Fungal Infections

There are 100,000 known fungi and only few infect humans mostly opportunistically. Only few are involved in human diseases because most fungi are destroyed by cell-mediated immune responses however, humoral immunity plays little or no role. 

Predisposing factors for fungal infections include: 

- Corticosteroid administration, acquired or congenital immunodeficiency states, defects in neutrophilic and macrophage functions 

-  Fungal infections are divided into superficial and deep fungal infections (mycosis). Here are few examples of systemic fungal infections

1. Candidiasis (Moniliasis)

Normally found in mouth, skin and gastrointestinal tracts. It is the most common fugal infection mostly caused by (C. albicans). It affects locally the skin, nail and mucous membranes and it  grows best in warm, moist surface and cause vaginitis, diaper rash & oral trush. Systemic candidiasis widespread in persons with depressed immune responses including lymphohemopiotic malignancy, immunosuppressive therapies and broad-spectrum antibiotic usage as well as patients with dialysis, cardiac surgery, IV drug abusers. 

 Pathogenesis: 

Candida has molecules on its surface that mediates its adherence to tissues including

1)  A homologue to human CR3 integrin 

2)  A lectin that binds sugars on epithelial cells 

3)  Mannose containing protein that binds to lectin like molecule on epithelial cells  

Finally, the transition of yeast to hyphal forms is important to fungal virulence because the hyphae appear to spear their way out of cells, which engulf them. 

Morphology: 

•  Oral trush & vaginitis are superficial lesions characterized by white patches (or fluffy membrane) 

•  Cutaneous eczematous lesion: Seen in moist area such as between fingers, & toes and in inguinal areas, inflammare folds and ano-genital regions. These lesions may contain acute and chronic inflammations with micro abscesses but in their chronic states granulomatous inflammations may develop.

•  Invasive candidiasis: seen in Immunosuppression.  Many organs may be involved for examples include kidney with micro  abscesses in 90%, and right side candidal endocarditis. The brain, liver subcutis etc may be involved with micro abscesses.

2. Cryptococcosis 

Cryptococcos neoformans is encapsulated yeast. It causes meningoencephalitis in normal individuals but more frequently in patients with AIDS, leukemias, lymphomas, SLE, Hodgkin’s lymphomas and transplant recipients and those on steroid therapy. 

Pathogenesis: 

- Found in soil and droppings of birds (peogons): Three factors associated with virulence 

1)  Capsular polysaccharides 

2)  Resistant to killing by alveolar macrophages 

3)  Production of phenol oxidase, which consumes host epinephrine oxidase system.

This enzyme consumes host epinephrine's in the synthesis of fungal melanin thus, preventing the fungus from epinephrine oxidase system C. neoformans affect brain because of CSF lacks the alternative pathway complement components that binds to carbohydrate capsule and facilitates phagocytosis and killing by Polymorphonuclear leukocytes. 

 Morphology:

Lung is the primary site of localization with minor or asymptomatic presentation; here solitary granulomatous lesions may appear.

The major pathologic changes are in the CNS involving  meninges, cortical grey matter and basal ganglia. The tissue response to C. neoformans is extremely variable. In immunosuppressed patients, the organisms may evoke no inflammatory reactions so; gelatinous masses of fungi grow in the meninges or in small cysts within the grey matter (soap bubble lesion)

3. Aspergillosis 

Aspergillus is a ubiquitous mold that causes allergies in otherwise healthy persons and serious sinusitis, pneumonia and fungemia in neutropenic persons. Aspargillus form fruiting bodies.

Pathogenesis: 

Aspargillus species have three toxins: 

-  Aflatoxin: Aspargillus species may grow on surfaces of peanuts and may be a major cause of cancer in Africa.

-  Resrictocin and mitogilin: They inhibit protein synthesis by degrading MRNA 

-  Mitogilin:  It also induce IgE production so may be associated with allergic Alveolitis by inducing type III & IV reactions, allergic bronchopulmonary aspargillosis which often-in asthmatic that eventually leads to COLD.

Morphology:

Colonizing Aspargilosis (Aspargiloma): It implies growth of fungus in pulmonary cavity with minimal or no invasion of the tissues. The cavity usually result from the pre-existing tuberculosis, bronchiactasis, old infracts and abscesses, Invasive Aspargilosis  It is an opportunistic infection confined to immunosuppressed and debilitated hosts. Common sites of disseminations include the heart valves, brain and kidneys.

The Aspargilus Species have a tendency to invade blood vessels and thus, areas of hemorrhages and infarction are usually superimposed on necrotizing inflammatory reactions .

4. Histoplasmosis 

-  The causative organism H. capsulatum  is recovered from dust particles of soil, bird or bat droppings contain small spores (micro conidia).

-   Histoplasmosis and Coccidiomycosis resemble pulmonary tuberculosis and  both are caused by fungi that are thermally dimorphic (hyphae and yeast forms)

-  Natural history of histoplasmosis  include. 

1) Self limited with subsequent coin lesions on X-ray films

2) Chronic progressive secondary lung disease in lung apices

3) Localized lesion in extra pulmonary site including mediastinum, adrenals, liver and meninges 

4) Widely disseminated disease especially in immunocompromised individuals  

Histopasma yeasts are phagocytosed by unstamulated macrophages and multiply in phagosomes and lyse host cells. Histopasma infection is controlled by T helper cells.

Subsequently secreted interferon gamma activates macrophages to kill intracellular yeasts. Tumour necrotizing factor alpha (TNF-α) is also secreted to kill histoplasma. Lacking cellular immunity, patients with AIDS are susceptible to disseminated disease.

Morphology:

 Granulomatous inflammation with areas of solidifications that may liquefy subsequently. The lesion may undergo fibrosis spontaneously or with drug therapy in the lungs. Fulminant disseminated histoplasmosis is seen in immunocompromized individuals where immune granulomas are not formed and mononuclear phagocytes are stuffed with numerous fungi throughout the body.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.