Other techniques

• Antibody tests: of limited usefulness
  
  • e.g. Aspergillus precipitins
• Antigen tests
  
  • Cryptococcus neoformans (cryptococcal antigen test done on serum or CSF, not on urine)
  • Galactomannan antigen assay: screening for
    possible Aspergillus infection
• Molecular techniques e.g. PCR
  
  

Diseases caused by fungi

• Poisoning etc, Allergy, Infections
  
  

Mycotoxins

• Poisonous substances produced by certain fungi
  
  • Poisoning: acute or chronic
  • Aflatoxins: liver cancer
    
    

Fungal infections: clinical classifications

• Superficial
• Subcutaneous
• Systemic

Vascular Infections

1. Candidemia
   

• Increasing in recent years, because of use of intravascular devices, better detection methods. Increasingly broader spectrum antibiotics
  

2. Cardiac
   

• Pericardium, myocardium, endocardium
  
  • Purulent pericarditis
  • Myocarditis (non - specific ECG changes - SVT, QRS changes mimicking infarction, pronounced T-wave changes)
    

3. Endocarditis
   

• Predisposing factors :Underlying heart disease, IVDA, cancer chemotherapy, prosthetic valves, prolonged use of intravenous catheters - right - sided endocarditis, superimposed on bacterial endocarditis

Urinary Tract

• Candiduria is common
• Antibiotic use, indwelling catheters related
• Most patients with candiduria and no predisposing factors for systemic candidiasis have good outcome without specific antifungal treatment.
• Upper tract involvement - kidneys
  
  • Haematogenous or ascending infection
  • Fungus balls, perinephric abscess, papillary necrosis
  • Liver, spleen, gall-bladder, Peritonitis, Eye, Bone and Joint, CNS, Disseminated

Candidosis (superficial)

• Mouth/throat; vagina
• Predisposing factors: infancy, old age, antibiotics, pregnancy
• Nail infections: wet hands
• Severe infections in AIDS
  
  • may be presenting symptom
• Oral candidosis (thrush), genital thrush
• Keratitis, corneal ulcers
• Treatment
  
  • Anti-fungal eye drop
  • Oral azole

Trichophyton rubrum

• Human Skin and Nail disease, Less commonly, hair disease
• Human to human. Spread through wet floor and direct contact
• World-wide distribution.Very common in Singapore

Trichophyton mentagraphytes var interdigitale

• Skin diseases of foot (Hong Kong Foot) and groin.
• Main source of infection is human
• Spread on wet surfaces and human to human
  contact
• World wide. Common in Singapore

M furfur
M pacydermatis
M sympodialis
M slooffiae
M obtusa
M restricta
M globosa
M dermatis
M japonica
M yamatoensis
M nana
M caprae
M equina
M cuniculi

Diseases associated with Malassezia

1. Tinea (Pityriasis) versicolor

• Commensal in healthy individuals
• Yeast may be transmitted from human to human
• Causes diseases in presence of predisposing factors
• Diagnosis made by Direct microscopy in 30% KOH with Parker's Ink (For staining)
• M. furfur - “Spaghetti & meat ball”
  
• i.e. yeast and mycelial form on skin
  
• Culture: yeast form only

2. Seborhhoeic dermatitis/Dandruff
   
3. Malassezia folliculitis/Pityrosporum
   
4. Peritonitis and septicemia in neonate
   

Other clinical symptoms

1. Tinea nigra (patch of black fungus)

• Generally affects skin of palms, occ soles
• Phaeoannellomyces werneckii
• Asymptomatic brown/black macules; non scaly
• Microscopy: brown branched septet hyphae & elongated budding cells
• Rx: topical azoles
  
  

2. Black piedra

• Confined to hair shafts
• Piedraia hortae
• Tropical regions
• Firmly adherent black hard
  nodules on hairs of scalp; beard, pubic area
• As fungus grows into hair shaft, it may fracture easily

• Subcuticular fungal growth > cuticle rupture

  
  
  • Fungus grows outside cuticle, completely surrounding hair shaft
    
    

  

  
  
  

Other clinical symptoms cont'

3. White piedra

• Confined to hair shafts
  
  • Scalp: Trichosporon ovoides
  • Crural region: T inkin, asahii, mucoides
• Soft white or light brown nodules
  
  • Transparent, easily detachable
• Commoner on beard, pubic region of scalp
  
  • Some cases may be sexually transmitted
• Grows within and outside hair shaft -> may break off easily
• Synergistic role of Brevibacterium in the infection?
• Histo: nodules in the form of a sheath which may extend around hair shaft
• Rx: shaving/cutting hair
  

4. Otomycocis

• Chronic inflamm condition of the external auditory canal caused by fungal infection
• Aspergillusniger, fumigatus
  
