Environmental and Social Determinants Related to Candidiasis

Abstract

Environmental, social, and economic factors are decisive for susceptibility to infectious diseases caused by opportunistic pathogens, such as Candida. Their incidence has increased significantly in recent years, mainly due to a greater number of immunocompromised people, the social and economic environment in which they develop and the current environmental crisis, climate change, which exacerbates health inequalities. Therefore, a literature review was conducted on the main social and environmental determinants of health and virulence factors as determinants of Candida spp. infection. Several studies provide valuable insights into the main predisposing determinants of Candida colonization and infection in relation to the health status of people and the virulence factors of the aetiological pathogen itself. Although there are some studies on the prevalence of Candida in different social classes, there are still few criteria to derive or claim an objective opinion on the social conditions under which this opportunistic pathogen occurs. Therefore, an overall picture that takes into account not only the intrinsic factors of the individual (human biology, health status, etc.) but also the social determinants of health, which may be related to differences in colonization and infection by different Candida species, is still lacking.

1. Introduction

Lifestyle, human biology, health care, and natural and socioeconomic environment are factors that determine a person health status and are collectively referred to as social determinants of health (SDH) [1]. Different circumstances, in which people are born and develop, are crucial for the emergence and spread of emerging diseases as a result of environmental changes [2], lifestyle, human biology, and the distribution of economic resources [1, 3, 4]. Emerging diseases caused by emerging pathogens include opportunistic fungal infections, which are a major cause of morbidity and mortality and are responsible for approximately 1.5 million deaths per year worldwide [5]. The fourth most common cause of all nosocomial fungal infections associated with increased risk factors is mainly due to Candida species [6].

Candidiasis is a disease caused by various species of the genus Candida. These are yeast fungi that are part of the human microbiome and can be the most common opportunistic fungal pathogens in various infections of the skin, mucous membranes, deep structures, and internal organs [7]. Candida albicans is the main cause of nosocomial infections in the bloodstream, known as candidemia [8]. Factors responsible for variations in the prevalence of Candida include the clinical setting, nutritional factors, geographic location, pharmacological therapies, invasive devices, immunosuppressive and chronic degenerative diseases, and hygienic conditions [9, 10, 11, 12, 13]. Due to the above factors, the emergence of non-albicans Candida species as opportunistic pathogens has been observed in recent years, particularly in underdeveloped countries, especially in vulnerable patients [11]. There is evidence that their emergence is due to the probably indiscriminate use of prophylactic and therapeutic antifungal agents [14], with a clear tendency toward more resistance [15, 16]; on the other hand, adaptation to climate change has had a strong impact on the pathogenicity of fungi. Candida spp. can also form biofilms and possess other virulence factors that protect them from the action of various antifungal agents. The aim of this literature review is, therefore, to outline the determinants that favor the development of Candida spp. with social determinants being of particular interest, and to examine the influence that the environment, particularly climate change, has on the pathogenicity of emerging species.

2. Candida and candidiasis, an overview

Candida belongs to Kingdom: Fungi, Phylum: Ascomycota, Subphylum: Ascomycotina, Class: Ascomycetes, Order: Saccharomycetales, Family: Saccharomycetaceae, and Genus: Candida. It is a dimorphic yeast that exhibits different morphological forms under different environmental conditions. For example, C. albicans and C. dubliniensis can form germ tubes and thick-walled chlamydoconidia in addition to yeast-like cells, whereas C. glabrata only has yeast-like cells. Candida yeasts are about 2–6 X 3–9 μm in size, depending on the species [7, 17, 18]. C. albicans use glucose as a carbon source and amino acids as nitrogen sources [19]. The cell wall of Candida spp. consists of mannan (20%), β-(1,3)-d-glucan (50 to 70%), chitin (10 to 20%), proteins (3 to 6%), lipids (1 to 5%), and pigments (melanin). Electron microscopic studies show differences in the organization and composition of the cell wall in the two different morphogenetic forms of this yeast [20]. The cell wall is important for the control of cell permeability and protection against osmotic and mechanical stress. It mediates interaction with the environment via adhesins and a large number of receptors that, when activated, trigger a complex signaling cascade within the cell [21]. Ergosterol is the most abundant sterol and is characteristic of the cell membrane. It provides stability, rigidity, and resistance to physical stress factors [21, 22].

Many species of the genus Candida are part of the normal biota of the skin, mucous membranes, and gastrointestinal tract of animals and humans; others have been isolated from soil, food, and hospital environments. Between 30 and 70% of healthy people carry at least one Candida species [23]. This genus comprises about 200 identified species, 20 of which have caused candidiasis. Ten species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii, C. famata, C. kefyr, C. krusei, C. lusitaniae and C. dubliniensis) are most frequently associated with the various clinical forms of this mycosis [7] and can affect both healthy and immunocompromised patients. An important finding is the identification of the species Candida auris, which has emerged as a global public health threat in recent years. C. auris poses a major challenge in hospitals as it is difficult to detect, resistance to multiple drugs, changes in its virulence factors, has a high patient mortality rate in patients, and is able to survive on surfaces for long periods of time [6, 24].

Candida is a common inhabitant of the skin and mucous membranes and is part of the natural microbiota of the human body. When its nature changes or the host organism’s resistance to Candida decreases, it can multiply excessively and cause local, disseminated, or systemic infections of the skin, mucous membranes, deeper structures, and internal organs, which is known as candidiasis [2]. The severity of the infection depends mainly on the primary alterations of the host and less on the pathogenic properties of the fungus. Most infections are endogenous, that is, they are caused by yeasts that are part of the patient’s indigenous microbiota [25]. However, infection can also originate from exogenous sources, such as intravenous catheters or cardiac prostheses, especially when these are used in immunodeficient patients [20]. There are also reports of Candida infections in immunocompetent patients without corresponding signs or symptoms [26]. The most common forms of candidiasis are those with superficial involvement, including vulvovaginitis and skin and nail infections [27].

Predisposing factors for candidiasis include extreme age (childhood or old age), increased concentrations of sex hormones such as estrogen in pregnancy (increased vaginal glycogen) creating a carbon-rich environment [28], occlusion of epithelial surfaces (by dentures or occlusive dressings), immune dysfunction (secondary: E.g. HIV/AIDS, leukemia, corticosteroid therapy), chemotherapy (immunosuppressants, antibiotics), endocrine diseases (diabetes mellitus), carcinomas, damaged nail folds, and others [29]. The fourth most common cause of all nosocomial infections associated with increased risk factors is mainly due to Candida species [6].

According to various epidemiological studies, about 90% of infections caused by Candida are due to five species, including C. albicans, and non-albicans such as C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei [14, 30]. However, C. albicans is still the main culprit for invasive infections [18, 31, 32]. Today, the list of reported species continues to grow as molecular diagnostics are used to identify them at the species level, which, given the differences in virulence and drug sensitivity, helps to optimize the treatment of infections caused by species other than C. albicans [33, 34].

