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Fungal Diseases of
Medical Importance
Dr. Samuel A. Fayemiwo
Department of Medical Microbiology & Parasitology
University of Ibadan / University College Hospital
Ibadan.
WACP Primary Revision Course in Internal Medicine August
2017
What is a fungus?
• An eukaryotic, heterotrophic organism devoid of
chlorophyll that obtains its nutrients by absorption.
• Fungi are unicellular to filamentous, rigid cell
walled, spore-bearing organisms
• It usually reproduces by both sexual and asexual
means.
• The primary carbohydrate storage product of fungi
is glycogen.
• Most fungi have a thallus composed of hyphae
(sing. hypha) that elongate by tip growth .
Introduction
• Fungi exist in the environment as saprophytes ,
symbionts and parasites mostly in the soil and on
decaying materials .
• Most are aerobes or facultative anaerobes.
• More than 100,000 spp exist , but fewer than 400
spp are presently known to be pathogenic for man.
• About 50 spp cause more than 90% of the fungal
infections of humans and other animals.
• They are insensitive to antibacterial antibiotics.
Characteristics of Fungi.
• They are typical eukaryotes with a complex cytoplasm.
• They have :
• a nucleus bound by a nuclear membrane
• a cell membrane containing glycoproteins , lipids and ergosterol.
• a multi-layered rigid cell wall containing CHITIN (glucose and mannose
polymers )
• The cell membrane contains sterol which prevent many antibiotics being
effective against fungi.
• Majority of the fungi are obligate aerobes and can be cultured on media
in the laboratory.
Classification of Fungi
• Glomerulomycota: - Vegetative hyphae are sparsely
septate or aseptate .
• Asexual reproduction occurs via sporangia, i.e. spores
contained in a sporangium.
• Sexual reproduction by production of zygospores which
are thick walled resting spores
• Examples are : Mucor , Rhizopus ,Lichtheimia ,
Cunninghamella , Absidia ,pilobolus.
• Ascomycota : Sac fungi , have septate hyphae.
• Asexual reproduction is by formation of conidia ,
• Sexual reproduction involve a sac or ascus in which
karyogamy and meiosis occur resulting in the formation
of ascospores.
• Examples are : Most pathogenic molds (Trichophyton
,Microsporium ,Blastomyces ,Histoplasma, Coccidioides)
Classification II
• Basidiomycota :
• Club fungi , They have Septate hyphae .
• Asexual reproduction by formation of conidia,
• Sexual reproduction results in four progeny ,
basidiospores supported by a club-like structure
called a basidium. Examples are: Filobasidiella
neoformans, Cryptococcus neoformans .
• Dueteromycota : Fungi imperfecti ,
• They have septate hyphae, Asexual reproduction
results in the production of conidia,
• Sexual phase not yet identified. e.g. Trichosporon,
Torulopsis , ,Pityosporum , Epidermophyton ,
paracoccidiodes.
CLASSIFICATION III
• Depending on cell morphology
• Yeasts
• Moulds
• Dimorphic fungi
Yeasts
• Unicellular fungi
• Spherical or oval
• Reproduce by budding
• Optimal temperature- 370C
• Non-filamentous
• may produce a pseudohyphae
• Yeast like fungi - Grow partly as yeasts and partly as
elongated cells resembling hyphae which are called
pseudohyphae.
Yeasts
• Candida albicans
• Cryptococcus neoformans
• Trichosporon spp
• Geotrichum spp
• Saccharomyces cerevisiae
• Malassezia furfur
Moulds
• Multicellular
• Filamentous fungi
• Optimal temperature- 250C
• Produce hyphae which may be septate or non-septate
• Hyphae form mycelia (tangled mass of hyphae).
• Vegetative/ aerial hyphae
• Reproduce by formation of different types of spores.
Mould form
Moulds
• Aspergillus flavus
• Penicillium spp
• Trichophyton rubrum
• Absidia spp
• Epidermophyton floccosum
• Fusarium spp
• Microsporum canis
Dimorphic fungi
• Thermally dimorphic fungi : Occur in 2 forms
• Can exist as either mold phase or yeast phase
• Moulds (Filaments) at 250 C (soil)
• Yeasts at 370C (in host tissue)
• Most fungi causing systemic infections are dimorphic
• Histoplasma capsulatum
• Blastomyces dermatidis
• Paracoccidioides brasiliensis
• Coccidioides immitis
• Sporothrix schenkii
Dimorphic Fungi
Clinical Syndromes
• The effects of fungi on humans are numerous but from a medical
perspective can be divided into 3 groups
• Mycotoxicosis
• Hypersensitivity diseases
• Colonization of the host with resultant disease.
• They do not cause widespread or dangerous epidemics ,but they
are major cause of individual distress , disability and disfigurement.
• They can cause life- threatening conditions in those with
immunosuppressive drugs , AIDS , malignancies.
Clinical Syndromes - 2
• Mycotoxicosis : These are the diseases caused by the ingestion of
fungal toxins.
• Most of these are accidental .
• Claviceps purpurea- Ergot alkaloids that causes tissue inflammation
, necrosis, and gangrene.
• amanita and phalloidin in Amanita mushroom
• Aspergillus flavus - Aflatoxin that causes liver damage and is
carcinogenic.
Clinical Syndrome -3
• Hypersensitivity Diseases :
• It occurs as a result of fungal spores in the air.
• One of the indices for air pollution is to measure the fungal
spore count
• Fungal spores trigger off asthmatics attacks, rhinitis ,
pneumonitis and alveolitis.
