Introduction

By comparison with diseases transmitted to dogs by hematophagous (blood-feeding) arthropods, veterinarians appear to be relatively unaware about the global importance of feline vector-borne diseases (FVBD) 1. However, with greater understanding of FVBD, it should come as no surprise that many of the factors responsible for emerging infectious diseases in canines and humans are also relevant to our feline patients. Whenever a blood transfusion for a client’s cat is required, or a feline patient presents with unexplained fever, anemia or thrombocytopenia, the clinician should always consider the possibility of a blood-borne, arthropod-transmitted infection. This brief review aims to provide veterinary practitioners with an insight to the key issues pertaining to the distribution, diagnosis, treatment, and prevention of FVBD.

 

 

FVBD: worldwide distribution, emergence and significance 

Vector-borne diseases are caused by pathogens transmitted by blood-feeding arthropods, including fleas, ticks, mosquitoes, sand flies, lice, and triatomine bugs. These diseases have a worldwide distribution (Table 1), yet there are important regional variations in their prevalence due to differences in the geographical ranges and habitat preferences of their respective arthropod vectors. Climate variations in temperature and humidity play key roles in explaining the presence of one species or another; for example, hygrophilic ticks such as Ixodes and Dermacentor spp. require humidity and do not tolerate heat and desiccation, whereas xerophilic ticks like Rhipicephalus live in warm areas and tolerate desiccation but not frost. The relative distributions of Rhipicephalus sanguineus and Dermacentor reticulatus in Europe clearly illustrate this point (Figure 1). Microenvironment is critical too; endophilic ticks such as R. sanguineus prefer enclosed environments (e.g., kennels) which explains their ability to establish in people’s homes, sometimes well beyond their usual geographical range (e.g., when the pet returns from a holiday in those regions). This contrasts with exophilic ticks that have free living stages present in forests, woods, fields, parks and gardens.

 

Global warming and changing habitats as a result of deforestation and residential expansion into sylvatic landscapes are among the many drivers for the emergence and re-emergence of vector-borne diseases, and probably exposes roaming cats to arthropods with unknown vector-potential 2 3. Land-cover areas favorable for tick habitats and climatic conditions that support the tick lifecycle are strong risk factors for feline cytauxzoonosis in the USA 4, and landscape change can influence the exposure of domestic cats to indirectly transmitted infections from wild felids such as pumas and bobcats 5. Therefore, practitioners need to be informed about the ectoparasites that occur in their region, but should be equally vigilant and “expect the unexpected” when it comes to vector-borne diseases.

Despite the geographical ranges referred to above, some vectors such as the cat flea Ctenocephalides felis are truly ubiquitous; this undoubtedly explains the worldwide occurrence of the two most common FVBD, namely feline hemoplasmas and Bartonella infections (Table 1). These common hemotropic bacteria between them illustrate many enigmatic features of arthropod-transmitted diseases. The feline hemotropic mycoplasmas (“hemoplasmas”) infect red blood cells by attaching to the erythrocyte cell surface; several species of varying pathogenicity have been identified by molecular studies. Bartonella species are Gram-negative bacteria that also infect erythrocytes, as well as endothelial cells. Both groups of organisms are vector-transmitted (mostly by fleas), although other routes of infection are recognized such as fighting and via blood products (see below). These are also sometimes referred to as “stealth organisms”; i.e., subclinical infection with these bacteria is common (making diagnosis problematic), but clinical disease is rare. That said, Mycoplasma haemofelis (Figure 2) in particular is a significant feline pathogen, causing pallor, lethargy, anorexia, weight loss, dehydration, and pyrexia, along with life-threatening anemia, and requires treatment with tetracycline, doxycycline or fluoroquinolones, together with compatible (typed or cross-matched) blood transfusions or other blood products in many cases.

As the cause of emerging infectious diseases, vector-borne pathogens may appear when least expected. Following Hurricane Katrina, dogs and cats were relocated from New Orleans to all parts of the United States, dispersing infectious animals (and their vector-borne pathogens) into areas where normally there would be a low index of suspicion for the diseases caused by those agents 6. Increasingly, pets, including cats, are ”rescued” by welfare organizations and relocated from one area to another (e.g., from southern to northern Europe) potentially bringing with them infectious organisms, and there is increasing concern within the veterinary community regarding abuse of the European Pet Travel Scheme and the risk of illegal imports. Additionally, cats travel great distances to shows or (increasingly) on holiday with their owners to regions where new vectors and their pathogens occur; it is critical that clients are made aware of the risks and advised about appropriate ectoparasite control (Table 2).

 

* Availability of products and licensing details for use in cats will vary from country to country

 

Since FVBD are also blood-borne infections, microscopic examination of a blood film is helpful for the diagnosis of some infections, notably protozoa infections such as babesiosis (Figure 3) and cytauxzoonosis; however, microscopy remains insensitive for detection of others such as hemoplasma or Bartonella infections. The good news is that the ability to detect many of the organisms responsible for FVBD is improving, largely due to the development and wide availability of highly sensitive DNA testing. Molecular epidemiological studies in cats have contributed to a greater understanding of the prevalence and distribution of FVBD as costs have decreased and high-throughput systems are developed 1, and there has been a shift from serology-based testing to increased use of PCR for detection of pathogen DNA. Importantly, this more accurately reflects the infection status of the animals being tested (assuming detection of DNA implies viable pathogen), as opposed to “previous exposure”, and knowing the prevalence of bacteremia, parasitemia, or viremia provides the practitioner with important data pertaining to the real infection status of their patients.

