Review of literature
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
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
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
(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.
floccosusm, M. gypseum,
Skin, hair, nail, feet Soil, contact with
arthrospores or conidia
animals and humans
Histoplasmosis H. capsulatum Lungs Soil, inhalation of
Blastomycosis B. dermatitidis Lungs, skin,
Soil, inhalation of
Coccidioidomycosis C. immitis, C. posadasii Lungs, bones, joints,
Soil, inhalation of
Candidiasis C. albicans, C. tropicalis, C.
glabrata, C. krusei,
Intestinal tract, vaginal
tract, skin, fingers, oral
contact with secretions
from infected person
Cryptococcosis C. neoformans Lungs, meninges,
kidney, liver, prostate,
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
Zygomycosis Rhizopus sp, Mucor sp and
Skin, cerebral, blood,
Soil, decaying plant
material, inhalation or
percutaneous contact of
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).
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.