ALLERGY
• Usually results from inhalation of spores
• Presents as asthmatic reaction
• An IgE mediated hypersensitivity response
• Eg – Allergic bronchopulmonary aspergillosis from spores of
Aspergillus
• Farmer’s lung – mouldy hay, Malt worker’s disease – mouldy
barley, Cheese washer’s lung – mouldy cheese, Wood
trimmer’s disease – mouldy wood
Fungi commonly associated with
allergic respiratory conditions
• Aspergillus fumigatus and other Aspergillus species
• Alternaria ,
• Cladosporium ,
• Penicillium ,
• Candida
• Botrytis
• Trichophyton
• Didymella
• ………and many others
Infections Secondary to Colonization
• These fungal infections can be classified on the basis of
the area of the body affected.
• Superficial mycosis: Limited to the outermost layer of the skin
and hair. no immune response ,and is caused mostly by yeasts
(Dandruff).
• Cutaneous mycosis: Caused by the dermatophytes. Affect the
deeper levels of the epidermis and invade the hair and nails.
evoke immune response Tinea (Ringworm, Athlete’s foot, jock
itch) .
• Subcutaneous mycosis : Chronic infection of sub dermal tissues
involving the dermis , subcutaneous tissue , muscles and fascia.
They result from the puncture of wounds by objects
contaminated by fungal species found in the soil. It may require
surgical intervention
InfectionsSecondaryto ColonizationII
• Systemic mycosis :
• Endemic Mycoses
Primarily infect the lungs then spreads to
the other organs. It is caused by virulent dimorphic
fungi . The disease can be spread from organ to
organ or tissue.
• Opportunistic mycosis :
Usually organisms of low pathogenicity
which produce disease only under condition of
lowered immunity.
Superficial / Cutaneous mycoses
• Dermatophytes
• Candida species
• Malassezia spp
• Piedra
• Tinea nigra
22
Superficial Fungal infections
• Superficial fungal infections arise from the
pathogen that is restricted to the stratum corneum
, with little or no tissue reactions.
• Superficial and Cutaneous infections are sometime
regarded as superficial.
• Superficial infections :
• Tinea( Pityriasis) vesicolor.
• Piedra ( asymptomatic fungal infection of the hair shaft.) and,
• Tinea nigra( noticed less usually in the black population)
Pityriasis (Tinea) vesicolor
• Tinea vesicolor :Caused by Malassezia furfur (called
Pityrosporum orbiculare in its yeast-like form)
• Nine different species of Malassezia have been identified and
the most common species cultured from pityriasis versicolor
patches is M. globosa. Others are M. restrica
• It is one of the most common pigmentary disorders worldwide
and its frequently seen in tropical regions with prevalence as
high as 40% .
• Infection can arise at any age but occurs mainly during
adolescence, when the sebaceous glands are more active.
• Pityriasis versicolor is common in people with hyperhidroisis
(sweat heavily).
Pityriasis (Tinea) vesicolor-2
• T.vesicolor is neither contagious nor due to poor hygiene.
• The infection results from a change to the mycelial state of
dimorphic lipophilic yeasts of the genus Malassezia ,which
colonizes the stratum corneum.
• Patients with this condition usually have many irregularly
shaped slightly scaling macules and patches covering large
areas of the body and separated by skip regions of the
normal skin.
• Distributions of patches parallel the density of the
sebaceous glands.
• Affected areas include the chest , back, neck and face. Facial
patches are more common in children. It can also be seen in
patients with AIDS.
P. Vesicolor
P. Vesicolor
• Tinea vesicolor.
Differentials P.V.
• Vitiligo
• Pityriasis alba
• Tinea corporis
• Seborrhoeic dermatitis
Piedra
• Piedra : Also known as Trichomycosis nodularis is an
asymptomatic fungal infection of the hair shaft.
• Both sexes and people of all ages are equally affected.
• Two types ; white and black piedra. White is more
prevalent in temperate and semi tropical countries while
black piedra is usually seen in the tropics worldwide
where it is hot and humid.
• The infection is caused by Trichosporon spp ( White ) and
Piedraia hortae ( Black ) .
• The minute hair shaft nodules of black piedra can have a gritty
feelings or be recognized as metallic sound when brushing the
hair.
• It usually affect the scalp hair.
Piedra (contd.)
• The nodules are hard, firmly attached and rarely produce hair
breakages . Beard, moustache, and pubic hair are not generally
affected.
• Nodules are most typical on the frontal scalp.
• White piedra caused by Trichosporon spp most usually affects
pubic hair, axillary hair , beards , moustache, eyebrows and
eyelashes .
• The nodules can easily be detached from the hair shaft because it
affects the outer lipid layers.
Tinea nigra
• Noticed less usually in the black population than in
others . The F/M predilection is about 3 : 1.
• It is caused by Hortae werneckii ( formerly known as
Cladosporium werneckii ).
• It arises after any inoculation subsequent to trauma
from soil, sewage, wood or compost .
• The fungus is lipophilic and it does not extend beyond
stratum corneum. It is characterized by the presence of
one oval shaped macule or patch that is painless ,
discrete , and light to brown in colour.
• Microscopy : Branched septate hyphae and budding yeast
cells with melanised cell wall.
