Bacterial and

Mycotic Infections in
Immunocompromised
Hosts: Clinical and
Microbiological
Aspects
Edited by
Maria Teresa Mascellino
Ibrahim Hashim
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www.esciencecentral.org/ebooks
001
Dimorph and Filamentous Fungi
Tim Sandle*
*Corresponding author: Tim Sandle, Bio Products Laboatory,
United Kingdom; E-mail: tim.sandle@bpl.co.uk

Introduction
An immunocompromised host is an individual whose immune response is weakened as a result of an immunodeficiency
disorder, exposure to immunosuppressive drugs or irradiation (for example, patients undergoing cancer chemotherapy or
bone marrow transplantation).The immune system is composed of many interdependent cell types that collectively protect
the body from bacterial, parasitic, fungal and viral infections, as well as from the growth of tumour cells. However, with
the immunocompromised host, due to the weakened nature of the individual’s immune system, the individual is relatively
susceptible to a microbiological infection of the type that healthy immune systems can ordinarily conquer (that is they
are susceptible to infectious agents in general and fungal “opportunists” in particular) [1]. The risk of infection relates to
the interaction between the epidemiologic exposures that the patient experiences and the net state of immunosuppression
(thus the greater the exposure, the greater the chances of infection even in an immunologically competent individual; and
the greater the net state of immunosuppression, then the greater the chances of infection even with minimal exposures
to microbes).
Many cases of immunodeficiency are acquired (so-termed secondary cases). However, some people are born with
defects in their immune system (described as primary immunodeficiency) [2]. In addition, people with weak immune
systems or systems that have not fully developed, such as premature babies with very low birth weights, are also at
increased risk from microbial infection (for example, a Candida blood stream infection is a common disease).
The primary risk to the immunocompromised patient arises from nosocomial infections (or hospital acquired
infections). A risk to patients additionally can arise from administered medicines. Until the late 1990s the primary risk
was generally regarded as arising from bacteria. However, since 2001 the second most common recall for pharmaceutical
medicines has been due to fungal contamination. Moulds are ubiquitous in nature and, therefore they pose a risk to
pharmaceutical manufacturing operations. Aspergillusspp, Penicilliumspp, Trychophytonspp, and other filamentous fungi
have, in some cases, caused significant microbial contamination issues in production environments and manufactured
products [3].
This chapter examines the risks to immunocompromised patients from fungal infections. In doing so the chapter
identifies and describes the most common types of infections. The chapter additionally discusses some of the steps taken
for the microbiological isolation and assessment of the clinically significant microorganisms and provides an introduction
to some of the treatment steps.