3. Superficial candidiasis

In superficial mycoses, fungi colonize the outermost keratinized layers of the skin, hair, and nails [35]. They are associated with changes in the hydration and pH of the skin, mouth, throat, and other superficial tissues [7]. Superficial candidiasis is divided into cutaneous and mucocutaneous. The former can manifest as intertrigo in folds, diaper dermatitis, paronychia, and candida onychomycosis, which can be acute or chronic. Superficial candidiasis is one of the most common clinical forms and is typically chronic and recurrent; it can also be the onset of systemic infection [29]. Mucocutaneous candidiasis includes oral candidiasis, digestive tract candidiasis (which can be superficial if invasion is limited to the mucosa and submucosa) [36], vaginitis, balanitis, bronchial, and pulmonary candidiasis. Chronic mucocutaneous candidiasis and Candida granuloma are forms of disseminated and deep candidiasis [20].

4. Systemic candidiasis

Over 90% of deaths from mycoses or invasive fungal infections (IFI) are due to candidiasis, aspergillosis, cryptococcosis, and pneumocystosis. Invasive candidiasis, the most widespread of these, leads to severe illness and death, especially in critically ill patients and people with weakened immune systems [15, 16]. With the increasing number of invasive medical procedures and the growing number of immunocompromised patients, an increased incidence of invasive candidiasis caused by non-albicans Candida species, including C. auris, a yeast with potential for nosocomial transmission that has spread rapidly worldwide, has been observed [37, 38].

Primary risk factors for IFI include neutropenia with less than 500 neutrophils/ml lasting longer than 10 days, blood-related cancers, bone marrow transplants, prolonged corticosteroid treatment of more than 4 weeks, long-term ICU stays of more than 7 days, chemotherapy, HIV infection, invasive medical procedures, and recently administered immunosuppressive drugs. Other risk factors include malnutrition, solid organ transplants, severe burns, major surgery, patients receiving parenteral nutrition, and the use of intravascular catheters [26].

Invasive candidiasis, which is often associated with hospitalization, involves blood infections (candidemia) and serious infections such as intra-abdominal abscesses, peritonitis and osteomyelitis [39], pneumonia [40], ocular candidiasis [26], endocarditis [41], candiduria [42], and fungal infection in the central nervous system [43]. Almost all organs can become secondarily infected after hematogenous dissemination of the fungus [19].

5. Virulence factors and resistance

Virulence factors allow Candida spp. to rapidly adapt to different host niches and cause infections in patients with risk factors. The strategies used to combat the host’s natural defense mechanisms are strongly influenced by the environment [38]. Virulence factors include: (a) the expression of surface molecules to achieve attachment of the microorganism to host cells using adhesion proteins; (b) the formation of biofilms is clinically important as their spatial arrangement facilitates the penetration of nutrients, and excretion of waste products [44], they are more resistant to antifungal drugs and provide protection from host’s immune defenses [45, 46]; therefore, Candida spp. can colonize long-term medical devices, such as intravascular catheters, and the cells can separate and lead to widespread infection [38, 47]; (c) secretion of hydrolytic enzymes that promote penetration and destruction of surrounding tissue, thereby releasing nutrients from host cells [48] and toxins such as candidalysin, a cytolytic peptide toxin that is essential for systemic and mucosal infections and enables epithelial damage [49]; (d) the ability to change its morphology (dimorphism), characterized by the morphological transition from blastoconidia to hyphae, and the form of transition between these are pseudohyphae [35]; (e) tigmotropism, a mechanism that allows invasion of invaginations [48]; (f) its metabolic adaptability due to a phenotypic change and response to stress mediated by heat shock proteins (HSP) [38, 50]. Several studies have shown that, unlike other Candida species, C. auris has adapted to hostile environments as it can grow at high temperatures (> 40°C) and tolerates high salt concentrations (> 10% NaCl, wt/vol) [51].

5.1 Resistance

Years of use of antifungal and antibacterial substances in agriculture and healthcare have altered the global microbiome, leading to an increase in fungal infections that are resistant to drugs in plants, animals, and humans [37, 52].

The sensitivity to antifungal agents can differ among various Candida species and even among strains of the same species. Resistance to microbes can develop with any type of antifungal agents, making the treatment of candidemia more complex. [30]. While resistance to multiple drugs is uncommon, there is a growing number of reports on inherent and developed resistance to several drugs (azoles, echinocandins, and polyenes) in various Candida species, particularly in C. glabrata and more recently in C. auris. In general, non-albicans species are associated with increased resistance and high mortality rates [53, 54]. First-line drugs, including echinocandins and azoles, have been effective, but resistance has increased in Candida species due to indiscriminate prophylactic and therapeutic use [52, 55]. Other factors responsible for increased resistance include subtherapeutic drug concentrations at infection/colonization sites, sequestration of the drug in the biofilm matrix [56], overexpression of the drug target (e.g. efflux pumps), development of compensatory pathways for ergosterol production, and activation of cellular stress responses [57, 58]. Recent research suggests that mutations of DNA repair genes for mating defects may facilitate the acquisition of resistance genes, which has been observed in C. glabrata [53].

Studies, in the USA, have reported a low incidence of fluconazole resistance in C. albicans, approximately 0.5 to 2%. In contrast, higher rates of resistance have been reported in C. tropicalis, C. parapsilosis, and C. glabrata: 4 to 9%, 2 to 6%, and 11 to 13%, respectively. The emerging yeast C. auris can have a resistance rate up to 93% to fluconazole, 35% to amphotericin B, and 7% to echinocandins [58]. On the other hand, several studies have observed that strains of C. glabrata exhibited reduced susceptibility to one or more echinocandins in addition to resistance to fluconazole [57, 59].

6. Environmental determinants conducive to the development of candidiasis

6.1 Adaptability to different environmental conditions and climate change

Clinically important Candida species have been isolated from different environmental sources whose substrates could be their main reservoirs or environmental niches. Therefore, it is important and necessary to conduct more studies that consider the ecological triad: Pathogen-Host-Environment. Environmental conditions, such as global warming and climate change, are a favorable scenario for the change and adaptability of different microorganisms.

There are several papers of great importance reporting the presence of C. auris in clinical settings and its potential to spread rapidly among patients. Arora et al. [59] found C. auris in samples of beach sand and wetlands in the Andaman Islands, India. Casadevall et al. [60] hypothesized that C. auris acts as an environmental fungus that may have existed as a saprophytic plant in specialized ecosystems, such as wetlands. The emergence of C. auris could be due to the rise in global temperatures due to anthropogenic climate change, which led to the selection of thermotolerant strains and their combined tolerance to salinity, resulting in its emergence as a pathogenic fungus in humans that has a wide geographic range. According to Casadevall et al. [61], the discovery of C. auris at two locations on the remote Andaman Islands confirms its status as an environmental organism, a necessary prerequisite for the hypothesis.