Cutaneous mycoses
• Dermatophytoses
• AKA Tinea, Ringworm
• Caused by dermatophytes
• Three genera- Trichophyton
- Epidermophyton
- Microsporum
• Anthropophilic, Zoophilic, Geophilic
• Worldwide distribution
• use keratin as a source of nutrition- keratin
degradation
• Infect skin, hair, nails
• Don’t tend to grow at 37 °C
• Transmission - infected skin scales
• Dermatophytes may be communicated from person to person
by combs, towels, etc.
• Characterized by itching, scaling skin patches that can become
inflamed and weeping
• Infection in different sites may be
due to different organisms but is given
one name
• Tinea pedis
• Tinea corporis
• Tinea capitis
• Tinea cruris
• Tinea barbae
• Tinea cruris
Tinea cruris
Onychomycosis: Nail infections
• Laborarory diagnosis
• Specimen- skin scrapings, nails clippings,
hair.
• Microscopic Examination-
• Add 10–20% potassium hydroxide to
specimen
• Branching hyphae or chains of
arthroconidia (arthrospores)
Culture –
• Sabouraud's dextrose agar or inhibitory mold agar
• Incubate for 1–3 weeks at room temperature
Identification of species
• colonial morphology (growth rate, surface texture, and any
pigmentation)
• microscopic morphology (macroconidia, microconidia)
• Treatment
• Therapy consists of thorough removal of infected and dead
epithelial structures
• Application of a topical antifungal agent
• Keep the area dry
• Avoid sharing sources of infection
Subcutaneous mycoses
• Causative organisms reside in the soil and in decaying or live
vegetation
• Almost always acquired through traumatic lacerations or
puncture wounds
• Grow in subcutaneous tissues, spread via lymphatics.
• May reach distant organs
• Common among those who work with soil and vegetation.
• Commoner in tropics and subtropics
• Sporothricosis- Sporothrix schenckii
• Chromomycosis - Phialophora
-Cladosporium
• Mycetoma - Madurella grisea, Actinomadura
madura
Mycetoma
• Common in Africa and South America
• Chronic destructive disease affecting
skin, underlying tissue and sometimes
adjacent bone
• Caused by various fungi including
Madurella spp., Scedosporium spp.,
• Infection results from traumatic
implantation of spores into the skin,
e.g. thorns, splinters
Mycetoma
• Mycetoma
• Diagnosis:
• Specimen: scrapings or biopsy from lesions
• Microscopy: scrapings in 10% potassium hydroxide (dark,
round fungus cells = sclerotic bodies diagnostic
• Culture in Saboraud Dextrose Agar.
• Treatment: surgical excision with wide margins for small
lesions, chemotherapy with flucytosine or itraconazole for
larger lesions
Endemic mycoses
• All caused by dimorphic fungi
• 4 diseases
• Histoplasmosis
• Blastomycosis
• Cocidioidomycosis
• Paracoccidioidomycosis
• Pathogenesis similar in all- transmitted by inhalation of spores,
result in chronic granulomatous disease in the lungs, resemble TB
Histoplasmosis
• Aetiology- Histoplasma capsulatum- a facultative
intracellular parasite
• Two varieties
• H. capsulatum var. capsulatum is the common
histoplasmosis
• H. capsulatum var. duboisii is the African type.
• Distribution -World wide
• Endemic in the Mississippi-Ohio River Valley in the
U.S.A.
• Also Africa, Australia and parts of East
Histoplasmosis
• Transmitted by inhaling dust from soil that contains bird
droppings.
• The severity varies widely, with the lungs the most common
site of infection.
• Clinical manifestations:
• Most cases are inapparent, subclinical or benign.
• Others have chronic progressive lung disease, chronic
cutaneous or systemic disease or an acute fulminating fatal
systemic disease.
• All stages of this disease may mimic tuberculosis.
Histoplasmosis
• Laboratory diagnosis:
• Specimen: Skin scrapings, sputum , bronchial washings, CSF,
pleural fluid, blood, bone marrow and tissue biopsies
• Microscopy:
• Skin scrapings- 10% KOH mounts;
• Tissue sections should be stained using PAS digest, Grocott's
methenamine silver (GMS) or Gram stain.
Histoplasmosis
• Culture:
• Slow growing- up to 4 weeks
• Culture on selective media eg Sabouraud's dextrose
agar
• Cultures of H. capsulatum represent a severe
biohazard
• Serology:
• Immunodiffusion and/or complement fixation tests
• Conversion of the mould form to the yeast phase
• Treatment -Itraconazole
-Amphotericin B
Opportunistic mycoses
• Opportunistic: These organisms generally have a low potential
for virulence but can produce severe disease involving a
variety of body tissues.
• Usually affect the immunocompromised but are rare in normal
individual
• Organ transplantation, post chemotherapy for cancer,
immunodeficiency due to AIDS and congenital
immunodeficiency states
• Cryptococcosis: Cryptococcus neoformans
• Candidiasis- Candida albicans
• Aspergillosis- Aspergillus species
• Zygomycosis- Rhizopus species
Candidosis
• This is referred to infections caused by yeasts belonging to the
ascomycetous genus Candida .
• More than 200 spp exist , 90-95% of boodstream infections
are caused by four spps , C. albicans , C. glabrata, C.
parapsilosis , and C. tropicalis . The remaining are C.
dubliniensis , C. gulliermondii , C. krusei , C. africana , C.
famata , C.rugosa , C.lusitaniae , C.incospicua , C. novegensis
etc .
• C.albicans remains the predominant cause of both superficial
and invasive forms of candidosis .
• C. glabrata incidence is rising
• Candida is part of normal flora of oral cavity , gut , airways ,
vagina and moist areas of the body .
