LymeNet Newsletter Volume 4 Issue 09

Volume: 4
Issue: 09
Date: 28-Jun-96

Table of Contents:

I. LDF: Clarifications and Errata from Issue 08 II. LDF: Notes from the IXth Annual LDF Scientific Conference (Part 2 of 3) III. About The LymeNet Newsletter

Newsletter:

*********************************************************************** * The National Lyme Disease Network * * LymeNet Newsletter * ***********************************************************************

IDX# Volume 4 - Number 09 - 6/28/96 IDX# INDEX IDX# IDX# I. LDF: Clarifications and Errata from Issue 08 IDX# II. LDF: Notes from the IXth Annual LDF Scientific Conference IDX# (Part 2 of 3) IDX# III. About The LymeNet Newsletter IDX#

I. LDF: Clarifications and Errata from Issue 08 --------------------------------------------------

Section: Effects of Borrelia burgdorferi on Human B- and T-Cells David W. Dorward, Ph.D.

The following comment requires clarification: "The process allows avoidance of phagosomal fusion of normal macrophages."

Dr. Dorward's clarification: "My only concern involves the note that the interactions we discovered inhibit phagocytosis by macrophage. If I left that impression, I am very regretful and should contact LDF to arrange for some form of clarification. To date, we have not assessed any effect of this interaction with lymphocytes (T- and B-cells) on subsequent interactions with macrophage (although it sounds like an excellent experiment to try). The data I reported did suggest that the interaction with lymphocytes appeared to inhibit binding of anti-OspA antibodies to spirochetal surfaces, and interfere with subsequent spirochetal killing by antibodies and serum complement. Whereas I believe that if this 'membrane cloaking' phenomenon occurs in vivo, it will probably result in a decreased ability for immune effector cells to recognize and target spirochetes as 'foreign,' we have not yet experimentally addressed such possibilities."

=====*=====

II. LDF: Notes from the IXth Annual LDF Scientific Conference (Part 2 of 3) ----------------------------------------------------------------------- Sender: Lloyd E. Miller, DVM <[email protected]>

Notes from the Ninth Annual Scientific Conference Lyme Disease Foundation -- April 19-20, 1996 -- Westin Copley Plaza Hotel, Boston, Massachusetts, USA Prepared by Lloyd E. Miller, DVM ----------------------------------------------------------------------- Every effort has been made to report the speaker's statements and to report suggested drug doses accurately. However, typos do occur and as information gets passed around or edited mistakes can occur. The reader is cautioned to not take any medication before checking the accuracy of name and dose recommendations with the speaker.

Selected abstract statements have been included in the notes.

The notes themselves are from statements made by the speakers.

My editorial comments will be found in brackets like this [COMMENT].

Full abstracts are available electronically from the Lyme/Other Zoonoses section in the Public Health Forum on Compuserve.

*** Ehrlichia equi in Ixodes scapularis: Relevance to Lyme Borreliosis - Louis A. Magnarelli, Ph.D.

FROM THE ABSTRACT: * During 1995, PCR analysis revealed the DNA of the human granulocytic ehrlichiosis (HGE) agent, presumably Ehrlichia equi or a closely related organism, in tissues from 59 (50%) of 118 adults and 1 of 2 nymphal I. scapularis tested from Connecticut. * xanalyses of 40 human sera from persons who had Lyme borreliosis, antibodies to E. equi, E. chaffeensis, or Babesia microti, the causative agent of human babesiosis, were detected in 8 to 20% specimens. * Laboratory studies indicate the presence of different human pathogens in Ixodes scapularis populations and that persons living in tick-infected areas are sometimes exposed to multiple tick-borne agents. * Ehrlichial or Babesia organisms may occur concurrently with B. burgdorferi in humans and may complicate Lyme borreliosis infections. Therefore, clinical diagnoses of tick-related illnesses should include laboratory testing for ehrlichiosis, babesiosis, and Lyme borreliosis.

FROM THE NOTES:

* From 3 sites in CT and 1 site in PA 30% of tested ticks were positive for E. equi. * From various locales in CT an average of about 50% of adult ticks tested were positive for HGE. One of two nymphs tested was positive. This does not imply a high transmission rate but rather that the agent that causes HGE is present in CT. * Transovarian transmission of Ehrlichia may occur in ticks. * The white footed mouse may also be a reservoir for Ehrlichia. * Co-infection of ticks with B. burgdorferi and babesiosis does occur. * Ticks can co-transmit these diseases. Nymphs are the chief vectors. * Suggested that an effort should be made to identify other organisms that may be transmitted from I. scapularis to man and other animals because I. scapularis feeds on multiple species.

*** The Cold Zone: A Convergence of Tick-transmitted Diseases in Areas Endemic for Lyme Disease - David H. Persing, M.D., Ph.D.

