Fleas as Vectors of Microbial Disease

Fleas are competent vectors for numerous microbial pathogens of medical and veterinary importance. There is increasing interest in the role of the cat flea, Ctenocephalides felis (Bouché, 1835), in the epidemiology of zoonotic flea-transmitted diseases including cat scratch disease (Bartonella species) and the spotted fever rickettsial species (Rickettsia felis). Although best adapted to parasitize domesticated cats and dogs, C. felis can feed on a wide range of hosts including peri-urban wildlife species. Under optimal conditions, large flea burdens can build up inside houses and C. felis will bite humans in this situation, particularly in the absence of a more suitable cat or dog host.

Adult C. felis are semi-obligate parasites on their preferred dog and cat hosts. However, horizontal transmission of fleas and the pathogens they transmit can occur in situations where there is close contact with infested bedding, lairs or through predation. C. felis has a variety of roles in the ecology of the pathogens it transmits. It is a biological vector for R. felis, which can be naturally maintained within a flea population by trans-ovarian transmission. The mechanisms involved in maintenance or amplification of Bartonella henselae within C. felis are still to be elucidated by micro-evaluation of attachment and invasion of the flea gut. The difference in pathogenesis of pathogen infection in the vector is reflected in variation of mechanisms in pathogen transmission to their mammalian hosts. Flea adapted Rickettsia species are transmitted occurring directly by flea bites, whereas B. henselae is transferred indirectly by inoculation of infected flea faeces through skin abrasions.

Bartonellosis

Bartonellosis is caused by fastidious, gram-negative, intraerythrocytic, arthropod-transmitted bacteria of the genus, Bartonella. Several species infect cats (Bartonella henselae, B. clarridgeiae, B. koehlerae) while B. vinsonii subsp berkhoffii, and to a lesser extent B. henselae, B. clarridgeiae and B. elizabethae, have been reported in association with disease in dogs.

Cat fleas are considered the main vector of B. henselae in cats and recent work has shown transmission by skin inoculation of infected flea faeces. However, the role of the cat flea in the transmission of B. henselae from cats to humans is not fully understood. The role of fleas in transmitting Bartonella species to dogs is unclear but they may be incriminated in cases of canine B. henselae infection. Ticks have been incriminated as vectors for the more commonly identified species B. vinsonii subsp. berkhoffii in domestic and wild dog species.

Bartonella infection has a worldwide distribution in cats and is increasingly widely reported in dogs. The prevalence of asymptomatic infection with Bartonella henselae (and B. clarridgeiae) is common but variable in cats; 40-70% have seropositivity and 9-90% are bacteraemia. The prevalence in dogs is low but improved diagnostics may change this pattern. The effect of climatic factors on the ecology of Bartonella infection may be blurred as in colder countries, domesticated animals are kept in heated domestic or confined environments, facilitating the maintenance of the flea life cycle.

Clinical Signs

Naturally occurring disease in cats infected with Bartonella is difficult to define because of its high prevalence in apparently asymptomatic cats; well described clinical signs (fever, lethargy, transient anaemia, lymphadenomegaly, neurological dysfunction or reproductive failure) have only been reported following experimental infections. Both B. clarridgeiae and B. henselae have been associated with rare clinical disease in dogs. B. clarridgeiae has been isolated from endocarditis in dogs particularly those predisposed to congenital valvular disease and B. henselae has been implicated in a rare case of peliosis hepatis.

Diagnosis

There are difficulties in interpreting the significance of positive blood cultures; serology, particularly in cats, necessitates the use of multiple diagnostic methods including culture, histopathology with special staining, serology and PCR.

1.  Blood culture of B. henselae and B. clarridgeiae from antibiotic-free cats is relatively simple but culture recovery from dogs is extremely difficult.

2.  In cats, persistent antibody limits the diagnostic usefulness of elevated antibody levels and its estimated positive predictive value as an indicator of bacteraemia is less than 50%. Significant antibody titres may also be present in apparently healthy dogs and the predictive value of serology for diagnosing clinical disease is limited. Interpretation is further compromised by cross-reactivity with the non-Bartonella α-subgroup Proteobacteria.

3.  PCR-based methods targeting the 16S rRNA-encoding gene, the 16S-23S intergenic spacer region, and the citrate synthase-encoding gene (gltA) are rapid and specific but sensitivity may be limited. Real time PCR is addressing this problem.

4.  The value of histopathology in the diagnosis of naturally occurring Bartonella infections has only really been explored in dogs and is supported by the use of Warthin-Starry (WS) silver stain to demonstrate the presence of organisms within compatible lesions.

Treatment

Because of the difficulty in eliminating bacteraemia, antibiotic therapy is only recommended for cats with confirmed Bartonella-associated disease or those in contact with immunosuppressed owners. Data relating to the treatment of naturally infected cats and although doxycycline, enrofloxacin, amoxicillin and amoxicillin/clavulanate used at higher than recommended dose rates suppress experimental bacteraemias, 4 weeks of single antibiotic therapy does not eliminate infection in all animals.

Treatment of canine endocarditis due to Bartonella infection is also difficult. There has been no clinical response reported to therapeutic protocols incorporating amoxicillin, enrofloxacin, cephalexin, doxycycline and amikacin in combination with diuretics and various combinations of cardiovascular drugs. Dogs with granulomatous disease appear to respond to antibiotics enrofloxacin (12.5 mg/kg q12 hr) or doxycycline (5.4 mg/kg q12 hr) for 21-30 days.

