Long-term surveillance and treatment of subclinical cryptococcosis and nasal colonization byCryptococcus neoformansandC. gattiispecies complex in captive koalas (Phascolarctes cinereus)

Abstract

Cryptococcosis is an important systemic mycosis caused by members of the Cryptococcus neoformans species complex. This disease is potentially fatal in various animals, including koalas. We describe the long-term surveillance and treatment of subclinical cryptococcosis and nasal colonization of koalas by Cryptococcus neoformans and C. gattii. Of the 15 animals investigated through the use of samples obtained by nasal swabs, antigen titer measurements, and pathologic examination, C. neoformans was found associated with nine koalas and C. gattii with one animal. Nine koalas showed subclinical disease and one clinical infections and antigenemia. Treatment with fluconazole, itraconazole and amphotericin B upon detection of C. neoformans or C. gattii was not effective. The results of the present study showed that C. neoformans was the predominant species isolated from the nasal swab samples and the fungus might have naturally become associated with the koalas' nasal cavities at Kanazawa Zoological Gardens. The unclear treatment effectiveness might have been caused by a shorter treatment period that is routinely used and unstable itraconazole absorption. This investigation also underscores the need for identifying effective treatment regimens for subclinical cryptococcosis and efficient measures for eradicating C. neoformans and C. gattii in koalas.

Global Molecular Epidemiology ofCryptococcus neoformansandCryptococcus gattii: An Atlas of the Molecular Types

“…Six percent of the isolates were recovered from the environment or from animals in Turkey, Israel, Iran, India, Nepal, China, Thailand, Malaysia, Taiwan, Republic of Korea, and Japan (Figure 3). In most of the environmental surveys, C. gattii was isolated from tree samples, namely, from Syzygium cumini , Mimusops elengi , Azadirachta indica , Acacia nilotica , Cassia fistola , Manikara hexandra , Polyalthia longifolia , Eucalyptus camaldulensis , Tamarindus indica , Cassia marginata , and Mangifera indica [32, 33, 177], while the only ten isolates from an animal source were recovered from koalas living in two different zoos in Japan [178, 179]. On the contrary, C. neoformans was prevalently isolated from pigeon and other birds excreta [180] and less frequently from trees such as Eucalyptus tree, Tamarindus arjuna , Tamarindus indica , Cassia fistola , Syzygium cumini , and Ficus religiosa [33, 177, 181, 182], as well as from some vegetables and fruit (tomato, carrot, banana, eggplant, papaya, apple, and guava) [183, 184].…”

Cryptococcus gattii Infections

“…Koalas are susceptible to invasive infection and may act as reservoir hosts for humans by amplifying the environmental burden of C. gattii (187,189). Of interest, in a recent Japanese study of 15 imported Australian koalas in a zoo in Yokohama, only 1 of 10 (66.7%) animals colonized with Cryptococcus was colonized with C. gattii (190). Koalas with invasive cryptococcosis most often present with pneumonia and meningoencephalitis, although nasal infection also occurs (187).…”

“…Koalas with invasive cryptococcosis most often present with pneumonia and meningoencephalitis, although nasal infection also occurs (187). Identification of C. gattii in asymptomatic koalas (188)(189)(190) has spawned studies of subclinical cryptococcosis, of the mechanisms that trigger clinical infection, and of the need for effective cryptococcal eradication measures to prevent the spread of infection.…”

“…It also poses a concern for veterinarians, and some animal infections, in particular those in feline and canine companion animals and Australian native koalas, represent sentinels for human exposure (37,176,188,190). Shifts in the appreciation of the clinical epidemiology of C. gattii in the past decade include the recognition that it affects immunocompromised (including those with HIV/AIDS) as well as immunocompetent (130)(131)(132)(133) hosts, the identification of multiple C. gattii molecular types (see Epidemiology, Origin, and Evolution, above) and their clinical implications, and the broadening of its geographic range beyond the tropical-subtropical locales of Northern Australia, Papua New Guinea (PNG), Southeast Asia, Africa, South America, and California (71) to the temperate regions of these and other countries (38,69,86,91,130,132,(196)(197)(198).…”

Review of some pharmacokinetic and pharmacodynamic properties of anti‐infective medicines administered to the koala (Phascolarctos cinereus)

“…Another study reported that 10 mg/kg, twice daily, p.o. as monotherapy, was inadequate for effective therapy (Kido et al., ). Thus, on the basis of clinical observations and in vivo studies (Black, Krockenberger, et al., ; Govendir et al., ), this group now recommends administration of oral FLC at 20–25 mg/kg, twice daily, p.o.…”