Chlamydial epidemiology and therapeutics in south east Queensland koalas

Amy Robbins

doi:10.25907/00070

Koalas (Phascolarctos cinereus) were once common in eastern Australia but are now listed as ‘vulnerable to extinction’ in Queensland, New South Wales and the Australian Capital Territory. Some populations in those states have declined by up to 80% over the last two decades, primarily due to habitat degradation resulting from tree clearing and climate change. Remaining koala habitat is becoming increasingly fragmented, exacerbating the threats of trauma from dogs and cars, and importantly, disease. Localised extinctions are predicted unless interventions occur, and population management programs will be crucial to the survival of koalas in some regions. Chlamydia pecorum is an important koala pathogen as it is endemic in almost all populations and can significantly negatively impact koala health, welfare and population viability. Chlamydial infections cause inflammation and fibrosis at mucosal sites, predominantly in the eyes and urogenital tract, and can lead to blindness, infertility and death. Successful treatment is challenging as antimicrobial use can be fatal in koalas and chronic cases often respond poorly. There appear to be important differences in the susceptibility of individuals to Chlamydia creating a spectrum of disease manifestations and responses to treatment. However, despite the importance of this pathogen, our understanding of the factors that drive these clinical outcomes is limited. A thorough understanding of chlamydial epidemiology and a cost-effective, ‘best practice’ methodology for chlamydial treatment is necessary for the efficiency and success of management interventions. Comprehensive, longitudinal population studies could provide this understanding, however these studies are currently lacking. Consequently, this body of work analysed data from two south east Queensland (SE Qld) koala populations undergoing longitudinal monitoring and population management to determine why some koalas have severe clinical outcomes after infection with C. pecorum and during chlamydial treatment. The Moreton Bay population was a peri-urban/urban koala population in eastern SE Qld that included 503 koalas monitored over a period of four years, whereas the Old Hidden Vale population was a rural koala population in western SE Qld that included 34 koalas monitored over a period of two years. Specifically, chlamydial disease dynamics in each of these populations were characterised to investigate some of the factors that were important for disease progression. Chlamydial treatment regimens employed during the Moreton Bay management program were also analysed to develop standardised treatment guidelines that achieve optimal clinical outcomes. Utilising molecular diagnostics and comprehensive records compiled during regular clinical examinations and field monitoring events, well-defined clinical groups were characterised by identifying and following chlamydial infections over time. This unique approach revealed that, in contrast to the current paradigm, at least two thirds of chlamydial infections in koalas progressed to disease instead of remaining chronic and asymptomatic. Interestingly, 29% of koalas were able to resolve their infections, without progressing to disease. Finally, although chronic chlamydial exposure was associated with severe disease outcomes, it was not necessary for female infertility. An in-depth analysis of some of the host- and pathogen-associated factors that might be important for disease progression showed that koala immunogenetics and chlamydial strains had a more direct effect than subtype-specific koala retrovirus (KoRV) co-infections. Major histocompatibility complex (MHC) gene profiling indicated that disease progression in the urogenital tract was associated with specific MHC alleles. Koalas with DCb allele 03 were almost four times more likely to progress to disease, whereas koalas with DAb allele 10 were more than five times less likely to progress to disease. Chlamydial strain typing suggested that chlamydial strains varied in pathogenicity and were associated with tissue tropisms. Disease progression was associated with multi-locus sequence typing sequence type (ST) 69 and ompA genotype F in the urogenital tract and ompA genotype E´ in the eyes. Further, urogenital tract infection loads were associated with the chlamydial strain, and significantly higher infections loads were detected when infections progressed to disease or were recently acquired. Finally, genetically distinct ompA genotypes, but identical STs, were detected over time in long-term infections, suggesting that mixed genotype infections might be important for chlamydial strain microevolution. Analysis of the short- and long-term outcomes of chlamydial treatment identified a safe and effective antimicrobial treatment regimen that resulted in the release of over 94% of treated koalas. A 14 to 28-day course of chloramphenicol injections still achieved microbiological cure, despite being significantly shorter than previously published regimens. When this shorter regimen was combined with surgical treatment (ovariohysterectomy), infertile female koalas remained healthy for 466 days of post-treatment monitoring, demonstrating its benefits. The prompt detection and treatment of iatrogenic conditions and specialised nursing care were critical for treatment success, and the combination of oral transfaunation and fluid therapy reduced mortality rates for cases of oxalate nephrosis. Successful treatment did not, however, provide long-term ‘protection’, and koalas became reinfected less than 6 months after release. This body of work has significantly expanded our understanding of koala chlamydial epidemiology. It identified a subset of SE Qld koalas that appear to be more resistant to disease progression, as well as putative susceptibility and protective MHC variants, providing focus for research into advantageous immune phenotypes to assist with selective breeding programs and vaccine development. It revealed that chlamydial strains seem to vary in pathogenicity, highlighting the risks of poorly planned translocations and restoration of habitat connectivity to naïve koalas. Finally, it provided a safe and effective treatment regimen that improved outcomes while also reducing costs. These new insights into chlamydial disease progression and treatment not only maximise the benefit of invested resources, they inform management practices to improve population viability and koala welfare. Critically, this research demonstrated that an effective Chlamydia vaccine is important for the survival of declining populations threatened by chlamydial disease. Disease progression occurs more commonly in SE Qld than previously recognised, indicating that prompt detection of infections with point-of-care molecular diagnostics is necessary to allow veterinary interventions aimed at averting disease progression. Koalas can, however, develop infertility without chronic chlamydial exposure and successful treatment does not provide long-term protection against reinfection. A vaccine that improves immune responses, both reducing transmission and preventing pathology, is a key management tool that will improve conservation outcomes.

Chlamydial epidemiology and therapeutics in south east Queensland koalas

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