GUIDELINE for Chlamydia felis

The Chlamydia felis (formerly Chlamydophila felis) guidelines were first published in the J Feline Med Surg 2009; 11: 605-609 by Tim Gruffydd-Jones et al. The present guideline was updated by Séverine Tasker and ABCD colleagues.

Key points

• Chlamydia (C.) felis is a Gram-negative bacterium that is an obligate intracellular parasite of cats
• C. felis does not survive outside of the host so close contact between cats is required for transmission, usually via ocular discharges
• Chlamydial disease typically affects young cats under 9 months of age; ocular signs (initially unilateral then bilateral) with conjunctivitis, hyperaemia of the nictitating membrane, blepharospasm, ocular discharge (initially serous then mucopurulent) and chemosis
• Diagnosis is PCR performed on conjunctival or oropharyngeal swabs
• Treatment comprises systemic antibiotics; doxycycline is usually used and should ideally be given for at least 4 weeks to eliminate infection, and at least 2 weeks beyond resolution of clinical signs
• Amoxycillin-clavulanate is an alternative antibiotic especially for young kittens
• Prompt diagnosis and treatment are associated with a favourable outcome, with signs typically improving within 48 hours of starting appropriate treatment
• Vaccination for C. felis is a non-core vaccine and is not indicated for all cats but may be recommended for those in multi-cat households (e.g. breeding catteries, shelters) at high risk of infection or if there has been a history of chlamydiosis

Agent properties

ABCD follows the nomenclature to classify all 11 currently recognized Chlamydiaceae species in a single genus, the genus Chlamydia (Sachse et al., 2015); these species include Chlamydia felis (formerly Chlamydophila felis), Chlamydia pneumoniae and Chlamydia psittaci. C. felis is the species typically seen infecting cats, although Chlamydia abortus has occasionally been identified in cats (Sostaric-Zuckermann et al., 2011; Bressan et al., 2021) and DNA that resembles that of the human pathogen C. pneumoniae has now also been detected in ocular swabs from cats with conjunctivitis from Europe (Sibitz et al., 2011). C. psittaci infection has also occasionally been reported in cats (Lipman et al., 1994; Sanderson et al., 2021).

Chlamydia felis, typical of the genus Chlamydia, is a Gram-negative rod-shaped coccoid bacterium; its cell wall is devoid of peptidoglycan (Sykes, 2023). As an obligate intracellular parasite, it lacks the ability to replicate autonomously (Becker, 1978).

The genome of C. felis is small in size (Sykes, 2023) and has been sequenced (Azuma et al., 2006). There is extensive nucleotide sequence homology between the genomes of various Chlamydia species. The membrane contains important families of proteins: the major outer membrane proteins (MOMPs) and polymorphic outer membrane proteins (POMPs). Based on sequence data from outer membrane protein genes of C. felis, all feline isolates appear to be genetically similar, but serological methods and DNA fingerprinting suggest that more than one strain of C. felis might exist (Sykes, 2023).

The organism attaches to sialic acid receptors of cells. It has a unique pattern of replication, involving non-infectious reticulate bodies (0.5 to 1.5 μm in diameter) that replicate with the host cell cytoplasm, and infectious elementary bodies (0.2 to 0.6 μm in diameter) which exist outside of the host cell (Sykes, 2023). Elementary bodies are released following cell lysis. Some C. felis isolates appear to contain plasmids, and this may be related to their pathogenic ability (Everson et al., 2003).

Chlamydiae are readily inactivated by detergent solutions and common disinfectants.

Epidemiology

Since C. felis (and the elementary bodies) have low viability outside the host, transmission requires close contact between cats; transfer of ocular secretions is probably the most important route of infection. Fomites may be a means of transmission among group-housed cats in heavily contaminated environments (Sykes, 2023). Rectal shedding of Chlamydia spp. has also been documented in 25% of infected cats (Bressan et al., 2021); this study suggested that Chlamydia spp. could replicate in the feline intestinal tract, but only secondary to an ocular infection with no evidence of persistent infection. Chlamydia spp. can also infect the genitourinary system (Sykes, 2023). It is unknown whether venereal transmission occurs but the organism is shed in vaginal discharges from some infected cats (Graham and Taylor, 2012; Sykes, 2023).

