been associated with anaemia in studies (unpublished data, mentioned in Sykes, 2010), but strain variation may exist with different capability of causing anaemia (Sykes, 2010). Thus, until more information becomes available regarding the pathogenic potential of this organism, blood testing negative for all haemoplasma species is preferred for transfusion purposes (Sykes, 2010).

In dogs, treatment of haemoplasma infections is not described as detailed as in cats in the literature. Therapy of Mycoplasma haemocanis (Mhc) or Candidatus Mycoplasma haematoparvum (CMhp) in dogs has been reported in single cases with tetracyclines and/or fluoroquinolones over different time intervals (Hulme-Moir et al., 2010; Kim et al., 2020; Pitorri et al., 2012; Sharifiyazdi et al., 2014).

 

Prevention

A clustered geographical distribution of feline haemoplasma infection has been observed in some studies which strongly supports the role of an arthropod vector in haemoplasma transmission (Sykes et al., 2007), so that flea control in cats should lessen the risk of acquiring haemopalsmosis (Lappin et al., 2020). Currently, regular administration of anti-ectoparasitic treatment seems prudent in cats (Barker, 2019). Aggressive interactions leading to the subcutaneous inoculation of infected blood have also been implicated in transmission of haemoplasma infection (Museux et al., 2009), so that indoor housing and separation of cats between which aggressive interactions are known to have occurred is also recommended (Barker, 2019). To be on the safe side, if the aim is to maintain haemoplasma-free status, uninfected cats should not be housed with haemoplasma-infected cats at all (Barker, 2019).

As in cats, the mode of transmission of haemoplasmas in dogs is still under debate. It was believed that Rhipicephalus sanguineus is involved in the transmission of canine haemoplasmas (Aktas and Ozubek, 2018; Novacco et al., 2010; Seneviratna et al., 1973), but the experimental transmission in pre-molecular times (Senevirtana et al., 1973) was never replicated. Apart from the potential role of the brown dog tick as vector, several studies confirmed an association of canine haemoplasma infection with general vector presence (Valle et al., 2014), with vector-borne pathogens (Roura et al., 2010) or suggested other vectors to play a potential role in the transmission, such as fleas (Pulex irritans, Millán et al., 2019) or mites (Willi et al., 2010). On the contrary, diverse studies could not confirm an association between canine haemoplasma infections and special tick species (Cabello et al., 2013; Millán et al., 2019) or ectoparasite occurrence in a wider range (e.g., Constantino et al., 2017; Di Cataldo et al., 2021). Thus, there is growing evidence that alternative or concurrent transmission routes besides tick transmission must exist (Di Cataldo et al., 2021). Higher incidences in male dogs (Barker et al., 2010; Di Cataldo et al., 2021) suggest that aggressive interactions may be involved in the transmission (Barker et al., 2010; Di Cataldo et al., 2021). Older age has also been correlated in some studies with canine haemoplasma infection (Cortese et al., 2020; Di Cataldo et al., 2021). Nevertheless, these correlations could not be proven in other studies (Kenny et al., 2004; Wengi et al., 2008; Novacco et al., 2010: no gender association; Novacco et al., 2010: young dogs with higher exposure). Finally, group housing in kennels, which could increase the rate of haemoplasma transmission between dogs due to potential vectors or by direct transmission (Novacco et al., 2010), and which could also represent a stress factor for individual dogs, and thus increase their susceptibility to infections (Brennan et al., 2008; Coppinger and Zuccotti, 1999; Paradies et al., 2007), has also been discussed (Novacco et al., 2010). Based on all these observations and considerations and until transmission of canine haemoplasma infection is better understood, ectoparasitic prophylaxis is also recommended in dogs and behavioural components should be considered by veterinarians.

Zoonotic Potential

Regarding the zoonotic aspect of haemoplasmas, the pathogens appear to be of low risk to people (Lappin et al., 2020; here for feline pathogens). Nevertheless, there have been reports of infection with similar organisms in humans and one reported infection in a human HIV patient with a concurrent Bartonella henselae infection describing Mycoplasma haemofelis that could have originated from a cat (Steer et al., 2011; dos Santos et al., 2008). Additionally, human infections with swine and ovine haemoplasmas have been reported (Sykes et al., 2010; Yuan et al., 2007, 2009), and haemoplasma-like bacteria with an intra- and extra-erythrocytic position and found inside megakaryocytes have been suggested to be associated with systemic lupus erythematosus in human patients (Kallick et al., 1972; Kallick et al. 2007). Thus, complete clearance of infection might be also advisable in case of an immunocompromised owner (Barker, 2019). Finally, until the risk and frequency of infection with a cat or dog adapted haemotrophic Mycoplasma is better understood, veterinary professionals are advised to use precautions in order to avoid bites, scratches and arthropod exposure (Compton et al., 2012). Considering these potential zoonotic aspects, ectoparasitic control in pets is again strongly advised.