What are the zoonotic implications of FBVD?

Human cohabitation with cats is common worldwide, with many households having at least one cat and many additional individuals participating in so-called “semi-ownership”, i.e., feeding or providing care to cats that they do not consider their own. A large number of humans are thus in daily contact with cats, with growing recognition of cats as family members and sleeping companions. Paralleling this is the expanding “One Health” concept, and veterinarians are increasingly called upon for advice regarding the risks that emerging and re-emerging infectious diseases pose to humans (including those who are very young, very old, or otherwise immunosuppressed) by in-contact cats and other companion animals. Clinicians must also be mindful of occupational exposure, as in many cases the exposure to cats infected with FVBD, and in particular with their vectors, is high for veterinary personnel. 

Vector-borne pathogens of importance to feline veterinarians as potential zoonoses include Bartonella spp., Rickettsia felis, Yersinia pestis, and Francisella tularensis. Leishmania infantum and Anaplasma phagocytophilum can also infect both humans and cats, and the role of cats as reservoirs for human disease continues to be investigated.

Bartonellosis

Bartonellosis is arguably the feline vector-borne zoonotic disease of greatest current global interest. Cats, amongst other mammalian species, can be infected by or act as a reservoir for several species of Bartonella bacteria. Disease in humans was once considered limited to the relatively benign cat scratch disease (CSD), which is characterized by fever and regional lymphadenopathy, but many additional manifestations of human bartonellosis in both immunosuppressed and (less frequently) immunocompetent individuals are now apparent 7. Knowledge continues to expand, and, in the past 25 years, the number of named Bartonella species has increased from two to greater than 24. The main species of interest in cats currently are B. henselae, B. clarridgeiae, and B. koehlerae (Table 1) with fleas implicated as important vectors 8.

Subclinical infection of cats with B. henselae is common worldwide, with only a small percentage of animals manifesting more serious disease. Risk factors for bacteremia in cats include young age, outdoor access, flea infestation and multi-cat environments 9. Cat-to-cat transmission primarily occurs via flea feces in contaminated claws, and the organism can survive for several days in the environment 8. 

Humans typically become infected with Bartonella spp. species when scratched by a cat with flea feces-contaminated claws, but infection from a cat bite and indirect transmission via cat fleas are also possible 10. Immunocompetent humans typically become subclinically infected, but immunocompromised people may suffer a range of illnesses, including endocarditis, neuroretinitis, relapsing fever, aseptic meningitis, and uveitis 11 12.

Veterinarians must be able to provide advice on minimizing cat-to-human transmission of Bartonella spp., most importantly for households with immunocompromised individuals. The prudent approach requires addressing cat, human and transmission factors. Recommendations include 13: 

• Choosing a cat less likely to be bacteremic: i.e., apparently healthy, older than one year of age, flea-free, and from a single-cat environment

• Minimizing transmission: trimming of claws, avoiding rough play, and rapid cleansing of any cat scratch or bite wounds

• Ensuring eradication of vectors: strict flea and tick control, and prevention of outdoor access

Should a young cat (e.g., < 2 years) living in a household with immunocompromised people or children be found to be infected with Bartonella spp., subclinical or otherwise, guidelines recommend antimicrobial treatment of the cat in order to decrease bacterial load and transmission risk 13.

Rickettsia felis infection

Rickettsia felis is a spotted fever group Rickettsia and the causal agent of cat flea typhus or flea-borne spotted fever (FBSF); it is also considered an emerging human pathogen. Clinical signs of FBSF in humans include macropapular rash and eschar, fever, fatigue, and headache 14. Interestingly, whilst R. felis DNA has been isolated from cat fleas, it appears that dogs are a more likely reservoir for the infection, and the rickettsial DNA has been identified in this species 15. Most attempts to isolate R. felis DNA from cat blood have failed and no clinical disease has been reported in cats, but their role in maintaining flea populations could be important in disease transmission.

Yersinia

Yersinia pestis, a Gram-negative coccobacillus, is the agent of plague, to which cats are very susceptible. Cats in endemic areas (areas of North and South America, Africa and Asia) can contract plague via infected rodent fleas or ingestion of infected small mammals. It has been suggested that the risk of cat-associated human plague might increase as residential development continues, encroaching on the natural environment where Y. pestisfoci exist in the western USA 2. Typical clinical signs in cats include mandibular and retropharyngeal lymphadenopathy; progression to septic shock and pneumonic forms of plague are less common 16. Humans can contract plague from cats indirectly through rodent fleas, or directly through aerosol spread, bites or scratches, and veterinary personnel have been amongst those infected. 

