Opportunisitc Mycosis

8/2/2019 Opportunisitc Mycosis

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OPPORTUNISTIC

MYCOSES

Ust Dept. of Lab. Medicine


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PREDISPOSING FACTORS

Neutropenia

Defective cell mediated immunity

Use of broad spectrum antibiotics

Intravascular catheters

Chemotherapeutic agents

Debilitating illness



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OPPORTUNISTICMYCOSES

Candidiasis

Cryptococcosis

Aspergillosis

Mucormycosis

Penicilliosis



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CANDIDIASIS

Most common systemicmycosis

Most common agent isCandida albicans



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CANDIDA ALBICANS

Major etiologic agent ofcandidiasis

Normal commensal of thegastrointestinal and genitourinarytracts of man (mostly endogenous)Mouth

RectumVaginaSkin



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CANDIDA ALBICANS

Infrequently isolated fromenvironmental sources such

polluted fresh and marinewaters, soil, air and plants(linked to recent contaminationby human or animalexcrement)



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PREDISPOSING FACTORSFOR CANDIDIASIS

AIDS

Previous surgery

Iatrogenic immunosuppresion

Intravenous catheters

Prolonged administration ofantimicrobials



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PREDISPOSING FACTORSFOR CANDIDIASIS

Cytoreductive chemotherapy

Neutropenia

Hematologic diseases

BurnsIV dug abuse



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Oral swabs from healthy subjectsof various age groups revealed

that infants aged 1 week to 18months have a higher carriagerate (mean 46.3%) than infants

aged 1 week old (mean 17.3%) orchildren older than 18 months(mean 15%)



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The carriage rate in adults ishigher than in young children

but lower than in infants



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Infants may acquire oralcandidiasis during passage

through the birth canal, duringnursing or from contaminatedfeeding bottles.



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High oral carriage rate

wearing dentures

High sugar diet

increased numbers of

circulating suppressor T

lymphocytes



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Tongue is the most prevalentsite followed by the palate and

buccal mucosa


G i i l


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Gastrointestinal tractcarriage:

high rates in the stomach andintestines

rise follows with antibacterialtherapy



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VAGINAL CARRIAGE

more prevalent in pregnantthan in non pregnant women

(third trimester)



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VAGINAL CARRIAGE

associated with changes invarious physiologic factors during

pregnancy concentrations of progesterone and

estradiol

vaginal pH

vaginal concentration of glycogen receptor status of the vaginal

epithelium



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SKIN

Candida albicans is not anormal flora of healthy

glabrous human skin

Organism isolated from toeclefts, fingers and fecallycontaminated diaper areas ofbabies



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SKIN

highest carriage rate is seenon the buttocks of babies with

dermatitis and the toes ofpatients with athlete's foot



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CLINICAL FEATURES OFCANDIDIASIS

Superficial Candidiasis

Deep Candidiasis

Hematogenously

disseminated infection


S C


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SUPERFICIALCANDIDIASIS

cutaneous infection

chronic mucocutaneous infection

onychomycosis

oropharyngeal infection

vulvovaginitis

keratitis

conjunctivitis



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DEEP CANDIDIASIS

Local inoculation

Esophagitis

Gastrointestinal candidiasisUrinary tract infection (includes

fungus ball of the ureter, cystitis,

renal abscess, and pyelitis

Peritonitis intra-abdominal abscess



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HEMATOGENOUSLYDISSEMINATED INFECTION

CandidemiaChronic disseminated

(hepatosplenic) candidiasisSuppurative phlebitisEndocarditis

Endophthalmitis

ArthritisOsteomyelitis



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SUPERFICIAL CANDIDIASIS

Infection of the skin, hair, nailsand mucous membranes



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CUTANEOUS CANDIDIASIS

moist, macular erythematous rashmost marked in the intertriginousareas of the gluteal crease,

perineum, and inguinal gold(diaper rash)

