Cryptococcus neoformans: pathogenesis and spectrum of disease
المؤلف:
Patricia M. Tille, PhD, MLS(ASCP)
المصدر:
Bailey & Scotts Diagnostic Microbiology
الجزء والصفحة:
13th Edition , p773-774
2025-12-07
68
Genus Cryptococcus
Cryptocococcosis is an acute, subacute, or chronic fungal infection that has several manifestations. Crytococcus neoformans var. grubii, C. neoformans var. neofromans, and C. gatti are considered the major human pathogens. Differences in the infections by Cryptococcus neoformans appear to be dependent on the host immune status and not the variant. C. neoformans infections can present initially as a chronic or subacute pulmonary infection. C. neoformans eventually makes its way to the central nervous system, where the yeast can cause cryptococcal meningitis. Disseminated disease with meningitis is commonly seen in immunocompromised patients. Patients with a moderately compromised immune system or who are early in the disease process of cryptococcal fungemia may present without concomitant meningitis. Disseminated cryptococcosis and cryptococcal meningitis became well recognized in patients with acquired immunodeficiency syndrome (AIDS), and they remain an important cause of morbidity and mortality in these patients in resource poor countries that do not have access to highly active antiretroviral therapy.
Patients with disseminated infection may have painless papular skin lesions that may ulcerate. Other, less common manifestations of cryptococcosis include endocarditis, hepatitis, renal infection, and pleural effusion. Interestingly, a review of patient records at the Mayo Clinic revealed that more than 100 immunocompetent patients with C. neoformans colonization of the respiratory tract did not develop subsequent infection. Follow-up on these patients was as long as 6 years, and none in this group were considered to be immunocompromised. This makes the clinical significance of C. neoformans somewhat difficult to assess. However, given the severity of disease it can cause, its presence in clinical specimens should be considered significant. In many instances, the clinical symptoms are suppressed by corticosteroid therapy, which is a risk factor for disease, and culture or serologic evidence (detection of cryptococcal antigens) provides the earliest proof of infection. Cryptococcal infection is strongly associated with such debilitating diseases as leukemia and lymphoma and the immunosuppressive therapy that may be required for these and other underlying diseases. In some cases the presence of C. neoformans in clinical specimens precedes the symptoms of an underlying disease.
C. neoformans can exhibit a very characteristic polysaccharide capsule. The capsule collapses and protects the yeast from desiccation under drying conditions. The capsule of C. neoformans is thought to help the organism survive through the pigeon gut before it is excreted. The reduction in the yeast’s cell size caused by capsular collapse places the organism in the ideal size range for alveolar deposition in the human host. In addition, a virulent property of the polysaccharide capsule is that it contains compounds that phagocytes do not recognize. The so-called acapsular strains of C. neoformans, which actually just have a very reduced capsule, are more easily phagocytosed. In some instances, C. neoformans elicits minimal tissue response in infected individuals, particularly severely immunocompromised patients.
Phenoloxidase, an enzyme found in C. neoformans, is responsible for melanin production. Some have speculated that melanin might act as a virulence factor by making the organism resistant to leukocyte attack. Evidence also has been presented that increased melanin production can decrease immune system functions, such as lymphocyte proliferation and tumor necrosis factor production. Whether phenoloxidase is truly a virulence factor has yet to be determined (Li SS, et al, 2010. (Cryptococcus. 2010 Proc Am Thorac Soc Vol 7 pp 186-196, 2010). An interesting question is whether the interactions of substances in the brain that are known to react with phenoloxidase may play a role in the affinity of C. neoformans and certain neurotropic dematiaceous fungi for invading the central nervous system (Li et al, 2010).
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