References

Introduction

Benjamin MM, Lumb WV: Haemobartonella canis infection in a dog. J Am Vet Med Assoc. 1959, 135, 388-90

Clark R: Eperythrozoon felis (sp. nov.) in a cat. J South Afr Vet Med Assoc. 1942, 13, 15-6

Donovan EF, Loeb WF: Hemobartonellosis in the dog. Vet Med. 1960, 55, 57-62

dos Santos AP, dos Santos RP, Biondo AW, et al.: Hemoplasma infection in an HIV-positive patient, Brazil. Emerg Infect Dis. 2008, 14, 1922-4

Flint JC, Moss LC: Infectious anemia in cats. J Am Vet Med Assoc. 1953, 122, 45-8

Foley JE, Harrus S, Poland A, et al.: Molecular, clinical, and pathologic comparison of two distinct strains of Haemobartonella felis in domestic cats. Am J Vet Res. 1998, 59, 1581-8

Kallick CA, Levin S, Reddi KT, et al.: Systemic lupus erythematosus associated with haemobartonella-like organisms. Nat New Biol. 1972, 236, 145-6

Kallick CA, inventor; Sphingomonas Research Partners, LP, assignee: Specific bacterial inclusions in bone marrow cells indicate systemic lupus erythematosus, and treatment for lupus. US patent, 2007, WO 2007/019415 A2, 15 February 2007

Messick JB: Hemotrophic mycoplasmas (hemoplasmas): a review and new insights into pathogenic potential. Vet Clin Pathol. 2004, 33, 2-13

Sykes JE: Feline hemotropic mycoplasmas. J Vet Emerg Crit Care (San Antonio). 2010, 20, 62-9

Sykes JE, Lindsay LL, Maggi RG, et al.: Human co-infection with Bartonella henselae and two hemotropic mycoplasma variants resembling Mycoplasma ovis. J Clin Microbiol. 2010, 48, 3782-5

Willi B, Boretti FS, Cattori V, et al.: Identification, molecular characterization, and experimental transmission of a new hemoplasma isolate from a cat with hemolytic anemia in Switzerland. J Clin Microbiol. 2005, 43, 2581-5

Willi B, Boretti FS, Tasker S, et al.: From Haemobartonella to hemoplasma: Molecular methods provide new insights. Vet Microbiol. 2007, 125, 197-209

Yuan C, Liang A, Yu F, et al.: Eperythrozoon infection identified in an unknown aetiology anaemic patient. Ann Microbiol. 2007, 57, 467-9

Yuan CL, Liang AB, Yao CB, et al.: Prevalence of Mycoplasma suis (Eperythrozoon suis) infection in swine and swine-farm workers in Shanghai, China. Am J Vet Res. 2009, 70, 890-4

 

Pathogens

Benjamin MM, Lumb WV: Haemobartonella canis infection in a dog. J Am Vet Med Assoc. 1959, 135, 388-90

Donovan EF, Loeb WF: Hemobartonellosis in the dog. Vet Med. 1960, 55, 57-62

Foley JE, Pedersen NC: ‘Candidatus Mycoplasma haemominutum’, a low-virulence epierythrocytic parasite of cats. Int J Sys Evol Microbiol. 2001, 51, 815-7

Knutti RE, Hawkins WB: Bartonella incidence in splenectomised bile-fistula dogs. J Exp Med. 1935, 61, 115-9

Kreier JP, Ristic M: Genus III Haemobartonella; genus IV Eperythrozoon. In: Krieg NR, Holt JG (eds.): Bergey’s Manual of Systematic Bacteriology. 1984, Williams & Wilkins, Baltimore, USA, pp. 724-9

Martínez-Díaz VL, Silvestre-Ferreira AC, Vilhena H, et al.: Prevalence and co-infection of haemotropic mycoplasmas in Portuguese cats by real-time polymerase chain reaction. J Feline Med Surg. 2013, 15, 879-85

McNaught JB, Woods FM, Scott V: Bartonella bodies in the blood of a nonsplectomized dog. J Exp Med. 1935, 62, 353-8

Messick JB, Walker PG, Raphael W, et al.: 'Candidatus Mycoplasma haemodidelphidis' sp. nov., 'Candidatus Mycoplasma haemolamae' sp. nov. and Mycoplasma haemocanis comb. nov., haemotrophic parasites from a naturally infected opossum (Didelphis virginiana), alpaca (Lama pacos) and dog (Canis familiaris): phylogenetic and secondary structural relatedness of their 16S rRNA genes to other mycoplasmas. Int J Syst Evol Microbiol. 2002, 52, 693-8

Neimark H, Johansson KE, Rikihisa Y, et al.: Proposal to transfer some members of the genera Haemobartonella and Eperythrozoon to the genus Mycoplasma with descriptions of ‘Candidatus Mycoplasma haemofelis’, ‘Candidatus Mycoplasma haemomuris’, ‘Candidatus Mycoplasma haemosuis’ and ‘Candidatus Mycoplasma wenyonii’. Int J Sys Evol Microbiol. 2001, 51, 891-9

