An In-Depth Exploration of Opportunistic Mycoses: Understanding the Fungal Infections That Exploit Weak Hosts

An In-Depth Exploration of Opportunistic Mycoses: Understanding the Fungal Infections That Exploit Weak Hosts

 

INTRODUCTION

Opportunistic fungi fail to induce illness in most immu-

nocompetent individuals however can accomplish that in these with impaired

host defenses. There are 5 genera of medically essential

fungi: Candida, Cryptococcus, Aspergillus, Mucor, and Rhizopus.

Necessary options of the opportunistic fungal illnesses are

described in Desk 50–1.

CANDIDA

Illnesses

Candida albicans, crucial species of Candida,

causes thrush, vaginitis, esophagitis, diaper rash, and continual

mucocutaneous candidiasis. It additionally causes disseminated infec-

tions corresponding to right-sided endocarditis (particularly in intravenous

drug customers), bloodstream infections (candidemia), and endo-

phthalmitis. Infections associated to indwelling intravenous and

urinary catheters are additionally essential. Candida glabrata is the

second most typical explanation for disseminated candidal infec-

tions and is extra drug resistant than C. albicans. Candida auris

causes severe bloodstream infections and is very antibiotic

resistant.

Properties

Candida albicans is an oval yeast with a single bud (Figures 50–1

and 50–2). It’s a part of the conventional flora of mucous membranes

of the higher respiratory, gastrointestinal, and feminine genital tracts.

In tissues, it seems most frequently as yeasts or as pseudohyphae

(Figures 50–1 and 50–3). Pseudohyphae are elongated yeasts

that visually resemble hyphae however should not true hyphae. True

hyphae are additionally fashioned when C. albicans invades tissues.

Carbohydrate fermentation reactions can be utilized to differ-

entiate it from different species (e.g., Candida tropicalis, Candida

parapsilosis, Candida krusei, and C. glabrata) that trigger human

infections.

Candida dubliniensis is carefully associated to C. albicans. It

additionally causes opportunistic infections in immunocompromised

sufferers, particularly AIDS sufferers. Each species type chlamydo-

spores, however C. albicans grows at 42°C, whereas C. dubliniensis

doesn’t.

Transmission

As a member of the conventional flora, C. albicans is already pres-

ent on the pores and skin and mucous membranes. Along with the

pores and skin, C. albicans is discovered all through the gastrointestinal tract

(particularly the mouth and esophagus) and within the vagina. Thrush

within the new child is the results of passage by means of a beginning canal

closely colonized by the organism. The presence of C. albicans

on the pores and skin predisposes to infections involving devices that

penetrate the pores and skin, corresponding to needles (intravenous drug use) and

indwelling catheters. It’s usually discovered within the urine of sufferers

with indwelling urinary (Foley) catheters.

Pathogenesis & Medical Findings

The primary line of protection towards Candida infections is undamaged

pores and skin and mucous membranes. The second line is cell-mediated

immunity, particularly Th-1 cells producing gamma-interferon

that prompts environment friendly killing by macrophages. Neutrophils are

additionally essential as evidenced by the discovering that neutropenia

predisposes to disseminated Candida infections.

When native or systemic host defenses are impaired, illness

could consequence. Overgrowth of C. albicans within the mouth produces

white patches known as thrush (Determine 50–4). (Be aware that thrush

is a pseudomembrane, a time period that’s outlined in Chapter 7 on

web page 38.) Vaginitis with itching and discharge is favored by excessive

pH, diabetes, or use of antibiotics. Antibiotics suppress the

regular flora Lactobacillus, which preserve the pH low. In consequence,

the pH rises, which favors the expansion of Candida.

Pores and skin invasion happens in heat, moist areas, which grow to be

crimson and weeping. Fingers and nails grow to be concerned when

repeatedly immersed in water; individuals employed as dishwash-

ers in eating places are generally affected. Thickening or loss

of the nail can happen. Diaper rash in infants happens when moist

diapers should not modified promptly (Determine 50–5).

In immunosuppressed people, Candida could dissemi-

nate to many organs or trigger continual mucocutaneous candidia-

sis (CMC). CMC is a chronic an infection of the pores and skin, oral and

genital mucosa, and nails that happens in people poor in

T-cell immunity. Sufferers with mutations within the gene encoding

interleukin-17 (IL-17) and the receptor for IL-17 are predis-

posed to CMC. After organ transplantation, sufferers receiving

immunosuppressive medication to forestall rejection are predisposed

to invasive Candida infections.