Dimorph and Filamentous Fungi

The fungi are more evolutionarily advanced forms of microorganisms, as compared to the prokaryotes (such as
bacteria).Fungi are commonly divided into two distinct morphological forms: yeasts and hyphae (or filamentous). Yeasts
are unicellular fungi which reproduce asexually by blastoconidia formation (budding) or fission. Pure forms of yeasts fall
outside the scope of this chapter.
Hyphae are multi-cellular fungi which reproduce asexually and/or sexually. Such fungi are more commonly referred
to as ilamentous fungi or simply as moulds. Filamentous fungi are composed of very fine threads (hyphae). Hyphae grow
at the tip and divide repeatedly along their length creating long and branching chains. Most filamentous fungi grow in
a polar fashion (by extension into one direction) by elongation at the tip (apex) of the hypha [4]. The hyphae continue
to grow and intertwine until they form a network of threads called a mycelium. Digestive enzymes are secreted from the
hyphal tip. These enzymes break down the organic matter found in the soil into smaller molecules which are used by the
fungus as a nutrient source. Some of the hyphal branches grow into the air and spores form on these aerial branches [5].
Fungal spores are either unicellular or multicellular, which develop into a number of different phases of the complex life
cycles of the fungi. Fungi are often classified according to their spore-producing structures, for example, spores produced
by an ascus are characteristic of ascomycetes.
Dimorphic fungi are fungi which can exist as mould/hyphal/filamentous form or as yeast [6]. Examples include
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Penicillium marneffei, Coccidioides immitis, Paracoccidioides brasiliensis, Candida albicans, Ustilago maydis, Blastomyces
dermatitidis, Histoplasma capsulatum, and Sporothrix schenckii. Dimorphism is a rare phenomenon and very few fungi
exhibit dimorphism. Most fungi occur in the hyphae form as branching, threadlike tubular filaments.
Many fungi produce biologically active compounds, several of which are toxic to animals or plants and are therefore
called mycotoxins. This can lead to human disease (mycotoxicosis). The symptoms of a mycotoxicosis depend on the type 005
of mycotoxin; the concentration and length of exposure; as well as age, health, and sex of the exposed individual [7].
Characterisation of Fungi
Accurate identification of an infecting fungal species is the key to selecting the appropriate anti-fungal treatment.
For example, many Candida species, including C. albicans, C. parapsilosis and C. tropicalis, are reliably susceptible to the
antifungal compound fluconazole, whereas others, such as C. glabrata and C. krusei, display reduced susceptibility or
resistance to fluconazole [8]. Therefore, characterising the fungus is important for targeting the specific treatment.
Identification of fungal isolates from clinical environments using standard identification procedures requires
experienced and skilled laboratory staff. When infections are assumed, accurate fungal identification is needed if the
contamination source has to be determined and tracked.
Some identification systems are available for the identification of fungi, including biochemical systems such as the API
Candida, Omnilog and Vitek [9]. There has also been some advancement with genotypic techniques. For filamentous
fungal identification, however, this needs more expensive methods such as PCR-based internal transcribed spacer
regions (ITS) sequencing by molecular methods. Advances have also been made with newer techniques, such as beta-D-
glucandetection (using a (1–3)-β-D-Glucanassays, based on the Limulus amebocytelysate test) for the detection of fungal
infections.
In contrast to such expensive tests, conventional culture and staining methods can be utilised for straightforward and
less expensive identification. Moreover, no single identification has been shown to be capable of detecting all species of
fungi and knowledge of cultural methods remains essential for the laboratory [10].
To evaluate colony characteristics of dimorphic and filamentous fungi the fungus must be grown on a suitable
microbiological culture medium. The cultural identification of fungi requires the use of selective media, for example
Sabouraud Dextrose Agar or Potato Dextrose Agar [11]. There are a range of different culture media available for the
characterisation and isolation of clinically important fungi. These include:
• Dixon’s Agar for Malassezia furfur,
• Czapek Dox Agar for Aspergillus and Penicillium,
• Bird Seed Agar,
• Cornmeal Glucose Sucrose Yeast Extract Agar for Zygomycetes,
• Sabouraud’s Dextrose Agar for Dermatophytes,
• Potato Dextrose Agar,
• Brain Heart Infusion Agar (BHIA) with 5% Sheep Blood,
• Cornmeal Agar,
• Malt Extract Agar,
• Sabouraud’s Dextrose Agar for yeasts and moulds,
• Lactrimel Agar for dermatophytes,
• Hair Perforation Test for dermatophytes,
• Urease Agar with 0.5% Glucose,
• Trichophyton Agars Nos 2-7,
• Rice Grain Medium for Microsporum,
• Littman Oxgall Agar,
• Sabouraud’s Dextrose Agar with 5% NACL,
• Vitamin Free Agar (Trichophyton Agar No 1),
• 1% Peptone Agar,
• CGB Agar.
From this list, Malt Extract Agar and Potato Dextrose Agar are general media for the routine cultivation and
identification of fungi; and Sabouraud’s Dextrose Agar is a general agar for the primary isolation and cultivation of
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dermatophytes (fungi that cause skin, hair, and nail infections). The other agars are more suited for specific types of fungi.
After growth at an appropriate temperature (normally 20-25°C) for an appropriate time (normally between five and
seven days), the fungus is examined macroscopically and microscopically [12]. Visual examination of the colony will
reveal important data concerning colour, texture, diffusible pigments, exudates (a fluid with a high content of protein and
cellular debris), growth zones, aerial and submerged hyphae, growth rate, colony topography, and macroscopic structures 006
such as ascocarps, pycnidia, sclerotia, sporodochia, and synnemata [13].
 Microscopic examination is achieved through staining and examination using a light microscope. For staining, the
lactophenol cotton blue (LPCB) wet mount preparation is the most widely used method of staining and observing fungi
and is simple to prepare. The preparation has three components: phenol, which will kill any live organisms and deactivates
lytic cellular enzymes thus the cells do not lyse; lactic acid which preserves fungal structures, and cotton blue which stains
the chitin in the fungal cell walls [14]. For the removal of a portion of the fungus for examination from agar, a method like
the adhesive tape technique is routinely used [15].
Where a confirmed culture of a mould (including Aspergillus species, Fusarium species, zygomycetes, Scedosporium
species) or C. neoformans from sputum is isolated, the likelihood of a fungal infection is high [16]. Fungi can also be
detected from a positive culture or cytology/direct microscopy for moulds from sinus aspirate; specific antigens from
blood; identification from sterile body fluids; urine samples; blood culture; or from pulmonary abnormality [17]. Where a
fungal infection is suspected, skin samples, scrapings, nail clippings and hair debris can additionally be taken.

