Dimorphic Fungi/ Blastomycosis/ Coccidiodomycosis/ Histoplasma

Question 1

Dimorphic fungi
Exist as what in what temperatures?

Answer 1

Exist in nature or lab at 25-30°C as moulds, and as yeast in tissues or if grown at 37°C

Question 2

Are dimorphic fungi pathogens? Explain

Answer 2

Primary pathogens - ability to cause disease in both immunosuppressed & immunocompetent

HIV & other immunosuppression facilitate disease progression, but normal hosts may have
symptoms as well

Question 3

MoT

Answer 3

,. Tendency to disseminate from lungs after inhalation & affect deep organs
SPORE INHALATION

Question 4

When does it manifest?

Answer 4

((May not manifest as clinical disease until patient left endemic region, or may reactivate years later))

Question 5

Blastomycosis

Blastomyces dermatitidis- found where + MoT

Answer 5

In decaying organic matter – inhalation of conidia from soil or leaf litter – outbreaks associated with occupational or recreational soil or lake contact

_ (No person-person transmission. Dogs also very susceptible, but do not transmit to humans)

Question 6

Blastomyces dermatitidis

Morphology / diagnostics

Answer 6

• Tissues & culture at 37°C: spherical non-encapsulated yeast cells
(• Observed with: H/E, Gomori Methenamine Silver or periodic acid-Schiff (PAS) )
• Nature or media at 25°C: mould colonies with hyphae

Question 7

Blastomyces dermatitidis

Clinical manifestations

Answer 7

Causes pulmonary disease or extrapulmonary disseminated disease (mostly skin & bones) ((• Other sites of haematogenous dissemination: prostate, liver, spleen, kidneys & CNS))

Pneumonia
• Most common, confused with community acquired pneumonia (lung infiltrate), tuberculosis
(miliary pattern or cavitation) or lung cancer (mass like lesions)
• Mild flu-like illness or acute pneumonia mimicking bacterial lung infection. Chronic pneumonia (2-
6m) may mimic TBC (persistent cough, fever, wasting, haemoptysis) or lung cancer

Question 8

Blastomyces dermatitidis
Skin manifestations

Answer 8

, 2nd most frequent, from haematogenous spread from lungs (lung symptoms usually absent)
• 2 forms, verrucous (elevated skin lesions with crusting above an abscess) & ulcerative (mimic
pyoderma gangrenosum), usually painless
• Usually on exposed areas (face, neck, hands) & may be confused with squamous cell carcinoma
• Lesions may be progressive & destructive & affect bones as well

Question 9

Blastomyces dermatitidis - diagnosis

Answer 9

Microscopic detection in tissue or other specimen – confirmation with culture both at 25°C & 37°C
• (Sputum, BAL, lung biopsy, CSF, skin scraping or biopsy material: depending on site of infection)
‘Gomori silver staining, Giemsa or PAS staining – identify yeast form
• NO COLONIZATION: If fungus is seen – diagnosis is definite
Serology unreliable, urine antigen assay can be used

Question 10

-Coccidioidomycosis spp
Coccidioides immitis (California) & C. posadasii (outside California)

Causative agent of

Answer 10

-“Valley fever”

Question 11

‘Coccidioidomycosis spp
Found where + MoT

Answer 11

In soil & growth enriched with bat or rodent droppings – inhalation of conidia esp. during
Summer when dusty conditions prevail

Question 12

Coccidioidomycosis spp

Morphology

Answer 12

• Dimorphic – mold in culture: white to grey moist colonies
• Arthroconidia inhaled

Question 13

Coccidioides spp – clinical manifestations

Answer 13

Of the most virulent fungi – inhalation of only few conidia may produce disease
Fever, cough & chest pain, usually self limited – some experience allergic reactions from immune
Complex formation, with erythematous rash or erythema nodes + migratory arthralgias
- “desert rheumatism”: fever, erythema nodosum + migratory arthralgia
- primary disease which usually resolves without Tx & confers strong immunity against reinfexn detected by coccidiosis skin test (like tb skin test)
, Fulminant pneumonia with ARDS & fungemia is mostly seen in immunosuppressed (AIDS)
Chronic pneumonia
• In 5% symptoms persist for >6wks, chronic pneumonia with pulmonary cavitation mimicking TBC

Question 14

‘Coccidioides spp
. Dissemination

Answer 14

‘• In severely immunosuppressed, HIV, haematologic malignancies, transplant recipients, antiTNF
• Usually skin, bones & CNS affected (almost always fatal if not treated)

Question 15

Coccidioides spp:

Diagnosis
Direct examination & culture
Serology

Answer 15

Diagnosis
• Exposure DOES NOT NEED to be prolonged, cases in patients changing planes in California.

