Mycology Lec5opportunistic

MICROBIOLOGY LECTURE M5 – Opportunistic Mycoses Lecture and Notes by Dr. Carandang USTMED ’07 Sec C – AsM

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OPPORTUNISTIC MYCOSIS

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PREDISPOSING FACTORS

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Neutropenia Defective cell mediated immunity Use of broad spectrum antibiotics Intravascular catheters Chemotherapeutic agents Debilitating illness

OPPORTUNISTIC MYCOSIS

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Candidiasis Cryptococcosis Aspergillosis Mucormycosis Penicilliosis

CLINICAL FEATURES OF CANDIDIASIS

CANDIDIASIS

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Gastrointestinal tract carriage:H o High rates in the stomach and intestines o rise follows with antibacterial therapy Vaginal Carriage o more prevalent in pregnant than in non pregnant women (third trimester) o associated with changes in various physiologic factors during pregnancy  concentrations of progesterone and estradiol  vaginal pH  vaginal concentration of glycogen  receptor status of the vaginal epithelium Skin o Candida albicans is not a normal flora of healthy glabrous human skin o Organism isolated from toe clefts, fingers and fecally contaminated diaper areas of babies o highest carriage rate is seen on the buttocks of babies with dermatitis and the toes of patients with athlete’s foot

Most common systemic mycosis Most common agent is Candida albicans

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Superficial Candidiasis Deep Candidiasis

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Hematogenously disseminated infection

1.

SUPERFICIAL CANDIDIASIS

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Infection of the skin, hair, nails and mucous membranes

OTHER SPECIES OF MEDICAL IMPORTANCE

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C. C. C. C. C. C. C.

tropicalis parapsilosis glabrata guilliermondii dubliniensis krusei lusitaniae

a. o

o

CANDIDA ALBICANS

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Major etiologic agent of candidiasis Normal commensal of the gastrointestinal and genitourinary tracts of man (mostly endogenous) o Mouth o Rectum o Vagina o Skin Infrequently isolated from environmental sources such polluted fresh and marine waters, soil, air and plants (linked to recent contamination by human or animal excrement)

PREDISPOSING FACTORS FOR CANDIDIASIS

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Oral swabs from healthy subjects of various age groups revealed that infants aged 1 week to 18 months have a higher carriage rate (mean 46.3%) than infants aged 1 week old (mean 17.3%) or children older than 18 months (mean 15%) The carriage rate in adults is higher than in young children but lower than in infants Infants may acquire oral candidiasis during passage through the birth canal, during nursing or from contaminated feeding bottles. High oral carriage rate o wearing dentures o High sugar diet o increased numbers of circulating suppressor T lymphocytes Tongue is the most prevalent site followed by the palate and buccal mucosa

chronic mucocutaneous infection

c. o

onychomycosis Involves the fingernails due to frequent exposure to water (laundry women, cannery workers etc)

d. o

oropharyngeal infection occurs in infants, patients with diabetes mellitus, those receiving broad spectrum antibiotics, and those with HIV infection white patches appear in the buccal mucosa and less commonly on the gums, tonsillar area, vulva, tongue and palate

e. o

o

EPIDEMIOLOGY

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b.

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AIDS Previous surgery Iatrogenic immunosuppresion Intravenous catheters Prolonged administration of antimicrobials Cytoreductive chemotherapy Neutropenia Hematologic diseases Burns IV dug abuse

vulvovaginitis occurs most commonly in postpubertal women who have DM, have been taking antibacterial drugs, are in the third trimester of pregnancy, or are sexually active vaginal discharge, which may be curd-like, itching, burning, and dyspareunia are the most common symptoms

f.

keratitis

g. o

conjunctivitis a complication of the long-term use of corticosteroid eye drops other risk factors are breaks in the corneal epithelium such as those caused by bullous keratopathy or corneal ulcers due to herpes simplex findings include conjunctival erythema, cheesy discharge in the conjunctival sac, and progressive corneal ulceration

o

o

2.

cutaneous infection moist, macular erythematous rash most marked in the intertriginous areas of the gluteal crease, perineum, and inguinal gold (diaper rash) In women, inframmamary fold may also be infected Burning and itching are the most common symptoms

DEEP CANDIDIASIS

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Local inoculation

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Esophagitis (candida esophagitis) may be completely asymptomatic may cause burning pain in the substernal area,

o o

o o c. o o o d. o

o o

e. o o

o o f. o o

epigastrium or throat most typical esophagoscopy findings are white mucosal plaques resembling oral thrush more notable in the distal third of the esophagus Complications include bleeding, perforation, and stenosis in chronic infection

a.

