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Review of literature - ... Tinea corporis or ringworm (trunk, extremities and face), Tinea barbae (hairs and skin in the beard and mustache area), Tinea faciei (nonbearded parts of

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    Review of literature

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    2.1. An introduction to human fungal infections

    Fungi are eukaryotic microorganisms that are more closely related to humans than

    bacteria at cellular level. They belong to group Eumycota and are chemoheterotrophs

    with a chitinous cell wall. More than 100,000 species have been described. Most species

    grow as multicellular filaments called hyphae forming mycelium such as molds; some

    species also grow as single cells like yeasts although some of them may grow as hyphae

    at room temperature and as yeast inside the host and are called as dimorphic. Some

    groups of fungi are pathogenic to humans, animals and plants, and require control


    Human fungal pathogens belong to four main groups namely zygomycetes, ascomycetes,

    deuteromycetes and basidiomycetes. The fungal infections caused by these pathogens are

    categorized as (i) superficial; affecting nails, skin, scalp or mucous membrane. (ii)

    systemic; affecting deeper tissues and organs. Superficial infections are by far commoner

    and comprise the various types of tinea or ring worms affecting the skin, hair, and nails.

    The fungi causing such infections are specialized saprophytes, with the capacity to digest

    keratin viz. Pityriasis vesicolor, Cladosporum spp and dermatophytes like Trichophyton

    spp, Microsporum spp, Epidermophyton spp and Candida albicans. Systemic mycoses

    are caused by fungi that are mostly soil saprophytes. Systemic mycoses occur in varying

    degree of severity, ranging from asymptomatic infection to fungal diseases. The causative

    agents include Cryptococcus spp, Sporothrix spp, Paracoccidioides spp, Blastomyces

    spp, Histoplasma spp etc. A third type of fungal infections caused by opportunistic

    pathogen occurr in patients with debilitating diseases such as AIDS, cancer, diabetes or in

    whom the physiological state has been upset by immunosuppressive drugs. The causative

    agents are Candida albicans, Aspergillus spp, Mucor spp and Penicillium spp, Fusarium

    spp and Rhizopus spp, which are normally avirulent in healthy people but could be

    disseminated to deep tissue and cause fatal disease in unhealthy people (Pfaller and

    Diekema 2004; Chakrabarti 2005; Reedy et al. 2007).

    Over the past few years, major advances in healthcare have led to an unwelcome increase

    in the number of life-threatening infections due to true pathogenic and opportunistic

    fungi. These infections are increasing in number largely because of the increasing size of

    the population at risk. This population includes transplant recipients, cancer patients and

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    other individuals receiving immunosuppressive treatment. Furthermore patients with

    burns, neutropenia, and HIV infections are now seriously exposed to fungal infections

    (Kuleta et al. 2009). Among such patients, novel and more intensive regimens have

    resulted in more profound levels of immuno-suppression that are sustained for longer

    periods. Likewise, the increasing use of invasive monitoring and aggressive therapeutic

    technologies in intensive care units has resulted in improved survival of individuals with

    life threatening illness, but contributing to an increase in the number of persons at risk for

    fungal infections (Richardson 2005). The increased incidence of fungal infections has

    coincided with a decrease in mortality from bacterial infections. This is probably the

    result of better antibiotic therapy, leading to increased survival of patients who are

    predisposed to fungal infections, as well as inappropriate broad spectrum antibiotic

    therapy disrupting the normal microbial flora on the skin and mucosal surfaces leading to

    opportunistic fungal pathogens to flourish.

    The estimated annual incidence of invasive mycoses is 72–228 infections per million

    populations for Candida species, 30–66 infections per million population for C.

    neoformans, and 12–34 infections per million populations for Aspergillus species (Pfaller

    et al. 2006). The morbidity and mortality rates caused by species of Candida,

    Aspergillus, Fusarium and Trichosporum are relatively higher (Fluckiger et al. 2006). In

    Europe, the fungal infections are accounting for 17% cases associated with intensive care

    unit (Rupp 2007) while in USA it has become 7 th

    most common cause of deaths among

    hospitalized patients (Martin et al. 2003).

