Epidemiology of fungal infections in China

Abstract

With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillus fumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country’s health.

Keywords

fungi / infection / epidemiology / China

Introduction

Fungi are eukaryotic organisms found throughout nature. They emerged about 1.6 million years ago and serve the important function of returning the nutrients removed by plants to the soil [1]. Historically, fungi are major pathogens of plants, rotifers, insects, and amphibians, with a relative few causing infections in humans. However, human modification of natural environments has intensified the dispersal of fungal infections [2]. Global warming has also augmented the prevalence of fungal infections in mammals by its selection of adaptive thermo-tolerant fungal species possessing significant pathogenic potential despite their current nonpathogenicity due to being restricted by mammalian temperatures [3]. To date, approximately 400 fungal species have been reported to be pathogenic to humans, with emerging pathogenic fungal species recorded annually [4].

The patterns of fungal infections are diverse and vary worldwide depending on the fungal species, host immune status, and infection site. For example, superficial fungal infections (SFIs), such as tinea capitis, are closely related to host lifestyle and socioeconomic conditions [5–7], whereas invasive fungal infections (IFIs), such as candidemia, are closely linked to host immune status and fungal species [8]. Since the 1950s, SFIs have steadily declined in incidence globally, especially in fast-developing countries, such as China, because of improving sanitary conditions [6,7]. By contrast, IFIs have been recognized as an increasing major threat to human health because of the growing prevalence of immunocompromised populations in recent decades [8]. For example, the human immunodeficiency virus (HIV) epidemic in Uganda has dramatically increased the incidence of IFIs that were once considered rare, such as cryptococcosis and disseminated histoplasmosis [9–11].

China, one of the largest countries in the world, is located at the western part of the Pacific Ocean. This country is rich in diversity of geographical environments and microorganisms. As the nation with the world’s largest population (1400 million people), China has also reportedly steadily increased in the number of immunocompromised hosts [12,13]. A retrospective research based on single-center autopsy data (3447 cases) in China indicated that the prevalence of IFIs has risen steadily for decades [13]. The drastic socioeconomic lifestyle transformation among Chinese people may have altered the epidemiological characteristics of fungal infections in the country. Nonetheless, epidemiological data on fungal infections in China remain scarce. In the present research, we systematically reviewed the epidemiological data on fungal infections across China to obtain the epidemiological profiles and trends of Chinese fungal infections.

Superficial fungal infections

SFIs are fungal infections limited to the outermost layers of the skin and appendages. These infections are believed to affect approximately 25% of the world’s population [5,6,14]. SFIs can be classified by infection site, for example tinea corporis, tinea pedis, tinea cruris, tinea manuum, onychomycosis, tinea capitis, and tinea faciei. The chief causative agents of SFIs are dermatophytes and yeasts. Dermatophytes are a group of filamentous fungi that infect keratin-rich tissues, such as the skin. The geographic distribution of dermatophytes is variable [5,6]. Currently, Trichophyton rubrum, Trichophyton interdigitale, Trichophyton tonsurans, and Microsporum canis are the major dermatophyte species globally [15]. Meanwhile, Malassezia spp. and Candida spp. are the principal yeast pathogens that cause SFIs [5,6]. To date, the majority of epidemiological studies on SFIs in China were conducted in separate disease categories or segmental regions [7]. Consequently, the epidemiological profile of SFIs in China remains thin and fragmented. In this portion of our research, we sought to summarize the epidemiological data on SFIs in China, particularly tinea capitis and onychomycosis.

Previous studies demonstrated that the patterns of SFIs and their chief causative agents vary across the many different geographical regions of China. Tinea corporis and tinea cruris (53.4%; 1682/3152) are the most prevalent types of SFIs in Northern China [16], whereas onychomycosis is the most prevalent in Eastern (55.2%; 5277/9566) and Southern China (28.6%; 199/697) [17,18]. Notably, tinea faciei is the most frequent SFI in Southern China among patients aged below 22 years (median age of 9 years). In Central China, tinea corporis (32.4%; 67/207) is the most prevalent type of SFI, and T. rubrum (50.7%; 34/67) is the predominant fungal pathogen [19]. In Northwestern and Northeastern China, tinea pedis (33.1%, 471/1422; 20.0%, 164/818, respectively) is the most prevalent type of SFI, and T. rubrum is again the predominant fungal pathogen [20,21]. In Southwestern China, tinea cruris (30.1%; 385/1279) is the most prevalent type of SFI, and T. rubrum is the predominant fungal pathogen [22].

In summary, dermatophytes, such as T. rubrum, remain as the most common fungal pathogens causing SFIs, especially onychomycosis, tinea pedis, and tinea cruris, in the majority of China. Similar observations were described by investigators in Brazil, America, Sweden, and France [23–26]. Tinea pedis is also the most prevalent type of SFI in Northern China, a finding compatible with previous epidemiological studies from Singapore [27].

Tinea capitis

Tinea capitis, an infection of scalp hair follicles and the surrounding skin caused mainly by dermatophyte fungi [28], is the most common SFI among children of school age, especially in developing countries [7]. From the 1950s through the 1960s, hyperendemic favus, generally a severe form of tinea capitis, was dominant in some provinces of China, such as Hubei, Jiangsu, and Jiangxi [7]. For example, in 1965, the prevalence of favus in Jiangxi reached 3410 per 100 000 [29]. However, after a prevention and treatment project for tinea capitis was initiated successfully in the 1960s, the incidence of favus decreased significantly, down from 1160 per 100 000 in the 1970s to below 1 per 100 000 in the 2000s [7,30–32]. Over time, the prevalence of tinea capitis gradually resurged in some regions of China. For example, in Shanghai, the number of tinea capitis cases increased from 25 cases in 1993 to 105 cases in 2001 [32]. These changes in incidence were probably related to the changing lifestyles of the population. Although finding a nationwide epidemiologic study on tinea capitis in China is difficult, a recent review suggested that anthropophilic fungi overwhelmed the zoophiles across vast regions of China before 1985 and that the dominant species nationwide was T. schoenleinii despite the variability of endemic species across different geographic regions [7]. Notably, the predominant etiology switched from T. schoenleinii to T. violaceum in Europe during 1963–1993, whereas the zoophile M. canis increased dramatically since 2000 [33]. Similarly, a shift of etiological agents from anthroponoses to zoonoses also occurred in contemporary China. Pets became the most likely sources of tinea capitis in modern society, replacing the earlier human-to-human transmission mode [7]. The details are provided in Fig. 1.

Onychomycosis

Onychomycosis is a chronic fungal infection involving the nails, nail bed, nail plate, and matrix. This infection is responsible for almost 50% of all nail diseases [34]. In 2015, Wang et al. reported that the dominant form of onychomycosis in China is distal lateral subungual onychomycosis (DLSO: 54%; 531/978), followed by total dystrophy (TD: 24%; 237/978), superficial white onychomycosis (SWO: 16%; 155/978), and proximal subungual onychomycosis (PSO: 6%; 55/978) [35]. The details are provided in Fig. 2. The global prevalence of onychomycosis was estimated to be 5.5% [36], but no accurate data exist about the incidence rate of onychomycosis in China. Onychomycosis can be caused by dermatophytes, non-dermatophyte molds, or yeasts. In China, the pathogenic fungi that cause onychomycosis were found to be most commonly composed of dermatophytes (84.0%; 672/800), followed by yeasts (11.4%; 91/800) and non-dermatophyte molds (4.6%; 37/800) [35]. These observations are consistent with those of some previous reports [6,34,37]. Among the dermatophyte species, T. rubrum was dominant (80.9%; 647/800) [35]. These observations are compatible with previous epidemiological studies from China and other countries, such as India and Italy [34,37–40], but different from the findings in Greece, Iran, and Brazil, where yeasts were the predominant agents of onychomycosis [41–43]. These differences may be attributed to the geography, regional climate, or population migration, among other factors, in the regions studied [38]. C.glabrata was the most frequently found pathogenic yeasts (16.8%; 135/805) in Guangdong Province [44]. Increasing reports of onychomycosis in China have also implicated a new yeast pathogen as a causative agent. For example, our team reported the first case of onychomycosis caused by Rhodotorula minuta in an immunocompetent girl in 2013 [45]. A nationwide epidemiology survey on onychomycosis in China is needed in the future.

Invasive fungal infections

Invasive fungal infections (IFIs) are opportunistic fungal pathogens that infect deep solid organs and/or the bloodstream mainly in immunocompromised patients, such as those with prolonged neutropenia or cancer [8,46]. IFIs are caused primarily by Candida spp., Aspergillus spp., Cryptococcus spp., and others, all of which are distributed universally in the environment [8,47–49]. In general, the epidemiological profile of IFIs is characterized by geographical and temporal variability, with different incidence rates and new emergence incidents revealed over the past 20 years [50]. Notably, two separate single-center autopsy studies conducted in the 2000s showed that the incidence of IFIs increased steadily over time [51,52]. Until recently, the epidemiology of IFIs in China was poorly understood because of insufficient and inaccurate data. Epidemiological studies on IFIs were reported mainly in numerous, separate case studies, and most of these studies were written in Chinese [53,54]. Consequently, information about the epidemiology of IFIs in China remains limited. In the following sections, we summarize the epidemiological data of IFIs in China with focus on the five main IFIs caused by Candida, Aspergillus, Cryptococcus, Mucorales, and Pneumocystis species.

Invasive candidiasis (IC)

Candida species are important nosocomial yeast pathogens that cause IC, including candidemia. These pathogens may be disseminated to internal organs [8,55,56]. The mortality rates can reach 35%–80% among immunocompromised and other seriously ill patients [57–60], a finding that is similar to the mortality rates reported by several studies (36.6%–60%) of IC in China [56,61–64]. Risk factors for IC include the extensive use of invasive procedures and devices, broad-spectrum antimicrobial agents, advanced life support, and aggressive chemotherapy [62,65]. Improved detection may also have raised the reported number of cases. The risk factors for Chinese patients infected with IC [56] are similar to the factors found by studies of patients from Spain and Canada [66,67], except for some unique risk factors. One such factor was IC caused by Candida albicans commonly found in patients with subclavian vein catheters or peritoneal drainage tubes [61]. The details are provided in Fig. 3.

For the past two decades, the incidence of candidemia doubled and currently ranks as the fourth and sixth most common nosocomial bloodstream infection in American and European studies, respectively [68,69]. Notably, the incidence of IC in intensive care units was 0.32% (32 per 1000 admissions) in a multicenter prospective observational study in China from November 2009 to April 2011. This rate was consistent with the global incidence rates of 0.03%–0.5% in hospital-based studies [59].

Although C. albicans remains the most common etiological agent worldwide, Candida species other than C. albicans have been encountered more often than previously reported [8,64,70–76]. In some countries, these species account for increased number of episodes of IC, including candidemia, relative to C. albicans [50,56,77–79]. In China, C. albicans (40.1%; 156/389) also remains the most common causative agent of IC in recent decades, followed by C. parapsilosis (21.3%; 83/389), C. tropicalis (17.2%; 67/389), C. glabrata (12.9%; 50/389), C. krusei (2%; 1/389), and others (8.2%; 32/389) [56,61,78,80,81]. These findings differ slightly from the results based on data of ARTEMIS DISK Global Antifungal Surveillance Program, associated with China from 1997 to 2007, which showed that C. tropicalis was the second most common Candida species found in IC patients within the Asia-Pacific regions, including China’s Taiwan [71,82,83]. Moreover, C. parapsilosis was the most common Candida isolates from blood in China (33.2%; 107/322) [78].

Significant geographical differences exist in the distribution of Candida species involved in IC worldwide. Similarly, variations are present in the distribution among different geographic regions in China [62,84–89]. In general, C. albicans is the strain most commonly isolated from candidemia in China, particularly in Southern China, but C. tropicalis (28.6%; 38/133) is the most common cause of candidemia in Nanjing [62,84–89].