On the other hand, C. albicans is not only a commensal yeast of humans and animals but also has been detected in soils, freshwater, seawater, vegetables, and wetlands [62]. Studies by Nunn et al. [63] showed the presence of C. dubliniensis in ticks associated with seabirds in Ireland. C. tropicalis has been detected in agricultural fields, forest soils, oil, and mud contaminated soils, fresh and seawater, beach sand, rivers and lakes, sugar cane bagasse, and coconut water [64]. C. parapsilosis, a ubiquitous microorganism, is part of the human microbiota and colonizes mucous membranes, skin, and nails. C. auris is widely distributed in nature and is often found in various nonhuman sources such as domestic animals, insects, soil, seawater, and plants [65, 66]. C. glabrata is a species commonly found in the environment, especially from various sources such as water, soil, surfaces, and plants [67]. In another study, the presence of C. glabrata was detected in the gut microbiota of yellow-legged gulls [68]. Randhawa et al. [69] isolated C. krusei from the decaying wood of Ficus religiosa, and it has also been isolated from mammals, birds, springs, and fruits [70]. Another unusual Candida species that rarely infects humans is C. melibiosica, which is often isolated from rivers and oceans, but there are also studies reporting its presence in some traditional beers. However, in 2010, the first case of nosocomial fungemia in an 82-year-old patient caused by C. melibiosica was described [71].

Global warming and climate change have a significant impact on the pathogenicity and survival of fungi, as well as on the environmental reservoir of the pathogen. Adaptation to higher temperatures increases its ability to multiply in the human body, which has a high basal temperature. This leads to an increased potential for disease, even in species previously considered nonpathogenic. This affects the spread of fungi as the increase in heat-resistant species facilitates interaction with humans, infection and transmission through skin contact, inhalation, and/or ingestion [2, 72].

7. Contamination of the clinical environment and the hands of healthcare personnel

One of the risk factors for invasive fungal infection (IFI) in immunocompromised patients is prolonged hospitalization. IFIs with Candida spp. associated with hospitalizations are associated with 20 to 40% of all deaths, with a mortality rate of 15 to 35% in adults and 10 to 15% in newborns. Nearly 50% of candidemia episodes occur in intensive care units, contributing to prolonged hospitalization and significant healthcare costs [14, 34], with mortality ranging from 40 to 60% [33, 73, 74].

In healthcare settings, contaminated surfaces in the environment contribute significantly to the spread of infectious diseases. Despite regular cleaning, some microorganisms can form biofilms that lead to permanent contamination. In addition to reducing susceptibility to antimicrobials and biocides, biofilms also protect microorganisms from a hostile environment, including desiccation over extended periods of time [75].

In a study by Welsh et al. [76], the ability of C. auris and C. parapsilosis to persist on common plastic surfaces in healthcare settings was investigated. The results showed that C. auris remained viable for at least 14 days and C. parapsilosis for at least 28 days. In addition, Kramer et al. [77] reported that C. albicans survived on surfaces for up to 4 months. In another study, persistence of various Candida species in the hospital environment was reported on both dry and mostly moist surfaces, indicating a potential route of spread for emerging multidrug-resistant fungal pathogens, such as C. auris [78] and colonization or infection of hospital patients and healthcare workers [75].

Although most Candida infections originate from endogenous sources, it is increasingly reported that the hands of healthcare workers serve as carriers for pathogen transmission. Sakita et al. [79] investigated the susceptibility of five yeasts (C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei) isolated from the hands of healthcare workers (physicians, nurses, and assistants) to different antifungal agents. Their results showed that the hand isolates had high resistance rates, with C. glabrata being the most resistant and C. parapsilosis the most common. In another study conducted in a neonatal intensive care unit in Brazil, Candida species were isolated from the hands of healthcare workers, including isolates of Candida spp., C. parapsilosis sensu stricto, C. parapsilosis sensu, C. metapsilosis, C. orthopsilosis, C. famata, C. albicans, C. lusitaniae, C. kefyr, C. krusei, C. glabrata, C. tropicalis, and C. guilliermondii [80]. Delfino, Scordino [81], reported the presence of yeasts on the hands of nurses, orderlies, residents, and physicians in three intensive care units of a hospital in Milan, Italy. Approximately, 39% of the healthcare staff tested positive for yeast. C. parapsilosis was the most frequently isolated species followed by C. albicans, C. glabrata, C. tropicalis, C. lambica, C. lusitaniae, and C. krusei.

A study conducted by Kordecka et al. [82] in a hospital in Poland revealed a high prevalence of Candida, with C. albicans, C. glabrata, and C. krusei being the predominant species in samples collected from cell phones and especially on the hands of medical staff. Community data show that the frequency of colonization of the hands of hospital staff with yeasts of the genus Candida is about 20% for medical staff and 80% for nursing staff and paramedical assistants. This shows how environmental factors, such as the hospital environment, directly influence the colonization of individuals with the genus Candida [83, 84].

7.1 HIV/aids

Both acquired and congenital immunodeficiencies can be associated with an increased susceptibility to systemic infections [26]. Immunocompromised patients have an increased risk of candidemia and deep infections with visceral disease [33].

HIV/AIDS is the most common factor associated with oropharyngeal candidiasis in children and adolescents. It is directly related to low peripheral blood CD4+ T lymphocyte counts, below 200 cells/μL, so its presence has been used as a clinical marker for infection, prior antifungal use, and changes in the oral environment [85]. In contrast to oropharyngeal candidiasis, it has been observed that patients with HIV/AIDS who develop esophageal candidiasis have lower CD4+ T lymphocyte counts [86]. The presence of oropharyngeal or esophageal candidiasis is considered an indicator of inmunosuppression [87].

C. dubliniensis has a high prevalence in the oral cavities of people infected with the human immunodeficiency virus [57], and other associated species in both HIV-infected children and adults are C. albicans and C. glabrata [85]. In a study conducted in Kerman, Iran, to compare the demographic characteristics and frequency of Candida species causing oropharyngeal infection between patients with HIV/AIDS and individuals without HIV, it was found that both groups differed significantly in terms of species prevalence. According to the results, C. albicans was the most common species isolated from patients with HIV/AIDS, followed by C. glabrata, and other species isolated were included C. parapsilosis, C. krusei, and C. kefyr [87].