Obara H, Fujihara M, Watanabe Y, et al.: A feline hemoplasma, ‘Candidatus Mycoplasma haemominutum’, detected in dog in Japan. J Vet Med Sci. 2011, 73, 841-3

Rikihisa Y, Kawahara M, Wen B, et al.: Western immunoblot analysis of Haemobartonella muris and comparison of 16S rRNA gene sequences of H. muris, H. felis, and Eperythrozoon suis. J Clin Microbiol. 1997, 35, 823-9

Soto F, Walker R, Sepulveda M, et al.: Occurrence of canine hemotropic mycoplasmas in domestic dogs from urban and rural areas of the Valdivia Province, southern Chile. Comp Immunol Microbiol Infect Dis. 2017, 50, 70-7

Sykes JE: Feline hemotropic mycoplasmas. Vet Clin North Am Small Anim Pract. 2010, 40, 1157-70

Sykes JE, Bailiff NL, Ball LM, et al.: Identification of a novel hemotropic mycoplasma in a splenectomized dog with hemic neoplasia. J Am Vet Med Assoc. 2004, 224, 1946-51

Sykes JE, Ball LM, Bailiff NL, et al.: ‘Candidatus Mycoplasma haematoparvum’, a novel small hemotropic mycoplasma from a dog. Int J Syst Evol Microbiol. 2005, 55, 27-30

Sykes JE, Drazenovich NL, Ball LM, et al.: Use of conventional and real‐time polymerase chain reaction to determine the epidemiology of hemoplasma infections in anemic and nonanemic cats. J Vet Int Med. 2007, 21, 685-93

Tasker S, Lappin M: Haemobartonella felis: Recent developments in diagnosis and treatment. J Feline Med Surg. 2002, 4, 3-11

Vergara RW, Galleguillos FM, Jaramillo MG, et al.: Prevalence, risk factor analysis, and hematological findings of hemoplasma infection in domestic cats from Valdivia, Southern Chile. Comp Immunol Microbiol Infect Dis. 2016, 46, 20-6

Willi B, Boretti FS, Baumgartner C, et al.: Prevalence, risk factor analysis, and follow-up of infections caused by three feline hemoplasma species in cats in Switzerland. J Clin Microbiol. 2006, 44, 961-9

Willi B, Boretti FS, Cattori V, et al.: Identification, molecular characterization, and experimental transmission of a new hemoplasma isolate from a cat with hemolytic anemia in Switzerland. J Clin Microbiol. 2005, 43, 2581-5

Willi B, Boretti FS, Tasker S, et al.: From Haemobartonella to hemoplasma: Molecular methods provide new insights. Vet Microbiol. 2007, 125, 197-209

 

Epidemiology

Aquino LC, Hicks CA, Scalon MC, et al.: Prevalence and phylogenetic analysis of haemoplasmas from cats infected with multiple species. J Microbiol Methods. 2014, 107, 189-96

Barker EN, Tasker S, Day MJ, et al.: Development and use of real-time PCR to detect and quantify Mycoplasma haemocanis and "Candidatus Mycoplasma haematoparvum" in dogs. Vet Microbiol. 2010, 140, 167-70

Bauer N, Balzer HJ, Thüre S, et al.: Prevalence of feline haemotropic mycoplasmas in convenience samples of cats in Germany. J Feline Med Surg. 2008, 10, 252-8

Cabello J, Altet L, Napolitano C, et al.: Survey of infectious agents in the endangered Darwin's fox (Lycalopex fulvipes): high prevalence and diversity of hemotrophic mycoplasmas. Vet. Microbiol. 2013, 167, 44854

Dean RS, Helps CR, Gruffydd-Jones TJ, et al.: Use of real-time PCR to detect Mycoplasma haemofelis and ‘Candidatus M. haemominutum’ in the saliva and salivary glands of haemoplasma-infected cats. J Fel Med Surg. 2008, 10, 413-7

Di Cataldo S, Cevidanes A, Ulloa-Contreras C, et al.: Widespread infection with hemotropic mycoplasmas in free-ranging dogs and wild foxes across six bioclimatic regions of Chile. Microorganisms. 2021, 9, 919

Gentilini F, Novacco M, Turba ME, et al.: Use of combined conventional and real-time PCR to determine the epidemiology of feline haemoplasma infections in northern Italy. J Feline Med Surg. 2009, 11, 277-85

Grindem CB, Corbett WT, Tomkins MT: Risk factors for Haemobartonella felis infection in cats. J Am Vet Med Assoc. 1990, 196, 96-9

Harvey JW, Gaskin JM: Experimental feline haemobartonellosis. J Am Anim Hosp Assoc. 1977, 13, 28-38

Jensen WA, Lappin MR, Kamkar S, et al.: Use of a polymerase chain reaction assay to detect and differentiate two strains of Haemobartonella felis in naturally infected cats. Am J Vet Res. 2001, 62, 604-8