Recently, uncommon Candida species, such as C. guilliermondii, C. rugosa, C. quercitrusa, and C. auris, have emerged worldwide, including in China [90–93]. For example, C. guilliermondii has been recently reported to cause candidemia in Taibei, Shanghai, and Nanjing and has been proven to be more resistant to both fluconazole (FLU) and voriconazole (VRC) in the Asia-Pacific region than in other regions [62,71,94,95]. More recently, C. auris emerged globally as a nosocomial pathogen, which is the multidrug-resistant yeast that exhibits resistance to FLU and shows a markedly variable susceptibility to other azoles, including amphotericin B (AMB) and echinocandins [93,96–98]. To date, IC caused by C. auris remains unreported in China, but this new yeast pathogen has been found recently in India and Oman and hence must still be monitored by mycologists [99,100].

In China, the majority of studies on the antifungal susceptibility patterns of Candida spp.-associated IC were defined partially in specific regions and/or particular populations [80,86,101–103]. Consequently, results reflecting the distribution and the associated antifungal susceptibility patterns of Candida species frequently differed among these studies. Because many non-albicans Candida spp. are resistant or mildly susceptible to antifungal agents [90–92], the timely and continuous determination of the antifungal susceptibility patterns of these yeasts is required. In the multicenter nationwide China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study, most (>94%) of the isolates of C. albicans, C. tropicalis, and C. parapsilosis were susceptible to FLU and VRC, although such susceptibility varied with the species [78]. Again, this result was consistent with those of other studies, such as the ARTEMIS DISK Global Antifungal Surveillance Program [56,66,72,87,104]. Notably, 12.2% of the C. glabrata isolates were FLU resistant, and 17.8% exhibited a non-wild-type susceptibility to VRC [78].

The China Survey of Candidiasis reported a widespread resistance to itraconazole (ITC) [56]. Only 0.6% C. albicans showed susceptibility to ITC, and 96.0% of C. glabrata were ITC resistant. No resistance to caspofungin (CFG) was identified in any Candida strain isolated from China [56]. Regarding ketoconazole (KTC), the resistance rate was particularly high in Candida spp. (61.9%), and almost all isolates were resistant to KTC [62]. AMB and 5-flucytosine (5-FC) remained close to 100% effective against common Candida spp. in China, except for C. krusei and C. guilliermondii (which were only 20% and 71.4% susceptible to 5-FC, respectively) [72,85]. Notably, the resistance to FLU and VRC of Candida species other than C. albicans in elderly patients was approximately double that of younger patients (30.6% vs. 15.1% and 8.3% vs. 3.8%, respectively). However, the distribution of Candida species did not differ between the elderly and younger patients in China [86].

In conclusion, C. albicans remains the most common causative agent of IC in China, whereas the number of cases of IC caused by other Candida species has increased in the last decade. C. parapsilosis is the most common pathogen causing candidemia, but with geographical variation in China. FLU and VRC demonstrated good activity against C. albicans, C. parapsilosis, and C. tropicalis but not against C. glabrata. Cross-resistance to both azoles was noted in C. glabrata and in uncommon Candida strains, such as C. auris. Continued surveillance of IC in China is warranted. Details are shown in Fig. 3.

Invasive aspergillosis

Invasive aspergillosis (IA) is a serious opportunistic infection that mainly affects immunocompromised patients, with an extremely high mortality rate ranging between 40% and 90% [105,106]. Inevitably, people inhale Aspergillus spores or conidia daily; these particles can induce the occurrence of the following four main types of IA: invasive pulmonary aspergillosis (IPA), chronic necrotizing aspergillosis (CNA), allergic bronchopulmonary aspergillosis (ABPA), and aspergilloma [107]. Approximately 60 000 IA cases per year occurred in Europe, whereas more than 160 000 IA patients per year were estimated to have occurred in China, suggesting a heavy burden [108].

In China, the most dominant pattern of aspergillosis is IPA (approximately 15%), followed by ABPA (approximately 4%), CNA (approximately 3%), and aspergilloma (approximately 1%) [107]. IPA is the most severe type of pulmonary aspergillosis, with a high mortality in immunocompromised individuals (39%–100%), especially in patients with malignant hematological disorders, such as neutropenia, or who have undergone hematopoietic stem cell transplantation (HSCT) [109–111]. The mortality rate of IPA in China is similar to the rates found in various countries of Europe, including Italy [50,112].

Previous studies revealed that the overall IA infection rate in China ranged from 0.29%–14% depending on different underlying diseases or conditions [13,110,111,113]. Overall, this rate is similar to the rates exhibited in other countries, such as Italy (0.2%; 13/5561), and in Europe (6.9%; 127/1850) [50,112]. In addition, the lung (71.9%; 1047/1457) is the most frequent site of aspergillosis infection in China [53], followed by sinus infection (18.7%; 273/1457), eye infection (5.0%; 72/1457), and others (4.4%; 64/1457), all of which is consistent with reports from other nations [106,114]. However, the proportion of lung infections in China was lower than noted in an international, multicenter observational study in which lung infections accounted for 94% of the cases [114].

Currently, more than 30 Aspergillus species have been implicated in IA, the most common are the following: A. fumigatus, A. flavus, A. niger, A. terreus, and A. nidulans [115]. In China, A. fumigatus was the most commonly isolated Aspergillus species (59.3%; 153/258), followed by A. flavus (27.5%; 71/258), A. niger (5.8%; 15/258), A. terreus (2%; 5/258), A. sydowii (2%; 5/258), and others (3.4%; 9/258) [53]. These preponderance levels are higher than those found by an Italian study, where A. fumigatus accounted for 41.7% (5/12) [50], but lower than those in an international, multicenter observational study and a European study, where A. fumigatus accounted for 92.2% (519/563) and 96.1% (98/102), respectively [112,114].

The occurrence of IA caused by Aspergillus species other than A. fumigatus has increased in China recently [53]. For example, Li et al. reported an elevated number of IA cases caused by A. niger and A. tubingensis, the main black Aspergillus species present in clinical and environmental samples in China [116]. Wang et al. also found that for patients with HBV-related liver failure, the number of IPA occurrences caused by A. flavus (37.9%; 25/66 cases) was greater than that attributed to A. fumigatus (27.3%; 18/66 cases) [117].

Since 1997, azole-resistant A. fumigatus has been widely identified in clinical isolates from all over the world [118]. Currently, most A. fumigatus azole-resistant strains have been associated with mutations of cyp51A, followed by TR34/L98H and TR46/Y121F/T289A mutations [118]. In 2011, the ARTEMIS DISK Global Antifungal Surveillance Program first reported that the TR34/L98H mutation can be found in A. fumigatus isolates collected in China [115]. Subsequently, Liu et al. found that the TR34/L98H mutation (or isolates containing the S297T/F495I mutation) remains the predominant mutation in China and is fairly common in Europe and some other Asian countries [118,119]. Studies in China found that mutations in A. fumigatus isolates were the TR34/L98H/S297T/F495I mutation, TR34/L98H mutation, G432A, M220I mutation, and TR46/Y121F/T289A mutation [115,118,120,121]. At present, azole-resistant A. fumigatus has spread mainly across Southeastern and Northern China [108]. Until recently, no infection caused by A. fumigatus in China has developed the TR/L98H mutation under pressure of triazole therapy, which has proposed that the increase in frequency of this particular mutation in clinical isolates from the Netherlands is driven by the use of azole compounds as fungicides in agricultural practice [115].

In summary, the incidence of IA in China has increased over the past 20 years, with new emerging Aspergillus species and azole-resistant A. fumigatus. The lung is the most frequent site of IA in China. Molecular methods are essential for the identification of uncommon Aspergillus pathogens, such as azole-resistant Aspergillus species, in China. Further nationwide surveillance of IA is needed in China.

Cryptococcosis

Cryptococcosis is a life-threatening infection afflicting both immunosuppressed and immunocompetent individuals, which is caused primarily by two sibling basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii [122]. In general, C. neoformans and C. gattii have been further subdivided into several genotypes, such as VN I – VN IV genotypes in C. neoformans and VG I – VG IV genotypes in C. gattii [12,123,124]. Recent phylogenetic tools have improved our understanding of molecular epidemiological cryptococcosis. In 2009, multilocus sequence typing (MLST) was recommended by the International Society of Human and Animal Mycoses as the preferred method for typing cryptococcal strains [125]. According to research based on the MLST analysis of 305 Chinese clinical C. neoformans isolates, sequence type 5 (ST 5) was the predominant sequence type (89.2%) in C. neoformans isolates, followed by ST 31 (6.2%) [126]. The predominance of ST 5 genotype in Chinese clinical C. neoformans isolates was also reported by Dou et al. (94.9%; 75/79) and Wu et al. (82.9%; 34/41) [127]. Actually, ST 5 is the major sequence type in C. neoformans isolates from East Asian countries where cryptococcal data were available, including China, Japan, and South Korea [128–130]. However, in Thailand, ST 4 and ST 6 were found to be the major MLST types, whereas ST 93 was dominant in India and Indonesia [128,131]. Recent MLST analysis has indicated that the evolutionary origin of C. neoformans var. grubii in Thailand is in Africa [131]. The C. neoformans var. grubii in China was of the same low molecular diversity as the C. neoformans var. grubii in Thailand. Thus, the C. neoformans var. grubii in China may have the same evolutionary origin followed by a global expansion and is potentially vector transmitted by avian migration.

In China, cryptococcosis caused by C. gattii has been reportedly increasing mostly in patients living in subtropical and tropical regions [132,133]. VG I genotype strains were predominant in Chinese C. gattii isolates, whereas the VG IIb genotype strain has been reported in recent studies [134]. The C. gattii isolates from China may be distantly related to the highly virulent strain (VG IIa genotype) that caused the outbreaks of cryptococcal infection in western North America. In 2010, the VG IIa genotype strain was reported to have caused infections in Japan, which is adjacent to China [135]. This observation suggests that the VG IIa genotype strain has spread already to the Asia Pacific as a result of international travel and commerce and animal migration. Xue et al. [132] stated that if a greater number of laboratories undertook MLST analysis, more cases of C. gattii would be diagnosed.

Although an accurate incidence rate of cryptococcosis in China is unavailable, the number of reported cryptococcosis cases in China has increased gradually over the past two decades [12]. A recent survey of invasive yeast infections has indicated that cryptococcosis has become the second most common invasive yeast infection (7.7%) in China [78]. Moreover, meningitis is the most frequent meningoencephalitis in cryptococcosis in China. According to the latest literature review of cryptococcosis in Chinese mailand (1985–2010), central nervous system (CNS) infections occurred in 83.4% (7315/8769) of cryptococcosis patients [136]. A high CNS prevalence involving cryptococcosis was also reported in China’s Taiwan (58.9%) and Hong Kong (67.4%) [137,138]. Cryptococcosis is an opportunistic fungal infection because it occurs mainly in immunocompromised populations, such as patients with AIDS, organ transplant recipients, and patients with autoimmune diseases. Notably, a significantly high proportion of cryptococcosis cases have been reported in immunocompetent individuals in China [139–141], which might be the result of a predisposition in the ethnic Chinese population [142]. However, in accordance with a recent meta-analysis of cryptococcosis in China based on 8769 cases in 1032 reports, only 17% of the cases were without identifiable underlying diseases [136]. Therefore, a large-scale epidemiological study is necessary for further understanding of cryptococcosis in China.

Research on environmental Cryptococcus strains has been relatively lacking in China. Existing research is either limited in geographic area [143] or lacking the application of the latest molecular typing techniques [144]. Soil enriched with pigeon excreta, decaying wood, and tree detritus such as Eucalyptus species and Laurus species are ecological niches for C. neoformans and C. gattii, respectively [144]. Our research group has already isolated C. gattii from eucalyptus trees in Yunnan Province (unpublished data). Further high-density sampling of the environmental strain of Cryptococcus is needed.

