Social, environmental and microbiologic aspects of endemic mycoses in Brazil

Abstract

Many factors that lead to host immunosuppression are clearly known to predispose the host to fungal diseases, significantly influencing the occurrence of mycoses. However, little or nothing has been discussed regarding social or economic factors that can influence the occurrence of diseases caused by fungi. In this minireview, we discuss several factors that may affect the occurrence of mycoses in Brazil, a continentally extended country that is marked by large climatic variations and severe socioeconomic distortions that may limit access to health services for the population.

Introduction

Mycoses are diseases that occur when fungi colonize and damage a host. Fungi that cause disease in humans and other animals are endogenous (when they are components of the host's normal microbiota) or exogenous (when they are acquired from the environment). In all cases, factors such as immunosuppression and external factors such as access to health services (even preventive or therapeutic) influence the incidence of mycoses. It is also important to consider additional factors, such as occupational conditions and climatic variations. Brazil has both humid and drier regions, ranging from the north (near the Equator), through a centre with low humidity, to the south (which is below the Tropic of Capricorn); and extremes can influence the survival and proliferation of environmental microorganisms, and consequently affect the contact of these microorganisms with hosts [1], [2].

The Brazilian territory is marked by deep regional economic inequalities; the distribution of poor cities remains concentrated in the north and northeast [3]. Unfortunately, in 2010, there were 14.6 million people, 10 years of age or older, who did not know how to read, a 9.0% illiteracy rate that reached 29.4% for the elderly. The average monthly income in 2010 was only R$1202 (equivalent to US$707 in that year), with lower incomes in the north and northeast regions, which also suffered from lower access to sanitary sewage and had the highest rates of malnutrition [4], [5]. Furthermore, diagnostic and therapeutic equipment of medium and high complexity is concentrated mainly in capitals, metropolitan regions and in a few regional poles, resulting in a large variation in their availability to patients [3]. Considering the impediments to health services access, it is probable that the epidemiologic data currently available do not reflect reality because correct diagnoses may not be performed.

AIDS and organ transplants are classic conditions capable of immunocompromising a host. In Brazil, from 1980 to 2017, 882 810 AIDS cases were identified, with an average of 40 000 new cases in the last 5 years. Interestingly, there was a reduction in the detection rate of AIDS in south and southeastern states and an increase in detection in the north and northeastern states [6]. From 2007 to 2017, there were 72 807 solid organ transplantations (heart, liver, lungs, pancreas and kidney) performed [7].

In this minireview we provide details available on endemic mycoses with high occurrence in Brazil, taking into account all the information mentioned above. Table 1 summarizes the data discussed in the text.

Table 1.

Summary of aetiologic agents and occurrence of endemic mycosis in Brazil

Site	Mycoses	Aetiologic agent	Local of more incidence	Risk group
Superficial	Malasseziosis [11], [12], [13], [22]	Malassezia spp.	Cosmopolitan disease, with high influence of seasonality of moist and humid climates	Patients undergoing systemic corticotherapy and hosts with intense sweat
Cutaneous	Dermatophytosis [14], [15], [16], [18], [19], [20]	Trichophyton spp., Microsporum spp. and Epidermophyton floccosum	Cosmopolitan disease	People with dry skin, school-age children, rural workers and athletes. People with diabetes, HIV/AIDS infection, immunosuppressed and obese
Subcutaneous	Sporotrichosis [29], [31]	Sporothrix spp.	Higher incidence occurs in Rio de Janeiro and São Paulo	Children or housewives with frequent contact with domestic and stray cats
	Chromoblastomycosis [23], [25], [26], [27]	Fonsecaea, Cladophialophora and Rhinocladiella	Higher incidence occurs in Maranhão and Pará	Rural workers, mainly babassu extractors
Systemic (primary pathogens)	Paracoccidioidomycosis [37], [38], [39], [41], [42], [44]	Paracoccidioides spp.	Several endemic areas with higher incidence: São Paulo, Paraná, Rio Grande do Sul, Goiás; and also regions with progressive devastation of tropical forests	Working-age men and farmers in contact with soil
	Histoplasmosis [47], [48]	Histoplasma capsulatum	Higher incidence occurs in regions with caves and/or with progressive devastation of tropical forests	HIV/AIDS patients, rural workers, speleologists, tourists in contact with bat guano and soil
	Coccidioidomycosis [49], [50], [52], [53]	Coccidioides immitis	Endemic areas with dry climates, mainly Piauí, Ceará, Bahia and Maranhão; also regions with progressive devastation of tropical forests	Rural workers, armadillo hunters and constructors in contact with soil
Opportunistic yeasts and moulds	Candidiasis [12], [13], [69], [70], [71] (dermatitis, mucocutaneous, bloodstream)	Candida spp.	Cosmopolitan disease	Immunocompromised hosts, HIV/AIDS patients, patients with haematologic cancer and stem-cell transplant recipients
	Cryptococcosis [57], [58], [59]	Cryptococcus spp.	Cosmopolitan disease	Immunocompromised male hosts, HIV/AIDS patients, transplant recipients
	Aspergillosis and fusariosis [72], [73], [74], [75]	Aspergillus spp., Fusarium spp.	Cosmopolitan disease	Hospitalized and immunocompromised hosts, patients with HIV/AIDS, haematologic cancer and stem-cell transplant recipients

