TREATMENT AND CONTROL
6.1 Treatment
The aim of treatment is to achieve a microbiological cure and eliminate clinical signs and discomfort. However, not all koalas are candidates for treatment. In most cases, animals with comorbidities, such as KoRV-associated disease, and those with chronic disease and in poor body condition are not suitable candidates.
At least in Qld and NSW, a substantial proportion of koalas with chlamydio- sis are euthanased because of the severity of their disease and associated poor prognosis. Chloramphenicol and doxycycline are currently the drugs of choice for treatment of chlamydiosis (Chen et al. 2023) (see Appendix 4). The efficacy and pharmacokinetics of several alternative antibiotics have been reported. Enrofloxacin and florfen- icol (Black et al. 2015) and marbofloxacin (Griffith et al. 2010) for chlamydial treatment in koalas have been investigated. Despite some clinical improvement, doses of fluoroquinolones and florfenicol do not reach therapeutic levels and may cause fatal dysbiosis (Griffith et al. 2010; Govendir et al. 2012; Budd et al. 2017). Novel compounds, such as a serine protease inhibitor (JO146), which binds to chlamydial putative virulence factor high temperature requirement A (HtrA), inhibiting its proteolytic activity, have also been proposed (Lawrence et al. 2016). The use of doxycycline long-acting injection (doxycycline hydrochloride 50 mg/mL, Psittavet Injection, Vetafarm, Wagga Wagga, NSW) at 5 mg/kg SC (diluted 50:50 with sterile water immediately before injection to reduce reaction at injection site) q 7 d for 4-6 wk has shown some promise. Results suggest it has good therapeutic effect, with clinical cure and negative qPCR at the end of a treatment course. Treatment is more successful in cases of conjunctivitis than cystitis. Due to the increased risk of side effects (primarily dysbiosis) after three injections of doxycycline, recommended treatment duration is no more than four doses, with only two in cases with low to moderate qPCR chlamydial loads or mild disease. Once weekly injections may be highly desirable in wild, anxious or aggressive animals (Booth and Nyari 2020; Chen et al. 2023).Koalas that are anxious and stressed when entering care have poorer outcomes and higher incidences of secondary complications when antimicrobial therapy is initiated immediately. Therefore, allowing these koalas time to settle into care (often 3-5 d) and establish stable eating patterns before commencing antimicrobial therapy can improve outcomes.
For chlamydial keratoconjunctivitis, combined systemic treatment and topical ophthalmic preparations are required (Blanshard and Bodley 2008). Surgical intervention is only warranted if tags of proliferative conjunctiva that are likely to impair vision remain at the completion of medical treatment. Koalas with persistent exudative build-up following treatment should have their nasolacrimal ducts examined for patency and flushed if blocked. Ducts can be flushed using a flexible 26G catheter and are best accessed through the nostril (duct located ventromedially deep within the nostril).
Injectable chloramphenicol is the preferred treatment of cystitis. Chlamydial DNA from mucosal urogenital and ocular swabs is generally undetectable on qPCR within 14 d of treatment, suggesting microbial cure (Markey et al. 2007; Robbins et al. 2018), though immune- mediated inflammation may persist beyond this time. To reduce side effects associated with treatment it is now recommended that koalas are treated for 14 d. Those with severe active disease (severe pyuria/renal infections) and high qPCR loads pre-treatment may require 21-28 d of chloramphenicol. The judicious use of analgesia is recommended (Table 35.1). In more severe cases, oral prednisolone provides adequate analgesia and reduces inflammation and fibrosis.
Chloramphenicol is also recommended for treating reproductive tract disease. Ovariohysterectomy (see Chapter 10) is warranted in cases of bilateral chronic structural change in the reproductive tract, as this is invariably associated with permanent infertility, persistence and progression of inflammation, fibrous adhesions and pain (Robbins et al.