* We have focused on two major areasx: 1/ an examination of the role of genetic heterogeneity of Borrelia burgdorferi, the Lyme disease spirochete, in disease expression and 2/ the role of co-infecting pathogens in alteration of host susceptibility. * An extensive genetic analysis of over 200 isolates of B. burgdorferi from the U.S. and worldwide has provided us with an unprecedented appreciation of the genetic diversity of this organism on the North American continent.

Using this information as a foundation for analysis of human clinical material, we can examine the role of B. burgdorferi genetic heterogeneity in the differential expression of human disease by recovering and sequencing spirochetal nucleic acids directly from human tissues.

* It is now becoming clear that cotransmission with B. burgdorferi of other pathogens, including Babesia microti and granulocytic Ehrlichia spp., may occur via the same tick vector, an examination is needed of the role of these known immunosuppressive agents in the modulation of Lyme disease.

FROM THE NOTES: * There is "enormous" genetic diversity of Bb spirochete in the USA. 300 strains identified so far. * In PCR studies contamination is a big problem especially in the nested PCR. * Babesia can cause a flu-like illness - sometimes subclinical - only in severe cases do patients get serious symptoms. * Co-infection of Bb and babesia makes symptoms of fatigue, nausea and headache more common. Presence of both organisms increases the severity of the disease. * It is suspected that babesia causes immunosuppression. * HGE organism has been found in tick specimens from 1987 and also from Switzerland. Therefore, HGE is not limited to the USA. * Suggested that patients should be tested for multiple tick borne pathogens.

*** Is Human Granulocytic Ehrlichiosis (HGE) another Lyme Disease? A Comparison of Clinical, Laboratory, and Epidemiologic Features - J. Stephen Dumler, M.D.

FROM THE ABSTRACT: * Human granulocytic ehrlichiosis (HGE) isx caused by a zoonotic pathogen in the genus Ehrlichia that is transmitted via the bite of Ixodes ricinus complex ticks. The causative agent is an obligate intracellular bacterium. HGE and LB are geographically co- distributed and a proportion of LB and HGE patients have evidence of concurrent infection by B. burgdorferi, Babesia microti, or the HGE agent. * HGE is characterized as an acute febrile illness with or without headache, myalgias, gastrointestinal or respiratory symptoms and signs, CNS involvement, leukopenia, thrombocytopenia, and elevations in hepatic transaminase levels. The usual presentation is acute and relatively severe, with life-threatening complications in 7% and death secondary to opportunistic infections in up to 5% of patients. * Persistent infection associated with disease caused by Ehrlichia species is well documented in animals and is increasingly recognized in humans.

FROM THE NOTES: * HGE organism is very closely related to E. equi if it is not the same organism. It responds rapidly to doxycycline. * Early HGE is severe 50% +/- requiring hospitalization. Average hospital stay is 5.5 days. * Peak incidence is May to July with a secondary peak in the late fall. * Most cases have been found in Wisconsin and Minnesota. Westchester County, NY has also had several cases. Cases have also been identified to lesser extent in CT, RI, MA, MD, PA, FL, AK, and GA. * Co-infection varies from area to area from 9% to 21%. * HGE has been diagnosed in about 100 patients so far - 4 have died. He feels that fatalities were related to secondary infections from immune suppression. * Ehrlichia can cause persistent infection post treatment. * Co-infection can make Lyme disease worse.

*** Multivariate Analysis of 160 Patients with Lyme Disease - Lesley Ann Fein, M.D., M.P.H.

FROM THE ABSTRACT: * Data of 160 patients treated for Lyme disease were examined in a retrospective multifactorial analysis. Of these patients 27% reported a history of tick bite; 34% reported an erythema migrans rash; on initial evaluation, 2% had abnormal EKG, 6% abnormal MRI findings consistent with Lyme disease, 67% had arthralgias and 47% reported swollen joints.

FROM THE NOTES: * Commented that she felt that the risk of infection is greater than is currently published and that new information is due to be published soon. * Some statistics on symptom presentation (Dr. Fein is a rheumatologist so symptoms may be skewed toward this discipline): 1. Stiff neck (91%); arthralgias (86%); myalgias (72%); joint swelling (62%); trigger points (4.4%). 2. Joints affected: knee (65%); hand (35%); shoulder (30%); hip (31%); feet (30%); sacroiliac (15%); TMJ (9.4% - she feels this is under reported); wrists (1.5% - this joint is commonly affected in rheumatoid arthritis) 3. Neurologic symptoms: constant headache (18%); cyclical headaches every 21 to 28 days (77% - both are very common); paraesthesia (65%); dizziness (64%); ringing in the ears (29%); hearing loss (15.6%) seizures (2.5%); abnormal MRI (7%); abnormal SPECT scan (100% - cited Logigan) 4. Rheumatoid factor test positive in 10% at initial exam and 6%
six months later. CPK increased in 7% at initial exam and 4% six months later. * Approximately two-thirds of patients are seropositive at initial diagnosis. Approximately another 20% seroconvert to positive after treatment is begun. * Lyme disease often presents as an autoimmune disease, chronic fatigue syndrome, chronic Epstein Barr Virus or fibromyalgia. * 50% of neuro-Lyme patients have increased anticardiolepin levels. * Some patients have false positive rheumatoid factor and ANA tests. * She uses plaquenil for 1 year as maintenance post treatment especially in patients that present as autoimmune like disease. * Treats with oral and IV antibiotics - uses those that have been recommended and reported effective. IV antibiotics reported to be less effective than oral or Bicillin primarily because insurance and cost often limit the length of treatment to about 1 month. * Reported treatment response to be better the longer a patient is treated; Prolonged treatment gave better response. Saw no increase
in side effects with increased length of treatment

