Lyme TimesPublication of the Lyme Disease Resource Center

Education, Support, Advocacy, Research

See New Jersey on page 15

NUMBER 22 JULY–OCTOBER 1998

See Massachusetts on page 16

Tickborne coinfections complicate diagnosis and treatment - page 36

Inside...

by Nelson Sigelman

Tick-borne diseases and increasednumbers of deer, which help increasethe number of ticks, are a growingpublic health issue that must beaddressed by Island officials, says Dr.Sam R. Telford, a leading tickspecialist and research scientist fromthe Harvard School of Public Health.Dr. Telford made his remarks beforea talk sponsored by the Martha’sVineyard Lyme Disease ActionCommittee on the subject of ticks anddiseases at the Tisbury Senior Centerlast week [Sept.].

The issue of tick-borne diseasesreceived added attention followingthe tick-related death this summer ofFrancis “Sancy” Pachico, a popularIsland resident and retired schooladministrator.

Dr. Telford says Island officialsmust take a more proactive approachto deer management in order toreduce tick populations and protectpublic health, now, but more impor-tantly for the future. In part, hisIsland talk is meant to stimulatediscussion because any decisionsmust be made by the community.It is also part of a regional approachto tick-borne diseases conducted byhis laboratory, which is the leadingcenter in the nation for identifyinghow many diseases are transmittedby ticks and what is the burden onthe community.

Every month, as part of a Capeand islands survey, Dr. Telford

This year, the New Jersey LymeDisease Association (LDANJ)decided to award its grants toresearchers who are working onprojects that could lead to a cure forchronic Lyme.

“This has been a banner year,”

Ticks and deercombine in healthrisks to Islanders

New Jersey Associationoffers grants for Lymedisease research

said LDANJ president Pat Smith.“Over $60,000 has been awarded.”

Summaries of the 1997-98 fundedprojects follow:

Dr. Steven Schutzer, UMDNJ,received $30,000 for his project. He

the

The Connecticut-based LymeDisease Foundation (LDF) hasreceived an international award - tophonors (medal) and “Award ofExcellence” for healthcare communi-cations excellence for the “Faces ofLyme Disease” Lifetime TV Special.

According to LDF director/founder Karen Vanderhoof-Forschner, the judges were commu-nications specialists with many yearsof international communications,public relations and advertisingexperience. The CDC, NIH, mostlarge pharmaceuticals, and otherswere competitors in this event. TheLDF was the only one chosen for amedal.

Both the Many Faces of LymeDisease book and the Faces of LymeDisease video are available from theLDF for $15 each. Call 860-525-2000 for more information.

Lyme DiseaseFoundationreceivesinternationalaward

Updated 1998 Diag-nostic Hints and Treat-ment Guidelines ofJoseph J. Burrascano,Jr., MD. See page 21

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July-October 1998Page 2

Lyme TimesNUMBER 22

JULY–OCTOBER

1998

the ©

In this issue...

3 Editorial4 Letters9 Beginners' Pages11 Patient Stories13 Patient Support15 Regional News18 Research47 Conference48 Calendar

From the Editor

The Lyme Disease Resource Center was founded in 1990 as a nonprofit education and communications center for the public, for Lyme diseasepatients, for physicians, and other interested people. The goals of the LDRC are to educate the public about Lyme and other tick-borne diseases,including risk factors and prevention; to provide services for Lyme disease patients and their families and friends; to provide a forum forphysicians and health care professionals for the exchange of ideas and information about symptoms, diagnosis, and treatment of Lyme disease;to be a communications center for individuals and groups who are working to help patients with Lyme disease; and to encourage Lyme diseaseresearch. The LDRC gratefully accepts tax-deductible contributions to assist its efforts.

Publication of the Lyme Disease Resource Center

5 Critique of ACPdiagnostic standards bylab experts

6 Mental healthprofessionals make a"Modest Proposal."

21 1998 Treatmentand Diagnostic Guide-lines of JosephBurrascano, Jr, MD

36 “The New Lyme”--A Look at Coinfectionwith Lyme and Babesia,by Jean Hubbard

Features

Erratum: The sensitivity of theIgeneX Lyme urine antigen assayranges from 30 to 80% dependingupon the number of collectionevents and also whether thepatient has been given antibioticsto promote antigenuria, not 30 to50% as previously stated.

Dear Readers:

An apology is due.

One of the problems with runninga volunteer organization is that thevolunteer work tends to be relegatedto a lower status than other liferesponsibilities such as family, withhealth running a close second. We atthe Lyme Disease Resource Centertake our responsibility to our readersseriously, but sometimes duties tofamily and vagaries of health causeus to fall short of our goals. We donot have a large staff of fulltimeemployees; just a small staff ofparttime volunteers, most of whommust earn a living as well as dealwith lingering Lyme deficits.

The publishing schedule of theLyme Times is one of the elementsthat has suffered periodically. Thisissue was completed two monthsbehind schedule, which meant that ithad to wait an additional severalweeks for the printer who was in themiddle of his holiday rush. We hopeto have another issue out shortly,early in the new year, to make up forthis delay. Also you will notice that

this issue is 16 pages larger thanusual. Regardless, we will make surethat each subscriber receives a fullfour issues of the Lyme Times,whether the schedule is completedwithin a 12-month timeframe or not.People who can't tolerate the sus-pense of dealing with an erraticschedule may request a proratedrefund of their subscription fee. Wehope that most people will “hang inthere.”

Whatever our limitations, we stillbelieve that we are doing an impor-tant job. Education, patient support,support of the many groups servingpatients and researchers around thecountry and indeed, around the world(Germany has a new network ofsupport groups – see page 14) – arevital. The Lyme Times also perceivesas part of its mission fighting forrecognition of new tests and newtherapies which hold promise forpatients. We are privileged to be ableto print papers which have beenrejected by editors of the peer-reviewed literature for reasons weview with some disdain.

We hope you agree that this issueof the Lyme Times is worth waitingfor. Thank you for your tolerance.

Phyllis Mervine, Editor

The recipient of the LDRC 1998Distinguished Physician Award will beannounced in the next Lyme Times.Nominations are welcome. See p. 14.

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Editorialthe Lyme TimesJuly -October, 1998

PublisherLyme Disease Resource Center

the Lyme Times StaffEditor: Phyllis MervineAssociate Editor: Jean HubbardContributors: Susan Fein, Richard Tilton,Mary Sand, Nick Harris, Robert Bransfield,Brian Fallon, Bernard Raxlen, Lynn Shepler,Virginia Sherr, Judy Foreman, DavidBartholomew, Kathy Cavert, Lee Lull, LindellMcElfresh, Joseph Burrascano

The Lyme Times (Library of Congress cardno.92-595999) is published four times a yearby the Lyme Disease Resource Center,266 40th Street Way,Oakland CA 94611

Address correspondence to:

Phyllis Mervine, Editorthe Lyme TimesPO Box 1423Ukiah CA 95482or email at <pcm@pacific.net>

Individual subscription rates 1 year (4issues): domestic $25; Canada & Mexico$35; Foreign $45. Institutional/Library rates$50. Send check to:LDRCPO Box 707Weaverville CA 96093

Send address changes to:

Nancy BrownPO Box 707Weaverville CA 96093or email LDRCsec@snowcrest.net

Include both old and new addresses.

The articles in the Lyme Times are notintended as medical advice regarding thetreatment of any symptoms or disease.Medical advice of your personal physicianshould be obtained before pursuing anycourse of treatment. The Lyme Timesmakes no express or implied warranties asto the efficacy or safety of any treatment inits articles or letters and disclaims all liabilityfor any use of any such treatment. Opinionsexpressed in articles are those of theauthors alone and are not necessarily thoseof the Editor or the LDRC.

Republication of any portion of the LymeTimes without written permission isprohibited. Please contact the Editor if youwish to duplicate articles.

To submit articles, please send electronicfiles on disk to the Editor or via Internet to<pcm@pacific.net>. Original articles arepreferred. Published articles become theproperty of the Lyme Disease ResourceCenter.

© Copyright 1998 Lyme Disease ResourceCenter.

Medical politics impedesscientific progress

Lyme disease has long been abattleground of medical politics –the long-treaters vs. the short-treaters, the over-diagnosers vs. theunder-diagnosers, the strict vs. theliberal case definers. When there is adivergence of opinion, partisanssometimes resort to hyperbole,innuendo, and outright slander. Inthe battle, the patients are the losers.

All most patients want is theirhealth. Surely reasonable people canagree that there may be a multiplic-ity of routes to that goal. According

to a recent article in ScientificAmerican, even placebos have a validrole. Certainly no one would claimthat we already know all there is toknow about Lyme disease or health orthe human mind and body.

Yet some people have alreadyclosed their minds to new informa-tion. We see it in the peer reviewprocess; we see it in the grantfunding; we see it in the name-callingand character assassinations. Thisunwillingness to admit that new

Continued on next page

the Lyme Times

July-October 1998Page 4

We do not recommend any of the doctors or treatments which may bementioned here by writers. You should discuss any treatment options with yourphysician. Signed letters of general interest may be printed.

Letters

I’m writing to inform you of myson’s apparent cure from clinicallydiagnosed Lyme disease, a disablingillness he suffered from for 3 1/2years, beginning on his 8th birthday.I’m not writing simply to share myjoy at this development (though wecan all stand to hear some news likethis once in a while!) but because hissudden, dramatic return to healthraises some very important, funda-mental questions about how “Lymedisease” is defined.

Some background: My son firstbecame acutely ill with fever, severehead, abdominal, back and leg pain,fatigue, irritability and insomnia. Healso had frequent ulcerated, red sorethroats. These were preceded byseveral weeks of occasional vomit-ing/retching, episodes of extremepaleness, “lightning” leg pains, and ared, roughened area over the knuck-les of each hand, with white circlesor disc shaped spots on his facesurrounded/connected by a pale, lacy,

red rash.

Based upon his acute symptoms,negative Lyme tests and a palpablyswollen liver and tender, distendedspleen, he was initially diagnosedwith mononeucleosis, which serologyfailed to confirm. For the following 31/2 years, his most frequent anddisabling symptoms were head andabdominal pain, fatigue, hyperacusisand insomnia.

He was diagnosed with Lymedisease after a year of illness, andtook a variety of oral antibiotics,some in combination, and he alwaysimproved, but remained less thanwell on them, always incapable ofphysical exertion or athletics. Hisgreatest improvement was this pastyear with doxycycline. He alwaysrelapsed, nearly 6 weeks to the day,each time we took him off of antibi-otics. Last June, I asked his Lymedoctor about attempting a trial ofMepron; I had always suspectedbabesiosis (even though my son hadNEVER tested positive for it), basedupon my reading of the literature onit (and the fact that incidents of

coinfection appear to be highest inour area), but neither his doc nor Iwas ever willing to do an empirictrial of the harsh combination ofClindamycin/quinine on a youngchild. Because Mepron seemed to beso “well tolerated” by his youngpatients, the doctor agreed, andprescribed half the adult dose for myson, in combination with Zithromax.

Within a week and a half to twoweeks, my son was in agony;everything hurt, including his bonesand joints (a symptom he had neverreally suffered much from), hisfatigue, head pain and hyperacusiswere extraordinarily bad. His doctorsuggested taking him off of Mepron afew days shy of the three-week mark,and resuming it again in a week if hewere better; if the Mepron weremaking him sick, we would knowonce we resumed it.

My son became well within 24 -48 hours of stopping that first roundof Mepron, then easily toleratedsubsequent courses with no difficultyand has had NO RESIDUALSYMPTOMS since!

He is doing about 3-4 hours ofstrenuous karate per week, gym classthree times per week, walking toschool, and had lots of stamina forhiking, biking and swimming thispast Summer. He is no longer takingany medications. Some questions,made particularly salient by therecent Krause publication [Krause etal, “Concurrent Lyme Disease andbabesiosis. Evidence for increasedseverity and duration of illness,”JAMA 275(21):1657-1660 (1996)]:

1) Was Lyme disease in Con-necticut or anywhere else EVER asimple borrelial infection, or did theyjust stop looking for pathogens onceBurgdorfer found Bb?

2) In a case like my son’s, are wedealing with seronegative babesiosis,as suggested by his response toMepron, or are there even MOREpathogens/parasites etc. implicated in“Lyme disease” than we know?

3) As the prevalence of HGE,

Child with seronegativebabesiosis respondsdramatically to Mepron

findings may have merit is neitherrational nor scientific. People tryingto report discoveries that threaten thestatus quo are rejected by publishersand subjected to personal attacks byprofessional colleagues. This is notscience, rather a nasty picture ofincumbents protecting their turf.

Given the current state of ourknowledge about tick-borne diseases– knowledge that is still veryrudimentary – it is premature to formhard-line positions. Our advice tophysicians is to keep an open mind,listen to your patients, and try tomake them well. Stay current withthe basic research. Respect others’

opinions. They have a differentexperience set. There may be yet-to-be-discovered factors at play andyour own ignorance may be the causeof your lack of understanding.

Both science and professionalethics certainly demand a higherstandard than we have been witness-ing. Politics may make money andreputations, but it does not curedisease. As patient advocates, we callfor an end to the posturing which hasmade a political football out of Lymedisease, but does not help thepatients. We beg for a return toscience.

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HME and babesia, along with RMSF,encephalitis-inducing deer tick virusand who-knows-what-else becomebetter known, are we completelyblowing our Lyme disease researchbudget at NIAID by doing anantibiotic treatment study before weknow what the totality of the diseaseIS and why some folks get better andsome can’t seem to throw it off withany amount of antibiotics?

Additionally, I want to make theobvious observation: often we justdon’t know for sure what we actuallyhave with tick borne diseases or withsuspected TBDs. Most academicresearchers make the case (and, infact, some denied that my son waseven ill, despite his pediatrician’sreport and grave concerns) that ifthey don’t get the magic lab result oreyeball and measure the rashthemselves, no treatment is in order.The problem is, they are routinelycasting vulnerable lives aside,making no effort to relieve suffering.When children are involved, this isparticularly shameful and must notbe tolerated.

At the same time, I am acutelyaware of the risks of pouring power-ful drugs into anyone’s body, muchless my child’s, and for years at atime! My husband and I agonizedover our choices often, as did myson’s Lyme doc, but it always camedown to our trying to buy our childsome quality of life each time itslipped away again. With competent,compassionate and educated carefrom a clinically astute doctor notafraid to try to help despite theprevailing orthodoxy, we just keptpushing buttons for two and a halfyears until we hit the right ones.

I know we got very, very lucky.

I’m hoping the news of ourexperience brings the same kind of“luck” to some other Lyme diseasepatients. I guess I’m describingeducated guesswork here, and thesemay not have been acceptable odds toplay for some orthodox academicmedical folks or clinicians whoweigh risk/benefit by another

We have several concerns withthe report entitled “Guidelines forLaboratory Evaluation in theDiagnosis of Lyme Disease” (AnnalsInt. Med 127, 1106-1123. 1997)

• The Centers for Disease Controlhave developed a set of clinical anddiagnostic criteria for surveillancepurposes. The authors of these“Guidelines” state that these criteria,with no substitution, are alsoapplicable to the clinical diagnosis ofLyme disease. To our knowledge, nosuch evidence exists. It would appearthat the published “Guidelines” have

Lab experts criticize ACPdiagnostic guidelines

Introduction by Dr. Harris:Richard Tilton, Ph.D, ABMM, MarySand, Ph.D. and I responded to theposition statement on Lyme DiseaseDiagnosis which was published inthe Annals of Internal Medicine(127:1106-23,1997). After ninemonths the editors have decided notto publish our response. The three ofus are all board certified in ourrespective fields of laboratoryscience and have over sixty years ofexperience running the most techno-logically advanced immunology,microbiology and molecular diag-nostic laboratories in the nation. Wehave serious reservations about thearticle in question and felt the“Letter to the Editor” was the mostappropriate forum for discoursebetween us and the authors. Appar-ently the Editors did not see it thatway. Our concerns are still validand need to be aired. That is thereason for presenting it in thecurrent format.

standard. But he’s not their kid.

I wonder -- what if he had been?

Susan L. FeinLong Island, NY

Please read our articles on co-infection and Mepron in this issue:pages 36-47.

as a basis a clinical criterion forLyme disease diagnosis which hasnever been tested except for clinicalstudies published by the authorsthemselves. There is no externalvalidation to support the claim ofequivalence between clinical diag-nostic criteria and the CDC surveil-lance definition.

• The authors state that “testingwith ELISA is the cornerstone oflaboratory diagnosis for Lymedisease”. In fact, it is not. Thecommercially available ELISA assaysfor Lyme disease do not meetacceptable criteria according to thegroup that is responsible for much ofthe United States Laboratory profi-ciency testing program in Lymedisease. The data, from a recentstudy by Bakken et al.. (J. Clin.Microbiol. 35:537-543,1997),indicated “that the sensitivity andspecificity of the currently used testsfor Lyme disease are not adequate tomeet the two-tier test approach beingrecommended by the CDC/ASTPHLD group”. Bakken et al.(1997) also stated that a screeningtest must have >95% sensitivity toadequately screen for Lyme diseaseand that the currently availableELISA tests do not perform at thatlevel.

• The authors have not followedthe CDC/ASTPHLD recommenda-tion for two-tiered testing. That is,all indeterminate and reactiveELISAs should be reflexed toWestern blot (WB), not just indeter-minate ELISAs as the authors of the“Guidelines” suggest. Certainly theauthors realize that reactive LymeELISA results may be nonspecificbecause of a number of cross reactingantibodies (e.g. antibody to the 41Kda flagellin protein).

• The authors have missed someimportant studies of Westernblotting, especially those that may becritical of the recommendations ofDressler et al. (J. Infect. Dis. 167,392-400,1993) and the CDC/ASTPHLD. The report by Engstromet al (J.Clin.Microbiol. 33:419-427,

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July-October 1998Page 6

1995) found, for example, that 20%of their Lyme patients remainedseronegative throughout the studyand that fewer bands on the IgG WBcould be appropriately used forinterpretation. They noted that theWB was more specific and moresensitive than the ELISA. Theirstudy also showed that only 19% ofpatients treated with antibiotics for20 days still had a positive ELISAantibody response after one year, yetalmost 60% of their patients contin-ued to be WB positive at the end ofthe first year. The study by Aguero-Rosenfeld et al. (J. Clin. Micro. 34:1-9, 1996) reported that 89% ofpatients with culture-confirmederythema migrans (EM), developedspecific IgG antibodies by WB, butonly 22% of these patients werepositive by the interpretive criteriaproposed by the CDC/ASTPHLD.They further reported that theduration of the antibody responsewas related to the duration of theEM. Tilton et al. (1997) stated that ahighly sensitive and specific Westernblot is desirable for a two tiered testapproach or as a primary test.Despite the CDC/ASTPHLD recom-mendations, many physicians whotreat patients for LD do not believethat an ELISA is an appropriatescreening test and consequently usethe Western blot as a primary test.

• The authors state that patientsnot be tested for Lyme disease unlessthe pretest probability of disease isbetween 0.20 and 0.80. Theserecommendations will:

a ) rule out any laboratorydetection of B. burgdorferiantibodies,antigens, and/or DNA in non-endemic areas.

b) require physicians to screenpatients based on epidemiologicaldata which may not be available tothem outside their own local area

c) require physicians to knowthe performance characteristics of awide variety of Lyme disease tests.

• The authors in their commenton non-antibody based tests havechosen to overlook a number of

publications on the utility of directdetection tests for Lyme disease. Acomprehensive review of moleculartechniques for diagnosis of Lymedisease has recently been publishedby Schmidt (Clin. Micro Rev. 10,185-201, 1997). They state “evidenceis growing that a positive PCR testcan be associated with active disease;after adequate therapy, PCR resultsare usually negative.” Manak et al.(J. Spirochet. Tick-Borne Dis. 4., 11-20. 1997), in a well controlled studyusing the CDC criteria for selectionof patients, indicated that PCR onserum, plasma, or buffy coat could beeffectively used to monitor theefficacy of therapy. Similarly, Harriset al. (J. Spirochet. Tick Borne Dis.237, 1995) have validated the Lymeurinary antigen test (LUAT) in morethan 700 LD patients and controls.The LUAT has a specificity of >95%.

These “Guidelines” only compli-cate an already complex diseasediagnostic process.

Richard C. Tilton, Ph.D.,Diplomate American BoardMedical MicrobiologyMary N. Sand, Ph.D.BBI Clinical Laboratories, Inc.75 North Mountain Rd.New Britain, CT 06053Nick S Harris, Ph.D., DiplomateAmerican Board MedicalLaboratory ImmunologyIGeneX Inc. Reference Laboratory797 San Antonio RoadPalo Alto, CA

The Lyme Times is pleased tohave the opportunity to publish thisimportant critique of the AmericanCollege of Physicians “Guidelinesfor Laboratory Evaluation in theDiagnosis of Lyme Disease.” Part ofour mission is to ensure that worthyideas are allowed free expression inthe public foruum. We regret that theACP peer-reviewers and editors haveapparently found it expedient toclose the door to healthy debatewhen so many questions about thediagnosis of Lyme disease stillremain unanswered.

In response to Dr. VirginiaSherr’s letter in the July 3 issueabout the increase in the number ofpatients showing an unusual syn-drome of neurological soft signs thatmay be linked to Lyme and othertick-borne diseases, and in theinterest of health, public safety, andquality of life, we, as psychiatrists,state the following:

Whereas:

1. Lyme disease and other tick-borne diseases are a serious publichealth threat;

2. These often cryptic diseases areassociated with a broad spectrum ofmental and other physical disorders,birth defects, and cognitive impair-ments that increase the risk ofaccidents, violence, memory loss,disabilities, and suffering;

3. Mental illnesses associatedwith these frequently unsuspectedinfections include, but are not limitedto, depression, phobias, obsessive-compulsive disorders, panic disor-ders, aggressiveness, delusions,irritability, suicidality, exhaustion,sexual dysfunction, sleep disorders,eating disorders, and a broadspectrum of cognitive and neurologi-cal impairments. Findings morecommon in children include autism,Tourette syndrome, attention deficitdisorder, dyslexia, lethargy, and adecline in grades, tantrums;

4. Since late-stage Lyme diseasepresents primarily as a neuropsychi-atric rather than an arthritic disease,psychiatrists are encouraged tobecome more active in the diagnosisand treatment of Lyme disease;

5. The diagnosis of Lyme diseaseshould take into consideration

Physicians make a “Mod-est Proposal” regardingneuroborreliosis

From American PsychiatricAssociation’s newsletter, “PsychiatryNews,” Sept. 18th, 1998 issue,Letters to the Editor. Reprinted bypermission.

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Late stages of Borreliaburgdorferiinfection are sometimesdifficult to treat, and even repeatedcourses of intravenous penicillin Gand/or cephalosporins may fail(1,2,3). Urban, Rahal and Luft haverecently demonstrated in vitro thatBorrelia burgdorferiis able toproduce β-lactam hydrolyzingproteins which can be effectivelycounteracted by tazobactam, a beta-lactamase inhibitor (4,5).

Here we present 7 cases ofverified late Lyme borreliosis (ECMhistory, pos. IgG, pos. Western blot)who have undergone repeatedcourses of high dose intravenouspenicillin G and/or various cepha-losporins for more than 2 years. Inthese patients the first course of i.v.treatment usually has brought abouttransient improvement of symptoms,but none of the subsequent regimenhas had any marked therapeuticeffect.

The patients now were treated

Successful treatment bycefoperazone sulbactamof late Lyme borreliosisrefractory to repeatedintravenous antibiotictherapy (includingcefoperazone itself)

epidemiological risk factors fordisease and be based upon a thoroughhistory, physical findings (includingneuropsychiatric), laboratory testing,and response to antibiotic therapy.Commonly used tests include theWestern Blot, neuropsychologicaltesting for the cognitive component,and SPECT scans. Tests that arebeing used with increasing accep-tance include PCR, cultures, Lymeurine antigen test, and PET. Spinaltaps are most commonly negative inthe late-stage neuropsychiatricsyndrome;

6. Research on early Lymedisease has been mistakenly utilizedby some insurance companies as thestandard that determines diagnosticand treatment guidelines for late-stage Lyme disease. This positionresults in the inappropriate denial ofreimbursement for vital ongoingmedical care;

7. We recognize the need forlong-term antibiotic treatment insome of these patients. We areconcerned that financially motivated,restrictive treatment guidelines ofsome of the insurance companies areharmful to patients and the overallpublic welfare;

8. Public awareness, education,prevention, vaccines, early diagnosis,correct psychiatric diagnosis,effective treatment, guidancethroughout the treatment, advocacy,and research help to reduce theseriousness of this epidemic;

9. We acknowledge and supportthe efforts of patients, supportgroups, clinicians, researchers, drugcompanies, and advocates who showthe commitment, courage, andcreativity to meet the challenge oftick-borne diseases;

10. In addition to tick-bornediseases, other infectious diseasesand complex interactive infectiousdiseases are increasingly recognizedas being associated with mentalillness.

We therefore advise that:

1. An APA committee be estab-

lished to better coordinate informa-tion, research, education, policy, andguidelines in this area;

2. The name of the committeeshall be the Committee on Tick-Borne and Other Complex InfectiousEncephalopathies.

Robert C. Bransfield, M.DRed Bank, New JerseyBrian Fallon, M.D., M.P.H.New York, New YorkBernard Raxlen, M.D.Greenwich, ConnecticutLynn Shepler, M.D., J.D.Falmouth, MassachusettsVirginia Sherr, M.D.Holland, Pennsylvania

with cefoperazone 2g plus sulbactam(6) lg bid i.v. for 14 days, which wasfollowed in 6 patients by a typicalJarisch-Herxheimer reaction. It isnoteworthy, that 4 patients alreadyhad received cefoperazone withoutimprovement of symptoms.

At the end of treatment, allpatients were symptom-free and haveremained so for the following sixmonths. At this time, IgG againstBorrelia burgdrorferi has beendecreased in 4 patients and waswithin the normal range in the other3 patients.

