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By: Hussain Salha
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*A 32-year-old man with known AIDS is broughtto the emergency room with headache andfever for the past 3 days.
*According to family members who are withhim, he has been confused, forgetful, andirritable for a few weeks prior to the onset ofthese symptoms.
*They state that he has advanced AIDS with alow CD4 count and has had bouts ofpneumocystis pneumonia, candidal esophagitis,and Kaposi sarcoma.
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*On physical examination:
*On examination, he is cachetic and frail
appearing.
*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 abdominalexaminations are normal.
*He is hyperreflexic.
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*A head CT scan is normal.
*A report of the microscopic examination of hiscerebrospinal fluid obtained by lumbar
puncture comes back from the lab and statesthat there were numerous white blood cells,predominantly lymphocytes, and no organismsidentified on Gram stain but a positive Indiaink test.
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*Bacteria:
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae type B
Escherichia coli
group B streptococci
staphylococcipseudomonas and other Gram-negative bacilli.
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*Viral:
Enteroviruses
herpes simplex virus type 2varicella zoster virus
mumps virus
HIV
LCMV
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*Parasitic:
Angiostrongylus cantonensis
Gnathostoma spinigerum
Schistosoma
Cysticercosis
toxocariasis
baylisascariasis
paragonimiasis
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*Introduction:
Cryptococcus neoformans is an encapsulated
monomorphic fungi that commonly causes
chronic meningitis in immune-suppressed
individuals and occasionally in immune-competent persons.
The lungs are the primary site of infection,
although the organism appears to have specific
affinity for the brain and meninges on systemicspread.
C. neoformans is the leading cause of fungal
meningitis and is an important cause of
mortality in AIDS patients.
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Meningitis: Inflammation of the meninges.
Nuchal rigidity: Stiffness of the neck associated
with meningitis.
Cachetic: Weight loss or wasting because of
disease or illness.
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*C. neoformans is an encapsulated yeast, 4-6mm in diameter, which is distributed globally.
*The most common serotypes are found in high
concentrations in pigeon and other birddroppings, although they do not appear to
cause disease in these hosts.
*The most common route of transmission tohumans is via aerosolization of the organism
followed by inhalation into the lungs.
*Direct animal-to-person transmission has not
been shown.
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*Unlike other systemic fungi, C. neoformans is
monomorphic, not dimorphic, and grows as
budding yeast cells at both 25C in culture andat 37C in tissues.
*When grown in culture, C. neoformans produces
white- or tan-colored mucoid colonies in 2-3 days
on a variety of common fungal media.*Microscopically, the organism appears as
spherical budding yeast, surrounded by a thick
capsule.
*C. neoformans differs from the other
nonpathogenic cryptococcal strains by its ability
to produce phenol oxidase and growth at 37C.
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*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 immuneresponses at sites of infection.
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*This suppression of an immune response can
allow for multiplication of the organism and
promotion of its spread outside the respiratorytract.
*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.
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*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.
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*The most commonly diagnosed cryptococcal
disease is meningitis, which results from
hematogenous spread of the organism from thelung 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.
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*Cryptococcal meningitis may be insidious in its
onset, slowly causing mental status changes,
irritability, or confusion that occurs over weeksto months, or it can occur acutely, with
immediate changes in mentation and meningeal
symptoms.
*Clinical disease may present with intermittent
headache, irritability, dizziness, and difficulty
with complex cerebral functions and may even
be mistaken as psychoses.
*Seizures, cranial nerve signs, and papilledema
may appear in late clinical course.
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*A diagnosis ofC. neoformans infection is made
primarily by clinical presentation and
examination of CSF for increased pressure,
increased number of white cells, and low glucoselevels.
*Serum and CSF specimens should also be tested
for polysaccharide capsular antigen by latexagglutination or enzyme immunoassay.
*Another classic test for C. neoformans is the
India ink test, which is an easy and rapid testthat is positive in approximately 50 percent of
patients with cryptococcal disease.
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*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.
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*C. neoformans infections can be treated withantifungal agents such as amphotericin B or
fluconazole.
*Amphotericin B is a broad-spectrumchemotherapeutic agent and is the most
effective drug for severe systemic mycoses.
*However, it is an extremely nephrotoxic agentto which all patients have adverse reactions
such as fever, chills, dyspnea, hypotension, and
nausea.
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*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 fungalinfection.
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