Infection Control Measures

There are three models of anti-fungal control. These are therapeutic administration to treat clinical infection using
anti-fungal drugs; and prophylactic and pre-emptive administration to prevent or abort a clinical infection [18].
In terms of prophylactic approaches, the emphasis is upon prevention of infection. Infections of immunocompromised
hosts can arise from several settings. These include: the general environment (termed ‘community based’); from within
clinical and hospital settings; and from contaminated medications.
Many of the disease causing microorganisms which cause infections in immunocompromised hosts are spread via
hospitals, such as through hospital air-systems, especially where the air has not passed through a HEPA (high efficiency
particulate air) filter [19]; and via transmission by healthcare workers. Hand hygiene is a primary part of preventing
multidrug-resistant organism (MDRO) transmission. Facilities should ensure that healthcare personnel are trained in
correct hand hygiene technique, using alcohol based hand sanitizers (such as 70% iso-propyl alcohol) [20]. Effective
hand sanitisation should apply to hospital visitors as well as to healthcare workers. Other effective measures include
observing strict isolation procedures, observing aseptic technique, and the careful cleaning, disinfection and monitoring
of respirators, catheters, and other instruments.
Patients in acute care settings who are colonised or infected with pathogenic microorganisms should be placed under
special precautions (which may include isolation). It also stands that systems should be in place to identify patients
with a history of colonisation or infection at the time of admission so that they can additionally be placed under special
precautions if required.
Controls should also be applied to medical devices. The use of devices (such as central venous catheters, endotracheal
tubes, urinary catheters) can put patients at risk from device-associated infections, especially if they are not handled
or disinfected correctly [21]. Control can be achieved through a robust cleaning and disinfection strategy, as well as by
minimising device use. Such measures can decrease the incidence of associated infections.
Antimicrobial stewardship is another primary part of MDRO control. MDROs are disease-causing microorganisms
that are resistant to a range of different chemicals. Facilities should ensure that antimicrobials are used for appropriate
indications and duration and that the narrowest spectrum antimicrobial that is appropriate for the specific clinical scenario
is used [22]. A further measure is the education of healthcare workers and staff in relation to cross-contamination [23].
Control measures should also be applied to the cleaning and disinfection of hospital wards and to maintaining hospital
water systems in a sanitary state so that the bio burden levels are low [24].

