Cryptococcus neoformans is a major cause of fungal meningoencephalitis in immunocompromised patients. Despite recent advances in the genetics and molecular biology of C. neoformans, and improved techniques for molecular epidemiology, aspects of the ecology, population structure, and mode of reproduction of this environmental pathogen remain to be established. Application of recent insights into the life cycle of C. neoformans and its different ways of engaging in sexual reproduction under laboratory conditions has just begun to affect research on the ecology and epidemiology of this human pathogenic fungus. The melding of these disparate disciplines should yield rich dividends in our understanding of the evolution of microbial pathogens, providing insights relevant to diagnosis, treatment, and prevention.

The Biology of the Cryptococcus neoformans Species Complex

Cryptococcus neoformans var. neoformans was repeatedly isolated from decaying wood forming hollows in living trees growing in urban areas of Rio de Janeiro, Brazil. A new natural habitat for C. neoformans var. neoformans has been found that is not associated with specific trees.

/pdf/natural-habitat-of-cryptococcus-neoformans-var-neoformans-in-v9tv6ezx0z.pdf

Natural habitat of Cryptococcus neoformans var. neoformans in decaying wood forming hollows in living trees

(1992). Fungal infections in AIDS patients. Journal of Medical and Veterinary Mycology: Vol. 30, No. sup1, pp. 19-28.

Fungal infections in AIDS patients

Cryptococcus neoformans is an important zoopathogen, and it is one of the most prevalent lethal mycotic agents. Its polysaccharide capsule, synthesized in vivo and in vitro, is a virulence factor, contains predominantly glucuronoxylomannan, and is responsible for the antigenic differentiation of serotypes A, B, C, D, and AD. A total of 467 isolates of C. neoformans obtained from clinical and environmental sources from Brazilian regions were studied serologically by using the Crypto Check Iatron RM 304-K kit. Serotyping of the clinical isolates showed the following prevalences of the serotypes: A (77.95%), followed by B (18.2%), AD (1.3%), D (0.4%), C (0.2%), and untypeable (1.93%). The epidemiology of serotype A in the Brazilian southern and southeastern regions reproduces the picture observed worldwide. In contrast, serotype B was the most frequent agent of cryptococcosis in the northeastern region, occurring nearly equally in male and female healthy hosts. Among the isolates from environmental sources, serotypes A and B were found to occur in the hollows of tropical trees of the genera Cassia, Ficus, and Moquillea. The few isolates from Eucalyptus camaldulensis debris were serotypes A and B and untypeable. Overall, no association with a specific host tree was identified for these serotypes, denoting a distinct ecoepidemiological regional pattern. The one serotype C isolate was recovered from a human immunodeficiency virus-negative host. Serotype AD predominated over serotype D among both clinical and environmental isolates.

/pdf/serotyping-of-467-cryptococcus-neoformans-isolates-from-1ngfuc0gpc.pdf

Serotyping of 467 Cryptococcus neoformans Isolates from Clinical and Environmental Sources in Brazil: Analysis of Host and Regional Patterns

