GUIDELINE for Francisella tularensis infection

Published: 01/01/2013
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The Francisella tularensis infection in cats guidelines were published in J Feline Med Surg 2013; 15: 585-587; this update has been compiled by Maria Grazia Pennisi.

Key points

  • Tularaemia is a potentially fatal zoonosis mostly found in the Northern hemisphere caused by virulent strains of Francisella tularensis.
  • Host range is extremely wide (mammals, birds, reptiles, amphibians, and fish) and modes of transmission include inoculation by bite, skin/mucosal contact, inhalation, ingestion, and vectorial transmission (ticks, flies, mosquitoes).
  • Outdoor cats are at higher risk for infection in case of exposure to ticks, rodents and lagomorphs.
  • Most cats and humans either develop a localized infection of the skin with severe inflammation and draining lymph nodes (the ulceroglandular form) or a systemic infection (typhoidal tularaemia) with high fever and sepsis.
  • Kittens usually suffer from more severe forms of the disease.
  • Oropharyngeal and pneumonic syndromes are rare.
  • Acute and convalescent serology is required to confirm diagnosis by antibody detection.
  • Samples for culture and PCR investigations should be obtained before starting antibiotic treatment.
  • Gentamycin is suggested as first choice antibiotic treatment with isolation of cats at least for the first 72 hours.
  • Regular external parasiticidal treatment to prevent tick infestations is recommended for outdoor cats.
  • In case of manipulation of suspected cases, the veterinary staff has to worn gloves, gown, a mask and goggles.

Agent properties

Francisella (F.) tularensis (formerly Pasteurella tularensis) is a small, facultative intracellular Gram-negative, non-motile, aerobic, zoonotic bacterium (Sykes et al., 2023). This bacterial species was discovered in ground squirrels in Tulare County, California, in 1911. Two biovars have been described as causing disease in the cat: Type A or F. tularensis tularensis present in North America (virulent, associated with a tick/rabbit cycle), and Type B or F. tularensis holarctica (used in the past for a human live attenuated vaccine) with a broader distribution. The latter has a more complex life cycle involving lagomorphs and ticks or mosquitoes, as well as contaminated water. F. tularensis has a wide host range involving more than 100 mammals, birds, fish, reptiles and amphibians. Cats are more susceptible than dogs, but rodents (included pet hamsters) and lagomorphs are considered the most susceptible mammalian hosts, that can suffer from an often fatal disease (Rhyan et al., 1990).

Epidemiology and vectors

Tularaemia (rabbit fever) is a rare, potentially fatal zoonosis sporadically occurring throughout rural temperate zones of the Northern hemisphere: North America, Eurasia, parts of the Middle East and the North coast of Africa (Goetherth et al., 2004; Foley and Nieto, 2010). In Europe, tularaemia has been reported in all countries – except Iceland, Ireland and United Kingdom – and in some areas of Sweden and Finland the highest European incidence is reported (Cross et al., 2019; ECDC, 2020). F. tularensis infection can be acquired through many species of blood-sucking arthropods, included fleas. Flies and mosquitos are considered mechanical vectors; however, in Sweden transstadial passage in mosquitos able to sustain transmission to a new host has been demonstrated (Sykes et al., 2023). Only ticks (Dermacentor, Amblyomma, Haemaphysalis and Ixodes) are also long-term reservoir hosts and pass the infection to a new generation transovarially (Foley and Nieto, 2010). Cats and dogs can also be infected by their rodent or lagomorph prey carrying the bacteria.

Infected domestic cats can transmit tularaemia to humans by bites and scratches but also through direct contact with infected body fluids or tissues with the skin (Petersson and Athlin, 2017). Persons can also become infected by ingestion of contaminated food or water, by contact with lagomorphs, or by inhalation during farming activities (Foley and Nieto, 2010).

In the USA, the incidence of human disease slightly increased in the decade 2008-2018 with about 200 cases per year, and the infection has been reported in almost all states, but is most common in the south central USA (Anonymous, 2022). Magnarelli et al. (2007) reported that 12-24% of client-owned cats had antibodies against F. tularensis in the USA. Moreover, investigation on 106 isolates detected a high percentage of feline-associated strains from regions where the bacterium is endemic (Larson et al., 2014).