*** The Long-Term Follow-up of Lyme Disease: A Population-Based Retrospective Cohort Study - Nancy A. Shadick, M.D., M.P.H.

FROM THE ABSTRACT: * Population-based retrospective cohort study. Setting: An island in the northeast endemic for Lyme disease. (Nantucket, MA) * Results: In univariate analyses, the Lyme group (n=176) (mean duration from infection to evaluation, 5.2 years) had a higher prevalence of arthralgias (p<0.0001), fatigue (P<0.004), memory (p<0.004) and word finding difficulties (p<0.003) than controls (n=160). They had more knee swelling on physical exam (p<0.03), poorer functional status (p<0.004) and on neurocognitive testing, the Lyme group had lower attention scores than controls (p<0.05). Seventy-three (73) individuals complained of persistent symptoms following Lyme disease and were more likely to have had neurologic symptoms or manifestations during their acute illness (p<0.01) and a longer duration of infection (p<0.02) than those who had completely recovered. * Forty-seven (47) individuals reported relapses after initial treatment, and were more likely to have had erythromycin,
penicillin or tetracycline than amoxicillin or doxycycline as initial oral therapy (p<0.007). * Conclusions: Risk factors for persisting symptoms after Lyme disease include neurologic dissemination and a longer duration of infection.

FROM THE NOTES: * This was an epidemiologic study (not clinical) based on the CDC definition. * Survey of all permanent residents of the island -13% prevalence rate. 3% had positive serology with no clinical symptoms. * Patients who had Lyme disease 5 years ago still had many symptoms - many more than controls even when adjusted for age and sex.

[ COMMENT: Two well respected participants commented that the laboratory used in this study for serology was not considered by them to be particularly accurate which would affect the data. ]

*** Disseminated Lyme Disease and Pregnancy - Martina H. Ziska, M.D.

FROM THE ABSTRACT: * A cohort of nine patients living in LB endemic areas was analyzed. Five patients (55%) had history of EM, 6 patients (66%) had laboratory confirmation later in the course of the disease. LB was contracted 2 to 96 months (median 53.8 months) before conception. Median length of treatment before conception was 5.5 months. Seven women were symptomatic at the time of conception, 6 of whom received antibiotics through the entire pregnancy. Except for one case, all test results were negative. On the follow-up (4 to 16 months), all but one infant had no complications. Antibiotic therapy was continued in 4 women after delivery, whose symptoms worsened. Seven women, 5 of which were symptomatic, breastfed. * No case of transplacental transmission was documented using serological and PCR assays. Breast feeding by LB symptomatic mothers has no harmful effect on the infant.

FROM THE NOTES: * Dr. Ziska cited several small studies that have demonstrated Bb infection of the fetus. * Possible adverse outcomes of gestational Lyme disease: congenital anomaly, congenital cortical blindness, miscarriage, small birth size, still birth or toxemia. * There may not be as many similarities with syphilis as originally thought. * Because of the small number of patients that completed this study it is difficult to make many concrete statements. More studies with larger numbers of patients are needed.

=====*=====

III. ABOUT THE LYMENET NEWSLETTER ----------------------------------- For the most current information on LymeNet subscriptions, contributions, and other sources of information on Lyme disease, please refer to the LymeNet Home Page at: http://www.lymenet.org----------------------------------------------------------------------- To unsubscribe from the LymeNet newsletter, send a message to: [email protected] On the first line of the message, write: unsub lymenet-l ----------------------------------------------------------------------- LymeNet - The Internet Lyme Disease Information Source ----------------------------------------------------------------------- Editor-in-Chief: Marc C. Gabriel <[email protected]> FAX (for contributions ONLY): 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. Stolow, President <[email protected]> The Lyme Disease Network of New Jersey ----------------------------------------------------------------------- WHEN COMMENTS ARE PRESENTED WITH AN ATTRIBUTION, THEY DO NOT NECESSARILY REPRESENT THE OPINIONS/ANALYSES OF THE EDITORS. ----------------------------------------------------------------------- THIS NEWSLETTER MAY BE REPRODUCED AND/OR POSTED ON BULLETIN BOARDS FREELY AS LONG AS IT IS NOT MODIFIED OR ABRIDGED IN ANY WAY. ----------------------------------------------------------------------- SEND ALL BUG REPORTS TO [email protected] -----------------------------------------------------------------------