Systemic

• Blastomycosis


  • Caused by dimorphic fungi
  • Infections may involve lymph node, bone, subcutaneous tissue, meninges, skin
  • Symptomatic infections may present signs of mild or more severe but self-limited disease
  • Infection must be with positive supportive evidence from cultural or immunologic findings
  • Patients with disseminated or progressive infection have severe symptoms
  • Spread of initial disease, often from a pulmonary locus to several distant organs
  • Some cases show little signs and symptoms for long periods but showing exacerbation later
  • Immunocompromised patients present disseminated infection (HIV-AIDS, on corticosteroid therapy)

  
• Dimorphic fungi causing blastomycosis

  • Blastomyces dermatitidis
  • Coccidioides immitis
  • Histoplasma capsulatum
  • Paracoccidioides brasiliensis
  • Penicillium marneffei
  • Sporothrix schenckii

  
• Exact ecologic niche in nature not been determined
• Patients with blastomycosis


  • Often have history of exposure to soil or wood
  • Several outbreaks have been reported related to exposure to soil and wood
  • More common in men associated with outdoors occupation
  • Also seen in dogs

  
• • Blastomycosis is commonly found in North America and extends southward from Canada to the Mississippi, Ohio and Missouri River Valleys, Mexico and Central America
  • Some isolated cases reported in Africa
  • Large numbers of cases occur in the Mississippi, Ohio and Missouri River Valley Regions

  
• Blastomycosis


  • Begins as respiratory infection through inhalation of the conidia or hyphal fragments of the organism
  • Infection may spread and involve secondary sites of infection in the lungs, long bones, soft tissue and skin

  
• Blastomyces dermatitidis growth


  • Requires incubation for 5 days to 4 weeks or longer at 25°C before growth can be detected, however can be detected in as short as 2 to 3 days
  • On enriched culture media, mold form develops initially as a glabrous or waxy-appearing colony and is off-white to white
  • With age, aerial hyphae often turn gray to brown
  • The waxy, yeast like appearance is typified on media enriched with blood
  • Tufts of hyphae often project upward from the colonies -"PRICKLY STATE"
  • Some isolates appear fluffy on primary recovery and remains so throughout the incubation period
  • On BAP at 37°C, colonies are waxy, wrinkled and yeast like
  • Mold to yeast conversion usually requires 4 – 5 days

  
• Microscopic features of Blastomyces dermatitidis

  • Direct microscopy of clinical specimen: Large, spherical, thick-walled yeast cells 8 – 15 µm in diameter usually with a single bud connected to a parent cell by a broad base
  • Microscopically, hyphae of mold form are septate and delicate measuring approximately 2 µm in diameter
  • Rope-like strands of hyphae seen (common to all dimorphic fungi)
  • Single, circular to pyriform conidia produced on short conidiophores resembling lollipops
  • Some strains may produce yeast cells as small as 2 – 5 µm called microforms
  • Resembles Cryptococcus neoformans var neoformans or Histoplasma capsulatum
  • Microforms maybe present but a thorough search should reveal more typical yeast forms

  
• There is no vaccine to prevent blastomycosis

  
• Avoiding blastomycosis


  • May not be possible to completely avoid being exposed to the fungus that causes blastomycosis in areas where it is common in the environment
  • People who have weakened immune systems may want to consider avoiding activities that involve disrupting soil in these areas

  
• Coccidioidomycosis


  • Acquired through inhalation of the infective arthroconidia
  • 60% are asymptomatic and have self-limited respiratory tract infections
  • Infection may become disseminated with extension to visceral organs, meninges, bone, skin, lymph nodes and subcutaneous tissues
  • Fewer than 1% ever become seriously ill
  • Dissemination does occur, most frequently on individuals of dark-skinned races
  • Pregnancy predispose women to disseminated infection
  • Occur in epidemic proportions – 1992 in Northern California, 4000 cases seen

  
• Endemic mycoses be considered for travel history

  
• Coccidioides immitis cultures


  • Cultures are biohazard to laboratory workers
  • Strict safety precautions be followed
  • Mature colonies may appear within 2- 5 days of incubation
  • May be present on most media including those used in bacteriology
  • Laboratory workers are cautioned not to open cultures of fluffy white molds unless they are placed inside BSC
  • Colonies appear as a delicate, cobweb-like growth after 3 – 21 days incubation
  • Some portions of growth show aerial hyphae, while others, hyphae adhere to agar surface
  • Most isolates appear as fluffy white, however colonies of varying colors have been reported, ranging from pink to yellow to purple and black
  • Some colonies exhibit a greenish discoloration on blood agar and others appear as yeast-like, smooth, wrinkled and tan
• Microscopic features of Coccidioides immitis