straliaCryptococcus neoformansis a basidiomycetous,yeast-like fungus which, following inhalation from anenvironmental source, causes respiratory and neurologicaldisease in humans and animals. Though the ecology ofC. neoformansis poorly understood, recent observationsprovide clues about its life-cycle in nature. Two biotypesof C. neoformansare recognised, C. neoformansvar. neo-formans (serotypes A, D, AD) and C. neoformansvar.gattii(serotypes B, C).C. neoformansvar. neoformans. This biotype hasbeen isolated from various sources in nature and is notedfor its association with accumulations of avian guano,especially pigeon excreta. It has also been isolated fromdroppings of caged birds including canaries, parrots andbudgerigars. Other environmental isolations have beenmade from rotting vegetables, wood, dairy products andsoil. The pigeon is unlikely to be the major source ofcryptococci in nature, since only low concentrations oforganisms are found in samples from the beak, crop, feetand rectal swabs [1]. The internal temperature of the birdis 42 °C, which is inhibitory to cryptococcal multiplica-tion; the high concentrations of ammonia in fresh drop-pings are also inhibitory to growth. In contrast, very highconcentrations of the yeast (asexual) form of the organismare found in weathered pigeon droppings, an environmentwhich is unfavourable to the growth of most other micro-organisms. The natural environmental niche of C. neofor-mansvar. neoformans has been predicted to be a plantspecies, based on the discovery by Ellis and Pfeiffer ofcertain species of eucalypt as the natural habitat of C. neo-formans var. gattii (see below, [2]). A recent report fromBrasil is of great interest in this regard [3]. C. neoformansvar. neoformans was consistently isolated from decayingwood in the hollows of several species of tree in suburbanRio de Janeiro. No specific association with a bird, animalor insect vector could be established.C. neoformansvar. gattii. This biotype has a morerestricted geographical distribution than C. neoformansvar. neoformans, causing human disease in climates ran-ging from temperate to tropical in Australia, Papua NewGuinea, parts of Africa, India, South-East Asia, Mexico,Brasil, Paraguay and Southern California [4,5]. The firstenvironmental isolation of the organism was made byEllis and Pfeiffer, in the Barossa Valley of SouthAustralia. These investigators established its specific eco-logical association with Eucalyptus camaldulensis, a spe-cies of red gum widely distributed in mainland Australia.Subsequently, another species of red gum, Eucalyptustereticornis, has been confirmed as a natural habitat. Highconcentrations of C. neoformansvar. gattiihave been iso-lated from single specimens of the related Eucalyptusrudis and an unrelated species, Eucalyptus gomphocepha-la (tuart) in the southwest of Western Australia. Three ofthese species (E. camaldulensis, E. tereticornis, E. gomp-hocephala) have been exported to several of the countriesin which human disease due to C. neoformansvar. gattiihas been reported though the association is not exact.Outside of Australia limited isolations of C. neoformansvar. gattiihave been made from eucalypts in Californiaand recently, in Apulia, Italy [6], but not in other coun-tries. In Australia, 92% of human isolates and all of thosefrom koalas (a native animal which feeds on the leaves ofE. camaldulensis and E. tereticornis) and host eucalypts,exhibit the same genetic fingerprint (VGI) when identifiedby random amplification of polymorphic DNA and PCR-fingerprinting [7], consistent with an epidemiologicalassociation between mammalian disease and exposure tohost eucalypts. The occurrence of disease in countriessuch as Malaysia which lack the host trees, and our ownobservation of a distinct genetic type (VGII) in certainlocations in Australia suggest that additional environmen-tal niches are yet to be discovered. The life cycle ofC. neoformansvar. gattiiin association with the trees isunknown. Since both varieties of C. neoformansgrowwell on water-agar containing sterilised eucalyptus leaves,the specificity of the association between C. neoformansvar. gattiiand the trees in nature may depend on aeucalypt-associated transport vector. For example, crypto-cocci may be transported to this niche by animals livingwithin a restricted range (e.g. koalas, which harbour theorganism in the web spaces of their claws and move atnight between trees), or across greater distances by windor eucalypt-using birds (consistent with a single moleculartype of C. neoformansvar. gattiibeing distributed widelyacross Australia). Highest concentrations of the organism(up to 1,000 cfu/g) are found in woody debris in hollowsof aged trees, where it is protected from the lethal effectof sunlight and from drying. C. neoformans can utilise thiswoody material, which is rich in polyphenol compoundsand lignin, as a substrate for growth, due to its phenol oxi-dase activity. Following their early observations that cryp-tococci were isolated from flowers, leaves and air aroundE. camaldulensistrees during the flowering season andthat fungal forms morphologically consistent with basi-diospores, were present in material from which large num-bers of cryptococci were cultured, Ellis and Pfeifferproposed that the life cycle of the fungus involves basi-diospore formation (presumably indicating that the sexualstate of the fungus exists in nature) and that dispersal ofthis potentially infectious propagule occurs during the flo-wering season [2]. However, cryptococcosis in humans inAustralia is not seasonal and the occurrence of high levelsof cryptococcoci in woody debris may indicate a primaryassociation with bark, as has been described for otherbasidiomycetes [8].

Ecology of Cryptococcus neoformans.

Cryptococcus neoformans var. neoformans was isolated from domestic dust in 54% of houses occupied or recently occupied by AIDS+ cryptococcosis patients and in 20% of control houses randomly chosen in Bujumbura, Burundi. It was not isolated from wards of similar patients in the University Hospital. This seems to prove that patients could not contaminate their own environment and that the presence of C. neoformans var. neoformans had another origin.In 40% of the cases, patients admitted contact with pigeons in the city and pigeon coops are frequently positive.We are convinced that the pigeon coops of the city play a part in the contamination of HIV+/AIDS patients; however, some patients denied any contact with pigeons and in these cases, the only possible source of contamination identified thus far is domestic dust, although the origin of the yeast remains unknown.

AIDS-associated cryptococcosis in Bujumbura, Burundi: an epidemiological study

La cryptococcose au cours du SIDA est tres frequente a Bujumbura: 12,7%. Les donnees clinique, biologique et therapeutique sont ensuite analysees. La cryptococcose est au Burundi une cause majeure de morbidite et de mortalite au cours du SIDA

La cryptococcose à Bujumbura (Burundi). A propos de 80 cas observés en 42 mois

Dans le cadre des manifestations centrales de l'infection au VIH, la cryptococcose a Cryptococcus neoformans (CN) est tres frequente au Burundi. Il s'agit d'une analyse retrospective de 80 patients admis de decembre 1983 a octobre 1985 (30 cas) et juin 1987 a decembre 1988 (50 cas) a l'hopital de Bujumbura. Tous les patients ont un SIDA

La cryptococcose à Bujumbura, Burundi: à propos de 80 cas observés en 42 mois

Cryptococcosis is a systemic fungal disease and meningeal or meningoencephalitis involvement is the most serious complication. This is a retrospective analysis of 80 patients admitted from December 1983 to October 1985 (30 cases) and June 1987 to December 1988 (50 cases) in hospital of Bujumbura, Burundi, Central Africa. All patients have an AIDS. Clinically, the meningeal and meningoencephalitis attack prevails in 87% cases. The diagnosis in our study is essentially based on the examination of the CRL. Before the new antifungals, the treatment involved the association of amphotericin B and 5-fluorocytosine, during 6 to 8 weeks. This treatment was badly tolerated and the second falls, when the therapy was stopped, were frequent. Presently, the fluconazole is the best treatment of this affection (ailment?): it enables maintenance therapy for a disease in which the risks of recurrence and reinfection by the environment are not negligible in Africa.

[Cryptococcosis in Bujumbura, Burundi. Apropos of 80 observed cases in 42 months].

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AIDS-associated cryptococcosis in Bujumbura, Burundi: an epidemiological study

La cryptococcose à Bujumbura (Burundi). A propos de 80 cas observés en 42 mois

La cryptococcose à Bujumbura, Burundi: à propos de 80 cas observés en 42 mois

[Cryptococcosis in Bujumbura, Burundi. Apropos of 80 observed cases in 42 months].