  • Light growth from swabs taken from ear is of little significance
  • Presenceoflargemasses
• In immunocompromised, may result in extensive erosions + necrosis
  
  • May spread to middle ear, mastoids
    

5. Keratomycosis (Mycotic keratitis)

• Posttraumatic / postsurgical Contact lens related corneal inf.
• Etio: Saprophytic fungi
  
  • Aspergillus, Fusarium, Alternaria, Candida
• Clinical findings: Corneal ulcer

3. Nattrasia Mangifera (Scytalidium dimidiatum )

• Able to invade healthy nail and skin
• Increasing importance. Not treatable with
  current drugs
• Direct microscopy: Quite similar to Dermatophytes.
• Culture: Fast growing,black variety or pale variety

4. Moulds

• Refered to as Non-Dermatophyte Moulds)
• Usually causes nail infection
• Fusarium, Aspergillus, Onychocola etc.

5. Candida

Diseases :

• Oral (Mouth and tongue)
  
• Genital (Vagina, Glans penis)
• Intertrigo (Axillae,groin, Toe-webs, Finger webs)
  
• Finger Nails
• Candida Paronychia and Onychomycosis
  
  • Several fingers affected
  • Nail fold red swollen, loss of cuticle, detachment of the nail fold from dorsal surface of nail plate
    
  • Thick white pus may discharge
  • Tender
    
    
    

Definition

• An acute or chronic fungal infection caused by sporothrix schenckii
• Both temperate/tropical
• Not contagious (No human to human infection)
• Systemic sporotrichosis is rare, portal of entry – lung
• Histo: Granulomatous rxn, asteroid bodies
  
  

General and Clinical Features

• Chronic inf
• In divers
• Polypoid masses at nasal mucosa, conjunctiva, genitalia and rectum

• Seropurulent discharge from nasal lesions

  
  
  

  

Definition

• Fungi in soil, plants, rotting vegetation etc
• Enter subcutaneous tissues during injury
• Common in tropical climates
• Causative agents
  
  • Fungi (Eumycetoma)
  • Actinomyces (Actinomycetoma)
    

Clinical Features

• Usu foot/lower leg
• Firm, painless nodule > appearance of papules/pastules > break down to form draining sinuses containing sulphur granules
• Purulent pus from multiple tracts/sinuses
• No significant pain
• Dissemination: muscles and bones
• Extension to deeper tissues eg. Periositits, osteomyelitis

• Advanced cases > destruction of bone with gross deformity

  
  
  

  

Causative agent: Rhinosporidium seeberi

• Natural reservoir: fish, aquatic insects.
• Asc with swimming/working in stagnant water
• Human to human spread unknown
  
  

Diagnosis

• Spherules filled with endospores (in tissue)
• Has not been cultured in vitro on artificial media

• KOH preparation on sputum
• Lung biopsy
• Aspergillus precipitins (antibody test)
• Serial measurement of circulating galactomannan

Aspergillosis

• Keratitis, corneal ulcers - anti-fungal eyedrops
• Aspergillus species: several different types of disease:
  
  • Allergic forms
    
    • Fungus ball (aspergilloma) in lung (forms in cavity) - precipitin test positive

• Immunocompromised patients: invasive aspergillosis - lung. Hard to diagnose, empirical amphotericin often used
• Disseminated aspergillosis: brain abscesses
  

• Allergic bronchopulmonary aspergillosis
  
  • Hypersensitivity response to Aspergillus- asthma-like symptoms – cough, wheezing, shortness of breath
• Invasive aspergillosis
  
  • Most commonly seen in the lungs, but can disseminate to other tissues including the central nervous system, sinuses, bone, heart, kidney, eye, blood and skin
• Risk factors for invasive aspergillosis include patients on steroids, chemotherapy treatment resulting in severe neutropenia, stem cell and solid organ transplantation, AIDS

Transmission

• By airborne spores
• Lung, sinuses, skin portals, eye, CNS
  
  

Factors predisposing to infections

• Immune suppression e.g. HIV, leukaemia, transplantation
• Construction activity
• Diseased lung e.g. old tuberculosis

Clinical findings

1. Primary Infection

• Asymptomatic in most
• Fever, chest pain, cough, weight loss
• Nodular lesions in lungs
  

2. Secondary (Disseminated) Infection

• Chronic / fulminant
• Infection of lungs, meninges, bones and skin

Features

• A primary respiratory fungal infection Coccidioides immitis
• Endemic is desert areas of South west USA Mexico, Central and South America.
• Soil inhabitant, acquired by inhalation of fungus laden dust
• Lung infections ,usually self healing
• Primary infection of skin is rare, firm painless
  indurated nodules after trauma
• Clinical presentation simulates influenza or pul TB

Diagnosis

• Samples: Sputum, tissue
  

1. Direct examination

• KOH, H&E spherule
  

2. Culture

• SDA: Mould colonies at 25 °C Spherule production in vitro by incubation in an enriched medium at 40°C, 20% CO2

Features

• Highly infectious
• Mainly respiratory
• Histoplasma capsulate (Var capsulate, Var duboisii)
• Intracellular, parasites reticulenodothelial
  system and involving the spleen, liver, CNS

• Rarely becomes chronic, progressive and fatal

  
  

• Natural reservoir: soil, bat and avian habitats

• Location: May be prevalent all over the world, but the incidence varies widely (most endemic in Ohio, Mississipi, Kentucky)

Human Infection & Disease

• Transmitted by inhalation, not from humans to humans or animal to human.
  