7.2 Nutritional factors

The root causes of child malnutrition include lack of access to food, lack of health care, use of unsafe water and sanitation systems, and poor care and feeding practices. These underlying problems are caused by conflict, inadequate education, poverty, gender inequality, inadequate infrastructure, and other fundamental problems [88]. Globally, malnutrition is the leading of immunodeficiency and is considered a risk factor for infant death. Malnutrition has been found to increase the risk of oral colonization with Candida by 4.5 to 5.3 times compared to apparently healthy infants. In this study, the Candida species found in children aged 6 to 13 years with malnutrition were C. albicans, C. tropicalis, C. krusei, and C. glabrata [10]. Lu [89] reported a high prevalence of oral Candida spp. infections in patients (males and females aged 16 to 76 years) from a hospital in Kaohsiung, Taiwan, who had iron deficiency anemia. A high incidence of oral Candida infections was found in 85% of patients with iron deficiency. Another study reported that malnourished infants and low birth weight infants were at increased risk of C. parapsilosis infection due to the administration of parenteral nutrition to ICU patients [90]. In a study of 18 of 54 patients (older adults) in two geriatric hospitals who had oral candidiasis, it was associated with protein-calorie malnutrition, in addition to other conditions, most notably poor dental hygiene [91]. Another study in France, conducted in hospitalized older adults, found a positive correlation between oral condition, dysphagia, and malnutrition with Candida spp. infections [92].

7.3 Chronic degenerative diseases

In the last decade, the increase in the immunocompromised population has led to a high incidence of invasive Candida infections [93]. Diabetes mellitus (DM) is one of the most common endocrine diseases, affecting the immune system. Patients with DM are susceptible to opportunistic infections due to elevated serum glucose levels and a weakened cellular immune system [94]. Type 2 diabetes mellitus (DM2), which affects ninety percent of people, is primarily associated with personal lifestyle, including a high-calorie diet, lack of physical activity, and smoking [93]. Several studies have shown that patients with DM are more likely to be oral Candida carriers and have an increased risk of candidiasis, which is related to poor metabolic control, neutrophil dysfunction, decreased salivary flow, increased blood and salivary glucose concentrations, and poor immune response. It is well known that patients with diabetes mellitus are more susceptible to fungal infections, especially C. albicans [95, 96]. In a study by Aitken et al. [95] in Chile, five Candida species were identified, with C. albicans being the most common followed by C. glabrata, C. tropicalis and C. guilliermondii in saliva samples from people with DM2.

In Shiraz, Iran, Zomorodian et al. [94] conducted a study on the prevalence of oral Candida colonization in patients with DM1 and DM2. The results showed different Candida species of the oral mucosa, with C. albicans being the predominant species, followed by C. dubliniensis, C. glabrata, C. parapsilosis, C. guilliermondii, C. krusei, C. kefyr, and C. tropicalis. One population at potential risk for candidemia is patients with cancer. Both hematologic and solid neoplasms have been reported to be predictors of this infection. In addition, this infection could worsen the prognosis of malignant diseases (30-day mortality is up to 56%). According to the results of a study on the epidemiology and risk factors of candidemia in cancer patients in a cancer center in China, mortality was significantly higher than that of bacterial bloodstream infections, with C. albicans being the leading pathogen, followed by C. parapsilosis, C. tropicalis, C. glabrata, C. lusitaniae, and C. famata. In addition to hematologic and solid neoplasms, total parenteral nutrition, urinary catheters, cancer metastases in distant organs, and gastrointestinal cancers were shown to be predictors of candidemia [97].

Clinical data on candidemia in adult cancer patients reported that C. albicans was the most common species in both hematologic and oncologic patients. In hematologic patients, C. albicans was the most common species, followed by C. parapsilosis, C. krusei, and C. glabrata, while in oncologic patients, the second most common species was C. glabrata, followed by C. parapsilosis and only one case of candidemia due to C. krusei in an oncologic patient. Other isolated species were C. tropicalis, C. guilliermondii, C. kefyr, C. lusitanae, C. famata, C. rugosa, and C. sake [98].

The increased susceptibility of cancer patients to Candida infections is largely due to the weakening of innate immune cells and epithelial barriers caused by chemotherapy. These are the body’s main defense mechanisms against fungal infections. In addition, conventional chemotherapeutic agents have a negative effect on the components of the adaptive immune system that play a crucial role in the antifungal response [99].

7.4 Extreme age

According to the literature, the prevalence of oral candidiasis in newborns varies between 4 and 15%, with C. albicans most commonly associated with thrush. The prevalence of invasive candidiasis correlates with low birth weight [100] and prolonged hospitalization, affecting 2 to 20% of newborns. It accounts for 10% of all cases of sepsis in low birth weight neonates (<1500 g) and is the second most common cause of death due to opportunistic infections [101]. Several surveillance studies have shown that most cases of invasive candidiasis in infants and neonates are due to C. parapsilosis as a first or second cause, both in Europe and North America [90]. In particular, CNS candidiasis in neonates is largely due to the immaturity of the physical (blood-brain) barrier to Candida spp. [102].

Candida colonization increases with age because older adults have several metabolic disorders, including decreased liver and kidney function, use of multiple medications, and malnutrition. As the immune system deteriorates with age, this leads to increased susceptibility to infectious diseases, reduced response to vaccines, higher incidence of cancer, and an increase in autoimmune and other chronic diseases. Both the innate and adaptive immune responses are impaired by the aging process [103]. Studies based on oral cavity cultures in middle-aged and older adults have identified C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis [104]. It has been observed that C. glabrata in particular is more common in adults than in children and neonates [57]. In the geriatric population, oral candidiasis is one of the three main reasons for consultation due to stomatitis caused by the use of dentures [105].

7.5 Hygienic conditions

Candida grows on surfaces and often colonizes dentures, leading to denture stomatitis or subplate stomatitis. The diagnosis of denture stomatitis is important. According to Ibañez et al. [105], about 50% of the people in their study population with an average age of 65 to 74 years and 70% from 75 to 84 years used removable dentures. Regarding the factors associated with the development of subplaque candidiasis, in the studies conducted in different populations, the colonization of the surface of removable dentures by Candida species is mainly attributed to the poor or absent hygiene that patients perform both in the oral cavity and on their dentures.

Another condition that is particularly common in young children and the elderly who live in poor hygienic conditions is intertrigo caused by Candida, which is favored by the following factors: Moisture, heat, friction, and maceration [106].

7.6 Occupational exposure

There are different types of occupational hazards that can cause various clinical manifestations, most of which are superficial and cause high morbidity in the working population. A link has been observed between working conditions and dermatological diseases. An example of this is intertrigo and onychomycosis of the hands, which is not only related to the humid environment but also to contact with highly sugary foods processed by bakers, cooks, manual strawberry pickers, fruit packers, food handlers, or food shippers, in which case it is an occupational disease [20]. Leal et al. [107] investigated superficial mycoses in 21 workers of a metal smelting company, 81% of whom were infected [17] with some type of dermatomycosis. Five cases belonged to intertriginous candidiasis caused by C. albicans. The authors concluded that the high incidence of superficial mycosis (including candidiasis) among the workers was due to the environmental conditions in the workplace such as humidity, high temperature, personal hygiene in a communal bathroom, and occlusive footwear for long working hours.

