ASM_101st_General_Meeting_Press_Releases

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ASM_101st_General_Meeting _Press_Releases

Date: Sun, 8 Jul 2001 23:25:36 -0700

http://www.asmusa.org/pcsrc/gm2001/31159.htm

101st General Meeting

May 20-24, 2001

Orlando, Florida

101st General Meeting of the American Society for Microbiology

May 20-24, 2001, Orlando, Florida

For more information on any presentation at the 101st General Meeting

contact Jim Sliwa, ASM Communications at jsliwa@....

Spirochetes may " love the brain to death "

(Session 179 )

Diego Cadavid

UMDNJ-New Jersey Medical School

Newark, NJ

United States

973-972-8686

cadavidi@...

Chronic infection of the brain is a prominent feature of spirochetal

infections. These include syphilis, caused by Treponema pallidum;

Relapsing Fever, caused by different Borrelia species worldwide; and

Lyme disease, caused by Borrelia burgdorferi in Europe and North

America. The word " spirochete " comes from the characteristic spiral

morphology of these bacteria under the microscope. Lyme disease and

relapsing fever are transmitted to humans by ticks in endemic areas,

while syphilis is sexually transmitted. As early as 1822, dementia

was recognized as a prominent complication of syphilis. Soon it

became apparent that multiple other neurological complications can

occur. Examination of the brain revealed the presence of spirochetes,

in cases of dementia 20 to 30 years after the initial infection. As

with Treponema pallidum in syphilis, chronic brain infection is also

prominent with the relapsing fever spirochetes. During relapsing

fever, patients have recurrent periods of fever separated by periods

of well being. The fever is caused by the presence of large numbers

of spirochetes in the blood. Studies in relapsing fever showed that,

like in syphilis, the brain could remain infected with spirochetes

for years after the infection disappears from the blood. In the

earlier 1980's, Lyme disease was identified as a previously

unrecognized spirochetal infection with prominent neurological

manifestations. These include headache and stiff neck from

meningitis, back pain and weakness from radiculitis, paralysis of the

face, and problems with attention and concentration. Lyme disease is

today the most common vector-borne disease in North America and

Europe, with an estimated 5-40% of cases developing neurological

complications. Although spirochetal infections are readily treatable

with antibiotics, severe and permanent neurological damage can occur

if they go undiagnosed or if the treatment is inadequate or delayed.

Our laboratory is investigating the mechanisms responsible for

neurological complications during spirochetal infections. Studies

with Treponema pallidum and Lyme disease spirochetes are limited

because of the paucity of animal models featuring neurological

infection. In contrast, several animal models of Relapsing fever show

prominent neurological infection. The majority of our research has

been done in laboratory mice infected with a strain of relapsing

fever spirochetes from South Western United States. The data

indicates that not all spirochetes are equally capable of entering

into the brain. The antibody response to the infection is critical

for elimination of infection from the brain. The localization of

spirochetes in the brain is mainly in the membranes covering it,

known as the leptomeninges. Spirochetes are also found in the brain

tissue itself, although in much lower numbers. Infection of the inner

ear results in prominent vertigo. Different serotypes vary in their

ability to infect the brain. The main route of entry into the brain

appears to be the blood-brain barrier. However, alternative routes of

entry may be used. Spirochetal entry into the brain results in

infiltration of the brain tissue by large numbers of inflammatory

cells, known as microglia, and increased statement of inflammatory

molecules, like Interleukin 6. We are currently investigating whether

chronic inflammation could result in damage to brain cells and in

neurological disease. Using monkeys infected with Lyme disease

spirochetes, we confirmed that the localization of spirochetes in the

brain is leptomeningeal. In this monkey model of Lyme disease, the

number of spirochetes in the brain is very low compared with

peripheral tissues like the heart or skeletal muscle, even in

immunosuppressed animals. About 10% of infected monkeys examined 4-24

months after infection show evidence of inflammation in the brain,

which is mild.

The work on the mouse model started at the University of Texas Health

Science Center at San in the early 1990's in the

Laboratory

of Dr. Alan G. Barbour, with grant funding from NIH. At present, it

continues at the Medical School of The University of Medicine and

Dentistry of New Jersey (UMDNJ) in Newark, with funding to Dr.

Cadavid from the Foundation of UMDNJ and the Hispanic Center of

Excellence at UMDNJ. The monkey model was developed by Dr. R.

Pachner at town University, who continues it at UMDNJ-New

Jersey Medical School in collaboration with The University of

California at under a contract from NIH.

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