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Bacterial and Mycotic Infections in Immunocompromised Hosts: Clinical and Microbiological Aspects

Edited by

Maria Teresa Mascellino

www.esciencecentral.org/ebooks

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Dimorph and Filamentous Fungi

Introduction

An immunocompromised host is an individual whose immune response is weakened as a result of an immunodeiciency

disorder, exposure to immunosuppressive drugs or irradiation (for example, patients undergoing cancer chemotherapy or

bone marrow transplantation).he 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]. he 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 immunodeiciency are acquired (so-termed secondary cases). However, some people are born with

defects in their immune system (described as primary immunodeiciency) [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).

he 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 ilamentous fungi

have, in some cases, caused signiicant microbial contamination issues in production environments and manufactured

products [3].

his chapter examines the risks to immunocompromised patients from fungal infections. In doing so the chapter

identiies and describes the most common types of infections. he chapter additionally discusses some of the steps taken

for the microbiological isolation and assessment of the clinically signiicant microorganisms and provides an introduction

to some of the treatment steps.

Dimorph and Filamentous Fungi

he 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 ilamentous). Yeasts are unicellular fungi which reproduce asexually by blastoconidia formation (budding) or ission. 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 ine threads (hyphae). Hyphae grow at the tip and divide repeatedly along their length creating long and branching chains. Most ilamentous fungi grow in a polar fashion (by extension into one direction) by elongation at the tip (apex) of the hypha [4]. he hyphae continue to grow and intertwine until they form a network of threads called a mycelium. Digestive enzymes are secreted from the hyphal tip. hese 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 diferent phases of the complex life cycles of the fungi. Fungi are oten classiied 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/ilamentous form or as yeast [6]. Examples include Penicillium marnefei, 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 ilaments.

Many fungi produce biologically active compounds, several of which are toxic to animals or plants and are therefore

called mycotoxins. his can lead to human disease (mycotoxicosis). he symptoms of a mycotoxicosis depend on the type

of mycotoxin; the concentration and length of exposure; as well as age, health, and sex of the exposed individual [7].

Tim Sandle*

*Corresponding author: Tim Sandle, Bio Products Laboatory,

United Kingdom; E-mail: tim.sandle@bpl.co.uk

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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]. herefore, characterising the fungus is important for targeting the speciic treatment.

Identiication of fungal isolates from clinical environments using standard identiication procedures requires

experienced and skilled laboratory staf. When infections are assumed, accurate fungal identiication is needed if the

contamination source has to be determined and tracked.

Some identiication systems are available for the identiication of fungi, including biochemical systems such as the API

Candida, Omnilog and Vitek [9]. here has also been some advancement with genotypic techniques. For ilamentous

fungal identiication, 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 identiication. Moreover, no single identiication 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 ilamentous fungi the fungus must be grown on a suitable

microbiological culture medium. he cultural identiication of fungi requires the use of selective media, for example

Sabouraud Dextrose Agar or Potato Dextrose Agar [11]. here are a range of diferent culture media available for the

characterisation and isolation of clinically important fungi. hese 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

identiication of fungi; and Sabouraud’s Dextrose Agar is a general agar for the primary isolation and cultivation of

dermatophytes (fungi that cause skin, hair, and nail infections). he other agars are more suited for speciic types of fungi.

Ater growth at an appropriate temperature (normally 20-25°C) for an appropriate time (normally between ive and

seven days), the fungus is examined macroscopically and microscopically [12]. Visual examination of the colony will

reveal important data concerning colour, texture, difusible pigments, exudates (a luid with a high content of protein and

cellular debris), growth zones, aerial and submerged hyphae, growth rate, colony topography, and macroscopic structures

such as ascocarps, pycnidia, sclerotia, sporodochia, and synnemata [13].

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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. he 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 conirmed 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; speciic antigens from

blood; identiication 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

here are three models of anti-fungal control. hese 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. hese 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 eiciency particulate air) ilter [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]. Efective hand sanitisation should apply to hospital visitors as well as to healthcare workers. Other efective 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. he 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 diferent chemicals. Facilities should ensure that antimicrobials are used for appropriate indications and duration and that the narrowest spectrum antimicrobial that is appropriate for the speciic clinical scenario is used [22]. A further measure is the education of healthcare workers and staf 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. his innate resistance is due to: fatty acid content of the skin, pH of the skin, mucosal surfaces and body luids,

epithelial turnover, normal lora, transferrin (iron-binding blood plasma glycoproteins), and the cilia of respiratory tract.

Nonetheless, when the immune system is weakened fungal infections are relatively common. here are a range

of diferent dimorphic and ilamentous fungi that can cause infections in the immunocompromised host. Any list of

infectious agents would be quite extensive and there are many factors which afect 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.

Clinical criteria

When fungi pass the resistance barriers of the human body and establish infections, the infections are normally

classiied according to the tissue levels initially colonised. For example:

• Supericial mycoses: infections limited to the outermost layers of the skin and hair. For example, an infection

caused by the fungus Trichosporum beigelii that causes the condition white piedra.

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• 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. hese

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. his is because these species have biochemical

and structural features that enable it to evade host defences, not least the ability to adapt through diferent 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 deiciencies who

would otherwise not be infected), are associated with signiicant morbidity and mortality. Risk factors for invasive fungal

infection include malignancy, haematopoietic stem cell or solid organ transplantation, neutropenia, chemotherapy,

corticosteroid use, acquired immunodeiciency 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].

he three main types of fungal infections, and those that pose the greatest risk to immunocompromised hosts, are

fungal meningitis, fungal keratitis and onychomycosis.

hese are discussed below.

a) Fungal meningtis

Fungal meningitis can develop ater a fungus spreads through the bloodstream from somewhere else within the body.

he 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 ater taking medications that weaken the immune system. Examples of these

medications include steroids (such as prednisone), medications given ater organ transplantation, or anti-TNF (anti-

tumor necrosis factor) medications, which are sometimes given for treatment of rheumatoid arthritis or other autoimmune

conditions.

