Background
Trichosporon are yeast-like anamorphic organisms that belong to the basidiomycetes yeasts. [1] Trichosporon yeasts are found worldwide, but most commonly in tropical and temperate regions such as South America, the Middle East, India, Southeast Asia, Africa, Europe, Japan, and parts of Southeastern United States. [2] Trichosporon spp are distributed mainly in soil, decomposing wood, water, foods, beetles, bird droppings, cattle, and bats. They can form part of the oral and gastrointestinal tract and transiently colonize the respiratory tract. They also may colonize the perianal and inguinal skin. [3]
Most Trichosporon spp are saprophytic, however some can be pathogenic and cause both superficial and invasive disease. [3] Historically this organism was known to cause white piedra, which is characterized by soft nodules along the hair shaft. The etiology of this disease was identified as Trichospron ovoides in 1890. Since then, several other species have been described. Trichosporon asahii is the most common species, followed by Trichosporon inkin, Trichosporon faecale, Trichosporon asteroides, and Trichosporon mucoides. [3, 4] T asahii, T mucoides, and T asteroides tend to cause invasive disease. T cutaneum, T ovoides, and T inkin all cause superficial infections of the skin, scalp and hair, and pubic hair, respectively. [3, 4, 5]
Although first identified as a superficial infection of the skin or hair, Trichosporon is an opportunistic pathogen capable of causing invasive disease in immunocompromised patients or those with invasive medical devices. Trichosporon can adhere to polystyrene on medical devices and subsequently form biofilms, hence the association with peritoneal, bladder, and central venous catheters. [4] Similar to Candida, Trichosporon can form biofilms, which are complex, organized structures consisting of dense microbial communities encased in a self-produced extracellular matrix composed mainly of polysaccharides, extracellular DNA, and secreted proteins. [4, 6, 7]
Invasive Trichosporon infections occur mostly in immunosuppressed patients, particularly those with hematological malignancies or AIDS. Unfortunately, diagnosing and treating invasive trichosporonosis can be challenging, and its global incidence is on the rise. [5]
Pathophysiology
Trichosporon species can harmlessly exist as commensals on the skin and in the gastrointestinal tract of healthy individuals, where they are monitored by the immune system and interact with the resident microbiome. [8] However, changes in the surrounding microenvironment can trigger their pathogenicity and result in clinically signficant disease. The pathophysiology of Trichosporonosis depends on whether the infection is superficial or invasive.
Superficial infection
The most common superficial Trichosporon infection is known as white piedra (piedra is the Spanish word for “stone”). In this condition, Trichosporin grows beneath the hair cuticle until a stone like nodule is formed which weakens the hair shaft resulting in breakage. Hair texture may be rough or broken as a result. White piedra may be confused with dandruff; however, dandruff appears as white flakes falling from the scalp, whereas white piedra are whitish tan nodules attached to the hair shaft itself. [9, 10]
Invasive infection
In general, invasive infection occurs as three possible syndromes; disseminated disease (the most common invasive disease presentation), invasive disease localized to a major organ (such as the bladder, lungs, or other organ), or an invasive infection that is related to a indwelling catheter. The pathophysiology of invasive Trichosporon infection involves several pathogen virulence factors and host risk factors which may determine which of these three syndromes develop.