We conclude that the addition ofβ-lactamase inhibitors to intravenoustreatment could be beneficial inLyme disease refractory to conven-tional treatment.

REFERENCES

1. Dattwyler R . J., Halpern J . J.,Volkman D.J., Luft B.J.: Treatment of lateLyme borreliosis - randomised comparisonof ceftriaxone and penicillin. Lancet i:1988; 1191-1194

2. Johnson R.C., Kodner C., Russel M.:In vitro and in vivo suscepibility of theLyme disease spirochete Borreliaburgdorferito four antimicrobial agents.Antimicrob Agents Chemother 1987; 31:164-167

3. Gasser R., Dusleag J, Reisinger E,Stauber R, Feigl B, Pongratz S, Klein W,Furian C & Pierer K: Reversal byceftriaxone of dilated cardiomyopathyBorrelia burgdorferiinfection. Lancet i1992: 339, 1174-1175

4. Stapleton JT, Stamm LV, Baseford PJJr: Potential development of antibioticresistance in pathogenic treponemes. RevInfect Dis 1985; 7 Suppl 2: S314-317

5. Urban C, Rahal JJ & luft B: Effect of aβ-lactamase inhibitor, tazobactam, ongrowth and penicillin-binding proteins ofBorrelia burgdorferi. FEMS MicrobiolLett 1991; 66: 113-116

6. Jones RN, Barry AL, Thornsberry C etal.: The cefoperazone-sulbactam combina-tion. In vitro qualities including ‘3-lactamase stability, antimicrobial activity,and interpretive criteria for disk diffusiontests. Am J Clin Pathol 1985; 84: 496-504

Robert Gasser, E. Reisinger, B.Eber, S. Auer, J. Bergloff & W.Klein

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July-October 1998Page 8

Recently, I have had my BatMitzvah, a Jewish celebration of achild’s graduation to adulthood.Because this is a very special holiday,a common gift is money, and I wouldlike to donate a portion of that moneyto this cause.

I would like to donate to thisorganization because many of myrelatives, including my very ownmother, have and are suffering fromLyme disease. You may alreadyknow my cousin, BarbaraBarsocchini, from all the work she isdoing to help people with thisterrible disease. I would like tocontribute as well. I hope the moneywill be put to good use.

Jenna CarlssonDanville, California

We were very touched to receivethis special donation. It will be put towork supporting patients andeducating people about Lymedisease. And we certainly do knowBarbara Barsocchini; she is a veryactive member of the LDRC Board ofDirectors.

Youngster shares her BatMitzvah gift with LDRC

I am a 35-year-old woman whoselife has been destroyed by Lymedisease. I was bitten by a tick when Iwas 15 years old, but did not knowwhat was wrong with me until 12years later, when I became com-pletely disabled.

When I found out I had Lymedisease I spent 2 and 1/2 yearssearching for a doctor to treat me. Idid finally find someone, but by thenit was too late; the i.v. antibiotics hadno effect.

Now I have gone from being veryactive in singing and dancing inmusicals to being overjoyed when Imake it to the bathroom in time. Ihave 2 bachelor’s degrees and hadplanned a long and successful careerin Human Resource Management,but now it takes me 3 days just toreconcile my checkbook!

I am an organized, motivated,goal-oriented young womanimprisioned by a disease that thedoctors should no longer be ignorantabout. Unfortunately, we seem tohave the insurance companiesrunning our treatments and not thedoctors.

Because of my experiences withfamily, friends, doctors and mourn-ing of losses, I have written pam-phlets and created a web site of myown to minister to all who aresuffering from debilitating, chronicillness. The devastation of living as aprisoner inside a diseased body isunfathomable; and, getting through italone is a tragedy! Therefore, I havefocused on educating the friends and

Disabled patient createsweb site to supportpeople with chronic dis-eases

family of chronic illness sufferersabout how we need their support,understanding and belief!

Please access my site andconsider linking it to yours. Iappreciate your endeavor to educateothers about this monsterous diseaseand the tragic use of misinformationto keep it alive; thousands of peopleare suffering as lives are beingcrushed needlessly, because ofpolitical and financial pressures; theleast I can do is to help others gainthe support they need from theirskeptical families.

IDA (The Invisable DisabilitiesAdvocate)Web site address:www.orci.com/~invisibleE-mail address:invisible@orci.com

The Borreliosis Study GroupDepts. Medicine & OphthalmologyAuenbruggerplatz 15University of GrazA-8036 Graz, Austria

Will substance in lizardblood provide a cure?

I read about Dr. Robert Lane’sdiscovery regarding the ability oflizards’ blood to kill Lyme spiro-chetes in ticks [the Lyme Times #21].Is anyone using his research to try toexplore the possibility that a sub-stance in lizard blood might killLyme spirochetes in humans? Itwould be tragic if this obviouspossibility were not being investi-gated by any researcher.

I have chronic Lyme and recentlyhad a 100% relapse after beling instable condition for several years. Asyou know, IV antibiotics are notterribly effective and cause dangerousside effeccts. Due to side effects anddrug allergies, I can no longer betreated with IV antibiotics nor withany oral drugs except perhapstatracycline, which gave me an ulcerafter six days.

I was a successful writer whosigned a contract with a major talentagence the same week that I relapsedfrom Lyme, destroying any chancethat I will be well enough to work.

Is anyone doing research on non-antibiotic treatments for Lyme. Ifnot, why not, since antibiotics don’twork?

Shouldn’t the LDRC make it itstop priority to interest a researcher instudying this question? This, notantibiotics, may be the only hope forchronic Lyme.

Staton RabinTarrytown, New York

Researchers are studying thesubstance in lizard blood to see ifthere is a possible pharmacologicaluse for it in treating Lyme disease.However, it is unlikely that lizardblood substance will be useful tohumans, at least not for a long time.

We can never be sure that theopinion we are endeavoring to stifleis a false opinion; and if we weresure, stifling it would be an evil still.

John Stuart MillOn Liberty (1859)

Number 22

Publication of the Lyme Disesase Resource Center

Page 9

Lyme disease: It'sfrustrating, mystifying andvery sneakyby Judy Foreman

Lyme disease is one of the mostinsidious illnesses around. It getsyouwhile you’re doing somethingpleasant — like walking in the woodson a summer day.

The tick that carries it is so tiny —the size of the period at the end of thissentence — that you can barely see it.And seeing it is important, because ifyou pick it off with tweezers within 24to 48 hours, chances are you won’t getsick.

Finally, the circular red rash thatdevelops around the tick bite is easy tomiss. Yet if you ignore it, or the fever,chills, headache and fatigue that willfollow in the next few weeks, you maymiss your best chance to stop the dis-ease before it turns chronic — andcauses trouble for years.

Like chronic fatigue syndrome orfibromyalgia, Lyme disease, especiallythe chronic form, has been so misun-derstood that frustrated patients andmystified doctors have long been atodds. But following a conference ofdoctors and activists last month [April1997] at the National Institutes ofHealth, the hostilities seem to be sim-mering down and the scientific contro-versies coming into sharper focus.

Both activists and researchers agreethat preventing Lyme disease is bothpossible and critical. They also agreethat no one really knows how manypeople have it — it’s both vastlyunderdiagnosed and, in some cases,wrongly diagnosed in people who don’treally have it. The federal Centers forDisease Control and Prevention inAtlanta counted 16,197 new cases na-tionwide last year, up from roughly12,000 the year before. In Massachu-setts, there were 361 new cases last

year, up from the roughly 150 to 250 ayear in recent years. No particular “hotspots” are expected this year, but thedisease is spreading slowly through-out the state [Massachusetts].

“Only a fraction of the true casesare identified and reported,” says Dr.Bela Matyas, medical director of theepidemiology or disease tracking pro-gram at the state Department of PublicHealth. And reporting may actually bebetter in the Northeast than elsewhere.

Lyme disease was discovered inConnecticut in the 1970s, and condi-tions in the New England region areideal for the Lyme disease spirochete,the bacterium that lives in ticks. Thetick that spreads Lyme disease — andtwo other diseases called babesiosisand ehrlichiosis — has a complex lifecycle. In the larval stage, the tick liveson white-footed mice. The tick thenmolts, becomes a nymph, drops off themouse and sits in low brush waiting foranother animal to feed on.

It is at this stage that a tick bite ismost infectious to humans. In its adultstage, the ticks live on deer. This meansthat large deer populations —like thoseon Nantucket, where residents and stateofficials last week held a hearing toconsider culling herds — help keepthe ticks’ life cycle humming. Adultticks can also infect humans, but lessreadily.

It’s the diagnosis and treatment ofLyme disease that really gets compli-cated — and controversial. Once thetell-tale rash is gone, for instance, it isdifficult even to diagnose Lyme dis-ease.

CDC’s guidelines suggest using alab test, called ELISA, to check forantibodies against the spirochete. But

this test can be inconclusive, so a sec-ond more specific antibody test calleda Western blot is often done. But eventhis may not be decisive. It can takeweeks for the body to make antibodies,so a newly infected person may testnegative but still have the disease. Andsome people seem to have Lyme dis-ease without any detectable antibodyresponse.

Some doctors also use another test,called PCR, or polymerase chain reac-tion, to look for pieces of DNA fromthe spirochete itself. But if, as somesuspect, the spirochete can hide insidenerve and immune cells, this couldmake it harder to detect by PCR.

For some people who never noticeda bite or rash, the first sign of acuteinfection is meningitis, an inflamma-tion of the lining of the brain, or a typeof facial paralysis called Bell’s palsy,or fainting due to heart block – anelectrical malfunction caused when thespirochete infects the heart.

Once acute Lyme disease is diag-nosed, the usual remedy is 10 to 30days of oral antibiotics — usually doxy-cycline or amoxicillin, says Dr. AllenSteere, chief of rheumatology and im-munology at the New England Medi-cal Center, although a newer drugcalled Ceftin can also work. (Doxycy-cline and other drugs in the tetracy-cline family also fight ehrlichiosis, butit takes a more complex antibiotic regi-men to treat babesiosis.)

Even though antibiotics work mostof the time, Karen Vanderhoof-Forschner, founder of the Connecti-cut-based Lyme Disease Foundation,worries because data from animal stud-ies suggest that treatment does notalways make infection go away. And ifthe initial infection is not adequatelytreated, the bacteria can lurk in thejoints and the nervous system, produc-ing chronic Lyme disease — even yearslater.

In some people, the result is arthri-tis in the knee, in others, it’s a brainproblem called encephalopathy whichleads to memory impairment and irri-tability. Still others develop pain,numbness, and tingling in the hands

Beginners’ Pages

the Lyme Times

July-October 1998Page 10

Prevention is the key• Learn to look for the deer tick, Ixodes dammini [sic.], on your skin orclothing after walking in fields or woods. It looks like a dark speck about thesize of the period at the end of this sentence.• If you can’t avoid areas where ticks thrive — woods, marshy areas, highgrass and bush — wear long pants tucked into high socks and long-sleeved shirts. Wearing light colors make it easier to spot ticks that get onyour clothes.• Insect repellants may also help. One called permethrin works, but youmust apply this only to your clothing, not your skin. Standard repellantscontaining DEET (diethyltoluamide) are also effective and can be applied tothe skin.• Because too much DEET can cause nerve damage, adults should notuse it at concentrations higher than 30 to 35 percent; children should notuse concentrations higher than 10 to 15 percent. Never put DEET oninfants under age 1.• When you get home from a tick-infested area, shower or bathe and checkyourself and your children carefully for ticks.• Remove ticks with a pair of tweezers within 24 to 48 hours.• If pets have been in tick-infested areas, check them, too, as well as areaswhere they sit or lie. Ticks can drop off from pets onto couches and rugs.

JUDY FOREMANFor more information:• If you are interested in enrolling in the New England Medical Center studyof the treatment of chronic Lyme disease, call: 1-888-LYME-CTR. (1-888-5963-287)• Lyme Disease Foundation hotline 1-800-886-LYME (1-800-886-5963)• American Lyme Disease Foundation, Inc., 914-277-6970.

and feet.

It’s still unclear whether these prob-lems result chiefly from a flareup of alatent infection or, as may happen witharthritis, from an auto-immune attackin which the body attacks tissues har-boring the spirochete.

“I think chronic Lyme disease is apersistent infection and that we haven’tfigured out how to get rid of enoughbacteria to cure people,” says Dr. SamDonta, an infectious disease specialistat Boston Medical Center and BostonVeterans Affairs Medical Center.

For chronic Lyme, Donta advo-cates long term treatment — 6 monthsor more — with oral antibiotics suchas tetracycline or an erythromycin-like drug that can kill bacteria insidecells.

“My advice is that if a patient startsto improve after two weeks, don’t stop.Keep going until he’s all better,” hesays. Other specialists advocate longterm treatment with intravenous anti-biotics, which may penetrate the ner-vous system better.

But all this is hotly debated. Steere,for instance, says, “Nowhere in themedical literature is there informationto support the value of giving antibiot-ics for 10 months, and there is poten-tial danger — such as allergic reac-tions, colitis or gall bladder problems.”

Rosalie Trevejo, a CDC veterinar-ian, agrees: “Treatment for over a yearwould be dangerous.”

Some answers may come from a$4.2 million study now getting underway at NEMC by Dr. Mark Klempner,who plans to follow 260 chronic Lymedisease patients, giving half of them90 days of antibiotics and the otherhalf a placebo.

Ideally, a vaccine could head offmuch of this misery, but that vaccine“fix” may not come as easily as oncethought.

Two similar vaccines — one byConnaught Laboratories, Inc. and theother by SmithKline Beecham — havebeen tested in thousands of people andthe results are now being analyzed,

says Steere, the principal investigatorof the SmithKline study.

But, he says, “There’s no vaccineready for this season and I don’t yetknow about next year.”

Others say the antigen, or marker,used in both these vaccines may not bethe most effective one. A third com-pany, MedImmune, Inc. is betting thata vaccine based on a different proteinon the spirochete may work better, butit won’t even begin to be tested inpeople until next summer.

And some researchers worry thatvaccines might reactivate infection inpeople who have had Lyme disease inthe past. Donta has several recoveredpatients who were vaccinated and then“started to have symptoms after get-ting the vaccine, usually the booster. Itmakes you wonder whether the vac-cine didn’t set something off.”

Other issues still simmer, too.Karen Vanderhoof-Forschner, who hashad Lyme disease, believes her soncaught it from her while she was preg-nant. He died six years later.

But researchers are still unsurewhether the Lyme spirochete can crossthe placenta. So far, there’s some evi-dence in mice that it can, and threeunconfirmed cases in people.

All of which means, saysVanderhoof-Forschner, that the bestway to deal with Lyme disease is toprevent it.

Reprinted by permission from TheBoston Globe, May 19, 1997. JudyForeman is a member of the Globestaff. Her email address is<foreman@globe.com>

Number 22

Publication of the Lyme Disesase Resource Center

Page 11

Patient stories

I took me a long time to stick thisnewsletter together. I tried to writesomething, but trashed it a few times.For some reason nothing I wrote feltquite right. Last letter was Marchand it’s now September.

On June 3rd (Yale Protest Day) Idid manage to call the office ofDavid Kessler twice. He’s the Deanof the School of Medicine at Yale. Igot to talk to two different secretar-ies: I called twice. I asked for astatement from his office in defenseof Yale against the protest going onoutside his office. And I furnishedthem with all my personal informa-tion; email and snail mail addressesas well as my phone number.

I mentioned three main things forwhich I would have liked to see somedefense. In reference to the March1998 article from Yale’s LymeClinic, “The Consequences ofOverdiagnosis and Overtreatment ofLyme disease: An ObservationalStudy,” I looked for justification ofthese:

1) The practice of makingpsychiatric conclusions based ontelephone conversations up to twoyears after seeing the patient.

2) The unsupported assertionthat Lyme disease is an inflammatorydisorder (only).

3) Because of disregard forcurrent information in peer-reviewedand easily available medical litera-ture, at least some of us feel thatwhat their Lyme clinic publishedborders on academic fraud.

There was no attempt by theDean of the Medical School to makea response to me. I don’t blameKessler for that: I surely would not

by David Bartholomew

“For me, theproblem centers ondecisions: Which fileshould I put this in?Do I remember if Ieven started a file forthis?”

want to be the one to attempt todefend that kind of thing.

Yale’s article appeared in theMarch 1st, 1998 Annals of Internal

David Bartholomew is a Mensa member with Lyme diseaseneuroencephalopathy. He is also editor of LymeSig Newsletter (LymeSig is aSpecial Interest Group of American Mensa, Ltd. The following article waspublished in the September issue.

On the more personal side ofthings, the old house I lived in wasdemolished on April first. I had tomove my stuff quick... just to next-door but still not an easy task. I canremember dashing into the house tosave something I forgot, lookingtowards an awful noise, and watch-ing the rear wall come crashingdown. From my kitchen I lookedpast the wrecking shovel-dozer allthe way down the alley. Fortunately,a couple of friends helped carrythings out for a couple of days. Sixmonths later, I am still ponderingwhere to put the things I haven’talready thrown away.

I took this change as an opportu-nity to be as creative as I could. Iconsidered it a mental and physicalchallenge. The new landscaping andthe new lawn, which are now fully upand beautiful, I consider to be alandmark victory in my own personalbattle with my disease.

Of course, except for keepingdoctors appointments and resting, Iwas not able to do much else.

That is one reason why there hasnot been a newsletter since March.Disorganization coupled with thephysical inability, pain and fatiguewere the main handicaps to over-come to get anything at all done.

For me, the problem centers ondecisions: Which file should I putthis in? Do I remember if I evenstarted a file for this? Which shelfshould this book be put on, and whatwas that telephone call I was sup-posed to make? I hope I didn’t missa doctor appointment again. Wheredid I put my appointment cards thelast time I tried to decide where tokeep them? That note I wrote tomyself two days ago on a post-itsticky is around here somewhere...where the blazes did I put that?

When faced with the dilemma ofthis type of disorganization, the onlything I can do is to Stop. Stop stonecold completely. I have to get up andwalk away from the things demand-

Medicine, and my review of that isavailable on my Website at thefollowing address: http://pages.prodigy.com/JRQR18A/yale.htm. If it bothers you whensomeone calls clinicians and profes-sors at Yale “Witchdoctors,” thenperhaps you may not want to read myreview.

One of Yale’s alumni, Douglas S.Dodge, class of ‘43, bothered to writeDean Kessler. He asked why theclinic does not use direct detectiontests such as the LUAT instead ofrelying only on Elisa and Westernblots, which measure antibodyresponses of the infected host, aresponse that may or may not occuror be at measurable levels in manypatients. His letter was passed by theDean’s office to the clinic. Theresponse was that the LUAT is “notreproducible.”

See Douglas Dodge’s website atthe following address for details.He’s not very happy about this either.The address is <http://www.lymetruth.org>. Continued on next page

the Lyme Times

July-October 1998Page 12

ing decisions and memory. A whileago, finding myself frustrated to thepoint of self-hatred when trying toforce myself to “get the job done,” Irealized that there was simplynothing I could do: not at thepresent time. Rather than allowingmyself to become upset about mynon-responding mental faculties, Iwalk away and do.... anything else.Anything. Because if I do not, I havelearned that I will trigger anotherfoul period of depression. And theonly thing depression does for me ismake a bad situation worse. So Ihave learned to accept my chronicrelapsing mental debility. But I onlyachieved this because I have learned

to recognize it for what it is: Lymeencephalopathy. Later, when I amnot as encephalopathic, more clarityand lucidity will return. Maybe foran hour, maybe for several hours.That is how I cope with chronicrelapsing encephalopathy.

I am interested in learning moretechniques for managing and copingwith encephalopathy.

My own survival demands it.

David Bartholomew may bereached at 323 Chapel Avenue,Allentown, PA 18103-3457 or emailat

I have a friend who almost diedfrom undiagnosed Lyme disease. Shehad an MRI of her brain before shewas treated for Lyme disease. Thedoctor who read the MRI said if hehadn’t known it was the MRI of thebrain of a 37-year-old woman, hewould have guessed that she was anadvanced Alzheimer’s patient. Shewas given five months of IV antibiot-ics and relapsed after three monthsoff. She had another three moremonths of IV antibiotics and relapsedagain. Finally, after flying crosscountry to see a Lyme-literate doctor(LLMD), she had one year of IVantibiotic treatment and has been onorals for five years and is doing verywell.

She has a bad day now and then.When she had her last MRI the whitematter lesions were gone. She nowruns a business and has two veryactive teenagers. She is the person Iknew before she became so ill. Shewas bedridden for one year—mostlybecause of very stupid mistakes bydoctors who didn’t know and didn’tcare. She now has a life. She

wouldn’t if she had not had theantibiotic treatment.

Each time my friend was off ofantibiotics she would regress to thepoint where she would not recognizeme if I left the room and re-entered.She could not remember somethingwe had talked about or a film we hadwatched five minutes before.

Each time she was started on IVantibiotics, the results were miracu-lous. You had to be there to see it. Ithink it must be hard for someonewho hasn’t witnessed this to under-stand. The improvement was soprofound there is no way anyone canblame it on the placebo effect. I was athird party and believe me it hap-pened.

My friend was lucky that she gottreatment. This was before the HMOsreally took off and before anyone inthe area she lived knew anything atall about Lyme disease. You can getbetter but you need the LLMD andthe antibiotics.

The Mayo Clinic told my friendthat she had panic anxiety disorder.

She went through nine doctors beforeshe saw an LLMD.

I also know of a six year old boywhose mother was told he wouldneed to be in a wheelchair for the restof his life. After one week of antibi-otic treatment, he was running. Thedoctors called it miraculous. Too badthey didn’t get it.

After eight weeks on antibiotics(IV) he was near normal and theystopped the treatment. He relapsedafter several months and the doctorsare still trying to figure the wholething out. They see that this childimproves dramatically with IVantibiotic treament—even with oralantibiotic treament — but just can’tadd two plus two and come up withfour. When off of the antibiotics he isplagued by sinus infections andseizures.

The one thing anyone with Lymedisease needs to do is learn about thedisease. That way they know if thedoctor they are seeing is an LLMD.

On the importance of seeing an LLMD(Lyme-Literate Medical Doctor)

This article was previously published on the internet Lyme diseasediscussion group at sci.med.diseases.lyme.

DRACUNSLAYER@prodigy.net.Suscription for LymeSig Newsletteris $9/year.

Advertisement

Number 22

Publication of the Lyme Disesase Resource Center

Page 13

Patient Support

East Coast

The Southeastern ConnecticutChronic Lyme Self-Help Groupmeets the third Friday of each monthat the Waterford Jordan Firehouse,89 Rope Ferry Road, Waterford, CT.

For more information contactGroup Co-Facilitators KathleenDickson at 860-599-5451 or JudiKarol at 860-437-9865.

TRISHA (Tick Related IllnessesSelf-Help Alliance) meets the 3rdFriday of each month at McSweeneyRegional Senior Center, WillimanticCT, 7:00-8:30 pm. All are welcome.

For more information, call 860-450-0841 (leave message or wait forcoordinator to pick up).

The Long Island Lyme Associa-tion (LILA) meets on Mondays mid-month. Meetings are at 7:30 MidIsland Hospital 4295 HempsteadTurnpike Bethpage, NY. ContactDiane Leary at (516) 893-LYME(5963) or email Pat Sprague at<PSpatches@aol.com> for moreinformation.

Southeast

The Lyme Disease Network ofMiddle Tennessee meets on the firstThursdays at 7pm of February, May,August, November and 6pm inDecember (which also features aHoliday party complete with livemusic, food and fun!) We willcontact members by phone if theweather is terribly bad...(such as inan ice storm or Tornadowarnings....in which case we cancel.We also encourage all to call us first

before coming when that happens.)Address & Directions: DonelsonChurch of the Nazarene (no religion,just a hall to meet) 208 DonelsonPike Nashville, TN Interstate 40 E.towards Knoxville, Exit 216 C (afterNashville Airport’s second Exit).Phone Contacts: Church Phone (usedonly if members get lost): 615-889-2860Facilitator:Bonnie Huntsinger, Co-Facilitator615-646-0400Norma Engelhardt, Coordinator615-883-6147 or email<Aheart@usit.net>Brenda Christy,Co-Coordinator615-883-5428Marie Taft Turley615-885-7091

Midwest

For information aboutthe Northern IllinoisLyme Resources group,contact Jeanette Wheat,telephone 630-406-0393or email<jwwdgk@aol.com>,Virginia Grom, email<ggrom48@aol.com>, orEve Fayes, email<OTEVE01@aol.com>.This group does not meetbut keeps up telephonecommunications.

The Madison,Wisconsin Lyme DiseaseSupport Group meets onthe 2nd Wed of themonth in the Leonard

Dozens of support groups exist around the United States, plus a few inforeign countries. They offer a variety of services, including moral support,information, networking, and physician referrals. Here are a few highlights.More complete lists are available on the internet websites of Lyme Net<www.lymenet.org> which the LDRC is currently helping to update, andLyme Alliance <www.lymealliance.org>.

Support groups performimportant service for patients

Room, Meriter Hospital-Park 202 S.Park Street Madison, WI 53705. CallLora Mermin at 608-231-2199 oremail her at<smermin@facstaff.wisc.edu> forinformation.

Pacific Northwest

The Marin [northern California]Lyme Disease Support Group held itsfirst meeting September 23, 1998 at7:00 pm at Marin General Hospital inthe Medical Staff Library, MarinCounty, CA.

Thereafter meetings will be heldon the 4th Wednesday of every monthat the same time and place. Forinformation, contact Lee Lull, phone415-927-9553 or email<leema@earthlink.net>.

Oregon has two groups that worktogether. The NW Lyme DiseaseSupport Group (Portland, OR) meetson the second Sunday of each monthfrom 2:00-4:00 pm in ConferenceRoom D, sixth floor NeurologicalSciences Center Community HealthEducation Services, Good SamaritanHospital, 1040 NW 22nd Ave,

The first meeting [of the Marin LymeDisease Support Group] had a turnout of 11people. The second had five (two of whomwere information gatherers: a landscaper and anurse) Hopefully the third on Nov. 18 willhave more as we will have a guest speaker, anentomologist, talking on the ticks of Marin.

