Opportunistic Mycoses Flashcards
(59 cards)
1
Q
major human opportunistic mycoses
A
- candidiasis
- cryptococcosis
- aspergilliosis
- murcormycosis
- fusariosis
2
Q
themes in opportunistic mycoses
A
- diseases and severity are widely varied
- depends on the patients’ pre-existing conditions
- most important predisposition is prolonged neutropenia
- optimal treatment addresses both the infection and the underlying problem
3
Q
ways to get prolonged neutropenia? and why is prolonged neutropenia bad?
A
- most important predisposition for opportunistic mycoses
- infections
- aplastic anemia
- arsenic poisoning
- cancer
- chemo
- radiation
- medications
- hereditary disorders
- vitamin deficiency
- autoimmunity
- hemodialysis
- splenic sequestration
4
Q
cryptococcosis organisms
A
- neoformans and gattii form 5 serotypes
- A and D are neoformans and most common
- B and C are gattii
- cause cryptococcosis, especially cryptococcal meningitis
- neoformans is environmental, found worldwide in soil contaminated with bird droppings, especially pigeons
- gatti found in litter under eucalyptus trees, cause less severe disease but prefers immunocompetent hosts (west coast)
- oval yeasts with narrow based buds and wide polysaccharide capsule
- pathogenic strains grow at 37 degrees
- not thermally dimorphic, moldlike sexually reproducing form has a different trigger
- no human to human transmission except organ transplant or needle sticks (which cause local cutaneous disease)
- meningitis rare before 1946, now we have more immunocompromised patients living on steroids and chemo
- disseminated disease was fatal before Amphotericin B in 1968
5
Q
pathogenesis of cryptococcosis
A
- transmitted by inhalation, pigeon droppings may be contagious for years
- lung infection may be asymptomatic or lead to pneumonia
- can be intracellular infection in alveolar macrophages
- immunocompetent hosts restrict infection to lungs and raises Helper T cells; they have skin test conversion and antibodies to capsule
- in people with deficient CMI, esp AIDS, dissemination leads to meningitis with skin nodules
6
Q
inflammatory response to C neoformans
A
- very blunted inflammatory response
- can have granuloma formation
- organ damage is by tissue distortion from growing yeast
- blunted response complicates diagnosis and means that presentation is late in disease
7
Q
virulence factors of cryptococcosis
A
- capsule is most important
- melanin in cell wall is antiphagocytic
- phospholipase B for invading tissue
8
Q
cryptococcosis diagnosis on exam: Hx
A
- steroid use
- malignant disease
- transplantation
- HIV infection
9
Q
cryptococcosis diagnosis on exam: skin
A
-take biopsies of nodules, can grow yeast
10
Q
cryptococcosis diagnosis on exam: pulmonary
A
- range from asymptomatic to ARDS
- cough and chest pain common
11
Q
cryptococcosis diagnosis on exam: cryptococcus and HIV
A
- fever
- cough
- headache
- weight loss
- positive cultures from blood, CSF, urine
12
Q
cryptococcosis diagnosis on exam: CNS
A
- subacute meningitis or meningoencephalitis
- antifungal therapy required for survival
- CT and MRI
- meningitis: headache, AMS, N/V
- fever and stiff neck less common (arise from IF)
- may also be sensory issues with eyes or ears
- if not acute pyogenic, may wait for CT/MRI before LP
- cryptococcomas: granulomas in brain cause focal neuro deficits
13
Q
additional areas for cryptococcosis infection?
A
- prostate
- eyes
- medullary cavity of bones
14
Q
cryptococcosis diagnosis on lab: CSF
A
-stain with India Ink to observe yeast with wide capsule
15
Q
cryptococcosis diagnosis on lab: biopsies
A
-stain with methenamine silver, periodic acid-schiff, mucicarmine
16
Q
cryptococcosis diagnosis on lab: culture
A
- at 37 degrees from CSF, blood, urine, sputum
- look for mucoid colonies on Sabouraud again
- will produce melanin in culture on special media
17
Q
cryptococcosis diagnosis on lab: serology
A
- crag for soluble cryptococcal antigen in blood and CSF
- one of the only useful serologic tests for microbes
- routine bloodwork may be normal
18
Q
cryptococcosis treatment: meningitis
A
- Amphotericin B (liposomal if kidney problems) plus flucytosine for 2 weeks followed by 10 more weeks of fluconazole
- in AIDS patients, use fluconazole for long term suppression, clearance may not be an option
19
Q
cryptococcosis treatment: prostate
A
-fluconazole
20
Q
cryptococcosis treatment: pulmonary
A
- in immunocompetent patients may not neat treatment
- can use 6-12 mo of fluconazole or itraconazole
21
Q
cryptococcosis treatment: skin, bones, other
A
-Amphotericin B
22
Q
how often do you have to check the CSF for crypto progress of treatment?
