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Volume: 3
Issue: 18
Date: 22-Nov-95

Table of Contents:

I.    MISSOURI MED: Lyme and/or Lyme-line Disease in Missouri
II.   J INFECT DIS: Epidemiologic and diagnostic studies of
      patients with suspected early Lyme disease, Missouri,
III.  LYMENET: Report on Human Granulocytic Ehrlichiosis
IV.   About The LymeNet Newsletter


*                  The National Lyme Disease Network                  *
*                         LymeNet Newsletter                          *

IDX#                Volume 3 - Number 18 - 11/22/95
IDX#                            INDEX
IDX#  I.    MISSOURI MED: Lyme and/or Lyme-line Disease in Missouri
IDX#  II.   J INFECT DIS: Epidemiologic and diagnostic studies of
IDX#        patients with suspected early Lyme disease, Missouri,
IDX#        1990-1993
IDX#  III.  LYMENET: Report on Human Granulocytic Ehrlichiosis
IDX#  IV.   About The LymeNet Newsletter

EDITORIAL NOTE: Missouri Lyme Disease Controversy Continues

Beginning in the late 1980's, the state of Missouri has seen a
dramatic increase in the number of Lyme disease cases reported to the
Centers for Disease Control.  However, several teams of researchers
have been unable to culture Borrelia burgdorferi in Missouri from
either ticks or humans.  In 1990, the CDC dispatched several
investigators to Missouri to work with Dr. Edwin Masters, the Cape
Girardeau physician who first identified the illness, on an
epidemiological study of the emerging disease.  

Dr. Masters has stated unequivocally that the Missouri patients
fulfill the CDC reporting criteria for Lyme disease -- an expanding
lesion indistinguishable from "classic" erythema migrans; and/or
late arthritic, neurologic or cardiac manifestations and
seroreactivity to B. burgdorferi.  The CDC maintains that the patients
are not in fact seropositive and thatin the absence of successful
B. burgdorferi cultures, the disease remains idiopathic.

The investigation in Missouri was marked by intense acrimony between
local Missouri physicians and the CDC research team.  As a result,
both Dr. Masters and the Missouri State Epidemiologist, Dr. H. Denny
Donnell, have refused to "sign on" as co-authors to the CDC report of
the investigation, which was published in August in the Journal of
Infectious Diseases.  Instead, they have published their own paper
in the journal Missouri Medicine.  The abstracts of each paper are
presented below.  Readers are urged to consult the full text of each
article for a more detailed understanding of the nature of this
scientific dispute.

[Addendum: Earlier this year, a group of researchers led by Dr. Alan
Barbour identified a suspected new Borrelia species, not yet fully
characterized, in Amblyomma americanum, the suspected vector of the
Missouri illness.]

I.    MISSOURI MED: Lyme and/or Lyme-line Disease in Missouri
AUTHORS: Masters EJ, Donnell, HD
ORGANIZATION: Regional Primary Care, Inc, and Missouri Department
             of Health
REFERENCE: Missouri Med 1995 Jul;92:346-53

Missouri patients who fulfill the strict CDC surveillance definition
for Lyme disease have been reported in significant numbers since
1989, although there are no viable Missouri human cultures of
Borrelia burgdorferi.  The Missouri erythema migrans rashes are
indistinguishable from those in other areas, and the clinical
syndrome appears similar to Lyme disease nationally.  The authors
suspect atypical B. burgdorferi, and/or other Borrelia spirochetes
of causing this clinical borreliosis syndrome.


II.   J INFECT DIS: Epidemiologic and diagnostic studies of
     patients with suspected early Lyme disease, Missouri,
AUTHORS: Campbell GL, Paul WS, Schriefer ME, Craven RB, Robbins KE
        Dennis DT
ORGANIZATION: Division of Vector-Borne Infectious Diseases, Centers
             for Disease Control and Prevention, Fort Collins,
             Colorado, USA
REFERENCE: J Infect Dis 1995 Aug;172(2):470-80

A retrospective case-control study investigated 45 Missouri
outpatients with annular rashes meeting a surveillance case
definition for erythema migrans and with onset in 1990-1991.
Risk factors included being male, living near a body of water, and
hunting.  Twenty patients (44%) associated their rash with the bite
of a tick; of these, 5 described an adult Amblyomma americanum.  A
typical rash was described as expanding over time and measuring 8 cm
in diameter at 4 days after onset.  Mild constitutional symptoms were
common but fever was uncommon.  Serologic tests failed to incriminate
Borrelia burgdorferi or selected other arthropodborne pathogens.
Skin specimens from suspected erythema migrans lesions of 23 Missouri
patients sampled prospectively in 1991-1993 were culture-negative for
B. burgdorferi.  Thus, tick bite-associated annular rashes in
Missouri remain idiopathic.  Possible causes include infection with a
novel A. americanum-transmitted pathogen and an atypical toxic or
immunologic reaction to tick-associated proteins.


III.  LYMENET: Report on Human Granulocytic Ehrlichiosis
Sender: Tom Grier <[email protected]>

Human Granulocytic Ehrlichiosis
(A New Deadly Tick-Borne Disease)

A brief report by Tom Grier for the members of the
Duluth/Superior MN Lyme Disease Support Group.

There is a newly discovered tick-borne disease in our local woods,
and it lurks inside the same ticks that carry Lyme Disease.  
Ehrlichiosis was first described in dogs in Africa in 1935.
It is only recently that a relative of this same bacteria has been
found to cause a monocytic form of the disease, and more recently a
granulocytic form in humans.  (The term granulocytic refers to the
bacterium's attachment to a type of blood cell called a granulocyte.
Granulocytes are mature granular leukocytes -- neutrophils,
eosinophils and basophils.).  More importantly, the granulocytic form
was reported by a Duluth Clinic Physician, Dr. Johan S. Bakken M.D.,
to be right here in our local area.  (Bakken JS, Dumler JS, Chen S-M,
et al.  Human granulocytic ehrlichiosis in the Upper Midwest United
States: a new species emerging? JAMA 1994;272:212-8.)