Intravenous drug abuse, indwelling intravenous catheters,

and hyperalimentation additionally predispose to disseminated candi-

diasis, particularly right-sided endocarditis and endophthalmitis

(an infection throughout the eye). Candida esophagitis, usually accompa-

nied by involvement of the abdomen and small gut, is seen

in sufferers with leukemia and lymphoma. Subcutaneous nod-

ules are sometimes seen in neutropenic sufferers with disseminated

FIGURE 50–4 Candida albicans—thrush in mouth. Be aware whitish

plaques on tongue. (Reproduced with permission from Usatine, RP et al. The

Coloration Atlas of Household Drugs, New York, NY: McGraw-Hill; 2009. Courtesy of

Richard P. Usatine, MD.)

FIGURE 50–5 Candida albicans—diaper rash. Be aware in depth

space of irritation in perineal area. (Reproduced with permission from

Wolff Ok, Johnson R, eds. Fitzpatrick’s Coloration Atlas & Synopsis of Medical Dermatology.

sixth ed. New York, NY: McGraw-Hill; 2009.)

illness. Candida albicans is the commonest species to trigger

disseminated illness in these sufferers, however C. tropicalis, C. auris,

and C. parapsilosis are essential pathogens additionally.

Laboratory Prognosis

In exudates or tissues, budding yeasts and pseudohyphae

seem gram-positive and will be visualized through the use of calcofluor-

white staining. In tradition, typical yeast colonies are fashioned

that resemble massive staphylococcal colonies. Candida albicans

varieties germ tubes in serum at 37°C, whereas most different spe-

cies of pathogenic Candida species don’t (see Determine 50–1).

Chlamydospores are sometimes fashioned by C. albicans however not

by most different species of Candida. Be aware that C. dubliniensis additionally

varieties chlamydospores however is not going to develop at 42°C, whereas

C. albicans will. Serologic testing is never useful.

Molecular strategies are additionally helpful for the analysis of

Candida infections. Two present strategies are (1) polymerase

chain response (PCR)-based assays that detect the DNA

encoding the ribosomal RNA of Candida species and (2) mass

spectrometry (matrix-assisted laser desorption ionization-

time of flight [MALDI-TOF]) assays that detect the proteins

of Candida species.

Remedy & Prevention

The drug of selection for many candidal infections is fluconazole,

together with oropharyngeal or esophageal thrush. Itraconazole

and voriconazole are additionally efficient. An echinocandin, corresponding to

caspofungin or micafungin, will also be used for esophageal

candidiasis.

Remedy of pores and skin infections consists of topical antifungal

medication (e.g., clotrimazole or nystatin). Candida vaginitis is

handled both with topical (intravaginal) azole medication, corresponding to

clotrimazole or miconazole, or with oral fluconazole. Continual

mucocutaneous candidiasis will be managed by fluconazole

or itraconazole. Remedy of disseminated candidiasis consists

of both fluconazole or an echinocandin corresponding to caspofungin.

Remedy of candidal infections with antifungal medication

must be supplemented by discount of predisposing components.

Strains of C. albicans proof against azole medication have emerged in

sufferers with acquired immunodeficiency syndrome (AIDS)

receiving long-term prophylaxis with fluconazole. Most isolates

of C. glabrata are proof against fluconazole and voriconazole. An

echinocandin corresponding to caspofungin or amphotericin B must be

used. Candida auris is usually multidrug resistant.

Sure candidal infections (e.g., thrush) will be prevented

by oral clotrimazole troches, buccal miconazole tablets, or

nystatin “swish and swallow.” Fluconazole is beneficial in prevent-

ing candidal infections in high-risk sufferers, corresponding to these

present process bone marrow transplantation and untimely infants.

Micafungin will also be used. There is no such thing as a vaccine.

CRYPTOCOCCUS

Illness

Cryptococcus neoformans causes cryptococcosis, particularly cryp-

tococcal meningitis. Cryptococcosis is the commonest, life-

threatening, invasive fungal illness worldwide. It’s particularly

essential in AIDS sufferers. One other species, Cryptococcus

gattii causes human illness much less regularly than C. neoformans.