In women, inframmamary fold mayalso be infected

Burning and itching are the mostcommon symptoms



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Intertriginous candidiasis


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Cutaneous candidiasis


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Candida granuloma


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Candida granuloma


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Diaper candidiasis


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Chronicmucocutaneous

candidiasis


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ONYCHOMYCOSIS

Involves the fingernails due tofrequent exposure to water

(laundry women, canneryworkers etc)



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CandidiasisOnychomycosis


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Candida paronychia


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OROPHARYNGEAL CANDIDIASIS

occurs in infants, patients withdiabetes mellitus, those receiving

broad spectrum antibiotics, andthose with HIV infection

white patches appear in the buccal

mucosa and less commonly on thegums, tonsillar area, uvula, tongueand palate



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CandidiasisOral thrush


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Oral candidiasis


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VULVOVAGINAL CANDIDIASIS

occurs most commonly inpostpubertal women who have

DM, have been taking antibacterialdrugs, are in the third trimester ofpregnancy, or are sexually active

vaginal discharge, which may be

curd-like, itching, burning, anddyspareunia are the most commonsymptoms



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OCULAR CANDIDIASIS

a complication of the long-term use ofcorticosteroid eye drops

other risk factors are breaks in thecorneal epithelium such as thosecaused by bullous keratopathy orcorneal ulcers due to herpes simplex

findings include conjunctival erythema,cheesy discharge in the conjunctivalsac, and progressive corneal ulceration



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CANDIDA ESOPHAGITIS

may be completely asymptomatic may cause burning pain in the

substernal area, epigastrium or throat

most typical esophagoscopy findingsare white mucosal plaques resemblingoral thrush more notable in the distalthird of the esophagus

Complications include bleeding,perforation, and stenosis in chronicinfection



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GASTROINTESTINAL CANDIDIASIS

Second to the esophagus as asite of gastrointestinal

candidiasisDeeply invasive and spread

hematogenous to the liver,

spleen, and other organsFever is the only manifestion


PERITONITIS AND


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PERITONITIS ANDINTRAABDOMINAL ABSCESS

an uncommon complications ofchronic ambulatory peritoneal

dialysismay follow complicated abdominal

surgery, particularly re-exploration

in the early post operative courseand usually originates from aleaking intestinal anastomosis


PERITONITIS AND


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PERITONITIS ANDINTRAABDOMINAL ABSCESS

symptom include abdominalpain and tenderness with or

without nausea, vomiting, orlow grade fever

peritoneal dialysate cloudy,candida can be cultured butnot seen on smear


RESPIRATORY TRACT


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RESPIRATORY TRACTCANDIDIASIS

Laryngitis may occur in the absence oforopharyngeal or esophagealcandidiasis

Pulmonary candidiasis is more of anautopsy finding than a clinical entity. causes diffuse reticulonodular streaking

which is difficult to see in chest X-ray

unless another pulmonary disorder is alsopresent like adult respiratory distresssyndrome or congestive heart failure


URINARY TRACT


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URINARY TRACTCANDIDIASIS

Candida in culture of femalevoided urine usually are

contaminants from the vulva orvaginal secretions

Colonization of the bladder isa complication of prolongedcatheterization


URINARY TRACT


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URINARY TRACTCANDIDIASIS

Colonization is most oftenasymptomatic but it can lead toinvasion of the bladder wall in thepresence of complete obstruction,bacterial cystitis, or damage to thebladder epithelium by

cyclophosphamide or topicalchemotherapy of bladdercarcinoma


HEMATOGENOUSLY


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HEMATOGENOUSLYDISSEMINATED CANDIDIASIS

Seen in 10-15% of cases ofsepticemia in tertiary carehospitals

Most common species involved isalbicans, followed by parapsilosis,then tropicalis

Symptoms of Candida sepsissimilar to bacterial sepsis (fever,shock, DIC)


CHRONIC DISSEMINATED


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CHRONIC DISSEMINATED(Hepatosplenic) Candidiasis

Occurs in patients with severeneutropenia usually from acute

leukemiaUsual agent is C. albicans or

C. tropicalis


CHRONIC DISSEMINATED


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CHRONIC DISSEMINATED(Hepatosplenic) Candidiasis