Kenny MJ, Shaw SE, Beugnet F, et al.: Demonstration of two distinct haemotropic mycoplasmas in French dogs. J Clin Microbiol. 2004, 42, 5397-9

Lappin MR: Update on flea and tick associated diseases of cats. Vet Parasitol. 2018, 254, 26-9

Lappin MR, Dingman P, Levy J, et al.: Detection of hemoplasma DNA on the gingival and claw beds of naturally exposed cats (abstract). J Vet Intern Med. 2008, 22, 779

Luria BJ, Levy JK, Lappin MR, et al.: Prevalence of infectious diseases in feral cats in northern Florida. J Feline Med Surg. 2004, 6, 287-96

Martínez-Díaz VL, Silvestre-Ferreira AC, Vilhena H, et al.: Prevalence and co-infection of haemotropic mycoplasmas in Portuguese cats by real-time polymerase chain reaction. J Feline Med Surg. 2013, 15, 879-85

Millán J, Travaini A, Cevidanes A, et al.: Assessing the natural circulation of canine vector-borne pathogens in foxes, ticks and fleas in protected areas of Argentine Patagonia with negligible dog participation. Int J Parasitol Parasites Wildl. 2019, 8, 63-70

Neimark H, Johansson KE, Rikihisa Y, et al.: Proposal to transfer some members of the genera Haemobartonella and Eperythrozoon to the genus Mycoplasma with descriptions of ‘Candidatus Mycoplasma haemofelis’, ‘Candidatus Mycoplasma haemomuris’, ‘Candidatus Mycoplasma haemosuis’ and ‘Candidatus Mycoplasma wenyonii’. Int J Sys Evol Microbiol. 2001, 51, 891-9

Obara H, Fujihara M, Watanabe Y, et al.: A feline hemoplasma, ‘Candidatus Mycoplasma haemominutum’, detected in dog in Japan. J Vet Med Sci. 2011, 73, 841-3

Persichetti MF, Pennisi MG, Vullo A, et al.: Clinical evaluation of outdoor cats exposed to ectoparasites and associated risk for vector-borne infections in southern Italy. Parasit Vectors. 2018, 11, 136

Ravagnan S, Carli E, Piseddu E, et al.: Prevalence and molecular characterization of canine and feline hemotropic mycoplasmas (hemoplasmas) in northern Italy. Parasit Vectors. 2017, 10, 132

Roura X, Peters IR, Altet L, et al.: Prevalence of hemotropic mycoplasmas in healthy and unhealthy cats and dogs in Spain. J Vet Diagn Invest. 2010, 22, 270-4

Sasaki M, Ohta K, Matsuu A, et al.: A molecular survey of Mycoplasma haemocanis in dogs and foxes in Aomori Prefecture, Japan. J Protozool Res. 2008, 18, 57-60

Soto F, Walker R, Sepulveda M, et al.: Occurrence of canine hemotropic mycoplasmas in domestic dogs from urban and rural areas of the Valdivia Province, southern Chile. Comp Immunol Microbiol Infect Dis. 2017, 50, 70-7

Sykes JE, Drazenovich NL, Ball LM, et al.: Use of conventional and real‐time polymerase chain reaction to determine the epidemiology of hemoplasma infections in anemic and nonanemic cats. J Vet Int Med. 2007, 21, 685-93

Sykes JE, Terry JC, Lindsay LL, et al.: Prevalences of various hemoplasma species among cats in the United States with possible hemoplasmosis. J Am Vet Med Assoc. 2008, 232, 372-9

Tasker S, Binns SH, Day MJ, et al.: Use of a PCR assay to assess the prevalence and risk factors for Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’ in cats in the United Kingdom. Vet Rec. 2003, 152, 193-8

Vergara RW, Galleguillos FM, Jaramillo MG, et al.: Prevalence, risk factor analysis, and hematological findings of hemoplasma infection in domestic cats from Valdivia, Southern Chile. Comp Immunol Microbiol Infect Dis. 2016, 46, 20-6

Weingart C, Tasker S, Kohn B: Infection with haemoplasma species in 22 cats with anaemia. J Feline Med Surg. 2016, 18, 129-36

Wengi N, Willi B, Boretti FS, et al.: Real-time PCR-based prevalence study, infection follow-up and molecular characterization of canine haemotropic mycoplasmas. Vet Microbiol. 2008, 126, 132-41

Willi B, Boretti FS, Baumgartner C, et al.: Prevalence, risk factor analysis, and follow-up of infections caused by three feline hemoplasma species in cats in Switzerland. J Clin Microbiol. 2006a, 44, 961-9

Willi B, Boretti FS, Meli ML, et al.: Real-time PCR investigation of potential vectors, reservoirs, and shedding patterns of feline hemotropic mycoplasmas. Appl Environ Microbiol. 2007a, 73, 3798-802

