Invasive Fungal Infections

INVASIVE FUNGAL
INFECTIONS
AN OVERVIEW
By
Dr Anyamele Ibuchim
NTRODUCTION
PIDEMIOLOGY
ATHOGENESIS
LINICAL PRESENTATION
IAGNOSIS
REATMENT
REVENTION
INTRODUCTION
IFI- Presence of fungal elements

either as mould or yeast in deep
tissues of biopsy or needle aspirates
that is confirmed on culture and
histopathological examination
Mostly seen in the immunodeficient

Can affect all parts of the body
Associated with high mortality
Rising incidence due to increased

prevalence of At-Risk patients e.g
- immunosuppression
- malignancies
-chronic debilitating conditions
Common causative agents include
 YEASTS
 CANDIDA SPP
 CRYPTOCOCCUS SPP
 MOULDS
 ASPERGILLUS SPP
 FUSARIUM SPP
 MUCOR
 RHIZOPUS
 SCEDOSPORIUM PROLIFICANS
DIMORPHIC FUNGI
 HISTOPLASMA CAPSULATUM
 COCCIDIOIDES IMMITIS
 PARACOCCIDIODES SPP
 BLASTOMYCES DERMATITIDIS
 SPOROTHRIX SPP
 PENICILLIUM MARNEFFI
EPIDEMIOLOGY
 Fungi increasingly recognised as
major pathogens in the very ill
 Candida spp and Cryptococcus spp
most commonly isolated yeasts
 Aspergillus spp most commonly
isolated mould
 Others include: Fusarium
spp,Penicillium spp, Zygomycetes
 Dimorphic fungi also implicated
Increasing incidence worldwide due

increase in prevalence of AT-RISK grou
Most risk factors associated with

immunosuppression
Some risk factors have other underlying

mechanisms
Risk Factors Include
 HIV/AIDS
 Immunosuppressive Agents
 Neutropenic Patients
 Prosthetic Devices and Graft
 Solid Organ Transplantation
 Major and Aggressive surgery
 Broad Spectrum Antibiotics
 Prior Extensive Colonization
 Antineoplastic Agents
Disseminated candidiasis associated
with > 25% mortality
Candida albicans most often isolated
Non-Albicans Candida increasing
Normal Commensal of skin,GIT and

GUT
C. Albicans account for 79.4% of Can
didaemias in ICU patient
Cryptoccosus neoformans commone
cause of Cryptoccocosis
Usual mode of entry- inhalation
Causes pulmonary disease
Meningitis also common, especially

AIDS and solid organ transplants
Aspergillus spp most common
invasive mould
Major pathogens include:
A. fumigatus, A. niger,
A. flavus
A. fumigatus commonest isolate
Accounted for 82% of cases in 1985
66% of stem cell recipients in 1999
Lung and Heart recipients at high ris
Other Moulds and dimorphic fungi
play important causative roles
Usually causes disease in the severely

immunocompromised
Other Moulds and dimorphic fungi
play important causative roles
Usually causes disease in the severely

immunocompromised
PATHOGENESIS
 Fungi can be classified as
Pathogenic and Opportunistic
 Development of IFI due to
interplay between
1. Fungal Virulence
2. Host Predisposing Factors
3. Environment
Virulence properties of fungi
• Ability to grow at 37°C and adapt

to the environment inside the host
tissues
• Factors responsible for fungal
pathogenecity are specific to the
fungus.
 Enzymes,toxins and other
products
 Aspergillus spp: Proteases and Toxins
 Cryptococcocus spp- Phenoloxidase/Mela-

nin synthesis, presence of capsule
 Candida spp – form biofilms
 C. neoformans, C. albicans, A. fumigatus

produce SREBP
- helps fungus tolerate hypoxic tissue in hos
- also helps in antifungal resistance
Host Factors
IMMUNOLOGICAL DEFICIENCY
NEUTROPENIA
AUTOIMMUNE DISEASES
TRANSPLANT PATIENTS
SEVERE TRAUMA(ACCIDENT)
MAJOR SURGICAL PROCEDURE
INDWELLING PROSTHETIC
DEVICES
FUNGAL COLONIZATION IN
MUCOSAL SURFACES
CHRONIC AIRWAY
OBSTRUCTION(COPD/ASTH
MA
IMMUNOSUPPRESSIVE
THERAPY
CHRONIC BROAD
SPECTRUM ANTIBIOTICS
EXTREMES OF AGE
INFECTIONS
Cytomegalovirus
HIV
Mycobacterium tuberculosis
Inadequate treatment of
superficial fungal infection
MALIGNANCIES
Haematological Malignancies
Non-Haematological Malignancies
DEBILITATED PATIENTS
Critically ill on Mechanical

Ventilation
Patients in ICU`S and NICU`S
Environmental Exposure
1. Endogenous colonization
 Patient`s skin and GIT colonised
 Chemotherapy or Radiotherapy
induced mucositis, GIT surgeries,
Indwelling catheters
 Organisms translocate from GIT
and Skin to blood, causing systemic
infection
 Exposure to opportunistic fungi
 Aspergillus spp- contaminated

heating/cooling systems
 Candida spp from healthcare workers
 Fusarium spp from hospital water

Can also be community acquired
e.g Cryptoccocus and Pidgeon rearing
These pathogens may cause primary

infection or reactivation of latent infection
CLINICAL PRESENTATION
Depends on
 Site of infection
 Its Pathogenesis(angioinvasive or
not)
 Severity and nature of