2018). Koalas with associated chronic disease (e.g. advanced chlamydial cystitis or severe keratoconjunctivitis), poor body condition or aged individuals are not suitable surgical candidates. Individual state legislation should be consulted to determine if animals can be returned to the wild following surgery. In Qld, koalas treated for reproductive tract disease by ovariohysterectomy or other treatment may be released back to the wild at their point of capture if deemed otherwise physically fit for release by a veterinarian. Release at other locations requires prior approval by the Qld environment department (Wildlife and Threatened Species Operations 2023). Currently, no specific guidelines relating to this exist for other States.Table 35.1. Summary of commonly used treatment regimens for chlamydiosis in koalas (Phascolarctos cinereus)
| Condition | Treatment | Dose and duration | Comment |
| Keratoconjunctivitis | Dexamethasone1 eye drops | bid, 5-21 d (based on response) | Rapidly reduces conjunctival inflammation and proliferation |
| Chloramphenicol2,3 eye ointment (with or without hydrocortisone component) or ofloxacin4 drops | bid, tid, 14-21 d (based on response) | Adjunct to systemic antibiotics. Hydrocortisone reduces inflammation (use for severe proliferative inflammation) | |
| Chloramphenicol5 | 60 mg/kg SC sid, 14-28 d | Vary injection site each day | |
| Doxycycline8,9 | 5 mg/kg SC (diluted 50:50 with water for injection), q 7 d for 2-4 doses | Higher risk of fatal dysbiosis after third dose | |
| Cystitis | Chloramphenicol5 | 60 mg/kg SC sid, 14-28 d | Vary injection site each day |
| Prednisolone6 5mg/mL oral paediatric solution | Commence at 0.5 mg/kg PO sid if marked bladder wall thickening and dysuria/stranguria. Reduce to q 2 d after 3 doses, 5-14 doses | Gradually reduce over 5-10 d and discontinue if the patient becomes inappetent or develops GI candidiasis or elevated blood glucose above 8 mmol/L | |
| Paracetamol/paracetamol- codeine7 paediatric suspension | 15 mg/kg PO q 6-8 hr, duration as required | Avoid prolonged use of codeine | |
| Reproductive tract disease | Chloramphenicol5 Ovariohysterectomy | 60 mg/kg SC sid, 14-28 d Perform after 7-10 d of antibiotic therapy | Vary injection site each day Only if confirmed bilateral chronic disease |
1Maxidex 0.1% eye drops, Alcon Laboratories Pty Ltd, Frenchs Forest, NSW; 2Chlorsig 1% eye ointment, Sigma Pharmaceuticals Pty Ltd, Rowville, Vic.; 3Chloroptsone eye ointment, Ceva Animal Health Pty Ltd, Glenorie, NSW; 4Ocuflox® eye drops, Allergan Australian Pty Ltd, Gordon, NSW; 5Chloramphenicol 150 Injection, Ceva Animal Health, Glenorie, NSW; 6Redipred liquid, Aspen Pharmacare Australia Pty Ltd, St Leonards, NSW; 7Painstop for children, (Daytime), Care Pharmaceuticals Pty Ltd, Bondi Junction, NSW ; 8Booth and Nyari 2020; 9Chen etal. 2023.
6.2 Vaccination
Several studies on the development and/or application of chlamydial vaccines for koalas have been undertaken (Kol- lipara et al. 2012; Kollipara et al. 2013; Khan et al. 2014; Khan et al. 2016a; Khan et al. 2016b; Waugh et al. 2016a; Nyari et al. 2018; Nyari et al. 2019; Phillips et al. 2020; Quigley et al. 2023; Simpson et al. 2023). Koala vaccination offers an alternative management tool to reduce transmission and limit progression of chlamydial disease. Modelling has suggested that an effective chlamydial vaccine might be a valuable tool in the management of Chlamydia- infected koala populations (Craig et al.