Candidemia

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Chronic disseminated (hepatosplenic) candidiasis Occurs in patients with severe neutropenia usually from acute leukemia Usual agent is C. albicans or C. tropicalis Clinical clues  fever that reappear after discontinuation of emperic Amphotericin B  Fever fails to disappear when neutrophil count return to normal  Increased alkaline phosphatase a helpful sign

c. o o o

o o

Disseminated Candidiasis due to heroin abuse Clinical syndrome has been encountered in France, Spain, Switzerland, and Australia 2-8 hours after heroin injection, patient have sudder onset of high fever, chills, myalgia, headache and sweating After 1-4 days, painful nodules or pustules on

Suppurative phlebitis Associated with catheters in peripheral veins, subclavian and internal carotid artery Fever and candidemia present Endocarditis Seen in patient with a previously abdominal native valve or a prosthetic heart valve Most common predisposing factors are intravenous drug abuse and intravenous catheters Symptoms include fever, embolic phenomena and cardiac failure

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Endophthalmitis

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Arthritis (Candida Arthritis) Common in patients with prosthetic or rheumatoid joints Via hematogenous spread or by inadvertent direct inhalation during joint surgery or intraarticular corticosteroid injection May also be a late sequelae of candidemia in neonates or neutropenic patients Knee joint involvement most common Onset of pain and of effusion is indolent and erythema and warmth of the joint are not striking

o o o o o

h. o o o i. o o

Respiratory Tract Candidiasis Laryngitis may occur in the absence of oropharyngeal or esophageal candidiasis Pulmonary candidiasis is more of an autopsy finding than a clinical entity.  causes diffuse reticulonodular streaking which is difficult to see in chest X-ray unless another pulmonary disorder is also present like adult respiratory distress syndrome or congestive heart failure

Seen in 10-15% of cases of septicemia in tertiary care hospitals Most common species involved is albicans, followed by parapsilosis, then tropicalis Symptoms of Candida sepsis similar to bacterial sepsis (fever, shock, DIC)

o o

e. o

Peritonitis – intra-abdominal abscess an uncommon complications of chronic ambulatory peritoneal dialysis may follow complicated abdominal surgery, particularly re-exploration in the early post operative course and usually originates from a leaking intestinal anastomosis symptom include abdominal pain and tenderness with or without nausea, vomiting, or low grade fever peritoneal dialysate cloudy, candida can be cultured but not seen on smear

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Urinary tract infection (includes “fungus ball of the ureter, cystitis, renal abscess, and pyelitis Candida in culture of female voided urine usually are contaminants from the vulva or vaginal secretions Colonization of the bladder is a complication of prolonged catheterization Colonization is most often asymptomatic but it can lead to invasion of the bladder wall in the presence of comple obstruction, bacterial cystitis, or damage to the bladder epithelium by cyclophosphamide or topical chemotherapy of bladder carcinoma

HEMATOGENOUSLY DISSEMINATED INFECTION

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d. o

Gastrointestinal candidiasis Second to the esophagus as a site of gastrointestinal candidiasis Deeply invasive and spread hematogenous to the liver, spleen, and other organs Fever is the only manifestion

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the scalps and other hairy areas (Candida forms into the hair shafts causing purulent folliculitis)

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Osteomyelitis (Candida Osteomyelitis) Hematogenously spread except for external infection complicating median sternotomy Indolent onset of fever and back pain followed by radiculopathy Osteolytic lesion with paravertebral pus is characteristic Candida Endysphthalmitis Present in 10-37% of adults with Candidemia White retinal lesions in the posterior pole are the earliest sign Retinal lesion enlarge forming abscess CNS Candidiasis Seen in low-birth weight neonates with Candidemia and in patients with complicated surgery, or intracerebral prothetic devices such as ventriculoperitoneal shunts Floppy, inattentive infant maybe the only early sigh in neonate with previous candidemia