Until today, our understanding on the epidemiological features of Cryptococcus and cryptococcosis in China was mainly based on single-center retrospective studies, which cannot reflect the overall prevalence and fungal burden of cryptococcosis in China. The large numbers of reported cryptococcosis in immunocompetent patients but low numbers in immunocompromised hosts in China warrant re-evaluation. Thus, an effective nationwide surveillance of cryptococcosis in China is necessary.

Mucormycosis

Mucormycosis (previously called zygomycosis) is an opportunistic infection caused by fungi belonging to the order Mucorales and the family Mucoraceae [145,146]. Rhizopus, Mucor, and Lichtheimia (formerly Absidia) are the most common genera that cause mucormycosis [147]. With the augmented size of immunocompromised populations, the prevalence of mucormycosis has also increased annually.

In places such as California and Spain, the annual incidence of mucormycosis was 0.43–1.7 cases per 1 million individuals [148–150]. By contrast, the morbidity in China is unclear. A review conducted in 2016 found that the prevalence of diabetes combined with mucormycosis increased in Chinese mainland from 10 cases before 2000 to 28 cases in 2010–2016 [151]. Several researchers reported that the overall mortality rate was 29.4% (126/428)–40.8% (40/98) [151–153], which is similar to the rate reported by non-Chinese sources. For example, the rate for Europe ranged from 23.5% (125/531) to 54.3% (504/929) [145,154,155]. The most frequent pathogen of mucormycosis in China is Mucor spp. (54.3%; 19/35), followed by Rhizopus spp. (28.6%; 10/35) [152]. These statistics vary from the findings in Europe, where Rhizopus spp. accounted for 33.7% (58/172), Mucor spp. accounted for 19.2% (33/172), and Lichtheimia spp. accounted for 18.6% (32/172) [145].

According to one report external to China [147], the variability of susceptibility to AMB, along with resistance to most other conventional antifungal agents, leads to high mortality. Currently, no large sample studies in China conducted the antifungal susceptibility testing of Mucorales.

Because mucormycosis is an opportunistic infectious disease, patients with underlying diseases are more likely to be infected than healthy individuals [151]. Internationally, mucormycosis is most common in patients with malignant tumors, diabetes, or organ transplants [154]. However, in China, this disease is more common in patients with diabetes, HIV infection, and viral hepatitis and in individuals who are long-term steroid or immunosuppressant users [152]. The close connection of mucormycosis with diabetes is worth noting because China has seen a rising burden of diabetes (92.4 million adults above the age of 20 years) [156].

In China, mucormycosis has occurred mainly on the coast and in humid areas [152]. The most common sites of infection are pulmonary (36.5%; 27/74), followed by rhinocerebral (32.4%; 24/74), skin (10.8%; 8/74), intracranial (6.8%; 5/74), and others (13.5%; 10/74) [151]. This finding is similar to the observations in Europe [145] but differs from the results of an international review that reported the sinus area as the most common site (39%; 359/929) [154].

To date, epidemiological data for this type of mucormycosis are scant in China. Most reports about mucormycosis lack evidence of molecular biological diagnosis. Additional effort should be exerted to identify species by molecular biology, and antifungal susceptibility testing is needed. Mucormycosis and diabetes are closely related; thus, attention must be focused on preventing and controlling diabetes.

Pneumocystis pneumonia

Pneumocystis pneumonia (PCP) is a potentially fatal pulmonary infection that occurs in immunocompromised individuals, especially in AIDS patients with a low CD4 cell count (below 200/mm³) [157,158]. PCP in humans is only caused by Pneumocystis jirovecii, which has recently been reclassified as fungal species [159–163]. Given the widespread use of PCP prophylaxis and highly active antiretroviral therapy, the incidence of PCP has declined significantly in developed countries [164].

However, PCP remains a common opportunistic infection in HIV-infected patients in developing countries, including China [165–167]. The earliest HIV/AIDS-associated PCP case in China was reported in 1985 [167]. From 1985 to 2009, the number of PCP patients afflicted by HIV/AIDS increased dramatically in China, apparently 70.2% (1646/2344) of which were identified along with HIV infection [167]. PCP also affects other immunocompromised patients [168]. In China, the prevalence of P. jirovecii colonization in patients with chronic pulmonary diseases is apparently 63.3% (62/98), which is higher than previous reports in North Lebanon (17.3%; 4/23) and Iran (7.9%; 7/89) [169]. However, the incidence of PCP in China is rare among HIV-positive and HIV-negative hosts because all performed epidemiological studies on PCP in China were retrospective studies [170].

The mortality of PCP is diverse among different studies in the world, including China. A retrospective study in Beijing showed that mortality (15.2% vs. 12.4%) did not significantly differ between the PCP cases of HIV-positive and HIV-negative populations [171], which differ from studies in Beijing. Moreover, the mortality of non-HIV–PCP (30%–60%) in other countries, such as Japan, is higher than that of HIV–PCP (11.3%–20%) [157,172–174]. The difference in mortality may be associated with the different genetic backgrounds of P. jirovecii and anti-PCP treatment strategy.

Although trimethoprim (TMP)–sulfamethoxazole (SMX) remains the first-line agent for PCP [170], mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of P. jirovecii with resistance to TMP and SMX, respectively, have progressively emerged [170]. Currently, the prevalence of P. jirovecii DHPS and DHFR mutations in HIV-positive patients in China remains low, which is similar to that in other developing countries [175]. Approximately 60% of P. jirovecii isolates harbor nucleotide mutations in the DHFR gene in China. The majority (>90%) of these mutations were synonymous, similar to the data reported in Japan and Thailand [175–177]. Meanwhile, the prevalence of P. jirovecii DHPS mutations in China was 12.0% (3/25) [175], which is similar to those reported from other developing countries, such as South Africa (3.8%; 2/53) [178], but lower than those determined from developed countries, such as the United States (40%; 58/145) [179].

In summary, the epidemiological data on PCP are limited in China to date, although the above-mentioned retrospective studies suggested that the epidemiological characteristics of PCP in China are similar to those in other developing countries. A prospective epidemiological survey focused on PCP in China is needed.

Endemic fungal infections

Sporotrichosis

Sporotrichosis is a subcutaneous mycosis caused by several Sporothrix species, namely, S. brasiliensis, S. globosa, S. mexicana, and S. luriei, besides the classical species S. schenckii [180]. Sporotrichosis is globally distributed, but Sporothrix species have shown high degrees of endemicity [180]. Given the data in existing literature, the most endemic regions are China (3299 cases), South Africa (3154 cases), and Brazil (5814 cases) [181]. In China, since sporotrichosis was first found in 1916 [182], the disease has existed nationwide but has been observed mainly in Northeastern China, including Jilin Province, Heilongjiang Province, and Liaoning Province [180,183]. S. globosa exhibits a global distribution with nearly identical genotypes, and this species is the only pathogenic Sporothrix species that has been reported to date in China [180,183–186]. Such pattern is similar to those found in India and Spain [181].

Although the transmission mode of sporotrichosis remains unclear, trauma may be strongly implicated. Contact with decaying plant material was frequently noted in S. globosa and S. schenckii, whereas S. brasiliensis was significantly associated with transmission by cats [181]. Relative immune impairment and underlying metabolic diseases are important risk factors for sporotrichosis [180].

Sporotrichosis presents as the following three main clinical types: lymphocutaneous, fixed cutaneous, and multifocal or disseminated cutaneous sporotrichosis [187]. Globally, the most common clinical form is lymphocutaneous sporotrichosis, but in China, the fixed cutaneous form is prevalent, followed by the lymphocutaneous form [180,181,187,188]. Classically, sporotrichosis occurs in temperate and subtropical climates of relatively high humidity. By contrast, the climate is relatively cold in the hyperendemic area of Northeastern China, where S. globosa is prevalent [181].

As the number of immunocompromised patients rises, the epidemiological monitoring of sporotrichosis is increasingly needed, and research is necessary to indicate whether S. schenckii or other Sporothrix species exist in China. Additional protective measures should be undertaken to avoid infection during agricultural activities.

Penicilliosis

Penicilliosis is a deep fungal infection caused mainly by the dimorphic fungus Talaromyces marneffei (formerly known as Penicillium marneffei), a species endemic to Southeast Asia, including some districts in China (e.g., Guangdong, Guangxi, Yunnan, Fujian, Yunnan, and Hong Kong) [189–191]. The organism was discovered in 1956 in bamboo rats [192], and the first natural human case of infection was reported in 1973 [193]. In China, the first case of T. marneffei infection was noted in 1984 [194]. After the 1990s, with the prevalence of AIDS in Southeast Asia, the number of patients with T. marneffei infection increased rapidly in this area, including Chinese mainland [195,196]. More than 87% of the number of reported T. marneffei infections was noted with HIV infection in China [196], and nearly 16% of the patients with AIDS were infected with T. marneffei in Guangxi [197]. To date, more than 600 cases of T. marneffei infection have been identified in China, with 82% of the cases reported in Guangxi and Guangdong [196,198]. The mortality of T. marneffei infection is higher in patients without antifungal therapy (50.6%; 45/89) than in patients with antifungal therapy (24.3%; 138/569) [196]. Cao et al. confirmed that the T. marneffei isolates from humans are similar to those from infected bamboo rats, and in some cases, the isolates are identical, which parallel the data from Thailand and India [197,199,200]. Although the potential sources of infection are rodent species, particularly bamboo rats, the transmission route of T. marneffei to humans remains a mystery [197]. In recent years, T. marneffei infection has increasingly impacted immunocompromised patients in Southern China, especially individuals with HIV/AIDS [196]. Additional studies should be conducted to determine the transmission route of T. marneffei, and raised attention should be paid to immunocompromised patients, especially those in endemic areas.

Histoplasmosis

Histoplasmosis, caused by the soil-based dimorphic fungus Histoplasma capsulatum, is a common endemic mycosis in midwestern United States and in Central America [201]. However, sporadic cases of autochthonous histoplasmosis have been encountered in China, a region traditionally considered non-endemic for H. capsulatum [202]. The first case of histoplasmosis in China was reported in 1958 in an individual returning from the USA [203]. Since 1990, 300 cases of histoplasmosis have been reported in China, of which only 17 cases were potentially imported cases [204]. The majority of these cases (75.0%; 225/300) occurred in nine provinces and regions traversed by the Yangtze River. Among these regions, Yunnan Province accounted for more than 27.7% (83/300) of the reported cases of histoplasmosis [204]. Pan et al. found that Chinese H. capsulatum isolates may have originated from Australia or other continents, such as North America [202].

Underlying diseases associated with histoplasmosis include HIV infection (22.0%; 38/173), diabetes mellitus (10.4%; 18/173), and liver diseases (7.5%; 13/173). Diabetes and malignancy are common in patients with pulmonary infection, but HIV-infected patients are prone to systemic dissemination. This information suggests that the clinical spectrum of histoplasmosis depends on the underlying host immune status [204]. Although histoplasmosis may prefer infecting individuals with underlying illness, research demonstrated that 49.1% (85/173) of patients lack an identifiable underlying disease [204].

At the time of our research, the epidemiology and ecology of H. capsulatum in China were unknown. As international travel becomes increasingly accessible, H. capsulatum may progressively spread globally from China or other endemic countries. A further detailed epidemiologic investigation of H. capsulatum is worthwhile.

Coccidioidomycosis

Coccidioidomycosis (CM) is a deep mycotic infection endemic to the Americas [205]. Although China is not a known endemic area for CM, the number of case reports of CM has risen [206]. Since 1958 when the first case was reported, 30 CM cases, of which 27 cases were from Southern China, have been recorded in China. Risk factors for infection include residence in or travel to a CM-endemic region, occupations with high exposure risk, immunocompromising conditions, or other underlying diseases [206]. However, the majority of Chinese patients (80.0%; 24/30) presented with no history of exposure to CM-endemic areas [206]. Since CM has been reported rarely in China, the possible local sources of CM in such region or in other countries remain uncertain.