A
- weekly
- glucose and cell count will return to normal but protein anomalies may persist for years
- do not discontinue therapy until cultures consistently fail
23
Q
Aspergillosis organism
A
- fumigatus (most common), niger, flavus, clavatus
- ubiquitous environmental molds
- only mold, not dimorphic, therefore can’t get into blood easily
24
Q
Shape of aspergillus?
A
- septate hyphae with V shaped branches
- walls are nearly parallel
- conidia form radiating chains
25
what four syndromes does aspergillus cause?
1. allergic bronchopulmonary aspergillosis (ABPA)
2. Aspergilloma or colonizing aspergilliosis (fungus ball in lung)
3. chronic necrotizing pulmonary aspergillosis (CNPA)
4. invasive aspergillosis
* which one of these syndromes the patient gets depends on immune status
26
pathogenesis of aspergillosis
- widespread on decaying vegetation worldwide
- infectious conidia are airborned
- conidia colonize abraded skin, burns, cornea, ear, sinuses, lung
- healthy macrophage and neutrophil response eradicates fungus
- some aspergillus produce toxic metabolites that inhibit macrophage responses (like steroids)
27
allergic bronchopulmonary aspergillosis (ABPA)
- hypersensitivity reaction to infection of bronchi
- found in 1-10% of asthmatics, 7% of CF patients
- presents as an exacerbation of current condition
28
aspergilloma
- fungus ball forms when aspergillus invades already formed cavitary lesions of TB or CF
- associated with hemoptysis, may be life threatening
29
chronic necrotizing pulmonary aspergillosis (CNPA)
- in immunocompromised
- can invade lungs
- cause pneumonia with hemoptysis and granulomas
- may find hyphae in granulomas
- rare
- hard to diagnose
- often found at autopsy
- 10-100% mortality
30
invasive aspergillosis
- rapidly progressive invasion of blood vessels in severely immunocompromised patients
- involves infarction, hemorrhage, necrosis, often fatal
- relatively common in severely immunosuppressed patients (5-20%)
31
virulence factors of aspergillus
- gliotoxin- immunosuppressive
- toxic metabolites interfere with phagocytosis and opsonization
- proteases may be involved in tissue invastion
32
diagnosis of ABPA
- positive skin test for aspergillus allergy with asthma or CF
- coughing up brownish bronchial plugs containing hyphae
- fever
- wheezing
- pulmonary infiltrates
- unresponsive to antibiotics
- hemoptysis
- uncontrolled asthma
- purulent sinus drainage
- Xray or CT may show grape cluster or hand in mitten mucous clogged bronchi
33
diagnosis of aspergilloma
- fungus ball is visible on Xray or CT (mass in a cavity)
- changes position when patient sits up/ lies down
- does not invade tissue but may cause dangerous hemoptysis
- cough and fever
- may appear as a complication of chronic necrotizing pulmonary aspergillosis (CNPA) or invasive aspergillosis
34
diagnosis of CNPA
- subacute pneumonia that is unresponsive to antibiotics
- underlying disease of alcoholism, collagen vascular disease, chronic granulomatous disease or COPD with long term corticosteroid therapy
- needly biopsy, aspirate fluid if present for histo and culture
35
diagnosis of invasive aspergillosis
- history of profound immunosuppression or COPD with long term steroid therapy
- fever, cough, dyspnea, pleuritic chest pain, neutropenia, sometimes hemoptysis, worsening hypoexemia
- CXR is abnormal but variable
- CT may show a halo sign: ground glass infiltrate surrounding a nodular density
- represents a hemorrhage, invasive aspergillosis most common cause
- bronchoscopy, needle biopsy, or open lung biopsy for culture and histology
36
diagnosis of aspergillus on lab
- culture from sputum, needly biopsy, or bronchoalveolar lavage fluid
- visualize with silver stains, colonies with radiating chains of conidia
37
invasive aspergillus on lab
- septate hyphae branching at acute angles invading tissue
- acute IF infiltrate
- tissue necrosis
- blood vessel invasion
- high serum levels of glactomannan antigen
38
ABPA on lab
- high levels of aspergillus specific IgE
- eosinophilia
- mucus with degenerating eosinophils and hyphae
39
treatment for ABPA
- oral corticosteroids!-because need to dampen IgE
- itraconazole
- consider sinus surgery and/or omalizumab (anitbody to IgE that breaks up the chain to activate mast cells
40
treatment for aspergilloma
- remove surgically if hemoptysis
| - oral itraconazole
41
treatment for invasive aspergillus or CNPA
- vorionazole and/or ampho B (liposomal if kidney probs)
- alternative is capsofungin, might not works
- decrease immunosuppression if possible
- surgical resection of diseased area may be considered
42
mucormycosis organism
- RHIZOPUS
- very rare (500/year in US)
- life threatening (50-85%) mortality
