C.neoformans.ppt

7/29/2019 C.neoformans.ppt

1/22

By: Hussain Salha

*


2/22

*

*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.


3/22

*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.


4/22

*

*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.


5/22

*

*Bacteria:

Neisseria meningitidis

Streptococcus pneumoniae

Haemophilus influenzae type B

Escherichia coli

group B streptococci

staphylococcipseudomonas and other Gram-negative bacilli.


6/22

*Viral:

Enteroviruses

herpes simplex virus type 2varicella zoster virus

mumps virus

HIV

LCMV


7/22

*Parasitic:

Angiostrongylus cantonensis

Gnathostoma spinigerum

Schistosoma

Cysticercosis

toxocariasis

baylisascariasis

paragonimiasis


8/22

*

*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.


9/22

*

Meningitis: Inflammation of the meninges.

Nuchal rigidity: Stiffness of the neck associated

with meningitis.

Cachetic: Weight loss or wasting because of

disease or illness.


10/22

*

*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.


11/22

*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.


12/22

*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.


13/22

*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.


14/22


15/22

*

*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.


16/22

*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.


17/22

*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.


18/22

*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.


19/22

*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.


20/22

*

*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.


21/22

*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.


22/22

Date post:	14-Apr-2018
Category:	Documents
Upload:	hus100
View:	213 times
Download:	0 times

C.neoformans.ppt

Documents