Candidosis
• Infections or colorizations depend on:
• Fungal load , formation of hyphae , presence of biofilms , invasions and
elucidations of immune response .
• Candida may cause - Superficial infections which include :
• Vulvo-vaginal candidiasis
• Oral candidosis
• Predisposing factors are :
• Altered oral flora , poor oral hygiene ,impaired local defence mechanisms
and impaired systemic defence mechanisms .
Candidosis
• Skin and Nail infections
• Sepsis and disseminated diseases
• Candidemia is almost seen in patients with risk factors like :
• GI surgery , Immunosupprssion , malignancy ( Heamatological etc)
• Disseminations to other organs causing – Arthritis , Meningitis ,
Osteomyelitis , Endocarditis and Retinitis .
Candidemia
• Most common incidence
• Mortality – 40%
• Candida albicans is the most common
• Other species increasing incidence- C. glabrata, C. krusei , C.
parapsilosis etc.
• Dissemination to other organs:
• Arthritis
• Osteomyelitis
• Endocarditis
• Meningitis , Renal tracts , eyes…
Candidaemia
• Early treatment of Candidaemia is critical to good outcome
• Rx < 12hrs – Mortality 11.1%
• Rx- 12-24hrs – Mortality 15.4%
• Rx 24-48hrs – Mortality 36.5%
• Rx > 72hrs – Mortality 41.4%
• Roosen Mayo Clinic Proc. 2000; 75: 562-7
Candidaemia
• Anidulafungin-200/100mg
• Caspofungin – 70/50mg
• Micafungin- 100mg
• Ambisome- 3mg/kg
• Voroconazole 6/3mg/kg
• Fluconazole-400-800mg
Cryptococcosis
• Cryptococcus neoformans, found worldwide
• Especially found in soil containing bird (esp.
pigeons) droppings
• Characteristic thick capsule that surrounds
budding yeast cell –seen using Indian Ink
• Most common form is mild subclinical lung
infection
• In the immunocompromised often disseminates
to the brain
• Cryptococcal meningitis- commoner in AIDS
patients, often fatal
Cryptococcosis–Clinicalpresentation
• Cryptococcus
• Studies show that from 10 % to 30 % of AIDS patients have
cryptococcal meningitis and they will require maintenance
therapy with fluconazole for the remainder of their life.
Fluconazole penetrates the CSF
• Mortality: Without treatment 100%
• With treatment 20%
• Relapse:
• Non-AIDS 15-20%
• AIDS patients 50% ,With relapse there is 60% mortality.
Aspergillosis
• Several species of genus Aspergillus, mostly
Aspergillus fumigatus
• Worldwide distribution, ubiquitous
• Filamentous moluds, produce large numbers of
conidiospores.
• Reside in soil, decomposing organic matter and
dust
• Associated outbreaks with construction work
• Disease presentation depends on immunologic
status of patients.
Aspergillosis
• Acute Aspergillus infections
• Most severe and often fatal form of aspergillosis is acute
invasive infection of the lung. May disseminate to the brain
etc
• Less severe form gives rise to a fungus ball (aspergilloma) , a
mass of hyphal tissue that forms in lung cavities derived from
prior disease
Aspergillosis
• Allergic Broncho-pulmonary Aspergillosis ( ABPA)- Uncontrolled
Asthma , wheezing , fever , malaise , Productive coughs , mucus
plugs.
• Severe Asthma with fungal sensitization (SAFS).
• Chronic Pulmonary Aspergillosis .
• Invasive Aspergillosis
Aspergillosis-Interactionsof Aspergilluswiththehost
Immune dysfunction
Frequency
of
aspergillosis
Immune hyperactivity
Frequency
of
aspergillosis
Acute IA
Subacute IA
Otitis externa
Onychomycosis
Aspergillus keratitis
Aspergillus bronchitis
Chronic pulmonary
ABPA
Severe asthma with
fungal sensitisation
Allergic sinusitis
.
After Casadevall & Pirofski, Infect Immun 1999;67:3703
Lung/tissue damage
Unusual Pathogens
•
• Penicillium marneffei
• Dimorphic,
• Produces a red pigment and reproduces by
fission.
• Requires amphotericin B therapy and oral
itraconazole maintenance.
• Pneumocystis jirovecii
• Formerly thought to be a protozoan.
Presently believed to be a fungus.
Diagnosis of fungal infections
• Specimens: Systemic -Blood culture, Pneumonia-
Bronchoscopy washings or brushings or
bronchial biopsy, sputum, Meningitis: CSF
tissue biopsies, skin scrapings , nail clippings
• Microscopy – direct staining of fungi in sections
can distinguish between yeasts and molds
• Identification by the morphology of conidia
structures
• India ink- demonstrates capsule of Cryptococcus
Culture
• Standard media –Saborauds dextrose agar (SDA), potato
dextrose agar, (PDA), low PH 5.0
• Plain or with antibiotics
• Culture at 370C (Body temperature) and 250C (room
temperature)
Serology
• Most serological tests for fungi measure antibody.
• Newer tests to measure antigen are available e.g.
Cryptococcal, Histoplasma and Aspergillus antigen
• Molecular diagnosis- PCR not used on a routine basis on
samples
• Skin testing for a delayed hypersensitivity response
• useful for epidemiologic purposes
• determine cellular defense mechanisms
• but often not for diagnosis.
• Germ tube test- for Candida albicans
• Carbohydrate assimilation tests
Control
• Good hygiene.
