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Volume: 5
Issue: 06
Date: 09-Jun-97


Table of Contents:

I.    ANN INTERN MED: Fatal pancarditis in a patient with
      coexistent Lyme disease and babesiosis.  Demonstration of
      spirochetes in the myocardium.
II.   EUR J CLIN MICROBIOL INFECT DIS: Serological evidence of
      human granulocytic ehrlichiosis in Norway.
III.  AM J CLIN PATHOL: Positive Lyme disease serology in
      patients with clinical and laboratory evidence of human
      granulocytic ehrlichiosis.
IV.   SCAND J INFECT DIS: A case of concurrent Lyme meningitis
      with ehrlichiosis.
V.    J CLIN MICROBIOL: Immunoserologic evidence of coinfection
      with Borrelia burgdorferi, Babesia microti, and human
      granulocytic Ehrlichia species in residents of Wisconsin
      and Minnesota.
VI.   J CLIN MICROBIOL: Coexistence of antibodies to tick-borne
      pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis
      in human sera.
VII.  JAMA: Concurrent Lyme disease and babesiosis. Evidence for
      increased severity and duration of illness.
VIII. EXP PARASITOL:  Borrelia burgdorferi and Babesia microti:
      efficiency of transmission from reservoirs to vector ticks
      (Ixodes dammini).
IX.   About The LymeNet Newsletter


Newsletter:

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IDX#                Volume 5 / Number 06 / 09-JUN-97
IDX#                            INDEX
IDX#
IDX#                    **** SPECIAL ISSUE ****
IDX#             ***** LYME DISEASE CO-INFECTIONS *****
IDX#
IDX#  I.    ANN INTERN MED: Fatal pancarditis in a patient with
IDX#        coexistent Lyme disease and babesiosis.  Demonstration of
IDX#        spirochetes in the myocardium.
IDX#  II.   EUR J CLIN MICROBIOL INFECT DIS: Serological evidence of
IDX#        human granulocytic ehrlichiosis in Norway.
IDX#  III.  AM J CLIN PATHOL: Positive Lyme disease serology in
IDX#        patients with clinical and laboratory evidence of human
IDX#        granulocytic ehrlichiosis.
IDX#  IV.   SCAND J INFECT DIS: A case of concurrent Lyme meningitis
IDX#        with ehrlichiosis.
IDX#  V.    J CLIN MICROBIOL: Immunoserologic evidence of coinfection
IDX#        with Borrelia burgdorferi, Babesia microti, and human
IDX#        granulocytic Ehrlichia species in residents of Wisconsin
IDX#        and Minnesota.
IDX#  VI.   J CLIN MICROBIOL: Coexistence of antibodies to tick-borne

IDX#        pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis
IDX#        in human sera.
IDX#  VII.  JAMA: Concurrent Lyme disease and babesiosis. Evidence for
IDX#        increased severity and duration of illness.
IDX#  VIII. EXP PARASITOL:  Borrelia burgdorferi and Babesia microti:
IDX#        efficiency of transmission from reservoirs to vector ticks
IDX#        (Ixodes dammini).
IDX#  IX.   About The LymeNet Newsletter
IDX#



    "These results provide evidence for coinfection, perhaps
     explaining the variable manifestations and clinical
     responses noted in some patients with tick-transmitted
     diseases. "  -- Mitchell, et al.



=====*=====


INTRODUCTION:
The emergence of two previously obscure tick-borne diseases is causing
many heath care professionals to re-examine how they diagnose and treat
the condition we refer to as Lyme disease.  Babesiosis and Human
Granulocytic Ehrlichiosis (HGE) have recently made headlines in the
popular press and are being hyped as the next generation of tick-borne
illness.  However, these diseases may have already added a new
dimension of complexity to the diagnostic and treatment assessment
process.