The whole support group stemmed fromthe responses I received to an article I hadwritten and published in our local newspaperon my personal quest for a diagnosis. Itincluded symptoms of Lyme, a blurb about thenot always accurate tests, the difficulty ofdiagnosis and differences of opinion within themedical profession on both diagnosis andtreatment. My goal is to educate doctors andthe public. I cannot believe the ignorance.And I don’t want anyone else to go throughwhat I did.

by Lee Lull

Letter from a newsupport group leader

the Lyme Times

July-October 1998Page 14

Portland, OR. Call (503) 413-7348for directions and/or information, ore-mail Rita Stanley at<ritastan@worldnet.att.net>

The November meeting of theNW Lyme Disease Support Network(The Dalles) will be held at Colum-bia Medical Center ConferenceRoom #1 The Dalles, Oregon. Callthe hospital at 541-296-1111 fordirections and contact Vickie Lawson<vickie@gorge.net> for information.

Basic information about bothgroups (and others) may be found atthe Lyme Alliance website at <http://www.lymealliance.org/html/support.html#ORG_WASH_IDAHO>.

The Resource Center at GoodSamaritan has tapes and books thatpatients can borrow for free. Theywill be sent to you if you live withina reasonable distance simply bycalling the Resource Center at 503-413-7348

BOOKS: “Everything You Needto Know About Lyme Disease” “TheMany Faces of Lyme Disease”“Coping with Lyme Disease” “TheWidening Circle”

VIDEOS: “Lyme Disease: WhatYou should Know” LDF Tape “LymeDisease: Facts for Kids” LDF Tape“Lyme Disease: Diagnosis &Treatment” 1993 LDF Tape Dr.Burrascano Dr. Brain Fallon –Neuropsychiatric Lyme Dr. KennethLiegner – Chronic and NeurologicLyme disease.

International

Canadians are invited to contactMelanie Chernipeski, president ofthe Lyme Disease Society ofSaskatchewan, Canada. She may bereached at:

Box 7Tugaske, SK SOH 4BOTel. 306-759-2880Fax 306-759-2324

For German readers, the firstissue of Borreliose Magazin,Gesundheitspolitisches Magazin derBorreliose Selbsthilfe [Health PoliticsMagazine for Borreliosis Self-Help]

appeared in April, 1998. For infor-mation, send name and address to:

Borreliose MagazinGrosse Strasse 20521075 Hamburg, Germany

Support (“Self-Help”) groups arespringing up in cities all overGermany. Write to Jurgen Peters atthe above address for information.

Chris Blatch, Vice President ofTAGS (Tick Alert Group Support) inAustralia wrote, “We are prettyisolated. The government does notrecognize the disease exists here.”The Aussies raved about the Lyme

Times, saying, “ I can’t say howmuch we have enjoyed your backissues of the Lyme Times. It isbrilliant! So informative, greatauthors, wonderful articles.” Theysent copies of their “own humblenewsletter,” Tick Bytes. For moreinformation, write to:

Chris Blatch, Vice PresidentTAGS (Tick Alert Group Support)PO Box 1551Dee Why, New South Wales 2099Australia

Groups are invited to send reportsto the Lyme Times editor.

An AOL (America Online)chatroom meets on Wednesdays at3PM eastern standard time, 2PMcentral time and 12 noon pacifictime.

“We hope that you will come tothink of this place as a haven forthose with Lyme disease,” says“Jim,” one of the hosts, “a placewhere you can come to meet withother fellow “Lymies” who under-

Patients start new onlinechatroom and newsletter

stand what you are going through,better then anyone else in the world.”

Jim's partner, Pat, is coeditor of anewsletter “America On Lyme”published once a month, (mid-month) and emailed for free. All thatis required is to email a messagerequesting the newsletter to<PSpatches@aol.com.>.

“We also have a very informativepamphlet on Lyme disease...ChatRoom Pamphlet,” states Pat. “Iwould be happy to add names to thelist for the monthly newsletter andemail out a copy of the Chat RoomPamphlet.”

Pat will snail mail copy of thepamphlet or newsletter in return for abusiness size SASE with 64 centspostage. Send requests to: AmericaOn Lyme, Pat Sprague, 224Vanderbilt Blvd., Oakdale, NY11769-2000.

According to the organizers,“Our mission is to provide assis-tance, support and information to allwho need it, to disseminate the truthabout Lyme disease, to support thoseorganizations, doctors and research-ers who seek the truth, and to exposethe lies and distortions in themainstream medical literature.”

LDRC 1998DistinguishedPhysician Award

Nominations are open for theLDRC 1998 Distinguished PhysicianAward. This is a way for patients togive something back to their doctors.The recipient will be announced in afeature story in the next Lyme Times.

The award is given for clinicalexcellence, leadership, compassion,and dedication to the treatment ofLyme disease. Last year's Awardwent to Dr. Edwin Masters of CapeGiradou, Missouri.

Recipients receive a plaque andhis/her name is added to the plaquekept at the LDRC office.

Number 22

Publication of the Lyme Disesase Resource Center

Page 15

Regional News

will be trying to arrive at a goldstandard or surrogate gold standardtest for active infection in Lymedisease, including chronic Lymedisease, that can be used on a widescale. Schutzer believes that theimmune complex test will “fill avoid.” It is adaptable to previouslyand newly discovered antigens thatare unique to Borrelia burgdorferi.The presence of the immune com-plexes will serve as a marker orbarometer that infection is present.The disappearance of the immunecomplexes will serve as a marker thatthe infection is going away.

According to Schutzer, thecontents of the immune complexeswill be confirmed even further byusing synthetic protein targets forthe antibodies and monoclonal andother specific antibodies to prove theantigen content of the immune com-plexes. Further proof will be pro-vided by using molecular structureanalysis to prove “beyond a shadowof a doubt” what the antigen is.

This approach has already beenfeasible on a limited scale on humansand animals in previous studies. Itshould provide a sound step inestablishing not only the existence ofchronic infectious Lyme disease, butits resolution or resistance to thera-pies.

Dr. Manfred Bayer of Fox ChaseCancer Center in Philadelphia hasbeen awarded $22,122 to study theeffects of low frequency radiation onB. burgdorferi cultures. Bayer willexplore the use of controlled pulsesof low frequency electromagneticradiation as a tool to damage andultimately destroy Borreliaburgdorferi cells.

This type of radiation has been

New Jersey LDA fundsresearch to find cure for Lymecontinued from page 1

used with varying success in thetreatment of persons suffering fromLyme disease and related symptoms.The question remains unansweredwhether such treatment affects thespirochete directly or whether host-related mechanisms are activated thateventually may destroy the bacte-rium.

Bayer's experiments will addressthe effect of the radiation on thespirochetes. He will test the viabilityof B. burgdorferi cultures aftervarying exposure times, radiationintensities and frequencies. Theeffect of single or repeated treatmentson the spirochete will be studiedimmediately as well as at timedintervals using high-resolution videolight microscopy in parallel tobacterial counts.

Furthermore, the question will beaddressed whether the efficiency ofantibiotic treatment of all cultures isenhanced by the radiation treatment.Test results will be recorded onmicrophotographs, videotapes anddisk data storage programs.

Dr. Brian Fallon, College ofPhysicians & Surgeons at ColumbiaUniversity is in charge of the 1998LDANJ annual project. He isworking with LDANJ in developingresearch in the area of neuropsychiat-ric Lyme disease.

Many patients with PersistentLyme Encephalopathy (PLE) havestructural and/or functional imaging

abnormalities. The SPECT abnor-malities suggest either problems withvascular perfusion or problems withnerve cell metabolism. The MRIhyperintensities suggest that theremay be problems of small vesselblood flow, resulting in demyelina-tion. The SPECT and MRI abnor-malities are reversible in somepatients, but not in others. In ourproposed study, we will use the moresophisticated technology of PETimaging to examine both blood flowand metabolism.

The questions the research teamwill begin to address with this pilotstudy are: a) are there brain differ-ences on MRI or PET that distin-guish antibiotic responders fromantibiotic non-responders? b) are theMRI and SPECT abnormalitiesprimarily vascular or metabolic? andc) is functional brain imaging (PETand SPECT) useful as a diagnostictool?

Drs. Liegner, Niasi, Pavia wereawarded $12,500 to evaluate theeffectiveness of certain alternativetreatment methods.

One of the reasons for thedifficulty in treating Lyme disease isdelayed diagnosis, but the other isthe resilience of the Borrelia spiro-chete, which can survive evenyearlong intravenous antibiotictherapies.

According to Liegner, they wantto identify a cheaper and moreeffective method of treatment forLyme disease. This prospective studywith both in-vitro and in-vivo(animal) components is designed toidentify whether Potassium Iodideand/or Hyperbaric Oxygen will beeffective in the treatment of Lymedisease.

Since starting its grant program,LDANJ has awarded over $94,000for research into a cure for Lymedisease. To apply for a grant or formore information, contact Pat Smith,email LYMELITER@aol.com, orBarbara Muniz, 732-255-2083.

Subscribe now to theLyme Times! Use thehandy return envelope inthe centerfold.

the Lyme Times

July-October 1998Page 16

Massachusetts coastalenvironment is ideal for TBDscontinued from page 1spends four days on Martha’sVineyard trapping mice. A total of49 live traps are set at two Islandsites, Menemsha Hills and FelixNeck. Each mouse caught is exam-ined, tagged, and all of the ticksremoved. The mouse is then set free.”There is no question that mice arepart of the equation,” says Dr.Telford, adding that weather alsoaffects tick numbers. This time ofyear, he says, he might find from 10to 15 ticks, which represents aweek’s accumulation.

“We still have no way of predict-ing what kind of year we are goingto have,” he says about collectiondata that might eventually lead toreliable methods of prediction.

The need for more informationabout deer ticks is related to theserious health risks posed by diseasecarrying ticks. While Lyme diseaseis the best known and most commontick-borne illness, two others,babesiosis and HGE, or erlichiosis,are also found on the islands.

Still, ticks and the diseases theyspread are not limited to our part ofthe world but exist throughout the

The Michigan Lyme DiseaseAssociation (MLDA) raised over$10,000 for education and researchat its third annual benefit, Laughingat Lyme 3, in May. Holding the eventduring National Lyme AwarenessMonth underscored the nationalattention already given to Lyme atthat time of year.

The MLDA sent out publicservice announcements on preventionto radio and TV stations around thestate. One radio station featured aninterview with a local official whosedaughter has been battling Lymedisease. All the publicity of LymeDisease Awareness Month served aspromotion for the Laughing at Lymeevent.

The funds raised will be used foreducation and research. Funds fromprevious years’ events have sup-ported Lyme disease research, theMLDA Lyme awareness campaign,and a medical conference jointlyorganized with the MichiganMedical Society.

To become a member of theMLDA and receive TICK TALKnewsletter, send your name andaddress to MLDA, 5340 HollowDrive, Bloomfield Hills, MI 48302.

In California, Ellis Paul, whosestorytelling songs are described asnew folk music, entertained a sell-outcrowd at Malibu Health on Septem-ber 5. Guitarist Francesco Lupicaopened for Paul. Proceeds from theevent go to the Lyme DiseaseResource Center.

Catie Norris, one of severalMalibu residents to have contractedLyme disease, organized the event.She is a director at Malibu Health.She said about $2000 was raised forlocal education about the tick-bornedisease, its prevention and cure.Local businesses, celebrities, and

Fundraisers raise moneyfor Lyme education,research

health club patrons donated items tothe silent auction and providedrefreshments.

The Lyme Disease Association ofNew Jersey (LDANJ) annualfundraising efforts culminated in its8th Great Imitator Family Masquer-ade Party on October 25. They haveraised a total of $57,000 this year.

The LDANJ is a nonprofit, all

volunteer organization whose goalsare Lyme disease education, preven-tion, and research. One hundredpercent of the proceeds from thisyear’s fundraiser are being directedto a brain imaging pilot study underthe direction of Dr. Brian Fallon,College of Physicians and Surgeonsof Columbia University, NYC. [Seestory on page 1]

LDANJ welcomes tax freedonations toward Dr. Fallon’sresearch project in any amount.Please make checks payable toLDANJ and mail to PO Box 1438Jackson, NJ 08527.

temperate zone. In the Siberian areaof Russia, deer ticks also transmit atype of tick-borne encephalitis that isapproximately 40 percent fatal, saysDr. Telford, who has traveled toRussia to study the problem.

Asked if any similar diseasesexist in our area, he says he diddescribe an encephalitis case causedby deer ticks two years ago in thetown of Ipswich but adds, “I havenot found it on the islands yet.”

Asked why some areas of theworld might experience differenttick-borne diseases, Dr. Telford sayswhat we see today is a legacy of aperiod before the ice ages whenmany of today’s viruses werecontinually distributed.

“What we see now are just littlefragments of what used to be a verywide distribution,” he says of tick-borne illnesses.

He adds, “And now with theproliferation of deer and peopleusing habitat more, these things arebeing amplified again. After the iceages, they were at a very low leveland it has taken this long to build it

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back up again. And we are reallystimulating it to the point that thesethings will come out in force as theywere before the ice ages.”

Dr. Telford says, “Once upon atime, Nantucket and the Vineyarddid not have a problem with thesetick-borne agents. Part of that wasbecause there were fewer deer, butalso because of the brush.”

But the growth of the white-tailed deer population and thechange in the Island’s landscapefrom clear-cut fields that wereheavily grazed by sheep to low thickshrubs have contributed to a growthin the tick population.

“The brush has gotten to such apoint that it serves as a wonderfulplace for the ticks to hide, and themice to hide and the deer to hide.These ticks require a micro-habitatof a particular relative humidity andtemperature, and the brush that yousee out there is perfect for that. Butyou go walking through some of thesheep pastures on the south end ofthe island and you are not going tofind any deer ticks,” says Dr.Telford.

But compared to the Vineyard,Nantucket “suffers worse,” he says.Unlike the Vineyard with its pine andhardwood forests, Nantucket’s unvary-ing scrub oak, bayberry, and high bushblueberries provide perfect cover fortick habitat over much of the island.That has lead to an effort by Nantucket’sConservation Foundation to promotemowing of brush.

Dr. Telford says, “Certainlyanywhere where the sun and thewind can go through and reduce therelative humidity is going to dimin-ish the number of deer ticks.”

But he emphasizes, “The dogticks you’ve probably seen walkingacross the hot sand on the beach.They could care less. Dog ticks youare not going to do anything aboutuntil you get rid of your raccoonsand skunks because they are theculprits there.”

Nantucket and the Wampanoag

Tribe of Aquinnah have both soughtand received increases in the lengthof the deer hunting seasons. Dr.Telford says the rest of the Vineyardneeds to follow their example.

“As far as I’m concerned. theVineyard has less of a problem thanNantucket, but it is clear that it stillhas a problem,” he says.

And it is one that will get worse asa result of development which createslittle patches of deer habitat and anincrease in the numbers of ticks.

“We’ll never get rid of the tick, itis here to stay,” says Dr. Telford. Butthe numbers can be reduced prima-rily, he says, by aggressive manage-ment of the deer population throughexpanded hunting. The alternative ofhabitat management is not as easilydone, he says. And while deercontraception may be useful, thenumber of deer must be reducedbefore any contraceptive programcan be expected to have any effect,he explains.

“Out on Nantucket, where weworked for so long, we think that theburden of Lyme disease on thatcommunity is equivalent to theburden that gonorrhea is in the innercity,” he says.

Nantucket, with approximately20 cases per year, is also the “hottestspot in the whole world” for cases ofbabesiosis. The disease carries a 5percent fatality rate even whentreated.

Dr. Telford says the risk ofcontracting a tick-borne disease ishighest in May and June, when thesmall nymphal tick is seeking ablood meal, On warm winter daysthere is also the risk of a bite froman adult tick but because the tick islarger, half the size of an apple seed,it is more easily discovered.

Reprinted with permission fromthe Martha's Vineyard Times, Sept.24, 1998.

Two clinically similar butmicrobiologically distinct forms ofehrlichiosis have been identified inCalifornia residents. Ehrlichiosis isan infection of circulating leukocytesand is caused by rickettsial organ-isms of the genus Ehrlichia: specifi-cally, E chaffeensis and a closeanalog of E equi are the agents of themonocytic and granulocyticehrlichioses, respectively.

Symptoms commonly associatedwith ehrlichiosis include fever,headache, muscle pain, and fatigue;leukopenia, thrombocytopenia, andelevated hepatocellular enzymes arealso consistent clinical features. Fiveacute cases of ehrlichiosis have beenrecognized and reported to date inCalifornia residents who had no

From the California Department of Health Services, July 6, 1998

Californians are beingexposed to ehrhlichiosis

history of travel preceding theirillness (three granulocytic [SantaCruz and Humboldt counties] andtwo monocytic [Marin and Humboldtcounties]).

Recent serologic studies haveindicated that exposure to thesepathogens among California resi-dents may be more common than thepaucity of recognized clinical casessuggests. Serologic diagnosis of bothforms of ehrlichiosis by IFA isavailable through the CDHS Viraland Rickettsial Diseases Laboratory.As an adjunct to serology, buffy coatsmears may be useful for identifyingthe characteristic inclusion bodies ofEhrlichia, but these procedures arefairly insensitive.

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July-October 1998Page 18

On Thursday, September 24, adinner was held in Boston and Dr.Steere was awarded the Sabin GoldMedal for discovering the pathogen-esis of Lyme disease. This pivotalresearch enabled development of avaccine to prevent the disease. TheSabin Vaccine Institute encouragestranslational research — from benchto bedside — and for that Dr. Steerewas also recognized.

Sabin Institute honorsAllen Steere for research

Research

The role of the Lone Star tick(Amblyomma americanum) in thetransmission of Lyme disease,erythema migrans, or Lymelikeillness has been controversial sincefirst reported in 1984. (Schulze et al.)The recent isolation of Borreliaburgdorferi sensu lato from ticks,including a Lone Star tick, collectedat the Missouri farm of a patient witha physician-diagnosed erythemamigrans rash following a witnessedLone Star tick bite raises the possi-bility that the Lone Star tick may actas a “bridge vector” much like Ixodespacificus in the western UnitedStates.

This study was designed todifferentiate cases of physician-diagnosed erythema migrans fromerythema migrans-like rashesassociated with Lone Star tick bites.Seventeen patients who presentedwith rashes similar, if not identical,to erythema migrans and documentedLone Star tick bites were studied.Positive identification of the tick wasrequired – the adult female has adistinctive white dot on its back.Fourteen of the rashes had biopsyspecimens available (some of thepatients were in other studies aswell).

All rashes were measured andphotographed. The median incuba-tion time was 7 days, with a rangefrom 2 to 15 days. The median rashdiameter was 7.5 cm, with the largestbeing 15 cm (range 2.5-15). Allrashes were similar to, and oftenindistinguishable from, erythemamigrans in patients from areas withendemic Lyme disease.

Lyme-like disease isclinically indistinguishablefrom true Lyme disease

Masters E, Granter, S, Duray P, Cordes, P. Physician-DiagnosedErythema Migrans and Erythema Migrans-like Rashes Following Lone StarTick Bites. Arch Dermatol 134:955-960 (1998).

Ten of the 17 case patients hadLyme serology results inconsistentwith test-negative non-Lyme(uninfected) controls. Eight of theLyme serology results were sugges-tive of a borreliosis. Extensive testingfor other diseases and causes ofpossible cross-reactivity werenegative with one exception (onepatients tested positive for Coxiellaburnetii – Q-fever agent). Westernblots on several patients showed an

unusually high frequency of 4 ormore IgG bands. Several had positiveELISAs.

Although most of the data pointsto a disease clinically indistinguish-able from Lyme disease, the re-searchers were unable to culturespirochetes in BSK II media. Theysuggest that BSL II media may not besatisfactory for isolation of potentialspirochetes associated with non-ixodid ticks. Norris et al. showed thatBSK II can select for specificgenotypes of Borrelia burgdorferi.

The serology also argues againsta B31 B burgdorferi cause. Theauthors point out that different strainvariants can have different testresults. They conclude that erythemamigrans-like rashes may be causedby a Lone Star-vectored borrelia, andshould be treated with antibiotics aswould an erythema migrans rash inan accepted endemic area.

Representatives of the CDC, theNew England Journal of Medicine,Georgetown University andSmithKline Beecham spoke duringthe program. And by proclamationof the Governor, September 24th wasAllen C. Steere Day in Connecticut.

The reaction to the news in theonline Lyme patient community wasuniformly negative. Some expressedoutrage, others disbelief.

Many patients fault Steere for hisnarrow definition of Lyme diseaseand for his ultraconservative positionon treatment. Wide circulation of hispaper “Overdiagnosis of LymeDisease” has resulted in costlydenials and delays of treatment formany patients. Steere has also beenslow to recognize persistent, chronicinfection, preferring instead toconsign patients who fail treatmentto the diagnostic limbo of

Pfizer Central Researchoffers an informativeLyme disease pamphletwith good illustrations.You can order 50 freepamphlets by calling 1-860-441-5544. Additionalcopies are 4 cents each.

Continued on next page

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For five days, beginning August23rd, I could be found at the NIHcampus in Bethesda Md. You wouldhave found me in a better state ofmind than had been possible in along while. Applying to take part inthis study is the best thing I havedone since the tick bit me.

At the end of this you will findout how to learn more about thisstudy as well as how to apply to takepart in it.

The support staff:

Starting with the help I got overthe phone while applying, the shuttledriver that collected me at theairport, the ladies that registered me,the patient representative, the socialworker, the food service people, thelibrarian, the escorts that got mewhere I needed to be, right thru tothe travel agent who arranged mytrip home, I was treated withpoliteness at worst and cheerfulhelpfulness more times than not.This was a far cry from the bureau-cratic malaise I was prepared to findat such a large institution. The food,both selection and quality, wassurprisingly good as well.

The doctors and technicians:

Patient reports onexperience in NIH study

fibromyalgia or chronic fatigue.

Donna Herrell, author of theLyme Disease Information Resource,suggests that patients might want tocontact the Institute to let them knowtheir feelings about this award.

“If you are writing or calling youmight want to familiarize yourselfwith the Institute. Their website is:http://www.sabin.georgetown.edu.”

To contact the Sabine Institute,

call or write:

John Clymer, Director of ExternalAffairs and/orH.R. Shephard, ChairmanThe Albert Sabin Institute4000 Reservoir Rd. NWBldg. D Suite 154Washington, DC 20007(202) 687-9145 Phone(202) 687-9242 FAXemail info@sabin.georgetown.edu

All the doctors and technicianswho looked after,tested, poked,prodded, x-rayed, and scanned mewere wonderful. Not once was Iconfronted with indifference muchless arrogance.

The nursing staff:

Each nurse was kind, friendlyand caring. When a shift changedand I was dissapointed at not seeingthe nurse who had been so niceyesterday, it wasn't long before thenew nurse would win me over with asmile and some care and attention.

I would like to thank the peopleresponsible for the fact that it seemsas if a helpful attitude and friendlydisposition are required to get andkeep a job at this clinic

The principle investigator:

At this point it becomes difficultfor me to express my feelings for Dr.Adriana R. Marques and her associ-ate Dr. Norberto E. Soto. To beginwith they took great care andattention with my physical examina-tion. During my stay they spent agood deal of time explaining allaspects of the protocol, its tests,examinations and procedures.Both doctors listened attentively to

what I had to say about my experi-ence with Lyme disease. They tookthe time to answer all my questionsabout the study and the many aspectsof Lyme disease that concern me.The compassion that they showedwith regard to the emotionaldilemmas that the disease presentsme has resulted in my seeking helpin addressing this difficult issue. Iknow that my Lyme world is a muchbetter place with these two in it.

How did I benefit?

When I told some people in theLyme community that I wanted totell this positive story and to encour-age others to take part in this study,they wanted to know, “How did youbenefit from the study?”

Well the first thing I got out of itwas hope. Without insurance andunable to work, there seemed to beno way possible for me, to getadequate testing for Lyme disease.Not to mention co-infection or any ofthe myriad of afflictions that Lymedisease mimics.

Participation in the study hasprovided me with a full workup ofmy disease. I was advised as to thestatus of all my test results while atthe clinic and Dr. Marques or Dr.Soto sat and explained what theresults meant to me. As some of thetests involve some slow growingcultures, it will be two to three weeksbefore I know my final status withinthe protocol.

If I qualify for reevaluation, Iwould certainly look forward totracking my progress with the diseaseby going back to Bethesda as isneccessary. Just knowing that peoplelike Dr. Marques and Dr. Soto areworking at solving some of the greatmysteries surrounding Lyme diseasehas bought me some piece of mind.

Having actually been able to sitand talk with them has given meknowledge and confidence as well ashope that I can get through thisdisease. That has not always been thecase. I might also be able to takesome small satisfaction in knowing

The author is participating in the intramuural arm of the NationalInstitutes of Health Study of chronic Lyme disease.

by Lindell Lee McElfresh

the Lyme Times

July-October 1998Page 20

that my participation in the studymight help just a little bit in the waragainst Lyme disease.

To learn more about this study:Go to http://www.niaid.nih.gov/recruit/lyme.htm or write to: NIAIDChronic Lyme Disease StudyBuilding 10 Room 11n228 10 CenterDrive MSC 1888 Bethesda, MD20892-1888 or fax: 301-496-7383

For an application to the studycall 1-800-772-5464 Ext.605

Please contact me if you have anyquestions: LindellLee@aol.com. Thestudy that Dr. Marques is conductingdoes not make use of placebos.

“I am about ready to ask Santa foran electron microscope forChristmas because, at the rate theyare going, I don’t see these guysfinding anything relevant aboutpersistent Lyme in this lifetime.”Patient writing about the NIH study

A differing opinion:

In order to understand better thenormal life cycle of B. burgdorferi,an experimental chain of infectionwas devised that involved multiplesequential arthropod and mammalianpassages. By examining populations

of B. burgdorferiemerging fromdifferent points in this infectiouschain, we demonstrate that selectionof B. burgdorferipopulations peculiarto arthropod or vertebrate hosts is aproperty of at least one of the twoecologically distinct strains weexamined.