Willi B, Boretti FS, Tasker S, et al.: From Haemobartonella to hemoplasma: Molecular methods provide new insights. Vet Microbiol. 2007b, 125, 197-209

Willi B, Filoni C, Catao-Dias JL, et al.: Worldwide occurrence of feline hemoplasma infections in wild felid species. J Clin Microbiol. 2007c, 45, 1159-66

Willi B, Tasker S, Boretti FS, et al.: Phylogenetic analysis of ‘Candidatus Mycoplasma turicensis’ isolates from pet cats in the United Kingdom, Australia, and South Africa, with analysis of risk factors for infection. J Clin Microbiol. 2006b, 44, 4430-5

Woods JE, Wisnewski N, Lappin MR: Attempted transmission of ‘Candidatus Mycoplasma haemominutum’ and Mycoplasma haemofelis by feeding cats infected Ctenocephalides felis. Am J Vet Res. 2006, 67, 494-7

 

Diagnosis

Berent LM, Messick JB, Cooper SK: Detection of Haemobartonella felis in cats with experimentally induced acute and chronic infections, using a polymerase chain reaction assay. Am J Vet Res. 1998, 59, 1215-20

Ghazisaeedi F, Atyabi N, Zahrai Salehi T, et al.: A molecular study of hemotropic mycoplasmas (hemoplasmas) in cats in Iran. Vet Clin Pathol. 2014, 43, 381-6

Jensen WA, Lappin MR, Kamkar S, et al.: Use of a polymerase chain reaction assay to detect and differentiate two strains of Haemobartonella felis in naturally infected cats. Am J Vet Res. 2001, 62, 604-8

Lappin MR: Update on flea and tick associated diseases of cats. Vet Parasitol. 2018, 254, 26-9

Lappin MR, Tasker S, Roura X: Role of vector-borne pathogens in the development of fever in cats: 1. Flea-associated diseases. J Feline Med Surg. 2020, 22, 31-9

Messick JB: New perspectives about Hemotrophic mycoplasma (formerly, Haemobartonella and Eperythrozoon species) infections in dogs and cats. Vet Clin North Am Small Anim Pract. 2003, 33, 1453-65

Roura X, Peters IR, Altet L, et al.: Prevalence of hemotropic mycoplasmas in healthy and unhealthy cats and dogs in Spain. J Vet Diagn Invest. 2010, 22, 270-4

Tasker S, Binns SH, Day MJ, et al.: Use of a PCR assay to assess the prevalence and risk factors for Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’ in cats in the United Kingdom. Vet Rec. 2003a, 152, 193-8

Tasker S, Helps CR, Day MJ, et al.: Use of real-time PCR to detect and quantify Mycoplasma haemofelis and “Candidatus Mycoplasma haemominutum” DNA. J Clin Microbiol. 2003b, 41, 439-41

Peters IR, Helps CR, Willi B, et al.: The prevalence of three species of feline haemoplasmas in samples submitted to a diagnostics service as determined by three novel real-time duplex PCR assays. Vet Microbiol. 2008, 126, 142-50

Westfall DS, Jensen WA, Reagan WJ, et al.: Inoculation of two genotypes of Hemobartonella felis (California and Ohio variants) to induce infection in cats and the response to treatment with azithromycin. Am J Vet Res. 2001, 62, 687–91

Willi B, Boretti FS, Baumgartner C, et al.: Prevalence, risk factor analysis, and follow-up of infections caused by three feline hemoplasma species in cats in Switzerland. J Clin Microbiol. 2006, 44, 961-9

Willi B, Boretti FS, Meli ML, et al.: Real-time PCR investigation of potential vectors, reservoirs, and shedding patterns of feline hemotropic mycoplasmas. Appl Environ Microbiol. 2007, 73, 3798-802

 

Clinical Signs

Alleman AR, Pate MG, Harvey JW, et al.: Western immunoblot analysis of the antigens of Haemobartonella felis with sera from experimentally infected cats. J Clin Microbiol. 1999, 37, 1474-9

Austerman JW: Haemobartonellosis in a nonsplenectomized dog. Vet Med Small Anim Clin. 1979, 74, 954

Berent LM, Messick JB, Cooper SK: Detection of Haemobartonella felis in cats with experimentally induced acute and chronic infections, using a polymerase chain reaction assay. Am J Vet Res. 1998, 59, 1215-20

Foley JE, Harrus S, Poland A, et al.: Molecular, clinical, and pathologic comparison of two distinct strains of Haemobartonella felis in domestic cats. Am J Vet Res. 1998, 59, 1581-8

George JW, Rideout BA, Griffey SM, et al.: Effect of preexisting FeLV infection or FeLV and feline immunodeficiency virus coinfection on pathogenicity of the small variant of Haemobartonella felis in cats. Am J Vet Res. 2002, 63, 1172-8

Grindem CB, Corbett WT, Tomkins MT: Risk factors for Haemobartonella felis infection in cats. J Am Vet Med Assoc. 1990, 196, 96-9