Properties

Cryptococcus neoformans is an oval, budding yeast surrounded

by a large polysaccharide capsule (Figures 50–6 and 50–7). It

shouldn’t be dimorphic. Be aware that this organism varieties a narrow-based

bud, whereas the yeast type of Blastomyces dermatitidis varieties

a broad-based bud.

FIGURE 50–6 Cryptococcus neoformans. India ink preparation

exhibits budding yeasts with a large capsule. India ink varieties a darkish

background; it doesn’t stain the yeast itself. (Reproduced with permis-

sion from Brooks GF et al. Medical Microbiology. twentieth ed. Initially revealed by

Appleton & Lange. Copyright 1995, McGraw-Hill.)

FIGURE 50–7 Cryptococcus neoformans—India ink preparation.

Arrow factors to a budding yeast of Cryptococcus neoformans. Be aware

the thick, translucent polysaccharide capsule outlined by the darkish

India ink particles. (Supply: Dr. L. Haley, Public Well being Picture Library, Facilities for

Illness Management and Prevention.)

Transmission

Cryptococcus neoformans happens broadly in nature and grows

abundantly in soil containing chicken (particularly pigeon)

droppings. The birds should not contaminated. Human an infection outcomes

from inhalation of the organism. There is no such thing as a human-to-

human transmission. Cryptococcus gattii is related to

eucalyptus timber, most frequently within the northwestern states of the

United States. Additionally it is present in subtropical and tropical areas

of many international locations.

Pathogenesis & Medical Findings

Lung an infection is usually asymptomatic or could produce pneumo-

nia. Illness brought on by C. neoformans happens primarily in sufferers

with lowered cell-mediated immunity, particularly AIDS sufferers,

in whom the organism disseminates to the central nervous sys-

tem (meningitis) and different organs. Subcutaneous nodules are

usually seen in disseminated illness. Be aware, nonetheless, that roughly

half the sufferers with cryptococcal meningitis fail to indicate evi-

dence of immunosuppression.

In some sufferers with AIDS who’re contaminated with Cryptococ-

cus, treating the affected person with extremely lively antiretroviral remedy

(HAART) causes an exacerbation of signs. This phenom-

enon known as immune reconstitution inflammatory syndrome

(IRIS). The reason of the exacerbation of signs is that

HAART will increase the variety of CD4 cells, which will increase the

inflammatory response. Some sufferers have died on account of

cryptococcal IRIS. To forestall IRIS, sufferers must be handled

for the underlying an infection earlier than beginning HAART.

Cryptococcus gattii causes human illness much less regularly however

is extra able to inflicting illness in an immunocompetent

individual than C. neoformans. Cryptococcus gattii is extra seemingly

to trigger cryptococcomas (granulomas), particularly within the mind,

than C. neoformans.

Laboratory Prognosis

In spinal fluid blended with India ink, the yeast cell is seen micro-

scopically surrounded by a large, unstained capsule. Look

of the organism in Gram stain is unreliable, however stains such

as periodic acid–Schiff (PAS stain), methenamine silver,

and mucicarmine will enable the organism to be visualized

(Determine 50–8). The organism will be cultured from spinal fluid

and different specimens. The colonies are extremely mucoid—a reflec-

tion of the big quantity of capsular polysaccharide produced

by the organism.

Serologic assessments will be achieved for each antibody and antigen. In

contaminated spinal fluid, capsular antigen happens in excessive titer and

will be detected by the latex particle agglutination take a look at. This

take a look at known as the cryptococcal antigen take a look at, usually abbreviated

as “crag.” PCR-based assays that detect the ribosomal DNA of

Cryptococcus are additionally helpful.

Distinguishing between C. neoformans and C. gattii within the

laboratory requires specialised media not usually out there, so

many C. gattii infections could go undiagnosed.

Remedy & Prevention

Mixed therapy with amphotericin B and flucytosine is

utilized in meningitis and different disseminated illness. Liposomal

amphotericin B must be utilized in sufferers with preexisting

kidney harm. There are not any particular technique of prevention.

Fluconazole is utilized in AIDS sufferers for long-term suppression

of cryptococcal meningitis. Cryptococcus gattii is much less responsive

to antifungal medication than is C. neoformans.