Clinical clues fever that reappear after

discontinuation of empericAmphotericin B

Fever fails to disappear whenneutrophil count return to normal

Increased alkaline phosphatase ahelpful sign


DISSEMINATED CANDIDIASIS DUE


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DISSEMINATED CANDIDIASIS DUETO HEROIN ABUSE

Clinical syndrome has been encounteredin France, Spain, Switzerland, andAustralia

2-8 hours after heroin injection, patienthave sudder onset of high fever, chills,myalgia, headache and sweating

After 1-4 days, painful nodules or pustuleson the scalps and other hairy areas(Candida grows into the hair shaftscausing purulent folliculitis)


CANDIDA SUPPURATIVE


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CANDIDA SUPPURATIVEPHLEBITIS

Associated with catheters inperipheral veins, subclavian

vein and internal carotid arteryFever and candidemia present


CANDIDA ENDOCARDITIS


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CANDIDA ENDOCARDITISAND PERICARDITIS

Seen in patient with a previouslyabnormal native valve or aprosthetic heart valve

Most common predisposingfactors are intravenous drugabuse and intravenous catheters

Symptoms include fever, embolicphenomena and cardiac failure



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CANDIDA ARTHRITIS

Common in patients withprosthetic or rheumatoid joints

Via hematogenous spread orby inadvertent direct

inoculation during joint surgeryor intra-articular corticosteroidinjection



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CANDIDA ARTHRITIS

May also be a late sequelae ofcandidemia in neonates orneutropenic patients

Knee joint involvement mostcommon

Onset of pain and of effusion is

indolent and erythema and warmthof the joint are not striking



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CANDIDA OSTEOMYELITIS

Hematogenously spread exceptfor external infection complicating

median sternotomyIndolent onset of fever and back

pain followed by radiculopathy

Osteolytic lesion withparavertebral pus is characteristic


CANDIDA


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CANDIDAENDOPHTHALMITIS

Present in 10-37% of adultswith Candidemia

White retinal lesions in theposterior pole are the earliestsign

Retinal lesion enlarge formingabscess



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CNS CANDIDIASIS

Seen in low-birth weight neonateswith Candidemia and in patientswith complicated surgery, orintracerebral prothetic devicessuch as ventriculoperitonealshunts

Floppy, inattentive infant maybethe only early sigh in neonate withprevious candidemia



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LABORATORY DIAGNOSIS

Superficial Candidiasis

Demonstration of pseudohyphae

on a smear of cutaneous, oral,esophageal and vaginal lesions isthe single best diagnostic test



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Deep Candidiasis

Blood culture using lysis

centrifugation is the mostsensitive and rapid method forisolation

Biopsy and culture of deeptissue



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Gram-stained smears forpseudohyphae and budding yeastof the following specimen

BloodSpinal fluidTissue biopsiesUrineExudatesMaterial from intravenous catheters



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Ust Dept. of Lab. MedicineCandida albicans growing on sheep blood agar plates

Gross


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Gross


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Ust Dept. of Lab. MedicineOral budding yeast cells


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Candida albicansBlood culture


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Candida albicans grown on a corn meal agar


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C. albicans. Chlamydospores


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Chrom agar Candida

TREATMENT


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TREATMENT

Thrush or mucocutaneous

Topical: Nystatin, Clotrimazole,

TioconazoleOral: Fluconazole, Ketoconazole


TREATMENT


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TREATMENT

Systemic Candidiasis

Amphotericin B

Oral flucytosine

Fluconazole

Caspofungin



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CRYPTOCOCCOSIS

ETIOLOGY


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22 strains of pathogenic and non-pathogenic fungi

Cryptococcus neoformansvar. neoformans (Serotypes A andD) var. gatti (serotype B and C)

Cryptococcus albidusCryptococcus laurentii


ETIOLOGY

ECOLOGY


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Fungus is found in the respiratorytract or skin in healthy people as well

as in patients with variousbronchopulmonary diseases otherthan cryptococcosis, as transient

flora or as an incidental colonizer.