Co-infection with two or more of these agents may present the physician
with mixed signals that can lead to misdiagnosis.  A single tick can
carry more than one pathogen and transmit the infection to an
unsuspecting human or canine victim.  Indeed, a recent study last
November of 100 ticks by the Hunterdon County Tickborne Disease
Research Group confirmed the existence of co-infection in at least one
New Jersey county.  Forty-three ticks were infected with the Lyme
disease agent, seventeen tested positive for HGE, and five for
Babesiosis.  Six ticks were co-infected with two or more agents.  
The ticks were tested at New York Medical College in Valhalla, NY.  


Until recently, little work had been done to investigate the clinical
and therapeutic ramifications of co-infections.  In this LymeNet
Newsletter, we highlight the issue of co-infection in an effort to
emphasize to physicians the importance of remaining vigilant.  The
first abstract demonstrates that concern over co-infection was raised
as early as 1985.



=====*=====


I.    ANN INTERN MED: Fatal pancarditis in a patient with coexistent
     Lyme disease and babesiosis.  Demonstration of spirochetes in
     the myocardium.
--------------------------------------------------------------------
AUTHORS: Marcus LC, Steere AC, Duray PH, Anderson AE, Mahoney EB
REFERENCE: Ann Intern Med 1985 Sep;103(3):374-6
ABSTRACT:


A 66-year-old man developed fever, chills, myalgias, three
erythematous skin lesions, and transient left eyelid lag.  Because of
persistent fever, he was hospitalized 4 weeks after the onset of
disease; a peripheral blood smear showed Babesia microti in 3% of his
erythrocytes.  Eighteen hours later, he died unexpectedly.  Autopsy
showed pancarditis with a diffuse lymphoplasmacytic infiltrate, and
spirochetes were found in the myocardium.  Antibody titers to both the
Lyme disease spirochete Borrelia burgdorferi and Babesia microti were
elevated.  The finding of spirochetes in the myocardium and the
elevated antibody titers to Borrelia burgdorferi suggest that the
patient died from cardiac involvement of Lyme disease.



=====*=====


II.   EUR J CLIN MICROBIOL INFECT DIS: Serological evidence of human
     granulocytic ehrlichiosis in Norway.
--------------------------------------------------------------------
AUTHORS: Bakken JS, Krueth J, Tilden RL, Dumler JS, Kristiansen BE
ORGANIZATION: Section of Infectious Diseases, Duluth Clinic, Minnesota
REFERENCE: Eur J Clin Microbiol Infect Dis 1996 Oct;15(10):829-32
ABSTRACT:


Human granulocytic ehrlichoisis was first described in 1994.  This
tick-transmitted illness is increasingly recognized in the USA as well
as in Europe in areas where ixodes ticks and Lyme borreliosis are
endemic.  Blood samples from 58 Norwegian patients with physician-
diagnosed Lyme borreliosis were examined for the presence of
antibodies to Ehrlichia equi, a surrogate marker of the agent of
human granulocytic ehrlichiosis. The results indicated that 10.2% of
the patients may have been co-infected with human granulocytic
ehrlichiosis and Lyme borreliosis. Human granulocytic ehrlichiosis
appears to be established in southern Norway.



=====*=====


III.  AM J CLIN PATHOL: Positive Lyme disease serology in patients
     with clinical and laboratory evidence of human granulocytic
     ehrlichiosis.
------------------------------------------------------------------
AUTHORS: Wormser GP, Horowitz HW, Nowakowski J, McKenna D, Dumler JS
        Varde S, Schwartz I, Carbonaro C, Aguero-Rosenfeld M
ORGANIZATION: Department of Medicine, New York Medical College,
             Valhalla, NY
REFERENCE: Am J Clin Pathol 1997 Feb;107(2):142-7
ABSTRACT:


In 10 consecutive patients with an acute febrile illness, human
granulocytic ehrlichiosis was confirmed with specific polymerase chain
reaction studies, serologic conversion, or both.  Although no
patients had the clinical features most suggestive of early Lyme
disease (eg, erythema migrans or cranial nerve palsy), tests for
antibody to Borrelia burgdorferi produced a reaction in most patients.
In 6 of 7 patients (86%) with evaluable results, enzyme-linked
immunosorbent assay yielded positive or equivocal findings, and an
immunoblot technique yielded positive findings in 60% to 90% of
patients, depending on the criteria used for interpretation. Inasmuch
as approximately 25% of nymphal Ixodes scapularis ticks in Westchester
County, New York, are infected with B burgdorferi, the probability that
at least 9 of these patients were coinfected with B burgdorferi and
human granulocytic ehrlichiosis by the same tick bite is estimated to
be .00003. These observations suggest that serodiagnosis is
insufficient to establish the presence of coinfection with B

burgdorferi.