Rare fungal infections

With the development of molecular diagnosis approaches, the number of case reports on fungal infections caused by rare fungal species has been increasing in China since 2000 [45,207–219]. For example, Pan et al. reported a case of meningitis caused by azole- and FLU-resistant Filobasidium uniguttulatum in 2012 [211]. Chen et al. also published the first case of a fungus ball (Penicillium capsulatum) in the left lung of a patient with type 2 diabetes [214]. Fungal infections caused by newly reported species should be monitored in China in the future. The details are provided in Table 1.

Conclusions

We systematically reviewed the epidemiological data of fungal infections across China to understand the related epidemiological profiles and trends. Our analysis demonstrated that the overall incidence of SFIs in China was stable. The overall incidence of IFIs in China continued to increase in both immunocompromised and immunocompetent individuals, with rising numbers caused by Candida species besides C.albicans, azole-resistant A. fumigatus, and Cryptococcus species. Moreover, epidemiological studies on mucormycosis and Pneumocystis are scarce in China. As regards the endemic fungal infections in China, sporotrichosis, penicilliosis, and histoplasmosis showed obvious regional distribution characteristics with raised number of cases. In addition, the occurrence of fungal infections caused by rare fungal species has augmented in China during the last decade. Considering these findings, we conclude that a nationwide epidemiological research focused on fungal infections in China is direly needed.

References

[1] Wang DY, Kumar  S, Hedges SB. Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi. Proc Biol Sci 1999; 266(1415): 163–171

[2] Fisher MC, Henk  DA, Briggs CJ, Brownstein JS, Madoff  LC, McCraw SL,  Gurr SJ. Emerging fungal threats to animal, plant and ecosystem health. Nature 2012; 484(7393): 186–194

[3] Garcia-Solache MA, Casadevall  A. Global warming will bring new fungal diseases for mammals. MBio 2010; 1(1): e00061-10

[4] Taylor LH, Latham  SM, Woolhouse ME. Risk factors for human disease emergence. Philos Trans R Soc Lond B Biol Sci 2001; 356(1411): 983–989

[5] Kaushik N, Pujalte  GG, Reese ST. Superficial fungal infections. Prim Care 2015; 42(4): 501–516

[6] Ameen M. Epidemiology of superficial fungal infections. Clin Dermatol 2010; 28(2): 197–201

[7] Zhan P, Li  D, Wang C,  Sun J, Geng  C, Xiong Z,  Seyedmousavi S,  Liu W, de Hoog  GS. Epidemiological changes in tinea capitis over the sixty years of economic growth in China. Med Mycol 2015; 53(7): 691–698

[8] Miceli MH, Díaz  JA, Lee SA. Emerging opportunistic yeast infections. Lancet Infect Dis 2011; 11(2): 142–151

[9] Adams P. Cryptococcal meningitis: a blind spot in curbing AIDS. Lancet 2016; 387(10028): 1605–1606

[10] Bahr NC, Sarosi  GA, Meya DB,  Bohjanen PR,  Richer SM,  Swartzentruber S,  Halupnick R,  Jarrett D,  Wheat LJ,  Boulware DR. Seroprevalence of histoplasmosis in Kampala, Uganda. Med Mycol 2016; 54(3): 295–300

[11] Parkes-Ratanshi R, Achan  B, Kwizera R,  Kambugu A,  Meya D, Denning  DW. Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them? Mycoses 2015; 58(Suppl 5): 85–93

[12] Wu SX, Guo  NR, Li XF,  Liao WQ,  Chen M, Zhang  QQ, Li CY,  Li RY, Bulmer  GS, Li DM,  Xi LY, Lu  S, Liu B,  Zheng YC,  Ran YP, Kuan  YZ. Human pathogenic fungi in China—emerging trends from ongoing national survey for 1986, 1996, and 2006. Mycopathologia 2011; 171(6): 387–393

[13] Liao Y, Chen  M, Hartmann T,  Yang RY,  Liao WQ. Epidemiology of opportunistic invasive fungal infections in China: review of literature. Chin Med J (Engl) 2013; 126(2): 361–368

[14] Havlickova B, Czaika  VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses 2008; 51(Suppl 4): 2–15

[15] Zhan P, Liu  W. The changing face of dermatophytic infections worldwide. Mycopathologia 2017; 182(1-2): 77–86

[16] Li GZ, Liu  YH, Chen XW. Etiologic analysis of 4000 cases of superficial mycosis in Tianjin region. China J Lepr Skin Dis (Zhongguo Ma Feng Pi Fu Bing Za Zhi) 2010; 26(8): 602 (in Chinese) 

[17] Cai W, Lu  C, Li X,  Zhang J,  Zhan P, Xi  L, Sun J,  Yu X. Epidemiology of superficial fungal infections in Guangdong, Southern China: a retrospective study from 2004 to 2014. Mycopathologia 2016; 181(5-6): 387–395

[18] Zhu JH, Han  DM, Zhao Y,  Li L, Zhang  QQ. Etiologic analysis of 9566 cases of superficial mycosis in Shanghai region. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2016; 11(3): 178–180 (in Chinese)

[19] LI LN. Zhang SM, Liu HW, Gao L, Lei DC, Li ZL, Yu HQ, Li JG. Analysis of superficial mycoses and pathogenic fungi in 668 cases. Chin J Derm Venereol (Zhongguo Pi Fu Xing Bing Xue Za Zhi) 2016; 30(3): 259–260 (in Chinese)

[20] Ma XN, Zhang  H, Han XH,  Wang HD,  Shi LQ, Ren  Y. Clinical analysis of 1422 cases of superficial mycoses in Yan’an Area. Chin J Derm Venereol (Zhongguo Pi Fu Xing Bing Xue Za Zhi) 2016; 30(9): 908–910 (in Chinese)

[21] Xu W, Li  Y. Clinical analysis of 818 cases of superficial mycosis. Guide China Med (Zhongguo Yi Yao Zhi Nan) 2010; 8(13): 131–132 (in Chinese) 

[22] Xiong Y, Zhou  CJ, Li QJ,  Huang XY,  Huang YH,  Zhong BY,  Tang SQ,  Dai W, Hao  F. Etiologic analysis of 2135 cases of superficial mycosis in Chongqing region. J Clin Dermatol (Lin Chuang Pi Fu Ke Za Zhi) 2008; 37(11): 711–713 (in Chinese)

[23] Silva-Rocha WP, de Azevedo  MF, Chaves GM. Epidemiology and fungal species distribution of superficial mycoses in Northeast Brazil. J Mycol Med 2017; 27(1): 57–64

[24] Foster KW, Ghannoum  MA, Elewski BE. Epidemiologic surveillance of cutaneous fungal infection in the United States from 1999 to 2002. J Am Acad Dermatol 2004; 50(5): 748–752

[25] Drakensjö IT, Chryssanthou  E. Epidemiology of dermatophyte infections in Stockholm, Sweden: a retrospective study from 2005-2009. Med Mycol 2011; 49(5): 484–488

[26] Simonnet C, Berger  F, Gantier JC. Epidemiology of superficial fungal diseases in French Guiana: a three-year retrospective analysis. Med Mycol 2011; 49(6): 608–611

[27] Tan HH. Superficial fungal infections seen at the National Skin Centre, Singapore. Nihon Ishinkin Gakkai Zasshi 2005; 46(2): 77–80

[28] Fuller LC, Barton  RC, Mohd Mustapa MF, Proudfoot LE,  Punjabi SP,  Higgins EM. British Association of Dermatologists’ guidelines for the management of tinea capitis 2014. Br J Dermatol 2014; 171(3): 454–463

[29] Zhan P, Geng  C, Li Z,  Jin Y, Jiang  Q, Tao L,  Luo Y, Xiong  Z, Wu S,  Li D, Liu  W, de Hoog GS. Evolution of tinea capitis in the Nanchang area, Southern China: a 50-year survey (1965–2014). Mycoses 2015; 58(5): 261–266

[30] Liu ZS, Fu  XQ, Xie SW, Wang Y,  Sun JB. Analysis of situation of tinea capitis in Hubei from 1995 to 2000. China J Lepr Skin Dis (Zhongguo Ma Feng Pi Fu Bing Za Zhi) 2003; 14(4): 54–55 (in Chinese)

[31] Yu J, Li  R, Bulmer G. Current topics of tinea capitis in China. Nihon Ishinkin Gakkai Zasshi 2005; 46(2): 61–66

[32] Zhu M, Li  L, Wang J,  Zhang C,  Kang K, Zhang  Q. Tinea capitis in Southeastern China: a 16-year survey. Mycopathologia 2010; 169(4): 235–239

[33] Korstanje MJ, Staats  CG. Tinea capitis in Northwestern Europe 1963–1993: etiologic agents and their changing prevalence. Int J Dermatol 1994; 33(8): 548–549

[34] Sigurgeirsson B, Baran  R. The prevalence of onychomycosis in the global population: a literature study. J Eur Acad Dermatol Venereol 2014; 28(11): 1480–1491

[35] Wang AP, Yu  J, Wan Z,  Li FQ, Zeng  JS, Liu WD,  Zhang QQ,  Hao F, Ran  YP, Xi LY,  Lai W, Li  RY. Multi-center epidemiological survey of pathogenic fungi of onychomycosis in China. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2015; 10(4): 197–202 (in Chinese)

[36] Gupta AK, Versteeg  SG, Shear NH. Onychomycosis in the 21st century: an update on diagnosis, epidemiology, and treatment. J Cutan Med Surg 2017 Jun 1 [Epub ahead of print]

[37] Papini M, Piraccini  BM, Difonzo E,  Brunoro A. Epidemiology of onychomycosis in Italy: prevalence data and risk factor identification. Mycoses 2015; 58(11): 659–664

[38] Ribeiro CS, Zaitz  C, Framil VM,  Ottoboni TS,  Tonoli MS,  Ribeiro RP. Descriptive study of onychomycosis in a hospital in São Paulo. Braz J Microbiol 2015; 46(2): 485–492

[39] Gupta C, Jongman  M, Das S,  Snehaa K,  Bhattacharya SN,  Seyedmousavi S,  van Diepeningen AD. Genotyping and in vitro antifungal susceptibility testing of fusarium isolates from onychomycosis in India. Mycopathologia 2016; 181(7-8): 497–504

[40] Segal R, Shemer  A, Hochberg M,  Keness Y,  Shvarzman R,  Mandelblat M,  Frenkel M,  Segal E. Onychomycosis in Israel: epidemiological aspects. Mycoses 2015; 58(3): 133–139

[41] Maraki S, Mavromanolaki  VE. Epidemiology of onychomycosis in Crete, Greece: a 12-year study. Mycoses 2016; 59(12): 798–802

[42] Hashemi SJ, Gerami  M, Zibafar E,  Daei M, Moazeni  M, Nasrollahi A. Onychomycosis in Tehran: mycological study of 504 patients. Mycoses 2010; 53(3): 251–255

[43] Souza LK, Fernandes  OF, Passos XS,  Costa CR,  Lemos JA,  Silva MR. Epidemiological and mycological data of onychomycosis in Goiania, Brazil. Mycoses 2010; 53(1): 68–71

[44] Yin SC, Zhang  YQ, Tan YF,  Yang JY,  Huang HQ,  Li H, Lai  W. Analysis of pathogenic fungi of 805 cases with onychomycosis. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2013; 8(4): 214–216 (in Chinese)

[45] Zhou J, Chen  M, Chen H,  Pan W, Liao  W. Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and literature review. Mycoses 2014; 57(3): 191–195

[46] Meersseman W, Van Wijngaerden  E. Invasive aspergillosis in the ICU: an emerging disease. Intensive Care Med 2007; 33(10): 1679–1681

