Volume: 3 Table of Contents: I. NIAID: Lyme Disease Agent Changes Its Surface Before Infecting People II. Q&A: Experience with timentin or cefpodoxime in LD? (A) III. JAOA: Lyme Disease With Concurrent Ehrlichiosis IV. LYMENET: National LymeNet Suffers Hardware Failure V. About The LymeNet Newsletter Newsletter: *********************************************************************** * The National Lyme Disease Network * * LymeNet Newsletter * *********************************************************************** IDX# Volume 3 - Number 08 - 5/30/95 IDX# INDEX IDX# IDX# I. NIAID: Lyme Disease Agent Changes Its Surface Before IDX# Infecting People IDX# II. Q&A: Experience with timentin or cefpodoxime in LD? (A) IDX# III. JAOA: Lyme Disease With Concurrent Ehrlichiosis IDX# IV. LYMENET: National LymeNet Suffers Hardware Failure IDX# V. About The LymeNet Newsletter IDX# QUOTE OF THE WEEK: "The lack of OspA and the possible shutdown of OspC by spirochetes after they enter into humans may play a role in persistent infection and the spirochetes' evasion of the immune response" -- Tom Schwan (See Section I) I. NIAID: Lyme Disease Agent Changes Its Surface Before Infecting People ---------------------------------------------------------- For Immediate Release DATE: April 5, 1995 BETHESDA, MD -- The Lyme disease bacterium changes its coat prior to being transmitted from ticks to humans and other mammals, scientists from the National Institutes of Allergy and Infectious Diseases (NIAID) and their colleagues have discovered, a finding that has important implications for designing diagnostic tests and vaccines to control he disease. As noted in their April 1, 1995 Proceedings of the National Academy of Sciences, this adaptation likely evolved to ensure that the bacteria can be transmitted to and thrive in two very different hosts, ticks and mammals. In the United States, the spiral-shaped bacteria are passed on to people through the bites of infected back-legged ticks. According to NIAID Director Anthony S. Fauci, M.D., "This new finding underscores why investment in basic research is so important. The specific adaptation of the Lyme disease spirochete that has now been identified will assist efforts to improve the diagnosis and prevention of this illness." The investigators knew from previous studies that when a tick first becomes infected, the Lyme spirochetes settle in its midgut and make OspA surface protein. But as the new laboratory experiments reveal, when an infected tick subsequently attaches to a warm-blooded mammal and begins feasting on blood, two environmental cues -- something in the blood itself and an increase in temperature -- signal the spirochete to stop producing OspA and make OspC surface protein instead. "We believe that OspC is critical for the dissemination and transmission of Lyme spirochetes during the tick feeding," comments lead author Tom G. Schwan, Ph.D., a microbiologist with NIAID's Rocky Mountain Labs (RML) in Hamilton, Mont. Describing the relevance of their observations to diagnosis, Dr. Schwan says their research suggests that OspC is the first abundant surface protein the immune system encounters when spirochetes enter the body, which explains why people rarely make an antibody response to OspA and why they develop antibodies to OspC early on. "The lack of OspA and the possible shutdown of OspC by spirochetes after they enter into humans may play a role in persistent infection and the spirochetes' evasion of the immune response," adds Dr. Schwan. When U.S. Lyme experts recently drafted standards for the Western blot -- a confirmatory diagnostic test that detects antibodies to specific proteins -- they agreed that OspC should be one of the required proteins to look for in the patient's sera. Their findings also bear on vaccine development. Currently, two companies have OspA-based Lyme vaccines in human trials. In experiments with mice, other researchers have shown that these vaccines work in a non-traditional way. When the tick feeds in a vaccinated mouse, the tick ingests anti-OspA antibodies. These antibodies kill the spirochetes inside the tick, preventing migration of the spirochetes from the tick to the host animal rather than preventing infection or disease inside the host. According to Edward McSweegan, Ph.D., Lyme disease program officer for NIAID, "This new report suggests that like OspA vaccines, an OspC vaccine would also be an anti-transmission vaccine. In this light, it would be worth considering combining both proteins into one vaccine." Nymphal ticks -- the immature, freckle-sized form that most often transmits Lyme disease -- usually complete feeding within three to six days. In their report, the scientists write that the spirochete "is rarely if ever transmitted by ticks to mammals during the first two days of attachment and feeding. From two days onwards, however, the frequency of transmission of spirochetes by ticks increases dramatically." In their experiments, they successfully infected mice by inoculating them with infected midguts from ticks that had fed for three or more days and therefore had begun producing OspC. This lag time in transmission during early tick feeding had been attributed solely to the spirochete's location in the midgut. But the new research suggest that the change to OspC begins while the spirochete is still in the midgut and may be required for the spirochete to migrate out of that location. As a tick feeds, the spirochetes multiply, pass through the midgut wall to the tick's bloodlike fluid, invade the salivary glands, and are transmitted to the animal or human host in tick saliva. "This entire phenomenon takes time, during which both ticks and spirochetes first warm to approximately 