ECOLOGY

SOURCE


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var. neoformans - weathered

pigeon droppings and soil

contaminated with avian droppings

var. gattii - only known environ-

mental source is eucalyptuscamaldulensis (red gum)


SOURCE

ASSOCIATED DISEASE


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var. neoformans - most commoncause of meningitis in AIDSpatient

var. gatti - more common pathogen

in non-immunocompromisedpatients in subtropical areas


ASSOCIATED DISEASE

FORMS OF THE DISEASE


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PulmonaryA. Acute Infection

Rarely diagnosed except in AIDSpatients who may present withsevere acute respiratory distress

(ARDS)


FORMS OF THE DISEASE


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B. Chronic PulmonaryMay produce nodules or masses

(usually in the upper lobes),cavities, segmental pnuemonia,pleural effusion or

lymphadenopathy



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Pulmonarycryptococcosis

Disseminated forms


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Disseminated forms

Central nervous systemMeningitis that follows a subacutecourse is typical. Complications

include papilledema, cranial nerveinvolvement, visual loss, andhydrocephalus. Single or multiple

intracerebral fungal masses mayalso occur, but are rare



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Cutaneous

Painless lesions that may appearas papules, pustules, plaques,ulcers, subcutaneous masses, or

cellulitis



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Cryptococcosis


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Cutaneous cryptococcosis


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Cryptococcus neoformans, skin lesion


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Cryptococcosis


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Cryptococcosis


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OthersEndophthalmitis, chorioretinitis,

conjunctivitis, sinusitis, otitis,myocarditis, pericarditis,endocarditis, gastroduodenitis,

hepatitis, cholecystitis


DIAGNOSIS


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1. Direct examination

- CSF and pulmonary tissuemounted in 10% KOH or India ink


DIAGNOSIS


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Cryptococcus neoformans

India ink preparation


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India ink of Cryptococcus neoformans


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2. Culture

- medium without cycloheximide(Sabouraud glucose agar,Inhibitory Mould Agar, in BHI

incubated at 30C- CSF should be processed byfiltration or centrifugation

technique- creamy white to yellow browncolonies



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C. neoformans


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Histopathology

>may be difficult to see in H and Estained slides> mucicarmine technique stains

the capsule pink



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Cryptococcosis, brain tissue


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Urease test forCryptococcusneoformans


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Serology

> latex particle agglutination test(detects the cryptococcalpolysaccharide antigen)


TREATMENT


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CNS > best treatment is AmphoterecinB with Fluorocytosine for 6-10 weeksor> 2 weeks Amphoterecin B + 5 FU

then Fluconazole for at least 10weeks


TREATMENT

ASPERGILLOSIS


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Etiologic agent Genus Aspergillus

132 species and 18 varities only 16species and 1 variety have beendocumented as pathogenic to man


ASPERGILLOSIS


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A. fumigatus- most common cause of

invasive and non-invasiveaspergillosis

A. flavus- second most common species

isolated from invasiveaspergillosis in immunosup-pressed patients

A. niger- 3rd most common cause ofinvasive pulmonary aspergillosis


Three main forms ofA ill i


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1. Allergic bronchopulmonary type2. Colonization in an old healed

lung cavity (Aspergilloma)(most common form)

3. Tissue invasion by the fungus

(GI, CNS, Heart, Lung, Kidney,Liver, Thyroid)


Aspergillosis


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EcologyMost Aspegillus species are found insoil, grain, vegetation, food products

and nasopharyngeal passages ofhumansA. fumigatus - most abundantly seen

in decomposing material, grows wellat temperature up to 55C


Mode of transmission


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> principally acquired from inhalationof spores (spores are bet. 2-5microns)

> airborne spores probably infect

tissue exposed during surgery


Mode of transmission


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> inadvertently gain entrance to

susceptible patients by contaminatedhospital supplies ( arm boards, boardwrapping material, and adhesive

tapes)



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Symptoms of PulmonaryAspergillosis

> cough

> hemoptysis> wheezing with allergic type> weight loss


Symptoms of invasiveaspergillosis


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aspergillosis> fever

> chills

> headache> symptoms involving specific

organ* brain - meningitis* eye - blindness/visual

impairment

* sinuses - sinusitis

* heart - endocarditis Ust Dept. of Lab. Medicine


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Aspergillosis fumigatus, eye