Infection is most common in multi-cat environments, particularly breeding catteries, and therefore prevalence may be higher among pedigree cats (Wills et al., 1987). However, other studies have highlighted a high prevalence of C. felis in stray cats (Wu et al., 2013), including those with conjunctivitis (Halanova et al., 2011). One study of cats in Slovakia (Halanova et al., 2019) found that the risk of C. felis infection was significantly greater in cats with conjunctivitis and/or upper respiratory tract signs (30% positive by PCR) than healthy cats (4%); additionally, cats from shelters (31% positive by PCR) and street stray cats (36%) were significantly more at risk of infection than indoor only cats (0%). The prevalence of C. felis was also higher (at 19%) in stray, compared to pet (12%), cats in Switzerland with significantly higher rates in cats with signs of conjunctivitis (88%) (Bressan et al., 2021). In a study from China, 7% of cats showing clinical signs of upper respiratory tract infection were C. felis PCR positive (Gao et al., 2023), yet the prevalence was 29% in 93 nasal or pharyngeal swabs collected from 39 cats, mainly from shelters, with respiratory disease (Thieulent et al., 2024).

Most cases of chlamydial disease occur in young cats, particularly under one year of age. Cats older than 5 years are very unlikely to be infected with C. felis (Sykes, 2023). C. felis is the infectious organism most frequently associated with conjunctivitis in cats and is isolated from up to 30% of affected cats, particularly in those with chronic conjunctivitis (Wills et al., 1987). Infection is associated with more severe ocular disease and conjunctivitis (Fernandez et al., 2017). However a study of 60 shelter cats with ocular disease in the USA found no evidence of C. felis infection by PCR (Zirofsky et al., 2018). Studies by PCR in cats with ocular or upper respiratory tract disease signs have shown prevalences of 12 to 20%. The prevalence in healthy cats is low, and with less than 2-3% positivity by PCR in cats without clinical signs (Di Francesco et al., 2004; Fernandez et al., 2017; Chan et al., 2023). Amongst pet cats, those that were clinically healthy, those with a history of conjunctivitis, and those with current active conjunctivitis, showed positive PCR results of 0%, 5% and 7%, respectively (Low et al., 2007). In a study of pet cats, cats from rescue shelters and from breeders in Europe (Helps et al., 2005), C. felis infection was more common in cats with respiratory disease (10%) than those without (3%).

Studies have shown variable results when investigating for any association between gingivostomatitis and C. felis (Fernandez et al., 2017; Nakanishi et al., 2019). Serological surveys have shown that 10% or more of unvaccinated household pets have antibodies (Lang, 1992; Gunn-Moore et al., 1995).

Pathogenesis

Chlamydia spp. target mucosal tissues and the primary target for C. felis is the conjunctiva. After uptake of the infectious elementary bodies, the elementary bodies develop into reticulate bodies, which are non-infectious and replicate by binary fission in a membrane-enclosed vacuole within the cytoplasm of the host cell, avoiding lysosomal fusion. The reticulate bodies then transition back into the elementary body form, which are released into the extracellular space after cell lysis to infect other host cells (Sykes, 2023). The entire replication cycle takes about 2 days to complete. The incubation period before clinical signs occur is generally 2-5 days, although many cats remain well following infection. C. felis can also spread from the eye via the bloodstream to other organs such as the tonsil, lung, liver, spleen, intestinal tract and kidney (Sykes, 2023). In most cats, conjunctival shedding ceases at around 60 days after infection, although some may continue to become persistently infected (O’Dair et al., 1994). C. felis has been isolated from the conjunctiva of untreated cats for up to 215 days after experimental infection (Wills, 1986).

Chlamydia spp. primarily cause ocular disease and conjunctivitis, with ocular discharge, hyperaemia of the nictitating membrane, chemosis and blepharospasm, can all occur. Chlamydia spp. can infect the epithelial cells of the ocular, respiratory, gastrointestinal and/or reproductive systems, although association with disease in some of these systems is poorly understood. There is circumstantial evidence that Chlamydia spp. may cause reproductive disease (Graham and Taylor, 2012).

Immunity

Passive immunity

Infected cats develop antibodies and kittens appear to be protected initially for the first one or two months of life by maternally derived antibodies (Wills, 1986).

Active immunity

The nature of the protective immune responses to chlamydial infection is uncertain. However cellular immune responses are believed to play a crucial role in protection (Longbottom and Livingstone, 2006). The MOMPs and POMPs are important targets for protective immune responses in other species (Longbottom and Livingstone, 2006) and have been shown to exist in the cat (Harley et al., 2007). Immunity to natural infection appears to be short-lived and does not protect against reinfection (Sykes, 2023). There may be an age-related resistance to infection (Sykes, 2023).

Clinical signs

Unilateral ocular disease may be seen initially, but this generally progresses to become bilateral. There can be intense conjunctivitis with extreme hyperaemia of the nictitating membrane, blepharospasm and ocular discomfort (Fig. 1). Ocular discharges are initially watery but later become mucoid or mucopurulent (Fig. 2). Chemosis of the conjunctiva is a characteristic feature of chlamydiosis. Respiratory signs are generally minimal with C. felis infections but can include nasal discharge and stertor (Sykes, 2023). In cats with respiratory disease but without concurrent ocular signs, C. felis infection is unlikely. Ocular complications such as adhesions of the conjunctiva, may occur but keratitis and corneal ulcers are not generally associated with chlamydial infection; if keratitis is present, it is more likely to be due to feline herpesvirus. Transient fever, inappetence and weight loss may occur shortly after infection, although most cats remain well and continue to eat.

