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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


*                  The National Lyme Disease Network                  *
*                         LymeNet Newsletter                          *

IDX#                Volume 4 - Number 09 - 6/28/96
IDX#                            INDEX
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

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


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.

*  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%
*  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
*  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 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

*  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.

*  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

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

*  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.

*  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
*  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.

*  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.

*  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.

*  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

*  This was an epidemiologic study (not clinical) based on the CDC
*  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.

*  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.

*  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
*  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.


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