Diferent 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,

• Stif neck,

• Nausea and vomiting,

• Photophobia (sensitivity to light),

• Altered mental status.

Fungal meningitis can be treated with long courses of high dose anti-fungal medications. hese are usually given

through an intravenous feed in a hospital. he 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

conditions, like AIDS, diabetes, or cancer, treatment is oten longer.

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b) Fungal keratitis

Keratitis is an inlammation of the cornea and it is oten caused by an infection. Bacteria, viruses, amoeba, and fungi

can all cause keratitis. Fungal keratitis is an inlammation of the cornea. he 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, oten 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. he species that cause the condition include

dermatophytes, non-dermatophyte moulds and yeasts (mainly Candida species). he toenails are afected 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

he 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 diferent 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, oten used intravenously

for systemic fungal infections; it was originally extracted from the bacterium Streptomyces nodosus. It is efective 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-efects associated with significant toxicity, including infusion-

related events, such as chills, fever, headache, nausea and vomiting, and dose-limiting nephrotoxicity [31]. AmpthotericinB

is also inefective against the fungi Scedosporium and Trichosporon.

Despite the general use of ampthotericin, treatment is increasingly being orientated towards speciic agents for certain

fungal disease (azole agents) [32]. Azole agents attack the plasma membrane causing selective leakage and increased

osmotic sensitivity. hey also disrupt chitin synthesis.

Oten a combination of diferent anti-fungal agents is required. For example, with Candida, luconazole, 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 speciic causative organism [35].

In vitro antifungal susceptibility tests are performed by a clinical microbiology laboratory on a wide range of yeasts and

moulds. he main practical diiculties with antifungal susceptibility testing are usually with the inoculum preparation

and end point determination [36].

Pathogenic Dimoprhic and Filamentous Fungi

here are several species of fungi that are known, and common, pathogens to human hosts [37]. hese can be divided

into three groups:

a) Opportunistic infections

Opportunistic infections include ecryptococcosis and aspergillosis. hese 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

new and drug-resistant fungi to emerge in hospital settings [38].

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c) Community-acquired infections

Infections within the general populace include coccidioidomycosis, blastomycosis, and histoplasmosis. hese diseases

are caused by fungi that are abundant in the environment, such as soil, on plants, or in compost heaps. Climate change

may afect these fungi, given that small changes in temperature or moisture can afect fungal growth, leading to an

increased level of incidents.

Primary fungal infections

he 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. hese fungi are also common contaminants in air. Most

people breathe in Aspergillus spores every day without being afected.

Aspergillosis is a disease caused by fungi within this genus and it usually occurs in people with lung diseases (such as

cystic ibrosis) or weakened immune systems [39]. he 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 afects patients with respiratory diseases such as asthma,

cystic ibrosis, 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].

he clinical manifestation and severity of the disease depends upon the immunologic state of the patient [43].here

are three clinical types of pulmonary aspergillosis:

1. Allergic hypersensitivity to the organism. Symptoms may vary from mild respiratory distress to alveolar ibrosis.

2. Aggressive tissue invasion. Aspergillosis is primarily a pulmonary disease, but the aspergilli may disseminate to any organ. hey

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).

he 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

oten 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. his species is thermo tolerant and grows at temperatures up to 55°C [46].

he 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. he fungus

lives in moist soil and in association with decomposing organic matter such as wood and leaves. Lung infection can occur

ater a person inhales airborne microscopic fungal spores from the environment; however, many people who inhale the

spores do not get sick [49]. he symptoms of blastomycosis are similar to lu 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].

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]. he 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

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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].

here 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 deicits 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.

he growth rate of Cladosporium colonies is moderate on Potato Dextrose Agar at 25°C and the texture is velvety to

powdery. he 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.

he 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)

here are over thirty diferent 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). he fungus is found in soil

throughout the world. People at risk can become infected ater 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. here are primarily two types of commercial

tests, latex agglutination and ELISA systems [60].

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

clothing, towels, and bedding [62].

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h) Exserohilum rostratum

Exserohilum rostratum is a dematiaceous fungus that rarely causes infection (phaeohyphomycosis) in people. he 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].

he 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). he fungus lives in the environment, usually in association with large amounts of bird or bat droppings. Lung infection can occur ater 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 scientiic name has recently been changed. hese fungi are typically found in the soil and in association with decaying organic matter, such as leaves, compost piles, or rotten wood. he three most common genera causing this clinical entity are Rhizopus species, Mucor species, and Absidia species.

Mucormycosis is an acute inlammation of sot 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 signiicant public health problem [68].

l) Sporothrix schenckii

Sporotrichosis is an infection caused by a fungus called Sporothrix schenckii (a dimorphic fungus). he fungus lives throughout the world in soil, plants, and decaying vegetation. Cutaneous (skin) infection is the most common form of infection and usually occurs ater 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

his chapter has examined the primary mycotic diseases (arising from dimorphs and ilamentous fungi) that pose a

signiicant risk to the immunocompromised host. What is clear from the list of diferent 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). hus the immunocompromised person is especially vulnerable to opportunistic infections.

As well as outlining the diferent infectious agents, the chapter has discussed some of the microbiological and diagnostic

attributes required for the identiication of the disease within the infected person and for the characterisation of the

organism through microbiological identiication 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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