Harrus S, Klement E, Aroch I, et al.: Retrospective study of 46 cases of feline haemobartonellosis in Israel and their relationships with FeLV and FIV infections. Vet Rec. 2002, 151, 82-5

Harvey JW, Gaskin JM: Experimental feline haemobartonellosis. J Am Anim Hosp Assoc. 1977, 13, 28-38

Harvey JW, Gaskin JM: Feline haemobartonellosis: attempts to induce relapses of clinical disease in chronically infected cats. J Am Anim Hosp Assoc. 1978, 14, 453-6

Lappin MR: Opportunistic infections associated with retroviral infections in cats. Semin Vet Med Surg (Small Anim). 1995, 10, 244-50

Lappin MR: Update on flea and tick associated diseases of cats. Vet Parasitol. 2018, 254, 26-9

Maede Y: Sequestration and phagocytosis of Haemobartonella felis in the spleen. Am J Vet Res. 1979, 40, 691-5

Messick JB: Hemotrophic mycoplasmas (hemoplasmas): a review and new insights into pathogenic potential. Vet Clin Pathol. 2004, 33, 2-13

Messick JB, Harvey JW: Chapter 31: Hemotropic Mycoplasmosis (Hemobartonellosis). Veterinarian Key – Fastest Veterinary Medicine Insight Engine, 2016, https://veteriankey.com/hemotropic-mycoplasmosis-hemobartonellosis/

Messick JB, Walker PG, Raphael W, et al.: 'Candidatus Mycoplasma haemodidelphidis' sp. nov., 'Candidatus Mycoplasma haemolamae' sp. nov. and Mycoplasma haemocanis comb. nov., haemotrophic parasites from a naturally infected opossum (Didelphis virginiana), alpaca (Lama pacos) and dog (Canis familiaris): phylogenetic and secondary structural relatedness of their 16S rRNA genes to other mycoplasmas. Int J Syst Evol Microbiol. 2002, 52, 693-8

Neimark H, Johansson KE, Rikihisa Y, et al.: Proposal to transfer some members of the genera Haemobartonella and Eperythrozoon to the genus Mycoplasma with descriptions of 'Candidatus Mycoplasma haemofelis', 'Candidatus Mycoplasma haemomuris', 'Candidatus Mycoplasma haemosuis' and 'Candidatus Mycoplasma wenyonii'. Int J Syst Evol Microbiol. 2001, 51, 891-9

Sykes JE: Feline hemotropic mycoplasmas. J Vet Emerg Crit Care (San Antonio). 2010, 20, 62-9

Sykes JE, Tasker S: Chapter 41: Hemoplasma Infections. Veterinarian Key – Fastest Veterinary Medicine Insight Engine, 2016, https://veteriankey.com/hemoplasma-infections/

Sykes JE, Bailiff NL, Ball LM, et al.: Identification of a novel hemotropic mycoplasma in a splenectomized dog with hemic neoplasia. J Am Vet Med Assoc. 2004, 224, 1946-51

Sykes JE, Henn JB, Kasten RW, et al.: Bartonella henselae infection in splenectomized domestic cats previously infected with hemotropic Mycoplasma species. Vet Immunol Immunopathol. 2007, 116, 104-8

Tasker S: Chapter 82: Canine and Feline Hemotropic Mycoplasmosis. Veterinarian Key – Fastest Veterinary Medicine Insight Engine, 2016, https://veteriankey.com/chapter-82-canine-and-feline-hemotropic-mycoplasmosis/

Tasker S, Peters IR, Papasouliotis K, et al.: Description of outcomes of experimental infection with feline haemoplasmas: copy numbers, haematology, Coombs’ testing and blood glucose concentrations. Vet Microbiol. 2009, 139, 323–32

Westfall DS, Jensen WA, Reagan WJ, et al.: Inoculation of two genotypes of Hemobartonella felis (California and Ohio variants) to induce infection in cats and the response to treatment with azithromycin. Am J Vet Res. 2001, 62, 687–91

Willi B, Boretti FS, Cattori V, et al.: Identification, molecular characterization, and experimental transmission of a new hemoplasma isolate from a cat with hemolytic anemia in Switzerland. J Clin Microbiol. 2005, 43, 2581-5

Willi B, Novacco M, Meli M, et al.: Haemotropic mycoplasmas of cats and dogs: transmission, diagnosis, prevalence and importance in Europe. Schweiz Arch Tierheilkd. 2010, 152, 237-44

Zulty JC, Kociba GJ: Cold agglutinins in cats with haemobartonellosis. J Am Vet Med Assoc. 1990, 196, 907-10

 

Treatment & Prevention

Aktas M, Ozubek S: A molecular survey of hemoplasmas in domestic dogs from Turkey. Vet Microbiol. 2018, 221, 94-7

Barker EN: Update on feline hemoplasmosis. Vet Clin North Am Small Anim Pract. 2019, 49, 733-43