Immunosuppression
 Unexplained fever in a patient
with risk factors

Pneumonia
Progressive pulmonary infiltrates,
despite broad spectrum antibiotics,
particularly with associated fever,
dyspnoea,non-productive cough and
pruritic chest pain is suggestive of IFI
of the lungs e.g
Invasive pulmonary aspergillosis
Disseminated candidiasis with lung involvement
Cryptococcus neoformans
Coccidioides immitis,Histoplasma spp, Blastomyce
Sinonasal Syndromes
 Rhinocerebral Zygomycosis: Affects
the
nasal cavity;later involves the paranasal
sinuses
 Other forms of fungal sinusitis:

usually
starts in the paranasal sinuses
Presentation
 Facial pain and swelling
 Ptosis,Proptosis,Pupillary dilation,fixation
 Dark serosanguineous nasal or ocular

discharge
 Palatal or Orbital cellulitis

 Ulceration with necrosis and perforation
of the nasal septum and nearby structures
 Could extend intracranially, with

devastating effects
 Treatment involves extensive surgical

debridement, with disfigurement
CNS Infections
One of the most serious

manifestations of IFI
Many forms associated with high

mortality
Two principle modes of entry:

 By haematogenous spread(candida,
other yeasts, moulds) or
 Through direct extension from a

sinonasal infection(moulds)
Symptoms include headaches,seizures,

focal deficits, loss of consciousness…
Gastrointestinal Syndromes
 Usually results from haematogenous
seeding
-- Primary infection of GIT very rare
--ingestion of a large fungal inoculum
 Enterocolitis (fever, abdominal pain)
 Life threatening Haematochezia
 Bowel
obstruction,infarction,perforation
Other Manifestations
 Central venous catheter related infection
 Otitis, Endophthalmitis
 Osteoarthritis, Septic arthritis
 Native and Prosthetic valve endocarditis

 Isolated involvement of any organ
DIAGNOSIS
Diagnosis will be based on history,exam
findings, laboratory investigations and
imaging studies
A high index of suspicion is needed
Late diagnosis linked with poor outcomes

Laboratory Diagnosis
 Samples include tissue biopsies,
aspirates and bronchoalveolar
lavage
 Conventional laboratory techniques
like
--Microscopy using KOH, Gram stain,
Giemsa, Indian ink and fluorescent
staining with calcofluor white
Immunohistochemistry and
immunufluorescence increases sensitivity
and specificity of microscopy
• Culture on media like;

Sabouraud dextrose agar,
Corn meal agar
Chromogenic media
mmunologic tests to detect:
 Antibodies(Anti-candida, Anti-Aspergillus)
 Antigen of fungi in general(mannan,

galactomannan)
 Specific fungal antigens(Cryptococcal Antigen)

Molecular methods:
 PCR, Microarray
 Nucleic acid sequence based amplification

(NASBA) and Pyrosequencing
Rapid methods: MALDI-TOF

maging Studies
 Plain radiographs have a role to play
 CT and MRI – can detect nodules in

various tissues involved in IFIs
Treatment
 Prompt commencement of empirical
therapy in highly suspicious cases
 High incidence and Fatality rates for IFIs
 Insufficient diagnostics
- Culture and Non-culture based methods

have high false negative rates
 Diagnosis often too late, or at autopsy
vailable drugs include:
Deoxycholate amphotericin B
5-Flucytosine
Azoles- Posaconazole, voriconazole

fluconazole
Echinocandins– Caspofungin,Micafungin,
Anidulafungin
Prevention
 Minimize length of
immunosuppression
 Use of GM-CSF in Neutropenic patients
 Prophylactic Anti-fungals:
-Primary Prophylaxis
-Secondary Prophylaxis
THANK YOU

Invasive Fungal Infections

Uploaded by

Copyright:

Available Formats

Invasive Fungal Infections

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Invasive Fungal Infections

Uploaded by

Copyright:

Available Formats

INVASIVE FUNGAL

IFI- Presence of fungal elements

Mostly seen in the immunodeficient

Associated with high mortality

Rising incidence due to increased

Increasing incidence worldwide due

Most risk factors associated with

Some risk factors have other underlying

Normal Commensal of skin,GIT and

Causes pulmonary disease

Meningitis also common, especially

Usually causes disease in the severely

Usually causes disease in the severely

• Ability to grow at 37°C and adapt

 Cryptococcocus spp- Phenoloxidase/Mela-

 Candida spp – form biofilms

 C. neoformans, C. albicans, A. fumigatus

Critically ill on Mechanical

 Aspergillus spp- contaminated

 Candida spp from healthcare workers

 Fusarium spp from hospital water

These pathogens may cause primary

 Severity and nature of

 Other forms of fungal sinusitis:

 Facial pain and swelling

 Dark serosanguineous nasal or ocular

 Palatal or Orbital cellulitis

 Could extend intracranially, with

 Treatment involves extensive surgical

One of the most serious

Many forms associated with high

Two principle modes of entry:

 Through direct extension from a

Symptoms include headaches,seizures,

 Life threatening Haematochezia

 Osteoarthritis, Septic arthritis

 Native and Prosthetic valve endocarditis

A high index of suspicion is needed

Late diagnosis linked with poor outcomes

• Culture on media like;

 Antigen of fungi in general(mannan,

 Specific fungal antigens(Cryptococcal Antigen)

 Nucleic acid sequence based amplification

Rapid methods: MALDI-TOF

 Plain radiographs have a role to play

 CT and MRI – can detect nodules in

- Culture and Non-culture based methods

Azoles- Posaconazole, voriconazole

 Use of GM-CSF in Neutropenic patients

You might also like