Edited December, 2016
Chlamydophila (Chlamydia) 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.
ABCD follows a recent nomenclature proposal to classify all 11 currently recognized Chlamydiaceae species in a single genus, the genus Chlamydia (Sachse et al., 2015).
Chlamydia felis is a gram-negative rod-shaped coccoid bacterium; its cell wall is devoid of peptidoglycan. As an obligate intracellular parasite it lacks the ability to replicate autonomously (Becker, 1978).
The genome of C. felis has been sequenced (Azuma et al., 2006). There is extensive homology between Chlamydia species. The membrane contains important families of proteins: the major outer membrane proteins (MOMPs) and polymorphic outer membrane proteins (POMPs). The organism attaches to sialic acid receptors of cells. It has a unique pattern of replication within cells, involving reticulate bodies and elementary bodies. The latter represent the infectious forms of the micro-organism that 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).
Since C. felis is unable to survive outside the host, transmission requires close contact between cats; transfer of ocular secretions is probably the most important method of infection. The infection is most common in multicat environments, particularly breeding catteries, and therefore the prevalence of infection may be more common among pedigree cats (Wills et al., 1987). However, recent work has highlighted a high prevalence of C. felis in stray cats (Wu et al., 2013), including those with conjunctivitis (Halanova et al., 2011). The majority of cases occur in young cats, particularly under one year of age. 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., 1988) and more severe ocular disease and conjunctivitis (Fernandez et al., 2016). Serological surveys have shown that 10% or more of unvaccinated household pets have antibodies (Gunn-Moore et al., 1995; Lang, 1992). Studies by PCR in cats with ocular or upper respiratory tract disease signs have resulted in prevalences of 12 to 20%. Prevalence in healthy cats is low, by PCR some studies show less than 2-3% in cats without clinical signs (Di Francesco et al., 2004).
There is no epidemiological evidence for a significant zoonotic risk. Conjunctivitis caused by C. felis was reported in an HIV-infected patient (Hartley et al., 2001). Recently Chlamydia 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.
Pathogenesis and Clinical signs
Chlamydia target mucosal tissues and the primary target for C. felis is the conjunctiva. The incubation period is generally 2-5 days. In the first day or two after clinical signs develop, unilateral ocular disease may be seen, 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 Chlamydia infections. 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 infection. Transient fever, inappetence and weight loss may occur shortly after infection, although most cats remain well and continue to eat. Chlamydial organisms can be isolated from the vagina and rectum of cats, but it is unclear whether venereal transmission occurs. Although there is circumstantial evidence that Chlamydia may cause abortion, there is no evidence of a link with gastro-intestinal disease.
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).
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).
The nature of the protective immune response to Chlamydia infection is uncertain. However cellular immune responses are believed to play a crucial role in protection (Longbottom & Livingstone, 2004). The MOMPs and POMPs are important targets for protective immune responses in other species (Longbottom & Livingstone, 2004) and have been shown to exist in the cat (Harley et al., 2007).
Direct detection methods
It is possible to identify infection by culture but PCR techniques are now the preferred option for diagnosing Chlamydia infection (EBM grade III). Such techniques are extremely sensitive and avoid problems with poor viability of the organisms. Ocular swabs are generally used as samples (Fig. 3), although a recent study did not find a significant difference in the ability to detect C. felis by PCR from ocular, oropharyngeal, nasal and tongue swabs, suggesting that other sampling sites can be used (Schulz et al., 2015). 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 cells. 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).
Other techniques for demonstrating the organism are less sensitive and less reliable than PCR. Chlamydial antigen tests based on detecting group specific antigen using ELISA or similar techniques are available. Also, conjunctival smears can be Giemsa-stained to check for inclusions, but chlamydial inclusions are easily confused with other basophilic inclusions (Streeten & Streeten,1985).
Indirect detection methods
In unvaccinated cats, antibody detection can confirm the diagnosis of C. felis infection. 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 are 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 Chlamydia may be an aetiological factor, whereas a low titre discounts likely chlamydial involvement.
Chlamydia infection in cats can be treated very effectively with antibiotics. Systemic antibiotics are more effective than local topical treatment (Sparkes et al., 1999). Tetracyclines are generally regarded as the antibiotics of choice for chlamydial infections (Déan 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. Recent studies have shown that treatment must be maintained for 4 weeks to ensure elimination of the organism (Déan et al., 2005). In some cats recrudescence may be noted some time after discontinuation of therapy. Continuation of treatment for two weeks after resolution of clinical signs is 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. Fluoroquinolones are effective against Chlamydia (Gerhardt et al., 2006; Hartmann et al., 2008), but a 4-week course of therapy with clavulanic acid potentiated amoxicillin may represent the safest choice in young kittens (Sturgess et al., 2001).
Both inactivated and modified live vaccines based on whole Chlamydia organism are available as part of multivalent vaccine preparations. Vaccines are effective in protecting against disease but not against infection (Wills et al., 1987). No reliable data are available to compare efficacy of inactivated versus modified live vaccines.
Vaccination should be considered for cats at risk of exposure to infection, particularly in multicat environments, and if there has been a previous history of Chlamydia infection.
Vaccination of kittens generally begins at 8-10 weeks of age with a second injection 3-4 weeks later. 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
Chlamydia 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.
In catteries with endemic Chlamydia 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 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 should only be vaccinated when it is deemed absolutely necessary, and then an inactivated vaccine should be used.
Azuma Y, Hirakawa H, Yamashita A, et al (2006): Genome sequence of the Cat Pathogen Chlamydia felis. DNA Res 13, 15-23.
Becker Y (1978): The chlamydia: molecular biology of procaryotic obligate parasites of encaryocytes. Microbiol Rev 42, 274-306.