In the strain exhibiting selectionin the different hosts, transition fromone host to another produced astriking series of alternating pheno-typical signatures down the chain ofinfection. At the molecular level, thealternating signatures were mani-fested as a reciprocal relationshipbetween the expression of certainantigenic forms of outer surfaceprotein (Osp) B and OspC.

Selection of distinct populationsin the tick may be responsible for themicroorganism’s ability to infect awide range of vertebrate hostsefficiently, in that the tick mightprovide selective pressure for theelimination of the populationselected in the previous host.

Ryan JR, Levine JF, Apperson CS, Lubke L, Wirtz RA, Spears PA,Orndorff PE. An experimental chain of infection reveals that distinct Borreliaburgdorferipopulations are selected in arthropod and mammalian hosts. MolMicrobiol 1998 Oct;30(2):365-79

B. burgdorferi strainsselect in different hosts

Please help if you can. Noprotocol is ideal, but these people areworking really hard to help solvesome of the mysteries surroundingLyme disease.

According to a Reuters report, aspecies of Babesia that has yet to beidentified is believed to be the culpritin a flu-like illness increasinglybeing reported in the Pacific states.

Dubbed “WA1” by investigators,it has been linked to one death so farand has been documented to betransmitted through a transfusion—by a completely asymptomaticpatient. It is similar to, but “molecu-larly distinct,” from Babesia microti,which is the cause of babesiosisalong the eastern seaboard.

The elusive Babesia species of thewest is similar, or perhaps even thesame, as the one turning up in muledeer, dogs and Bighorn sheep inCalifornia, UC Davis researcher Dr.Pat Conrad said. “They are potentialcandidates” as reservoirs, sheacknowledged, but more definitivestudies need to be done to affirm thattheory. In populations throughoutCalifornia, there appears to be 4% to6% seropositivity for the one-celledparasite, she said.

Discovery of this newly recog-nized cause of babesiosis was madewhen a middle-aged farmer from the

likely to turn up the characteristicintraerythrocytic smears that typifythe infection.

“It takes an astute technician,”she observed. “What is helpful, isjust to raise awareness,” she said. “Ifwe are testing more, we are bound tofind more cases”—and more an-swers.

Symptoms include those usuallyassociated with flu: fatigue, vomit-ing, myalgia, shaking and chills.Although the tick-vector has yet to beconfirmed, it is known to inhabitgrassy areas, hiking trails and evenleaf litter, she added.

Species of Babesia a possibleculprit in flu-like illness

Pacific Northwest was hospitalizedfor a malaria-like illness but did nothave antibody titers indicative of B.microti. Nonetheless, the conditionproved remarkably easy to treat:clindamycin and quinine are curative,she said.

However, because malaria is sorare in the United States, physiciansmay fail to conduct the kinds of testsnecessary to detect WA1, she sug-gested. The automated diagnosticprocedures currently in use are not

NIH study experience, cont.

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TABLE OF CONTENTS(Page numbers are not included

because they do not conform to theLyme Times layout.)

IntroductionBackground InformationDiagnostic Hints: Piroplasmosis(Babesiosis)EhrlichiosisBorrelia burgdorferiErythema migransDiagnosing Late DiseaseDiagnostic criteriaSymptom ChecklistLyme Disease Treatment GuidelinesGeneral InformationPiroplasmosis (Babesiosis)EhrlichiosisLyme BorreliosisCourse During TherapyAntibiotic ChoicesTreatment CategoriesProphylaxis for Known Tick BitesDisseminated Disease:1. Early2. LateAlternate Scheduling of AntibioticTreatments:1. Pulse Therapy2. Combination TherapyRefractory Disease:1. Responsive to antibiotic therapy2. Non-responsive to antibiotictherapyAdjunctive TherapyNutritional Supplements in ChronicLyme DiseaseLyme Disease RehabilitationRehab Therapy PrescriptionManaging Yeast Infections

Lyme expertpublishes updatedguidelines

THE NEW LYME DISEASE: DIAGNOSTIC HINTS AND TREAT-MENT GUIDELINES FOR TICK BORNE ILLNESSES. Twelfth EditionCopyright October, 1998. Reprinted by permission.

by Joseph J. Burrascano Jr., M.D.

Patient Instructions on Tick SitePrevention and Tick RemovalAppendix:Rational for treating tick bitesRationale for treatment recommenda-tionsSuggested Reading

Introduction

THE NEW LYME DISEASE…

I humbly propose we redefinewhat we have been calling Lyme. Ahuge body of research and clinicalexperience has demonstrated thenearly universal phenomenon inLyme patients of co-infection withmultiple tick-borne pathogens. Asmany have heard me say, coinfectionis not surprising, for ticks arearachnids that literally live in dirtand drink the blood of wild animals.To think that a significant tick bitetransmits only one infection isnarrow minded indeed. Studies haveshown that concurrent Borrelial andEhrlichial and/or Babesial infectionsresult in a change in their individualclinical presentations, with differentsymptoms, atypical signs, decreasedreliability of standard diagnostictests, and most importantly, thecreation of chronic, persistent formsof each of these infections. As timegoes by, I am convinced that morepathogens will be found.

Therefore, Lyme, as we hadcome to know it, probably representsa mixed infection. I will leave to thereader the implications of how this

may explain the discrepancy betweenlaboratory study of pure Borreliainfections, and what front linephysicians have been seeing for yearsin real patients.

It is still early in our efforts tosort out the individual contributionsof each of these pathogens in thecoinfected patient, so the suggestionsthat follow are quite preliminary.However, I believe this informationis so important, I did not want todelay any further this edition of myGuidelines.

I will refer to the general symp-tom complex as “Lyme”, but willrefer to the separate entities as LymeBorreliosis (LB) or Borreliaburgdorferi(Bb), Babesia microti(Bm), and the Ehrlichia species as agroup. In past editions, I mentionedhow the diagnosis and treatment ofLyme Disease had entered a new era,as simplistic approaches were beingreplaced by more modern ones basedon better knowledge, more experi-ence, and the application of commonsense. Seronegativity, the existenceof chronic persistent infection,relapses and treatment failures hadall been confirmed, as well as theneed for many months of therapy inthose ill for a long time. Unfortu-nately, many health care workers andhealth reporters have not kept upwith these facts. It is only throughknowledge that we will be able toconquer this misinformation. Pleasecontinue your efforts to educate theunaware.

The concept of a “therapeuticalliance” between the caregiver andpatient must again be emphasized.This means that the patient has towork with and become part of themedical team, and must take respon-sibility for complying with therecommendations given, maintainingthe best possible health status,reporting promptly any problems ornew symptoms, and especially inrealizing that despite all our bestefforts, success in diagnosis andtreatment is never assured. Themedical team must make great efforts

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July-October 1998Page 22

to listen carefully to the patient andnot be too quick to dismiss seeminglybizarre or illogical complaints.

I extend my best wishes to themany patients and caregivers whodeal with Lyme, and a sincere thankyou to my colleagues whose endlesscontributions have helped me shapemy approach to tick borne illnesses. Ihope that my new approach proves tobe useful. Happy reading!

Backgrouond Information

The evaluation of a Lyme patientmust begin with testing for allcurrently known tick borne patho-gens. Serological studies for Borrelia,Babesia and Erlichia should becombined where appropriate withdirect antigen assays. Antigendetection tests (antigen Capture andPCR) are especially helpful inevaluating the seronegative patientand those still ill or relapsing aftertherapy. Unfortunately, over a dozenprotozoans other than Babesiamicroti can be found in ticks, yetcommercial tests for only B. microtiare available at this time, so as inBorrelia, clinical assessment is theprimary diagnostic tool. InErlichiosis, test for both the mono-cyte and granulocytic forms. Manypresently uncharacterized Ehrlichia-like organisms can be found in ticksand may not be picked up by cur-rently available assays, so in thisillness, too, serologies are only anadjunct in making the diagnosis.

Babesia are parasites, and Isuggest that if a coinfection is foundinvolving this organism, treat thisfirst, so that subsequent therapy forBorrelia and Ehrlichia will be moreeffective.

Experience has shown thatcollateral conditions exist in thosewho have been ill a long time. TestB12 levels, and be prepared toaggressively treat with parenteralformulations of the B-vitamins:100mg each of Bl and B6 and 1000mcg of B12 IM at least weekly in themore ill patient. Magnesium defi-ciency is very often present and quitesevere. Magnesium is predominantly

an intracellular ion, so blood leveltesting is of little value. Oralpreparations are acceptable formaintenance, but most needparenteral dosing: 1 gram IV or IMat least weekly until neuromuscularirritability has cleared. Because theLyme syndrome has been associatedwith faulty activation of T4, measurefree T3 levels by RIA and basal A.M.body temperatures. If hypothyroid-ism is found, treat with T3 prepara-tions.

SPECT scanning of the brain, ifdone by knowledgeable radiologistsusing high-resolution equipment,will show characteristic abnormali-ties in Lyme encephalopathy. Thisnot only helps with the differentialdiagnosis, but if done before andafter acetazolamide, it will guide inthe use of vasodilators, which mayclear up some cognitive symptoms.Therapy can also include serotoninagonists, pentoxiphylline and evenGingko biloba. Therapeutic trialsmay be needed.

Tilt table testing is anotherpowerful tool which, just as inCFIDS, may demonstrate neurallymediated hypotension(NMH). Iffound, therapy is based on bloodvolume expansion (increased sodiumand fluid intake and possibly Florinefplus potassium). If not sufficient,beta blockade may be added based onresponse to Isuprel challenge duringtesting. If NMH is present, treatmentcan dramatically lessen fatigue andpalpitations, and increase stamina.

Diagnostic Hints

Lyme is diagnosed clinically, asno currently available tests, no matterthe source or type, are definitive inruling in or ruling out infection withthese pathogens, or whether theseinfections are responsible for thepatient’s symptoms. The entireclinical picture must be taken intoaccount, including a search forconcurrent conditions and alternatediagnoses, and other reasons forsome of the presenting complaints.Often, much of the diagnosticprocess in late, disseminated Lyme

involves ruling out other illnessesand defining the extent of damagethat might require separate evalua-tion and treatment.

Consideration should begiven to tick exposure, rashes (evenatypical ones), evolution of typicalsymptoms in a previously asymptom-atic individual, and results of testsfor tick borne pathogens. Anothervery important factor is response totreatment-presence or absence ofJarisch Herxheimer-like reactions,and improvement with therapy.

Piroplasmosis (Babesiosis)

Classic teachings state that acuteinfections are usually only seen inthose with some form of immunecompromise. Flu-like symptomsrapidly evolve to include shakingchills, high fevers, hemolysis andpancytopenia. Fatalities have beenreported. Visualizing Babesial formson peripheral smears can make thediagnosis in this situation. In thosewith intact immune systems, a mildflu-like illness appears one to twoweeks after exposure and clearswithout treatment over six to eightweeks. In either case, it is imperativeto test for Borrelia and Ehrlichia.

However, when coinfectionexists, this acute presentation ismuch less common, and it is rare tosee parasite forms on smear. Signs ofcoinfection include severe headaches,dizziness and encephalopathy out ofproportion to the other Borrelialsymptoms. Testing is not at alldefinitive, yet should include CBC,Babesia smear (very low yield),serologies (IgG and IgM) and ifnecessary, PCR of peripheral blood.Newer direct assays are currentlybeing researched, as this is an activearea of investigation. Alwaysconsider coinfection in your currentLyme patients who are not respond-ing fully.

Ehrlichiosis

While it is true that this illnesscan have a fulminant presentation, Iam convinced that milder forms doexist, especially when other tick-

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borne organisms were transmitted.When present in a Lyme patient,persistent leucopenia is an importantclue. Thrombocytopenia is much lesscommon, but likewise should not beignored. Headaches, myalgias, andongoing fatigue seem to relate to thisillness, but are extremely difficult toseparate from symptoms caused byBb. At this time, we only haveserologies for laboratory diagnosis, asno direct assay currently exists.There is no way at this time to judgethe accuracy of these tests, especiallysince there may be a variety ofpathogenic Ehrlichia-like organismsthat will not be picked up by currenttesting technology. Direct visualiza-tion of this organism in leukocyteshas been reported, but is rare.Again, consider this diagnosis in aLB patient not responding well totherapy.

Lyme Borreliosis

Erythema Migrans

Erythema migrans (EM) isdiagnostic of Bb infection, but ispresent in fewer than half. Even ifpresent, it may go unnoticed by thepatient. It is an erythematous,centrifugally expanding lesion that israised and warm. Sometimes there ismild stinging or pruritus. The EMrash will begin four days to severalweeks after the bite, and may beassociated with constitutionalsymptoms. Multiple lesions arepresent less than 10% of the time,and represent disseminated disease.Some lesions have an atypicalappearance and skin biopsy speci-mens may be helpful. When anulcerated or vesicular center is seen,this may represent a mixed infection,involving other organisms besides B.burgdorferi.

After a tick bite, serologic tests(ELISA, IFA, western blots, etc.) arenot expected to become positive untilseveral weeks have passed. There-fore, if EM is present, treatment mustbegin immediately, and one shouldnot wait for results of Borrelia tests.You should not miss the chance totreat early disease, for this is when

the success rate is the highest.Indeed, many knowledgeableclinicians will not even order aBorrelia test in this circumstance.

Diagnosing Late Disease

When reactive, serologiesindicate exposure only and do notdirectly indicate whether the spiro-chete is now currently present.Because Bb serologies often giveinconsistent results, test at more thanone laboratory using if possibledifferent methods. I recommendordering both ELISAs and westernblots. Be aware that in late disease

60KD, 66KD, and 73KD are nonspe-cific and nondiagnostic.

Antigen detection testsincluding PCR are now available,and although they are very specific,sensitivity remains poor, possibly lessthan 30%. This is because Bb causesa deep tissue infection and is onlytransiently found in body humors.Therefore, multiple specimens mustbe collected to increase yield, and anegative result does not rule outinfection, yet a positive one issignificant. The patient must beantibiotic free for at least six weeksbefore testing. Antigen capture canbe done on urine, CSF, and synovialfluid. PCR can be done on blood(buffy coat is best), urine, CSF, anyother body fluid including breastmilk, and on tissue biopsy speci-mens.

Spinal taps are not routinelyrecommended, as a negative tap doesnot rule out Lyme. Antibodies to Bbcan be detected in the CSF in just20% of patients with late disease.Therefore, spinal taps are onlyperformed on patients with pro-nounced neurological manifestations,if they are seronegative, or are stillsignificantly symptomatic aftercompletion of treatment. When done,the goal is to rule out other condi-tions, and to determine if Bb anti-gens are present. It is especiallyimportant to look for elevated proteinand mononuclear cells, which woulddictate the need for more aggressivetherapy, as well as the openingpressure, which can be elevated andadd to headaches, especially inchildren.

To aid the clinician, a workableset of diagnostic criteria weredeveloped with the input of dozens offront line physicians. The resultantdocument has proven to be extremelyuseful not only to the clinician, but italso can help clarify the diagnosis forthird party payers and utilizationreview committees. It is important tonote that the CDC’s publishedreporting criteria are for surveillanceonly, not for diagnosis.

there may be repeatedly peakingIgM’s and therefore a reactive IgMmay not differentiate early from latedisease, but it does suggest an activeinfection. When late cases of LB areseronegative, 36% will transientlybecome seropositive at the comple-tion of successful therapy.

Western blots are reportedby showing which bands are reactive.41KD bands appear the earliest butcross react with T. pallidum andseveral other spirochetes. The 18KD,23-25KD (Osp C), 31KD (Osp A),34KD (Osp B), 39KD, 83KD and the93KD bands are the most specific butappear later or may not appear at all.You need to see at least the 41KDand one of the specific bands. 55KD,

“Indeed, the veryreal consequences ofuntreated chronicpersistent infection byB. burgdorferi can befar worse than thepotentialconsequences of thistreatment.”

J. Burrascano, MD

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Lyme Borreliosis DiagnosticCriteria Relative Value

Tick exposure in an endemic region ....................................................... 1

Historical facts and evolution of symptoms consistent with Lyme ... 2

Systemic signs & symptoms consistent with Bb infection (otherpotential diagnoses excluded):

Single system. e.g. monoarthritis ............................................................ 1

Two or more systems. e.g. monoarthritis and facial palsy ................. 2

Erythema migrans, physician confirmed ............................................... 7

Acrodermatitis Chronica Atrophicans, biopsy confirmed .................. 7

Seropositivity ............................................................................................... 3

Seroconversion on paired sera .................................................................. 4

Tissue microscopy, silver stain ................................................................ 3

Tissue microscopy, monoclonal immunofluorescence ........................ 4

Culture positivity ........................................................................................ 4

B. burgdorferiantigen recovery ................................................................ 4

B. burgdorferiDNA/RNA recovery ......................................................... 4

DIAGNOSIS Lyme Borreliosis Highly Likely 7 or above

Lyme Borreliosis Possible 5-6

Lyme Borreliosis Unlikely 4 or below

I suggest that when using these criteria, you state Lyme Borreliosis is“unlikely’, “possible”, or “highly likely” based upon the followingcriteria - then list the criteria.

Lyme Disease Treatment Guide-lines

Piroplasmosis (Babesiosis)

Piroplasms are not bacteria, theyare protozoans. Therefore, they willnot be eradicated by any of thecurrently used Lyme treatmentregimens. Therein lies the signifi-cance of coinfections- If a Lymepatient has been extensively treatedyet is still ill, suspect a piroplasm.

Just as in Lyme Borreliosis, thelonger one has been infected, thelonger the course of therapy must be.Similarly, clinical assessment is theonly guide to treatment endpoint.

Treatment choices are limited.Pentamidine is a treatment given asdaily IM shots- very painful, they

cause sterile abscesses and perma-nent fibrous scars on the buttocks.More importantly, response is poor,and the patient risks development ofglucose intolerance. Clearly, not afirst choice.

Clindemycin, 600 mg qid plusQuinine, has been the publishedstandard but the suggested two weekcourse is nearly impossible to tolerate(hearing loss, rash, fever, headache)and treatment failures have beenreported.

Gentamicin in combination witheither penicillin or a first generationcephalosporin is used in treatinglivestock infected with piroplasms.There are only anecdotal reports ofefficacy in Humans and the dose andduration of therapy (14 days) has not

been well worked out. The main sideeffect is hearing loss from thegentamicin, and the need for IM orIV doses.

Mepron (atavoquone), 750 mgbid, has demonstrated efficacy, butshould be given concurrently withazithromtcin, 250 to 600 mg daily, orresistance may develop. Efficacy isby far the best with this combination,but surprisingly, Herxheimer-likereactions are almost always seen atthe fourth day, and at the fourth weekof therapy. Does this represent anewly described phenomenon intreating Piroplasms, or does thiscombination have heretofore unrec-ognized efficacy in killing Bb?Although I do not have the answer, Isuspect the latter simply based on thefamiliar (in Bb) four-week cycle. Inlate, longstanding cases, one monthof treatment is the minimum, andfour or more months are oftenneeded. Problems during therapyinclude diarrhea, mild nausea, theexpense of Mepron ($600.00 perbottle- enough for one month oftreatment), and rarely, a temporaryyellowish discoloration of the vision.Regular blood counts and liverpanels are recommended during anyprolonged course of therapy.

Ehhrlichiosis

Treatment recommendations atthis time are very preliminary,mainly due to the lack of directdetection methods needed to guide usin developing a solid clinical feel.The mainstay of treatment is doxycy-cline, either orally or IV, given for atleast two weeks for an early infec-tion, or at least four weeks in alongstanding one. Interestingly, theunexpected efficacy of IV doxycy-cline in treating Lyme cases whichhad previously responded poorly tocell wall agents, may in fact reflectconcurrent therapy of coinfectionwith Bb and Ehrlichial species. Thenew concern for Ehrlichia is themain reason that Doxycycline is nowthe first choice in treating tlck bitesand early Lyme, before serologiescan become positive.

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SYMPTOM CHECK LISTThis is not meant to be used as a diagnostic scheme, but is provided to streamline the office interview. Note the

format - complaints referable to specific organ systems are clustered to better display multisystem involvement.

NAME __________________________________________________________ DATE _______________

RISK PROFILE (PLEASE CHECK)

Tick infested area__ Frequent outdoor activities__ Hiking__ Fishing ___ Camping ___

Gardening ___ Hunting ___ Ticks noted on pets ___

Do you remember being bitten by a tick? No__ Yes__ When? _________

Do you remember having the “bull’s eye rash”? No__ Yes__

Any other rash? No__ Yes__

Have you had any of the following? (CIRCLE ALL YES ANSWERS)

1. Unexplained fevers, sweats, chills, or flushing 2. Unexplained weight change—loss or gain 3. Fatigue, tiredness, poor stamina 4. Unexplained hair loss 5. Swollen glands: list areas _______________________________________________________________________ 6. Sore throat 7. Testicular pain/pelvic pain 8. Unexplained menstrual irregularity 9. Unexplained milk production: breast pain10. Irritable bladder or bladder dysfunction11. Sexual dysfunction or loss of libido12. Upset stomach13. Change in bowel function-constipation, diarrhea14. Chest pain or rib soreness15. Shortness of breath, cough16. Heart palpitations, pulse skips, heart block17. Any history of a heart murmur or valve prolapse?18. Joint pain or swelling: list joints _________________________________________________________________19. Stiffness of the joints, neck, or back20. Muscle pain or cramps21. Twitching of the face or other muscles22. Headache23. Neck creeks and cracks, neck stiffness, neck pain24. Tingling, numbness, burning or stabbing sensations, shooting pains25. Facial paralysis (Bell’s Palsy)26. Eyes/Vision: double, blurry, increased floaters, light sensitivity27. Ears/Hearing: buzzing, ringing, ear pain, sound sensitivity28. lncreased motion sickness, vertigo, poor balance29. Lightheadedness, wooziness30. Tremor31. Confusion, difficulty in thinking32. Diffculty with concentration, reading33. Forgetfuiness, poor short term memory34. Disorientation: getting lost, going to wrong places35. Difficulty with speech or writing36. Mood swings, irritability, depression37. Disturbed sleep-too much, too little, early awakening38. Exaggerated symptoms or worse hangover from alcohol

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Lyme Borreliosis (LB)

General Information

After a tick bite, Bb undergoesrapid hematogenous dissemination,and for example, can be found withinthe central nervous system as soon astwelve hours after entering thebloodstream. This is why even earlyinfections require full dose antibiotictherapy with an agent able topenetrate all tissues in adequateconcentrations to be bactericidal tothe organism.

It has been shown that the longera patient had been ill with Bb priorto first definitive therapy, the longerthe duration or treatment must be,and the need for more aggressivetreatment increases. Bb contains betalactamases, which, with some strains,may confer resistance to cephalospor-ins and penicillins. This is appar-ently a slowly acting enzyme system,and may be overcome by higher ormore continuous drug levels espe-cially when maintained by continu-ous infusions (cefotaxime) and bydepot preparations (benzathinepenicillin). Nevertheless, somepenicillin and cephalosporin treat-ment failures do occur and haveresponded to sulbactam/ampicillin,imipenim, and vancomycin, whichact on different cell wall sites thanpenicillin and the cephalosporins.

There is now evidence that B.burgdorferi can remain viablewithin cells, such as macrophages,lymphocytes, endothelial cells,neurons, and fibroblasts, and evadethe effects of antibiotics in vitro bysequestering in these intracellularniches. In addition, Bb secretes aglycoprotein that can encapsulate theorganism (an “S-layer”). This mayimpair immune recognition andblock antibiotic penetration. Becausethis glycoprotein binds host IgM, it ispossible that Borrelial antigens arehidden by host protein, and in theoryat least, this will interfere withimmune recognition, and causeseronegativity.

There are multiple strains ofBorrelia burgdorferi and they vary

in their antigen profile and antibioticsusceptabilities. In addition, L-formsexist which do not contain cell walls,and thus cell wall antibiotics will notaffect them. Apparently, Bb can shiftbetween the two forms during thecourse of the infection and cause thevarying serologic responses seen overtime, including seronegativity.Because of this, it may be necessaryto change antibiotics or even pre-scribe a combination of agents.

Vegetative endocarditis has beenassociated with Borrelia burgdorferi,but the vegetations may be too smallto detect with echocardiography.Keep this in mind when evaluatingpatients with murmurs, as this mayexplain why some patients seem tocontinually relapse after even longcourses of antibiotics.

Course Curing Therapy

As the spirochete has a very longgeneration time (12 to 24 hours invitro and possibly much longer inliving systems) and may have periodsof dormancy, during which timeantibiotics will not kill the organism,treatment has to be continued for along period of time to eradicate allthe active symptoms and prevent arelapse, especially in late infections.If treatment is discontinued before allsymptoms of active infection havecleared, the patient will remain illand possibly relapse further. Ingeneral, early disseminated LB istreated for four to six weeks, and lateLB usually requires a minimum offour to six months of continuoustreatment. All patients responddifferently and therapy must beindividualized. It is not uncommonfor a patient who has been ill formany years to require open endedtreatment regimens: indeed, somepatients will require ongoingmaintenance therapy to remain well.

It has been observed that symp-toms will flare in cycles every fourweeks. It is thought that this repre-sents the organism’s cell cycle, withthe growth phase occurring once permonth. As antibiotics will only killbacteria during their growth phase,

therapy is designed to bracket at leastone whole generation cycle. This iswhy the minimum treatment durationshould be at least four weeks. If theantibiotics are working, over timethese flares will lessen in severityand duration. The very occurrence ofongoing monthly cycles indicatesthat living organisms are still presentand that antibiotics should becontinued.