ASPERGILLUS

Illness

Aspergillus species, particularly Aspergillus fumigatus, trigger infec-

tions of the pores and skin, eyes, ears, and different organs; “fungus ball” in

the lungs; and allergic bronchopulmonary aspergillosis.

FIGURE 50–8 Cryptococcus neoformans—Mucicarmine stain.

Be aware many crimson, oval yeasts of C. neoformans in lung tissue of affected person

with AIDS. (Supply: Dr. Edwin P. Ewing, Jr, Public Well being Picture Library, Facilities for

Illness Management and Prevention.)

Properties

Aspergillus species exist solely as molds; they aren’t dimorphic.

They’ve septate hyphae that type V-shaped (dichotomous)

branches (Figures 50–9 and 50–10). The partitions are kind of

parallel, in distinction to Mucor and Rhizopus partitions, that are

irregular (Figures 50–9 and 50–11). The conidia of Aspergillus

type radiating chains, in distinction to these of Mucor and Rhizopus,

that are enclosed inside a sporangium (Determine 50–12).

Transmission

These molds are broadly distributed in nature. They develop on

decaying vegetation, producing chains of conidia. Transmission

is by airborne conidia.

Pathogenesis & Medical Findings

Aspergillus fumigatus can colonize and later invade abraded

pores and skin, wounds, burns, the cornea, the exterior ear, or parana-

sal sinuses. It’s the commonest explanation for fungal sinusitis.

In immunocompromised individuals, particularly these with neu-

tropenia, it could possibly invade the lungs, producing hemoptysis, and

the mind, inflicting an abscess. Neutropenic sufferers are additionally

predisposed to intravenous catheter infections brought on by this

organism.

Aspergilli are well-known for his or her means to develop in cavi-

ties throughout the lungs, particularly cavities brought on by tuberculosis.

Throughout the cavities, they produce an aspergilloma (fungus ball),

which will be seen on chest X-ray as a radiopaque construction that

adjustments its place when the affected person is moved from an erect to

a supine place.

Allergic bronchopulmonary aspergillosis (ABPA) is a hyper-

sensitivity response to the presence of Aspergillus within the bronchi.

Sufferers with ABPA have asthmatic signs and a excessive IgE

titer towards Aspergillus antigens, they usually expectorate brownish

bronchial plugs containing hyphae. Bronchial asthma brought on by the inha-

lation of airborne conidia, particularly in sure occupational set-

tings, additionally happens. Aspergillus flavus rising on cereals or nuts

produces aflatoxins that could be carcinogenic or acutely poisonous.

Laboratory Prognosis

Biopsy specimens present septate, branching hyphae invading

tissue (see Determine 50–10). Cultures present colonies with charac-

teristic radiating chains of conidia (see Determine 50–12). Nevertheless,

optimistic cultures don’t show illness as a result of colonization is

frequent. In individuals with invasive aspergillosis, there could also be

excessive titers of galactomannan antigen in serum. Sufferers with

ABPA have excessive ranges of IgE particular for Aspergillus antigens

and distinguished eosinophilia. IgG precipitins are additionally current.

Remedy & Prevention

Voriconazole is the drug of selection for invasive aspergillosis.

Liposomal amphotericin B, posaconazole, caspofungin, and

isavuconazonium are different medication. A fungus ball rising

in a sinus or in a pulmonary cavity will be surgically eliminated.

Sufferers with ABPA will be handled with corticosteroids and

antifungal brokers, corresponding to itraconazole. There are not any particular

technique of prevention.

MUCOR & RHIZOPUS

Mucormycosis (zygomycosis, phycomycosis) is a illness precipitated

by saprophytic molds (e.g., Mucor, Rhizopus, and Absidia)

discovered broadly within the setting. They aren’t dimorphic.

These organisms are transmitted by airborne asexual spores and

invade tissues of sufferers with lowered host defenses. They pro-

liferate within the partitions of blood vessels, significantly of the paranasal

sinuses, lungs, or intestine, a

If analysis is made early, therapy of the underlying disor-

der, plus administration of amphotericin B and surgical removing

of necrotic contaminated tissue, has resulted in some remissions and

cures. Liposomal amphotericin B must be utilized in sufferers

with preexisting kidney harm. Posaconazole will also be used

to deal with mucormycosis. Posaconazole can be used for prophy-

laxis towards Mucor infections in severely immunocompromised

sufferers.