Silias et al. [108] carried out a study on 109 female workers (seamstresses) in a lingerie factory in Puebla, Mexico, 56 of whom had athlete’s foot. The laboratory data showed that Candida spp. grew in 15 patients, with women being the most affected, as well as patients with diabetes mellitus, carriers of systemic lupus erythematosus, and the only patient with leukemia. The authors conclude that the following factors predispose to the development of an athlete’s foot: the heat generated by the machines, the duration of exposure, the wrapping of the foot by synthetic footwear, and poor personal hygiene. Occupational mycoses can seriously harm the working population.

8. Epidemiology

The epidemiology of candidemia and the distribution of Candida species varies over time, between geographic regions and hospitals, and under the considerable influence of patient characteristics, antifungal drug administration, and clinical practices [109]. Although C. albicans is considered the most common and virulent cause of candidemia worldwide, currently, more than half of candidemia cases are attributed to non-albicans Candida species, mainly C. parapsilosis, C. glabrata, C. krusei, and C. tropicalis, as well as other emerging pathogens such as C. auris, probably as a consequence of the increasing use of azoles, echinocandins or other prophylactic/therapeutic antifungals [14, 32]. This is consistent with the 20-year surveillance study of the SENTRY antifungal surveillance program 1997–2016, which observed that the overall proportion of infections attributable to C. albicans decreased from 57.4 to 46.4% [110]. In the USA, more than 30% of candidemia cases are now caused by C. glabrata, with other commonly isolated species being C. tropicalis and C. parapsilosis a worrying trend given the higher rates of antifungal resistance in associated with this species [37, 111]. In northwestern Europe, as in the USA, the second most common species is generally C. glabrata. In Latin America, southern Europe, India, and Pakistan, C. parapsilosis and C. tropicalis are found more frequently than C. glabrata [111].

The rapid emergence and spread resistant C. auris [39] have significantly altered the epidemiology of candidemia in different geographical locations and healthcare facilities as it has become a major cause of invasive infections [112]. As of February 2021, C. auris has been reported in 47 countries [113]. The first isolate was reported in late May 2020 from the bloodstream of a patient with severe endometriosis and multiple gastrointestinal complications; the infection subsequently spread to 12 patients in the ICU [114, 115].

Table 1 shows a summary of the main determinants of Candida colonization infection, which include intrinsic factors of the etiological agent (virulence factors, resistance to fungi, adaptation to different environments and climate change) and risk factors related to the host (immunosuppression, habits, occupation, and hospitalization).

Determinants	Main effects	References
Virulence factors	Surface molecules; Biofilm; Secretion of hydrolytic enzymes and toxins; Dimorphism; Metabolic adaptability; Tigmotropism	[35, 44, 45, 46, 47, 48, 49, 50, 116]
Antifungal resistance	Intrinsic and acquired resistance; Indiscriminate use of antifungals; (Varies according to each Candida species and even within strains of the same species)	[30, 53, 54, 55, 56, 57, 58]
Adaptation to different environmental conditions	Beach sand, wetlands, soils (agricultural, forestry, contaminated with oil and mud), fresh water, seawater, rivers, springs, decomposing plants and vegetables, domestic and wild animals, insects	[59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71]
Adaptation to climate change / global warming	Acclimatization to higher temperatures enhances human interaction	[2, 60, 61, 72]
Contamination of different environments	Clinical environment (hospitalization)	[75, 76, 77, 78]
	Healthcare personnel’s hands	[79, 80, 81, 82]
HIV/AIDS	Oropharyngeal Candidiasis	[57, 85, 87, 117]
	Esophageal candidiasis	[86]
	Candidemia	[26, 33]
Nutrition	Malnutrition	[10, 90, 91, 92]
	Iron deficiency anemia	[89]
Chronic degenerative diseases	DM1	[94]
	DM2	[94, 95]
	Hematologic and solid neoplasms	[97, 98]
Age extremes	Newborns (immature immune system)	[90, 100, 102]
	Older adults (immune system weakened by aging)	[57, 103, 104, 105]
Hygiene	Lack of hygiene (stomatitis and intertrigo)	[105, 118]
Occupational exposure	Superficial candidiasis (Intertrigo, onychomycosis)	[20, 107, 108]

Table 1.

Main determinants associated with candidiasis.

9. Social determinants of health in the context Candida infection

9.1 Social determinants of health (SDH)

The World Health Organization (WHO) defines health as a state of complete physical, mental, and social well-being and not merely the absence of disease. This definition makes it possible to consider different perspectives such as the social aspects of health as social determinants of health [119].

SDH are the social, economic, and environmental conditions that influence an individual’s state of health. According to the World Health Organization (WHO), SDH such as education, housing, nutrition, work environment, access to services, unemployment, and health care are essential for equitable health. In recent years, it has also become widely accepted that the socioeconomic conditions in which people live strongly influence their chances of good health. Health and illness follow a social gradient: The lower a person’s socioeconomic position, the lower their chances of good health [120].

Poor environmental, social, and economic conditions have a negative impact on health, increase susceptibility to infectious diseases caused by emerging pathogens; these factors contribute to health inequalities that can span multiple generations. Technological advances, increasing unplanned urbanization, and climate change are new and emerging trends that may exacerbate existing inequalities and further increase inequalities in health opportunities and outcomes [121].

9.2 State of the art in DSS associated with candidiasis

One of the populations that are particularly vulnerable to opportunistic infections is those living in poverty, who suffer from precarious health conditions and have limited or no access to health facilities [122]. For example, dermatophytosis is more common in people living in crowded or promiscuous conditions such as in barracks, prisons, or nursing homes, where confined spaces favor contact with infectious material. Subcutaneous mycoses, such as mycetoma, sporotrichosis, and chromoblastomycosis, are common in underdeveloped countries, due to the fact that agricultural activities are performed manually, while in highly developed countries, they do not occur and the cases observed are imported [123]. Therefore, below are several some articles describing some social factors that favor the development of Candida spp. The available published research articles on socioeconomic factors were retrieved and reviewed from three reliable databases: PubMed, Google Scholar, and Scopus, with a total of 31 articles. The search was performed using the keywords: “Candida,” “candidiasis,” and “socioeconomic,” in both English and Spanish and without limiting the date of publication as there is little information on this topic. The selection of articles was based on the title, abstract, and in some cases, related documents.

Of the publications found describing sociodemographic characteristics or socioeconomic factors of patients colonized or infected with Candida, 29 articles referred to superficial infections and/or colonization, of which the most common clinical form was vulvovaginal with 20 (65%) publications followed by oral colonization and/or candidiasis (7; 23%) and 2 (6%) onychomycoses. Only 2 (6%) published articles on systemic candidiasis or candidemia were found (Table 2). The prevalence of Candida colonization/infection was estimated based on the total number of patients with Candida and the total population.