Mycoticinfections
Most people have a high level of innate immunity to fungi and most of the infections caused by fungi are mild and self-
limiting. This innate resistance is due to: fatty acid content of the skin, pH of the skin, mucosal surfaces and body fluids,
epithelial turnover, normal flora, transferrin (iron-binding blood plasma glycoproteins), and the cilia of respiratory tract.
Nonetheless, when the immune system is weakened fungal infections are relatively common. There are a range
of different dimorphic and filamentous fungi that can cause infections in the immunocompromised host. Any list of
infectious agents would be quite extensive and there are many factors which affect whether a microorganism is likely
to lead to an infection (relating to the host, the immune system, geographical factors and so forth). Nonetheless, there
are certain types of microorganisms that are responsible for the majority of infections worldwide. Based on surveys
undertaken by the U.S. Center for Disease Control (CDC), the World Health Organization (WHO) and the U.K. Health
Protection Agency (HPA), this chapter lists and describes the fungal species most commonly associated with infections.
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Clinical criteria
When fungi pass the resistance barriers of the human body and establish infections, the infections are normally
classified according to the tissue levels initially colonised. For example:
• Superficial mycoses: infections limited to the outermost layers of the skin and hair. For example, an infection 007
caused by the fungus Trichosporum beigelii that causes the condition white piedra.
 • Cutaneous mycoses: infections that extend deeper into the epidermis, as well as invasive hair and nail diseases. For
example, ringworm (the itching condition Tineacapitis) caused by the fungus Trichophyton spp.
• Subcutaneous mycoses: infections involving the dermis, subcutaneous tissues, muscle and fascia. For example, the
sinus infection mycetoma, caused by the fungus Madurella grisea.
• Systemic mycoses: infections that originate primarily in the lung and may spread to many organ systems. These
can be divided into [25]:
o Lower Respiratory Tract Infection, such as cough, chest pain, haemoptysis (coughing of blood originating from
the respiratory tract), and dyspnoea (shortness of breath).
o Sino-nasal Infection, such as erosion of sinus walls or extension of infection to neighbouring structures,
extensive skull base destruction) nasal discharge, stuffiness.
It is with lung infections that dimorphic fungi pose the greatest risk. This is because these species have biochemical
and structural features that enable it to evade host defences, not least the ability to adapt through different physiological
forms. For example:
• Central Nervous System Infection, such as meningitis extending from a paranasal, auricular, or vertebral process;
intracerebral abscesses or infarcts.
• Some fungi have been associated with acute pneumonia, where fungi usually enter the body through mouth, nose
and eyes, and then infect the lungs, especially the air sacs or alveoli of the lungs.
Invasive fungal infections, particularly opportunistic mycoses (infections in patients with immune deficiencies who
would otherwise not be infected), are associated with significant morbidity and mortality. Risk factors for invasive fungal
infection include malignancy, haematopoietic stem cell or solid organ transplantation, neutropenia, chemotherapy,
corticosteroid use, acquired immunodeficiency and broad spectrum antimicrobial use. Arguably, the number of at risk
patients for invasive mycotic infection has increased since the early 2000s, as more patients have undergone chemotherapy
and transplantation and received a growing array of immunosuppressive agents [26].
The three main types of fungal infections, and those that pose the greatest risk to immunocompromised hosts, are
fungal meningitis, fungal keratitis and onychomycosis.
These are discussed below.
a) Fungal meningtis
Fungal meningitis can develop after a fungus spreads through the bloodstream from somewhere else within the body.
The condition develops as a result of the fungus being introduced directly into the central nervous system, or from an
infected body site infection next to the central nervous system. One of the most common causes of fungal meningitis for
people with weak immune systems is Cryptococcus.
Fungal meningitis can also occur after taking medications that weaken the immune system. Examples of these
medications include steroids (such as prednisone), medications given after organ transplantation, or anti-TNF (anti-
tumor necrosis factor) medications, which are sometimes given for treatment of rheumatoid arthritis or other autoimmune
conditions.
Different types of fungi are transmitted in several ways. Cryptococcus is considered to be acquired through inhaling
soil contaminated with bird droppings; similarly Histoplasma is found in environments with heavy contamination of bird
or bat droppings. In contrast, Blastomyces is thought to exist in soil rich in decaying organic matter; whereas Coccidioides
is found in the soil of endemic areas (for example: South western US and parts of Central and South America). When
these environments are disturbed, the fungal spores can be inhaled. Aside from these environmental sources, Candida is
usually acquired in a hospital setting.
Signs and symptoms of fungal meningitis may include the following:
• Fever,
• Headache,
• Stiff neck,
• Nausea and vomiting,
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• Photophobia (sensitivity to light),

