Opportunistic Moulds

13th March 2014

 Frequency of invasive mycoses has increased in

recent past
Associated with morbidity and mortality
Increased patient population at risk for the
development of serious fungal infections
Most well known causes of opportunistic
mycoses include: Candida albicans,
Cryptococcus neoformans and Aspergillus
fumigatus, (zygomycetes, other hyaline moulds,
dematicious moulds, Pneumocystis jiroveci)

 These plus new and emerging mycoses

tend to cause such infections:
catheter associated fungaemia,
peritonitis,, more localised infections e.g
lung,skin, paranasal sinuses,
haematogenous dissemination

Factors predisposing
Antimicrobial agents (no
and duration)colonisation, iv
Adrenal corticosteroids
-lower immunity
Chemotherapy -lower
immunity
Haematologic /solid
organ malignancy -lower
immunity
Previous colonisation

Indwelling catheter
Total parenteral nutrition
Neutropenia (<500/mm3)
Excessive surgery/burns
Assisted ventilation
ICU stay
Haemo/peritoneal dialysis
Malnutrition
HIV/AIDs
Extreme age

Patients at risk
Blood and Marrow
transplantation (BMT)
Solid organ transplant
Major surgery esp GIt
Immunosupprtessive
therapy

AIDS
Neoplastic disease
Neoplastic disease
Advanced age
Born premature

Host factors
Compromised individuals are at risk for
systemic candidiasis, cryptococcal
meningitis,invasive aspergillosis,
rhinocerebral or cerebral mucormycosis
The agents are ubiquitous in the
environment or are part of the normal
microbial flora
Life threatening, most frequently
encountered of the systemic mycoses

Host response?
The fungicidal activity of the neutrophil is
essential for normal defense against systemic
candidiasis, aspergillus and mucormycosis
Tissue forms of Aspergillus fumigatus and
Rhizopus oryzae are killed by
neutrophilsNeutropenia/ neutrophils with
impaired killing capacity (leukaemia or chronic
granulomatous disease)-susceptible

Host response?
CMI does not influence the course of systemic
candidiasis, aspergillus or mucormycosis
Antibodies and other humoral factors are not
protective
(not due to phagocytosis but more of fungal
susceptibility to oxidative killing,degree of
phagosome-lysosome fusion,fungal production
of catalase and superoxide dismutase,
elaboration of neutrophil inhibitors

Aspergillus
Diseases caused:
-Immediate hypersensitivity response without fungal growth-inhalation of spores or
mycelial fragments (atopic individuals-immediate ,asthmatic reaction(reaginic
antibody(IgE))
-allergic bronchopulmonary aspergillosis-actual infection by an aspergillus
species and organism grows in the bronchial tree; recurrent pulmonary
densities (X-ray), oesinophilia, asthma and hypersensitivity to aspergillus
antigen
-invasive aspergillosis occurs in immunocompromised patients and involves
invasion of tissue-localised in lung or generalised and disseminated. Hyphae
exhibit a propensity to invade lumen and walls of blood vessels causing
thrombosis , infarction and haemorrhage. From lungs generalised
git,brain,liver, kidneys. May present as acute pneumonia( cancer or transplant
patients on corticosteroids) or chronic necrotising pulmonary aspergillosis
(DM, connective tissue disorders, chronic obstructive lung disease, poor
nutrition, low dose corticosteroides)
-

Aspergillus
non invasive colonisation of exposed tissue e.g pulmonary cavity,
external ear canal, nail plate, or cornea (conidia germinate and
colonise surfaces of open cavities, paranasal sinuses, and ear
canals-Aspergilloma (follows cavity from
bronchiectasis,carcinoma,histoplasmosis,malformatios, sarcoidosis,
tb-most common type of pulmonary aspergillosis
paranasalsinuses (immunosuppressed), ears(follows allergy superficial
trauma) nasal cavity). Otomycosis due to A. niger, primary localised
infection of conjuctiva, eyelids, cornea, orbit and intraocular
structures. Cutaneous lesions and onychomycosis (A.flavus,
nidulans, glaucus
-certain secondary metabolites produced by species are toxic and
carcinogenic