In Scandinavian countries, recurrent outbreaks of disease in humans and hare are linked to mosquito transmission – although feline cases have never been reported (Dryselius et al., 2019). However, in the past contact with cats was also thought to be important in an outbreak in Sweden. In that Swedish outbreak, pneumonia was related with farm work (Eliasson et al., 2002). Tularaemia after a cat bite has been reported from Norway (Yaqub et al., 2004) and the US (Whitsell and Becker, 2020; Clary et al., 2022). A case of a cat urinary infection was reported in Switzerland, where human cases have increased in last years. Genome sequencing of the feline isolate showed its close phylogenetic relationship with a contemporary hare isolate from a nearby geographic area; thus, the cat and the hare infections possibly shared epidemiological backgrounds (Kittl et al., 2020). Based on the number of reported cases, the risk of feline tularaemia is small, even in endemic areas but it is probably underdiagnosed because clinical manifestations are not specific (Sykes et al., 2023). The risk for free roaming cats is related to tick exposure and to hunting rodents and lagomorphs.

Pathogenesis

Pathogenicity of F. tularensis is linked to various virulence factors (Sykes et al., 2023).

Immunity

Natural infection induces protection against reinfection (Sykes et al., 2023).

Clinical signs in cats

Most cases have been reported retrospectively, when cats were suspected of having transmitted tularaemia to humans, because clinical signs are often uncharacteristic. The incubation period is considered of 1-5 days and severity of the disease is variable, ranging from a mild chronic localized infection (the ulceroglandular form) to a fatal acute disease (systemic). Kittens develop a more severe systemic disease (typhoidal), associated with sudden onset of fever, depression, anorexia, enlargement of peripheral and/or abdominal lymph nodes, liver and spleen, jaundice (Baldwin et al., 1991; Woods et al., 1998). The localized form is represented by chronically draining subcutaneous abscesses (Valentine et al., 2004). Some cats show severe oral and/or lingual ulcerations in case of oral transmission (Sykes et al., 2023).

Interestingly, F. tularensis subsp. holoarctica bacteriuria was incidentally observed in a cat routinely followed up for the management of the bilateral subcutaneous ureteral bypass placed four years before (Kittl et al., 2020). Previous urine cultures had always been negative and culture positivity was associated with weight loss and IRIS stage III chronic kidney disease (Kittl et al., 2020).

Diagnosis

Lesions and signs can be similar to those of the plague caused by Yersinia pestis, and the two bacteria have also similar epidemiological characteristics (Rhyan et al., 1990). Tularaemia should be included in the differential diagnosis of fever of unknown origin in cats in endemic areas, as well as of chronic subcutaneous infections or affected draining tracts. History about hunting behaviour of cats is useful for considering the suspicion of both tularaemia and plague.

Laboratory changes

Laboratory abnormalities are variable and can include leukocytosis or panleukopenia, thrombocytopenia, increased serum aminotransferase and alkaline phosphatase activities, and hyperbilirubinaemia.

Hyperplastic lymph nodes are found upon cytological examination but in advanced course of disease macrophages and degenerate neutrophils can be observed. Compared to Yersinia pestis, F. tularensis is tiny and stains only faintly, and organisms are unlikely to be visualised on cytology (Sykes et al., 2023).

Diagnostic imaging

Few information is available, however hepatomegaly, splenomegaly, abdominal lymphadenomegaly, and fluid filled content of intestinal loops are sonographic and/or radiographic findings (Sykes et al., 2023).

Detection of the infectious agent

Direct detection

Direct detection from cytological slides can be obtained by immunofluorescent or immunoperoxidase antibody stains by experienced laboratories.

Lateral-flow assays are used for rapid detection of antigens in human clinical samples but they have not been validated in cats.

Definitive diagnosis is only possible through bacterial culture, which appeared to be more sensitive than immunohistochemistry in one case report (Valentine et al., 2004). Culturing requires special media and all biosafety measures when handling infected tissues. However, F. tularensis was identified by MALDI-TOF testing of bacterial colonies grown in routine culture performed on Tripycase Soy Agar II with 5% sheep blood (Kittl et al., 2020).

Samples for culture and PCR investigations should preferably be obtained before starting antibiotic treatment.