LABORATORY DIAGNOSIS

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Superficial Candidiasis

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Demonstration of pseudohyphae on a smear of cutaneous, oral, esophageal and vaginal lesions is the single best diagnostic test

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Deep Candidiasis

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Blood culture using lysis centrifugation is the most sensitive and rapid method for isolation Biopsy and culture of deep tissue Gram-stained smears for pseudohyphae and budding yeast of the following specimen o Blood o Spinal fluid o Tissue biopsies o Urine o Exudates o Material from intravenous catheters

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DIAGONOSIS

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3.

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TREATMENT

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Systemic o o o o

Candidiasis Amphotericin B Oral flucytosine Fluconazole Caspofungin

CRYPTOCOCCOSIS

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TREATMENT

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Torulosis, European blastomycosis, Busse-Buschke disease

CNS > best treatment is Amphoterecin B with Fluorocytosine for 6-10 weeks or > 2 weeks Amphoterecin B + 5 FU then Fluconazole for at least 10 weeks

ASPERGILLOSIS

ETIOLOGY

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Direct examination CSF and pulmonary tissue mounted in 10% KOH or India ink Cultre medium without cycloheximide (Sabouraud glucose agar, Inhibitory Mould Agar, in BHI incubated at 30°C) CSF should be processed by filtration or centrifugation technique creamy white to yellow brown colonies Histopathology may be difficult to see in H and E stained slides mucicarmine technique stains the capsule pink Serology latex particle agglutination test(detects the cryptococcal polysaccharide antigen)

22 strains of pathogenic and non-pathogenic fungi o Cryptococcus neoformans var. neoformans (Serotypes A and D) var. gatti (serotype B and C) o Cryptococcus albidus o Cryptococcus laurentii

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Etiologic agent – Genus Aspergillus 132 species and 18 varities only 16 species and 1 variety have been documented as pathogenic to man

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A. fumigatus - most common cause of invasive and noninvasive aspergillosis

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A. flavus - second most common species isolated from invasive aspergillosis in immunosuppressed patients

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A. niger - 3rd most common cause of invasive pulmonary aspergillosis

ECOLOGY

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Fungus is found in the respiratory tract or skin in healthy people as well as in patients with various bronchopulmonary diseases other than cryptococcosis, as transient flora or as an incidental colonizer.

SOURCE

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var. neoformans - weathered pigeon droppings and soil contaminated with avian droppings var. gattii - only known environmental source is eucalyptus camaldulensis (red gum)

ASSOCIATED DISEASE

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var. neoformans - most common cause of meningitis in AIDS patient var. gatti - more common pathogen in nonimmunocompromised patients in subtropical areas

FORMS OF DISEASE

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A. B.

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Pulmonary Acute Infection rarely diagnosed except in AIDS patients who may present with severe acute respiratory distress (ARDS) Chronic Pulmonary May produce nodules or masses (usually in the upper lobes), cavities, segmental pnuemonia, pleural effusion or lymphadenopathy Disseminated forms 1. Central nervous system o Meningitis that follows a subacute course is typical. Complications. Include papilledema, cranial nerve involvement, visual loss, and hydrocephalus. Single or multiple intracerebral fungal masses may also occur, but are rare 2. Cutaneous o Painless lesions that may appear as papules, pustules, plaques, ulcers, subcutaneous masses, or cellulites 3. Others o Endophthalmitis, chorioretinitis, conjunctivitis, sinusitis, otitis, myocarditis, pericarditis, endocarditis, gastroduodenitis, hepatitis, cholecystitis

TRHEE MAIN FORMS OF ASPERGILLOSIS

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2. 3.