Fig. 1. Conjunctivitis in a cat with Chlamydia felis infection. Courtesy of The Feline Centre, Langford Vets, University of Bristol, UK

Fig. 2. Purulent conjunctivitis and chemosis in a cat with Chlamydia felis infection. Courtesy of Eric Déan

Co-infections with other respiratory pathogens, such as feline herpesvirus, feline calicivirus or Mycoplasma felis (Chan et al., 2023; Thieulent et al., 2024) may occur, and this may contribute to increased severity of clinical signs.

Diagnosis

Direct detection methods

It is possible to identify chlamydial infections by culture, but this technique has now been superceded by more senstivie molecular methods (PCR) and so is generally only used in research settings. It requires special chlamydial transport media for transportation of the conjunctival swab used for sampling. False negatives can result from organisms losing their viability during transport or in chronic infections, when organism numbers are very low (Sykes, 2023).

PCR techniques are now the preferred option for diagnosing chlamydial infections. PCR techniques are extremely sensitive and avoid problems with poor viability of the organisms. Quantitative PCR methods are also available (Helps et al., 2001). Ocular swabs are generally used as samples (Fig. 3), although a study did not find a significant difference in the ability to detect C. felis by PCR from ocular, oropharyngeal, nasal and tongue swabs (Schulz et al., 2015) and another study has successfully used owner-collected buccal swabs for analysis (Chan et al., 2023). Additionally, organisms may also be detected in vaginal swabs, aborted foetuses and rectal swabs, although these are seldom used diagnostically. Since the organism is intracellular, it is necessary to obtain good quality swabs that include the epithelial cells the organisms have infected. It has been shown that the topical anaesthetic proxymetacaine does not appear to affect PCR amplification of chlamydial DNA from ocular swabs (Segarra et al., 2011). Generic or species specific PCR assays are avaiable, or sequencing methods performed on amplified PCR products can also be used to determine the infecting chlamydial species or type e.g. C. felis typing using the gene pmp9, which encodes a polymorphic membrane protein (Bressan et al., 2021). The sensitivity of PCR means that occasionally positive results are obtained in cats without signs of disease, so interpretation is important. Additionally, cats can continue to be PCR positive for several days following the start of antibiotic treatment (Sykes et al., 1999; Dean et al., 2005).

A recombinase-aided amplification test for C. felis using specific enzymes in isothermal amplification technology has been developed to enable simpler and faster diagnosis than PCR (Liu et al., 2023), but is not widely used or available.

Other techniques for demonstrating the organism are less sensitive and less reliable than PCR. Conjunctival smears can be Giemsa-stained to check for intracytoplasmic inclusions (basophilic clusters of coccoid bacteria, ~10 μm in diameter) (Streeten and Streeten, 1985). However, chlamydial inclusions are easily confused with other basophilic inclusions such as melanin granules and are only present early in infection, making their detection insensitive. Chlamydial antigen tests (including those developed for human chlamydial infections) based on detecting group specific antigen using ELISA or similar techniques are also available but have lower sensitivity and specificity than culture or PCR (Sykes, 2023).

Fig. 3. Collecting a conjunctival swab; the sample must contain enough cells for PCR diagnosis. Courtesy of The Feline Centre, Langford Vets, University of Bristol, UK

Indirect detection methods

Antibody detection in unvaccinated cats has been used to diagnose previous or current C. felis infections, although this is not widely available and variable results are also reported (Sykes, 2023). Immunofluorescence (IF; Fig. 4) and ELISA techniques are used for determining antibody titres. Some cross reactivity with other bacteria occurs, and low IF titres (≤ 32) are generally considered as being negative. Established active or recent infections can be associated with high titres, often of ≥ 512. Serology can be particularly useful to establish whether infection is endemic in a group. It can also be of value in investigating cases with chronic ocular signs. A high titre suggests that C. felis may be an aetiological factor, whereas a low titre discounts likely chlamydial involvement. Vaccination with a chlamydial vaccine may interfere with result interpretation, although an ELISA antibody test that differentiated between natural infection and vaccination has been described (Ohya et al., 2010).