• Altered mental status.
Fungal meningitis can be treated with long courses of high dose anti-fungal medications. These are usually given
through an intravenous feed in a hospital. The length of treatment depends on the status of the immune system and the
type of fungus that caused the infection. For people with immune systems that do not function well because of other 008
conditions, like AIDS, diabetes, or cancer, treatment is often longer.
 b) Fungal keratitis
Keratitis is an inflammation of the cornea and it is often caused by an infection. Bacteria, viruses, amoeba, and fungi
can all cause keratitis. Fungal keratitis is an inflammation of the cornea. The types of fungi that have been known to cause
fungal keratitis include: Fusarium spp., Aspergillus spp., and Candida spp [27].
Of this list, Fusarium and Aspergillus species live in the environment, often in association with plant matter. Candida
species are some of the microorganisms that normally live on human skin and mucous membranes. Although fungal
keratitis can be a serious condition, it is relatively are.
c) Onychomycosis
Onychomycosis is an infection of the nail apparatus by fungi. The species that cause the condition include
dermatophytes, non-dermatophyte moulds and yeasts (mainly Candida species). The toenails are affected in most cases of
onychomycosis. Nychomycosis is classified clinically as distal and lateral subungual onychomycosis (DLSO), superficial
white onychomycosis (SWO), proximal subungual onychomycosis (PSO), Candidal onychomycosis and total dystrophic
onychomycosis [28].
Antifungal treatments
The management of patients with invasive fungal infection is becoming more complex with an increasing number of
antifungal agents available. Four classes of drugs for the treatment of invasive fungal infections exist: polyenes, triazoles,
echinocandins and nucleoside analogues [29].
Of the different antifungal drugs available, conventional amphotericin B (Fungizone) remains the standard therapy
for many invasive or life-threatening mycoses. Amphotericin B is a polyene antifungal drug, often used intravenously
for systemic fungal infections; it was originally extracted from the bacterium Streptomyces nodosus. It is effective against
Aspergillus species, Blastomycesdermatitidis, Candida species, Coccidioides immitis, Cryptococcus neoformans, Fusarium
species, Sporothrix shenckii, Histoplasma capsulatum, Paracoccidioides brasiliensis [30]. Amphotericin B functions by
binding to ergosterol moiety in the plasma membrane causing derangement of the membrane integrity and leakage of
cytoplasmic contents.
As an anti-fungal agent Amphotericin B has known side-effects associated with significant toxicity, including infusion-
related events, such as chills, fever, headache, nausea and vomiting, and dose-limiting nephrotoxicity [31]. AmpthotericinB
is also ineffective against the fungi Scedosporium and Trichosporon.
Despite the general use of ampthotericin, treatment is increasingly being orientated towards specific agents for certain
fungal disease (azole agents) [32]. Azole agents attack the plasma membrane causing selective leakage and increased
osmotic sensitivity. They also disrupt chitin synthesis.
Often a combination of different anti-fungal agents is required. For example, with Candida, fluconazole, Amphotericin
B (AmB) deoxycholate, caspofungin and voriconazole are the primary treatment options [33]. With a second example,
for Aspergillus species, drugs active against the genus include AmBdeoxycholate and its lipid formulations, itraconazole,
voriconazole, posaconazole and caspofungin [34].
In the immunocompetent host, the duration of antifungal treatment is dependent upon the site and extent of the
infection. A typical course of antifungal medicine lasts anywhere between two weeks and three months, depending upon
the type of fungus and host factors. In ideal circumstances, antifungal susceptibility testing should be carried out against
the specific causative organism [35].
In vitro antifungal susceptibility tests are performed by a clinical microbiology laboratory on a wide range of yeasts and
moulds. The main practical difficulties with antifungal susceptibility testing are usually with the inoculum preparation
and end point determination [36].