Allergic bronchopulmonary type Colonization in an old healed lung cavity (Aspergilloma) - most common form Tissue invasion by the fungus (GI, CNS, Heart, Lung, Kidney, Liver, Thyroid)

ECOLOGY

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Most Aspegillus species are found in soil, grain, vegetation, food products and nasopharyngeal passages of humans A. fumigatus - most abundantly seen in decomposing material, grows well at temperature up to 55°C

MODE OF TRANSMISSION

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principally acquired from inhalation of spores (spores are bet. 2-5 microns) airborne spores probably infect tissue exposed during surgery inadvertently gain entrance to susceptible patients by contaminated hospital supplies ( arm boards, board wrapping material, and adhesive tapes)

Symptoms of Pulmonary Aspergillosis • cough • hemoptysis

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wheezing with allergic type weight loss

Symptoms of invasive aspergillosis

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fever chills headache symptoms involving specific organ o brain – meningitis o eye - blindness/visual impairment o sinuses – sinusitis o heart – endocarditis

LABORATORY DIAGNOSIS

1. Allergic Pulmonary Aspegillosis (ABA) - Direct Examination: sputum and expectorated bronchial mucus plugs usually positive - Histology: not done Culture: sputum usually positive for colony formation 2. Aspergilloma - Direct examination: sputum often negative - Histology: rings of growth seen with fungus ball Culture: usually positive

MUCORMYCOSIS

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Molds belong to class zygomycetes in order Mucorales Fungi ubiquitous thermotolerant saphrophytes Genus included are Rhizopus, Rhizomucor, Absidia, Cunninghamella, Mucor, and Syncephalastrum

Rhizopus

3. Invasive Pulmonary and Disseminated Disease: - Direct Examination:sputum usually negative; tissue digested with KOH may show the dichotomous septate hyphae - Histology: branching, septate hyphae in tissue; indistinguishable from many other fungi - Culture: necessary for diagnosis, sputum usually negative; biopsy usually positive by culture TREATMENT

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Aspergilloma - surgical removal of infected tissue

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Invasive Pulmonary and Disseminated Disease a. Amphoterecin B preferred regimen b. Itraconanazole 2nd line regimen

Rhizomucor

A. fumigatus

Syncephalastrum

A. flavus

Mucor

A. niger

Absidia

RISK FACTORS FOR MYCORMYCOSIS

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Acodosis especially that associated with DM Leukemias Lymphoma Corticosteroid treatment Severe burns Immune deficiencies Debilitating disease Dialysis with the iron chelator deferoxamine

CLINICAL MANIFESTATIONS

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LABORATORY DIAGNOSIS

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CLINICAL FORM OF MUCORMYCOSIS

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Rhinocerebral mucormycosis – major clinical forms o Germination of the sporangiospores in the nasal passage o Invasion of the hyphae into the blood vessels causing thrombosis and necrosis o Invasion of the sinuses, eyes, cranial bones and brain o Damage blood vessels and nerves, edema of the facial area, bloody nasal exudate and orbital cellulitis Thoracic mucormycosis o Follows inhalation of the sporangiosphores with the invasion of the lung parenchyma and vasculature o Causes ischemic necrosis with massive tissue destruction

LABORATORY DIAGNOSIS

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Direct examination or culture of nasal discharge, tissue, or sputum will reveal broad hyphae with uneven thickness, irregular branching, and sparse septations

TREATMENT

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Surgical debridement Rapid administration of Amphotericin B Control of underlying disease

PENICILLOSIS MARNEFFEI

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Causative agent is Penicillin marneffei Was first isolated from a hepatic lesion in a bamboo rat (Rhizomys sinensis) an animal found throughout Southeast Asia 30 cases reported by 1990

RISK FACTORS

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Corticosteroid therapy for patients with SLE, hemolytic anemia, renal transplantation, dermatomyositis, Hodgkin’s disease AIDS

ORGANS COMMONLY INVOLVED

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Lymph nodes – involved multiple sites which become ulcerative, suppurative and draining Lungs – localized or patchy infiltrates with or without abscess or enpyema Liver – hepatomegaly but with no jaundice Skin – multiple, erythematous, deeply set subcutaneous abscess

Fever Weight loss Anemia Gradual progression to death unless treated

Culture or histopathologic study of lesions usually skin, bone or liver

TREATMENT

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Amphoterecin B is the drug of choice Ampoterecin B alone or in combination with Flucytosine Ketoconazole?

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