Superficial and cutaneous mycosis

Superficial fungal infections affect the skin, hair and nails of 40% of world's population, making these one of the most prevalent forms of infection [8], [9], [10]. The main aetiologic agents are the dermatophytes (Trichophyton, Microsporum and Epidermophyton) and yeasts (Candida and Malassezia) [11], [12], [13].

Dermatophytes affect healthy individuals, but predisposing factors includes dry skin, diabetes, HIV infection, immunosuppressed states, obesity, certain athletic activities and possibly smoking [14], [15]. T. rubrum (35.6%) is the most frequent species in many studies, most likely representing the profile of urban dermatophyte microbiota, followed by T. mentagrophytes, T. interdigitale, M. gypseum, T. tonsurans, E. floccosum and M. canis [12], [13], [15], [16]. Onychomycosis is the most common clinical condition in adults; T. rubrum is the fungus most frequently isolated and Candida parapsilosis ranks second [8], [17]. In children aged ≤10 years, the most frequent site of infection was the scalp, mainly caused by M. canis (in the south and southeastern regions) and T. tonsurans (in the north and northeastern regions) [12], [18]. Onychomycoses are frequently associated with nail trauma, excessively sweaty feet, not wearing sandals in public bathrooms and the prolonged use of shoes during the day [19], [20], [21]. Onychomycoses affect military, construction, agricultural and forestry workers; and housewives and manual labourers are also at risk as a result of long hours of immersion of hands and feet in water.

Malassezia is member of the human skin microbiota and a health problem in Brazil. This pathogen grows better in moist and humid environments and causes pityriasis versicolor, prevalent in tropical and subtropical countries. In retrospective studies in south and northwest of Brazil, the disease is more prevalent in men than women, and reports show that growth of Malassezia tends to increase in summer when temperatures are high and is due to sweat [13], [22]. The age group that commonly is affected with pityriasis versicolor is 20 to 40 years [12], [13].

Warmer temperatures and altered rainfall patterns are likely to increase the range and burden of dermatomycosis. However, heterogeneous study design has limited the assessment of numerous, potentially confounding factors, and the striking differences that have been observed cannot reliably be attributed to variations in climate. Furthermore, despite the large occurrence of these diseases, the diagnostic methodologies (direct microscopy and culture) remain ineffective to assess actual epidemiology, although there is no demand for more sensitive and rapid methodologies.