Barker EN, Tasker S, Day MJ, et al.: Development and use of real-time PCR to detect and quantify Mycoplasma haemocanis and "Candidatus Mycoplasma haematoparvum" in dogs. Vet Microbiol. 2010, 140, 167-70

Berent LM, Messick JB, Cooper SK: Detection of Haemobartonella felis in cats with experimentally induced acute and chronic infections, using a polymerase chain reaction assay. Am J Vet Res. 1998, 59, 1215-20

Brennan SJ, Ngeleka M, Philibert HM, et al.: Canine brucellosis in a Saskatchewan kennel. Can Vet J. 2008, 49, 703-8

Cabello J, Altet L, Napolitano C, et al.: Survey of infectious agents in the endangered Darwin's fox (Lycalopex fulvipes): high prevalence and diversity of hemotrophic mycoplasmas. Vet. Microbiol. 2013, 167, 44854

Constantino C, de Paula EF, Brandão AP, et al.: Survey of spatial distribution of vector-borne disease in neighborhood dogs in southern Brazil. Open Vet J. 2017, 7, 50-6

Coppinger R, Zuccotti J: Kennel enrichment: exercise and socialization of dogs. J Appl Anim Welf Sci. 1999, 2, 281-96

Cortese L, Beall M, Buono F, et al.: Distribution and risk factors of canine haemotropic mycoplasmas in hunting dogs from southern Italy. Vet Microbiol. 2020, 251, 108910

Di Cataldo S, Cevidanes A, Ulloa-Contreras C, et al.: Widespread infection with hemotropic mycoplasmas in free-ranging dogs and wild foxes across six bioclimatic regions of Chile. Microorganisms. 2021, 9, 919

Dowers KL, Olver CS, Radecki SV, et al.: Use of enrofloxacin for treatment of large-form Haemobartonella felis in experimentally infected cats. J Am Vet Med Assoc. 2002, 221, 250-3

Dowers KL, Tasker S, Radecki SV, et al.: Use of pradofloxacin to treat experimentally induced Mycoplasma hemofelis infection in cats. Am J Vet Res. 2009, 70, 105-11

Foley JE, Harrus S, Poland A, et al.: Molecular, clinical, and pathologic comparison of two distinct strains of Haemobartonella felis in domestic cats. Am J Vet Res. 1998, 59, 1581-8

Harvey JW, Gaskin JM: Experimental feline haemobartonellosis. J Am Anim Hosp Assoc. 1977, 13, 28-38

Harvey JW, Gaskin JM: Feline haemobartonellosis: attempts to induce relapses of clinical disease in chronically infected cats. J Am Anim Hosp Assoc. 1978, 14, 453-6

Hulme-Moir KL, Barker EN, Stonelake A, et al.: Use of real-time quantitative polymerase chain reaction to monitor antibiotic therapy in a dog with naturally acquired Mycoplasma haemocanis infection. J Vet Diagn Invest. 2010, 22, 582-7

Ishak AM, Dowers KL, Cavanaugh MT, et al.: Marbofloxacin for the treatment of experimentally-induced Mycoplasma haemofelis infection in cats. J Vet Intern Med. 2008, 22, 288-92

Kenny MJ, Shaw SE, Beugnet F, et al.: Demonstration of two distinct haemotropic mycoplasmas in French dogs. J Clin Microbiol. 2004, 42, 5397-9

Kim J, Lee D, Yoon E, et al.: Clinical case of a transfusion-associated canine Mycoplasma haemocanis infection in the Republic of Korea: a case report. Korean J Parasitol. 2020, 58, 565-9

Lappin MR, Tasker S, Roura X: Role of vector-borne pathogens in the development of fever in cats: 1. Flea-associated diseases. J Feline Med Surg. 2020, 22, 31-9

Millán J, Travaini A, Cevidanes A, et al.: Assessing the natural circulation of canine vector-borne pathogens in foxes, ticks and fleas in protected areas of Argentine Patagonia with negligible dog participation. Int J Parasitol Parasites Wildl. 2019, 8, 63-70

Museux K, Boretti FS, Willi B, et al.: In vivo transmission studies of 'Candidatus Mycoplasma turicensis' in the domestic cat. Vet Res. 2009, 40, 45

Novacco M, Meli ML, Gentilini F, et al.: Prevalence and geographical distribution of canine hemotropic mycoplasma infections in Mediterranean countries and analysis of risk factors for infection. Vet Microbiol. 2010, 142, 276-84

Novacco M, Sugiarto S, Willi B, et al.: Consecutive antibiotic treatment with doxycycline and marbofloxacin clears bacteremia in Mycoplasma haemofelis-infected cats. Vet Microbiol. 2018, 217, 112-20

Paradies P, Capelli G, Testini G, et al.: Risk factors for canine neosporosis in farm and kennel dogs in southern Italy. Vet Parasitol. 2007, 145, 240-4