• Chemotherapy:
• Topical powders and creams
• most contain azole derivatives (miconazole,
clotrimazole, ketoconazole)
• useful against superficial dermatophytes.
• Systemic infections are generally treated by
Amphotericin B , 5- Flourocytosine, Azoles-
miconazole, Fluconazole or ketoconazole,
Echinocandins.
• No vaccines are currently available.
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fungal disease of medical importance.pptx

  • 1. Fungal Diseases of Medical Importance Dr. Samuel A. Fayemiwo Department of Medical Microbiology & Parasitology University of Ibadan / University College Hospital Ibadan. WACP Primary Revision Course in Internal Medicine August 2017
  • 2. What is a fungus? • An eukaryotic, heterotrophic organism devoid of chlorophyll that obtains its nutrients by absorption. • Fungi are unicellular to filamentous, rigid cell walled, spore-bearing organisms • It usually reproduces by both sexual and asexual means. • The primary carbohydrate storage product of fungi is glycogen. • Most fungi have a thallus composed of hyphae (sing. hypha) that elongate by tip growth .
  • 3. Introduction • Fungi exist in the environment as saprophytes , symbionts and parasites mostly in the soil and on decaying materials . • Most are aerobes or facultative anaerobes. • More than 100,000 spp exist , but fewer than 400 spp are presently known to be pathogenic for man. • About 50 spp cause more than 90% of the fungal infections of humans and other animals. • They are insensitive to antibacterial antibiotics.
  • 4. Characteristics of Fungi. • They are typical eukaryotes with a complex cytoplasm. • They have : • a nucleus bound by a nuclear membrane • a cell membrane containing glycoproteins , lipids and ergosterol. • a multi-layered rigid cell wall containing CHITIN (glucose and mannose polymers ) • The cell membrane contains sterol which prevent many antibiotics being effective against fungi. • Majority of the fungi are obligate aerobes and can be cultured on media in the laboratory.
  • 5. Classification of Fungi • Glomerulomycota: - Vegetative hyphae are sparsely septate or aseptate . • Asexual reproduction occurs via sporangia, i.e. spores contained in a sporangium. • Sexual reproduction by production of zygospores which are thick walled resting spores • Examples are : Mucor , Rhizopus ,Lichtheimia , Cunninghamella , Absidia ,pilobolus. • Ascomycota : Sac fungi , have septate hyphae. • Asexual reproduction is by formation of conidia , • Sexual reproduction involve a sac or ascus in which karyogamy and meiosis occur resulting in the formation of ascospores. • Examples are : Most pathogenic molds (Trichophyton ,Microsporium ,Blastomyces ,Histoplasma, Coccidioides)
  • 6. Classification II • Basidiomycota : • Club fungi , They have Septate hyphae . • Asexual reproduction by formation of conidia, • Sexual reproduction results in four progeny , basidiospores supported by a club-like structure called a basidium. Examples are: Filobasidiella neoformans, Cryptococcus neoformans . • Dueteromycota : Fungi imperfecti , • They have septate hyphae, Asexual reproduction results in the production of conidia, • Sexual phase not yet identified. e.g. Trichosporon, Torulopsis , ,Pityosporum , Epidermophyton , paracoccidiodes.
  • 7. CLASSIFICATION III • Depending on cell morphology • Yeasts • Moulds • Dimorphic fungi
  • 8. Yeasts • Unicellular fungi • Spherical or oval • Reproduce by budding • Optimal temperature- 370C • Non-filamentous • may produce a pseudohyphae • Yeast like fungi - Grow partly as yeasts and partly as elongated cells resembling hyphae which are called pseudohyphae.
  • 9. Yeasts • Candida albicans • Cryptococcus neoformans • Trichosporon spp • Geotrichum spp • Saccharomyces cerevisiae • Malassezia furfur
  • 10. Moulds • Multicellular • Filamentous fungi • Optimal temperature- 250C • Produce hyphae which may be septate or non-septate • Hyphae form mycelia (tangled mass of hyphae). • Vegetative/ aerial hyphae • Reproduce by formation of different types of spores.
  • 12. Moulds • Aspergillus flavus • Penicillium spp • Trichophyton rubrum • Absidia spp • Epidermophyton floccosum • Fusarium spp • Microsporum canis
  • 13. Dimorphic fungi • Thermally dimorphic fungi : Occur in 2 forms • Can exist as either mold phase or yeast phase • Moulds (Filaments) at 250 C (soil) • Yeasts at 370C (in host tissue) • Most fungi causing systemic infections are dimorphic • Histoplasma capsulatum • Blastomyces dermatidis • Paracoccidioides brasiliensis • Coccidioides immitis • Sporothrix schenkii
  • 15. Clinical Syndromes • The effects of fungi on humans are numerous but from a medical perspective can be divided into 3 groups • Mycotoxicosis • Hypersensitivity diseases • Colonization of the host with resultant disease. • They do not cause widespread or dangerous epidemics ,but they are major cause of individual distress , disability and disfigurement. • They can cause life- threatening conditions in those with immunosuppressive drugs , AIDS , malignancies.
  • 16. Clinical Syndromes - 2 • Mycotoxicosis : These are the diseases caused by the ingestion of fungal toxins. • Most of these are accidental . • Claviceps purpurea- Ergot alkaloids that causes tissue inflammation , necrosis, and gangrene. • amanita and phalloidin in Amanita mushroom • Aspergillus flavus - Aflatoxin that causes liver damage and is carcinogenic.