Pathogenic Dimoprhic and Filamentous Fungi

There are several species of fungi that are known, and common, pathogens to human hosts [37]. These can be divided
into three groups:
a) Opportunistic infections
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Opportunistic infections include ecryptococcosis and aspergillosis. These infections are problematic for people with
weakened immune systems, such as cancer patients, transplant recipients, and people with HIV/AIDS.
b) Hospital-associated infections
Hospital acquired infections include candidemia, which is the leading cause of bloodstream infections. An associated
risk is that advancements and changes in healthcare practices can, as this chapter has discussed, provide opportunities for 009
new and drug-resistant fungi to emerge in hospital settings [38].
 c) Community-acquired infections
Infections within the general populace include coccidioidomycosis, blastomycosis, and histoplasmosis. These diseases
are caused by fungi that are abundant in the environment, such as soil, on plants, or in compost heaps. Climate change
may affect these fungi, given that small changes in temperature or moisture can affect fungal growth, leading to an
increased level of incidents.
Primary fungal infections
The main species of fungi which are most commonly associated with diseases in immunocompromised hosts are:
a) Aspergillus
Aspergillus is a common fungus that can be found in indoor and outdoor environments. Aspergillus thrives on a
variety of substrates such as corn, decaying vegetation and soil. These fungi are also common contaminants in air. Most
people breathe in Aspergillus spores every day without being affected.
Aspergillosis is a disease caused by fungi within this genus and it usually occurs in people with lung diseases (such as
cystic fibrosis) or weakened immune systems [39]. The spectrum of illness includes allergic reactions, lung infections, and
infections in other organs [40]. In humans, the major forms of disease are:
• Allergic broncho pulmonary aspergillosis or ABPA, which affects patients with respiratory diseases such as asthma,
cystic fibrosis, and sinusitis [41].
• Acute invasive aspergillosis, a form that grows into surrounding tissue, more common in those with weakened
immune systems such as AIDS or chemotherapy patients.
• Disseminated invasive aspergillosis, an infection spread widely through the body.
• Aspergilloma, a “fungus ball” that can form within cavities such as the lung [42].
The clinical manifestation and severity of the disease depends upon the immunologic state of the patient [43].There
are three clinical types of pulmonary aspergillosis:
1. Allergic hypersensitivity to the organism. Symptoms may vary from mild respiratory distress to alveolar fibrosis.

2. Aggressive tissue invasion. Aspergillosis is primarily a pulmonary disease, but the aspergilli may disseminate to any organ. They
may cause endocarditis, osteomyelitis, otomycosis and cutaneous lesions.

3. Fungus ball where the ‘lesion’ (actually a colony of mould growing in the cavity) is shaped like a half-moon (semi-lunar growth).
The patients may cough up the fungus elements because the organism frequently invades the bronchus. Chains of conidia can
sometimes be seen in the sputum.

