Abstract Details

Title The Role of Cryptococcal Capsule in Pathogenesis of Cryptococcal Meningitis

Topic Infections/AIDS/Prion Disease

Presentation(s) P04 - (-)

Poster/Presentation
Number 007

Objective

Background BACKGROUND: The Cryptococcus neoformans capsule is a major virulence factor for the organism. It is frequently hypothesized that elevated intracranial pressure in this infection is due to obstruction of arachnoid granulations by capsule. However, this has not been experimentally demonstrated.

Design/Methods DESIGN/METHODS: We have used three isogenic Cryptococcus neoformans strains: normocapsular H99, hypercapsular PKR1-33, and acapsular CAP59. Mice were intravenously inoculated, observed, and brains were collected at 1, 3, or 7 days post-inoculation. Mice were assessed daily for symptoms of hydrocephalus and meningitis, using daily pictures and a rating scale. Brain weights were recorded. India ink staining was used to quantify invasion of the CNS by the different strains, as well as size of cryptoccocal capsule.

Results RESULTS: Mice infected with normocapsular H99 lived an average of seven days post-inoculation, becoming more severely and rapidly symptomatic than both PKR1-33 and CAP59. PKR1-33 and CAP59 mice survived to an average of 14 days post-inoculation. On day 3, there was no difference in the brain weights of the three mice. However, by day 7, mice infected with H99 had much greater brain weights compared to mice infected with PKR1-33, indicating development of brain edema. A greater burden of H99 is found in the mice brains, but PKR1-33 has a larger capsule in vivo.

Conclusions CONCLUSIONS: Virulence of cryptococcus in this model associates with ability to cross the blood brain barrier and/or to replicate more rapidly in the brain. Virulence is not associated with capsule size per organism, but may be associated with absolute capsule amount, since there are more H99 organisms in the brain. Future studies will determine the exact mechanism by which H99 causes greater virulence despite smaller capsule.

Authors/Disclosures
Jeffrey Rumbaugh, MD (Pathway Neurology) PRESENTER	No disclosure on file
Amy Gelfand, MD (UCSF)	An immediate family member of Dr. Gelfand has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Headache Society. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of an immediate family member of Dr. Gelfand has received research support from Hoffman LaRoche. The institution of an immediate family member of Dr. Gelfand has received research support from Vigil Neuroscience. The institution of an immediate family member of Dr. Gelfand has received research support from NIH/NINDS. The institution of Dr. Gelfand has received research support from PCORI. The institution of Dr. Gelfand has received research support from UCSF RAP grant. Dr. Gelfand has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Weill Cornell Neurology Department. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Taiwan Headache Society. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Author with Elsevier. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Speaker with College Board SSD. Dr. Gelfand has received personal compensation in the range of $0-$499 for serving as a Speaker with Kobenhavns Unversitet. An immediate family member of Dr. Gelfand has a non-compensated relationship as a Clinical Trial Steering Committee Member with Roche/Genentech that is relevant to AAN interests or activities.
Amy Gelfand, MD (UCSF)	An immediate family member of Dr. Gelfand has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Headache Society. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of an immediate family member of Dr. Gelfand has received research support from Hoffman LaRoche. The institution of an immediate family member of Dr. Gelfand has received research support from Vigil Neuroscience. The institution of an immediate family member of Dr. Gelfand has received research support from NIH/NINDS. The institution of Dr. Gelfand has received research support from PCORI. The institution of Dr. Gelfand has received research support from UCSF RAP grant. Dr. Gelfand has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Weill Cornell Neurology Department. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Taiwan Headache Society. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Author with Elsevier. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Speaker with College Board SSD. Dr. Gelfand has received personal compensation in the range of $0-$499 for serving as a Speaker with Kobenhavns Unversitet. An immediate family member of Dr. Gelfand has a non-compensated relationship as a Clinical Trial Steering Committee Member with Roche/Genentech that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
Kavita Sail, PhD (Abbvie)	No disclosure on file
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��