Rickettsial Infections

Rickettsia felis has been identified in cats, dogs and in cat fleas (Ctenocephalides felis) with a worldwide distribution. The reservoir potential of cats and dogs has not been determined but it is likely that C. felis itself is the major reservoir. Experimental infection of cats with R. felis has been demonstrated. Cats infected with R. felis by repeat exposure to feeding fleas, develop a sub-clinical illness with an incubation period of 2-4 months. However, the pathogenic potential of natural infection with R. felis species in dogs and cats is unknown. What is in no doubt, is that cats and dogs will transport C. felis into domestic surroundings and as transovarial and trans-stadial transmission of R. felis has been shown, a domestic focus of infection for humans could be established.

Diagnosis

Diagnosis has until recently depended on identification of serological methods including micro-immunofluorescence for IgM or rising IgG titres at 2 to 3 week interval. However, cross reactivity may occur between different Rickettsia species. PCR methods have been used to identify rickettsial DNA in blood or tissue specimens. Rickettsial culture involves risk and can only be done in high bio-containment facilities.

Treatment

Tetracyclines including doxycycline (5-10mg/kg) are the antibiotics of choice and treatment should be continued for 3-4 weeks.

Yersiniosis (Plague)

Plague is caused by the non-spore-forming bacterium, Yersinia pestis. Localised foci of disease occur in temperate, semi-arid areas throughout the world and infection is maintained in reservoir rodent populations via transmission by rodent fleas (such as Xenopsylla species). The cat flea C. felis, is a relatively ineffective vector for plague transmission. Epizootic outbreaks of disease occur when Y. pestis infection spills over into more highly susceptible small mammal populations. Cats are more susceptible to clinical disease than dogs. With semi-urban development now extending into endemic areas of plague, there is increasing risk of domestic cats, being infected by bites from rodent fleas acquired during hunting and ingestion of infected small mammals.

Bacteraemic pets may be a source for human infection either directly through aerosol spread, bites or scratches or indirectly by transporting infected fleas into the domestic environment.

Pathogenesis and Clinical Signs

Following an infected flea-bite, organisms spread to local lymph nodes. Lymphadenitis develops, and this is followed by dissemination of infection and bacteraemia within 2-6 days. In contrast, after ingestion or inhalation of organisms, dissemination and onset of bacteraemia is more rapid (1-3 days).

Clinical disease in infected dogs is mild and self limiting. In naturally infected cats, both bubonic and primary pneumonic syndromes (rare) are reported. Bubonic plague is associated with fever, dehydration, weight loss and lymphadenopathy with abscessation and draining tracts affecting the cervical, tonsillar, retropharyngeal and submandibular lymph nodes. Recovery may occur following this stage or there is haematogenous spread with progression to a septicaemic syndrome. Multiple organ involvement, endotoxic shock, oedema and disseminated intravascular coagulation (DIC) with marked leucocytosis are characteristic. Pneumonic involvement during this stage is common and dissemination by aerosol may occur to in-contact humans.

Diagnosis

Notification of Government veterinary health services may be required in some countries when plague is suspected. Diagnosis is by cytological or histopathological demonstration of bacteria in affected tonsillar tissue or lymph node aspirates, followed by culture. Stringent biosafety procedures are required in collection, transport and culture of specimens. Demonstration of a rising serum IFA titre provides diagnostic support. PCR is also available in Yersinia reference laboratories.

Treatment

The decision to treat cats with plague should always take into consideration the potential for aerosol spread from pulmonary lesions and this should be evaluated by thoracic radiology. Appropriate biosecurity procedures are essential. Yersinia pestis is sensitive to routine disinfectants and a variety of antibiotics including doxycycline, aminoglycosides, chloramphenicol and fluoroquinolones. Therapy should be continued for a minimum of 21 days. Doxycycline is most commonly used in the bubonic syndrome and can be used for prophylaxis in exposed, subclinical cats.

Feline Viral Infections

The competency of C. felis as a vector (mechanical or biological) for feline leukaemia has been investigated over the past five years. Specific FeLV RNA can be detected by PCR in fleas and their faeces after artificial feeding on blood from infected cats. RNA was detected from fleas for 30 hours post-feeding and for up to 2 weeks in faeces. The pathogenesis of infection (if present) in the flea vector requires further study.

Prevention and Control

Minimising the flea population in-contact with cats and dogs is obviously important in decreasing the risk of disease transmission. Safe, effective, residual insecticides combined with insect development inhibitors are available which if used regularly will provide excellent vector control. However, as flea feeding commences almost immediately fleas are in contact with the host, the efficacy of individual drugs in decreasing or preventing pathogen transmission by fleas has not been determined.

References

1.  Shaw SE, Birtles RJ, Day MJ. 2001. Arthropod-transmitted infectious diseases of cats. Journal of Feline Medicine and Surgery 3, 193-209.

2.  Breitschwerdt EB, Kordick DL. 2000. Bartonella Infection in Animals: Carriership, Reservoir Potential, Pathogenicity, and Zoonotic Potential for Human Infection Clinical Microbiological Review 13: 428-438.

3.  Birtles RJ. Bartonellosis. In Arthropod-borne Infectious Diseases of the Dog and Cat. Shaw SE and Day MJ Eds. Manson Publishing, London. 2005: 110-119.

4.  American Association of Feline Practitioners. 2006. Panel Report on Diagnosis, Treatment and Prevention of Bartonella spp. infections. In press.

5.  Vobis M, D'Haese J, Mehlhorn H, Mencke N. 2005. Experimental quantification of the feline leukaemia virus in the cat flea (Ctenocephalides felis) and its faeces. Parasitological Research 97: S102-S106.