FUNGAL INFECTION

Aspergillosis

Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.

Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.

Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.

Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.

 Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache

Cholecystitis 
 
It is inflammation of the gall bladder. It may be acute or chronic.
In 80-90% of cases, it is associated with gall stones (Calcular cholecystis). 

Causes and pathogenesis:-
Obstruction of cystic or common bile duct- By stones, strictures, pressure from the outside, tumors etc.
Obstruction , chemical irritation of the gall bladder, Secondary bacterial infection, stone formation, trauma to the wall of gall
bladder 

Secondary bacterial infection

Usually by intestinal commensals E.coli, streptococcus fecalis. They reach the gall bladder by lymphatics. 
S.typhi reaches the gall bladder after systemic infection

Acute cholecystitis

Gall bladder is enlarged edematous and fiery red in color. 
- Wall is edematous, hyperemic, may show abscesses or gangrenous dark brown or green or black foci which may perforate.
Serous covering show fibrinosuppurative inflammation and exudation. Mucosa is edematous, hyperemic and ulcerated.
- If associated with stones, obstruction results in accumulation of pus leading to Empyaema of the gall bladder.

Fate:-  Healing by fibrosis and adhesions.

Complications:-  
- Pericholecystic abscess.
- Rupture leading to acute peritonitis.
- Ascending suppurative cholangitis and liver abscess 

Chronic cholecystitis
May follow Acute cholecystitis or starts chronic. Gall stones are usually present. 

Pathology

1. If associated with obstruction: Gall bladder is dilated. Wall may be thickened or thinned out. Contents may be clear, turbid or purulent. 
2. If not associated with obstruction: - Gall bladder is contracted, wall is markedly thickened.
3. Serosa is smooth with fibrous adhesions. Draining lymph nodes are enlarged.  
4. Wall is thickened, opaque and gray-white with red tinge.
5. Mucosa is gray- red with ulcerations and pouches.
6. Stones are usually present

Enterococci

Most common are E. fecalis and E. fecium.  Cause inflammation at site of colonization.

Serious resistance to antibiotics.  E. fecium is now a vancomycin resistant enterococcus (VRE)

Nephrolithiasis, urolithiasis

Formation of calculi (calcium stones) in the kidney (nephrolithiasis) or urinary tract (urolithiasis).
Commonly associated with hyperparathyroidism.
Signs and symptoms 

urinary tract obstruction, severe pain, and pyelonephritis.

Note: an enlarged prostate can also cause urinary tract obstruction in males.

Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.

b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.

3. Virion characteristics

a. The HIV genome includes:

(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.

b. HIV enzymes

(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins. 

4. Pathogenicity

a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into  the host DNA. New virions are synthesized and released by lysis of the host cell.

b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.

5. HIV infection versus acquired immunodeficiency syndrome (AIDS).

a. AIDS describes an HIV-infected person who has one of the following conditions:

(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.

6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii). 
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.

7. Laboratory diagnosis of HIV

a. ELISA test—detects HIV antibodies.
False negatives do occur.

b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.

8. Treatment
a. Inhibitors of reverse transcriptase.

(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.

(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.

Coccidioidomycosis (Valley Fever; San Joaquin Fever)

A disease caused by the fungus Coccidioides immitis, usually occurring in a primary form as an acute benign asymptomatic or self-limited respiratory infection, occasionally disseminating to cause focal lesions in skin, subcutaneous tissues, lymph nodes, bones, liver, kidneys, meninges, brain, or other tissues.

Primary coccidioidomycosis is usually asymptomatic, but nonspecific respiratory symptoms resembling influenza or acute bronchitis sometimes occur or, less often, acute pneumonia or pleural effusion. Symptoms, in decreasing order of frequency, include fever, cough, chest pain, chills, sputum production, sore throat, and hemoptysis.

Progressive disseminated coccidioidomycosis may develop a few weeks, months, or occasionally years after primary infections,, is more common in men than women and is more likely to occur in association with HIV infection, immunosuppressive therapy

Symptoms often are nonspecific, including low-grade fever, anorexia, weight loss, and weakness. Extensive pulmonary involvement may cause progressive cyanosis, dyspnea, and discharge of mucopurulent or bloody sputum. Extrapulmonary lesions are usually focal, involving one or more tissue sites in bones, joints, skin, subcutaneous tissues, viscera, brain, or meninges. Draining sinus tracts sometimes connect deeper lesions to the skin. Localized extrapulmonary lesions often become chronic and recur frequently, sometimes long after completion of seemingly successful antifungal therapy.