Studies have indicated that Aspergillus fumigatus is the most common species recovered from cases of invasive
aspergillosis [44]. On Potato Dextrose Agar, colonies of this fungus show typical blue-green surface pigmentation with a
suede-like surface consisting of a dense felt of conidiophores. Conidial heads are typically columnar (up to 400x50 μm but
often much shorter and smaller) and uniseriate [45]. Conidiophores are short, smooth-walled and have conical-shaped
terminal vesicles which support a single row of phialides on the upper two thirds of the vesicle. Conidia are produced
in basipetal succession forming long chains and are globose to subglobose (2.5–3.0 μm in diameter), green and rough-
walled. This species is thermo tolerant and grows at temperatures up to 55°C [46].
The next most commonly recovered species are Aspergillus flavus, Aspergillu sniger, and Aspergillus terreu [47].
Aspergillus spp. are frequently secondary opportunistic pathogens in patients with bronchiectasis, carcinoma, other
mycoses, sarcoid, and tuberculosis [48].
b) Blastomyces dermatitidis
Blastomycosis is a disease caused by the fungus Blastomyces dermatitidis, a thermally dimorphic fungus. The fungus
lives in moist soil and in association with decomposing organic matter such as wood and leaves. Lung infection can occur
after a person inhales airborne microscopic fungal spores from the environment; however, many people who inhale the
spores do not get sick [49]. The symptoms of blastomycosis are similar to flu symptoms, and the infection can sometimes
become serious if it is not treated. Blastomycosis is associated with a spectrum of illness ranging from subclinical infection
to acute or chronicpneumonia; a subset of individuals with acute pulmonary blastomycosis can progress to fulminant or
multi lobar pneumonia and acute respiratory distress syndrome (ARDS), a life-threatening lung condition that prevents
enough oxygen from getting to the lungs and into the blood [49].
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c) Candida
Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. Candida are thin-walled, small
yeasts (4 to 6 microns) that reproduce by budding. Candida species are the most common cause of invasive fungal
infections in humans, producing infections that range from non–life-threatening mucocutaneous disorders to invasive
disease that can involve any organ [50]. The most frequently implicated risk factors include the use of broad-spectrum
antibacterial agents, use of central venous catheters, receipt of parenteral nutrition, receipt of renal replacement therapy
010
by patients in infection control units, neutropenia (a condition of an abnormally low number of white blood cells), use of
implantable prosthetic devices, and receipt of immunosuppressive agents [51].
There are over twenty species of Candida yeasts that can cause infection in humans, the most common of which is
Candida albicans. Candida yeasts normally live on the skin and mucous membranes without causing infection; however,
overgrowth of these organisms can cause symptoms to develop. Candida spp. can also be found in soil, inanimate objects,
food, and hospital environments. Symptoms of candidiasis vary depending on the area of the body that is infected.
Candidiasis that develops in the mouth or throat is called “thrush” or oropharyngeal candidiasis. Candidiasis in
the vagina is commonly referred to as a “yeast infection.” Invasive candidiasis occurs when Candida species enter the
bloodstream and spread throughout the body. Clinical manifestations of candidiasis include [52]:
• Vaginal. Recurrent episodes of Candida vaginitis associated with the classic symptoms of pruritus, burning and
abnormal discharge.
• Gastrointestinal. Heartburn, bloating, diarrhea or constipation.
• Respiratory allergy. Rhinitis, sneezing and/or wheezing.
• Central nervous system. Anxiety, depression, memory deficits and/or loss of ability to concentrate.
• Menstrual abnormalities. Severe premenstrual tension and/or menstrual irregularities.
• Other Systemic Symptoms. Fatigue, headache and/or irritability.
d) Cladosporium
Cladosporium is a common mould found outdoors, on soil and plants, and indoors, on wet surfaces, including wallpaper
and carpet. Many species are cosmopolitan fungi isolated from soil, plant debris and leaf surfaces. Cladosporium is very
frequently isolated from air, especially during seasons in which humidity is elevated.
The growth rate of Cladosporium colonies is moderate on Potato Dextrose Agar at 25°C and the texture is velvety to
powdery. The colony colour ranges from olivaceous green to black, from the front and black from the reverse. Most of
the Cladosporium spp. do not grow at temperatures above 35°C [53]. Examples include Cladosporium cladosporioides,
Cladosporium sphaerospermum and Cladosporium herbarum.
The most common infections caused by Cladosporium are skin and toenail infections, but the fungus can cause sinus
and lung infections and eye (corneal) ulcers [54]. Cladosporium can also cause allergies and asthma attacks. Although
Cladosporium rarely causes infections for people, Cladosporium is till recognised as a human pathogen [55].
e) Coccidioides
Coccidioidomycosis is the infection caused by the dimorphic fungus Coccidio idesimmitis [56]. Coccidioides is a
fungus found in the soil of dry, low rainfall areas. Coccidioidomycosis, also known as Valley Fever, is a common cause
of pneumonia in endemic areas. At least 30% – 60% of people who live in an endemic region are exposed to the fungus
at some point during their lives. In most people the infection is short lasting and not life threatening, however for people
who develop severe infections or chronic pneumonia, medical treatment is necessary. Certain groups of people are at
higher risk of developing severe disease [57].
f) Cryptococcus
Cryptococcus is a fungus (a heterothallic basidiomycete) that is found in the soil and produces spores that can be