Tularemia

Tularemia is a rare disease seen in North America and Europe caused by the Gram-negative coccobacillus Francisella tularensis. Major reservoirs for the organism include a large variety of small mammals, with cats becoming infected when they hunt and ingest their prey 17. Infected cats manifest clinical signs including fever, peripheral lymphadenopathy, hepatomegaly, and splenomegaly 18. Cat-to-human transmission occurs through bites (or less likely scratches), and clinical signs in humans include lymphadenopathy and transient flu-like illness, with possible progression to pneumonia 19.

FVBD and co-morbid conditions

The association between human immunosuppression and vector-borne diseases is well recognized. One of the most compelling examples is the apparent interaction between human immunodeficiency virus (HIV) and visceral leishmaniasis, which has been reported in a large number of countries worldwide. Leishmaniasis has become an important cause of death in AIDS patients, and HIV-associated immunosuppression has changed the spectrum of the disease, with an increased risk of visceral disease in retrovirus infected individuals in comparison to the cutaneous forms typically seen in immunocompetent people 20. 

A small number of studies have examined the relationship between Bartonella seropositivity and FIV and/or FeLV 21 22. No association has been found, but there may be an increased risk of oral cavity disease (stomatitis, gingivitis) in Bartonella seropositive cats. An association between feline retroviruses and M. haemofelis has been found in some, but not all, studies. Additionally, whilst not a cause of significant anemia in immunocompetent cats, “Ca. M. haemominutum” and “Ca. M. turicensis” have been shown to cause more marked anemia in the presence of FeLV infection and concurrent immunosuppression, respectively 23 24. No association between feline leishmaniasis and retroviruses has been reported to date, but only small numbers of infected cats have been examined.

A recent case report described a cat co-infected with Anaplasma platys, B. henselae, B. koehlerae and “Ca. M. haemominutum” 25. The cat was also diagnosed with multiple myeloma based on splenic plasmacytosis and a monoclonal gammopathy. It was suggested that infection with one or more of the pathogens may have mimicked or played a role in a myeloma-related disorder (MRD). Alternatively, immunosuppression related to MRD may have predisposed the cat to infection with multiple VBD.

Blood transfusions and FVBD 

Veterinarians must be mindful of the potential risks of vector-borne disease associated with transfusion of blood products in cats, and need to convey these to owners. Many cats that receive blood transfusions are intrinsically immunosuppressed, or will subsequently be medically immunosuppressed, and thus may be more susceptible to clinical infection with FVBD pathogens inadvertently transmitted via infected blood.

Excellent guidelines for minimizing the risk of transmission of infectious disease via transfusion of feline blood products are available 26 27, the former including a useful “potential feline blood donor evaluation form” for practitioners. The guidelines are centered on choosing donors least likely to be infected, and screening for regionally appropriate pathogens.

With regard to FVBD, the ideal feline blood donor 26 has:

• An age of > 3 years (to minimize the risk of Bartonella bacteremia)

• Always lived in a single-cat household

• Good flea and tick prophylaxis

• No history of travel

• No history of VBD

In terms of screening feline blood donors for FVBD, a minimum core panel including blood PCR screening for M. haemofelis, B. henselae, and A. phagocytophilum is recommended 27. However, additional PCR screening for A. platys, other Bartonella spp., Cytauxzoon felis, Ehrlichia canis, “Ca. M. haemominutum” and “Ca. M. turicensis” is optimally recommended, along with confirmation of seronegativity to A. platys and B. henselae. Additional pathogens for which feline blood donors should be screened, based on local knowledge of disease or subclinical carriage, include A. phagocytophilum, Babesia spp., C. felis, Ehrlichia spp. and Leishmania infantum.

Whilst the risk of FVBD transmission via blood products can be minimized with appropriate screening, it should always be emphasized to owners that the blood transfusion procedure is not risk-free, both with regard to FVBD and other complications.

Control of FVBD

In conclusion, arthropod-transmitted pathogens are a worldwide cause of emerging infectious diseases in cats, and the implications for the health of cats themselves and also of their owners require feline veterinarians to be knowledgeable with regard to their recognition and appropriate management. FBVD need to be controlled and prevented whenever possible 28. Given the key role of the cat flea in transmission of many of the above-mentioned zoonotic diseases, as well as the risk to individual cats, the importance of strict flea control, ideally encompassing other arthropod vectors such as ticks, cannot be over-emphasized. The mainstay of prevention is the use of ectoparasiticides and compounds that interfere with the development of the egg or other life stages (Insect Growth Regulators (IGRs) and Insect Development Inhibitors (IDIs)) 29, along with chemoprophylaxis with ivermectin in heartworm-endemic areas to prevent feline dirofilariasis. Other strategies available for dogs such as vaccination to prevent diseases including babesiosis, leishmaniasis, and Lyme disease, is either not necessary or not available in cats due to differences in their role as reservoirs. Commonly used treatments for the prevention of FVBD are listed in Table 2. Note that due to limitations in the capacity for feline hepatic glucuronidation, a number of pulicides, acaricides and ectoparasiticide groups such as organophosphates, carbamates, amitraz, and most pyrethroids (especially, permethrin) must not be applied to this species because of their toxicity.