With treatment, these monthlysymptom flares are exaggerated andpresumably represent recurrentHerxheimer-like reactions as Bbenters its vulnerable growth phase.For unknown reasons, the worstoccurs at the fourth week of treat-ment. Observation is that the moresevere this reaction, the higher thegerm load, and the more ill thepatient. In those with long-standinghighly symptomatic disease who areon I.V. therapy, the week-four flarecan be very severe, similar to a serumsickness reaction, and be associatedwith transient leucopenia and/orelevations in liver enzymes. If thishappens, decrease the dose tempo-rarily, or interrupt treatment forseveral days, then resume with alower dose. If you are able to con-tinue or resume therapy, thenpatients dramatically improve. Thosewhose treatment is stopped and notrestarted at this point usually willneed retreatment in the future due toongoing or recurrent symptoms.Patients on I.V. therapy who have astrong reaction at the fourth weekwill need to continue parenteralantibiotics for several months, forwhen this monthly reaction finallylessens in severity, then oral or IMmedications can be substituted,indeed, it is just this observation thatguides the clinician in determiningthe endpoint of I.V. treatment. Ingeneral, I.V. therapy is given untilthere is a clear positive response,then treatment is changed to IM orpo until free of signs of activeinfection for 4 to 8 weeks. Somepatients, however, will not respond toIM or po treatment and I.V. therapywill have to be used throughout. As

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mentioned earlier, leucopenia may bea sign of persistent Ehrlichiosis, sobe sure to look into this. Repeatedtreatment failures should alert theclinician to the possibility of anotherwise inapparent immunedeficiency, and a workup for thismay be advised.

There are three things that willpredict treatment failure regardless ofwhich regimen is chosen: Non-compliance, alcohol use on a regularbasis, and failure of the patient toobtain proper rest. Advise them totake a break when (or ideally before)the inevitable mid afternoon fatiguesets in. All patients must keep acarefully detailed daily diary of theirsymptoms to help us judge the effectsof treatment, the presence of theclassic four week cycle, and treat-ment endpoint. One must follow suchdiaries, temperature readings in lateafternoon, physical findings, notesfrom physical therapists, andcognitive testing to best judge whento change or end antibiotics.

Remember-there currently is notest for cure, so this clinical follow-up assumes a major role in Lymedisease care.

Treatment Informaion

There is no universally effectiveantibiotic for treating LB. The choiceof medication used and the dosageprescribed will vary for differentpeople based on multiple factors.These include age, weight, gas-trointestinal function, blood levelsachieved, and patient tolerance.Doses found to be effective clinicallyare often higher than those recom-mended in older texts. This is due todeep issue penetration by Bb, itspresence in the CNS including theeye, within tendons, and because veryfew of the many strains of thisorganism now known to exist havebeen studied for antibiotic suscepti-bility. In addition, all animal studiesto date have only addressed earlydisease in models that behavedifferently than human hosts.Therefore, begin with a regimenappropriate to the setting and modify

it over time based upon responsesand refer to the suggested reading listand the appendix at the end of thisdocument.

Antibiotics

There are four types of antibioticsin general use for Bb treatment. Thetetracyclines, including doxycyclineand minocycline, are bacteriostaticunless given in high doses. If highblood levels are not attained, treat-ment failures in early and latedisease are common. However, thesehigh doses can be difficult to tolerate.For example, doxycycline can be veryeffective but only if adequate bloodlevels are achieved ether by high oraldoses (300 to 800 mg daily) or byparenteral administration.

Penicillins are bactericidal. Aswould be expected in managing aninfection with a gram negativeorganism such as Bb, amoxicillin hasbeen shown to be more effective thanoral penicillin V. Because of its shorthalf-life and need for high levels,amoxicillin is usually administeredalong with probenecid. Since bloodlevels are extremely variable theyshould be measured.

Cephalosporins must be ofadvanced generation: first generationdrugs are not effective, and secondgeneration drugs are comparable toamoxicillin and doxycycline both in-vitro and in-vivo. Third generationagents are currently the mosteffective of the cephalosporinsbecause of their very low MBC’s(0.06 for ceftriaxone) and have beenshown to be effective in penicillinand tetracycline failures. Cefuroximeaxetil (Ceftin), a second generationagent, is also effective against staphand thus is useful in treating atypicalerythema migrans that may representa mixed infection, containing someof the more common skin pathogensin addition to Bb. Because of thisagent’s GI side effects and high cost,it is not used as first line drug.

When choosing a third genera-tion cephalosporin, there are severalpoints to remember: Ceftriaxone isadministered once daily (an advan-

tage for home therapy), but has 95%biliary excretion and can crystallizein the biliary tree with resultant colicand possible cholecystitis. GIexcretion results in a large impact ongut flora. Biliary and superinfectionproblems with ceftriaxone can belessened if this drug is given ininterrupted courses, such as five daysin a row each week. Cefotaxime,which must be given at least everytwelve, and preferably every eighthours, is less convenient, but as ithas only 5% biliary excretion, itnever causes biliary concretions, andmay have less impact on gut flora. Itis the experience of some cliniciansthat cefotaxime can be even moreefficacious if given as a continuousinfusion, rather than in inter-rupted doses.

Erythromycin has been shown tobe almost ineffective asmonotherapy. The advancedmacrolides and azalides such asazithromycin and clarithromycin canbe difficult to tolerate orally due totheir tendency to promote yeastovergrowth and poor GI tolerance atthe high doses needed. As they haveimpressively low MBCs and doconcentrate in tissues and penetratecells, they theoretically should beideal agents. However, initialclinical results were disappointing, ithas been suggested that when Bb Iswithin a cell, it is held within avacuole and bathed in fluid of lowpH, and this acidity may inactivatethis class of antibiotics. Therefore,they are administered concurrentlywith hydroxychloroquine or amanta-dine, which raise vacuolar pH,rendering these agents much moreeffective. It is not known whetherthis same technique will makeerythromycin a more effectiveantibiotic in LB. Another alternativeis to administer azithromycinparenterally. Results are excellent,but expect to see abrupt Jarisch-Herxheimer reactions.

Other agents with demon-strated in-vitro efficacy have beenused successfully in treating patientswith Bb and are listed further below.

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Monitoring Therapy

Drug levels are measured untilthe most acceptable dose is found,and then at any time major changesin the treatment regimen occur. Withparenteral therapy, CBC and chem/liver panels are done at least twiceeach month during symptom flares,with urinalysis and prothrombin timemonitored monthly.

Antibiotic Choices

Oral Therapy: Always checkblood levels when using agentsmarked with an *, and adjust dose toachieve a peak level in the mid-teensand a trough greater than five.Because of this, the doses listedbelow may have to be raised. Con-sider Doxycycline first due toconcern for Ehrlichlia.

*Amoxicillin - Adults: 1g q8hplus probenecid 500mg q8h; dosesup to 6 grams daily are often needed

Pregnancy: 1g q6h and adjust.

Children: 50 mg/kg/day dividedinto q8h doses.

*Doxycycline - Adults: 100 mg tidwith food; doses of up to 600 mg dailyare often needed, as doxycycline is onlyeffective at high blood levels. Not forchildren or in pregnancy.

If levels are too low at tolerateddoses, give parenterally

*Cefuroximeaxetil - Oralalternative that may be effective inamoxicillin and doxycycline failures.Useful in EM rashes co-infected withcommon skin pathogens.

Adults and pregnancy: 1g ql2hand adjust. Children: 125 to 500 mgql2h based on weight.

Tetracycline - Adults only andnot in pregnancy. 500 mg tid to qid

Erythromycin - Poor responseand not recommended.

Azithromycin - Adults: 500 to1200 mg/d. Adolescents; 250 to 500mg/d add hydroxychloroquine, 200-400 mg/d or amantadine 100-200mg/d

Cannot be used in pregnancy or

in younger children.

Clarithromycin - Adults: 250 to500 mg q6h plus hydroxychloroquine200-400 mg/d or amantadine 100-200 mg/d. Cannot be used inpregnancy or in younger children.

Augmentin - Cannot exceedthree tablets daily due to the clavula-nate, thus is given with amoxicillin.

Chloramphenicol - Not recom-mended as not proven and potentiallytoxic.

Parenteral Therapy

Ceftriaxone - Risk of biliarysludging can be minimized withintermittent breaks in therapy (ie:infuse five days in a row per week).

Adults and pregnancy: 2g q24h.For large body habitus or moresevere illness: up to 4g daily

Children: 75 mg/kg/day up to 2g/day

Cefotaxime - Comparableefficacy to ceftriaxone: no biliarycomplications.

Adults and pregnancy: 2g q8h;may dose as high as 12g daily.Consider continuous infusion.

Children: 90 to 180 mg/kg/daydosed q6h (preferred) or q8h, not toexceed 12 g daily.

*Doxycycline - Requires centralline as is caustic. Surprisinglyeffective, probably because bloodlevels are higher when givenparenterally. Always measure bloodlevels.

Adults: 400 mg q24h and adjustbased on levels Cannot be used inpregnancy or in younger children.

Azithromycin - Requires centralline as is caustic. Dose: 500 to 1000mg daily in adolescents and adults.

Penicillin G - IV penicillin G isminimally effective and not recom-mended.

Benzathine penicillin - Surpris-ingly effective IM alternative to oraltherapy. May need to begin at lowerdoses as strong, prolonged (6 or moreweek) Herxheimer-like reactions

have been observed.

Adults: 1.2 million U once totwice weekly

Adolescents: 300,000 to 1.2million U weekly.

Should not be used in pregnancy.

Poorly studied but anecdotallyeffective

Vancomycin - observed to be oneof the best drugs in treating Lyme,but potential toxicity limits its use. Itis a perfect candidate for pulsetherapy to minimize these concerns.Use standard doses and confirmlevels.

Imipenim and Unisyn - similarin efficacy to cefotaxime, but oftenworks when cephalosporins havefailed. Must be given q6 to q8 hours.

Cefuroxime - useful but notdemonstrably better than ceftriaxoneor cefotaxime, Ampicillin IV- moreeffective than penicillin G. Must begiven q6 hours.

Treatment Categories

Prophylaxis of high risk groups-education and preventive measures.Antibiotics are not given.

Tick Bites - Embedded DeerTick With No Signs or Symptoms ofLyme (see appendix):

Decide to treat based on the typeof tick, whether it came from anendemic area and percent infected,how it was removed, and length ofattachment (nymphs; at least oneday: adults; anecdotally, as little asfour hours). The risk of transmissionis greater if the tick is engorged, or ifit was removed improperly allowingthe tick’s contents to spill into thebite wound. High risk bites aretreated as follows (remember thepossibility of coinfection!):

1)Adults: Oral therapy for 21 days.

2) Pregnancy: Amoxicillin 1000mg q6h for 6 weeks. Test for Babesiaand Ehrlichia. Alternative: Cefuroximeaxetil 1000 mg q12h for 6 weeks.

3) Young Children: Oral therapyfor 21 days.

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Early Localized - Singleerythema migrans with no constitu-tional symptoms: 1) Adults: oraltherapy for 6 weeks. 2) Pregnancy:1st and 2nd trimesters; I.V. X 21days then oral X 6 weeks 3rdtrimester: Oral therapy x 6 weeks.Any trimester- test for Babesia andEhrlichia 3) Children: oral therapyfor 6 weeks.

Disseminated Disease - Multiplelesions, constitutional symptoms,lymphadenopathy. or any othermanifestations of dissemination.

Early Disseminated: Mildersymptoms present for less than oneyear and not complicated by immunedeficiency or prior steroid treatment:

1) Adults: oral therapy until noactive disease for 4 weeks (4-6months typical)

2) Pregnancy: As in localizeddisease, but duration as above. Someexperienced clinicians treat through-out pregnancy

3) Children: Oral therapy withduration based upon clinical re-sponse.

Parenteral Alternatives for moreill patients and those unresponsive toor intolerant of oral medications:

1) Adults and children: I.V.therapy for 6 weeks or until clearlyimproved. Follow with oral therapyor IM benzathine penicillin until noactive disease for 8 weeks. I.V. mayhave to be resumed if oral or IMtherapy fails.

2) Pregnancy: IV then oraltherapy as above.

Late Disseminated: presentgreater than one year, more severelyill patients, and those with priorsignificant steroid therapy or anyother cause of impaired immunity:

1) Adults and pregnancy;extended IV therapy (6 to 10 or moreweeks), then oral or IM, if effective,to same endpoint.

2) Children; IV therapy for 6 ormore weeks, then oral or IM followup as above.

Alternate Scheduling of AntibioticTherapy

Pulse Therapy

Pulse therapy consists of adminis-tering antibiotics (usually parenteralones) two to three days in a row perweek. This allows for severaladvantages:

• Dosages are doubled (ie:cefotaxime, 12 g daily), increasingefficacy• More toxic medications can beused with increased safety (ie;vancomycin)• May be effective when conven-tional, daily regimens have failed.• IV access may be easier or moretolerable• More agreeable lifestyle for thepatient• Often less costly than dailyregimens

Note that this type of treatment isexpected to continue for a minimumof ten weeks, and often must con-tinue beyond twenty weeks. Theefficacy of this regimen is based onthe fact that it takes 48 to 72 hours ofcontinuous bactericidal antibioticlevels to kill the spirochete, yet it willtake longer than the four to five daysbetween pulses for the spirochetes torecover. As with all Lyme treat-ments, specific dosing and schedul-ing must be tailored to the individualpatient’s clinical picture based uponthe treating physician’s best clinicaljudgment.

Combination Therapy

This consists of using two ormore dissimilar antibiotics simulta-neously for antibiotic synergism andto better compensate for differingkilling profiles and sites of action ofthe individual medications. A typicalcombination is the use of a cell wallagent plus a protein inhibitor (ie:amoxicillin plus clarithromycin).Note that GI intolerance and yeastsuperinfections are the biggestdrawbacks to this type of treatment.However, these complications canoften be prevented or easily treated,and the clinically observed benefitsof this type of regimen clearly have

outweighed these problems inselected patients.

Refractory Disease

Persistent Signs and Symptomsthat Respond to Antibiotic Therapy

Patients in this group improve onantibiotics yet relapse repeatedlywhen medications are Discontinued.Some patients in this category havebeen proven, in peer reviewedmedical literature, to have persistentinfection. The treating physician maydecide on chronic therapy in order toavoid clinical deterioration. Recom-mend you confirm blood levels, andstudy immune competence. Thisincludes T- and B- cell function andcounts, Natural Killer cell functionalassays, complement levels, neutro-phil function, and vaccine respon-siveness.

Options for treatment:

• Longer duration. including openended maintenance therapy• Increased dose

• Different drug

• Change method of administration(oral to IV)• Combination or pulse therapy

• Synovetomy

• Search for and treat concurrentillnesses• Supportive therapy as needed

Persistent Signs and Symptoms NotResponsive to Antibiotics

• Reconsider the diagnosis, andperform specific Bb antigen testsafter antibiotic free for 6 to 12 weeks.• Search for and treat concurrentillnesses and coinfections• Supportive therapy based onsymptoms• NSAIDS and hydroxychloroquine

• Antidepressants, analgesics, musclerelaxants, and amantadine• Synovectomy

• Psychiatric/psychometric evalua-tion and treatment if indicated• Long-term follow-up

• Consider retreatment if conditionchanges

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Adjunctive Therapy

Recommended in All LymePatients:

• daily yogurt and acidophiluspreparations• multivitamins and B complex 50mg daily• Physical therapy, rehabilitation,and a graded exercise program

Prescribe as needed, especiallyin more severe cases:

• vitamin and nutritional supple-ments as listed below• Psychosocial evaluation andpossibly refer for counseling• NSAIDS and remittive agents

• antidepressants, analgesics, musclerelaxants, and amantadine• immune globulins and otherimmunotherapy if indicated• Sinequan (DAW) in low doses (5 to50 mg daily) reportedly improves T-cell function

Contraindicated:

• alcohol use• excessive caffeine intake• any avoidable stresses• sleep deprivation

Safety

Over a decade of experience intreating thousands of patients withLyme has proven that therapy asdescribed above, although intense, isgenerally well tolerated. The mostcommon adverse reaction seen isallergv to probenecid. In addition,yeast superinfections are seen, butthese are generally easily recognizedand managed. The induction ofClostridium difficile toxin productionis seen most commonly withceftriaxone, but can occur with anyof the antibiotic regimens mentionedin this document. However, regularuse of the lactobacillus preparationsseems to be helpful in controllingyeast and antibiotic related colitis, asthe number of cases of C. difficile inLyme patients is low when theseguidelines are followed.

When using PICC lines (periph-

erally inserted central catheters), ifANY line problems arise, it isrecommended that the line be pulledfor patient safety. Salvage attempts(urokinase, repairing holes) are oftenineffective and may not be safe

Please advise all patients whotake the tetracyclines of skin and eyesensitivity to sunlight and the properprecautions. When doxycycline isgiven parenterally, do not freeze thesolution prior to use!

Years of experience with chronicantibiotic therapy in other condi-tions, including rheumatic fever,acne, recurrent otitis, recurrentcystitis, COPD, bronchiectasis, andothers have not revealed any consis-tent dire consequences as a result ofsuch medication use. Indeed, the veryreal consequences of untreatedchronic persistent infection by B.burgdorferi can be far worse than thepotential consequences of thistreatment.

Nutritional Supplements inChronic Lyme Disease

Studies on patients withchronic Lyme Disease and in thosewith the Chronic Fatigue Syndromehave demonstrated that some of thelate symptoms are related to cellulardamage and deficiencies in certainessential nutrients. Double blinded,placebo controlled studies, and inone case direct assay of biopsyspecimens have proven the value ofthe supplements listed.

Essential Fatty Acids:

Studies show that when EFAs aretaken regularly, statistically signifi-cant improvements in fatigue, aches,weakness, vertigo, dizziness,memory, concentration and depres-sion are likely. There are two broadclasses: GLA and EPA, derivedrespectively from plant and fish oils.The plant sources are many, sochoose one from the list below.

Plant Oils: evening primrose oil,black currant seed oil, borage oil(probably the best choice), fish oil:(“MAX EPA” or any similar prepa-ration containing 1,000 mg of EPA)

Recommendation: four plant oilcapsules and two to four EPAcapsules dairy, taken with the largestmeal of the day. Benefit beginswithin several days, but furtherimprovement continues to occur overtime. Continue for three to fourmonths.

CO-Q 10 (ubiquinone): This is avitamin B- like compound essentialto every living cell. Deficiencies havebeen related to poor function of theheart, limitations of stamina, andpoor resistance to infections. Tissuebiopsy studies have resulted in therecommendation that a patient withchronic Lyme should take between200 and 300 mg daily, in two orthree equal doses.

Improvements in stamina andgeneral well being do not begin forseveral weeks. The body will manu-facture its own Co-Q 10 when theoriginal infection is controlled, butonly if stimulated by aggressiveexercise. Therefore use this supple-ment until the patient is feeling welland is exercising regularly, usuallythree to four months.

Vitamin B: Studies in the 1950’sdemonstrated the need for supple-mental vitamin B in infections withother Borrellia. This enhancesclearing of neurological symptoms. Irecommend one 50 mg B-complexcapsule daily long term.

Magnesium: Magnesiumsupplementation very helpful for thetremors, twitches, cramps, musclesoreness, arrhythmias and weakness.It may also help in energy level andcognition. Unexplained hyperreflexiais an indicator of Mg deficiency.

The best source is magnesiumchloride (‘Bio-Mag”, one or two qid)or magnesium oxide (Mag-Ox, 400mg one or two daily). DO NOT relyon “cal-mag”, calcium plus magne-sium combination tablets, as they arenot well absorbed. In many cases,I.M. or I.V. magnesium is necessary.Continue long term.

Multi-Vitamin: I recommend theLife Pack family of supplements -

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choose LifePak for males under 40,LifePak Women for hormonallyactive women, and Lifepak Prime forpost menopausal women and menover 40. These are unique supple-ments-Pharmaceutical grade andUSP certified, and the only productsclinically proven to raise antioxidantlevels in the blood and lipids. Theyare available by mail order- call 1-800-487-1500, reference # US9256681. Continue long term.

All of these products are availablewithout a prescription.

Lyme Disease Rehabilitation

Those with long-standing tickborne illnesses end up in poorphysical condition. Even withsuccessful treatment of the infections,they will not return to normal unlessthey take an active role in personalrehabilitation.

In late stage disease, manynegative effects to the body areoccurring: muscles atrophy, and tosome degree, the heart muscle alsosuffers, as do the joints, tendons,nerves, etc. The percent fat contentof the body as a whole rises, thecholesterol rises, and the balancebetween HDL and LDL becomes lessfavorable. In at least 50% of thepatients, significant weight gainoccurs.

Because of the extreme fatigueand body pain, many Lyme sufferersend up spending inordinate amountsof time in bed, and get far lessexercise than they did before theybecame ill. This begins a debilitatingdownward spiral that can be verydifficult to reverse.

As a result, Lyme patients arestiff, weak, tired, have poor stamina,and are at increased risk for cardio-vascular disease and diabetes.Antibiotic treatment alone cannotcorrect these effects. Therefore, it isnecessary to prescribe physicaltherapy, the extent of which dependson an individual patients’ condition,followed by a graded exerciseprogram.

The earliest phase involves

multiple modalities (massage, heat,TENS, MENS, ultrasound. etc.) andaggressive range of motion exercisessupervised by a physical therapist.The goal is to relieve discomfort andto promote better sleep and flexibil-ity. This then evolves into stretchingand mild muscular toning which canlessen joint pain and increasemobility and stamina. Finally, theprogram must expand to includemuscular conditioning and strength-ening, ideally under the supervisionof a credentialed exercise physiolo-gist. “Body sculpture” classes areideal. Aerobics are not recommendeduntil the patient has fully recovered.

This is the time for the very bestof health habits. I recommend light,low fat food, with high qualitynutritional value, minimal amountsof starch and other simple carbohy-drates, absolute abstention fromalcohol, elimination of caffeine, and,if applicable, a serious commitmentto weight loss. Consider recommend-ing books that outline “Arthritisdiets”, as they can help somepatients.

Cessation of smoking is ex-tremely important and must beaddressed immediately. As writtenorders for physical therapy arerequired to initiate the program, anexample of the format of a typicalprescription for Lyme rehabilitationfollows. [See following page]

Managing Yeast Infections

Many patients with Lyme Diseasedevelop an overgrowth of yeast.Therefore, it is recommended that ona daily basis the patient eat a fullcontainer or yogurt that containsactive cultures, and take acidophilus,two after each meal. Here are somesuggestions on how to control yeast:

Mouth: A tongue with a beigecoating, bad breath, and dysgeusiaare signs of thrush. The patient mustbrush the tongue whenever theybrush their teeth, and use antisepticmouthwashes then. Because theeffectiveness of a mouthwash isrelated to how long it is in contact

with the germs, it should be kept inthe mouth while brushing.

Since yeast germs feed on sugars,have patients avoid simple carbohy-drates, starches, fruits, and juices forat least two weeks, or until theproblem is gone.

Prescription medications may benecessary. Mycelex troches andNystatin liquid are not recommendedfor they contain large amounts ofsimple sugars. Nystatin powder isused, mixed with water, to beswished end swallowed qid (pc andhs). Systemic antifungals (Diflucan,Nizoral) may be necessary. The mosteffective (and drastic) treatment,employed as a last resort, consists ofusing “Dakin’s Solution” as a mouthrinse. This is a mixture of householdliquid bleach (Clorox), one teaspoonin four ounces of water. A smallamount is held in the mouth whilebrushing, then spit out, and repeateduntil the mouth has cleared. This isusually a one-time treatment, butmay have to be repeated every fewweeks. After using an antiseptic toclean the mouth, it is necessary toimmediately eat yogurt or liquidacidophilus, or chew an acidophiluscapsule to replenish the beneficialflora in the mouth. Because the germcount after such a cleaning will beartificially reduced, and becauseyeast germs are opportunists, theywould be the first to come back. Byhaving the yogurt or acidophilusthen, a more normal oral flora willresult and thrush will be bettercontrolled.

Intestinal Tract: An overgrowthof yeast here will ferment dietarysugars and starches, forming acids,gas, and alcohols. Symptoms includegas, heartburn and/or pain in thestomach area, and because of thealcohol, there can be headaches,dizziness. lightheadedness, andwooziness. To clear intestinal yeast,first the tongue and mouth must becleared so yeast does not reenter thesystem with every swallow. Avoidsweets, starches, fruits and juices fortwo weeks or longer to starve the

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LYME REHAB-PHYSICAL THERAPY PRESCRIPTION

NAME ____________________________________________________________________________________

D.O.B. _________________________________________________ DATE ______________________________

Please enroll this patient in a program of therapy to rehabilitate him/her from the effects of Lyme Disease. Ifnecessary, begin with classic physical therapy, then progress when appropriate to a whole body conditioning program.Such therapy must be graded, carefully individualized, and be performed on a one-on-one basis, at least initially, toensure the maximal amount of supervision and guidance.

THERAPEUTlC GOALS (to be achieved in order as the patient’s ability allows):

PHYSICAL THERAPY:

1. Relieve pain and muscle spasms utilizing multiple modalities as available and as indicated: massage, heat,ultrasound, TENS, “micro amp”, etc.

2. Increase mobility while protecting damaged and weakened joints, tendons, and ligaments, to increase range ofmotion and relieve stiffness.

EXERCISE: Begin with a private trainer for careful direction and education.

PATIENT EDUCATION AND MANAGEMENT (to be done during the initial one-on-one sessions and reinforcedat all visits thereafter):

1. Instruct patients on correct exercise technique, including proper warm-up, breathing, joint protection, properbody positioning during the exercise, and how to cool-down and stretch afterwards.

2. Please work one muscle group at a time and perform extensive and extended stretches to each muscle groupimmediately after each one is exercised, before moving on to the next muscle group.

3. A careful interview should be performed at the start of each session to make apparent the effects, both good andbad, from the prior visits therapy, and adjust therapy accordingly.

PROGRAM:

1. Improve strength and reverse the poor conditioning that results from Lyme, through a whole-body exerciseprogram (“stretch and tone”, or “body sculpture” classes). This consists of light calisthenics and weight lifting, usingsmall weights and many repetitions.