37 degrees C, when ticks attach to the host's skin [TGS, unpublished data]," write the scientists. Dr. Schwan's team found that spirochetes produce OspC at 32 degrees C to 37 degrees C, but not at 24 degrees C. Merely raising the temperature, however, does not cause the switch. This change also required some as yet unidentified signal or nutrient in blood. Lyme disease mainly affects people living in the northeastern and upper north-central United States, and along the northern Pacific Coast. The Centers for Disease Control and Prevention (CDC) will hot have the final tally of the 1994 Lyme disease cases until all states submit their reports, but the provisional total is 12,973 based on the 41 states that have reported to date. It treated promptly with antibiotics, Lyme disease symptoms usually resolve. People who do not receive prompt treatment can develop chronic arthritis and neurological symptoms. Borrelia burgdorferi, the Lyme spirochete, was isolated and identified in 1981 by NIAID RML researchers Willy Burgdorfer, Ph.D., hon. M.D., and Alan Barbour, M.D. Since then the Institute has maintained a productive intramural Lyme disease research effort at RML. Dr. Schwan's collaborators on the paper include Patricia A. Rosa, Ph.D., of RML; and Joseph Piesman, Ph.D., William T. Golde, Ph.D., and Marc C. Dolan of the CDC in Fort Collins, Colo. NIAID, a component of the National Institutes of Health (NIH), supports biomedical research to prevent, diagnose and treat illnesses such as AIDS, tuberculosis, asthma and allergies. NIH and CDC are agencies of the U.S. Public Heath Service, part of the U.S. Department of Health and Human Services. =====*===== II. Q&A: Experience with timentin or cefpodoxime in LD? (A) ------------------------------------------------------------- Sender: Philip W. Paparone, D.O., Lyme Disease Center for South Jersey We have attempted to procure information concerning Cefpodoxime and invitro sensitivity of the Borrelia burgdorferi, and the manufacturer of Cefpodoxime-Vantin does not have data to support further investigation of the drug clinically since it appear not to have any activity against the Borrelia invitro. However, with Timentin it is know that Pipricillin is the same class as Ticarcillin, which is contained within Timentin, does have activity against Borrelia burgdorferi, and also that Clavulinic acid is active against the Borrelia burgdorferi in the test tube. There would possibly be synergy; however, this combination has not been tested. An attempt at testing Augmentin, to see if there was any synergistic effect was initiated by ourselves at the Lyme Disease Center of South Jersey, but then the FDA discontinued it stating that Amoxicillin was already known to be effective. They did not want to consider the possibility of synergy. As far as antibiotics for Thromocytopenia patients please note the article about ehrlichiosis [abstract in section III] which can demonstrate significant Thrombocytopenia as a clue to the possibility of ehrlichiosis. =====*===== III. JAOA: Lyme Disease With Concurrent Ehrlichiosis ----------------------------------------------------- AUTHORS: Paparone PW, Glenn, WB ORGANIZATION: Lyme Disease Center for South Jersey REFERENCE: JAOA 1994 July;97(7): 568-77 ABSTRACT: Lyme disease constitutes a major health hazard with an increased incidence throughout the United States, in particular the eastern states. Human ehrlichiosis, also a tick borne illness, has recently been identified. It is characterized by fever, headache, malaise, leukopenia, thrombocytopenia, and elevated liver enzyme titers, and has been reported to occur mainly in the South Central and South Atlantic states. As with Lyme disease, most patients have a history of tick exposure. These two diseases may be difficult to differentiate clinically. Physicians must consider the possibility of both infections when patients become ill with a systemic illness after tick exposure. Although certain demographic and clinical features are characteristic of these diseases, they can be misleading. Only serological evidence can confirm the diagnosis. Two cases of concurrent Borrelia and Ehrlichia infections have been previously reported. The authors herein describe a third case that further illustrates the potential diagnostic dilemma posed by the concurrence of these two entities. =====*===== IV. LYMENET: National LymeNet Suffers Hardware Failure -------------------------------------------------------- DATE: May 26, 1995 BYLINE: By Marc Gabriel The National LymeNet service suffered a major hardware failure on May 23. The system is not currently online due to this failure. The Lyme Disease Network of NJ is currently reviewing the situation and will keep readers of the Newsletter updated on the latest developments. =====*===== V. ABOUT THE LYMENET NEWSLETTER ---------------------------------- For the most current information on LymeNet subscriptions, contributions, and other sources of information on Lyme disease, please request the LymeNet Resource Guide. To obtain the Guide, send a blank message to: [email protected] ----------------------------------------------------------------------- The LymeNet Resource Guide is in Revision: 1.10 ----------------------------------------------------------------------- LymeNet - The Internet Lyme Disease Information Source ----------------------------------------------------------------------- Editor-in-Chief: Marc C. Gabriel <[email protected]> FAX: 908-789-0028 Contributing Editors: Carl Brenner <[email protected]> John Setel O'Donnell <[email protected]> Frank Demarest <[email protected]> Advisors: Carol-Jane Stolow, Director <[email protected]> William S. 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