Clinical manifestation	Year	Geographic region	Characteristics of the population	Related species	Prevalence (%)	DSS	References
Vulvovaginal Candidiasis (CVV)	1984		600 obstetrics-gynecology outpatients	C. albicans, C. tropicalis, C. stellatoidea, C. kefyr, C. parapsilosis, C. guilliermondi	43.5% (261)	Pregnancy, malnutrition, anemia, *medium socioeconomic status	[124]
	1995	Pavia, Italia	2374 gynecological patients from a vaginitis cliniC	C. albicans, C. glabrata, C. tropicalis, C. kefyr y C. parapsilosis.	33.1% (786)	*Women older than 38 years, lower educational and socioeconomic levels in patients with C. glabrata.	[125]
	2005	Paraguay	196 pediatric gynecological patients	Candida sp.	—	*Lower-middle socioeconomic level, primary and secondary parental education	[126]
	2004	Accra, Ghana	200 patients undergoing manual vacuum aspiration	C. albicans	17.2% [34]	Housing in marginal urban neighborhood	[127]
	2006	Goa, India	2432 gynecological patients	Candida sp.	8.5% (206)	Younger age, not being of Muslim origin, fewer children in the household, not having tap water in the house	[128]
	2018	Odisha, India	558 non-pregnant gynecological patients of reproductive age	C. albicans	34% (190)	Lack of hygiene, lower educational level	[129]
	2014	China	1341 gynecological patients	Candida spp.	51.37% (689)	Low educational level, older age, marriage, vaginal douching	[130]
	2022	19 countries worldwide	Pregnant patients	C. albicans, C. glabrata, C. krusei, C. tropicalis, C. lypolytica, C. kefyr, C. famata, C. parapsilosis y C. dubliniensis	17–90%	Age, gestational age, parity, low educational, and socioeconomic levels	[131]
	2020	Latin America	Gynecological patients of reproductive age	C. albicans	20–50%	Early sexual life, socioeconomic inequality, use of contraceptive methods, multiple partners, unprotected sexual activity	[132]
	2012	Detroit, MI, U.S.A.	25 patients referred to a Vaginitis Clinic	C. albicans	100%	*Married and insured white women with more than 12 years of formal education, average or above average socioeconomic level.	[133]
	2013	Juiz de Fora, Brazil	69 gynecological patients with CVV	C. albicans, C. glabrata, C. lusitaniae	100%	*White women, higher education, and married.	[134]
	1995	Taipei, Taiwán	17,047 gynecological patients	Candida spp.	3.4% (580)	College education or higher, age in adolescence.	[135]
Colonization and/or oral candidiasis	2014	Bolivia	75 elderly patients	C. albicans	61.3% [46]	Physiological changes, low defenses, poor hygiene, malnutrition, low income, low education.	[136]
	2012	México	60 children with HIV/AIDS; 60 malnourished children; 57 Tarahumara children	C. albicans, C. tropicalis; C. albicans, C. krusei, C. tropicalis, C. glabrata; C. albicans, C. krusei	57.1% [36]; 38.2% [27]; 17.5% [11]	Immunosuppression; Immunosuppression, * underlying causes; —	[122]
	2011	São Paulo, Brasil	117 pediatric AIDS patients	C. albicans, C. tropicalis, C. kefyr, C. krusei, C. glabrata, C. guilliermondii	62% [86]	Low socioeconomic level	[137]
	2022	U.S.A.	101 infants	C. albicans, C. krusei, C. glabrata	48%; [48]	Presence of S. mutans, maternal factors: oral carriage of C. albicans, lower education, disadvantaged socioeconomic status, more than three decayed teeth.	[138]
	2001	Piracicab, SP, Brasil	239 children	C. albicans, C. tropicalis, C. krusei, C. parapsilosis	47.3% [113]	—	[139]
	2019	U.S.A.	48 pregnant patients	C. albicans, C. krusei, C. glabrata, C. tropicalis, C. dubliniensis	100%	Socioeconomic disadvantage, hypertension, number of decayed teeth, level of S. mutans in saliva.	[140]
	2012	U.S.A.	249,092 patients diagnosed with oral candidiasis	Candida spp.	100%	Residence in geographic areas of low socioeconomic strata, comorbid condition	[141]
Nail, cutaneous and mucosal candidiasis	2006	México	3749 patients from rural communities	C. parapsilosis, C. albicans, C. guilliermondii, C. tropicalis, C. humicola,; C. famata	0.58% [22]	Marginalization	[142]
	2006	Manaos, Brasil	394 with clinical suspicion of superficial mycosis	Candida spp., C. albicans	18.3% [72]	Middle social class	[143]
Candidemia	2020	Grecia	522,197 hospitalized patients	C. albicans, C. parapsilosis complex, C. glabrata complex, C. tropicalis, C. krusei, Candida spp.	0.082% (429)	Economic crisis (limited resources for medical care), solid organ malignancies	[74]
	2016	U.S.A.	225 patients with home parenteral nutrition	Candida spp.	6.22% [14]	Anticoagulant therapy, ulcers or open wounds, public health insurance (low socioeconomic status)	[144]

Table 2.

Social determinants of health in Candida infection-colonization.

*

Predominance of factors in the population, but not a statistically significant relationship.

Regarding vulvovaginal candidiasis, only 12 out of 20 studies showed any kind of positive association between socioeconomic factors and clinical manifestations. In addition, Table 1 lists these factors or determinants observed in the different populations studied. López Martínez et al. [124] conducted a study of 600 obstetric-gynecology patients to investigate opportunistic factors in vaginal candidiasis. In relation to the total population and the number of patients with a positive test for Candida, the prevalence was 43.5% (261), of which 134 (22.3%) had this yeast as a part of the microbiota and in 127 (21.2%) it was considered a pathogen more frequently observed in patients of middle socioeconomic level. It was also found that pregnancy, followed by an association between pregnancy, malnutrition, and anemia, were the most common opportunistic factors for the development of vaginal candidiasis. C. albicans was the most common species (67.7%) followed by C. tropicalis (18.8%), C. stellatoidea (8.7%), C. pseudotropicalis (2.4%), C. parakrusei (1.6%), and C. guillermondi (0.8%). Studies by Spinillo et al. [125], in an obstetrics and gynecology clinic at the University of Pavia, Italy, found that patients with vaginal infections caused by C. glabrata compared to C. albicans had lower educational and socioeconomic levels, were associated with recurrent vaginal candidiasis, and were more common in women over 38 years of age. The prevalence of Candida infection was 33.1% (786/2374) in the population, with C. albicans being the most common species (79.5%) followed by C. glabrata (10.9%) and to a lesser extent other species such as C. tropicalis, C. kefyr, and C. parapsilosis.