[47] Pappas PG, Alexander  BD, Andes DR,  Hadley S,  Kauffman CA,  Freifeld A,  Anaissie EJ,  Brumble LM,  Herwaldt L,  Ito J, Kontoyiannis  DP, Lyon GM,  Marr KA,  Morrison VA,  Park BJ,  Patterson TF,  Perl TM,  Oster RA,  Schuster MG,  Walker R,  Walsh TJ,  Wannemuehler KA,  Chiller TM. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010; 50(8): 1101–1111

[48] Gavaldà J, Meije  Y, Fortún J,  Roilides E,  Saliba F,  Lortholary O,  Muñoz P,  Grossi P,  Cuenca-Estrella M; ESCMID Study Group for Infections in Compromised Hosts. Invasive fungal infections in solid organ transplant recipients. Clin Microbiol Infect 2014; 20(Suppl 7): 27–48

[49] Brown GD, Denning  DW, Gow NA,  Levitz SM,  Netea MG,  White TC. Hidden killers: human fungal infections. Sci Transl Med 2012; 4(165): 165rv13

[50] Montagna MT, Caggiano  G, Lovero G,  De Giglio O,  Coretti C,  Cuna T, Iatta  R, Giglio M,  Dalfino L,  Bruno F,  Puntillo F. Epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter Italian survey (AURORA Project). Infection 2013; 41(3): 645–653

[51] Feng WL, Yang  J, Xi ZQ,  Wang YQ,  Zhang RM,  Ji Y, Wu  Y, Jia XQ. Epidemiologic study on patients with invasive fungal infections. Chin J Epidemiol (Zhonghua Liu Xing Bing Xue Za Zhi) 2009; 30(10): 1043–1046 (in Chinese)

[52] Liu ZY, Sheng  RY, Li XL,  Li TS, Wang  AX. Nosocomial fungal infections, analysis of 149 cases. Natl Med J China (Zhonghua Yi Xue Za Zhi) 2003; 83(5): 399–402 (in Chinese)

[53] Gao LY, Yu  J, Li RY. Epidemiology of aspergillosis in mainland China. Chin J Mycol  (Zhongguo Zhen Jun Xue Za Zhi) 2010; 5(4): 247–251 (in Chinese)

[54] Liu YN, She  DY, Sun TY,  Tong ZH,  He B, Xiao  Y, He LX,  Qu JM, Liu  XQ, Li ER,  Chen P, Ma  ZS, Shi Y,  Feng YL,  Jiang SJ,  Xiong SD,  Hu CP. A multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007. Chin J Tubere Respir Dis (Zhonghua Jie He He Hu Xi Za Zhi) 2011; 34(2): 86–90 (in Chinese)

[55] Seneviratne CJ, Rajan  S, Wong SS,  Tsang DN,  Lai CK, Samaranayake  LP, Jin L. Antifungal susceptibility in serum and virulence determinants of Candida bloodstream isolates from Hong Kong. Front Microbiol 2016; 7: 216

[56] Guo F, Yang  Y, Kang Y,  Zang B, Cui  W, Qin B,  Qin Y, Fang  Q, Qin T,  Jiang D,  Li W, Gu  Q, Zhao H,  Liu D, Guan  X, Li J,  Ma X, Yu  K, Chan D,  Yan J, Tang  Y, Liu W,  Li R, Qiu  H; China-SCAN Team. Invasive candidiasis in intensive care units in China: a multicentre prospective observational study. J Antimicrob Chemother 2013; 68(7): 1660–1668

[57] Méan M, Marchetti  O, Calandra T. Bench-to-bedside review: Candida infections in the intensive care unit. Crit Care 2008; 12(1): 204

[58] Kett DH, Azoulay  E, Echeverria PM,  Vincent JL; Extended Prevalence of Infection in ICU Study (EPIC II) Group of Investigators. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med 2011; 39(4): 665–670

[59] Falagas ME, Roussos  N, Vardakas KZ. Relative frequency of albicans and the various non-albicans Candida spp. among candidemia isolates from inpatients in various parts of the world: a systematic review. Int J Infect Dis 2010; 14(11): e954–e966

[60] Horn DL, Neofytos  D, Anaissie EJ,  Fishman JA,  Steinbach WJ,  Olyaei AJ,  Marr KA,  Pfaller MA,  Chang CH,  Webster KM. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis 2009; 48(12): 1695–1703

[61] Gong X, Luan  T, Wu X,  Li G, Qiu  H, Kang Y,  Qin B, Fang  Q, Cui W,  Qin Y, Li  J, Zang B. Invasive candidiasis in intensive care units in China: Risk factors and prognoses of Candida albicans and non-albicans Candida infections. Am J Infect Control 2016; 44(5): e59–e63

[62] Ma CF, Li  FQ, Shi LN,  Hu YA, Wang  Y, Huang M,  Kong QQ. Surveillance study of species distribution, antifungal susceptibility and mortality of nosocomial candidemia in a tertiary care hospital in China. BMC Infect Dis 2013; 13(1): 337

[63] Li S, An  YZ. Retrospective analysis of invasive fungal infection in surgical intensive care unit. Natl Med J China (Zhonghua Yi Xue Za Zhi)  2010; 90(6): 382–385 (in Chinese)

[64] Cao B, Wang  H, Wu L,  Sun WJ, Li  F, Liu YM. Epidemiological study of invasive nosocomial candidiasis in 2 teaching hospitals in Beijing. Natl Med J China (Zhonghua Yi Xue Za Zhi) 2008; 88(28): 1970–1973 (in Chinese)

[65] Poikonen E, Lyytikäinen  O, Anttila VJ,  Koivula I,  Lumio J,  Kotilainen P,  Syrjälä H,  Ruutu P. Secular trend in candidemia and the use of fluconazole in Finland, 2004–2007. BMC Infect Dis 2010; 10(1): 312

[66] Almirante B, Rodríguez  D, Park BJ,  Cuenca-Estrella M,  Planes AM,  Almela M,  Mensa J,  Sanchez F,  Ayats J,  Gimenez M,  Saballs P,  Fridkin SK,  Morgan J,  Rodriguez-Tudela JL,  Warnock DW,  Pahissa A; Barcelona Candidemia Project Study Group. Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 2005; 43(4): 1829–1835

[67] Paphitou NI, Ostrosky-Zeichner  L, Rex JH. Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials. Med Mycol 2005; 43(3): 235–243

[68] Marchetti O, Bille  J, Fluckiger U,  Eggimann P,  Ruef C, Garbino  J, Calandra T,  Glauser MP,  Täuber MG,  Pittet D; Fungal Infection Network of Switzerland. Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis 2004; 38(3): 311–320

[69] Wisplinghoff H, Bischoff  T, Tallent SM,  Seifert H,  Wenzel RP,  Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39(3): 309–317

[70] González GM,  Treviño-Rangel RdeJ,  Palma-Nicolás JP,  Martínez C,  González JG,  Ayala J,  Caballero A,  Morfín-Otero R,  Rodríguez-Noriega E,  Velarde F,  Ascencio EP,  Tinoco JC,  Vázquez JA,  Cano MA,  León-Sicairos N,  González R,  Rincón J,  Elías MA,  Bonifaz A. Species distribution and antifungal susceptibility of bloodstream fungal isolates in paediatric patients in Mexico: a nationwide surveillance study. J Antimicrob Chemother 2013; 68(12): 2847–2851

[71] Pfaller MA, Diekema  DJ, Gibbs DL,  Newell VA,  Ellis D,  Tullio V,  Rodloff A,  Fu W, Ling  TA; Global Antifungal Surveillance Group. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol 2010; 48(4): 1366–1377

[72] Pu S, Niu  S, Zhang C,  Xu X, Qin  M, Huang S,  Zhang L. Epidemiology, antifungal susceptibilities, and risk factors for invasive candidiasis from 2011 to 2013 in a teaching hospital in southwest  China. J  Microbiol  Immunol  Infect  2017;  50(1):  97–103

[73] Li F, Wu  L, Cao B,  Zhang Y,  Li X, Liu  Y. Surveillance of the prevalence, antibiotic susceptibility, and genotypic characterization of invasive candidiasis in a teaching hospital in China between 2006 to 2011. BMC Infect Dis 2013; 13(1): 353

[74] Zhang Z, Zhao  SL, Pang LJ,  Wang H, Liu  WY, Yan W. The analysis and survey of 475 strains of fungi from clinical samples. Chin J Lab Med (Zhonghua Jian Yan Yi Xue Za Zhi) 1996; 19(5): 267–269 (in Chinese)

[75] Yu J, Li  RY, Wang D,  Zhao M, Jiang  H, Chen W,  Wang AP,  Wang DL. Analysis on species distribution and risk factors of nosocomial invasive Candida infection. China J Lepr Skin Dis (Zhongguo Ma Feng Pi Fu Bing Za Zhi) 2000; 16(4): 211–215 (in Chinese)

[76] Wang H, Xu  YC, Hsueh PR. Epidemiology of candidemia and antifungal susceptibility in invasive Candida species in the Asia-Pacific region. Future Microbiol 2016; 11(11): 1461–1477

[77] Nucci M, Queiroz-Telles  F, Tobón AM,  Restrepo A,  Colombo AL. Epidemiology of opportunistic fungal infections in Latin America. Clin Infect Dis 2010; 51(5): 561–570

[78] Wang H, Xiao  M, Chen SC,  Kong F, Sun  ZY, Liao K,  Lu J, Shao  HF, Yan Y,  Fan H, Hu  ZD, Chu YZ,  Hu TS, Ni  YX, Zou GL,  Xu YC. In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study. J Clin Microbiol 2012; 50(12): 3952–3959

[79] Puig-Asensio M, Pemán  J, Zaragoza R,  Garnacho-Montero J,  Martín-Mazuelos E,  Cuenca-Estrella M,  Almirante B; Prospective Population Study on Candidemia in Spain (CANDIPOP) Project; Hospital Infection Study Group (GEIH); Medical Mycology Study Group (GEMICOMED) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC); Spanish Network for Research in Infectious Diseases. Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med 2014; 42(6): 1423–1432

[80] Wu JQ, Zhu  LP, Ou XT,  Xu B, Hu  XP, Wang X,  Weng XH. Epidemiology and risk factors for non-Candida albicans candidemia in non-neutropenic patients at a Chinese teaching hospital. Med Mycol 2011; 49(5): 552–555

[81] Liu W, Tan  J, Sun J,  Xu Z, Li  M, Yang Q,  Shao H, Zhang  L, Liu W,  Wan Z, Cui  W, Zang B,  Jiang D,  Fang Q, Qin  B, Qin T,  Li W, Guo  F, Liu D,  Guan X, Yu  K, Qiu H,  Li R; China-SCAN team. Invasive candidiasis in intensive care units in China: in vitro antifungal susceptibility in the China-SCAN study. J Antimicrob Chemother 2014; 69(1): 162–167

[82] Chen TC, Chen  YH, Tsai JJ,  Peng CF,  Lu PL, Chang  K, Hsieh HC,  Chen TP. Epidemiologic analysis and antifungal susceptibility of Candida blood isolates in southern Taiwan. J Microbiol Immunol Infect 2005; 38(3): 200–210

[83] Chen PL, Lo  HJ, Wu CJ,  Lee HC, Chang  CM, Lee NY,  Wang AH,  Lin WL, Ko  NY, Lee CC,  Ko WC. Species distribution and antifungal susceptibility of blood Candida isolates at a tertiary hospital in southern Taiwan, 1999–2006. Mycoses 2011; 54(4): e17–e23

[84] Li Y, Du  M, Chen LA,  Liu Y, Liang  Z. Nosocomial bloodstream infection due to Candida spp. in China: species distribution, clinical features, and outcomes. Mycopathologia 2016; 181(7-8): 485–495

[85] Yang ZT, Wu  L, Liu XY,  Zhou M, Li  J, Wu JY,  Cai Y, Mao  EQ, Chen EZ,  Lortholary O. Epidemiology, species distribution and outcome of nosocomial Candida spp. bloodstream infection in Shanghai. BMC Infect Dis 2014; 14(1): 241