 Morphology: growth characteristics and microscopic

appearance refer to Practical
Epidemiology
World wide,blood dyscrasias, humoral
immunedeficiency, decrease in number or functional
capacity of neurophils,endocrine disturbances
Significant correlation of invasive aspergillosis with
cancer (acute or chronic leukaemia, lymphoma,
Hodgkinss disease), granulocytopenia, corticosteroid
therapy, antibacterial antibiotics, cytotoxic drugs
(need to filter air for patients, positive pressure rooms,
limited access)
Aspergilloma-pre existing pulmonary cavities

Aspergillus
Source: vegetation,nuts,grains (growth/storage),
from decaying matter,soil, and air. Affects plants,
insects,birds,birds and domestic animals
Aspergillus fumigatus-most common pathogenic
species for humans. Rare natural resistance
exists in healthy host.
Disease exposure is overwheling or when host
defenses are compromis e.g leukaemiaed

Aspergillus
Pathogeneis
Health Macrophages contain conidia and
hyphae. Hyphae are susceptible to neutrophil
and monocyte kiling mechanisms
Aspergillus produces substances that inhibit
activation of the alternate pathway of
complement
Allergic forms involve specific immunopathology
without fungal invasion

Aspergillus
Laboratory diagnosis:
Microscopic examination
-fresh sputum examined for the presence of branching
septate hyphae of uniform width (4-7um)(sparse
fillaments or plugs of mycelium)
-bronchi may have aerial hyphae, conidia and
conidiophores)
-Tissue sections-hyphae in blood vessels forming parallel
arrays with dichotomous branching at acute angles
Culture: Practicals
Serology-detect antigen in patients with invasive disease
(more sensitive than tests for precipitins)

Mucormycosis
Mucormycosis(phycomycosis
zygomycosis)-an opportunistic mycotic
infection caused by a number of mould
species from the order Mucorales,class
Zygomycetes
Fungi are ubiquitous, thermotolerant
saprophytes
Patients with acidosis, leukaemia, immune
deficiencies

Mucormycosis

Rhizopus oryzae,R. rhizopodiformis

Absidia corymbifera
Rhizomucor pusillus
Species of Rhizormucor, Mucor, Rhizopus,
Absidia, Mortierella, Cunninghamella,
Saksenaea
Isolated from air, soil, water and hospital
environments world wide

Mucormycosis
Epidemiology:
Patients with Ketoacidosis-DM,drugs, uremia
predisposed to invasive mucormycosis
Burns patients, leukaemia,, lymphoma, steroid
treatment, immunosupression
Pathogenesis
Sporangiophores germinate and thrive in the
nasal, oropharyngeal or resp mucosa of
compromised patients
Normal alveolar macrophages inhibit germination
of sporangiophores but dm steroides , not able.

Mucormycosis
Hyphae invade the lumen and walls of blood vessels
causig thrombosis, infarction and necrosis9process more
rapid cf aspergillus or candida)
A suppurative response is elicited, and local necrosis
develops
Manifests as :
-local infection-kidneys following tissue trauma
, colonising-cutaneous infection may complicate burn
wounds
Application of contaminated bandages for surgical dressing
has caused nosocomial infection of skin

Mucormycosis
Invasive mucormycosis
-Rhinocerebral mucormycosis; invasion
begins in the nasal region and progresses
rapidly to involve the sinuses, eye, brain
and meninges(oedema of involved facial
area (is characteristic), necrosis, and
bloody exudate
(fatal within 1 week)

Mucormycosis
Thoracic mucormycosis
Primary involvement in the lung after
inhalation of sporangiophores. Invasion of
blood vessels results in profound
destruction of lung parencyma. Pul lesions
may be focal or diffuse
Fatal (1-4 weeks)

Mucormycosis
Lab diagnosis
Specimens-tissue, sputum or nasal exudates;
hyphae are broad and irregular in width (1015um), exhibit branching often at right angles,
hyphae are distorted and often non septate
Blood cultures tend to be negative
Specimens of tissue or drainage should be
cultured. When no apparent disease positive
culture=contaminants