Opportunistic Fungal Infection I

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Opportunistic Fungal Infection I

• Lecture by Kanya Preechasuth
• July 4, 2005

CMB 508301 Division of Clinical
Microbiology Faculty of Associated Medical
Science, CMU
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Opportunistic fungal infections

• Fungi are organisms of low virulence and tend to
  infect human with immunocompromised immune
  systems
• Most frequently isolated from immunocompromised
  patients are saprophytic (environment) or
  endogenous (commensal)

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Opportunistic fungal infections

• The term immunocompromised hosts describes
  individuals with nonspecific and/or specific
  immunity defects
• Increased risk of infection with a variety of
  microorganisms that are not pathogenic for
  healthy individuals

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Predisposing factors

• Immune system
• Primary immunodeficiency affected CMI
• Secondary immunodeficiency AIDS, malignancy,
  chronic debilitating disease
• Therapeutic measures
• Organ transplantation
• Whole body irradiation therapy
• Administration of broad-spectrum antibacterial
• Therapy with cytotoxic drugs, corticosteroids or
  immunosuppressive drugs

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Predisposing factors

• Other conditions
• Severe burns
• Diabetes
• Tuberculosis

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Opportunistic infection in Thailand

• Opportunistic infection in HIV patients
• Pulmonary and nonpulmonary TB 29.6
• Pneumocystis carinii pneumonia (PCP) 21.29
• Cryptococcosis 16.21
• Candidiasis (esophagus, trachea, bronchi) 5.28
• Recurrent bacterial pneumonia 3.75
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Fungal infections

• Primary (endemic, dimorphic) fungal pathogen
• Histoplama capsulatum
• Coccidioides immitis
• Blastomyces dermatitidis
• Paracoccidioides
• Opportunistic fungal pathogen, e.g.
• Aspergillus
• Candida

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Secondary (opportunistic) fungal infections

• Aspergillosis
• Candidiasis
• Cryptococcosis
• Zygomycosis
• Penicillosis marneffei
• Pneumocystis carinii pneumonia (PCP)

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ASPERGILLOSIS
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Aspergillosis

• Aspergillosis is a spectrum of diseases of humans
  and animals caused by members of the genus
  Aspergillus
• Most frequently are A.fumigatus, A, niger and
  A.flavus
• Commonly found in soil, seed, food, paint, air
  vents, and even disinfectant

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Clinical disease

• Initial of disease by respiratory system
• Can invade almost any tissue in the body
• There are three primary types of pulmonary
  aspergillosis
• Allergic manifestations
• Aspergilloma
• Invasive aspergillosis

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Allergic manifestation

• Allergic bronchopulmonary aspergillosis (ABPA)
• asthma
• Non invasive
• positive skin test to Aspergillus antigen
• Eosinophilia
• A.fumigatus

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Aspergilloma

• Fungal ball
• colonization in an old healed lung cavity from
  previous disease (TB,lung abscess,PCP)
• does not invade the cavity wall
• hemoptysis

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Invasive Aspergillosis

• Severely immunosuppression
• Bone marrow, organ transplant recipients
• Leukemia, AIDS
• Disseminated aspergilosis heart, lungs, brain
  and kidneys

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• Central nervous system aspergillosis
• meningitis
• Cutaneous aspergillosis
• Burn, disseminated aspergillosis
• Nasal orbital aspergillosis
• Nasal sinuses

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Laboratory diagnosis

• Definitive diagnosis of invasive aspergillosis or
  chronic necrotrinizing aspergillus pneumonia
  depend on the demonstration of the organism in
  tissue
• Radiographs and clinical history may strongly
  suggest aspergillosis

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Laboratory diagnosis

• Clinical materials
• sputum, BAL, pus, tissue biopsy (dont fixed with
  formalin)
• Direct microscopy
• 10 KOH
• Histology

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Laboratory diagnosis
dichotomous branching septate hyphae
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Laboratory diagnosis

• Culture
• SDA, RT, 1 wk
• colony, microscopic
• Serology
• immunodiffusion test
• Latex agglutination

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Laboratory diagnosis
A.flavus
A.flavus
A.fumigatus
A.niger
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Treatments

• Depend on type of disease
• Allergic conditions are treated symptomatically,
  by avoiding exposure corticosteroid
• Aspergillomas are usually surgically excised
• Antimycotic therapy with AmpB is usually reserved
  for patients with invasive disease.
• Itraconazole may be an effective therapy for
  aspergillosis

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CANDIDIDASIS
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Candidiasis

• Infections due to Candida (Candida albicans,
  C.glabrata, C.parapsilosis) can present in a wide
  spectrum of clinical syndromes
• Distribution in worldwide water, food, soil,
  normal flora (upper respiratory tract,
  gastrointestinal tract, vagina)

