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Volume: 6
Issue: 04
Date: 17-Apr-98


Table of Contents:

I.    LDRC: CDC finds less Lyme but more tickborne diseases in a
      California community
II.   J Infect Dis: Seroepidemiology of emerging tickborne
      infectious diseases in a Northern California community.
III.  LYMENET: How to join the LYME-L discussion forum
IV.   ABOUT THE LYMENET NEWSLETTER


Newsletter:

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                   Volume 6 / Number 04 / 17-APR-98
                                INDEX


I.    LDRC: CDC finds less Lyme but more tickborne diseases in a
     California community
II.   J Infect Dis: Seroepidemiology of emerging tickborne
     infectious diseases in a Northern California community.
III.  LYMENET: How to join the LYME-L discussion forum
IV.   ABOUT THE LYMENET NEWSLETTER



=====*=====


I.    LDRC: CDC finds less Lyme but more tickborne diseases in a
     California community
----------------------------------------------------------------
Reprinted from the Lyme Times, Number 19, November / December 1997


The headline in the January 10, 1995, Sonoma Index-Tribune proclaimed,
"Community A [name changed] not a hot spot for tickborne Lyme
disease" - and the community breathed a sigh of relief.  But was it
really such good news?  A recently completed CDC research study
found that almost one quarter of the study participants had tested
positive for at least one of three tickborne diseases. And if the
humans weren't testing positive for Lyme disease in great numbers, an
astounding 37% & the local dogs did - but then the dogs were not
subjected to the rigid two tier Centers for Disease Control and
Prevention (CDC) testing protocol, and when dogs get sick, no one
calls them hypochondriacs.


Approximately 450 residents live in the semirural community in
Sonoma County in northern California, and 230 participated in the
serologic study.  Fifty-one tested positive for one or more of three
tickborne disease agents: Lyme disease, ehrlichiosis, and babesiosis.
Half of the children in the study tested positive.  Researchers from
the CDC along with University of California scientists and health
department personnel report the results in the June issue of the
Journal of Infectious Diseases. (1)


The Sonoma study was initiated by a local mother and horse-owner
Susie Merrill.  She had participated in a Lyme disease study of her
neighborhood, working with state and county biologists to trap
rodents and drag for ticks.  She conducted a phone survey and marked
suspected Lyme disease cases, including on her map dogs that had
tested positive for Lyme disease.


Maybe ehrlichiosis was to blame

Merrill's son had been diagnosed with Lyme disease in 1991, and
had not totally recovered after treatment.  Several of Merrill's
horses and her dog had also been diagnosed with ehrlichiosis.
Merrill began to wonder if chronic Lyme disease really was the
cause of her son's continuing headaches and other symptoms.  Maybe
ehrlichiosis was the culprit.  Perhaps it was responsible for the
chronic symptoms of some of her neighbors, too.  At the time,
ehrlichiosis was not thought to infect humans.


Merrill went back to the phone and called the neighbors again.
As she collected information, she became convinced that more than
one tickborne disease was being diagnosed as Lyme disease.  When she
plotted the cases of ehrlichiosis on her map, she noticed that sick
people seemed to be clustered near infected animals - but the animals
were infected with ehrlichiosis, not Lyme.


Merrill battles for recognition

Merrill's initial entreaties to public health agencies to
investigate the situation in her community fell on deaf ears. For the
next two years, she badgered health officials, enlisting the support
of her senators and congresspeople with a barrage of letters.  
Finally the CDC agreed to assist the state and county health agencies
in conducting a study.

The published results now suggest that Merrill's hunch was correct.  
Samples from 23% of the residents were seroreactive to antigens from
one or more tickborne disease agents: 1.4% to Borrelia burgdorferi,
0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeenis, and 17.8% to
the Babesia-like piroplasm WA1.

Some scientists are raising questions about the study conclusions,
however.  The incidence of Babesia is very high, raising suspicions
about the test, which is quite new. Then the researchers report
an incidence of Lyme disease barely over the 1% generally considered
as background seropositivity in a control group.  Serosurveys in
endemic areas have typically reported much higher incidences.  An

epidemiologic study of a community in Mendocino County found 24% of
the inhabitants had positive Lyme disease tests. (2)  Many were
symptomatic at the time and more have developed symptoms since,
including psychosis and pancarditis.  Later tests of that community
also showed two percent positive for babesiosis, an unrecognized
human disease in this area at the time of the original serosurvey
(unreported data).


The results of the Sonoma dog study are intriguing, also, although
the dog data were not included in the present study.  If the same
ticks were biting both dogs and humans, it is curious that such a
low percentage of humans were apparently acquiring the Lyme disease
bacterium, when, judging by the ehrlichiosis and babesiosis figures,
many of them were in fact being bitten by ticks.  The dog sera were
tested by Rance LeFebvre, PhD, at the University of California
laboratory in Davis.