PNEUMOCYSTIS

Pneumocystis jiroveci is classed as a yeast on the premise of

molecular evaluation, but it surely has many traits of a proto-

zoan. Some regard it as an “unclassified” organism. A abstract

of the essential scientific data is introduced right here, and

a extra detailed description is introduced in Chapter 52 with

the blood and tissue protozoa. In 2002, taxonomists renamed

the human species of Pneumocystis as P. jiroveci and recom-

mended that P. carinii be used solely to explain the rat species

of Pneumocystis.

Pneumocystis is acquired by inhalation of airborne organ-

isms into the lungs. An inflammatory exudate composed pri-

marily of plasma cells happens, oxygen alternate is lowered, and

dyspnea happens. A lowered variety of CD4-postive T lympho-

cytes, corresponding to happens in AIDS, predispose to pneumonia. Most

immunocompetent individuals have asymptomatic infections.

The scientific findings of Pneumocystis pneumonia embody

fever, nonproductive cough, and dyspnea. Rales are heard bilat-

erally, and the chest X-ray exhibits a “ground-glass” sample. The

mortality charge of untreated Pneumocystis pneumonia is approxi-

mately 100%.

The analysis is often made by discovering the cysts

of Pneumocystis in bronchial lavage specimens. Fluorescent

antibody stains or tissue stains, corresponding to methenamine silver or

Giemsa, are used to determine the organism. PCR-based assessments are

additionally used. Serologic assessments should not helpful.

The drug of selection for Pneumocystis pneumonia is trime-

thoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole or

aerosolized pentamidine can be utilized for prophylaxis in sufferers

with CD4 counts under 200.

FUNGI OF MINOR IMPORTANCE

PENICILLIUM MARNEFFEI

Penicillium marneffei is a dimorphic fungus that causes tuber-

culosis-like illness in AIDS sufferers, significantly in Southeast

Asian international locations corresponding to Thailand. It grows as a mildew that pro-

duces a rose-colored pigment at 25°C however at 37°C grows as a

small yeast that resembles Histoplasma capsulatum. Bamboo

rats are the one different identified hosts. The analysis is made

both by rising the organism in tradition or through the use of fluo-

rescent antibody staining of affected tissue. The therapy of

selection consists of amphotericin B for two weeks adopted by oral

itraconazole for 10 weeks. Relapses will be prevented with pro-

longed administration of oral itraconazole. Penicillium marneffei is

additionally known as Talaromyces marneffei.

PSEUDALLESCHERIA BOYDII &

SCEDOSPORIUM APIOSPERMUM

Pseudallescheria boydii is a mildew that causes illness primarily

in immunocompromised sufferers. The scientific findings and the

microscopic look of the septate hyphae in tissue carefully

resemble these of Aspergillus. In tradition, the looks of the

conidia (pear-shaped) and the colour of the mycelium (brownish-

grey) of P. boydii are totally different from these of Aspergillus. The

drug of selection is both ketoconazole or itraconazole as a result of the

response to amphotericin B is poor. Debridement of necrotic

tissue is essential as effectively.

Scedosporium apiospermum is the asexual type of P. boydii.

Scedosporium primarily causes illness in immunocompro-

mised sufferers but in addition causes mycetoma in immunocompetent

people. In immunocompromised sufferers, Scedosporium

causes angioinvasive illness, particularly pneumonia and dis-

seminated abscesses. A microbiologic analysis is made by

seeing septate hyphae in tissue and rising colorless mildew colo-

nies on fungal media. Scedosporium is proof against all presently

used antifungal medication. Mortality charges in immunocompromised

sufferers with disseminated illness vary from 85% to 100%.

FUSARIUM SOLANI

Fusarium solani is a mildew that causes illness primarily in neu-

tropenic sufferers. Fever and pores and skin lesions are the commonest

scientific options. The organism is much like Aspergillus in that

it’s a mildew with septate hyphae that tends to invade blood ves-

sels. Blood cultures are sometimes optimistic in disseminated illness.

In tradition, banana-shaped conidia are seen. Liposomal ampho-

tericin B is the drug of selection. Indwelling catheters must be

eliminated or changed. In 2006, an outbreak of Fusarium keratitis

(an infection of the cornea) occurred in individuals who used a sure

contact lens resolution.