  • 17. Clinical Syndrome -3 • Hypersensitivity Diseases : • It occurs as a result of fungal spores in the air. • One of the indices for air pollution is to measure the fungal spore count • Fungal spores trigger off asthmatics attacks, rhinitis , pneumonitis and alveolitis.
  • 18. ALLERGY • Usually results from inhalation of spores • Presents as asthmatic reaction • An IgE mediated hypersensitivity response • Eg – Allergic bronchopulmonary aspergillosis from spores of Aspergillus • Farmer’s lung – mouldy hay, Malt worker’s disease – mouldy barley, Cheese washer’s lung – mouldy cheese, Wood trimmer’s disease – mouldy wood
  • 19. Fungi commonly associated with allergic respiratory conditions • Aspergillus fumigatus and other Aspergillus species • Alternaria , • Cladosporium , • Penicillium , • Candida • Botrytis • Trichophyton • Didymella • ………and many others
  • 20. Infections Secondary to Colonization • These fungal infections can be classified on the basis of the area of the body affected. • Superficial mycosis: Limited to the outermost layer of the skin and hair. no immune response ,and is caused mostly by yeasts (Dandruff). • Cutaneous mycosis: Caused by the dermatophytes. Affect the deeper levels of the epidermis and invade the hair and nails. evoke immune response Tinea (Ringworm, Athlete’s foot, jock itch) . • Subcutaneous mycosis : Chronic infection of sub dermal tissues involving the dermis , subcutaneous tissue , muscles and fascia. They result from the puncture of wounds by objects contaminated by fungal species found in the soil. It may require surgical intervention
  • 21. InfectionsSecondaryto ColonizationII • Systemic mycosis : • Endemic Mycoses Primarily infect the lungs then spreads to the other organs. It is caused by virulent dimorphic fungi . The disease can be spread from organ to organ or tissue. • Opportunistic mycosis : Usually organisms of low pathogenicity which produce disease only under condition of lowered immunity.
  • 22. Superficial / Cutaneous mycoses • Dermatophytes • Candida species • Malassezia spp • Piedra • Tinea nigra 22
  • 23. Superficial Fungal infections • Superficial fungal infections arise from the pathogen that is restricted to the stratum corneum , with little or no tissue reactions. • Superficial and Cutaneous infections are sometime regarded as superficial. • Superficial infections : • Tinea( Pityriasis) vesicolor. • Piedra ( asymptomatic fungal infection of the hair shaft.) and, • Tinea nigra( noticed less usually in the black population)
  • 24. Pityriasis (Tinea) vesicolor • Tinea vesicolor :Caused by Malassezia furfur (called Pityrosporum orbiculare in its yeast-like form) • Nine different species of Malassezia have been identified and the most common species cultured from pityriasis versicolor patches is M. globosa. Others are M. restrica • It is one of the most common pigmentary disorders worldwide and its frequently seen in tropical regions with prevalence as high as 40% . • Infection can arise at any age but occurs mainly during adolescence, when the sebaceous glands are more active. • Pityriasis versicolor is common in people with hyperhidroisis (sweat heavily).
  • 25. Pityriasis (Tinea) vesicolor-2 • T.vesicolor is neither contagious nor due to poor hygiene. • The infection results from a change to the mycelial state of dimorphic lipophilic yeasts of the genus Malassezia ,which colonizes the stratum corneum. • Patients with this condition usually have many irregularly shaped slightly scaling macules and patches covering large areas of the body and separated by skip regions of the normal skin. • Distributions of patches parallel the density of the sebaceous glands. • Affected areas include the chest , back, neck and face. Facial patches are more common in children. It can also be seen in patients with AIDS.
  • 28. Differentials P.V. • Vitiligo • Pityriasis alba • Tinea corporis • Seborrhoeic dermatitis
  • 29. Piedra • Piedra : Also known as Trichomycosis nodularis is an asymptomatic fungal infection of the hair shaft. • Both sexes and people of all ages are equally affected. • Two types ; white and black piedra. White is more prevalent in temperate and semi tropical countries while black piedra is usually seen in the tropics worldwide where it is hot and humid. • The infection is caused by Trichosporon spp ( White ) and Piedraia hortae ( Black ) . • The minute hair shaft nodules of black piedra can have a gritty feelings or be recognized as metallic sound when brushing the hair. • It usually affect the scalp hair.
  • 30. Piedra (contd.) • The nodules are hard, firmly attached and rarely produce hair breakages . Beard, moustache, and pubic hair are not generally affected. • Nodules are most typical on the frontal scalp. • White piedra caused by Trichosporon spp most usually affects pubic hair, axillary hair , beards , moustache, eyebrows and eyelashes . • The nodules can easily be detached from the hair shaft because it affects the outer lipid layers.
  • 31. Tinea nigra • Noticed less usually in the black population than in others . The F/M predilection is about 3 : 1. • It is caused by Hortae werneckii ( formerly known as Cladosporium werneckii ). • It arises after any inoculation subsequent to trauma from soil, sewage, wood or compost . • The fungus is lipophilic and it does not extend beyond stratum corneum. It is characterized by the presence of one oval shaped macule or patch that is painless , discrete , and light to brown in colour. • Microscopy : Branched septate hyphae and budding yeast cells with melanised cell wall.