Direct examination & culture
• Tissues stained with H/E, Gomori Silver or PAS

Serology
• Several serologic tests or antigen detection used for initial diagnosis & monitoring response to Tx

Question 16

Histoplasma spp /“Histoplasmosis”

Different types

Answer 16

Dimorphic, H. capsulatum variant capsulatum & H.capsulatum var. duboisii
• H. capsulatum var. capsulatum causes pulmonary & disseminated disease in Eastern half of USA
• H. capsulatum var. duboisii predominantly skin & bone lesions in Latin America & Africa

Question 17

-Histoplasmosis
Morphology

Answer 17

• Nature & culture 25°C: mould
• Yeast cells: intracellular in vivo

Question 18

Histoplasmosis
Epidemiology & ecology

Answer 18

• Cases recorded in every continent except Antarctica. Highly endemic regions: Ohio & Mississippi river
• In soil with contaminated with bird or bat droppings
• Outbreaks: exposure to bird roosts, caves & decaying buildings or projects involving excavation
• Aerosolization of microconidia in disturbed soil,
inhalation
• ((Attack rates even 100% in some of these exposures, most asymptomatic & detected only by skin testing ))

Question 19

Histoplasmosis – pathogenesis

Answer 19

(((• Inhalation of aerosolized conidia & hyphae from soil, engulfed by PNFs & macrophages in lungs

• Transition to yeast in body, transferred within macrophages to local lymph nodes & later
hematogenously to distant organs (liver, spleen, bone marrow etc.) )))

• Cellular immunity is essential for restricting growth = takes almost 2 wks to develop

•T-cells, esp. CD4 T-cells = pivotal. Hallmark of tissue response: caseating or non-caseating granulomas, T-cells, IFN-γ & TNF are important in granuloma formation
• Delayed type IV hypersensitivity: develops 3-6wks after exposure
• HIV (+) with CD4<200 are extremely susceptible to disseminated disease

Question 20

Pulmonary Histoplasmosis Acute primary infection
Clinical manifestations

Answer 20

> 90% asymptomatic or flu-like symptoms

Rest: high fever, headache, non-productive cough & chest pain, from 10d to wks, X-ray, patchy pneumonitis with hilar or mediastinal adenopathy – most cases self limited

• A Ghon complex & pulmonary calcifications are common in healed Histoplasmosis (often
accompanied by liver or spleen calcifications)

• In endemic areas, these calcifications are mostly due to Histoplasmosis than Tuberculosis

Question 21

’ - Pulmonary Histoplasmosis
Chronic pulmonary infection
Clinical manifestations

Cavitation

Answer 21

Cavitation: upper lobes, mostly middle aged-men with history of smoking, COPD & emphysema
((• Low-grade fever, cough, weight loss & haemoptysis
• Fibrosis may be extensive & if mediastinum is involved, mediastinal fibrosis.))
• Mediastinal fibrosis, detrimental – constriction of
mediastinal structures, large vessels & heart

Question 22

Histoplasma capsulatum var. capsulatum – clinical manifestations

Disseminated Histoplasmosis – acute, subacute or chronic

Answer 22

Acute disseminated infection
• In severely immunosuppressed, AIDS, haematologic malignancies, transplant recipients, etc.
• Fever, malaise, weight loss, hepatosplenomegaly & pancytopenia, CNS involvement
• If untreated mortality of 100%

Subacute disseminated disease
• More prolonged symptoms, plus deep oropharyngeal ulcers mimicking malignancy
• Focal lesions in various organs, e.g. liver, spleen, CNS, bowel mucosa & endovascular structures

Chronic disseminated disease
• Often mild – deep, painless oropharyngeal ulcers

Question 23

Histoplasmosis – diagnosis & therapy

Answer 23

Culture
• Body fluids or tissues – prolonged incubation, biosafety cabinets required

Microscopy
• Tissue or bone marrow smear, Giemsa, Gomori Silver or PAS stain - cells of H. capsulatum var.
capsulatum are yeast like, usually intracellular & clustered together

Antigen detection
• Serum or urine, for disseminated disease. Monitor response to Tx

Serology
• Not useful for acute disease, may be negative in immunosuppressed