Indirect detection

Specific antibodies can be detected by microagglutination tests (MAT) as well as indirect fluorescent antibody test (IFAT); however, antibodies do not appear earlier than about three weeks after infection, and negative results are commonly obtained at the onset of clinical signs (Feldmann, 2003). A fourfold rise of antibody titre or a positive titre of 160 is considered suggestive of acute infection (Sykes et al., 2023). A MAT low positive titer (1:20) was observed in a cat after a three-week doxycycline course of treatment that was administered to clear bacteriuria (Kittl et al., 2020). Bacterial DNA could not be found by PCR in all cats with antibodies, which suggests residual antibody presence from prior subclinical or undiagnosed infections (Magnarelli et al., 2007).

Disease management and treatment

Because little has been published on the treatment of tularaemia in cats, recommendations for antimicrobial choices are often based on extrapolation from human data. Cats suspected to have tularaemia should be housed in isolation for at least the first 72 hours of antibiotic treatment (Sykes et al., 2023). Gentamycin appears to be the drug of choice for humans, and a 2-week course could be considered for cats with severe forms, and it has been suggested for initial therapy in cats to minimise exposure of the caregiver to F. tularensis (Sykes et al., 2023). However, tetracyclines (doxycycline) and fluoroquinolones (marbofloxacin) have also been recommended for treatment in cats (Sykes et al., 2023), but because these have been associated with higher relapse rates than gentamycin in humans, a 3-week, rather than a 2-week, course is recommended for cats (Sykes et al., 2023). Kittl et al. (2020) obtained negative urine cultures in a cat with bacteriuria treated with doxycycline (50 mg q24h PO for three weeks) (Kittl et al., 2020). However, urine real-time quantitative PCR remained positive, and the cat had to receive a further two-month doxycycline antibiotic course to become PCR negative in urine (Kittl et al., 2020).

Supportive care and topical treatment of skin lesions are also important.

Prognosis

In acutely diagnosed cases prognosis varies from good (early diagnosed and treated ulceroglandular forms) to poor (systemic forms with sepsis) and fatal cases may occur.

Vaccination

There is a strong interest in developing a vaccine for human tularaemia because F. tularensis is a possible weapon of bioterrorism (Sykes et al., 2023). There is no vaccine for feline tularaemia because the disease is rare and cats do not play an important epidemiological role for the human disease.

Prevention

Regular external parasiticidal treatment to prevent tick infestations is recommended for outdoor cats. Exposure of cats to rodents and lagomorphs should also be avoided in endemic areas (Sykes et al., 2023).

Zoonotic risk

Clinical signs in humans

F. tularensis is a select pathogen and tularaemia is a potentially fatal zoonosis (Anonymous, 2023). Various syndromes occur, but most patients either present with a localized infection of the skin and draining lymph nodes (the ulceroglandular form, Fig. 1) or with a systemic infection (typhoidal tularaemia). Localized infections typically occur after cat bites (Yaqub et al., 2004; Whitsell and Becker, 2020; Clary et al., 2022). Oropharyngeal and pneumonic forms are rarer. The clinical presentation is highly dependent on the route of transmission. Ingestion of food or contaminated water causes oropharyngeal disease, while transmission through inhalation of contaminated dust aerosols leads to a pneumonic presentation (Cross et al., 2019). The ulceroglandular form usually occurs following a tick or fly bite or after handing of an infected animal. A skin ulcer appears at the site where the organism entered the body (Fig. 1). The ulcer is accompanied by swelling of regional lymph glands, usually in the armpit or groin.

Fig. 1. Skin ulcer at the site where the organism entered the body - accompanied by swelling of regional lymph nodes. (The Centers for Disease Control and Prevention)

Fig. 1. Skin ulcer at the site where the organism entered the body – accompanied by swelling of regional lymph nodes. (The Centers for Disease Control and Prevention)

Recommendations to avoid zoonotic transmission from cats

The risk of acquiring infection from cats is low, but certainly not negligible for owners of outdoor cats, veterinarians and technicians/nurses in endemic areas (Liles and Burger, 1993).

Regular external parasiticidal treatment to prevent tick infestations is recommended for outdoor cats. When handling animals with suppurative or draining skin or lymph node lesions in endemic areas, gloves, gown, a mask and goggles should be worn. This also applies when examining the oral mucosa of any suspected cat. Cat bites are of concern in endemic areas, particularly in the case of cats with outdoor access. Handling diagnostic samples by laboratory staff should follow biosafety procedures (Sykes et al., 2023).

Acknowledgement

ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD), Virbac, IDEXX GmbH and MSD Animal Health.

References

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