2014). Using different vaccine combinations and delivery methods, it was demonstrated that healthy koalas can mount a strong and lasting immune response to vaccination with a chlamydial major outer membrane protein (MOMP)-based single or a multi-subunit vaccine derived from koala C. pecorum strains (Kollipara et al. 2013; Khan et al. 2016a; Khan et al. 2016b; Nyari et al. 2018; Quigley et al. 2023; Simpson et al. 2023). The vaccine was demonstrated to be safe to administer to both healthy and diseased koalas (Kollipara et al. 2012; Khan et al. 2016b). Although studies are ongoing, preliminary evidence suggests that vaccination may have some protective capacity to reduce the incidence of chlamydial disease in free-ranging koalas and improve clinical signs in koalas with chlamydial ocular and/or urogenital disease (Khan et al. 2014; Waugh et al. 2016b; Nyari et al. 2019; Phillips et al. 2020; Simpson et al. 2023).6.3 Biosecurity practices
Biosecurity practices ensure that chlamydia infected koalas (or those of unknown infection status) do not pose a risk to other koalas. This applies to zoos/fauna parks, wildlife hospitals, rehabilitation facilities, fieldwork and conservation translocations. Biosecurity practices include quarantine of incoming or outgoing animals, chlamydia screening, appropriate use of PPE, general hygiene, prophylactic treatment and disinfection practices (Wildlife Health Australia 2018; Vitali et al. 2023a, 2023b). Important practices for preventing transmission of Chlamydia from rehabilitation facilities to free-ranging koalas also include isolating animals from different locations while in care and releasing rehabilitated individuals at their location of origin (Casteriano et al. 2023; Vitali et al. 2023a, 2023b). These practices will also reduce the risk of the dissemination of novel Chlamydia genotypes. Decontamination practices have been shown to significantly reduce both chlamydial loads and pathogen viability in rehabilitation settings, however they cannot be assumed to completely remove the presence of infective chlamydial organisms.
Segregation of animals, staff and equipment is also necessary (Casteriano et al. 2023; Vitali et al. 2023a, 2023b). Specific decontamination procedures include physical removal of organic material through washing and scrubbing followed by chemical disinfection (using an appropriate disinfectant). This applies to but is not limited to koala transport containers and holding cages (including catch bags, using a clean bag for each koala, laundered in hot water), all catching equipment, examination tables, veterinary equipment and recovery crates/ baskets.6.4 Management of free-ranging Chlamydia-infected koala populations
There is some evidence for the efficacy of direct intervention in Chlamydia-infected and diseased free-ranging koala populations. Population-scale management of chlamydial disease requires that all or a significant proportion of koalas in the population are captured, subjected to thorough veterinary examinations and treated as necessary. Rigorous treatment and ongoing monitoring in such management programs may reverse koala population declines and restore population viability (Robbins et al. 2018). Using data from a well-studied koala population and an individual-based computer simulation model, it was predicted that if terminally diseased and sterile koalas are strategically euthanased, and other infected captured koalas are treated, chlamydial infection could be eliminated and population growth observed after 4 yr (Wilson et al. 2015). However, unless the target koala population is completely closed to immigration, it is unlikely that chlamydial infection will be eliminated from the population (Wilson et al. 2015; Hanger et al.
2016).
When conducting radio-tracking studies on koalas, an ethical dilemma arises if individual koalas affected by clinically significant chlamydial disease are located. Unless there is an explicitly stated and compelling need to avoid treatment of affected individuals, they should receive appropriate veterinary intervention, which in some cases may be euthanasia. An ‘explicitly stated or compelling need’ should be based on a clear objective of the scientific study that is sufficient to override the ethical imperative to provide treatment to an ill or suffering animal. Perhaps less compelling ethical obligations exist when the condition is mild or may be self-limiting, such as mild subclinical or low-grade cystitis and/or the access to suitable veterinary care/facilities is problematic. Regardless, the project plan should recognise and provide details on how sick koalas will be managed when they are encountered. Such planning requires veterinary input from those experienced in koala medicine and management and a critical analysis of the risks and benefits of each course of action.
Translocation of koalas has been suggested as a management option for declining northern koala populations (Waugh et al. 2016c). In a recent study in Qld, 11 koalas treated for either trauma and or chlamydial disease were translocated to suitable habitat without a resident koala population (locally extinct for >100 yr). All koalas were qPCR-negative at time of release and have remained clinically healthy and produced joeys (minimum monitoring period, 26 mo). However, in translocation trials of Chla- mydia-free koalas from French Is. to three forests near Ballarat, Vic., a high incidence of chlamydial infection was observed in translocated koalas within 6 mo of translocation, suggesting that movement of Chlamydia-free animals to areas where the status of the disease is unknown, or the movement of infected animals to other sites where koalas are present, should not be considered without detailed disease risk analysis (Santamaria and Schlagloth 2016). Thorough investigations of a range of factors, including infectious diseases present within donor and recipient populations, must be carefully considered when planning any wildlife translocation to ensure a successful outcome (Waugh et al. 2016c) (see Chapters 2 and 3).
ACKNOWLEDGEMENTS
We thank Danielle Madden for assistance with preparation of the chapter.