Pertinent factors include the following:
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Enzymatic virulence factors: Enzyme products of Trichosporon include proteinases, lipases, and phospholipases, but the specific contribution of an individual enzyme to human disease remains unclear. Trichosporon spp produce phospholipases that disrupt host cell membranes by destruction of cell membrane proteins and lipids. [11] Cell wall components such as Glucuronoxylomannan (GXM) may confer a survival advantage as they have been shown to impair the phagocytic capability of neutrophils and monocytes. [2, 6]
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Immune evasion: The cell wall of Trichosporon contains a 1,3-linked mannose backbone similar to that of Cryptococcus neoformans that inhibits phagocytosis by macrophages in a murine model. [12]
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Biofilm production: Biofilm production by Trichosporon facilitates colonization of indwelling devices, permitting both adherence to prosthetic material and reduction of the fungus’s exposure and susceptibility to antifungal drugs. [13, 14, 15] Some species such as T asahii and T inkin can be highly tolerant to amphotericin B, and produce persistent cells in the biofilm despite treatment with amphotericin B. [2, 4]
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Phenotypic switching: Trichosporin are physiologically complex and adaptable, able to survive in a variety of environmental and host niches including the skin, gut, and oral mucosa. Similar to the dimorphic fungi, T asahii can grow as a budding yeast or have filamentous growth, forming septate hyphae with arthroconidia and blastoconidia. [11] They are metabolically flexible and able to utilize a large variety of carbon and nitrogen sources. [8]
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Host risk factors: In most cases of severe disease, multiple host risk factors favor the development of tissue invasion. Chemotherapy used to treat hematologic malignancies can cause neutropenia and mucosal disruption allowing yeast to invade beyond their normal musocal surface sites. Patients with hematologic malignancies are the most common host for invasive trichosporonosis. These include patients with acute myeloid leukemia (AML), followed by acute lymphoid leukemia (ALL) and myelodysplastic syndrome (MDS).
Trichosporon peritonitis is described in association with peritoneal dialysis catheters and related to the combination of disrupted barrier immunity and immune dysfunction seen in end-stage renal disease. [16] This invasion of mucosal barriers appears to be followed by vascular invasion and dissemination to other sites. Occasionally, Trichosporon infections are limited to a single organ system (eg, the lungs), but scattered visceral lesions similar to those observed in hepatosplenic candidiasis also can occur, often in patients who are recovering from neutropenia and cannot clear the infection. [5]
Epidemiology
Frequency
Trichosporon infections are rare, even among patients with impaired host defenses.
Overall the number of cases of Trichosporon spp has grown. One systematic review noted a 74% increase in the number of invasive disease due to Trichosporon spp between 2005 to 2015 compared with 1994 to 2004. [5] Trichsporon spp causes invasive disease and deep-seated infections predominantly in immunocompromised hosts. Immunocompetent hosts usually present with superficial infections of the skin/hair or summer-type hypersensitivity pneumonitis. [4]
Corticosteroid use, solid tumors, HIV/AIDS, and intravascular devices, including catheters and prosthetic heart valves, [17] are other major risk factors. In one retrospective series, trichosporonosis (including B capitatus infections) developed in only 0.9% of patients with acute leukemia. [18] In another review of yeast bloodstream infection in patients with cancer at a major referral center, Trichosporon was identified in only 8 of 2,984 isolates (0.27%). Hematologic malignancy is the best-described risk factor. [19]
Despite the small number of cases, B capitatus may have a geographic predilection for Europe, with most reported cases arising there (especially in Spain and Italy).
T asahii may be a more common cause of breakthrough fungemia in neutropenic patients from Japan than other regions, [20] and this organism is the cause of summer-type hypersensitivity pneumonitis, a condition reported exclusively in Japan. [21, 22]
Mortality/Morbidity
The mortality rate of acute disseminated trichosporonosis previously has been documented at between 50% and 80% in most case series. [23, 24, 25] Other series have reported mortality rates of 40-50% in patients with invasive disease. [26, 27]
Benelli et al reviewed a series of 10 cases with severe COVID-19 who also developed invasive Trichosporonosis. Most of these cases were found in South America and the Middle East, and all required systemic steroids and mechanical ventilation. Outcomes in this group were fairly poor; all but one patient died. [28]
Sex
Trichosporonosis is much more common in males, with a 2:1 male-to-female predominance reported in multiple series. [24, 29]
Age
Invasive disease has been noted among all age groups, but most commonly adults between ages 40 to 50 years. [5, 26]
Diseases that confer susceptibility to Trichosporon infections are most prevalent in adults, with a median age of 44 years in one report. [24]
A small number of neonatal and pediatric invasive Trichosporon infections have been reported, including nosocomial outbreaks within neonatal intensive care units. [5, 30, 31]
Tables
Host Factors |
Clinical features |
Microbiologic criteria |
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