Corsaro D, Venditti D, Valassina M. (2002): New parachlamydial 16S rDNA phylotypes detected in human clinical samples. Res Microbiol 153, 563-567.
Déan R, Harley R, Helps C, Caney S, Gruffydd-Jones T (2005): Use of quantitative real-time PCR to monitor the response of Chlamydia felis infection to doxycycline treatment. J Clin Microbiol 43, 1858-1864.
Di Francesco A, Piva S, Baldelliw R (2004): Prevalence of Chlamydia felis by PCR among healthy pet cats in Italy. The New Microbiologica 27, 199-202.
Everson JS, Garner SA, Lambden PR, Fane BA, Clarke IN (2003): Host range of chlamydiaphages phiCPAR 39 and Chp3. J Bacteriol 185, 6490-6492.
Fernandez M, Manzanilla EG, Lloret A et al (2016): Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydophila felis and Mycoplasma felis DNA and associated risk factors in cats in Spain with upper respiratory tract disease, conjunctivitis and/or gingivostomatitis. J Feline Med Surg DOI: 10.1177/1098612X16634387.
Gerhardt N, Schulz BS, Werckenthin C, Hartmann K (2006): Pharmacokinetics of enrofloxacin and its efficacy in comparison with doxycycline in the treatment of Chlamydia felis infection in cats with conjunctivitis. Vet Rec 159, 591-594.
Gunn-Moore DA, Werrett G, Harbour DA, Fielden H, Gruffydd-Jones TJ (1995): Prevalence of Chlamydia psittaci antibodies in healthy pet cats in Britain. Vet Rec 136, 366-367.
Halanova M, Sulinova Z, Cislakova L et al (2011): Chlamydophila felis in cats–are the stray cats dangerous source of infection? Zoonoses Public Hlth 58, 519-522.
Harley R, Herring A, Egan K, Howard P, Gruffydd-Jones TJ, Azuma Y, Shirai M, Helps C (2007): Molecular characteristics of 12 Chlamydia felis polymorphic membrane protein genes. Vet Microbiol 124, 230-238.
Hartley JC, Stevenson S, Robinson AJ, Littlewood JD, Carder C, Cartledge J, Clark C, Ridgway GL (2001): Conjunctivitis due to Chlamydia felis (Chlamydia psittaci feline pneumonitis agent) acquired from a cat: case report with molecular characterization of isolates from the patient and cat. J Infect 43, 7-11.
Hartmann AD, Helps CR, Lappin MR, Werckenthin C, Hartmann K (2008): Efficacy of pradofloxacin in cats with feline upper respiratory tract disease due to Chlamydia felis or Mycoplasma infections. J Vet Intern Med 22, 44-52.
Lang GH (1992): Prevalence of antibodies to Coxiella and Chlamydia spp. in cats in Ontario. Can Vet J 33, 134.
Longbottom D, Livingstone M (2004): Vaccination against chlamydial infections of man and animals. Vet J 17, 263-275.
McManus CM, Levy JK, Andersen LA, et al (2014): Prevalence of upper respiratory pathogens in four management models for unowned cats in the Southeast United States. Vet J 201, 196-201.
O’Dair HA, Hopper CD, Gruffydd-Jones TJ, Harbour DA, Waters L (1994): Clinical aspects of Chlamydia psittaci infection in cats infected with feline immunodeficiency virus. Vet Rec 134, 365-368.
Sachse K, Bavoil PM, Kaltenboeck B, Stephens RS, Kuo CC, Rosselló-Móra R, Horn M (2015): Emendation of the family Chlamydiaceae: Proposal of a single genus, Chlamydia, to include all currently recognized species. Syst Appl Microbiol 38, 99–103.
Schulz C, Hartmann K, Mueller RS et al (2015): Sampling sites for detection of feline herpesvirus-1, feline calicivirus and Chlamydia felis in cats with feline upper respiratory tract disease. J Feline Med Surg 17, 1012-1019.
Segarra S, Papasouliotis K, Helps C (2011): The in vitro effects of proxymetacaine, fluorescein, and fusidic acid on real-time PCR assays used for the diagnosis of Feline herpesvirus 1 and Chlamydophila felis infections. Vet Ophthalmol 14 Suppl 1: 5-8.
Sibitz C, Rudnay EC, Wabnegger L, et al (2011): Detection of Chlamydophila pneumoniae in cats with conjunctivitis. Vet Ophthalmol 14 Suppl 1: 67-74.
Sparkes AH, Caney SMA, Sturgess CP, Gruffydd-Jones TJ (1999): The clinical efficacy of topical and systemic therapy for the treatment of feline ocular chlamydiosis. J Feline Med Surg 1, 31-35.
Streeten BW, Streeten EA (1985): “Blue-body” epithelial cell inclusions in conjunctivitis. Ophthalmol 92, 575-579.
Sturgess CP, Gruffydd-Jones TJ, Harbour DA, Jones RL (2001): Controlled study of the efficacy of clavulanic acid-potentiated amoxycillin in the treatment of Chlamydia psittaci in cats. Vet Rec 149, 73-76.
Wills JM (1986): Chlamydial infection in the cat. PhD Thesis University of Bristol.
Wills JM, Gruffydd-Jones TJ, Richmond SJ, Gaskell RM, Bourne FJ (1987): Effect of vaccination on feline Chlamydia psittaci infection. Infect Immun 55, 2653-2657.
Wills JM, Howard PE, Gruffydd-Jones TJ, Wathes CM (1988): Prevalence of chlamydia psittaci in different cat populations in Britain. J Small Anim Pract 29, 337-339.
Wu SM, Huang SY, Xu MJ, et al (2013): Chlamydia felis exposure in companion dogs and cats in Lanzhou, China: a public health concern. BMC Vet Res 9, 104.