  

1. Acute pulmonary

• Uncommon
• Cough fever. CXR shows diffuse mottling or local infiltration
  
  

2. Acute Disseminated

• Lung consolidation, hepatosplenomegaly, fever,
  anorexia, lymphadenopathy.
• Indurated Granulomatous ulcers of the mouth, nose, larynx
• In AIDs, multiple small skin nodules.
  
  

3. Chronic pulmonary

• Closely resembles miliary TB
  
  

4. Chronic disseminated

• Appears months to years after leaving endemic area
• Commonest presentation- oral ulceration or addison’s disease sec to adrenal infiltration
  
  

5. Primary cutaneous

• Very rare, occurs on inoculation
• Nodule or indurated ulcer with local lymphadenopathy
  

Blastomycosis

• Chronic granulomatous and supprative mycosis
• Blastomyces dermatitis
• Affects lung primarily, but can be disseminated
• Rarely isolated in env, natural substrate may be wood debris close to rivers
• No human to human spread
• Inhalational
• 3 clinical forms:
  
  

1. Primary cutaneous

• Very rare, post trauma with fungi introduction
• 1-2/52 post inoculation, erythematous indurated area with chancre appears
• Assoc lymphangitis and lymphadenopathy
• Spontaneous recovery
  
  

2. Pulmonary

• Similar to primary TB
• Assoc with EN
  
  

3. Disseminated

• Pulmonary, skin, bones, CNS
• Mucous membrane rarely involved
• Skin lesion
  
  • Symmetrical, trunk
  • Initially papule/nodule which may ulcerate and scar
  • Eventually, serpenginous, warty with violaceous margin studded with miliary abscess containing organisms
• Treatment: Amphotercin B, oral itraconazole

Paracoccidioidomycosis Clinical Findings

• Asymptomatic Inf
• Latent form (duration variable)
• Symptomatic Inf:
  
  • Noduler lesions in lungs
  • Dissemination to other organs (rare)

Paracoccidioidomycosis Diagnosis

• Samples: Sputum, tissue

1. Direct microscopy

   
   
   • KOH, H&E
   • Multiply budding yeasts; the buds are attached to the parent cell by a narrow base
     
     

2. Culture:

   
   
   • Mould at 25°C
   • Conversion to yeast on an enriched medium at 37°C

Systemic candidosis

• Many predisposing factors e.g.
  
  • Antibiotics
  • Immunocompromise
  • Surgery
  • Intravascular line
  • Preterm neonates
  • Retina, hepatosplenic

Cryptococcosis

• Lung: Asymptomatic,Cryptoccoma, Pulmonary infection
• Brain: Memingitiswith cranial nerve damages - Skin:Granuloma
• Systemic: Liver, kidney etc
  
  
  

Diagnosis

• Cryptococcus neoformans (MEN)
  
  • Gelatinous capsules of yeast cell
  • Indian-ink examination of CSF
  • Mucicarmine stain in tissue section
  • Culture:Yeast at both 26 and 37C, corn meal agar
    
    

Treatment

• For cryptococcus neoformans - Amphotericin + flucytosine. Then maintain on fluconazole

• Disease: Papules and abscess on skin
• Disseminated infection in ill patients
• Common disease in HIV patients.
• Fungus of Bamboo rats
• Endemnic in South west China, Vietnam , Thailand

Penicilliosis

• Penicillum marneffei, causes disseminate mycosis in both health and immunocompromised
• Originated from soil, confined to SE Asia
• Presents with Respiratory syms and
  hepatosplenomegaly
• Cough, malaise, generalized lymphadenopathy, fever, and weight loss, along with the skin lesions, are presenting symptoms.
• Other commonly affected organs include the lungs (infiltrates or cavities), lymph nodes, liver, spleen, and bone.
• 50% cases skin lesions Molloscum like lesions or papules/ulcers
• Fatal if untreated
• Treatment: IV amphotercin B or itraconazole 200-400mg/day
  
  

Clinical Manifestations

• The diagnosis is established by culture and skin biopsy

Diagnosis

• Tissue smear: Safety-pin shaped yeast
• Culture: Dimorphic
• Characteristic bright red pigment in culture at 26C