In another study conducted in Paraguay by Laspina et al. [126] between 1995 and 1996 in 196 girls with a clinical diagnosis of vulvovaginitis, it was that the prevalence of this infection caused by Candida spp. was 21.5%. The characteristics of the population studied showed that the girls generally came from families with a medium to low socioeconomic level, 50% of the mothers had secondary education, and 44.4% had only primary education. Lassey et al. [127] determined the transmission rates of potential lower genital tract pathogens and factors associated with colonization in 200 women with incomplete abortion treated at a hospital in Accra, Ghana. As a result, they found a combination of bacterial vaginosis and C. albicans in 17.2% (34 patients) of the study population and a significant association with the presence of potential pathogens and people living in an urban slum, malnutrition, and anemia, factors characteristic of low socioeconomic status.

In a population-based study of women in Goa, India, Patel et al. [128] investigated the burden and determinants of reproductive tract infections in 2432 patients. The results showed a population-wide prevalence of Candida of 8.5% (206 cases). Analysis of socioeconomic risk factors for candidiasis showed that this infection was significantly associated with younger age, non-Muslim origin, fewer children in the household, and lack of tap water in the home. The latter could have an impact on poor personal hygiene and social inequality, as factors Torondel et al. [129] found in a hospital in Odisha, India, to determine whether poor hygiene practices during menstruation were associated with three common lower reproductive tract infections. The data showed that C. albicans infection was the second most common (34%; 190) among the three types of infections. Women with this disease rarely practiced personal hygiene. In addition, socioeconomic studies showed that the prevalence of candidiasis was inversely proportional to a higher level of education.

In 2013, Na et al. [130] conducted a study in two tropical regions of China (Hainan and Sanya) in which they investigated the risk factors associated with genital tract infection caused by Candida spp. in 689 infected gynecological patients. The prevalence of Candida was 51.37% (689/1341). Age, low education, marriage, and vaginal douching were significant risk factors for Candida infection. Patients with higher levels of education were unlikely to be infected with Candida species and the incidence increased with age, which differs from the situation described by Wang et al. [135], where candidiasis decreased with age. Disha et al. [131] conducted a review study in which they investigated the prevalence and risk factors for vulvovaginal candidiasis (VVC) in pregnant women worldwide. The data collected indicate a high prevalence of CVV in pregnant women worldwide, particularly in Asian and African countries, with Kenya, Nigeria, and Yemen having rates of 90.38%, 62.2%, and 61.5%, respectively. However, the prevalence of CVV in pregnant women worldwide ranged from the lowest 17% (Selangor, Malaysia) to the highest 90% (Kenya). They also found that the prevalence of CVV during pregnancy varied with age (25–29 years), gestational period (last trimester), parity (multiple births), and low educational and socioeconomic level. The differences in prevalence rates worldwide may be due to geographical, ethnic, and socioeconomic factors, as well as differences in sampling and culture techniques.

In 2022, Duran Cañarte et al. [132] investigated the most common risk factors for vaginal infections in women of childbearing age in Latin America. The results showed that the main pathogens associated with vaginal infections in women aged 15 to 40 years were Gardnerella vaginalis, Trichomonas vaginalis, and C. albicans. In addition, the study found that C. albicans was the most common pathogen in countries such as Argentina 2018 (25%), Colombia 2018 (20.3%), Ecuador 2018 (50%), Peru 2019 (22.3%), Cuba 2019 (20–25%), and Mexico 2017 (20%). It was concluded that the most predisposing risk factors for acquiring vaginal infections include early sexual life, socioeconomic inequality, the use of contraceptive methods, multiple partners, and unprotected sexual activity. In contrast, a study by Marchaim et al. [133], conducted between 2000 and 2010, examined the incidence of vulvovaginitis due to fluconazole-resistant C. albicans and risk factors in female patients at a hospital in Detroit, MI. They found 25 cases of women with recurrent vaginitis over an 11-year period. Most patients were primarily married insured white women with more than 12 years of formal education and average or above average socioeconomic status.

Tavares Rodrigues et al. [134] conducted a study to investigate the epidemiologic profile of patients with vulvovaginal candidiasis (VVC) in Juiz de Fora, Brazil. Of the patients studied, aged 15 to 52 years, 79.7% were white women, 58% had higher education, 56.5% were married, and 97.1% were sexually active. The study showed that the most prevalent species were C. albicans (98.1%), followed by C. glabrata (5.4%) and only 3 with C. lusitaniae. Although sociodemographic characteristics such as age, marital status, and education were not significantly related to vulvovaginal candidiasis, this study showed a predominance of the disease in participants who were considered white, college educated, and married.

Wang et al. [135] investigated the epidemiological differences between candidiasis and trichomonads in cytological smears from 17,047 patients attending health centers and clinics in Taipei, Taiwan. The overall prevalence of Candida infection was 3.4%. Infection was higher in adolescents and decreased with age, especially in over 60 years of age. Adolescence showed a positive correlation with candidiasis as an independent risk factor, with indices of socioeconomic status and education (higher education or higher compared to illiterate women). There was no clear association between ethnicity and hygiene and candidiasis. On the other hand, eight publications were found in which sociodemographic factors of patients with vulvovaginal candidiasis such as socioeconomic and educational level, age, place of residence, occupation, behavior/habits, marital status, health services, and ethnicity were investigated or described, but no associations were found or were present as determinants for the development of candidiasis [145, 146, 147, 148, 149, 150, 151, 152].

Regarding socioeconomic factors in oral Candida infection/colonization, effects have been reported in the elderly, pregnant women, especially in the pediatric population. A study by Atalaya et al. [136] examined the prevalence of oral candidiasis in 75 elderly patients attending a medical consultation in a hospital in Bolivia. Candida was observed in 61.3% [46] of the study population. The predominant factors for the prevalence of oral candidiasis include physiological changes, age-related low defenses, poor oral hygiene habits, poor eating habits, low income, and low education, which favor infection with C. albicans. Gaitán Cepeda et al. [122] investigated the presence of Candida in the oral cavity of children susceptible to opportunistic infections and whether there is an association between this oral colonization and three types of at-risk populations. The results in the HIV/AIDS (n = 60) and malnutrition (n = 60) groups showed the highest frequency of Candida (51.7% and 38.2%, respectively), with the highest frequency of C. albicans isolates followed by C. tropicalis in HIV/AIDS patients; the malnutrition group showed the highest diversity, where C. albicans was most common, followed by C. krusei and only one isolate of C. tropicalis, C. glabrata and Candida spp. In the third group, Tarahumara children (n = 57), one of the poorest ethnic populations in Mexico, the frequency was similar to the control group (n = 29) (17.5% and. 10.3% respectively), with the most frequent species being C. albicans with eight isolates, two of C. krusei and one Candida spp. Isolate.

Domaneschi et al. [137] investigated the prevalence of factors associated with oral colonization by Candida spp. in pediatric AIDS patients in São Paulo, Brazil. The prevalence of oral Candida colonization was 62% (86/117). Only seven children had a clinical manifestation of oral candidiasis. Of the 86 yeast isolates, C. albicans was the most prevalent (69 of 86), followed by C. tropicalis (5 of 86), C. kefyr (4 of 86), C. krusei (3 of 86), C. glabrata (2 of 86), and C. guilliermondii (1 of 86). In the study, a positive correlation was observed between Candida colonization and sociodemographic characteristics in children. A higher incidence was found in children who did not live in their own home and in children with more than two siblings. These results indicate that people in unfavorable socioeconomic circumstances are more susceptible to Candida infections.