2. Exercise no more often than every other day

3. Each session should last one hour. If the patient is unable to continue for the whole hour, the program todecrease the intensity to allow him/her to do so.

4. This is what is required to achieve wellness and is the main focus of rehab. Simply placing the patient on atreadmill or an exercise bike is not acceptable, nor is a simple walking program.

5. Aerobic exercises are not allowed, not even low impact variety, until the patient has fully recovered.

Please feel free to contact my office if you would like to discuss this client’s situation in more detail.

PHYSICIAN’S SIGNATURE___________________________________________________________________

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germs. Systemic antifungals(Diflucan, Nizoral) usually areneeded.

Vaginal: An occasional vaginalyeast infection can be controlled withproducts such as Monistat cream orsuppositories. If it is a recurrent orongoing problem, then it oftenreflects a simultaneous intestinalinfection, reinfecting the genital areawith every bowel movement. There-fore treat the patient as above forintestinal overgrowth, and prescribetopical preparations such as Monistatconcurrently for two weeks.

Patient Instructions

Site Prevention and Tick Removal

How to Protect Yourself FromTickbites Properly

Remove wood piles, rock walls,and bird feeders as these attract tick-carrying small animals and canincrease the risk of acquiring Lyme.

Insecticides: Property should betreated with a product called“Damminix”. This consists ofcardboard tubes containing cottonballs that have been dipped ininsecticide. These tubes are placedaround the property in the woodedareas and below shrubs. Mice, whichare a key link in the propagation ofLyme disease, find the cotton andbring it back to their burrows to beused as nesting material, with theresult being a big decrease in thenumber of ticks in the area. Unfortu-nately, after two years tick popula-tions may rise again as other smallanimals that do not gather cottonbecome hosts to the ticks, Therefore,Damminix alone is not sufficient.Use this product in conjunction withliquid or granular insecticides.

Liquid and Granular Pesticides:Products meant for widespreadapplication include Dursban, Tempo,permethrin, and sevin. They areavailable as a liquid concentrate andas granules. If liquid insecticides areused, application should be byfogging, not by coarse sprays. Applythese products in a strip a few feetwide at the perimeter of the lawn at

any areas adjacent to woods andunderbrush. Also treat any ornamen-tal shrubs near the house that mayserve as a habitat for small animals.The best time to apply these productsis in late Spring and early Fall.

Clothing: When wearing longpants, tuck the cuffs into the socks soany ticks that get on shoes or sockswill crawl on the outside of the pantsand be less likely to bite. Also, lightcolored clothing should be worn sothe ticks will be easier to spot.Smooth materials such as windbreak-ers are harder for ticks to grab ontoand are preferable to knits, etc.

Tick repellents that contain“permethrin” (Permanone,Permakill) are meant to be sprayedonto clothing. Spray the clothesbefore they’re put on, and let themdry first. Do not apply this chemicaldirectly to the skin. Ticks are veryintolerant of being dried out. Afterbeing outdoors in an infested area,place clothes in the dryer for a fewminutes to kill any ticks that maystill be present.

Skin: Insect repellents thatcontain “DEET” are somewhateffective when applied to the arms,legs, and around the neck. Do notuse any repellent over wide areas ofthe body as they can be absorbedcausing toxicity. Also, it is inadvis-able to use a product that containsmore than 50% DEET, and 25%concentrations are preferred. Userepellents cautiously on smallchildren, as they are more susceptibleto their toxic effects. Be aware thatthis repellent evaporates quickly andmust be reapplied frequently. Checkcarefully for ticks not only whenhome but frequently while stilloutside!

How to Remove an Attached Tick

Using a tweezer (not fingers!),grasp the tick as close to the skin aspossible and pull straight out. Thenapply an antiseptic. Do not try toirritate them with heat or chemicals,or grasp them by the body, as thismay cause the tick to inject moregerms into your skin. Tape the tick to

a card and record the date andlocation of the bite. Remember, thesooner the tick is removed, the lesslikely an infection will result.

Appendix

Rationale for Treating Tick Bites

The Medical Advisory Committeeof the Lyme Disease Foundation nowrecommends antibiotic prophylactictreatment upon a known tick bite for:

1. People at higher health riskbitten by an unknown type of tick ortick capable of transmitting Borreliaburgdorferi, e.g. pregnant women,babies and young children, peoplewith serious health problems, andthose who are immunodeficient.

2. Persons bitten in an areaendemic for Lyme Borreliosis by anunidentified tick or tick capable oftransmitting B. burgdorferi,

3. Persons bitten by a tick capableof transmitting B. burgdorferi, wherethe tick is engorged, or the attach-ment duration of the tick is greaterthan four hours, and/or the tick wasimproperly removed. This meanswhen the tick is squeezed betweenthe fingers, irritated with toxicchemicals in an effort to get it toback out, or disrupted in such a waythat its contents were allowed tocontact the bite wound. Suchpractices increase the risk of diseasetransmission.

4. A patient, when bitten by aknown tick, clearly requests oralprophylaxis and understands therisks. This is a case-by-case decision.

The physician cannot rely on alaboratory test or clinical finding atthe time of the bite to definitely rulein or rule out Lyme Disease infec-tion, so must use clinical judgment asto whether to use antibiotic prophy-laxis. Testing the tick itself for thepresence of the spirochete, even withPCR technology, is not reliableenough to guide your decision totreat, as false positives and falsenegatives occur.

An established infection by B.burgdorferi can have serious, long-

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standing or permanent, and painfulmedical consequences, and beexpensive to treat. Since the likeli-hood of harm arising from prophy-lactically applied spirochetal antibi-otics is low, and since treatment isinexpensive and painless, it followsthat the risk benefit ratio favors tickbite prophylaxis.

It is the Medical AdvisoryCommittee’s recommendation thatantibiotic prophylactic treatment fortick bite in many circumstances isnot only justified but warranted. Theultimate decision for treatment ontick bite should be determined jointlybetween the physician and patient.

Rationale for Treatment Recom-mendations

When I began treating LymeBorreliosis (LB) in the mid 1980s, Irecognized that in disseminateddisease, the then recommended ten tofourteen day courses of antibioticswould either result in only a lessen-ing of the illness, or an initial goodoutcome followed by a relapse ofsymptoms. These patients would thenrespond again to a repeat course ofantibiotics.

Published studies by Steere andothers (1) had, at that time, definedsuccess as the elimination of the“major” symptoms of Lyme (arthri-tis, carditis, and Bell’s Palsy) eventhough they usually resolve over timewithout treatment. These samestudies go on to report the persis-tence of “minor symptoms” of Lymeeven after antibiotic therapy, and theauthors call it the “post Lymesyndrome”.

In 1987 I participated in a studyin which twenty six patients withactive disseminated LB who wereculture positive for Borreliaburgdorferi(Bb), were treated withceftriaxone I.V. for fourteen days,using either two or four grams a day.Although culture negative at theimmediate end of therapy, allpatients became culture positiveagain within several weeks, whichcorresponded to the time when theirsymptoms recurred. I concluded then

that the persistence of symptomsafter this type of therapy in factrepresented ongoing infection. Theresults of this study were presented in1989 at the national meeting of theLyme Borreliosis Foundation. Uponthe advice of colleagues who foryears have been involved in seminalLB research (2), I then studied theeffects of lengthened duration oftreatment. I found a direct correlationbetween treatment duration and theultimate outcome of patients’symptoms. Using amoxicillin 3g/dayplus probenecid 1.5g/day in divideddoses, the percent success wastabulated for therapies lasting for

antibiotic treatment necessary toachieve this was at least four months.

Further culture studies involving74 patients confirmed that thepatients had to be free of signs andsymptoms of active borreliosis beforeantibiotics were discontinued inorder to be both culture negative, andnot experience a relapse during threemonths of followup.

There are now a growing numberof published reports utilizing variousforms of Bb antigen detection thatdemonstrate the persistence ofinfection in antibiotically treatedpatients (3,4,5,6,7,8), confirming myearlier work. Even Steere hasproposed this as a mechanism forchronic arthritis in Lyme (9).

Although syphilis perhaps is nota synonymous spirochetosis to Lyme,similar findings of organism persis-tence despite presumed adequate(short course) therapy has beenreported in those who later becameimmune deficient (10). Indeed,Wassermann in 1936 recommendeda minimum of twenty six weeks oftreatment for established infection,based upon generation-time studies.

I had participated in an NIHstudy utilizing the antigen detectionmethod of Dorward et at (11) intesting over 130 patients withchronic persistent LB, in whomsymptoms of active disease continueddespite even prolonged treatment(indeed, some would describe asexcessive the treatment given toseveral participants), Bb could berecovered from blood, CSF, urine,and tears. Indeed, many of thesepatients had received months to yearsof aggressive, often parenteraltherapy for LB. For example, one hadreceived continual antibiotics forthree years, while another wastreated for 18 months with repeatedcourses of parenteral therapy. As amatter of record, neither one was apatient of mine.

These examples clearly indicatewhat researchers have recognized asthe ability of Bb to evade host

from one through six months.Success here is defined as theelimination of all LB symptoms, bothmajor and minor, without a relapseby three months after completion oftreatment.

The data clearly demonstrated adirect relationship between durationand success, starting at 17% for onemonth of therapy, and reaching aplateau at 67% at five monthsduration. These data were alsopresented at the 1989 meetingmentioned above.

Next, using ceftriaxone, results oftherapy were tabulated based onduration. Even with 45 days ofcontinuous antibiotic, none of thepatients returned to or maintainedtheir well, pre-Lyme state. However,if oral medications were continuedafter ceftriaxone, to the endpoint ofbeing free of signs and symptoms ofactive disease, then relapses did notoccur. Again, the average duration of

“Extended durationsof antibiotic therapyclearly have helpedliterally thousands ofpatients who were nothelped by shortcourses of treatment.”

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defenses (1,12,13,14,15) even in thepresence of antibiotics (5,6,7,8).

I do not now recommend treat-ment forever, but I point out theabove results to be able to makeseveral points:

1. There has never been a studyin the history of this illness that evenin the simplest way proves thatcurrently recognized short-course(two to four week) therapy results ina bacteriologic cure.

2. There has never been aconsensus in patients still symptom-atic after short treatment courses asto what constitutes the post Lymesyndrome, how Bb induces it, andwhat perpetuates it if bacteriologiccure is indeed presumed.

3. Patients must be kept ontherapy until free of active symptomsor they either will never recoverfully, or suffer a relapse.

4. Extended durations of antibi-otic therapy clearly have helpedliterally thousands of patients whowere not helped by short courses oftreatment.

5. Finally, we have to recognizethat in some patients, LB may not becurable in a strict bacteriologic sense.

Until sensitive and specificantigen detection tests become widelyavailable, treatment of LB willremain difficult, controversial, andthe subject of much discussion.

J.J. Burrascano, Jr., M.D

Suggested Reading

1. Asbrink, E., Hovmark, A.Successful cultivation of spirochetesfrom skin lesions of patients witherythema chronicum migransAfzelius and acrodermatitis Chronicaatrophicans. Acta Pathol MicrobImmunol Scand 1985; Sect B, 93:161-163

2. Berger, B.W., Johnson, R. C.,Schwann, T.G. Clinical and micro-biologic findings in six patients witherythema migrans of Lyme Disease,Am J Acad Dermatol 1989: 21:1186-91

3. Cimmino, M.A., Azzolini, A.,Tobia, F., Pesce, C.M. Spirochetes inthe spleen of a patient with chronicLyme Disease. Am J Clin Pathol1989; 91:95-97

4. Dorward, D.W., Schwan, T.G.,Garon, C.F. Immune capture anddetection of Borrelia burgdorferiantigens in urine, blood, or tissuesfrom infected ticks, mice, dogs, andhumans. J J Clin Microbiol1991:29(6):1162-70

5. Harris, N.S., Stephens, B.Detection of Borrelia burgdorferiantigen in urine from patients withLyme borreliosis, 1995; 2(2):37-41

6. Hassler, D., Riedel, K., Zorn,J., Preac-Mursic, V. Pulsed high dosecefotaxime therapy in refractoryLyme Borreliosis, Lancet1991:338:13

7. Kirsch, M. etal. Fatal adultrespiratory distress syndrome in apatient with Lyme Disease. JAMA1989; 259:2737-39

8. Lavoie, P.E. Lyme Disease. INConn’s Current Therapy 1991 pp101-105

9. Lawrence, C., Lipton, R.B.,Lowy, F. D., Coyle, P.K. Seronega-tive chronic relapsingneuroborreliosis, Eur Neurol 199535(2):113-117

10. Liegner, K.B. Lyme Disease:the Sensible Pursuit of Answers. JClin Microbiol 1993; 31(8): 1961-63

11. Logigian, E.L., Kapan, R.F.,Steere, A.C. Chronic neurologicmanifestations of Lyme Disease. NEngl J Med 1990; 323:1438-44

12. MacDonald, A.B. GestationalLyme Borreliosis. Implications forthe fetus. In Rheumatic DiseaseClinics of North America1989:15(4):657-677

13. MacDonald, A.B., Berger.B.W., Schwann, T.G. Clinicalimplications of delayed growth of theLyme Borreliosis spirochete, Borre-lia burgdorferi. Acta Tropica 1991;48:89-94

14. Musher, D.M. Syphilis,

Neurosyphilis, Penicillin, and AIDS.J Infect Dis 1991; 163:1201-1206

15. Rachner, A.R., Itano, A.Borrelia burgdorferi infection of thebrain: Characterization of theorganism and response to antibioticsand immune sera in the mousemodel. Neurology 1990; 40:1535-40

16. Pfister, H.W., Preac-Mursic,V., Wilske, B. Latent Lymeneuroborreliosis: Presence ofBorrelia burgdorferiin the CSFwithout concurrent inflammatorysigns. Neurology 1989: 39:1118-20

17. Preac-Mursic, V., Marget,W., Busch, U., Pleterski-Rigler, D.,Hagl, S. Kill kinetics of Borreliaburgdorferi and bacterial findings inthe relation to the treatment of Lymeborreliosis. Infection 1996; 24(1):11-18

18. Preac-Mursic, V., Wanner,G., Reinhardt, S., Wilske, B.,Marget, W. Formation and cultiva-tion of Borrelia burgdorferispheroblast L-form variants. Infec-tion 1996; 24(3):218-225

19. Preac-Mursic, V., Weber, K.,Pfister, H.W., Wilke, B. Survival ofBorrelia burgdorferi in antibioticallytreated patients with LymeBorrelliosis. Infection 1989:17(6):355-359

20. Steere, A,C. Lyme Disease, NEngI J Med 1989; 321:586-96 21.Steere. A.C., Dwyer, E., Winchester,R. Association of chronic Lymearthritis with HLA-DR4 and HLA-DR2 alleles. NEJM 1990; 323:219-23

22. Wahlberg, P., Granlund, H.,Nyman, D., Panelius, J., Sppaia, I.Treatment of late Lyme Borreliosis.Journal of Infection 1994: 29:255-261

“You do what you can with all thebrains you have; you practicehumility and anticipate the unantici-pated. It's science at its mostheartening.”

Jon Carroll, San FranciscoChronicle columnist

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“The New Lyme” — A Look atBabesia/Borrelia Co-infectionby Jean Hubbard

“I humbly propose we redefinewhat we have been calling Lyme,”suggests Dr. Joseph Burrascano,talking about what he calls “the newLyme disease” – prolonged diseasecaused by co-infections with multipletickborne agents. “Co-infection is notsurprising, for ticks ... literally live inthe dirt and drink the blood of wildanimals. To think that a significanttick bite transmits only one infectionis narrow minded indeed.” The priceof such narrow-mindedness? –“creation of chronic, persistent formsof each of these infections” [1].

This must sound alarming topeople who aren’t already so familiarwith chronic, persistent illness. Butfor chronic Lyme patients the newunderstanding of co-infections offersa ray of hope – the possibility ofmore effective treatment. It alsounderscores the need for promptrecognition, diagnosis and treatmentof tickborne diseases. Three articlesin this issue of the Lyme Timesreview some of what has beenlearned so far about the mostsystematically studied of these co-infections – Babesia microti plusBorrelia burgdorferi. In this articlewe look at how Babesia co-infectionaffects Lyme disease. A secondarticle discusses the people andregions most at risk for this co-infection [page 39, this issue], Thethird glances at a promising newtreatment for it [page 44, this issue].A final article, slated for our nextissue, will explore some informationrelated to diagnosis. [Ed note:References for all articles are onpages 45-47]

Debilitating fatigue, prolongedspirochetemia and persistingsymptoms characterize Babesia/Lyme disease co-infections

How does Babesia co-infectionaffect Lyme disease? The persistentillness Dr. Burrascano mentions hasbeen decisively demonstrated in earlyBabesia microti/Borrelia burgdorferico-infections [2]. And the initialillness is not only longer lasting, butalso substantially more severe thanLyme disease alone .

By itself, babesiosis – the diseaseresulting from infections of red bloodcells by Babesia parasites – varies inseverity. Early babesial infections infact are usually silent, i.e. withoutclinical symptoms [2,3,4]. Whensymptoms do occur, they vary fromlow-grade and brief to a “fulminantmalaria-like disease” that is persis-tent and severe and occasionally endsin death [5]. Symptoms may firstoccur after long periods of silentinfection. They may recur even aftertreatment, particularly followingsuppression of the immune system bysplenectomy, AIDS, cancer, chemo-therapy, corticosteroid use, or simplyaging [3,5,6,7]. Lyme disease byitself likewise varies from silent tosevere, and patients often note theirearly symptoms disappear quicklyonly to recur later.

But if the tick that carries Lymedisease also carries babesiosis, theperson bitten by that tick is verylikely – as much as 95% of the time –to become sick immediately, oftenvery sick and for a very long periodof time, according to an importantstudy led by infectious diseasepediatrician Peter Krause, MD of theUniversity of Connecticut School ofMedicine [2]. Debilitating andprolonged fatigue, accompanied byapparently increased and prolongedspirochetemia, dominated the clinicalpicture seen in co-infected patients.

Block Island, the site of the study,

is a small Rhode Island communityof about 1200 residents. Beginningin 1990, Dr. Krause, working withDave Persing of the Mayo Clinic andcolleagues from the NationalInstitute of Allergy and InfectiousDiseases, tried to estimate how manyBlock Islanders had been exposed totickborne diseases. They mounted animpressive campaign to educateisland residents about Lyme diseaseand babesiosis, using local newspa-pers and cable TV channels andposting information at the island’sonly medical center. Their educa-tional effort was so successful that anamazing 1156 of the 1200 residentshad their blood tested for bothdiseases, providing an unusualopportunity to compare the effects ofeach kind of infection in a populationrelatively free of selection bias.

Over the first five summers of thestudy, when members of this alertedand well-informed citizenry pre-sented to the island’s medical centerwith clinical symptoms suggestive ofeither disease, more than 200 werediagnosed, by strict CDC criteria,with either Lyme disease, babesiosis,or both. Most of them – 206 people –were diagnosed with early Lymedisease; 23 of the 206 Lyme diseasepatients – 11% – also had babesiosis,i.e., were co-infected. A total of 33patients were diagnosed withbabesiosis; 23 of them –70% – alsohad Lyme disease. This is more thantwice as many as had babesiosiswithout Borrelia co-infection – only10 of 23, or 30.3.%.

Co-infected people were not onlymore likely to become sick, butbecame impressively sicker, with awider array of symptoms, andremained ill significantly longer –even after antibiotic treatment – thanpatients with either disease alone.They also had PCR-detectableborrelial DNA in their blood moreoften and for longer durations thanthose with Lyme disease alone. Inone case spirochetemia persisted fornearly nine months despite earlyantibiotic treatment.

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Debilitating fatigue,prolongedspirochetemia andpersisting symptomscharacterize Babesia/Lyme disease co-infections.

Co-infection without illness wasrare indeed: only one of 19 BlockIslanders with a four-fold rise inantibody titer to both infectionsremained free of symptoms – i.e. thesilent co-infection rate by thisstandard was only 5%. The silentinfection rate in those infected onlyby B. burgdorferi was three timeshigher – 16%. In other words, 28 of175 people infected with B.burgdorferi, using the same criterionof a four-fold rise in titer, remainedsymptom-free and therefore were notdiagnosed with Lyme disease. In thisstudy it appears that an impressive79% (30 of 38) of those infected onlyby Babesia microti had silentinfections without symptoms [2],although in a later study Dr. Krauseestimates silent infections as closer toone-third [5], in agreement with anearly study by Ruebush [4].

Persistent, debilitating fatigue:

The most dramatically increasedsymptom of early co-infection wasfatigue, leading Dr. Krause toconclude that “persistent anddebilitating fatigue characterized co-infection.” Even after very earlyantibiotic treatment, begun anaverage of five days after illnessonset, more than one-third of the co-infected patients (35%) had fatiguethat lasted for longer than sixmonths, compared to only 3% ofpatients with Lyme disease alone.Their fatigue was serious anddebilitating, bad enough to limitdaily activities by at least 25%. Manyadditional co-infected patientsexperienced this degree of fatigue forshorter durations – four-fifths (81%)of them, compared to 48% of patientswith only Lyme disease. Prior healthseems not to have been a factor: nopatient had experienced persistentfatigue prior to the onset of thetickborne illnesses.

Other Lyme symptoms were alsoincreased in the patients with bothinfections: co-infected patientscomplained of headaches more oftenthan those with only Lyme disease(77% compared to 40%), as well as

nausea (23% compared to 5%),sweats (46% compared to 10%),chills (42% compared to 22%),anorexia (31% compared to 13%),emotional lability (23% compared to7%), and conjunctivitis (12%compared to 2%). Enlarged spleenswere found in 8% of patients withboth diagnoses and in one of the 10patients diagnosed with Babesiamicroti alone, but no patient in thiscohort with only Lyme disease haddetectable splenomegaly. All thesedifferences were statistically signifi-cant.

Neck stiffness and musculoskel-

etal complaints like arthralgia andmyalgia, on the other hand, werereported about as often by patientswith Lyme disease alone as by co-infected patients. Progression to jointswelling was relatively rare (3 to 4%)in these quickly diagnosed patients,presumably due to their earlytreatment, and co-infection did notincrease its occurrence. Patients didnot display signs indicative ofneurologic or cardiac Lyme disease,again most likely because of earlyantibiotic treatment.

Increased spirochetemia:

Co-infection with Babesiamicroti also intensified and pro-longed the presence of spirochetes inthe blood of Lyme disease patients.PCR was able to detect blood-borneB. burgdorferi spirochetal DNAmore than four times as often inpatients with both diagnoses as inLyme disease-only patients (27%compared to 6%), and for a dramati-cally longer time: Although they had

received early antibiotic treatment,Borrelial DNA was detectable for anaverage of three months (91 days) inthe co-infected patients, but for only12 days in those with Lyme diseasealone. One co-infected patient stillhad PCR-detectable Borrelial DNAwhen tested nearly nine months (265days) after illness began, againdespite antibiotic treatment. Thefinal PCR test on this patient’s bloodwas done a month prior to the nexttick season, and it was thoughtunlikely this persisting spirochetemiaresulted from re-infection.

Dr. Krause believes detection ofspirochetal DNA in blood by PCRimplies the presence of livingspirochetes in the body’s circulation.At a minimum the more frequentdetection of blood-borne B.burgdorferi DNA in the Block Islandco-infected patients than in patientswith only Lyme disease stronglysuggests they had larger numbers ofspirochetes in their blood. Theirrelatively prolonged PCR positivity isstrong evidence for relative prolonga-tion of the spirochetemia thatdisseminates B. burgdorferi to tissuesremote from the site of tick bite. InLyme disease by itself spirochetestypically are rapidly cleared from –or become undetectable in – thebloodstream (by about 12 days in thisBlock Island study). This studyexamined only the first year ofBorrelial/Babesial co-infections inpatients given early antibiotictreatment, but its findings seemlikely to have important conse-quences for later and chronic Lymedisease in co-infected patients aswell. Larger numbers of spirochetescirculating in the bloodstream overlonger durations would allow thespirochetes to more intensely invadetissues in more parts of the body,thus causing not only the morevaried and longer lasting symptomsseen during the first year of disease,but probably also increasing spiro-chetal loads in “immunologicallyprivileged sites” like tendons, eye,brain and within cells, where theywould be relatively protected from

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“Human babesiosismay be morepersistent and lessbenign thanpreviously thought”

control by antibodies or eradicationby antibiotics, thus setting the stagefor chronic illness, especially inpatients not receiving early treat-ment.

Babesia seems to suppress theimmune system in mice, cattle anddogs [8]. Whether this happens inhumans has yet to be examined, butKrause et al suggest that Babesia-induced immunosuppression couldunderlie the increased symptoms andmore persistent spirochetemia seen inLyme disease when babesiosis ispresent [2].

Persistent Parasitemia:

The effect of Lyme disease onbabesial infections is less clear.While fatigue, sweats, anorexia andnausea were experienced somewhatmore often by Borrelia/Babesia co-infected patients than by thoseinfected only with Babesia, thedifferences were not significant. Alater Block Island study [5] found noevidence that antibiotically treatedLyme disease co-infection increasedthe persistence of blood-bornebabesial parasites in patients withbabesiosis [but see 9]. However, inone patient with three tickbornediseases – Lyme disease, babesiosisand human granulocytic ehrlichiosis– PCR was able to detect Babesiamicroti DNA in blood for 208 days(nearly seven months), more thantwice as long as the average for thosewith babesiosis alone [5].

Babesial infection by itself,however, “may persist for months oreven years.” Even when it is asymp-tomatic or silent, it “may recrudescespontaneously, or after splenectomyor immunosuppression” [5]. Priorbeliefs about the persistence ofBabesia microti were based onactually seeing babesial parasiteswithin red blood cells under themicroscope, but this is not a sensitivetest because parasites are sparse inpeople [10]. In the most recent studyof Block Island and Connecticutpatients with newly diagnosedbabesiosis, published just thissummer [5], parasites were seen

within red blood cells only briefly,for less than a week, even though100 fields of thin blood smears wereexamined microscopically. PCR,however, detected blood-bornebabesial DNA for much longer in thesame patients – an average of 82days, or nearly three months.Persistent PCR-detected parasitemiawas often accompanied by persistentsymptoms.