Subcutaneous mycosis

With a high occurrence in Brazil, subcutaneous mycoses are caused by dematiaceous fungi and the Sporothrix schenckii complex [23], [24]. The infection occurs by traumatic inoculation of the pathogen, and the disease may be chronic, leading to fibrotic and granulomatous reactions. Although subcutaneous mycoses are relevant, studies reporting the global burden of neglected diseases rarely mention its occurrence in Brazil. Among patients, rural workers or farmers in regions without access to health services are commonly affected. The Amazon region of Brazil has been considered to be the main endemic area of chromoblastomycosis since the majority of patients are from areas with high pluviometric indexes, with elevated temperatures and dense forestation. Maranhão ranks first in chromoblastomycosis notifications [23], with higher occurrence in babassu (babaçu) coconut extractors. Also, there are epidemiologic data from the states of São Paulo, Rio de Janeiro and Rio Grande do Sul [25]. The species Fonsecaea pedrosoi, F. monophora and F. nubica are the most prevalent agents. Cladophialophora carrionii is the only species that is restricted to semiarid areas with Cactaceae as the main vegetation [23]. Rhinocladiella aquaspersa is an uncommon species found in humid as well as dry climates [26]. The diagnoses, which include diagnoses via tissue biopsy and culture (standard methods of subcutaneous mycosis diagnosis), are not always performed in endemic areas [27], which causes the epidemiologic data to be underestimated.

Obtained from animals and plant debris, sporotrichosis is a neglected zoonotic mycosis caused by pathogenic fungi belonging to the Sporothrix schenckii complex, with S. brasiliensis as the most prevalent aetiologic agent [24], [28]. Classical infection is associated with traumatic subcutaneous inoculation of soil, plants or organic matter contaminated with fungus; but a large number of data also report transmission occurring from infected animals, with cats being the main vehicle of fungi transmission between animal and human [29], [30]. In Rio de Janeiro state, this disease reached an epidemic status, with over 4700 domestic felines and around 4000 humans affected since the mid-1990s [31], [32]. Many patients are immunocompetent and often are from rural areas, i.e. farmers and gardeners [33]. In urban areas, endemic regions of sporotrichosis in Brazil are characterized by poor sanitation, substandard housing and little or no access to health services. Patients are mainly children or housewives with frequent contact with domestic and stray cats [29], [32], [33], [34]; indeed, patients report that they need to have cats in their houses as a mode of biological control of rodents. The most severe cases occur in HIV patients, with a higher number of hospitalizations and deaths [33], [35].

Systemic mycosis

The main agents of systemic mycosis are the thermodimorphic fungi belonging to the genera Paracoccidioides, Histoplasma, Coccidioides and also the yeast Cryptococcus, obtained by inhaling infectious propagules. Paracoccidioidomycosis is a granulomatous disease, endemic in South and Latin America, with about 80% of the patients from Brazil (3360 to 5600 cases of paracoccidioidomycosis annually), mainly in the states of São Paulo, Paraná, Rio Grande do Sul, Goiás and Rondônia [36], [37]. Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis (with a wide distribution in the country) and P. lutzii (restricted to the centre-west region) [38], [39], [40]. The most frequently affected individuals are working-age men, probably because the transition to parasitic forms of yeast can be inhibited by the action of mammalian oestrogen [41], [42]. Epidemiologic data have suggested that in the endemic regions, Paracoccidioides spp. exists as a saprophytic fungus in plants and soil. This corroborates the fact that the major risk factor for acquiring infection is any activity related to the management of soil contaminated with the fungus, such as agriculture, earthworks, soil preparation, gardening and transportation of vegetable products [43]. It has been suggested that the fungus resides at a depth of 2 to 20 cm in the soil, that it occurs in places containing natural and/or anthropic disturbed vegetation near water sources and that humidity, precipitation and soil water storage are factors that lead to the growth and sporulation of the fungus [43], [44].

Histoplasmosis is caused mainly by Histoplasma capsulatum, which is generally found in regions with nitrogen-rich, acid soil and with relative humidity between 60% and 87% and average temperature of 27°C. Frequently it is associated with the presence of bird and bat excreta, but air currents can carry the conidia for longer distances, making it possible for people who have not had direct contact with contaminated sites to contract the infection [45]. In Brazil, there is no compulsory notification (similar to other systemic mycoses), and most of the data are based on cutaneous tests with histoplasmin. Information presented in the surveillance and control proposal of the Ministry of Health in 2010 showed a significant prevalence of histoplasmosis in the south (6.30–89%), southeast (4.60–94.7%), northeast (2.60–61.50), central west (9.60–63.10%) and north (12.8- 50.1%) of the country, according to histoplasmin test results. Nevertheless, in Brazil, there are several endemic areas, and occasionally cases of small outbreaks arise as a result of activities that lead a group of people to have contact with contaminated sites [46], [47], [48]. In the state of Ceará, Brilhante et al. [47] estimated that the mortality rate by histoplasmosis among HIV/AIDS patients was 42.3% in a 5-year period.

