Public Health Considerations and Potential Risk of Transmission to Humans
12.7.1 Cryptococcus Isolation from Synanthropic Rodents
Rodents play a pivotal role in the epidemiology of several fungal diseases. Although they usually inhabit wild environments, murid omnivores are well known for their association with humans (Guimaraes et al.
2014). Rodents enrich the soil via their excrement, thereby supporting the growth of geophilic fungi. Almost a century ago, Sangiorgi described the presence of Cryptococcus in the large mononuclear cells of the liver and spleen of a brown rat (Rattus norvegicus) (Sangiorgi 1922). During an investigation of histoplasmosis, Emmons et al. (1947) isolated Cryptococcus from mice and rats (Emmons et al. 1947). After a long gap, a wild black rat (R. rattus) trapped in Papua New Guinea was noted to have chronic, cystic pulmonary cryptococcosis (Scrimgeour and Purohit 1984). Naturally acquired cryptococcosis was again reported but, this time, in the greater bandicoot rat (B. indica) (Singh et al. 2007). Although pathological lesions were observed only in the liver and lungs, other organs such as the kidneys, spleen, and brain were found to be positive for C. neoformans var. grubii. Singh et al. (2007) additionally isolated C. neoformans var. grubii from bandicoot burrows and the surrounding bamboo debris. These findings suggest that B. indica acts as a sentinel species, potentially amplifying the pathogen in the environment, and it could serve as a possible vector of human cryptococcosis.Recently, a cluster of cases of cryptococcosis was observed in a synanthropic Southeastern Asian murid (Mus musculus castaneus) (Singh et al. 2017). Unlike bandicoot rats, no lesions were recorded in any organ of these animals. Interestingly, C. neoformans var. grubii was recovered from cultures of tissue homogenates of the brain, lungs, liver, and kidneys. The habitat soil and fresh feces of the animals were also positive for the fungus.
It is fascinating to note that, despite the presence of Cryptococcus in the central vein, neither the liver nor any other organs exhibited pathological signs. Apparently, the pathogen passes through the animal host without affecting it, and all isolates recovered from M. musculus were only weakly pathogenic to experimental mice. These findings define the status of M. musculus as a “passenger host” for C. neoformans var. grubii in a more appropriate manner. It is noteworthy that across the range of species studies, Cryptococcus yeasts have been isolated from apparently healthy rodents in most cases.Of note, rodents—considered household pests and nuisance animals—may act as a continuous source of infection for humans and their pets, and in this context, it is important to think about cats as the major predator of rodents in many such situations. While rodents, especially rats and mice, have expanded their geographic range dramatically and significantly extended the territory of the pathogens they harbor (Aplin et al. 2011), they might play a role in preventing human infections by acting as sentinels for the presence of Cryptococcus in the environment (Morera et al. 2014). On the basis of the degree of interaction between the host and harbored pathogens, rodents might act as natural reservoirs, alternate hosts, sentinel animals, carriers, or even passenger hosts. Pulmonary exposure of experimental rats and mice with C. neoformans remains subclinical and does not usually lead to overt disease despite widespread dissemination, while C. gattii strains produce progressive and ultimately fatal pneumonia with late dissemination to the meninges as the terminal event (Coelho et al. 2014; Zaragoza et al. 2007; Goldman et al. 1994, 2000; Krockenberger et al. 2010).
12.7.2 Zoonotic Potential
Both C. neoformans and C. gattii cause infection in humans and animals, and both are thought to be acquired from the environment rather than from infected hosts (Spickler 2013).
The feces of pet birds have been implicated as a possible source of C. neoformans infection in immunocompromised individuals. Case clusters of cryptococcosis tend to occur worldwide in individuals exposed to large quantities of bird guano (Muchmore et al. 1963; Procknow et al. 1965). There is no evidence, however, of an increased incidence of active cryptococcosis among these groups (Levitz 1991). Naturally acquired cryptococcosis occurs in both animals (wild and domestic) and humans, although no mammal-to-mammal transmission has been documented. A bird (magpie)-to-human transmission (Lagrou et al. 2005) and two possible cases of person-to-person transmission have been reported (Levitz 1991). The incidence of cryptococcal infection cannot be correlated with race or age. However, in certain situations, asymptomatic animals (koalas) have been found to contribute to the amplification of cryptococci in certain man-made environments and possibly in natural habitat as well (Malik et al. 1997; Krockenberger et al. 2002; Singh et al. 2007, 2017; Morera et al. 2014).12.8