The first reports of suspected human ehrlichiosis were in 1986, but it
wasn't until 1990 that successful techniques were developed by
Jacqueline Dawson, M.S., of the Centers for Disease Control, to
isolate this unique bacteria.  The bacteria which was isolated in the
monocytic form was Ehrlichiosis chaffeensis.  The strain and species
of ehrlichia causing HGE has yet to be isolated and completely

Human Granulocytic Ehrlichiosis (HGE) is caused by a strain of
Ehrlichia which is more closely related to the species which cause
disease in sheep and horses -- Ehrlichia pagocytophilia, and E. equis.

Tick Vectors: The possible tick vectors of HGE are Ixodes scapularis
(the deer tick, or black legged tick, found in the eastern United
States), and the Lone-Star tick (a tick commonly found in the southern
United States).

Area of Reported Disease:  The distribution of HGE mirrors that of
Lyme disease.  This includes the central eastern border of Minnesota
and adjacent Wisconsin, the northeast United States, all of
California, and the four state area surrounding Missouri.

Symptoms: HGE is transmitted from the bite of an infected tick to the
human host, most probably from a deer tick bite.  The symptoms come on
suddenly, usually within a few days of the tick bite (range 1-30
days), perhaps even hours.  The first symptoms are a flu-like syndrome
of high fever 103+ (may last 10+ days), headache, a general ill
feeling, muscle aches, chills, joint pain, nausea, vomiting, even
breathing difficulties.  Less than 1 % of cases have reported a rash
in confirmed HGE.  If left untreated, HGE is potentially fatal.

There have been four deaths reported.  There have been over 300
confirmed cases of HGE in the USA.  Concomitant infection or mixed
infections from a single tick bite are possible!  From a single deer
tick bite it is possible to get babesiosis, Lyme disease, and HGE
simultaneously.  In one Rhode Island study of 116 Lyme patients,
16% were concomitantly infected with Babesia microti, the agent of
babesiosis in the U.S..  Of those with mixed infection 89 % went on
to develop chronic symptoms longer than six months.  In Lyme disease
without babesiosis, less than 7 % had symptoms beyond six months post


HGE - 14-21 days of tetracycline, doxycycline, or minocycline. Dosage
adjusted for weight.

Babesiosis - Clindamycin and Quinine.


Blood Smear: Three blood smears stained with Giemsa stain, and three
blood smears stained with acrodine orange are used to look for
bacterial inclusion bodies inside the neutrophils and lymphocytes.
700 neutrophils must be checked to rule out infection.  The
inclusions are called morulae.  A properly trained medical technician
could be taught to use blood smears as the main diagnostic tool for
HGE with 85 % accuracy.  (This test will also differentiate monocytic
infection from granulocytic.)

IFA (Immune Fluorescent Antibody Test):  The test for Ehrlichia
chaffeensis is not adequate for diagnosing HGE. Patients with HGE
will test antibody negative when the IFA test for E. chaffeensis is
used.  The HGE bacteria is more closely related to E. pagocytophilia
an E.equis.  80+ % of HGE patients do test positive on IFA.

PCR. (Polymerase Chain Reaction - DNA amplification): The PCR test
suffers from not having established acceptable primers of bacterial
DNA to initiate the reaction.  (The primer Mayo Clinic uses is the
16 S rDNA geGF/ge1Dr.)  There is some cross over to other Ehrlichia
species so a PCR negative result cannot rule out possible infection,
and a positive does not specify monocytic ehrlichiosis vs. HGE.

What to send to the labs: One orange cap and one red cap vacuum tube
of blood and six unstained blood smears.  (Do Not Send Heparinized
Blood!)  Only two labs at this time have a commercially available

North American Laboratory Group
1  Lake Street
New Britain, CT , 06052
For more information about testing have your doctor call at:
1-800-866-6254, or FAX 1-203-223-6279

The Duluth Clinic
400 E. 3rd St.
Duluth, MN 55805

Prevention: The same precautions used to prevent exposure to the ticks
that cause Lyme disease, are used to diminish the risk of exposure to

HGE Tidbits -

* The bacteria is intracytoplasmic and forms aggregations or clumps
 called morulae.

* 43 cases in the Duluth Area since 1990.  Washburn and Sawyer
 Counties most prevalent, with 80 and 71 cases per 100,000 population
 respectively.  This makes HGE highly endemic and the fastest growing
 tick illness in the country.

* 54 % of HGE cases require hospitalization.  Most patients have
 seizures.  Fevers of 103 + last about 10 days.

* Four deaths were associated with a pneumonia infiltrate.

* The organism which causes HGE is one base pair different from
 E. chaffeensis, and three base pairs different from E. equis, and
 is probably closely related.  This organism may have jumped from
 infected animals to man.

* Wood ticks test negative for Ehrlichia.

* The Deer ticks are not born infected.  They must get the bacteria
 from feeding on an infected host, such as a white tailed deer
 (O. virginianus) which harbors the bacteria without symptoms.
 About 18 % of white tailed deer test positive in MN / WI.

* July is the peak month HGE is reported, but most people are probably
 infected in the spring.

References: J. Clin Microbiol: Chen 32:589-594, 1994 Journal of the
American Medical Association "A New Species Emerging."

Lecture by Dr. Johan S. Bakken M.D. Duluth Clinic Oct, 12th 1995.


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