Fig. 4. Indirect immunofluorescence test to titrate antibody directed against Chlamydia felis; infected cell culture serves as the antigen substrate. Courtesy of The Feline Centre, Langford Vets, University of Bristol, UK

Treatment

Chlamydia infection in cats can be treated very effectively with antibiotics, with improvement often seen within a couple of days. Systemic antibiotics are more effective than local topical treatment (Sparkes et al., 1999) and so are recommended. Tetracyclines are generally regarded as the antibiotics of choice for chlamydial infections (Dean et al., 2005). Doxycycline has the advantage of requiring only a single daily dose and is most frequently used at a daily dosage of 10 mg/kg orally, although 5 mg/kg orally twice daily can be used if vomiting occurs with single day dosing. Administration of the hyclate preparation of doxycycline should always be followed by food or water because of the possibility of it inducing oesophagitis in cats with incomplete swallowing. Studies have shown that treatment must be maintained for four weeks to ensure elimination of the organism (Dean et al., 2005), as three weeks of treatment was not able to clear infection in some cats. In some cats, recrudescence may be noted some time after discontinuation of therapy. Continuation of treatment for two weeks after resolution of clinical signs has also been recommended. Tetracyclines have potential side effects in young cats although these appear to be less common with doxycycline than oxytetracycline. Alternative antibiotics may be considered if this is a concern. Both enrofloxacin and pradofloxacin have shown some efficacy against Chlamydia spp. (Gerhardt et al., 2006; Hartmann et al., 2008), although pradofloxacin would be preferred over enrofloxacin in view of the diffuse retinal degeneration and acute blindness that has been reported following enrofloxacin treatment in cats, albeit very rarely. However, doxycycline was more effective than pradofloxacin in one experimental study (Hartmann et al., 2008).  Azithromycin is ineffective for chlamydiosis (Owen et al., 2003).

A four week course of therapy with clavulanic acid potentiated amoxicillin may represent the safest choice of alternative to doxycycline in young kittens (Sturgess et al., 2001).

Prognosis

The prognosis is good for recovery from chlamydial disease, when effective treatment is instigated.

Vaccination

Chlamydia felis vaccines are non-core vaccines. Both inactivated and modified live (attenuated) vaccines, based on whole organisms, are available, but only as components of multivalent vaccine preparations (i.e. with feline herpesvirus, feline calicivirus, feline parvovirus, and with or without feline leukaemia virus in the vaccine). Vaccines are effective in protecting against clinical manifestation of the disease, however, not against occurrence of infection (Wills et al., 1987). No reliable data are available to compare the efficacy of inactivated versus modified live vaccines.

Vaccination should be considered for cats at risk of exposure to infection, particularly in multi-cat environments kept together long-term, and if there has been a previous history of C. felis infection.

Vaccination of kittens generally begins at 8-9 weeks of age with a second injection 3-4 weeks later at around 12 weeks of age. Limited information is available about the duration of immunity. There is some evidence that previously infected cats can become vulnerable to re-infection after a year or more. Annual boosters are recommended for cats that are at continued risk of exposure to infection.

Disease control in specific situations

Shelters

Chlamydia infection can be a significant cause of disease in rescue shelters but is generally a less significant problem than respiratory viruses (McManus et al., 2014). Vaccination should be considered if there has been a previous history of chlamydial disease in the shelter. Since close contact is necessary for transmission and the organism has low viability outside the host, single housing of cats and routine hygiene measures should avoid cross infection. Whenever cats are maintained together longer term, they should be vaccinated regularly.

Breeding catteries

In catteries with endemic C. felis infection, the first step is generally treatment of all cats in the household with doxycycline for at least 4 weeks to attempt to eliminate the infection. In some cattery cats a minimum of 6 to 8 weeks of treatment has been shown to be necessary to eliminate natural infection. Once clinical signs have been controlled, cats should be vaccinated to provide protection against disease should re-infection of the cattery occur.

Immunocompromised cats

Immunocompromised cats should only be vaccinated when it is deemed absolutely necessary, and then an inactivated vaccine should probably be used, although data confirming this are lacking.

Zoonotic risk

There is no epidemiological evidence for a significant zoonotic risk although chronic follicular conjunctivitis caused by C. felis has been reported; for example in an HIV-infected patient (Hartley et al., 2001), in an immunocompetent female (Wons et al., 2017) in which the source of infection was her pet kitten, and in three immunocompetent people (Hughes et al., 2024). Additionally, C. pneumoniae, a well-recognised human pathogen, has been identified in a small number of cats (Sibitz et al., 2011), although transmission from cats to humans has not been documented. C. psittaci primarily infects birds and is an important zoonotic agent which causes atypical pneumonia in humans. Occasionally, infection in cats is reported (Lipman et al., 1994). A case report of fatal C. psittaci infection in a 7-week old kitten has been reported (Sanderson et al., 2021); this kitten showed Gram negative sepsis with acute necrosuppurative hepatitis and nonsuppurative pneumonia and mild leptomeningitis, and infection of the kitten’s mother via bird hunting during pregnancy was suspected.

Acknowledgement

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

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