Aetiologic agents of coccidioidomycosis, Coccidioides immitis and C. posadasii, are isolated from areas of arid climate with alkaline and sandy soil and very hot summers [49]. In Brazil, the first reports of this disease are from the late 1970s, in the states of Piauí and Ceará [50], [51]. Currently endemic areas for coccidioidomycosis are recognized in the states of Piauí, Ceará, Bahia and Maranhão [46], [52]. In the state of Piauí, considered the highest density, most of the small outbreaks were associated with armadillo hunting [53].

Cryptococcosis is a systemic mycosis that can occur as both primary and opportunistic infections [54], with meningoencephalitis as the most severe manifestation [55]. This disease is caused by Cryptococcus neoformans and C. gattii, and is one of the most important opportunistic diseases in HIV/AIDS patients and one of the major contributors to the early mortality of immunocompromised patients, accounting for 13% to 44% of the deaths of HIV-infected individuals in poor countries [56]. It is estimated that in Latin America, C. neoformans is widespread and responsible for more than 90% of the cases of cryptococcosis, affecting predominantly patients with HIV [57]. In Brazil, mortality rate ranged from 32% to 60% in HIV-infected population. Meningeal cryptococcosis mostly caused by C. neoformans occurs predominantly in these patients despite highly active antiretroviral therapy being widely distributed in Brazil [58], [59], [60].

Invasive yeast and opportunistic mould diseases

Several filamentous fungi and yeast are agents of invasive fungal infections in immunocompromised patients. These are mainly patients with haematologic cancer and stem-cell transplant recipients [61], [62]. In Brazil, candidaemia is associated with high morbidity and mortality rates [63], [64]. In a multicentre surveillance study in Brazil, C. albicans (34.3%), C. parapsilosis (24.1%), C. tropicalis (15.3%) and C. glabrata (10.2%) were the most prevalent species in bloodstream infections. Emerging yeast, such as Saccharomyces cerevisiae, has also appeared, causing infection in Brazil [65], [66], [67]. It is also important to mention the emergence of the yeasts Trichosporon mycotoxinivorans, causing invasive infections in Latin America [68], and C. auris, a globally emerging yeast pathogen with a high capability of developing multidrug antifungal resistance, which has not been yet reported in the Brazil. This may have occurred because difficulty in identification, since it is not identified by most of the methods used within the hospital laboratories in Brazil. Usually the identification of yeast is made by CHROMagar Candida and other tests, such as germ tube or physiological tests. However, these techniques have failed to identify organisms at the species level, which has an impact on the treatment of patients since there are species resistant to certain antifungals [62], [69], [70], [71].

In Brazil, several moulds have already been isolated that cause opportunistic systemic infection, such as Aspergillus section Flavi [72]. Fusariosis was also reported in a haematology ward and was associated with the rise of Brazilian plantations (mainly soybean) and pasture areas where previously there was native vegetation, with a consequent loss of fungal richness and diversity [73], [74]. In general little is known about the prevalence of invasive yeast and opportunistic mould diseases because there are few medical centres able to perform accurate identification at the species level [72]. Indeed, this is true for the identification of opportunistic filamentous fungi, such as Aspergillus, that has been identified only by colony morphology and microscopic characteristics and may not be reliable for distinguishing between Aspergillus species [72], [75].

Conclusion

Performing research on these neglected mycosis, as well as knowing endemic areas, how climate influences their occurrence and the population at risk, may improve the ability to combat the high occurrence of these diseases. The attention of public health officials is vital to understanding the real situation of endemic mycoses in Brazil. Furthermore, new public policies and investment are needed to improve the clinical diagnosis, professional training and investment in antifungals for the treatment of fungal infections.

Conflict of interest

None declared.