  • 32. Cutaneous mycoses • Dermatophytoses • AKA Tinea, Ringworm • Caused by dermatophytes • Three genera- Trichophyton - Epidermophyton - Microsporum • Anthropophilic, Zoophilic, Geophilic • Worldwide distribution • use keratin as a source of nutrition- keratin degradation
  • 33. • Infect skin, hair, nails • Don’t tend to grow at 37 °C • Transmission - infected skin scales • Dermatophytes may be communicated from person to person by combs, towels, etc. • Characterized by itching, scaling skin patches that can become inflamed and weeping
  • 34. • Infection in different sites may be due to different organisms but is given one name • Tinea pedis • Tinea corporis • Tinea capitis • Tinea cruris • Tinea barbae • Tinea cruris
  • 37. • Laborarory diagnosis • Specimen- skin scrapings, nails clippings, hair. • Microscopic Examination- • Add 10–20% potassium hydroxide to specimen • Branching hyphae or chains of arthroconidia (arthrospores)
  • 38. Culture – • Sabouraud's dextrose agar or inhibitory mold agar • Incubate for 1–3 weeks at room temperature Identification of species • colonial morphology (growth rate, surface texture, and any pigmentation) • microscopic morphology (macroconidia, microconidia)
  • 39. • Treatment • Therapy consists of thorough removal of infected and dead epithelial structures • Application of a topical antifungal agent • Keep the area dry • Avoid sharing sources of infection
  • 40. Subcutaneous mycoses • Causative organisms reside in the soil and in decaying or live vegetation • Almost always acquired through traumatic lacerations or puncture wounds • Grow in subcutaneous tissues, spread via lymphatics. • May reach distant organs • Common among those who work with soil and vegetation. • Commoner in tropics and subtropics
  • 41. • Sporothricosis- Sporothrix schenckii • Chromomycosis - Phialophora -Cladosporium • Mycetoma - Madurella grisea, Actinomadura madura
  • 42. Mycetoma • Common in Africa and South America • Chronic destructive disease affecting skin, underlying tissue and sometimes adjacent bone • Caused by various fungi including Madurella spp., Scedosporium spp., • Infection results from traumatic implantation of spores into the skin, e.g. thorns, splinters
  • 44. • Diagnosis: • Specimen: scrapings or biopsy from lesions • Microscopy: scrapings in 10% potassium hydroxide (dark, round fungus cells = sclerotic bodies diagnostic • Culture in Saboraud Dextrose Agar. • Treatment: surgical excision with wide margins for small lesions, chemotherapy with flucytosine or itraconazole for larger lesions
  • 45. Endemic mycoses • All caused by dimorphic fungi • 4 diseases • Histoplasmosis • Blastomycosis • Cocidioidomycosis • Paracoccidioidomycosis • Pathogenesis similar in all- transmitted by inhalation of spores, result in chronic granulomatous disease in the lungs, resemble TB
  • 46. Histoplasmosis • Aetiology- Histoplasma capsulatum- a facultative intracellular parasite • Two varieties • H. capsulatum var. capsulatum is the common histoplasmosis • H. capsulatum var. duboisii is the African type. • Distribution -World wide • Endemic in the Mississippi-Ohio River Valley in the U.S.A. • Also Africa, Australia and parts of East
  • 47. Histoplasmosis • Transmitted by inhaling dust from soil that contains bird droppings. • The severity varies widely, with the lungs the most common site of infection. • Clinical manifestations: • Most cases are inapparent, subclinical or benign. • Others have chronic progressive lung disease, chronic cutaneous or systemic disease or an acute fulminating fatal systemic disease. • All stages of this disease may mimic tuberculosis.
  • 48. Histoplasmosis • Laboratory diagnosis: • Specimen: Skin scrapings, sputum , bronchial washings, CSF, pleural fluid, blood, bone marrow and tissue biopsies • Microscopy: • Skin scrapings- 10% KOH mounts; • Tissue sections should be stained using PAS digest, Grocott's methenamine silver (GMS) or Gram stain.
  • 49. Histoplasmosis • Culture: • Slow growing- up to 4 weeks • Culture on selective media eg Sabouraud's dextrose agar • Cultures of H. capsulatum represent a severe biohazard • Serology: • Immunodiffusion and/or complement fixation tests • Conversion of the mould form to the yeast phase • Treatment -Itraconazole -Amphotericin B
  • 50. Opportunistic mycoses • Opportunistic: These organisms generally have a low potential for virulence but can produce severe disease involving a variety of body tissues. • Usually affect the immunocompromised but are rare in normal individual • Organ transplantation, post chemotherapy for cancer, immunodeficiency due to AIDS and congenital immunodeficiency states
  • 51. • Cryptococcosis: Cryptococcus neoformans • Candidiasis- Candida albicans • Aspergillosis- Aspergillus species • Zygomycosis- Rhizopus species
  • 52. Candidosis • This is referred to infections caused by yeasts belonging to the ascomycetous genus Candida . • More than 200 spp exist , 90-95% of boodstream infections are caused by four spps , C. albicans , C. glabrata, C. parapsilosis , and C. tropicalis . The remaining are C. dubliniensis , C. gulliermondii , C. krusei , C. africana , C. famata , C.rugosa , C.lusitaniae , C.incospicua , C. novegensis etc . • C.albicans remains the predominant cause of both superficial and invasive forms of candidosis . • C. glabrata incidence is rising • Candida is part of normal flora of oral cavity , gut , airways , vagina and moist areas of the body .
