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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.
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.
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.
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.
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
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
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
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.