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Candidiasis

• Predisposing factors
• Impaired cellular immunity or neutropenia
• Prolong antibiotic therapy
• Increase colonization rate
• disruption of a colonized surface (skin or
  mucosa), allowing the organisms gain access to
  the bloodstream

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Clinical diseases

• Oral candidiasis
• Cutaneous candidiasis
• Genitourinary candidiasis
• Systemic candidiasis
• Chronic mucocutaneous candidiasis

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Superficial candidiasis

• Oral, esophageal candidiasis
• infant, diabetes mellitus, HIV
• Oral thrush

Oral thrush
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Cutaneous candidiasis

• Skin, nail

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Genitourinary candidiasis

• Vulvovaginal candidiasis (VVC, candida vaginitis)
  
• vaginal discharge, dysuria, erythematous
• oral contraceptive, pregnancy
• Candida balanitis

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Systemic candidiasis

• Candidemia
• Fever for several days unresponsive to broad-
  spectrum antimicrobials
• cause of endocarditis, endophthalmitis
• Disseminated candidiasis
• multiple or single deep organ infections
• Renal candidiasis, Myocarditis-pericarditis,
  Candida peritonitis, Candida splenic abscess.

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Laboratory diagnosis

• Clinical materials
• skin or nail scraping, sputum, vaginal swab
• Direct microscopy
• 10KOH, Gram stain, PAS, GMS

10KOH
PAS stain
Showing the presence of budding yeast cell and
pseudohyphae
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Laboratory diagnosis

• Culture
• SDA, RT 370C, 24-48 hrs, white to cream color,
  glabrous to waxy surface
• germ tube, chlamydospore
• CHO assimilation /fermentation test

Germ tube
Chlamydospore
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Laboratory diagnosis

• Serology
• antibodies to Candidda
• immunodiffusion, latex agglutination
• usually negative result in early infection

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Treatment

• Cutaneous infections
• cream or ointment containing nystatin or
  ketoconazole
• Esophageal, oral candidiasis
• oral clotrimazole
• Systemic infections Amphotericin B
• Prophylactic treatment in AIDS patients
• Fluconazole

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CRYPTOCOCCOSIS
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Cryptococcosis

• Cryptococcosis is a chronic, subacute to acute
  pulmonary, systemic or meningitis disease
• Cryptococcus neoformans var. neoformans and
  Cryptococcus neoformans var. gattii
• encapsulated yeast
• The species has 4 serotypes (A,B,C,D) based on
  capsular polysaccharide antigen
• C. neoformans var neoformans serotype A

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Cryptococcosis

• Epidermiology
• distributed worldwide, pigeon feces,
  eucalyptus trees (var. gattii)
• Transmission by inhalation of basidiospore or
  yeast cells
• Cryptococcal infections in hosts who are
  immunosuppressed, including patients with AIDS

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Cryptococcosis

• Determinants of pathogenicity
• The antiphagocytic polysaccharide capsule is the
  major virulence factor
• Melanin production may also be virulence factor
• Deposited in the cell wall
• Protect organism from oxidants released by
  phagocytic cells

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Cryptococcosis

• CNS cryptococcosis
• Most common clinical presentation of
  cryptococcosis Cryptococcal meningitis
• Prolong evolution of several months
• headache, vomiting, neck stiffness, mental status

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Cryptococcosis

• Pulmonary cryptococcosis
• asymptomatic
• x-ray

Right upper lobe
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Cryptococcosis

• Cutaneous mucocutaneous cyptococcosis
• Osseous cyrtococcosis bone
• Visceral crytococcosis heart, kidneys, liver,

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Laboratory diagnosis

• Clinical materials
• CSF, sputum, pus, urine, blood, tissue biopsy
• Examination of CSF
• Protein level , glucose level , number
  of leukocyte
• India ink test detect the extensive capsule

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Laboratory diagnosis

• Examination of CSF (cont.)
• Latex agglutination test detect cryptococcal
  antigen
• Patient improves titer
• No respond to therapy titer

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Laboratory diagnosis
capsule
capsule
India ink test
Mucicarmine stain
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Laboratory diagnosis

• Culture 370C, 1-2 days
• SDA with out cyclohexamide creamy, white and
  mucoid
• Birdseed agar brown to black colony
• Urease positive

SDA
- ve/ve
Birdseed agar
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Treatments

• Initial therapy oral fluconazole
• Severe symptoms Amphotericin B alone or
  combined with 5-flucytosine
• In AIDS patients life-long suppression of
  C. neoformans with Fluconazole