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By: Hussain Salha

* A 32-year-old man with known AIDS is brought
to the emergency room with headache and fever for the past 3 days.

* According to family members who are with

him, he has been confused, forgetful, and irritable for a few weeks prior to the onset of these symptoms.

* They state that he has advanced AIDS with a

low CD4 count and has had bouts of pneumocystis pneumonia, candidal esophagitis, and Kaposi sarcoma.

* On physical examination:
* On examination, he is cachetic and frail

* He is confused and only oriented to his name. * His temperature is 37.8C (100F), and his
other vital signs are normal.

* Examination of his cranial nerves is normal. * He has minimal nuchal rigidity. * Cardiovascular, pulmonary, and abdominal
examinations are normal.

* He is hyperreflexic.

* A head CT scan is normal. * A report of the microscopic examination of his
cerebrospinal fluid obtained by lumbar puncture comes back from the lab and states that there were numerous white blood cells, predominantly lymphocytes, and no organisms identified on Gram stain but a positive India ink test.

* Bacteria: Neisseria meningitidis Streptococcus pneumoniae Haemophilus influenzae type B Escherichia coli group B streptococci staphylococci pseudomonas and other Gram-negative bacilli.

* Viral: Enteroviruses herpes simplex virus type 2 varicella zoster virus mumps virus HIV LCMV

* Parasitic: Angiostrongylus cantonensis Gnathostoma spinigerum Schistosoma Cysticercosis toxocariasis baylisascariasis paragonimiasis

* Introduction:
Cryptococcus neoformans is an encapsulated monomorphic fungi that commonly causes chronic meningitis in immune-suppressed individuals and occasionally in immunecompetent persons.
The lungs are the primary site of infection, although the organism appears to have specific affinity for the brain and meninges on systemic spread. C. neoformans is the leading cause of fungal meningitis and is an important cause of mortality in AIDS patients.

Meningitis: Inflammation of the meninges. Nuchal rigidity: Stiffness of the neck associated with meningitis. Cachetic: Weight loss or wasting because of disease or illness.

* C. neoformans is an encapsulated yeast, 4-6

mm in diameter, which is distributed globally.

* The most common serotypes are found in high

concentrations in pigeon and other bird droppings, although they do not appear to cause disease in these hosts.

* The most common route of transmission to

humans is via aerosolization of the organism followed by inhalation into the lungs.
been shown.

* Direct animal-to-person transmission has not

* Unlike other systemic fungi, C. neoformans is

monomorphic, not dimorphic, and grows as budding yeast cells at both 25C in culture and at 37C in tissues. white- or tan-colored mucoid colonies in 2-3 days on a variety of common fungal media.

* When grown in culture, C. neoformans produces

* Microscopically, the organism appears as * C. neoformans differs from the other

spherical budding yeast, surrounded by a thick capsule.

nonpathogenic cryptococcal strains by its ability to produce phenol oxidase and growth at 37C.

* The capsule is an important virulence factor of

Cryptococcus, and it consists of long, unbranched polysaccharide polymers.

* Capsule production is normally repressed in

environmental settings and is stimulated by physiological conditions in the body.

* The capsule is antiphagocytic, because of its

large size and structure and has also been shown to interfere with antigen presentation and the development of T-cell-mediated immune responses at sites of infection.

* This suppression of an immune response can

allow for multiplication of the organism and promotion of its spread outside the respiratory tract.

* Once outside the lung, the organism appears to

have an affinity for the central nervous system (CNS), possibly because of its ability to bind C3 and the low levels of complement found in the CNS.

* Inhalation of these aerosolized yeast cells leads
to a primary pulmonary infection.

* The infection may be asymptomatic or may

result in a flu-like respiratory illness or pneumonia.

* Commonly, cryptococcal pulmonary infection is

identified only as an incidental finding on a chest x-ray being performed for other reasons.

* Often the infection and resulting lesions appear

suspicious for a malignancy, only to be diagnosed properly after surgical removal.

* The most commonly diagnosed cryptococcal

disease is meningitis, which results from hematogenous spread of the organism from the lung to the meninges.

* It occurs most commonly in persons with AIDS

or those who are immunosuppressed for other reasons, but it can occasionally occur in persons without underlying conditions.

* Outside the lungs, C. neoformans appears to

have a preference for the cerebrospinal fluid (CSF), but disseminated disease can also cause infections of the skin, eye, and bone.

* Cryptococcal meningitis may be insidious in its

onset, slowly causing mental status changes, irritability, or confusion that occurs over weeks to months, or it can occur acutely, with immediate changes in mentation and meningeal symptoms. headache, irritability, dizziness, and difficulty with complex cerebral functions and may even be mistaken as psychoses. may appear in late clinical course.

* Clinical disease may present with intermittent

* Seizures, cranial nerve signs, and papilledema

* A diagnosis of C. neoformans infection is made

primarily by clinical presentation and examination of CSF for increased pressure, increased number of white cells, and low glucose levels.

* Serum and CSF specimens should also be tested

for polysaccharide capsular antigen by latex agglutination or enzyme immunoassay.

* Another classic test for C. neoformans is the

India ink test, which is an easy and rapid test that is positive in approximately 50 percent of patients with cryptococcal disease.

* A drop of India ink is placed on a glass slide

and mixed with a loopful of CSF sediment or a small amount of isolated yeast cells.

* A cover slip is added and the slide is examined

microscopically for encapsulated yeast cells that exclude the ink particles.

* C. neoformans infections can be treated with
antifungal agents such as amphotericin B or fluconazole.

* Amphotericin B is a broad-spectrum

chemotherapeutic agent and is the most effective drug for severe systemic mycoses.

* However, it is an extremely nephrotoxic agent

to which all patients have adverse reactions such as fever, chills, dyspnea, hypotension, and nausea.

* Fluconazole is less toxic than amphotericin B and

produces fewer side effects; however, resistance to fluconazole has been shown to occur.

* AIDS patients with cryptococcosis are required to

continue lifelong suppressive therapy with fluconazole to prevent relapse of fungal infection.