  • Microscopically, some C. immitis cultures show small, septate hyphae than often exhibit right-angle branches and racquet forms
  • With age, hyphae form arthroconidia that are characteristically rectangular to barrel-shaped
  • Arthroconidia are larger than the hyphae from which they are produced
  • Stain darkly with lactophenol cotton or aniline blue

  
• Direct microscopic examination of Coccidioides immitis

  • Appear as a non budding thick-walled spherule, 20 – 200 µm in diameter
  • Containing either granular material or numerous small, 2 – 5 µm in diameter, non budding endospores
  • Endospores are freed by rupture of the spherule wall
  • Ghost spherules
  • When spherules are present, the endospores produce multiple hyphal strands

  
• If a culture is suspected of being C. immitis, it should be sealed with tape to prevent chances of laboratory acquired infection

  
• C. immitis is considered as the most infectious among the fungi
• Safety precautions for handling Coccidioides immitis cultures

  • If culture dishes are used, they should be handled in Level 3 BSC
  • Use of cotton plug test tubes is discouraged, screw-capped tubes should be used and must be handled in Level 3 BSC
  • All microscopic preparations for examination should be performed in Level 3 BSC
  • Cultures should be autoclaved as soon as final identification is made
• Currently, there is no vaccine to prevent Valley fever, but scientists have been trying to make one since the 1960s
• Avoiding exposure to Coccidioides immitis

  • Try to avoid areas with a lot of dust like construction or excavation sites. If you can't avoid these areas, wear an N95 respirator while you're there.
  • Stay inside during dust storms and close your windows.
  • Avoid activities that involve close contact to dirt or dust, including yard work, gardening, and digging.
  • Use air filtration measures indoors.
  • Clean skin injuries well with soap and water to reduce the chances of developing a skin infection, especially if the wound was exposed to dirt or dust.
  • Take preventive antifungal medication if your healthcare provider says you need it.
• Activities associated with Coccidioides immitis exposure


  • Cleaning out an old chicken coop or barn that had been undisturbed for long periods
  • Individuals who work in clean areas that have served as roosting places for starlings and similar birds
  • Spelunkers (cave explorers) exposed when it is aerosolized from bat guano in caves
• An estimated 500,000 people infected with Coccidioides immitis
• History of exposure often is impossible to document
• Histoplasmosis (Darling's Disease)


  • Common systemic fungal infection in the Midwest and South in the United States including areas along the Mississippi River, the Ohio Valley and the Appalachian Mountains
  • Commonly produces a chronic granulomatous infection
  • Primarily begins in the lung and eventually invades the Reticuloendothelial System (RES)
  • 95% of cases are asymptomatic and self-limited, although chronic pulmonary infections occur
  • Can be disseminated throughout the RES
  • Primary site of dissemination are lymph nodes, liver, spleen and bone marrow
  • Infections of the kidneys and meninges are also possible
  • Resolution of disseminated infection is the rule in immunocompetent hosts
  • Progressive disease is more common in immunocompromised patients (AIDS)

  
• Microscopic features of Histoplasma capsulatum

  • Direct microscopic examination of respiratory tract specimens and other similar specimens often fails to reveal the pathogen
  • May be detected when examining Wright or Giemsa stained specimens of bone marrow and in rare cases, peripheral blood
  • Found intracellularly in mononuclear cells as small, round to oval yeast cells, 2 – 5 µm in diameter

  
• Culturing Histoplasma capsulatum


  • Easily cultured from clinical specimens however, may be outgrown by rapidly growing bacteria and molds.
  • Useful procedure in the recovery of B. dematitidis, C. immitis and H. capsulatum from contaminated specimens like sputum is the use of yeast extract/phosphate medium and a drop of concentrated ammonium hydroxide placed on one side of the inoculated plate of medium
  • Recommended to process specimens at once as soon as received to ensure optimum recovery of H. capsulatum and other dimorphic fungi
  • Considered as sloe growing mold at 25°C – 30 °C
  • Requires 2 – 4 weeks or more for colonies to appear
  • Organism may be recovered in 5 days or less if many yeast cells are present in the sample
  • Blood culture processed with Isolator recovered in 8 days
  • White fluffy mold that turns brown to buff with age
  • Some isolates ranging from gray to red have been reported
  • May also produce wrinkled, moist, heaped, yeast like colonies that are soft and cream colored, tan or pink
  • Tufts of hyphae often project upward from the colonies
• Microscopic features of Histoplasma capsulatum