- sinus infections, invade brain
- may also affect other organs
- widespread environmental
- not dimorphic
- underlying risk factor include diabetes, neutropenia
- must treat underlying disease, add Amph B, aggressive surgery
43
pathogenesis of mucor
- transmitted by airborne asexual spores
- ubiquitous worldwide
- cause disease only in vulnerable patients
- usually inhaled, can also be ingested or introduced by trauma
- invade tissues of patients with reduced immunity- diabetes, burns, leukemia, IV steroids, TNF a blockers, Fe overload
- neutrophils are main defense
- not highly associated with AIDS (CMI might not be critical)
- proliferate in walls of blood vessels, particularly:
1. paranasal sinuses, invading brain (50-70% mort, even when cured requires disfiguring surgery),
2. lungs (harder to dx, higher mort),
3. gut (of extremely malnourished)- harder to dx, higher mort
4. skin, 15% mort
5. disseminated, nearly 100% mort
- cause infarction and necrosis of tissue downstream from blocked vessel
- symptoms are at affected site
44
rhinocerebral diagnosis of mucor
- unilateral retro-orbital headache, facial pain, numbness, fever
- progresses to diplopia and visual loss
- reduced consciousness
- black pus
- necrotic eschars
- CT may be useful for detecting sinusitis invading the brain
45
wound infections in mucor
-unresponsive to antibiotics
46
Lung and GI mucor
- not specific presentations
- bronchoalveolar lavage or biopsy may be useful
- CT scan of lung for cavitation with and air crescent is highly suggestive of fungal infection
- CT of gut may show mass
47
cutaneous presentation of mucor
-cellulitis progression to dermal necrosis and black eschar formation
48
mucor lab diagnosis
- neutropenia, diabetic acidosis, iron overload
- no useful antigen tests or CSF findings
- biopsy- H&E or fungal stains show NONSEPTATE HYPHAE with broad irregular walls and branches AT RIGHT ANGLES, vascular invasion and necrosis, neutrophil infiltration
- culture- colonies with spores contained in sporangium, difficult to culutre
49
treatment for mucor
- send to tertiary care facility
- change any pre-existing bandages/ splints (could be contaminated)
- if diagnosed early, treat underlyinf problem plus liposomal amphotericin B and aggressive surgical removal of necrotic tissue may helps
- alternative posaconazole
- repeated, disfiguring surgery required for survival
50
Fusarium mycology
- fusarium species are environmentally ubiquitous
- identified microscopically by banana shaped macroconidia
- primarily pathogens of plants, including important crops
- F. solani is most common causing infection (50%), random other species contribute other 50%
51
virulence factors of fusarium
- immunosuppressive mycotoxins
- collagenases and proteases
- ability to adhere to prosthetic material
52
three presentations of fusarium pathogenesis
- mycotoxicosis
- immunocompetent local infection
- immunosuppressed opportunistic infection
53
mycotoxicosis of fusarium
- trichothecene mycotoxins- alimentary toxic aleukia (nasty hemorrhagic syndrome from ingesting/ contact)
- widespread bleeding and immunosuppression with secondary sepsis
- often fatal
- 1940s USSR outbreaks in wheat
- yellow rain
54
immunocompetent local infection with fusarium
- skin-burns
- cornea (contaminated contact solution)
- allergic sinusitis like ABPA
- colonization of prosthetics and catheters
- treated with amphotericin B, voriconazole, posaconazole
55
immunosuppressed opportunistic infection with fusarium
- prolonged neutropenia
- long term steroids
- bone marrow transplants
- profound T cell recipients (HSCT recipientst)
56
disseminated fusarium
- usually invades from sinus or at wound site
- presents as a fungemia with skin lesions
- may also seed eye, lung, cause local sx there
- grows from inside out
- often lethal
57
fusarium diagnosis
- grows easily on fungal medial but environmentally ubiquitous
- need multiple samples and sites to differentiate from lab contamination
- histology may be helpful, but can only differentiate from aspergillus if yeast form is present with acute branching hyphae
- PCR based tests and fungal metabolism tests available
58
fusarium treatment
- clinical trial data to compare efficacy of drugs and dosages
- more resistant to antifungals than others
- surgical excision of localized infections
- try ampho B with natamycin or voriconazole
- prognosis in disseminated disease is poor
59
fusarium prevention
- high risk patients should be kept in HEPA filtered POSITIVE pressure rooms
- filtered water supplies and scrubbed down showers
- pre-op workup for HSCT must include screening for fusarial infection, which may appear trivial before immunosuppression