[86] Wang H, Liu  N, Yin M,  Han H, Yue  J, Zhang F,  Shan T, Guo  H, Wu D. The epidemiology, antifungal use and risk factors of death in elderly patients with candidemia: a multicentre retrospective study. BMC Infect Dis 2014; 14(1): 609

[87] Zhang XB, Yu  SJ, Yu JX,  Gong YL,  Feng W, Sun  FJ. Retrospective analysis of epidemiology and prognostic factors for candidemia at a hospital in China, 2000–2009. Jpn J Infect Dis 2012; 65(6): 510–515

[88] Yap HY, Kwok  KM, Gomersall CD,  Fung SC,  Lam TC, Leung  PN, Hui M,  Joynt GM. Epidemiology and outcome of Candida bloodstream infection in an intensive care unit in Hong Kong. Hong Kong Med J 2009; 15(4): 255–261

[89] Chen PY, Chuang  YC, Wang JT,  Sheng WH,  Yu CJ, Chu  CC, Hsueh PR,  Chang SC,  Chen YC. Comparison of epidemiology and treatment outcome of patients with candidemia at a teaching hospital in Northern Taiwan, in 2002 and 2010. J Microbiol Immunol Infect 2014; 47(2): 95–103

[90] Chen SC, Marriott  D, Playford EG,  Nguyen Q,  Ellis D,  Meyer W,  Sorrell TC,  Slavin M; Australian Candidaemia Study. Candidaemia with uncommon Candida species: predisposing factors, outcome, antifungal susceptibility, and implications for management. Clin Microbiol Infect 2009; 15(7): 662–669

[91] Pfaller MA, Diekema  DJ, Colombo AL,  Kibbler C,  Ng KP, Gibbs  DL, Newell VA. Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program. J Clin Microbiol 2006; 44(10): 3578–3582

[92] Xiao M, Wang  H, Lu J,  Chen SC,  Kong F, Ma  XJ, Xu YC. Three clustered cases of candidemia caused by Candida quercitrusa and mycological characteristics of this novel species. J Clin Microbiol 2014; 52(8): 3044–3048

[93] Chowdhary A, Sharma  C, Meis JF. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog 2017; 13(5): e1006290

[94] Wu Z, Liu  Y, Feng X,  Liu Y, Wang  S, Zhu X,  Chen Q, Pan  S. Candidemia: incidence rates, type of species, and risk factors at a tertiary care academic hospital in China. Int J Infect Dis 2014; 22: 4–8

[95] Huang YT, Liu  CY, Liao CH,  Chung KP,  Sheng WH,  Hsueh PR. Antifungal susceptibilities of Candida isolates causing bloodstream infections at a medical center in Taiwan, 2009–2010. Antimicrob Agents Chemother 2014; 58(7): 3814–3819

[96] Chowdhary A, Sharma  C, Duggal S,  Agarwal K,  Prakash A,  Singh PK,  Jain S, Kathuria  S, Randhawa HS,  Hagen F,  Meis JF. New clonal strain of Candida auris, Delhi, India. Emerg Infect Dis 2013; 19(10): 1670–1673

[97] Magobo RE, Corcoran  C, Seetharam S,  Govender NP. Candida auris-associated candidemia, South Africa. Emerg Infect Dis 2014; 20(7): 1250–1251

[98] Vallabhaneni S, Kallen  A, Tsay S,  Chow N, Welsh  R, Kerins J,  Kemble SK,  Pacilli M,  Black SR,  Landon E,  Ridgway J,  Palmore TN,  Zelzany A,  Adams EH,  Quinn M,  Chaturvedi S,  Greenko J,  Fernandez R,  Southwick K,  Furuya EY,  Calfee DP,  Hamula C,  Patel G,  Barrett P; MSD, Lafaro P,  Berkow EL,  Moulton-Meissner H,  Noble-Wang J,  Fagan RP,  Jackson BR,  Lockhart SR,  Litvintseva AP,  Chiller TM. Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus — United States, May 2013–August 2016. MMWR Morb Mortal Wkly Rep 2016; 65(44): 1234–1237

[99] Mohsin J, Hagen  F, Al-Balushi ZAM,  de Hoog GS,  Chowdhary A,  Meis JF,  Al-Hatmi AMS. The first cases of Candida auris candidaemia in Oman. Mycoses 2017; 60(9): 569–575

[100] Chowdhary A, Anil Kumar  V, Sharma C,  Prakash A,  Agarwal K,  Babu R, Dinesh  KR, Karim S,  Singh SK,  Hagen F,  Meis JF. Multidrug-resistant endemic clonal strain of Candida auris in India. Eur J Clin Microbiol Infect Dis 2014; 33(6): 919–926

[101] Wang FJ, Zhang  D, Liu ZH,  Wu WX, Bai  HH, Dong HY. Species distribution and in vitro antifungal susceptibility of vulvovaginal Candida isolates in China. Chin Med J (Engl) 2016; 129(10): 1161–1165

[102] Ding X, Yan  D, Sun W,  Zeng Z, Su  R, Su J. Epidemiology and risk factors for nosocomial non-Candida albicans candidemia in adult patients at a tertiary care hospital in North China. Med Mycol 2015; 53(7): 684–690

[103] Chen J, Jiang  Y, Wei B,  Ding Y, Xu  S, Qin P,  Fu J. Epidemiology of and risk factors for neonatal candidemia at a tertiary care hospital in western China. BMC Infect Dis 2016; 16(1): 700

[104] Pfaller MA, Castanheira  M, Messer SA,  Moet GJ,  Jones RN. Echinocandin and triazole antifungal susceptibility profiles for Candida spp., Cryptococcus neoformans, and Aspergillus fumigatus: application of new CLSI clinical breakpoints and epidemiologic cutoff values to characterize resistance in the SENTRY Antimicrobial Surveillance Program (2009). Diagn Microbiol Infect Dis 2011; 69(1): 45–50

[105] Montagna MT, Lovero  G, Coretti C,  Martinelli D,  Delia M,  De Giglio O,  Caira M,  Puntillo F,  D’Antonio D,  Venditti M,  Sambri V,  Di Bernardo F,  Barbui A,  Lo Cascio G,  Concia E,  Mikulska M,  Viscoli C,  Maximova N,  Candoni A,  Oliveri S,  Lombardi G,  Pitzurra L,  Sanguinetti M,  Masciari R,  Santantonio T,  Andreoni S,  Barchiesi F,  Pecile P,  Farina C,  Viale P,  Specchia G,  Caggiano G,  Pagano L. SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients. Infection 2014; 42(1): 141–151

[106] Lin SJ, Schranz  J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32(3): 358–366

[107] Zhang S, Wang  S, Wan Z,  Li R, Yu  J. The diagnosis of invasive and noninvasive pulmonary aspergillosis by serum and bronchoalveolar lavage fluid galactomannan assay. Biomed Res Int  2015; 2015: 943691

[108] Chen Y, Lu  ZY, Jin Y,  Han L, Huang  LY. Progress of research on azole resistance in Aspergillus fumigatus. Chin J Epidemiol (Zhonghua Liu Xing Bing Xue Za Zhi) 2016; 37(12): 1687–1692 (in Chinese) 

[109] He H, Ding  L, Li F,  Zhan Q. Clinical features of invasive bronchial-pulmonary aspergillosis in critically ill patients with chronic obstructive respiratory diseases: a prospective study. Crit Care 2011; 15(1): R5

[110] Chen J, Yang  Q, Huang J,  Li L. Clinical findings in 19 cases of invasive pulmonary aspergillosis with liver cirrhosis. Multidiscip Respir Med 2014; 9(1): 1

[111] Chen J, Yang  Q, Huang J,  Li L. Risk factors for invasive pulmonary aspergillosis and hospital mortality in acute-on-chronic liver failure patients: a retrospective-cohort study. Int J Med Sci 2013; 10(12): 1625–1631

[112] Meersseman W, Vandecasteele  SJ, Wilmer A,  Verbeken E,  Peetermans WE,  Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med 2004; 170(6): 621–625

[113] Yan X, Li  M, Jiang M,  Zou LQ, Luo  F, Jiang Y. Clinical characteristics of 45 patients with invasive pulmonary aspergillosis: retrospective analysis of 1711 lung cancer cases. Cancer 2009; 115(21): 5018–5025

[114] Taccone FS, Van den Abeele  AM, Bulpa P,  Misset B,  Meersseman W,  Cardoso T,  Paiva JA,  Blasco-Navalpotro M,  De Laere E,  Dimopoulos G,  Rello J,  Vogelaers D,  Blot SI; AspICU Study Investigators. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Crit Care 2015; 19(1): 7

[115] Lockhart SR, Frade  JP, Etienne KA,  Pfaller MA,  Diekema DJ,  Balajee SA. Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene. Antimicrob Agents Chemother 2011; 55(9): 4465–4468

[116] Li Y, Wan  Z, Liu W,  Li R. Identification and susceptibility of Aspergillus section nigri in china: prevalence of species and paradoxical growth in response to echinocandins. J Clin Microbiol 2015; 53(2): 702–705

[117] Wang W, Zhao  CY, Zhou JY,  Wang YD,  Shen C, Zhou  DF, Yin HZ. Invasive pulmonary aspergillosis in patients with HBV-related liver failure. Eur J Clin Microbiol Infect Dis 2011; 30(5): 661–667

[118] Liu M, Zeng  R, Zhang L,  Li D, Lv  G, Shen Y,  Zheng H,  Zhang Q,  Zhao J, Zheng  N, Liu W. Multiple cyp51A-based mechanisms identified in azole-resistant isolates of Aspergillus fumigatus from China. Antimicrob Agents Chemother 2015; 59(7): 4321–4325

[119] Chen Y, Lu  Z, Zhao J,  Zou Z, Gong  Y, Qu F,  Bao Z, Qiu  G, Song M,  Zhang Q,  Liu L, Hu  M, Han X,  Tian S, Zhao  J, Chen F,  Zhang C,  Sun Y, Verweij  PE, Huang L,  Han L. Epidemiology and molecular characterizations of azole resistance in clinical and environmental Aspergillus fumigatus isolates from China. Antimicrob Agents Chemother 2016; 60(10): 5878–5884

[120] Chen J, Li  H, Li R,  Bu D, Wan  Z. Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma. J Antimicrob Chemother 2005; 55(1): 31–37

[121] Chen Y, Wang  H, Lu Z,  Li P, Zhang  Q, Jia T,  Zhao J, Tian  S, Han X,  Chen F, Zhang  C, Jia X,  Huang L,  Qu F, Han  L. Emergence of TR46/Y121F/T289A in an Aspergillus fumigatus isolate from a Chinese patient. Antimicrob Agents Chemother 2015; 59(11): 7148–7150

[122] Sloan DJ, Parris  V. Cryptococcal meningitis: epidemiology and therapeutic options. Clin Epidemiol 2014; 6: 169–182

[123] Gullo FP, Rossi  SA, Sardi JdeC,  Teodoro VL,  Mendes-Giannini MJ,  Fusco-Almeida AM. Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment. Eur J Clin Microbiol Infect Dis 2013; 32(11): 1377–1391

[124] Cogliati M. Global molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii: an atlas of the molecular types. Scientifica (Cairo) 2013; 2013: 675213

[125] Meyer W, Aanensen  DM, Boekhout T,  Cogliati M,  Diaz MR,  Esposto MC,  Fisher M,  Gilgado F,  Hagen F,  Kaocharoen S,  Litvintseva AP,  Mitchell TG,  Simwami SP,  Trilles L,  Viviani MA,  Kwon-Chung J. Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol 2009; 47(6): 561–570