  • Hyphae are small approximately 2 µm in diameter, often intertwined to form ropelike strands
  • Large (8 – 14 µm in diameter) spherical or pyriform, smooth walled macroconidia are seen in young cultures
  • With age, macroconidia become roughened or tuberculate and provide enough evidence to make a tentative identification
  • Some isolates fail to sporulate despite numerous attempts to induce sporulation

  
• Preventing histoplasmosis


  • Spray contaminated surfaces.
  • Before you dig soil or work in an area that could harbor the fungus that causes histoplasmosis, soak it with water. This can help prevent spores from being released into the air. Spraying chicken coops and barns before cleaning them also can reduce your risk.
• Paracoccidioidomycosis


  • Commonly found in South America with highest prevalence at Brazil, Venezuela and Colombia
  • Has also been seen in many other areas including Mexico, Central America and Africa
  • Occasional imported cases are seen in United States and Europe
  • Unclear mode of transmission but inhalation and trauma to oropharynx are common mode of transmission
  • Commonly produces a chronic granulomatous infection begins as primary pulmonary infection
  • Often asymptomatic and disseminates to produce ulcerative lesions of the mucous membranes
  • Present in nasal and oral mucosa, gingivae and less commonly conjunctivae
  • Lesions are common in the face in association with oral mucous membrane infection
  • Lesions are
• Histoplasmosis prevention


  1. Soak soil with water to prevent spores from being released into the air

  2. Spray chicken coops and barns before cleaning to reduce risk
• Histoplasmosis - Symptoms and causes - Mayo Clinic


  Feb 20, 2020
• Histoplasmosis is commonly found in South America with highest prevalence in Brazil, Venezuela and Colombia
• Histoplasmosis has also been seen in many other areas including Mexico, Central America and Africa
• Occasional imported cases of histoplasmosis are seen in United States and Europe
• Mode of transmission for histoplasmosis

  Inhalation and trauma to oropharynx are common
• Paracoccidioidomycosis


  • Commonly produces a chronic granulomatous infection that begins as primary pulmonary infection
  • Often asymptomatic and disseminates to produce ulcerative lesions of the mucous membranes
• Paracoccidioidomycosis lesions


  • Present in nasal and oral mucosa, gingivae and less commonly conjunctivae
  • Lesions are characteristically ulcerative with a serpiginous (snakelike) active border and a crusted surface
  • Lymph node involvement in the cervical area is common
  • Pulmonary infection is frequently seen and progressive chronic pulmonary infection is found in approximately 50% of cases
  • Dissemination can occur to other anatomic sites – lymphatic system, spleen, intestines, liver, brain, meninges and adrenal glands
• Paracoccidioides brasiliensis microscopic characteristics

  • Large, round or oval multiple budding yeast cells (8 – 40 µm in diameter) usually recognized in sputum, mucosal biopsy specimens and other exudates
  • Characteristic multiply budding yeast forms resemble a "mariner's wheel"
  • Yeast cells surrounding the periphery of the parent cell range from 8 – 15 µm in diameter
  • Some cells may be as small as 2 – 5 µm in diameter but still exhibit multiple buds
• Paracoccidioides brasiliensis colony characteristics

  • Colonies grow very slow (21 – 28 days)
  • Colonies are heaped, wrinkled, moist and yeast-like
  • With age, colonies may become covered with a short aerial mycelium and turn tan to brown
  • Surface of colonies often is heaped with crater formation
• Paracoccidioides brasiliensis microscopic mold form

  • Small hyphae (2 µm in diameter) are seen long with numerous chlamydoconidia
  • Small (3 – 4 µm in diameter) delicate, globose or pyriform conidia may be seen arising from the sides of hyphae or on very short conidiophores
  • Most often cultures reveal only fine septate hyphae and numerous chlamydoconidia