Again Krause et al. argue that thepresence of detectable DNA in theblood implies persistence of infec-tion. They note that in one initially

asymptomatic patient, PCR was ableto detect blood-borne babesial DNAinitially and again five months later.At 17 months (in April, when re-infection was thought unlikely) thesame patient had what was appar-ently his first episode of babesialillness, with fever, chills, sweats,anorexia, nausea and stupor. Onexamination of blood smears, 3% ofhis erythrocytes (red blood cells)were found to contain parasites. Hewas hospitalized, found to have anintracapsular renal tumor, wastreated with clindamycin and quinineand became symptom-free andapparently parasite-free one weeklater. When he returned to hospitalfor removal of the kidney six weeksafter that – 27 months after theinitial parasitemia – again 1% of hiserythrocytes showed parasites [5].

Such findings heighten theconcern – echoed by other research-ers –that “human babesiosis may bemore persistent and less benign thanpreviously thought” [5]. In bothnaturally and experimentally infected

animals, “chronic infection is therule rather than the exception” [10].Some animals remain parasitemic forlife and may develop worseningchronic disease before death [3].Dogs infected with Babesia gibsoni,for example, have developed liverlesions and chronicmembranoproliferative glomerulone-phritis even after anti-babesialtreatment with clindamycin andquinine [11,12]. And of coursemalaria, a similar infection of redblood cells often indistinguishablefrom Babesia on blood smears, iswell known for its chronicity.

Like most good research, theBlock Island studies raise as manyquestions as they answer about howthese two infections affect oneanother. A few important ones,because they’re likely to affect manypeople: What happens when oneinfection follows another rather thanboth occurring simultaneously?Many Lyme patients report multipletick bites. What happens if antibodyresponses to one or both infectionsdon’t meet strict CDC criteria? Doesthe Babesia-induced immunosuppres-sion suspected in other animals [8]affect humans as well, and in waysthat might, as Burrascano [1] andMagnarelli [13] have suggested,complicate diagnostic testing?Antibody titers to Borreliaburgdorferi were higher rather thanlower in the acutely ill Block IslandBorrelia/Babesia co-infected patients,according to Persing [14], whothought this probably due to theincreased spirochetemia. But animalstudies show Babesia microti reducesantibody response to some toxicantigens, especially “memory”antibody responses, and mayheighten susceptibility to otherinfections [3,15,16].

Already there are four species ofbabesia known to be pathogenic tohumans (Babesia microti, Babesiadivergens, WA1 and MO1) [3], andPersing reports there are alsoregional strains of Babesia microti,showing different sequences of outersurface proteins [16]. Will co-

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Who is at risk for Borrelia/Babesia co-infection?

infections of Lyme disease and theseother species of Babesia produce thesame severe illness that B.burgdorferi/Babesia microti did inthe Block Islanders? Will co-infections of Lyme disease and theother species even be common, giventhat MO1 and WA1 may have othertick vectors [3,18]? What additionalcomplications arise when otherIxodes tickborne agents such ashuman granulocytic ehrlichiosis,flaviviruses, or infections not yetidentified are involved? Are people atrisk for Ixodes tick bites also more atrisk for bites from other human-biting ticks that carry yet moreinfections?

And, most urgently, whathappens when co-infections areuntreated and perhaps persist foryears? Untreated acute Borreliaburgdorferi/Babesia microti co-infection has resulted in at least threedeaths [19,20]. In fact one of the fewreported Lyme disease fatalities wasin a patient co-infected with Babesia;in spite of his having reported nocardiac symptoms, he died ofspirochetal invasion of heart musclewith all layers of his heart inflamed,i.e., with severe myocarditis, en-docarditis and pericarditis [19]. TheBlock Island researchers state thatbabesial infection enhances Lymedisease myocarditis in mice, and areconcerned that this co-infection may“synergize spirochete-induced lesionsin human joints, hearts, and nerves”[2]. Burrascano observes that “severeheadaches, dizziness and encephal-opathy out of proportion to the otherBorrelial symptoms” is a commonsign of co-infection [1]. Is this co-infection, probably undetected, infact resulting in more severe,persistent cardiovascular and centralnervous system Lyme disease?

Bosler and Schulze foundBabesia microti co-infection of B.burgdorferi-infected wild white-footed mice to correlate both withhematuria and the presence ofspirochetes in their urines andbladders [21]. Might Babesia microtialso promote spirochetal infections

and damage within the humanurinary tract, as is seen in some dogswith Lyme disease [22,23]?

Clearly, late interactions betweenspirochetes and babesial parasites,each with tendencies to persist,subside and reappear, are likely to becomplex. Research into even this oneknown co-infection has just begun,and there are unknown other

tickborne co-infections to consider,now that we all – researchers,physicians and patients alike – arebeginning to look at what Burrascanocalls “the New Lyme” andMagnarelli calls “the broaderpicture” [13]. The tick, as WillyBurgdorfer says, is a Pandora’s box[24].

Borrelia/Babesia co-infections –at least those that are already known– cluster along the New Englandseaboard and around the Great Lakesregion in the upper Midwest [3].Coastal islands of New England areinfamous hot spots for babesiosis,and these islands –Nantucket Island,Martha’s Vineyard, Naushon Islandand Cape Cod in Massachusetts;Block Island and elsewhere in RhodeIsland; Shelter Island and LongIsland in New York [20] – haveattracted most of the babesiosis andBorrelia/Babesia co-infectionresearch attention.

However, babesiosis is not easilyrecognized clinically. Symptoms areusually either absent or low-grade.When more intense illness develops,it is easily mistaken for a number ofother illnesses, including flu, malariaand other tickborne diseases [12,18].Until recently it was thought to bevery rare and a disease only of theelderly or immunocompromised[5,12]. Unless physicians know tolook for both, a diagnosis of Lymedisease would mask it, and review ofepidemiologic studies suggests thatthis happens often [see below]. Arecurring theme in the history ofbabesiosis research in any givenregion is how often the first caseswere diagnosed “incidentally” oraccidentally [e.g.12,25].

Researchers warn that whereverboth pathogens are endemic, peopleare at risk for Borrelia/Babesia co-

infection [2,3,5,26] because in theNortheast and Midwest the twopathogens share the same reservoirhosts (small rodents, especially thewhite-footed mouse) and vector(Ixodes scapularis), both of whichare often co-infected [13,14,17,27].

Given all this, it seems likely thatpublished cases and the epidemio-logic studies mentioned below mayrepresent only – as we hear so oftenabout tickborne diseases – “the tip ofthe iceberg.” A case in point is NewJersey: A Medline search disclosedonly one article about humanbabesiosis in the New Jersey,published in 1990 [28], but babesio-sis is probably highly endemic there.Varda et al.’s recent PCR study ofinfections in 100 adult Ixodesscapularis ticks in New Jersey’sHunterdon County found 5% of theticks infected with Babesia microti.The five Babesia-infected ticks werewidely distributed in the county –one each was found at half of the 10sites sampled. Four of these fiveBabesia-infected ticks carriedanother tickborne disease as well:two were co-infected with B.burgdorferi, and two were co-infected with the agent for HGE [29].

Stony Brook researcher Ed Boslerfound, on highly endemic LongIsland, rates of Babesia microtiinfection in adult ticks that rangedfrom 7% to 20% [30], and Telford, ina study of Nantucket (where babesio-sis is so endemic it used to be called

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“Nantucket fever”), found a 9%infection rate in adult ticks. The 5%rate in Hunterdon ticks is lower, butnot all that much lower. Hunterdon ishyperendemic for B. burgdorferi: in1996 it had the third-highest caserate of Lyme disease of all countiesin the United States (524/100,000)[29], and the state of New Jerseyreported 2,190 cases to the CDC thesame year [31]. The risk of Borrelia/Babesia co-infection in tick-infestedareas of New Jersey thus seems likelyto be substantial in spite of its nearlycomplete omission from the medicalliterature.

Published studies also report Bor-relia/Babesia co-infections in Connecti-cut [32], Wisconsin and Minnesota[33,34]. One study found Babesiamicroti in North Carolina [35], andnew species of human Babesia havebeen discovered very recently – WA1on the West Coast in 1991 [3,12], andMO1 in Missouri in 1992 [36]. On theWest Coast, in California and Wash-ington, research into babesiosis is stillvery new, and there seem to be nostudies of Oregon. There are anecdotalreports of Babesia microti cases inCalifornia [12], and some Lyme pa-tients say they’ve been diagnosed withco-infections, but published case stud-ies and serosurveys so far have foundonly Babesia WA1 [3,12,37,38]. In-sights into Borrelia/Babesia co-infec-tion gained from the Northeastern ex-perience [see the first article in thisseries, page 36] may or may not applyon the West Coast since the two infec-tions may well turn out to be vectoredby different ticks [3,17,37]. To datethere has been only one Missouri case,and again the vector and host are notyet known [36].

Data from some of these studiesare described in more detail below.But first, in the interest of correctinga dangerous myth about babesiosis,some more information from BlockIsland:

Children and babesiosis:

Children do get babesiosis. Theyare at least as susceptible as adults tobabesial infections, whether silent or

clinical, and to the more severe andpersistent illness caused by co-infec-tion with Lyme disease and babesiosis,despite the latter’s reputation as beinga disease mainly of older adults andpeople without spleens. As late as 1992,when pediatrician Peter Krause ad-dressed the problem, there were onlyfive published case reports of severebabesiosis in children [26]. One wasinfected by blood transfusion, one wasa splenectomized teenager, and threewere infants – raising the specter of

least as often [26].

Krause believes babesiosis hasbeen underdiagnosed in children –even more so than in adults –because physicians are taught thatbabesiosis is a geriatric rather than apediatric disease and don’t evenconsider the diagnosis in children.(Severity of babesiosis does seem tobe greatly increased in people over55, so their rate of diagnosedbabesiosis is much higher.) He notesthat there are a variety of morecommon childhood illnesses thatpresent with the persistent fever andflu-like symptoms typical of babesio-sis, and that these symptoms,particularly persistent fever, areusually more aggressively evaluatedin adults than in children [26].

Hu et al, in a serosurvey of otherareas of Rhode Island [40], alsofound children to be frequentlyinfected with Babesia microti.Looking at sera obtained from threehospitals, they found 4.1% of bloodsamples tested (24/589) to beBabesia-positive by IgG IFA.Children had a comparatively highrate of seropositivity (5% to 6% forchildren to age 19), second only topeople 70 years of age or older(6.7%). Young adults had a com-paratively low rate (1.3% to 1.5% forpeople age 30 to 39). The agedifferences in Babesia seropositivity,like those in the Krause study, aresuggestive but failed to reachstatistical significance.

A third serosurvey, of a semi-rural community near Sonoma,California, also found a higherproportion of children to be IFAseropositive for Babesia – in this casethe West Coast Babesia WA1 – andin this study the difference betweenchildren and adults was statisticallysignificant [38]. The actual numbersper age group weren’t published, butof a total of 219 community residentstested, including 18 children, 39(17.8%) were seropositive for WA1at high titers that ranged from 1:320to 1:2560 (nearly 10 times the titersfound in East Coast studies, which

congenitally acquired infection but notproving it [39]. Although four of thesefive cases were considered moderate tosevere, and three required treatment byreplacement transfusion, the medicalcommunity has generally believed thatotherwise healthy children either donot become infected with Babesia orfail to develop symptoms from it [26].

Since 1992, three serosurveyshave reported data about Babesiainfections in children. During thefirst five months of the Block Islandtickborne disease serosurvey by Dr.Krause et al, in the fall of 1990,nearly three-fourths of the island’s800 permanent (i.e. winter) residentswere tested for antibodies to Babesiamicroti by an immunofluorescenceassay (IFA); 12% of children and 9%of adults were seropositive, andpeople who had experienced typicalsymptoms of babesiosis during theprior season were as likely to bechildren as adults. Dr. Krauseconcluded that children are infectedat least as often as adults withBabesia microti and that the infec-tion also leads to actual illness at

Physicians aretaught that babesiosisis a geriatric ratherthan a pediatricdisease and don’teven consider thediagnosis in children.

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usually range from 1:32 to 1:256).Half the children up to age 16 werepositive for at least one tickbornedisease, and the majority werepositive for WA1. No one in thiscommunity had been diagnosed withbabesiosis, and no one wasseroreactive to Babesia microti.

Human Borrelia/Babesia co-infections in the Northeast:

The following review samplessome of the published studies onbabesiosis, focusing first – to theextent it is possible to separate thesequestions – on how often people withbabesiosis have been found to have aLyme disease co-infection, and thenon how often people with Lymedisease have been found to haveBabesia co-infection. There are alsosome clues about how often bothinfections go unrecognized andundiagnosed, and even some findingssuggesting that babesiosis has beenspreading into new areas. Note thatthe studies aren’t exactly comparablesince they use different criteria –some look at antibodies in blood asevidence of infections (serologicstudies or serosurveys), while somerequire actual diagnoses of thediseases, usually by the rigid CDCcriteria that may well miss manycases of B. burgdorferi infection.

How often do people with babesio-sis have Lyme disease?

In the Northeast, the single mostimportant risk factor for babesialinfection is a diagnosis of Lymedisease [40]. Babesiosis certainlyoccurs in people without Lymedisease, but co-infections seem to bemore common. In the seminal BlockIsland co-infection study by Krauseet al [2], for example, 33 people werediagnosed with babesiosis; 23 ofthem, or 69%, also had a diagnosedco-infection with Lyme disease.Borrelia/Babesia co-infections werethus twice as frequent as babesiosiswithout co-infection (23 with bothdiseases compared to 10 with onlybabesiosis).

Babesiosis patients in otherendemic regions also frequently have

Lyme disease. In Connecticut, morethan half (5/8) of babesiosis patientswho were tested for Lyme diseasehad high Lyme ELISA titers of 1:640to 1:5,120. Babesia parasites wereisolated from 27 of 59 mice capturedin or near the yards of patients, and25 of the mice were co-infected withB. burgdorferi [41].

This co-infection is amplydocumented on Long Island: In1981, Benach and Habicht et alreported that 21% (4/9) of babesiosis

diagnosed with babesiosis there. Sixof 102 Shelter Island residentsseroconverted to Babesia microti (afourfold rise in antibody titer) overjust one summer in the late 1970s[45]. Between 1982 and 1991,Shelter Island and northeastern LongIsland (East Hampton andSouthampton) had official annualincidence rates of diagnosed babesio-sis averaging 154.5, 22.1 and 7.5 per100,000 respectively. Travel to theseareas was thought to account for evenmore cases reported during thatperiod, and Meldrun cautioned, “Aswith Lyme disease, babesiosis maypose a threat to vacationers whoreturn to areas where local physi-cians may be unfamiliar with thedisease” [20].

How often do people with Lymedisease have babesiosis?

Krause’s initial Block Island co-infection study diagnosed 206patients with Lyme disease; 23 ofthem, or 11%, had Babesia co-infection [2]. According to MayoClinic microbiologist Dave Persing,another investigator in that study, thepercentage of Block Island Lymepatients with babesial co-infectionranged from 9% to 20% over theyears from 1990 to 1994, with theaverage being about 15% [14].

The Rhode Island serosurvey byHu et al [40] examined bloodsamples from 505 people seekingmedical care, using antibodies asevidence for infections. Babesialantibodies were much more commonin patients who were also seroposi-tive for B. burgdorferi infections(9.7%) than in patients who were B.burgdorferi-seronegative (3.2%) orin those who weren’t even tested forB. burgdorferi (1.8%). There were 24people seropositive for Babesiamicroti in this study, but none ofthem, whether co-infected withBorrelia or not, had been diagnosedwith babesiosis.

In the Connecticut serosurvey byKrause et al [32], Babesia microtiseropositivity was 9.5% in peoplediagnosed with Lyme disease,

patients had erythema migrans [42].In 1985, Benach et al reported that56% (23/41) of Long Island babesio-sis patients had Lyme disease [43]. In1992, Sean Meldrun of the NewYork State Department of Health andcolleagues reported that 23% ofbabesiosis patients (31/136) from thesame area had concurrent Lymedisease [20].

Stony Brook researcher WilliamGolde, in a study begun just last year,is using PCR to study co-infectionsin Long Islanders. As of June he hadbeen able to test only four patientswith a primary diagnosis of babesio-sis, but three of them were co-infected: two had PCR-documentedco-infections with B. burgdorferi aswell as HGE, i.e. were triply infected,and another was co-infected with justHGE [44].

These percentages of Long Islandbabesiosis patients who have a B.burgdorferi co-infection – 21%,56%, 23%, 50% –are impressive, butto fully appreciate what an impactthis co-infection is having on peoplein the Long Island vicinity, it helpsto know how often people are being

Babesial antibodieswere much morecommon in patientswho were alsoseropositive for B.burgdorferi infections.

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compared to 1.0%, 2.5% and 2.6% incollege students, people with noknown exposure to ticks, and randomoutpatients respectively. Thesepercentages are strikingly similar tothose found in Hu’s Rhode Islandstudy as well as to Krause’s earlierstudy of Block Island [above].

Another important finding fromthis study suggests that Babesiamicroti may have come ratherrecently to Connecticut: there was noevidence of babesial infection incollege students who had resided inConnecticut from 1959 to 1985,while 2.9% of college students wereseropositive in the years after 1985.Krause also notes that most of thepeople seropositive for Babesia camefrom the same Connecticut regionmost endemic for Lyme disease –near Mystic, on the southeasternshore of the state, a resort areavisited by many summer vacationers(including college students) duringthe summer season when transmis-sion of both diseases is at its height.

Another Connecticut serosurvey,reported in 1995 by Lou Magnarelliof the Connecticut AgricultureStation [46], found 7.5% of 40patients with Lyme disease diagnosedby strict CDC criteria and withhistories including erythema migrans[EM] to be seropositive to Babesiamicroti. Again this figure – 7.5% – isvery close to the figures found byKrause and Hu.

On the other hand, in this samestudy no co-infections of any sortwere found in 15 Lyme diseasepatients diagnosed with arthritis butwithout history of EM, or in 25 Lymedisease patients from Yale UniversityLyme Disease Clinic. The differencesin co-infection between patients withand without EM are curious, butlikely to be accidental or artifactual[47]. Babesia microti antibodies werealso absent from 112 healthy peoplefrom Connecticut, 25 healthy peoplefrom Minnesota, and 30 MinnesotaLyme disease patients with EM inthis study. (Two of the MinnesotaLyme disease patients had antibodies

to HME, however. Evidence for othertickborne diseases was also found inthe Connecticut Lyme patients withbabesial co-infection; their serarevealed that 10% were seropositivefor HME and 7.5% seropositive forHGE.).

Minnesota (and Wisconsin) Lymedisease patients were found to havebabesiosis co-infections the followingyear, however. A study by Mitchell etal of 96 Wisconsin and MinnesotaLyme disease patients found four ofthem, or 4.1%, to also have Babesiamicroti infections. Again other co-

parasites. He has developed a newPCR that is more sensitive for earlybabesial parasitemia and is nowlooking at sera from patients whopresented with erythema migrans thissummer. It is noteworthy that 14 ofthe 18 Lyme disease patients hadfairly strong documentation of co-infection with HGE. A number ofcommon threads connect thesestudies: HGE is sometimes involvedin double and even triple co-infec-tions with Babesia microti. Diag-nosed babesiosis patients very often,in fact more often than not, haveLyme disease co-infection even byrestrictive CDC diagnostic criteria.In areas where both pathogens arefound, diagnosed Lyme diseasepatients are co-infected with Babesiamicroti from 4.1% to 20% of thetime, with one outlying and perhapssuspect figure of 44%.

Babesia microti may haveexpanded into at least two newregions –Wisconsin and Connecticut– as recently as 1983 to 1985[27,32]. An apparently new focuswas also reported in 1986 on a NorthCarolina Indian reservation, wheresix of 185 serum samples fromchildren were found to be positive attiters of 1:256 or higher when theBabesia microti IFA test was beingevaluated for cross-reactivity [35].Babesiosis is often particularlyprevalent in resort areas, and patientswith diagnosed babesiosis hadtraveled to these resort areas, someimmediately prior to their illness[20,32]. Finally, seropositivity for B.microti is much more common thanactual diagnoses of babesiosis, evenwhen there is co-infection with B.burgdorferi [26,37,38,40].

The human co-infection data areconsistent with co-infection ratesfound in field studies of host animalsand ticks from the same regions [30]and with what is known about theendemicity of the two pathogens. B.burgdorferi still dominates the worldof tickborne infections. Even when itis looked for, Babesia microti is lessoften found; it is so dependent on the

infections were found: five Lymedisease patients (5.2%) were co-infected with HGE (human granulo-cytic ehrlichiosis) infections. Whenthese researchers examined the seraof 19 patients who had been diag-nosed with HGE, one was seroposi-tive for B. burgdorferi, one forBabesia microti and one for bothpathogens [33].

Golde’s new study [44] is alsousing PCR to look for other tickborneinfections in sera from Long Islandpatients with a primary diagnosis ofLyme disease. Although his firstPCR failed to detect babesial para-sitemia in 18 patients who presentedwith EM, eight of the 18 (44%) wereseropositive for Babesia microtiusing a new serology kit fromImmunetics for testing threetickborne diseases. Golde is unsurewhether the serologic results werefalse positives, or whether, as hesuspects, the PCR he was using wasinsufficiently sensitive and/or at leastsome of these patients had beeninfected but had fought off the

The human co-infection data areconsistent with co-infection rates foundin field studies of hostanimals and ticks fromthe same regions.

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same ecology that supports B.burgdorferi that, when found, it ismore often than not accompanied byits more prevalent companion –whether one looks at ticks, animalsor people.

More endemic areas to come?

Although nearly all systematicBorrelia/Babesia research has beendone in just a few sites in the highlyendemic, tickborne disease-awareNortheastern and Midwesternsections of the country, it is impor-tant to remember that both Lymedisease and babesiosis exist in otherparts of the United States, as well asin the rest of the world.

Babesiosis almost surely exists inregions where it has never beendiagnosed. Recognition of babesiosistakes a high degree of suspicion onthe part of patient and physician like.For example, in spite of babesiosishaving become a reportable diseasein Rhode Island in 1989, and in spiteof its now very clear importancethere – thanks to the impressive bodyof work by Krause and colleagues –no case of babesiosis had beenreported in that state prior to July,1991 [26]. Patients in areas wherebabesiosis is not already known to beendemic usually have to be very sickor even die, with high numbers oftheir erythrocytes invaded byparasites, before their cases arediagnosed and published [25,36]. AsPat Conrad of the University ofCalifornia at Davis puts it, “Fatalitiesare when they really get noticed”[12].

Conrad also tells a story [12]about one of the first known Califor-nia cases of WA1 that emphasizesjust how accidental discovery ofregional endemicity can be: a manwas diagnosed only after a week ofhospitalization at UCLA withworsening symptoms. The diagnosiswas made then only because aphysician visiting from the Northeastrecognized the syndrome – flusymptoms plus chills, headache anddark urine in a splenectomized youngman – and suggested looking at a

smear for Babesia. It showed manyparasites. When they looked backover 32 blood samples that hadalready been taken from this patient,parasites were found in all of them;on one smear there were parasites in28% of his red blood cells. He wasnegative on an IFA for Babesiamicroti but had a titer of 1:5120 forBabesia WA1 [37].

Will WA1 be another Borrelia/Babesial co-infection?

Are West Coast Lyme diseasepatients at risk for WA1 Babesia co-infections? Relevant research into therelationship between these twoinfections has barely begun and islikely to be complicated. Thestrongest evidence so far for Borrelia/WA1 co-infection comes fromDenmark, where 14 of 132 “definiteLyme neuroborreliosis patients” werefound to be reactive to WA1 at titersof 1:512 and above [48]. Still, asnoted above, it is not even known yetwhether the two infections share thesame vector tick.

The serologic study in theSonoma, California area that foundso many WA1 seropositive people(17.8% of those tested) was under-taken in part to address this question.Many members of the small commu-nity studied had been diagnosed withLyme disease, many with EM rashes,and had been treated with antibiotics;a fourth of sick dogs in the neighbor-hood had tested positive for B.burgdorferi. But at the time of thestudy, about three years later, none ofthe WA1-positive residents was alsoB. burgdorferi seropositive by thestrict two-tier CDC criteria usingeither B31 or CA92-0953 as antigen[38]. There are a number of reasonsto doubt the appropriateness of the B.burgdorferi serology used in thisstudy [49], but certainly no evidenceof Borrelia/Babesia co-infection wasfound. In a separate study of 11WA1-seropositive Californians(soldiers stationed at Fort Ord andresidents of a community in Ukiahhyperendemic for Lyme disease),only one was also seropositive for B.

burgdorferi [37].

Interestingly, however, 124 blooddonors from the Sacramento bloodbank were used as a comparisoncontrol for the WA1 serology in theSonoma study. To the surprise ofalmost everyone – since it was thenthought that Ixodes pacificus ticks(one of the suspects for the tickvector) were relatively rare in thisinland area – 20% were seropositiveto WA1, with high titers rangingfrom 1:320 to 1:1280. However, allbut one of the WA1 seropositivedonors lived in foothills of the Sierramountains (as determined by countyof residence and zip codes), in Butte,El Dorado, Nevada and Placercounties. Last year Butte became thecounty with the highest number ofCDC-confirmed Lyme disease casesin California. Many patients thereare very ill, and several hundred ofthem and some 150 of their healthcare providers attended the October1998 Lyme Disease Resource CenterTickborne Disease Conference inChico [50].