[126] Fan X, Xiao  M, Chen S,  Kong F, Dou  HT, Wang H,  Xiao YL,  Kang M, Sun  ZY, Hu ZD,  Wan Z, Chen  SL, Liao K,  Chu YZ, Hu  TS, Zou GL,  Hou X, Zhang  L, Zhao YP,  Xu YC, Liu  ZY. Predominance of Cryptococcus neoformans var. grubii multilocus sequence type 5 and emergence of isolates with non-wild-type minimum inhibitory concentrations to fluconazole: a multi-centre study in China. Clin Microbiol Infect 2016; 22(10): 887.e1–887.e9

[127] Dou HT, Xu  YC, Wang HZ,  Li TS. Molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii in China between 2007 and 2013 using multilocus sequence typing and the DiversiLab system. Eur J Clin Microbiol Infect Dis 2015; 34(4): 753–762

[128] Khayhan K, Hagen  F, Pan W,  Simwami S,  Fisher MC,  Wahyuningsih R,  Chakrabarti A,  Chowdhary A,  Ikeda R,  Taj-Aldeen SJ,  Khan Z, Ip  M, Imran D,  Sjam R, Sriburee  P, Liao W,  Chaicumpar K,  Vuddhakul V,  Meyer W,  Trilles L,  van Iersel LJ,  Meis JF,  Klaassen CH,  Boekhout T. Geographically structured populations of Cryptococcus neoformans variety grubii in Asia correlate with HIV status and show a clonal population structure. PLoS One 2013; 8(9): e72222

[129] Park SH, Kim  M, Joo SI,  Hwang SM. Molecular epidemiology of clinical Cryptococcus neoformans isolates in Seoul, Korea. Mycobiology 2014; 42(1): 73–78

[130] Mihara T, Izumikawa  K, Kakeya H,  Ngamskulrungroj P,  Umeyama T,  Takazono T,  Tashiro M,  Nakamura S,  Imamura Y,  Miyazaki T,  Ohno H, Yamamoto  Y, Yanagihara K,  Miyzaki Y,  Kohno S. Multilocus sequence typing of Cryptococcus neoformans in non-HIV associated cryptococcosis in Nagasaki, Japan. Med Mycol 2013; 51(3): 252–260

[131] Simwami SP, Khayhan  K, Henk DA,  Aanensen DM,  Boekhout T,  Hagen F,  Brouwer AE,  Harrison TS,  Donnelly CA,  Fisher MC. Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin. PLoS Pathog 2011; 7(4): e1001343

[132] Xue X, Wu  H, Wang K,  Cao J, Shen  D. Cryptococcosis by Cryptococcus gattii in China. Lancet Infect Dis 2015; 15(10): 1135–1136

[133] Kronstad JW, Attarian  R, Cadieux B,  Choi J, D’Souza  CA, Griffiths EJ,  Geddes JM,  Hu G, Jung  WH, Kretschmer M,  Saikia S,  Wang J. Expanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box. Nat Rev Microbiol 2011; 9(3): 193–203

[134] Feng X, Yao  Z, Ren D,  Liao W, Wu  J. Genotype and mating type analysis of Cryptococcus neoformans and Cryptococcus gattii isolates from China that mainly originated from non-HIV-infected patients. FEMS Yeast Res 2008; 8(6): 930–938

[135] Okamoto K, Hatakeyama  S, Itoyama S,  Nukui Y,  Yoshino Y,  Kitazawa T,  Yotsuyanagi H,  Ikeda R,  Sugita T,  Koike K. Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis 2010; 16(7): 1155–1157

[136] Yuchong C, Fubin  C, Jianghan C,  Fenglian W,  Nan X, Minghui  Y, Yalin S,  Zhizhong Z. Cryptococcosis in China (1985–2010): review of cases from Chinese database. Mycopathologia 2012; 173(5-6): 329–335

[137] Lui G, Lee  N, Ip M,  Choi KW,  Tso YK, Lam  E, Chau S,  Lai R, Cockram  CS. Cryptococcosis in apparently immunocompetent patients. QJM 2006; 99(3): 143–151

[138] Tseng HK, Liu  CP, Ho MW,  Lu PL, Lo  HJ, Lin YH,  Cho WL, Chen  YC; Taiwan Infectious Diseases Study Network for Cryptococcosis. Microbiological, epidemiological, and clinical characteristics and outcomes of patients with cryptococcosis in Taiwan, 1997–2010. PLoS One 2013; 8(4): e61921

[139] Chen J, Varma  A, Diaz MR,  Litvintseva AP,  Wollenberg KK,  Kwon-Chung KJ. Cryptococcus neoformans strains and infection in apparently immunocompetent patients, China. Emerg Infect Dis 2008; 14(5): 755–762

[140] Chen YY, Lai  CH. Nationwide population-based epidemiologic study of cryptococcal meningitis in Taiwan. Neuroepidemiology 2011; 36(2): 79–84

[141] Lu CH, Chang  WN, Chang HW,  Chuang YC. The prognostic factors of cryptococcal meningitis in HIV-negative patients. J Hosp Infect 1999; 42(4): 313–320

[142] Fang W, Fa  Z, Liao W. Epidemiology of Cryptococcus and cryptococcosis in China. Fungal Genet Biol 2015; 78: 7–15

[143] Dou H, Wang  H, Xie S,  Chen X, Xu  Z, Xu Y. Molecular characterization of Cryptococcus neoformans isolated from the environment in Beijing, China. Med Mycol 2017; 55(7):737–747

[144] Li AS, Pan  WH, Wu SX,  Hideaki T,  Guo NR, Shen  YN, Lu GX,  Pan RG, Zhu  MC, Chen M,  Shi WM, Liao  WQ. Ecological surveys of the Cryptococcus species complex in China. Chin Med J (Engl) 2012; 125(3): 511–516

[145] Skiada A, Pagano  L, Groll A,  Zimmerli S,  Dupont B,  Lagrou K,  Lass-Florl C,  Bouza E,  Klimko N,  Gaustad P,  Richardson M,  Hamal P,  Akova M,  Meis JF,  Rodriguez-Tudela JL,  Roilides E,  Mitrousia-Ziouva A,  Petrikkos G; European Confederation of Medical Mycology Working Group on Zygomycosis. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect 2011; 17(12): 1859–1867

[146] Ribes JA, Vanover-Sams  CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000; 13(2): 236–301

[147] Katragkou A, Walsh  TJ, Roilides E. Why is mucormycosis more difficult to cure than more common mycoses? Clin Microbiol Infect 2014; 20(Suppl 6): 74–81

[148] Rees JR, Pinner  RW, Hajjeh RA,  Brandt ME,  Reingold AL. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992–1993: results of population-based laboratory active surveillance. Clin Infect Dis 1998; 27(5): 1138–1147

[149] Torres-Narbona M, Guinea  J, Martínez-Alarcón  J, Muñoz P,  Gadea I,  Bouza E; MYCOMED Zygomycosis Study Group. Impact of zygomycosis on microbiology workload: a survey study in Spain. J Clin Microbiol 2007; 45(6): 2051–2053

[150] Bitar D, Van Cauteren  D, Lanternier F,  Dannaoui E,  Che D, Dromer  F, Desenclos JC,  Lortholary O. Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006. Emerg Infect Dis 2009; 15(9): 1395–1401

[151] Zhao JY, Fang  W, Yang YL,  Pan WH, Liao  WQ, Tang YC. Retrospective analysis of diabetes combined with zygomycosis in mainland China: a review of 74 cases. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2016; 11(1): 33–36 (in Chinese)

[152] Wang SB, Li  RY, Yu J. Epidemiology of zygomycosis in mainland China. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2013; 8(3): 163–168 (in Chinese)

[153] Zhao JY, Wang  GZ, Zhang JY,  Yang YL,  Jia HL, Fang  W, Pan WH,  Liao WQ. Retrospective analysis of pulmonary zygomycosis in mainland China: a review of 102 cases. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2014; 9(3): 150–154 (in Chinese)

[154] Roden MM, Zaoutis  TE, Buchanan WL,  Knudsen TA,  Sarkisova TA,  Schaufele RL,  Sein M, Sein  T, Chiou CC,  Chu JH, Kontoyiannis  DP, Walsh TJ. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41(5): 634–653

[155] Cornely OA, Arikan-Akdagli  S, Dannaoui E,  Groll AH,  Lagrou K,  Chakrabarti A,  Lanternier F,  Pagano L,  Skiada A,  Akova M,  Arendrup MC,  Boekhout T,  Chowdhary A,  Cuenca-Estrella M,  Freiberger T,  Guinea J,  Guarro J,  de Hoog S,  Hope W, Johnson  E, Kathuria S,  Lackner M,  Lass-Flörl C,  Lortholary O,  Meis JF,  Meletiadis J,  Muñoz P,  Richardson M,  Roilides E,  Tortorano AM,  Ullmann AJ,  van Diepeningen A,  Verweij P,  Petrikkos G; European Society of Clinical Microbiology and Infectious Diseases Fungal Infection Study Group; European Confederation of Medical Mycology. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect 2014; 20(Suppl 3): 5–26

[156] Yang W, Lu  J, Weng J,  Jia W, Ji  L, Xiao J,  Shan Z, Liu  J, Tian H,  Ji Q, Zhu  D, Ge J,  Lin L, Chen  L, Guo X,  Zhao Z, Li  Q, Zhou Z,  Shan G, He  J; China National Diabetes and Metabolic Disorders Study Group. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362(12): 1090–1101

[157] Thomas CF Jr, Limper  AH. Pneumocystis pneumonia. N Engl J Med 2004; 350(24): 2487–2498

[158] Thomas CF Jr, Limper  AH. Current insights into the biology and pathogenesis of Pneumocystis pneumonia. Nat Rev Microbiol 2007; 5(4): 298–308

[159] Edman JC, Kovacs  JA, Masur H,  Santi DV,  Elwood HJ,  Sogin ML. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988; 334(6182): 519–522

[160] Stringer SL, Stringer  JR, Blase MA,  Walzer PD,  Cushion MT. Pneumocystis carinii: sequence from ribosomal RNA implies a close relationship with fungi. Exp Parasitol 1989; 68(4): 450–461

[161] Gigliotti F, Limper  AH, Wright T. Pneumocystis. Cold Spring Harb Perspect Med 2014; 4(12): a019828

[162] Lu JJ, Lee  CH. Pneumocystis pneumonia. J Formos Med Assoc 2008; 107(11): 830–842

[163] Catherinot E, Lanternier  F, Bougnoux ME,  Lecuit M,  Couderc LJ,  Lortholary O. Pneumocystis jirovecii pneumonia. Infect Dis Clin North Am 2010; 24(1): 107–138

[164] Kaplan JE, Hanson  D, Dworkin MS,  Frederick T,  Bertolli J,  Lindegren ML,  Holmberg S,  Jones JL. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000; 30(s1 Suppl 1): S5–S14

[165] Ruxrungtham K, Brown  T, Phanuphak P. HIV/AIDS in Asia. Lancet 2004; 364(9428): 69–82

[166] Beck JM, Cushion  MT. Pneumocystis workshop: 10th anniversary summary. Eukaryot Cell 2009; 8(4): 446–460

[167] Wang XL, Wang  XL, Wei W,  An CL. Retrospective study of Pneumocystis pneumonia over half a century in mainland China. J Med Microbiol 2011; 60(Pt 5): 631–638

[168] Liu Y, Su  L, Jiang SJ,  Qu H. Risk factors for mortality from Pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget 2017; 8(35): 59729–59739

[169] Wang DD, Zheng  MQ, Zhang N,  An CL. Investigation of Pneumocystis jirovecii colonization in patients with chronic pulmonary diseases in the People’s Republic of China. Int J Chron Obstruct Pulmon Dis 2015; 10: 2079–2085

[170] Huang YS, Yang  JJ, Lee NY,  Chen GJ,  Ko WC, Sun  HY, Hung CC. Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review. Expert Rev Anti Infect Ther 2017; 15(9): 873–892