ELISA was used as screening test

Initially, community residents had to pass a screening blood test
before being allowed to participate in the study.  This blood test,
an ELISA, has been criticized for its lack of, sensitivity, i.e.
many true cases of Lyme disease test negative.  According to the
College of American Pathologists Proficiency Testing Program, which
receives samples from every laboratory in the United States, current
screening tests are inadequate.  In a paper published in March,
researchers concluded that "the sensitivity and specificity of the
currently used tests [ELISA or IFA] for Lyme disease are not adequate
to meet the two-tier approach being recommended [by the CDC].  
Ideally a screen test should have a high degree of sensitivity
(>95%)."  The data showed that the sensitivity of the ELISAs
fluctuated between 75 and 93%. (3)

Further, participants who may have been seronegative were not counted,
although the researchers acknowledge that they may have existed in
the population sample.  Several investigators have estimated

seronegativity in both early or chronic Lyme disease at 17 to 29.4%
of patients.  (4)(5)(6)  The low figure for Lyme disease reported in
the present study may be partly attributable to the use of the
restrictive CDC testing criteria, which were intended for
surveillance purposes and not for clinical diagnosis.  It may also
be related to the study's use of the B31 strain of Borrelia
burgdorferi used as antigen, although the researchers claim to have
observed no difference in the interpretation of reactivity.  The
Mendocino study found a 20% discrepancy between sera tested B31
and CA5 when people infected with the California strain were tested
against the B31 Shelter Island, NY, strain, and vice versa. (7)


After the study was underway, Merrill complained in a letter to Dr.
Duc Vugia, study collaborator and Chief of the Disease Investigations
and Surveillance Branch at California Department of Health Services,
that many of her neighbors had had a positive test for Lyme disease in
the past, but not in this study.  They had also responded to
treatment for Lyme disease.  She was concerned that these people had
Lyme disease but were being dropped from the study since they did
not meet the entry criteria.


CDC principal investigator Curtis Fritz didn't see it that way.  
At an interview after one of the community meetings for participants,
he assured residents, "Ninety-five percent of the people who have
been diagnosed with late Lyme disease but with negative antibody
tests in fact have never had Lyme disease."  He also claimed that
the CDC test was much better than those of commercial laboratories.
In a recent controversial paper, the CDC reported a 100% sensitivity,
89% specificity of their in-house ELISA test, exceeding previously
reported standards. (8)


People who passed the first screening test had additionally to pass
a second test, the Western Blot, in order to be considered positive
for Lyme disease. This test is sensitive, but the official criteria
for a positive are very restrictive, and are still being debated in
medical circles.

Criteria may be overly restrictive


Dr. [Nick] Harris, president of IGeneX, a laboratory in Palo Alto,
California, which specializes in Lyme disease testing, points out that
different patterns of reactivity and levels of antibody may be seen
in confirmed Lyme disease cases, but these were not considered in
the study.  Other experts feel that it is premature to apply such
restrictive criteria to a disease whose clinical spectrum is still
being defined.  Many agree standards used for surveillance are not
appropriate for clinical diagnosis.


No physical examinations were done to corroborate serologies, no
attempt was made to gather additional serologic data on people who
were symptomatic but ELISA negative, and no Western blots were
obtained on ELISA-negative people, although some investigators have
found Western Blot positive/ELISA negative patients.  (9)(10)


In addition, the questionnaire utilized in the study instructed
participants to skip over questions about symptoms if they had not
been diagnosed with Lyme disease.


"Even if people previously had symptoms of Lyme disease, some have
never been diagnosed with it, so they would have skipped these
questions," claims Merrill.


Nymphal tick infection rate may be much higher

This study assumed a low (1 to 2%) infection rate among ticks found
in the neighborhood.  While this figure reflects early assessments
of adult ticks in California, it is at variance with newer reports
on Ixodes pacificus nymphs, which are considered to be the main
vectors of Lyme disease to humans.  Some parts of Mendocino and
Sonoma Counties have a reported nymphal tick infection rate as high
as 14%. (11)


Dr. Fritz tried to mitigate public fears by assuring people that
seronegative late Lyme disease after treatment is a rare phenomenon
and that the chances of acquiring a tickborne disease are low.  Some
residents of the Sonoma community accepted his assurances, while
others did not.  Some worried that the neighborhood would be labeled
as a Lyme disease hot spot, adversely affecting real estate values.


However several were appreciative of Merrill's efforts to educate
their community.  Linda Marmaduke, one of Merrill's neighbors, said,
"This study was done after many people became ill, some chronically,
with undiagnosed or incorrectly diagnosed illnesses.  Susie Merrill
was instrumental in bringing this disease to the public's attention.  
If she had not shared her knowledge with others, my daughter. for
one, would not have received adequate and prompt treatment."


Perhaps it was an oversight that the study authors did not
acknowledge Merrill's initiative in instigating the study, nor her
work guiding biologists around the area and organizing community
meetings.  They omitted her name from the unusually lengthy list of
acknowledgments at the end of their article.  Still, it is curious,
since certainly without Merrill's persistence, no Sonoma study would
have been done, and without her help as liaison, community
participation probably would have been significantly curtailed.