Pitorri F, Dell'Orco M, Carmichael N, et al.: Use of real-time quantitative PCR to document successful treatment of Mycoplasma haemocanis infection with doxycycline in a dog. Vet Clin Pathol. 2012, 41, 493-6

Rikihisa Y, Kawahara M, Wen B, et al.: Western immunoblot analysis of Haemobartonella muris and comparison of 16S rRNA gene sequences of H. muris, H. felis, and Eperythrozoon suis. J Clin Microbiol. 1997, 35, 823-9

Roura X, Peters IR, Altet L, et al.: Prevalence of hemotropic mycoplasmas in healthy and unhealthy cats and dogs in Spain. J Vet Diagn Invest. 2010, 22, 270-4

Seneviratna P, Weerasinghe M, Ariyadasa S: Transmission of Haemobartonella canis by the dog tick, Rhipicephalus sanguineus. Res Vet Sci. 1973, 14, 1124

Sharifiyazdi H, Abbaszadeh Hasiri M, Amini AH: Intravascular hemolysis associated with Candidatus Mycoplasma hematoparvum in a non-splenectomized dog in the south region of Iran. Vet Res Forum. 2014, 5, 243-6

Sykes JE: Feline hemotropic mycoplasmas. J Vet Emerg Crit Care (San Antonio). 2010, 20, 62-9

Sykes JE, Drazenovich NL, Ball LM, et al.: Use of conventional and real‐time polymerase chain reaction to determine the epidemiology of hemoplasma infections in anemic and nonanemic cats. J Vet Int Med. 2007, 21, 685-93

Tasker S, Caney SM, Day MJ, et al.: Effect of chronic feline immunodeficiency infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection. Microbes Infect. 2006a, 8, 653-61

Tasker S, Caney SM, Day MJ, et al.: Effect of chronic FIV infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection. Vet Microbiol. 2006b, 117, 169-79

Tasker S, Helps CR, Day MJ, et al.: Use of a Taqman PCR to determine the response of Mycoplasma haemofelis infection to antibiotic treatment. J Microbiol Methods. 2004, 56, 63-71

Tasker S, Hofmann-Lehmann R, Belák S, et al.: Haemoplasmosis in cats: European guidelines from the ABCD on prevention and management. J Feline Med Surg. 2018, 20, 256-61

Valle S de F, Messick JB, Dos Santos AP, et al.: Identification, occurrence and clinical findings of canine hemoplasmas in southern Brazil. Comp Immunol Microbiol Infect Dis. 2014, 37, 259-65

Wengi N, Willi B, Boretti FS, et al.: Real-time PCR-based prevalence study, infection follow-up and molecular characterization of canine haemotropic mycoplasmas. Vet Microbiol. 2008, 126, 132-41

Willi B, Novacco M, Meli ML, et al.: Haemotropic mycoplasmas of cats and dogs: transmission, diagnosis, prevalence and importance in Europe. Schweiz Arch Tierheil. 2010, 152, 237-44

 

Zoonotic Potential

Barker EN: Update on feline hemoplasmosis. Vet Clin North Am Small Anim Pract. 2019, 49, 733-43

Compton SM, Maggi RG, Breitschwerdt EB: Candidatus Mycoplasma haematoparvum and Mycoplasma haemocanis infections in dogs from the United States. Comp Immunol Microbiol Infect Dis. 2012, 35, 557-62

dos Santos AP, dos Santos RP, Biondo AW, et al.: Hemoplasma infection in an HIV-positive patient, Brazil. Emerg Infect Dis. 2008, 14, 1922-4

Kallick CA, Levin S, Reddi KT, et al.: Systemic lupus erythematosus associated with haemobartonella-like organisms. Nat New Biol. 1972, 236, 145-6

Kallick CA, inventor; Sphingomonas Research Partners, LP, assignee: Specific bacterial inclusions in bone marrow cells indicate systemic lupus erythematosus, and treatment for lupus. US patent, 2007, WO 2007/019415 A2, 15 February 2007

Lappin MR, Tasker S, Roura X: Role of vector-borne pathogens in the development of fever in cats: 1. Flea-associated diseases. J Feline Med Surg. 2020, 22, 31-9

Steer JA, Tasker S, Barker EN, et al.: A novel hemotropic Mycoplasma (hemoplasma) in a patient with hemolytic anemia and pyrexia. Clin Infect Dis. 2011, 53, e147-51

Sykes JE, Lindsay LL, Maggi RG, et al.: Human co-infection with Bartonella henselae and two hemotropic mycoplasma variants resembling Mycoplasma ovis. J Clin Microbiol. 2010, 48, 3782-5

Yuan CL, Liang AB, Yao CB, et al.: Prevalence of Mycoplasma suis (Eperythrozoon suis) infection in swine and swine-farm workers in Shanghai, China. Am J Vet Res. 2009, 70, 890-4

Yuan C, Liang A, Yu F, et al.: Eperythrozoon infection identified in an unknown aetiology anaemic patient. Ann Microbiol. 2007, 57, 467-9