    Data from the late 1950’s and early 1960’s indicates that invasive fungal infections were

    extremely rare, even in immunocompromised cancer patients (Chakrabarti 2005).

    Candidaemia rates increased rapidly in the 1980s, so that Candida spp became the fourth-

    commonest cause of bloodstream infection in the USA (Edmond et al. 1999). The

    emergence of fungal rhinosinusitis, penicilliosis, marneffei and zygomycosis due to

    Apophysomyces elegans is unique in the Indian scenario. OPC is the most frequent

    opportunistic fungal infection among HIV-infected patients, and it has been estimated that

    more than 90% of HIV-infected patients develop this often debilitating infection at some

    time during progression of their disease (De Repentigny et al. 2004). Approximately 70%

    of woman experience vaginal candidiasis once in a life and 20% suffered from recurrence

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    (Fidel et al. 1999; Achkar and Fries 2010). Fungal infections now have also become more

    common in the healthy population. These diseases differ in their nature, causative agents

    and distribution. Description of such fungal diseases, their causative agents and major

    organs involved etc are summarized in table R-1.

    Table R-1 Examples of commonly caused fungal diseases (Source: Weitzman and Summerbell

    1995; Rappleye and Goldman 2006).

    Fungal diseases Causative agent Site of infection Transmission

    Dermatophytosis T. rubrum, T.

    mentagrophytes, E.

    floccosusm, M. gypseum,

    M. canis

    Skin, hair, nail, feet Soil, contact with

    arthrospores or conidia

    from contaminated

    animals and humans

    Histoplasmosis H. capsulatum Lungs Soil, inhalation of


    Blastomycosis B. dermatitidis Lungs, skin,

    genitourinary tract,


    Soil, inhalation of


    Coccidioidomycosis C. immitis, C. posadasii Lungs, bones, joints,


    Soil, inhalation of


    Candidiasis C. albicans, C. tropicalis, C.

    glabrata, C. krusei,

    C. dubliniensis

    Intestinal tract, vaginal

    tract, skin, fingers, oral


    Endogenous flora,

    contact with secretions

    from infected person

    Cryptococcosis C. neoformans Lungs, meninges,

    kidney, liver, prostate,


    Soil, contamination

    with bird feces

    Aspergillosis A. fumigatus, A. flavus, A.


    lungs Soil, inhalation of


    Hyalohyphomycosis Fusarium sp, Phecilomyces

    sp, Acremonium sp

    Keratin, nails, lungs Soil, plant debris,

    ingestion of toxin

    contaminated plant


    Zygomycosis Rhizopus sp, Mucor sp and

    Absidia sp

    Skin, cerebral, blood,

    lungs, genitourinary

    and gastrointestinal


    Soil, decaying plant

    material, inhalation or

    percutaneous contact of


    2.1.1. Candidiasis

    Candidiasis is the secondary or opportunistic infections ranging from acute, subacute and

    chronic to life threatening mycoses. Healthy persons generally encounter superficial

    infections but in immunocompromised patients invasive infections could also occur.

    Superficial infections include vulvovaginal candidiasis, candiduria, onychomycosis and

    oropharangeal candidiasis (OPC). Systemic candidiasis include infections of blood i.e.

    candidemia and disseminated candidiasis infecting multiple organs especially brain,

    myocardium, kidneys and eyes (Khan and Gyanchandani 1998).

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    A number of Candida spp are encountered in candidiasis like C. albicans, C. glabrata, C.

    tropicalis, C. krusei, C. dubliniensis, C. parapsilosis (Hayens and Westerneng 1996;

    Pfaller et al. 2006). Among the various species of Candida capable of causing human

    infections, C. albicans predominates in infections of genital, oral, and cutaneous sites,

    blood stream infections (BSI), intensive care unit, bone marrow transplantation and

    nosocomial infections (Pfaller et al. 2006). C. albicans is a member of commensal

    microflora of the intestine. It is pleomorphic and undergoes reversible morphogenic

    transitions between budding yeast, pseuodohyphal and hyphal growth forms.