In 2022, Alkhars et al. [138] examined Candida colonization in the oral cavity of 101 young children from low income and racial minorities in the USA. The results showed that Candida colonization and carriage in infants was positively associated with maternal factors such as oral carriage of C. albicans, low education, socioeconomic disadvantage, and more than three decayed teeth. In addition, 48% of infants were found to have Candida colonization at 6 months of age, which remained at the same level until 12 months of age. The most frequently detected species included C. albicans and C. krusei followed by C. glabrata. In contrast, Moreira et al. [139] studied Candida colonization in 239 Brazilian children divided into five different socioeconomic categories (A to E), with D and E being the least favored. The results showed the presence of Candida spp. in 47.3% of the samples. C. albicans was the most frequently isolated species in all socioeconomic categories, followed by C. krusei, C. tropicalis, and C. parapsilosis. Furthermore, the prevalence of Candida did not differ significantly between the groups. However, a significant correlation was found between caries rates and socioeconomic categories. Nevertheless, it is important to note that recent studies have associated the presence of Candida spp. with a higher prevalence of caries [153].

In a study conducted in the USA by Xiao et al. [140] on oral health and Candida colonization in socioeconomically disadvantaged pregnant women, it was found that 24 out of 48 patients had positive Candida detection; moreover, a higher frequency of Candida colonization in women was positively associated with hypertension. C. glabrata, C. krusei, C. tropicalis, and C. dubliniensis were also detected in the study participants. This suggests that more than 10% of socioeconomically disadvantaged pregnant women received only emergency dental treatment to relieve orofacial pain, inflammation, and advanced infections instead of routine prenatal oral health care. The oral health of these patients represents a major health inequality. In addition, Elangovan et al. [141] reported on 249,092 patient visits to the emergency department with a diagnosis of oral candidiasis. The following was found: the percentage of women (55%) with oral candidiasis was slightly higher than the percentage of men; a significantly higher proportion of young people under 19 years of age (32.2%), and many people living in geographical areas with low socioeconomic strata (64%). In addition, nearly all ED visits were found to be associated with ≥1 comorbid condition predisposing to or related to oral candidiasis such as fluid disorders, HIV infection, esophageal disease, nutritional deficiencies, and secondary malignant neoplasms.

In relation to the different dermatophytoses caused either by Candida or by other dermatophytes, it is believed that occupation and socioeconomic status are determining factors for these manifestations since patients with low socioeconomic status have a greater physiological impact due to the work they perform (laborers, farmers, artisans, among others) [154]. Méndez Tovar et al. [142] reported in 3749 cases from five Mexican rural communities with a high degree of marginalization that aimed to perform medical consultations with specialists in dermatology and mycology. The overall percentage of dermatoses caused by fungi was high at 13.75% (498); however, only 98 fungi were identified in three municipalities. The study showed that the inhabitants of these municipalities had a high morbidity associated with fungi. A total of 22 isolates (0.58%) belonged to Candida causing nail, skin, and mucosal candidiasis, with C. parapsilosis being the most frequent, followed by C. albicans, and others such as C. guilliermondii, C. tropicalis, C. humicola, C. famata, Pichia ohmeri, and Candida spp. Probably, the difficult living conditions in which these patients live lead to little attention being paid to these infections. Other pathologies indicative of underdevelopment, such as scabies, acarosis, pediculosis, and malnutrition of varying degrees, were found with great frequency.

De Oliveira et al. [143] examined 394 patients with clinically suspected superficial mycosis, 256 of whom were positive. They concluded that onychomycosis and pityriasis versicolor are the most common mycoses in the Amazon region and that Candida spp. (72; 31.57%) and Malassezia spp. (77; 33.77%) are the most common pathogens. The prevalence of Candida was 18.3%. Superficial mycoses were present in all social classes, but cases were more frequent in people of social class C (97; 37.89%), which is classified as moderate according to the Brazilian classification system.

Siopi et al. [74] reported on a 10-year (2009–2018) retrospective surveillance study in a tertiary hospital in Greece that collected information on the epidemiology of candidemia, especially during severe socioeconomic events (financial crisis). The number of hospitalized patients was 522,197, among whom a total of 429 candidemia attacks were recorded. C. albicans was the most common species (41%), followed by C. parapsilosis (37%), C. glabrata (11%), C. tropicalis (7%), C. krusei (1%), and Candida spp. (3%). They found that incidence of candidemia on internal medicine wards and of C. parapsilosis infections increased significantly during this period. It was suggested that the current economic crisis affecting the country may have contributed to candidemia. So limited resources for medical care difficulties in diagnosis. The reduction in specialized hospital staff and the increase in the number of patients in public clinics could have a negative impact on basic infection control measures, rather than being associated with critical differences in the characteristics of the population studied.

Durkin et al. [144] conducted a descriptive observational study of 225 patients discharged with home parenteral nutrition from a hospital in St. Louis, Missouri, USA, between 2007 and 2009. Among the catheter-related complications, infections were identified in 68 patients, of which 14 (20%) involved Candida. Predictive factors that were more common in patients who developed a catheter-related bloodstream infection included age, ulcers or open wounds, anticoagulation, and public insurance. This could be because publicly insured patients are generally older and/or have a lower socio-economic status, as stipulated by the admission criteria.

10. Conclusions

Several studies have been reported that provide valuable insights into the major predisposing determinants of Candida colonization and infections in relation to the health status of the individual and the virulence factors of Candida itself. Although there is some work examining the prevalence of Candida in different social classes, as well as a sociodemographic description, there are still few criteria to derive or assert an objective opinion on the social conditions in which this opportunistic pathogen occurs. In this sense, it remains only a poorly documented diagnosis of what might be happening. It is still inaccurate to claim that a particular species is prevalent in certain socioeconomic strata.

So, there is still a lack of a global overview that takes into account the social determinant of health in addition to the intrinsic factors of individuals (human biology, health status, etc.) that could be related to variations in colonization and infection by the different Candida species. Research is needed to assess the relationship between socioeconomic characteristics of people (social development, marginalization, the environment in which people live and develop, etc.) and variations in colonization and infection by different Candida species, applying a methodology and data analysis with tools such as descriptive and predictive mathematical models that allow understanding the impact of DSS on the development of the disease. This is done with the intention of identifying the social parameters that are more influential (in multispecies candidiasis) and can be controlled.

Acknowledgments

Author Morales-Ramírez gratefully acknowledges financial support for his PhD studies from Natl. Council for Science, Technology and Humanities of Mexico (CONAHCYT).

Conflict of interest

The authors declare no conflict of interest.