[171] Guo F, Chen  Y, Yang SL,  Xia H, Li  XW, Tong ZH. Pneumocystis pneumonia in HIV-infected and immunocompromised non-HIV infected patients: a retrospective study of two centers in China. PLoS One 2014; 9(7): e101943

[172] Chen M, Tian  X, Qin F,  Zhou J, Liu  J, Wang M,  Xu KF. Pneumocystis pneumonia in patients with autoimmune diseases: a retrospective study focused on clinical characteristics and prognostic factors related to death. PLoS One 2015; 10(9): e0139144

[173] Lemiale V, Debrumetz  A, Delannoy A,  Alberti C,  Azoulay E. Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia. Respir Res 2013; 14(1): 87

[174] Asai N, Motojima  S, Ohkuni Y,  Matsunuma R,  Nakashima K,  Iwasaki T,  Nakashita T,  Otsuka Y,  Kaneko N. Early diagnosis and treatment are crucial for the survival of Pneumocystis pneumonia patients without human immunodeficiency virus infection. J Infect Chemother 2012; 18(6): 898–905

[175] Deng X, Zhuo  L, Lan Y,  Dai Z, Chen  WS, Cai W,  Kovacs JA,  Ma L, Tang  X. Mutational analysis of Pneumocystis jirovecii dihydropteroate synthase and dihydrofolate reductase genes in HIV-infected patients in China. J Clin Microbiol 2014; 52(11): 4017–4019

[176] Takahashi T, Endo  T, Nakamura T,  Sakashitat H,  Kimurat K,  Ohnishit K,  Kitamura Y,  Iwamoto A. Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f. sp. hominis in Japan. J Med Microbiol 2002; 51(6): 510–515

[177] Siripattanapipong S,  Leelayoova S,  Mungthin M,  Worapong J,  Tan-Ariya P. Study of DHPS and DHFR genes of Pneumocystis jirovecii in Thai HIV-infected patients. Med Mycol 2008; 46(4): 389–392

[178] Robberts FJ, Chalkley  LJ, Weyer K,  Goussard P,  Liebowitz LD. Dihydropteroate synthase and novel dihydrofolate reductase gene mutations in strains of Pneumocystis jirovecii from South Africa. J Clin Microbiol 2005; 43(3): 1443–1444

[179] Kazanjian PH, Fisk  D, Armstrong W,  Shulin Q,  Liwei H,  Ke Z, Meshnick  S. Increase in prevalence of Pneumocystis carinii mutations in patients with AIDS and P. carinii pneumonia, in the United States and China. J Infect Dis 2004; 189(9): 1684–1687

[180] Zhang Y, Hagen  F, Wan Z,  Liu Y, Liu  Y, Wang Q,  de Hoog GS,  Li R, Zhang  J. Two cases of sporotrichosis of the right upper extremity in right-handed patients with diabetes mellitus. Rev Iberoam Micol 2016; 33(1): 38–42

[181] Zhang Y, Hagen  F, Stielow B,  Rodrigues AM,  Samerpitak K,  Zhou X, Feng  P, Yang L,  Chen M, Deng  S, Li S,  Liao W, Li  R, Li F,  Meis JF,  Guarro J,  Teixeira M,  Al-Zahrani HS,  Pires de Camargo Z,  Zhang L,  de Hoog GS. Phylogeography and evolutionary patterns in Sporothrix spanning more than 14 000 human and animal case reports. Persoonia 2015; 35(1): 1–20

[182] Chen YC. Sporotrichosis. Chin J Mycol (Zhongguo Zhen Jun Xue Za Zhi) 2008; 3(4): 233–241 (in Chinese)

[183] Liu TT, Zhang  K, Zhou X. Molecular identification of Sporothrix clinical isolates in China. J Zhejiang Univ Sci B 2014; 15(1): 100–108

[184] Yu X, Wan  Z, Zhang Z,  Li F, Li  R, Liu X. Phenotypic and molecular identification of Sporothrix isolates of clinical origin in Northeast China. Mycopathologia 2013; 176(1-2): 67–74

[185] Zhao MD, Zhou  X, Liu TT,  Yang ZB. Morphological and physiological comparison of taxa comprising the Sporothrix schenckii complex. J Zhejiang Univ Sci B 2015; 16(11): 940–947

[186] Marimon R, Cano  J, Gené J,  Sutton DA,  Kawasaki M,  Guarro J. Sporothrix brasiliensis, S. globosa, and S. mexicana, three new Sporothrix species of clinical interest. J Clin Microbiol 2007; 45(10): 3198–3206

[187] Mahajan VK. Sporotrichosis: an overview and therapeutic options. Dermatol Res Pract 2014; 2014: 272376

[188] Pappas PG, Tellez  I, Deep AE,  Nolasco D,  Holgado W,  Bustamante B. Sporotrichosis in Peru: description of an area of hyperendemicity. Clin Infect Dis 2000; 30(1): 65–70

[189] Sirisanthana T, Supparatpinyo  K. Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients. Int J Infect Dis 1998; 3(1): 48–53

[190] Li HR, Cai  SX, Chen YS,  Yu ME, Xu  NL, Xie BS,  Lin M, Hu  XL. Comparison of Talaromyces marneffei infection in human immunodeficiency virus-positive and human immunodeficiency virus-negative patients from Fujian, China. Chin Med J (Engl) 2016; 129(9): 1059–1065

[191] Zheng J, Gui  X, Cao Q,  Yang R, Yan  Y, Deng L,  Lio J. A clinical study of acquired immunodeficiency syndrome associated Penicillium marneffei infection from a non-endemic area in China. PLoS One 2015; 10(6): e0130376

[192] Capponi M, Segretain  G, Sureau P. Penicillosis from Rhizomys sinensis.  Bull Soc Pathol Exot 1956; 49(3): 418–421

[193] DiSalvo AF, Fickling  AM, Ajello L. Infection caused by Penicillium marneffei: description of first natural infection in man. Am J Clin Pathol 1973; 60(2): 259–263

[194] Deng ZL. Progressive disseminated penicilliosis caused by Penicillium marneffei .J Guangxi Med Col (Gangxi Yi Xue Yuan Xue Bao) 1984; 1(1): 1–4 (in Chinese)

[195] Chan JF, Lau  SK, Yuen KY,  Woo PC. Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients. Emerg Microbes Infect 2016; 5(3): e19

[196] Hu Y, Zhang  J, Li X,  Yang Y, Zhang  Y, Ma J,  Xi L. Penicillium marneffei infection: an emerging disease in mainland China. Mycopathologia 2013; 175(1-2): 57–67

[197] Cao C, Liang  L, Wang W,  Luo H, Huang  S, Liu D,  Xu J, Henk  DA, Fisher MC. Common reservoirs for Penicillium marneffei infection in humans and rodents, China. Emerg Infect Dis 2011; 17(2): 209–214

[198] Huang X, He  G, Lu S,  Liang Y,  Xi L. Role of Rhizomys pruinosus as a natural animal host of Penicillium marneffei in Guangdong, China. Microb Biotechnol 2015; 8(4): 659–664

[199] Gugnani H, Fisher  MC, Paliwal-Johsi A,  Vanittanakom N,  Singh I,  Yadav PS. Role of Cannomys badius as a natural animal host of Penicillium marneffei in India. J Clin Microbiol 2004; 42(11): 5070–5075

[200] Fisher MC, Hanage  WP, de Hoog S,  Johnson E,  Smith MD,  White NJ,  Vanittanakom N. Low effective dispersal of asexual genotypes in heterogeneous landscapes by the endemic pathogen Penicillium marneffei. PLoS Pathog 2005; 1(2): e20

[201] Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 2007; 20(1): 115–132

[202] Wang Y, Pan  B, Wu J,  Bi X, Liao  W, Pan W,  Gu J. Detection and phylogenetic characterization of a case of Histoplasma capsulatum infection in mainland China. Am J Trop Med Hyg 2014; 90(6): 1180–1183

[203] Ge L, Zhou  C, Song Z,  Zhang Y,  Wang L, Zhong  B, Hao F. Primary localized histoplasmosis with lesions restricted to the mouth in a Chinese HIV-negative patient. Int J Infect Dis 2010; 14(Suppl 3): e325–e328

[204] Pan B, Chen  M, Pan W,  Liao W. Histoplasmosis: a new endemic fungal infection in China? Review and analysis of cases. Mycoses 2013; 56(3): 212–221

[205] Stevens DA. Coccidioidomycosis. N Engl J Med 1995; 332(16): 1077–1082

[206] Wang XL, Wang  S, An CL. Mini-review of published reports on coccidioidomycosis in China. Mycopathologia 2015; 180(5-6): 299–303

[207] Xi L, Fukushima  K, Lu C,  Takizawa K,  Liao R, Nishimura  K. First case of Arthrographis kalrae ethmoid sinusitis and ophthalmitis in the People’s Republic of China. J Clin Microbiol 2004; 42(10): 4828–4831

[208] Zhang QQ, Zhu  LP, Weng XH,  Li L, Wang  JJ. Meningitis due to Prototheca wickerhamii: rare case in China. Med Mycol 2007; 45(1): 85–88

[209] Li DM, Li  RY, de Hoog GS,  Sudhadham M,  Wang DL. Fatal Exophiala infections in China, with a report of seven cases. Mycoses 2011; 54(4): e136–e142

[210] Li DM, Chen  XR. A new superficial fungal infection caused by Coniosporium epidermidis. J Am Acad Dermatol 2010; 63(4): 725–727

[211] Pan W, Liao  W, Hagen F,  Theelen B,  Shi W, Meis  JF, Boekhout T. Meningitis caused by Filobasidium uniguttulatum: case report and overview of the literature. Mycoses 2012; 55(2): 105–109

[212] Wu Y, Wang  J, Li W,  Jia H, Che  J, Lu J,  Liu L, Cheng  Y. Pichia fabianii blood infection in a premature infant in China: case report. BMC Res Notes 2013; 6(1): 77

[213] Fu M, Ge  Y, Chen W,  Feng S, She  X, Li X,  Liu W. Tinea faciei in a newborn due to Trichophyton tonsurans. J Biomed Res 2013; 27(1): 71–74

[214] Chen M, Houbraken  J, Pan W,  Zhang C,  Peng H, Wu  L, Xu D,  Xiao Y, Wang  Z, Liao W. Pulmonary fungus ball caused by Penicillium capsulatum in a patient with type 2 diabetes: a case report. BMC Infect Dis 2013; 13(1): 496

[215] Cai Q, Lv  GX, Jiang YQ,  Mei H, Hu  SQ, Xu HB,  Wu XF, Shen  YN, Liu WD. The first case of phaeohyphomycosis caused by Rhinocladiella basitona in an immunocompetent child in China. Mycopathologia 2013; 176(1-2): 101–105

[216] Zou Y, Bi  Y, Bu H,  He Y, Guo  L, Shi D. Infective meningitis caused by Phialemonium curvatum. J Clin Microbiol 2014; 52(8): 3111–3113

[217] Zhu CY, Yang  YP, Sheng P,  Li W, Huang  WM, Fan YM. Cutaneous chromoblastomycosis caused by Veronaea botryosa in a patient with pemphigus vulgaris and review of published reports. Mycopathologia 2015; 180(1-2): 123–129

[218] Wang L, Al-Hatmi  AM, Lai X,  Peng L, Yang  C, Lai H,  Li J, Meis  JF, de Hoog GS,  Zhuo C, Chen  M. Bipolaris oryzae, a novel fungal opportunist causing keratitis. Diagn Microbiol Infect Dis 2016; 85(1): 61–65

[219] Mijiti J, Pan  B, de Hoog S,  Horie Y,  Matsuzawa T,  Yilifan Y,  Liu Y, Abliz  P, Pan W,  Deng D, Guo  Y, Zhang P,  Liao W, Deng  S. Severe chromoblastomycosis-like cutaneous infection caused by Chrysosporium keratinophilum. Front Microbiol 2017; 8: 83

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