inhaled. People can become infected with Cryptococcus early in life but be unaware of the infection. If a person’s immune
system is weakened (for example, by HIV), Cryptococcus can cause a life-threatening infection called cryptococcal
meningitis [58], an infection of the meninges (the tissue covering the brain)
There are over thirty different species of Cryptococcus, but two species – Cryptococcus neoformans and Cryptococcus
gattii – cause nearly all cryptococcal infections in humans and animals. Of the two, C. neoformansis the most prevalent (C.
neoformans var. grubii (serotype A) accounts for the vast majority of the disease worldwide). The fungus is found in soil
throughout the world. People at risk can become infected after inhaling microscopic, airborne fungal spores. Sometimes
these spores cause symptoms of a lung infection, but other times there are no symptoms at all. In people with weakened
immune systems, the fungus can spread to other parts of the body and cause serious disease [59].
Cryptococcus is detected using a blood test for the cryptococcal antigen. There are primarily two types of commercial
tests, latex agglutination and ELISA systems [60].
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g) Dermatophytes
Dermatophytes are fungi that cause skin, hair, and nail infections. Infections caused by these fungi are also sometimes
known as “ringworm” or “tinea.” For example, Tineacapitis is an infection caused by dermatophyte fungi (usually species
in the genera Microsporum and Trichophyton) of scalp hair follicles and the surrounding skin [61].
Dermatophytes can live on moist areas of the skin, on environmental surfaces, and on household items such as 011
clothing, towels, and bedding [62].
 h) Exserohilum rostratum
Exserohilum rostratum is a dematiaceous fungus that rarely causes infection (phaeohyphomycosis) in people. The
most common type of infections are sinusitis and skin infections, although also a few cases of cerebral abscesses, keratitis,
osteomyelitis, prosthetic valve endocarditis and disseminated infection have been described [63].
The colony is characterised by moderately rapid growth; in terms of appearance it has a velvety texture and dark
olive to black colour on the surface and reverse underside. Microscopic observations include septate hyphae, pale brown
conidiophores brown, geniculate at the apex, proconidia cylindrical to ellipsoidal, multicellular, distoseptate (conidia
subdivided by inner wall layer only) with a protuberant hilum at the base [64].
i) Histoplasma capsulatum
Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum var.capsulatum (an anamorphic fungus).
The fungus lives in the environment, usually in association with large amounts of bird or bat droppings. Lung infection
can occur after a person inhales airborne, microscopic fungal spores from the environment [65]. Certain forms of
histoplasmosis can cause life-threatening illnesses and result in considerable morbidity, whereas other manifestations
cause no symptoms orminor self-limited illnesses. In the more serious cases, the symptoms of histoplasmosis are similar
to pneumonia [66].
j) Mucoromycotina
Mucormycosis (also called zygomycosis) is a relatively rare infection caused by organisms that belong to a group of
fungi called Mucoromycotina in the order Mucorales. At one time these fungi were called Zygomycota, but this scientific
name has recently been changed. These fungi are typically found in the soil and in association with decaying organic
matter, such as leaves, compost piles, or rotten wood. The three most common genera causing this clinical entity are
Rhizopus species, Mucor species, and Absidia species.
Mucormycosis is an acute inflammation of soft tissue, usually with fungal invasion of the blood vessels (angiotropic).
Infections are generally acute and rapidly developing in debilitated patients [67].
k) Pneumocystis jirovecii
Pneumocystis pneumonia (PCP) is a serious illness caused by the fungus Pneumocystis jirovecii. PCP is one of the
most frequent and severe opportunistic infections in people with weakened immune systems, particularly people with
HIV/AIDS. Although people with HIV/AIDS are less likely to get PCP today than in recent years, PCP is still a significant
public health problem [68].
l) Sporothrix schenckii
Sporotrichosis is an infection caused by a fungus called Sporothrix schenckii (a dimorphic fungus). The fungus lives
throughout the world in soil, plants, and decaying vegetation. Cutaneous (skin) infection is the most common form
of infection and usually occurs after handling contaminated plant material, when the fungus enters the skin through
a small cut or scrape. Pulmonary and disseminated forms of infection, although uncommon, can occur. Most cases of
sporotrichosis are localised to the skin and subcutaneous tissues [69].

Conclusion
This chapter has examined the primary mycotic diseases (arising from dimorphs and filamentous fungi) that pose a
significant risk to the immunocompromised host. What is clear from the list of different microorganisms is that many of
them are found in the general environment on the human body and that they do not; in general, pose a risk to those with
healthy immune systems. Such microorganisms become a risk when the immune system is weakened (due to primary or
secondary reasons). Thus the immunocompromised person is especially vulnerable to opportunistic infections.
As well as outlining the different infectious agents, the chapter has discussed some of the microbiological and diagnostic
attributes required for the identification of the disease within the infected person and for the characterisation of the
organism through microbiological identification methods. Understanding the type of fungus is important for considering
the treatment. In relation to treatments the chapter has outlined some of the common anti-fungal medicines.

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