Laboratory Diagnosis


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A. Allergic Pulmonary Aspegillosis(ABA)> Direct Examination: sputum and

expectorated bronchial mucusplugs usually positive

> Histology: not done

> Culture: sputum usually positivefor colony formation


y g



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B. Aspergilloma> Direct examination: sputum

often negative> Histology: rings of growth

seen with fungus ball

> Culture: usually positive


y g


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Gross pathology of

Aspergilloma in the lung apex



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C. Invasive Pulmonary andDisseminated Disease:

- Direct Examination: sputumusually negative; tissue digestedwith KOH may show the

dichotomous septate hyphae




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- Histology: branching, septatehyphae in tissue; indistinguishable

from many other fungi- Culture: necessary for diagnosis,sputum usually negative; biopsy

usually positive by culture



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Gram stain of Aspergillus fumigatus


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Aspergillus fumigatus (Sheep blood agar plate)


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Aspergillus flavus (Sheep blood agar plate)


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LPCB preparation of Aspergillus flavus

Treatment


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A. Aspergilloma - surgical removal ofinfected tissue

B. Invasive Pulmonary andDisseminated Disease> Amphoterecin B preferred

regimen> Itraconanazole 2nd line regimen


MUCORMYCOSIS


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Molds belong to classzygomycetes in order Mucorales

Fungi ubiquitous thermotolerantsaphrophytes

Genus included are Rhizopus,Rhizomucor, Absidia,

Cunninghamella, Mucor, andSyncephalastrum


RISK FACTORS FORMUCORMYCOSIS


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MUCORMYCOSIS

Acodosis especially thatassociated with diabetes

mellitusLeukemias

Lymphoma

Corticosteroid treatment


RISK FACTORS FORMYCORMYCOSIS


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MYCORMYCOSIS

Severe burns

Immune deficiencies

Debilitating diseases

Dialysis with the iron chelatordeferoxamine


CLINICAL FORM OFMUCORMYCOSIS


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MUCORMYCOSIS

Rhinocerebral mucormycosis majorclinical forms Germination of the sporangiospores in the

nasal passage Invasion of the hyphae into the blood

vessels causing thrombosis and necrosis

Invasion of the sinuses, eyes, cranialbones and brain

Damage blood vessels and nerves, edemaof the facial area, bloody nasal exudateand orbital cellulitis



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Thoracic mucormycosis

Follows inhalation of the

sporangiosphores with theinvasion of the lung parenchymaand vasculature

Causes ischemic necrosis withmassive tissue destruction




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Direct examination or cultureof nasal discharge, tissue, or

sputum will reveal broadhyphae with uneven thickness,irregular branching, and

sparse septations



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TREATMENT


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Surgical debridement

Rapid administration of

Amphotericin BControl of underlying disease


PENICILLOSIS MARNEFFEI


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Causative agent is Penicillinmarneffei

Was first isolated from a hepaticlesion in a bamboo rat (Rhizomyssinensis) an animal foundthroughout Southeast Asia

30 cases reported by 1990


RISK FACTORS


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Corticosteroid therapy forpatients with SLE, hemolytic

anemia, renal transplantation,dermatomyositis, Hodgkins

disease

AIDS


ORGANS COMMONLYINVOLVED:


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INVOLVED:

Lymph nodes involved multiple siteswhich become ulcerative, suppurativeand draining

Lungs localized or patchy infiltrateswith or without abscess or enpyema

Liver hepatomegaly but with nojaundice

Skin multiple, erythematous, deeplyset subcutaneous abscess


CLINICALMANIFESTATIONS


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Fever

Weight loss

Anemia

Gradual progression to deathunless treated




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Culture or histopathologicstudy of lesions usually skin,

bone or liver



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TREATMENT


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Amphoterecin B is the drug ofchoice

Ampoterecin B alone or incombination with Flucytosine

Ketoconazole?



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Opportunisitc Mycosis