Jerant and Arline [51] suggestSouthern California as anotherpossibility for an endemic WA1focus. Their patient – the first knownCalifornia case of WA1, had a titerof 1:64,000 to Babesia gibsoni, apathogen found, at that time, only inAsian and California dogs. A fewyears earlier Conrad et al hadreported on 11 dogs with Babesiagibsoni infections apparentlyacquired in Los Angeles, Kern andSan Bernardino counties [52]. Sincethen her students have foundwoodrats in the Sonoma area to beseropositive for WA1, as well as6.3% and 55% of two mouse speciesin the Malibu Canyon area of LosAngeles County [12], where anumber of patients have beendiagnosed with Lyme disease inrecent years.

It will be interesting to see iffuture studies discover any of theChico and Malibu patients to have B.burgdorferi/Babesia WA1 co-infections.

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Mepron — new drug bringshope to Lyme disease patientsco-infected with Babesia

Earlier this year one of theInternet Lyme disease discussiongroups was abuzz with talk ofMepron. Longtime chronic Lymedisease patients said that after beingdiagnosed with babesial co-infectionand taking this “new drug” they feltbetter than they had in years. Reportswere so glowing and enthusiastic thatsomeone asked if it was okay to takeit even if you didn’t have babesiosis[53]. The Lyme Times also received aletter describing its use in treating ayoung boy [see p 4, this issue].

There are other medications fortreating babesiosis, but most seem to“reduce parasitemia ... but noteradicate the infection” [54]. Therecommended treatment since 1983,based on its superior effectiveness,has been clindamycin plus quinine.However, some treatment failures arereported, relapses occur, and signifi-cant numbers of patients find quinineimpossible to tolerate. When Krauseand colleagues, for example, treated22 patients with recent-onsetbabesiosis with this regimen [5], itsignificantly reduced persistence ofparasites in the blood as detected byPCR, but PCR-detectable parasitemiapersisted for longer than a month in36% of the treated patients. Onepatient who wasn’t treated until laterin the course of infection (because atfirst he was symptom-free), displayedparasites on his blood smears thatfirst disappeared after treatment, thenreappeared six weeks later.

Reactions to treatment in thisstudy also prompted Krause et al. toobserve that “the quinine-containingregimen generally used to treathuman babesiosis appeared toproduce illness in nearly half thepatients” (actually 41%). Drugreactions included gastrointestinalsymptoms like anorexia, vomiting,

diarrhea and stomach pain; auditoryproblems like hearing loss andtinnitus; and acute hypotensionduring IV infusion. Six patients hadtoxic reactions so severe the drugswere either discontinued or thedosage reduced [5].

Case-report reviews and animalstudies reveal that a handful ofpeople with severe parasitemia

increased severity and persistence ofLyme disease in this co-infection[57], it may be dangerous not to treatit. Increased numbers of Borreliaspirochetes circulating in the bloodfor prolonged periods [58] maybecome, over time, something muchmore than a mild flu-like illness.

Mepron (atovaquone) is newenough that a Medline search revealsno published clinical trials of its useas a treatment for human babesiosis.However it has been used success-fully for several years as an antima-larial preventive and treatment andas a treatment for opportunisticparasitic infections like toxoplasmo-sis and Pneumocystis carinii pneu-monia in HIV patients, for which ithas FDA approval [59]. Clinicalstudies have been published describ-ing its success in treating thoseinfections, including trials specifi-cally assessing safety and efficacy inchildren [e.g. 60,61], and theseresearchers comment onatovaquone’s “remarkable safetyrecord.”

There are also several publishedstudies of its efficacy in treatingbabesiosis in animals, and againatovaquone (especially when com-bined with azithromycin) was foundto be more effective than othertreatment regimens and apparentlysafe. Promising preliminary datafrom a study that used Mepron andazithromycin to treat chronic Lymedisease patients was presented as aposter exhibit at this year’s LymeDisease Foundation conference, andthis combination is also recom-mended by Dr. Burrascano in hisnew Treatment Guidelines [see p 24,this issue.]

A few specifics from the babesio-sis studies: Pediatric infectiousdisease researchers Walter Hughesand Helieh Oz, in a study publishedin 1995 [54], compared the effects ofatovaquone, clindamycin plusquinine, and no treatment at all on30 hamsters experimentally infectedwith Babesia microti. All 30 ham-sters received vancomycin to prevent

[25,55] have died even afterclindamycin/quinine treatment fortheir babesiosis. Such severe drugreactions and treatment failures,combined with reports that babesiosisis commonly benign and patientsrecover without treatment [4], havecaused physicians to be very cautiousabout treating babesiosis unless thepatient is very ill. It is almost as ifthis treatment is worse than themilder forms of this disease (al-though no one actually says that).

But is it safe not to treat evenapparently mild babesiosis? Asevidence accumulates that babesiosisis likely to be more persistent thanpreviously thought, Krause et al. aswell as other researchers are callingfor better treatments [3,5].

Given the evidence that, at leastin some regions, human babesiosisoccurs more often as a co-infectionwith Lyme disease than as a simplesingle infection [56], and given the

...Physicians caringfor Lyme diseasepatients... shouldconsider theadditional diagnosisof babesiosis.

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colitis. All of the 10 untreatedhamsters had died by day 12 post-infection. Two of 10 hamsters treatedwith clindamycin plus quinine alsodied by day 12, and another two diedafter receiving a month of corticos-teroids to suppress their immunesystems. Although six hamsterstreated with clindamycin/quinineremained alive on day 54 aftertreatment, blood smears showed anaverage of 19% of their red bloodcells remained infected.

All but one of the 10 hamsterstreated with atovaquone survivedwith nearly undetectable parasitemia(no parasites at all were detected inany of them on day 54) despite 42days of immunosuppression withcorticosteroids. The only death in theatovaquone-treated group was due toanesthesia used to collect a bloodsample [54].

In 1996, Wittmer and colleaguesfrom the Departments of Parasitologyand Pathology at Albert EinsteinCollege of Medicine in the Bronxreported another study of hamstersinfected with Babesia microti [62].Their study compared atovaquonealone to atovaquone plusazithromycin. While both treatmentswere initially effective, hamsterstreated with atovaquone aloneoccasionally had later recurrence ofparasites. When babesial organismstaken from the hamsters withrecurrent infections were injectedinto uninfected hamsters, theinfections produced in the recipienthamsters were no longer responsiveto atovaquone, suggesting thedevelopment of atovaquone-resistantBabesia. Resistant organisms did notemerge in hamsters treated with theatovaquone plus azithromycinregimen. The investigators suggestthat this combined treatment shouldbe considered for babesiosis patientswho “have either failed standardtherapy or have become intolerant tosuch therapy.”

Krause et al. also advise, basedon their studies of persistent para-sitemia [5], babesiosis in children

[26], and Lyme disease/babesiosis co-infections [2], that physicians caringfor Lyme disease patients, especiallypatients “experiencing episodes of‘atypical Lyme disease’ or whoseresponse to antibiotic treatment isdelayed or absent,” should considerthe additional diagnosis of babesiosis[2]. They stop short of actuallyrecommending treatment withatovaquone and azithromycin, butnote that “recent observations ...suggest this therapy “may curehuman babesiosis” [5].

Internist Richard Horowitz, likeDr. Burrascano, clearly has been“considering this additional diagno-sis.” Dr. Horowitz described someinteresting preliminary observationsfrom his Hyde Park, NY practice in aposter presented at the Lyme DiseaseFoundation Conference this year[63]. He found 120 of his 800-pluschronic Lyme patients to havepositive antibody titers to Babesiamicroti as well as inadequateresponses to antibiotics for Lymedisease – they had experienced eitherlittle improvement or repeatedrelapses. He tried treating theBabesial infection in these patientswith two different medicationregimens, using pre- and posttreat-ment symptom questionnaires plus ahealth self-evaluation scale toevaluate treatment responses.

More than half the patientstreated with the currently recom-mended clindamycin plus quinineregimen stopped taking theirmedications because of severe sideeffects. His patients tolerated Mepronplus Zithromax (atovaquone plusazithromycin) better thanclindamycin plus quinine, althoughsome did stop treatment afterdeveloping severe rashes. Other sideeffects included poor taste, nausea,vomiting, diarrhea, fatigue, anddizziness. Herxheimer-like symptomflares were also noted (Burrascanoalso observes this in his patients[1].). None had serious changes onCBC and liver function panels. Ofthe 45 patients who completed 21days of Mepron plus Zithromax, 87%

experienced perceived improvementthat averaged about 40%.

Vomiting also seems to be aprominent side effect of atovaquoneplus proguanil treatment of childrenwith malaria, as observed by Lell etal. [60], who report no other obviousside effects. According to Korraa andSaadeh [59], rash, headache,diarrhea and gastrointestinal distur-bances are also common side effectswhen atovaquone is used to treatPneumocystis in AIDS patients. Theyalso state that atovaquone is excretedthrough the gastrointestinal tract andis therefore contraindicated inpatients with persistent diarrhea, as itmight not be absorbed well enough toachieve high serum concentrations.The United States PharmacopoeialConvention, Inc. [64], adds coughand trouble sleeping to the side-effectlist for AIDS patients taking Mepron,and advises them to report fevers andrashes to their doctors.

Dr. Horowitz’s patients withbabesiosis also had chronic, treat-ment-resistant Lyme disease. Theirsignificant clinical improvement onMepron plus Zithromax offers somehope that this treatment may beeffective even for chronic babesiosisand chronic co-infection (as reportedby the Internet patients), a possibilitythat has yet to be explored bypublished studies. Dr. Horowitzbelieves, along with Dr. Burrascano,that it also implies that chronicbabesial infection plays an importantrole in the ongoing symptomatologyof chronic Lyme disease. We lookforward to more information address-ing these important issues.

References:

1. Burrascano, “The new Lyme disease;diagnostic hints and treatment guidelinesfor tick-borne illnesses, 12th edition,”(October 1998). [See page 21 in this issueof Lyme Times].

2. Krause et al, “Concurrent Lyme diseaseand babesiosis. Evidence for increasedseverity and duration of illness,” JAMA275(21):1657-1660 (1996).

3. Persing and Conrad, “Babesiosis: newinsights from phylogenetic analysis,”

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July-October 1998Page 46

Infectious Agents and Disease 4:182-195(1995).

4. Ruebush et al, “Human babesiosis onNantucket Island: evidence for self-limitedand subclinical infections,” N Engl J Med297:825-827 (1977).

5. Krause et al., “Persistent parasitemiaafter acute babesiosis,” N Engl J Med339(3):160-165 (July 16, 1998).

6. Ruebush et al., “Experimental Babesiamicroti infections in Macaca mulatta:recurrent parasitemia before and aftersplenectomy,” Am J Trop Med Hyg30(2)304-307 (1981).

7. Falgas and Klempner, “Babesiosis inpatients with AIDS: a chronic infectionpresenting as fever of unknown origin,”Clin Infect Dis 22:809-812 (1996).

8. Purvis, “Immunodepression in Babesiamicroti infections,” Parasitology 75:197-205 (1977).

9. Use of restrictive CDC criteria for Lymedisease diagnosis may have left someundiagnosed Lyme disease patients in the“babesiosis only” group, possibly con-founding this comparison.

10. Krause et al., “Comparison of PCRwith blood smear and inoculation of smallanimals for diagnosis of Babesia microtiparasitemia,” J Clin Microbiol34(11):2791-2794 (1996).

11. Wozniak et al. (& Conrad), “Clinical,anatomic and immunopathologic character-ization of Babesia gibsoni infection in thedomestic dog (Canis familiaris),” J Parasitol83(4):692-699 (1997).

12. Conrad, “Babesiosis in California,”presentation at Lyme Disease ResourceCenter Conference on Tickborne Diseases,Malibu, CA (1997).

13. Magnarelli, “Emerging tickbornediseases,” presentation at 9th Annual LymeDisease Foundation International ScientificConference on Lyme Borreliosis and OtherTickborne Disorders, Boston, MA (1996).

14. Persing, “The cold zone, a convergenceof tick-transmitted diseases in areasendemic for Lyme disease,” presentation at9th Annual Lyme Disease FoundationInternational Scientific Conference onLyme Borreliosis and Other TickborneDisorders, Boston, MA (1996)

15. Gray and Phillips, “Suppression ofprimary and secondary antibody responsesand inhibition of antigen priming duringBabesia microti infections in mice,”Parasite Immunol 5(2):123-134 (1983).

16. Adachi et al., “Immunosuppression indogs naturally infected with Babesiagibsoni,” J Vet Med Sci 55(3):503-505

(1993)

17. Persing, “Naturally occurring co-infections in reservoir mice,” presentationat 10th Annual Lyme Disease FoundationInternational Scientific Conference onLyme Borreliosis and Other TickborneDisorders, Bethesda, MD (1997).

18. Conrad, “Babesiosis in California,”presentation at Northern California VectorControl Districts Symposium on EmergingTickborne Diseases, Rohnert Park, CA(1996).

19. Marcus et al. (with Steere and Duray),“Fatal pancarditis in a patient withcoexistent Lyme disease and babesiosis:demonstration of spirochetes in themyocardium,” Ann Intern Med103(3):374-376 (1985).

20. Meldrun, “Human babesiosis in NewYork State: an epidemiological descriptionof 136 cases,” Clin Infect Dis 15:1019-1023 (1992).

21. Bosler and Schulze, “The prevalenceand significance of Borrelia burgdorferi inthe urine of feral reservoir hosts,” ZentralblBaketeriol Mikrobiol Hyg [A] 263(1-2):40-44 (1986).

22. Damback et al., “Morphologic,immunohistochemical and ultrastructuralcharacterization of a distinctive renal lesionin dogs putatively associated with Borreliaburgdorferi infection: 49 cases (1987-1992). Vet Pathol 34 (2):85-96 (1997).

23. Evans et al., “Canine Lyme borreliosisI. Gross clinical observations of laboratorybeagles following exposure to ticks infectedwith Borrelia burgdorferi,” J Spirochetaland Tick-Borne Dis 2(1):28-32 (1995).

24. Burgdorfer, “The Tick – A Pandora’sBox,” Keynote Address, 10th Annual LymeDisease Foundation International ScientificConference on Lyme Borreliosis and OtherTickborne Disorders, Bethesda, MD(1997).

25. Herwaldt et al., “Babesiosis inWisconsin: a potentially fatal disease,” AmJ Trop Med Hyg 53(2):146-151 (1995).

26. Krause et al., “Babesiosis: anunderdiagnosed disease of children,”Pediatrics 89(6):1045-1048 (1992).

27. Steketee et al., “Babesiosis in Wiscon-sin, a new focus of disease transmission,”JAMA 253(18):2675-2678 (1985).

28. Moss, “Long odyssey of babesiosis,” NJ Med 87(4):291-294 (1990).

29. Varde et al., “Prevalence of tick-bornepathogens in Ixodes scapularis in a ruralNew Jersey county,” Emerg Infect Dis4(1). URL:http://www.cdc.gov/ncidod/EID/vol4no1/varde.htm (1998).

30. Edward Bosler, “Co-infection ofMammals and Ticks with Emerging Tick-borne Pathogens,” presentation at 11thAnnual Lyme Disease FoundationInternational Scientific Conference onLyme Borreliosis and Other TickborneDisorders, New York, NY (1998).

31. MMWR 46(23):533, Table 1 (1997).

32. Krause et al., “Geographical andtemporal distribution of babesial infectionin Connecticut,” J Clin Microbiol 29(1):1-4(1991).

33. Mitchell et al., “Immunoserologicevidence of coinfection with Borreliaburgdorferi, Babesia microti, and humangranulocytic Ehrlichia species in residentsof Wisconsin and Minnesota,” J ClinMicrobiol 34(3):724-727 (1996).

34. Sweeny et al., “Coinfection withBabesia microti and Borrelia burgdorferiin a western Wisconsin resident,” MayoClin Proc 73(4):338-341 (1998).

35. Chisholm, “Indirect immunofluores-cence test for human Babesia microtiinfection: antigenic specificity,” Am J TropMed Hyg 35(5):921-925 (1986).

36. Herwaldt et al., “A fatal case ofbabesiosis in Missouri: Identification ofanother piroplasm that infects humans,”Ann Intern Med 124:643-650 (1996).

37. Persing et al., “Infection with a babesia-like organism in Northern California,” NEngl J Med 332(5):298-303 (1995).

38. Fritz, CL et al., “Seroepidemiology ofemerging tickborne diseases in a NorthernCalifornia community,” J Infect Dis175:1432-1439 (1997).

39. Esernio-Jenssen et al., “Transplacental/perinatal babesiosis,” J Pediatr 110:570-572 (1987).

40. Hu et al., “Human infection with tick-transmitted Babesia microti in RhodeIsland: Serologic evidence and risk factorassessment,” J Spirochetal and Tick-BorneDis 3 (3/4):135-139 (1996).

41. Anderson et al., “Babesia microti,human babesiosis and Borrelia burgdorferiin Connecticut,” J Clin Microbiol29(12):2779-2783 (1991).

42. Benach and Habicht, “Clinicalcharacteristics of human babesiosis,” JInfect Dis 144:481 (1981).

43. Benach et al., “Serological evidence forsimultaneous occurrences of Lyme diseaseand babesiosis,” J Infect Dis 152:473-477(1985).

44. William Golde, “Co-infections in Lymedisease patients,” presentation at 11thAnnual Lyme Disease FoundationInternational Scientific Conference on

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Lyme Borreliosis and Other TickborneDisorders, New York, NY (1998) andpersonal communication.

45. Filstein et al., “Serosurvey for humanbabesiosis in New York,” J Infect Dis141(4):518-521 (1980).

46. Magnarelli et al., “Coexistence ofantibodies to tick-borne pathogens ofbabesiosis, ehrlichiosis and Lymeborreliosis in human sera,” J ClinMicrobiol 33(11):3054-3057 (1995).

47. It seems unlikely that Babesial co-infection increased the rate of EM in theseLyme disease patients: the co-infectedpatients on Block Island had fewer EMrashes than those diagnosed with Lymedisease alone [2]. The numbers here are sosmall (only three people with Babesiamicroti seropositivity) that the differencebetween EM and not-EM may well havebeen an accident of sampling. Alternatively,blood samples were probably collectedsooner after infection from patients withEM than for those without (whose first serawould have been collected weeks tomonths later when arthritis developed). Bythat time, any Babesia microti antibodies,which seem to fall off rapidly, might havedecreased to below this study’s cut-off titer(1:64).

48. Lebech et al., “Serologic evidence ofhuman granulocytic ehrlichiosis andpiroplasm WA1 in European patients withLyme neuroborreliosis,” poster presenta-tion, Abstract #E832, at VII InternationalCongress on Lyme Borreliosis, SanFrancisco, California (1996)

49. See Lyme Times No 19, November/December 1997 for a complete discussion.

50. See report of the Chico conference onthis page.

51. Jerant & Arline, “Babesiosis inCalifornia,” West J Med 158:622-625(1993).

52. Conrad et al, “Hemolytic anemiacaused by Babesia gibsoni in dogs,” J AmVet Med Assoc 199(5):601-605 (1991).

53. DejaNews; see threads “Mepron,”“Mepro” and “babesiosis.” Search can belimited to the “sci.med.diseases.lyme”newsgroup (where babesiosis and Mepronwere discussed); if an unlimited search isdone, one can read what AIDS patients sayabout Mepron.

54. Hughes & Oz, “Successful preventionand treatment of babesiosis withatovaquone,” J Infect Dis 172(4):1042-1046 (1995).

55. Byrd et al, “Respiratory manifestationsof tick-borne diseases in the southeastern

United States,” South Med J 90(1):1-4(1997).

56. See “How often do babesiosis patientshave Lyme disease,” page 41, this issue.

57. See “Debilitating fatigue...”, page 36,this issue.

58. See “Increased spirochetemia,” page37, this issue.

59. Korraa & Saadeh, “Options in themanagement of pneumonia cased byPneumocystis carinii in patients withacquired immune deficiency syndrome andintolerance to trimethoprim/sulfamethoxazole,” South Med J89(3):272-277.

60. Lell et al., “Randomized placebo-controlled study of atovaquone plusproguanil for malaria prophylaxis inchildren,” Lancet 351:709-12 (1998).

61. Hughes et al., “Phase I safety andpharmacokinetics study of micronized

atovaquone in human immunodeficiencyvirus-infected infants and children, areview. Pediatrics AIDS Clinical TrialsGroup,” Antimicrob Agents Chemother42(6):1309-1314 (1998).

62. Wittmer et al., “Atovaquone in thetreatment of Babesia microti infections inhamsters,” Am J Trop Med Hyg 55(2):219-222 (1996).

63. Horowitz, “Atovaquone andazithromycin therapy: a new treatmentprotocol for babesiosis in co-infected Lymepatients,” Poster Presentation, 11th AnnualLyme Disease Foundation InternationalScientific Conference on Lyme Disease andOther Spirochetal and Tickborne Disorders,New York, NY (1998).

64. “Atovaquone,” HealthAnswers, OrbisBroadcast Group, Interactive Media; http//www.healthanswers.com/database/usp_di/regular/AN-0919101.html.

Conference

The recent Lyme Disease Re-source Center tick-borne diseaseconference in the small college townof Chico, California, (pop. 53,000)attracted approximately 150 medicalprofessionals for a 3-hour program.

For several years there has beenan active fibromyalgia support groupin the Chico area, attracting up to400 patients from surrounding townsin the Sierra Nevada foothills.Recently many of these fibromyalgiapatients discovered that they testedpositive on both direct and indirecttests to Borrelia burgdorferi, theorganism that causes Lyme disease.They are currently being treated andmany have recovered.

Then, a number of children havebeen seriously ill with what ispresumed to be Lyme disease.Antibiotic treatments had limitedsuccess, so when William Fife ofTexas A & M announced hisexperimental study of the use ofhyperbaric oxygen (HBO) in thetreatment of Lyme disease, severalChico parents enrolled their childrenand made the trip to Texas. One boywho before HBO had been wheel-

chair bound and unable to attendschool because of severe neurologicproblems, is now riding his skate-board, roping steer, and carrying afull load as a sophomore at the localhigh school. Initially seronegative,after two years of treatment heseroconverted.

Then, four months ago, a youngman died after suffering from severeLyme disease for several years. Anavid deer hunter, he also wasseronegative and it took four yearsfor doctors to diagnose him, althoughhe had had tick bites and bull's-eyerashes. During his final illness hewas hospitalized and his spinal fluidtested. It was positive for Lyme. Atautopsy, his brain, heart and liverwere positive for spirochetes by PCR.

People in the small communitywere touched by this tragedy.Members of an enthusiastic Lymedisease patient support group lobbiedfor a conference and laid the ground-work for success by months ofpromotional activities. They turnedout in droves for the public forum.

continued on back page

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Calendar VIII InternationalConference onLyme Borreliosisand otherEmerging Tick-Borne DiseasesJune 20-24, 1999München Park HiltonMunich, Germany

Deadline for submission ofabstracts is February 1, 1999. Allcorrespondence and inquiries shouldbe addressed to the AdministrativeSecretariat: Lyme ’99, c/o AKMCongress Service, Clarastrasse 57,PO Box 6, CH-4005 Basel, Switzer-land, Tel ++41 61 691 51 11, Fax++41 61 691 81 89, Emailakm@aluewin.ch.

Scientific Secretariat are PD DrBettina Wilske and Dr VolkerFingerle of Max von PettenkoferInstitut. Email:Bettina.Wilske@mvp-bak.med.uni-muenchen.de.

In the opening presentation, ScottMonson, BA, an entomologist withthe Butte County Mosquito andVector Control, captivated theaudience with beautiful slides. Hispicture of hundreds of Ixodes tickscollected in one hour from the localarea impressed them that the vectortick was present in sufficient num-bers to pose a real threat; indeed,Butte County leads Californiacounties in numbers of cases of Lymedisease, accounting for 34% of thetotal reported. Humans frequent thefoothill habitats where ticks areabundant.

In field studies Monson and hiscolleagues mark ¼-acre plots withsurvey stakes and flag with largepieces of rough flannel attached tosticks. By marking ticks withnontoxic marker, they are able todetermine with greater accuracy howmany ticks infest a given area; not allticks are questing at one time (somemay be on the ground). They foundup to 5000 adults per acre; nymphswere more numerous. The infectedticks were clustered, presumably neara reservoir host, rather than beingevenly dispersed throughout the area.

Monson reported that theyexperimented with chemical controlby applying Sevin and Durisban.They achieved season-long reductionin the numbers of ticks from a singleapplication, and a 46% reduction inthe following year.

UC Berkeley entomologist RobertLane, PhD reviewed some Lymedisease history. In 1981, WillyBurgdorfer, described the Lymedisease spirochete in Ixodesscapularis ticks from Shelter Island,NY. His paper, “Lyme Disease: aTick-Borne Spirochetosis?” inspireda flurry of research. In 1982,Burgdorfer invited Lane to work on aLyme disease tick survey in theUnited States. The west coast vectorof Lyme disease, Ixodes pacificus,was found in 56 of 58 Californiacounties, and, Lane said, would

probably be found in the remainingcounties if field studies were con-ducted.

Ticks in California carry at leastnine disease agents: one virus(Colorado tick fever), seven bacteria(human granulocytic ehrlichiosis,human monocytic ehrlichiosis, Rockymountain spotted fever, tularemia,and one protozoa (Babesia microti).Total number of cases of Lymedisease reported in California since1991 is 862. Epidemiologists agreethat in general one in ten cases arereported. Lane credited a fewphysicians who apparently developeda particular interest in Lyme disease

Tapes of the Chico conferenceare available from the LDRC. Writeor email info@lymedisease.org forinformation. This report will becontinued in the next issue.

12th InternationalScientificConference onLyme Disease andOther Spirochetal& Tick-BorneDisordersApril 9 & 10,1999New York City

Deadline for submission of OralAbstracts - 12/22/98; Poster Submis-sions - 2/25/99. For more informa-tion contact:

Lyme Disease Foundation,One Financial Plaza,Hartford, CT 06103860-525-2000fax: 860-525-TICK24-hr Hotline: 800-886-LYMEemail: Lymefnd@aol.comwebsite: www.Lyme.org

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