  • 53. Candidosis • Infections or colorizations depend on: • Fungal load , formation of hyphae , presence of biofilms , invasions and elucidations of immune response . • Candida may cause - Superficial infections which include : • Vulvo-vaginal candidiasis • Oral candidosis • Predisposing factors are : • Altered oral flora , poor oral hygiene ,impaired local defence mechanisms and impaired systemic defence mechanisms .
  • 54. Candidosis • Skin and Nail infections • Sepsis and disseminated diseases • Candidemia is almost seen in patients with risk factors like : • GI surgery , Immunosupprssion , malignancy ( Heamatological etc) • Disseminations to other organs causing – Arthritis , Meningitis , Osteomyelitis , Endocarditis and Retinitis .
  • 55. Candidemia • Most common incidence • Mortality – 40% • Candida albicans is the most common • Other species increasing incidence- C. glabrata, C. krusei , C. parapsilosis etc. • Dissemination to other organs: • Arthritis • Osteomyelitis • Endocarditis • Meningitis , Renal tracts , eyes…
  • 56. Candidaemia • Early treatment of Candidaemia is critical to good outcome • Rx < 12hrs – Mortality 11.1% • Rx- 12-24hrs – Mortality 15.4% • Rx 24-48hrs – Mortality 36.5% • Rx > 72hrs – Mortality 41.4% • Roosen Mayo Clinic Proc. 2000; 75: 562-7
  • 57. Candidaemia • Anidulafungin-200/100mg • Caspofungin – 70/50mg • Micafungin- 100mg • Ambisome- 3mg/kg • Voroconazole 6/3mg/kg • Fluconazole-400-800mg
  • 58. Cryptococcosis • Cryptococcus neoformans, found worldwide • Especially found in soil containing bird (esp. pigeons) droppings • Characteristic thick capsule that surrounds budding yeast cell –seen using Indian Ink • Most common form is mild subclinical lung infection • In the immunocompromised often disseminates to the brain • Cryptococcal meningitis- commoner in AIDS patients, often fatal
  • 59. Cryptococcosis–Clinicalpresentation • Cryptococcus • Studies show that from 10 % to 30 % of AIDS patients have cryptococcal meningitis and they will require maintenance therapy with fluconazole for the remainder of their life. Fluconazole penetrates the CSF • Mortality: Without treatment 100% • With treatment 20% • Relapse: • Non-AIDS 15-20% • AIDS patients 50% ,With relapse there is 60% mortality.
  • 60. Aspergillosis • Several species of genus Aspergillus, mostly Aspergillus fumigatus • Worldwide distribution, ubiquitous • Filamentous moluds, produce large numbers of conidiospores. • Reside in soil, decomposing organic matter and dust • Associated outbreaks with construction work • Disease presentation depends on immunologic status of patients.
  • 61. Aspergillosis • Acute Aspergillus infections • Most severe and often fatal form of aspergillosis is acute invasive infection of the lung. May disseminate to the brain etc • Less severe form gives rise to a fungus ball (aspergilloma) , a mass of hyphal tissue that forms in lung cavities derived from prior disease
  • 62. Aspergillosis • Allergic Broncho-pulmonary Aspergillosis ( ABPA)- Uncontrolled Asthma , wheezing , fever , malaise , Productive coughs , mucus plugs. • Severe Asthma with fungal sensitization (SAFS). • Chronic Pulmonary Aspergillosis . • Invasive Aspergillosis
  • 63. Aspergillosis-Interactionsof Aspergilluswiththehost Immune dysfunction Frequency of aspergillosis Immune hyperactivity Frequency of aspergillosis Acute IA Subacute IA Otitis externa Onychomycosis Aspergillus keratitis Aspergillus bronchitis Chronic pulmonary ABPA Severe asthma with fungal sensitisation Allergic sinusitis . After Casadevall & Pirofski, Infect Immun 1999;67:3703 Lung/tissue damage
  • 64. Unusual Pathogens • • Penicillium marneffei • Dimorphic, • Produces a red pigment and reproduces by fission. • Requires amphotericin B therapy and oral itraconazole maintenance. • Pneumocystis jirovecii • Formerly thought to be a protozoan. Presently believed to be a fungus.
  • 65. Diagnosis of fungal infections • Specimens: Systemic -Blood culture, Pneumonia- Bronchoscopy washings or brushings or bronchial biopsy, sputum, Meningitis: CSF tissue biopsies, skin scrapings , nail clippings • Microscopy – direct staining of fungi in sections can distinguish between yeasts and molds • Identification by the morphology of conidia structures • India ink- demonstrates capsule of Cryptococcus
  • 66. Culture • Standard media –Saborauds dextrose agar (SDA), potato dextrose agar, (PDA), low PH 5.0 • Plain or with antibiotics • Culture at 370C (Body temperature) and 250C (room temperature) Serology • Most serological tests for fungi measure antibody. • Newer tests to measure antigen are available e.g. Cryptococcal, Histoplasma and Aspergillus antigen
  • 67. • Molecular diagnosis- PCR not used on a routine basis on samples • Skin testing for a delayed hypersensitivity response • useful for epidemiologic purposes • determine cellular defense mechanisms • but often not for diagnosis. • Germ tube test- for Candida albicans • Carbohydrate assimilation tests
  • 68. Control • Good hygiene. • Chemotherapy: • Topical powders and creams • most contain azole derivatives (miconazole, clotrimazole, ketoconazole) • useful against superficial dermatophytes. • Systemic infections are generally treated by Amphotericin B , 5- Flourocytosine, Azoles- miconazole, Fluconazole or ketoconazole, Echinocandins. • No vaccines are currently available.
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