Since the early l980s, over 1400 cases meeting the strict CDC case
surveillance definition have been reported from California.  This
figure is artificially low even for surveillance because many
physicians do not bother to report their cases since they will not
meet the case definition anyway. (12)  In addition, many West Coast
physicians still deny even the possibility of Lyme disease thinking
of it as an East Coast disease, in spite of the fact that biologists
with the California Department of Health have found the vector in
all but two of the California counties, and infected ticks in
more than half of those. (13)


This new study opens anew the debate about the risk of acquiring a
tickborne disease in northern California.  The Sonoma study
concluded, "The risk of infection with these emerging tickborne
diseases may be greater than previously recognized... particularly
in children."  (14)


REFERENCES:

(1)  Fritz CL, et al. Seroepidemiology of emerging tickborne
    infectious diseases in a Northern California community.
    http://search.lymenet.org/domino/abstract.nsf/UID/97323987

(2)  Lane RS, et al. Risk factors for Lyme disease in a small rural
    community in northern California.
    http://search.lymenet.org/domino/abstract.nsf/UID/93142776

(3)  Bakken LL, et al. Interlaboratory comparison of test results
    for detection of Lyme disease by 516 participants in the
    Wisconsin State Laboratory of Hygiene / College of American
    Pathologists Proficiency Testing Program.
    http://search.lymenet.org/domino/abstract.nsf/UID/97193799


(4)  Engstrom SM, et al. Immunoblot interpretation criteria for
    serodiagnosis of early Lyme disease.
    http://search.lymenet.org/domino/abstract.nsf/UID/95229937


(5)  Oksi J, et al. Antibodies against whole sonicated Borrelia
    burgdorferi spirochetes, 41-kilodalton flagellin, and P39
    protein in patients with PCR- or culture-proven late Lyme
    borreliosis.
    http://search.lymenet.org/domino/abstract.nsf/UID/96025135


(6)  Shadick, et al. The long-term clinical outcomes of Lyme disease.
    A population-based retrospective cohort study.
    http://search.lymenet.org/domino/abstract.nsf/UID/94367953


(7)  Lane RS, et al. Risk factors for Lyme disease in a small rural
    community in northern California.
    http://search.lymenet.org/domino/abstract.nsf/UID/93142776


(8)  Tugwell P, et al. Laboratory evaluation in the diagnosis of
    Lyme disease.
    http://search.lymenet.org/domino/abstract.nsf/UID/98049722


(9)  Cameron D. Non-confirmed ELISA Testing for Lyme Disease: Bayes'
    Theorem Consideration.  VII Int Congr Lyme Borreliosis, 1996,
    Abs E804.


(10) Kochvar JM, Liegner K. Simultaneous ELISA and Western Blot
    Testing in Evaulation of Patients for Suspected Lyme Disease.  
    10th LDF Conf, 1997, Poster.


(11) Clover JR, et al. Evidence implicating nymphal Ixodes pacificus
    (Acari: ixodidae) in the epidemiology of Lyme disease in
    California.
    http://search.lymenet.org/domino/abstract.nsf/UID/96033004


(12) Murray RM, CDHS epidemiologist, personal communication.

(13) Clover JR, CDHS Senior Biologist, map, 1994.

(14) Fritz CL, et al. Seroepidemiology of emerging tickborne
    infectious diseases in a Northern California community.
    http://search.lymenet.org/domino/abstract.nsf/UID/97323987



=====*=====


II.   J Infect Dis: Seroepidemiology of emerging tickborne
     infectious diseases in a Northern California community.
-------------------------------------------------------------
AUTHORS: Fritz CL, Kjemtrup AM, Conrad PA, Flores GR, Campbell GL
        Schriefer ME, Gallo D, Vugia DJ
ORGANIZATION: Division of Vector-Borne Infectious Diseases, National
             Center for Infectious Diseases, Centers for Disease
             Control and Prevention, Fort Collins, Colorado, USA.
REFERENCE: J Infect Dis 1997 Jun;175(6):1432-9
ABSTRACT:


A seroprevalence and risk factor study of emerging tickborne
infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was
conducted among 230 residents of a semirural community in Sonoma
County, California.  Over 50% of residents reported finding a tick on
themselves in the preceding 12 months.  Samples from 51(23%) residents
were seroreactive to antigens from one or more tickborne disease
agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to
Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1.
Only 14 (27%) of these seroreactive residents reported one or more
symptoms compatible with these diseases.  Seroreactivity was
significantly associated with younger age (<16 years), longer
residence in the community (11-20 years), and having had a
physician's diagnosis of Lyme disease.  In northern California, the
risk of infection with these emerging tickborne diseases, particularly
in children, may be greater than previously recognized.



=====*=====


III.  LYMENET: How to join the LYME-L discussion forum
------------------------------------------------------
Sender: Siegfried Schmitt <Siegfried.Schmitt@rz.uni-karlsruhe.de>
             
LYME-L is a discussion forum for researchers who are interested in
diagnosis, treatment, and prevention of Lyme disease.  If you want
to join LYME-L, you should send the command:


  sub lyme-l Your_first_name Your_last_name

via e-mail to

  listserv@listserv.net

If you want to know more about LYME-L, please contact

  LYME-L-request@HOME.EASE.LSOFT.COM (Siegfried Schmitt)


=====*=====


IV.   ABOUT THE LYMENET NEWSLETTER
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