Infections and infestations affecting the nail
Eckart Haneke in Histopathology of the NailOnychopathology, 2017
Cryptococcus neoformans is a saprophyte basidiomycete found worldwide in soil and pigeon droppings. Cryptococcus gattii is mainly found in the tropics. It is an opportunistic yeast causing invasive infections mainly in immunodepressed individuals, such as HIV infection, high-dose corticosteroid therapy and advanced cancer,300 and after organ transplantation.301–303 Fever and meningitis not responding to antibacterial antibiotics are the main clinical presentations.304 However, skin and nail involvement occurs in 10%–15% of patients with systemic cryptococcosis and primary cutaneous cryptococcosis occasionally occurs in solid organ transplant recipients, but also in otherwise healthy individuals, particularly after a minor trauma.305–307 Cutaneous cryptococcosis of the great toe was observed to precede systemic disease for several months.308 In the hand, tenosynovitis and osteomyelitis were observed.309 Skin lesions are usually very variable and nonspecific.310,311 There was severe ulcerating paronychia in a case of a cryptococcus nail unit infection and a hemorrhagic whitlow in another immunocompetent patient.312–314
Diagnosis of Cryptococcosis
Johan A. Maertens, Kieren A. Marr in Diagnosis of Fungal Infections, 2007
Cryptococcus neoformans is an encapsulated yeast that can cause life-threatening infectious diseases in both apparently immunocompetent and immunocompromised hosts in all areas of the world. This pathogenic yeast consists of four serotypes (A, B, C, and D) based on capsular agglutination reactions and three varieties or subspecies (1). Serotype A strains have been named C. neoformans var. grubii, serotype B and C strains were classified as C. neoformans var. gattii and recently considered to be a separate species, Cryptococcus gattii, and serotype D strains were named C. neoformans var. neoformans (2,3). About 95% of cryptococcal infections are caused by serotype A strains, whereas 4% to 5% of infections are caused by either serotype D or serotype B and C strains, depending on geographical location.
Micafungin
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Micafungin lacks clinically meaningful activity against basidiomycetes, including Trichosporon, Crypto-coccus neoformans, and Cryptococcus gattii, even though they possess a beta-glucan synthase enzyme which is sensitive to echinocandin inhibition (Maligie and Selitrennikoff, 2005). The inherent resistance observed in these fungi is thought to be a result of compensatory stress response pathways (e.g., protein kinase C and calcineurin), multidrug efflux pumps, melanin, and/or drug degradation pathways (Maligie and Selitrennikoff, 2005). While scarce, a limited number of in vitro and animal model studies have demonstrated that micafungin in combination with amphotericin B or azole can be synergistic against Cryptococcus and Trichosporon asahii (Serena AAC 2005a, 2005b). However, micafungin monotherapy should not be considered a viable treatment option for infections caused by these species.
Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004–2018
Published in Infectious Diseases, 2021
Anne Toivonen, Mari Eriksson, Nathalie Friberg, Timo Hautala, Sohvi Kääriäinen, Jaana Leppäaho-Lakka, Janne Mikkola, Tuomas Nieminen, Jarmo Oksi, Juha H. Salonen, Pekka Suomalainen, Markku Vänttinen, Hanna Jarva, Annemarjut J. Jääskeläinen
Encapsulated Cryptococcus neoformans and Cryptococcus gattii are the most common cryptococcal opportunistic fungal pathogens in humans [1]. The majority of cryptococcal infections worldwide are caused by C. neoformans, which occurs in most temperate regions whereas C. gattii has been found mainly in tropical and subtropical geographic regions [1,2]. Cryptococcus is transmitted by inhalation of infectious cells followed by an infection of the respiratory system. The pulmonary infection may disseminate by haematogenous route and further affect the central nervous system (CNS) causing meningoencephalitis [1]. The infection may also manifest as cryptococcemia, though the most common clinical features are meningoencephalitis and pulmonary cryptococcosis [3]. Moreover, a disseminated cryptococcal infection associates with higher mortality compared to respiratory disease [4]. However, the variable nature of clinical presentations may delay the diagnosis.
Advances in the diagnosis of fungal pneumonias
Published in Expert Review of Respiratory Medicine, 2020
Bryan T. Kelly, Kelly M. Pennington, Andrew H. Limper
Aside from endemic fungi, Candida and Cryptococcus spp. are the most common yeast forms to cause invasive disease. Candida spp. is a very rare cause of pulmonary infection and more typically causes catheter-related bloodstream and deep-tissue infections. Cryptococcus neoformans and Cryptococcus gattii are the main pathogenic Cryptococcal species causing disease in humans. The primary route of infection is through the respiratory tract, and dissemination, particularly to the CNS, is common amongst immunocompromised hosts. Diagnosis of pulmonary Cryptococcosis may be challenging owing to the varying presentation, which may be mild or asymptomatic.
Highlights of the mini-symposium on extracellular vesicles in inter-organismal communication, held in Munich, Germany, August 2018
Published in Journal of Extracellular Vesicles, 2019
E. Bielska, P.R.J. Birch, A.H. Buck, C. Abreu-Goodger, R.W. Innes, H. Jin, M.W. Pfaffl, S. Robatzek, N. Regev-Rudzki, C. Tisserant, S. Wang, A. Weiberg
It has been shown previously that pathogenic fungi release EVs and they are used in cross-kingdom modulation of host cells. Cryptococcus gattii, an encapsulated yeast-like fungal pathogen of humans and other animals, releases EVs and similarly to its sibling species C. neoformans, uses them in inter-organismal communication. Studies presented by Dr Ewa Bielska from the University of Birmingham, UK, showed that EVs released by a deadly isolate from the Pacific Northwest outbreak of cryptococcosis are able to increase virulence of less pathogenic C. gattii isolates in vitro [31]. Fungal proteins and RNAs associated with these EVs can overtake and modulate fungal cells inside mammalian phagocytes, allowing them higher internal proliferation in macrophages. This phenomenon may be associated with the presence of heat shock proteins and pyruvate kinase inside C. gattii EVs, where both classes of proteins are protective against heat stress in fungi [32]. Indeed, fungal growth at 37°C can be further accelerated in the presence of the EVs. Pre-treatment of macrophages with the EVs also leads to the small but significant increase of the intracellular proliferation of the less pathogenic C. gattii isolate [31], which may be associated with reduced interferon γ levels release by white blood cells. Contradictory to studies performed in C. neoformans [33], EVs isolated from C. gattii do not enhance phagocytic activity of macrophages. Incorporation of the fungal EVs by mammalian white blood cells is based on several endocytic routes and can be blocked using inhibitors of endocytosis like latrunculin A, cytochalasin D or methyl-β-cyclodextrin. In vitro studies showed that the uptake of fungal EVs by macrophages might be very fast with a half time to peak internalization of 17.5 min and that within initial 15 min EVs can colocalize with phagocytosed yeasts in the phagosome [31].
Related Knowledge Centers
- Cryptococcosis
- Cryptococcus Neoformans
- Lymph Node
- Meningitis
- Phenotype
- Pneumonia
- Sexual Reproduction
- Yeast
- Teleomorph, Anamorph & Holomorph
- Hydrocephalus