=====*======


IV.   SCAND J INFECT DIS: A case of concurrent Lyme meningitis with
     ehrlichiosis.
-------------------------------------------------------------------
AUTHORS: Ahkee S, Ramirez J
ORGANIZATION: Division of Infectious Diseases, University of
             Louisville School of Medicine, KY, USA.
REFERENCE: Scand J Infect Dis 1996;28(5):527-8
ABSTRACT:


We report on a case of concurrent Lyme meningitis and ehrlichiosis
in a patient with occupational exposure to ticks as a logger.  The
patient had a febrile Illness with a reticulate erythematous rash
on his upper torso, meningoencephalitis, thrombocytopenia, and
hepatitis.  Acute and convalescent serologies were consistent with
a dual infection with Lyme disease and ehrlichiosis.  Ixodes
scapularis is the tick that is associated with Lyme disease in our
area and this tick has also been reported to harbor the species of
Ehrlichia that causes human granulocytic ehrlichiosis.  Empiric
therapy for both Lyme disease and ehrlichiosis should be considered
in any patient suspected of having a tick-borne illness and presenting
with signs and symptoms compatible with both infections.



=====*=====


V.    J CLIN MICROBIOL: Immunoserologic evidence of coinfection with
     Borrelia burgdorferi, Babesia microti, and human granulocytic
     Ehrlichia species in residents of Wisconsin and Minnesota.
--------------------------------------------------------------------
AUTHORS: Mitchell PD, Reed KD, Hofkes JM
ORGANIZATION: Microbiology Section, Marshfield Laboratories, WI
             MitchelP@dgabby.mfldclin.edu
REFERENCE: J Clin Microbiol 1996 Mar;34(3):724-7
ABSTRACT:


In Wisconsin and Minnesota, Ixodes scapularis (Ixodes dammini) ticks
are the vector of three microorganisms that may cause significant
disease in humans and lower mammals.  These diseases include Lyme
borreliosis, which is caused by Borrelia burgdorferi, babesiosis,
which is caused by Babesia microti, and human granulocytic
ehrlichiosis (HGE), which is caused by an apparently new species
in the genus Ehrlichia.  Immunoserologic testing was performed on
sera from patients with a diagnosis of one of these diseases to
determine if there was evidence of coinfection with one or more
of the other agents.  Of 96 patients with Lyme borreliosis, 9
(9.4%) demonstrated immunoserologic evidence of coinfection:
5 (5.2%) with the agent of HGE, 2 (2.1%)  with B. microti, and 2 (2.1%)
with both microorganisms.  Of 19 patients diagnosed with HGE, 3 (15.8%)
showed immunoserologic evidence of coinfection: 1 (5.3%) with B.
burgdorferi, 1 (5.3%) with B. microti, and 1 (5.3%) with both
microorganisms.  One patient diagnosed with babesiosis was also

seropositive for ehrlichiosis.  These results provide evidence for
coinfection, perhaps explaining the variable manifestations and
clinical responses noted in some patients with tick-transmitted
diseases.  In certain clinical settings, laboratory testing for
coinfection is indicated to ensure that appropriate antimicrobial
treatment is given.



======*=====


VI.   J CLIN MICROBIOL: Coexistence of antibodies to tick-borne
     pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis in
     human sera.
--------------------------------------------------------------------
AUTHORS: Magnarelli LA, Dumler JS, Anderson JF, Johnson RC, Fikrig E
ORGANIZATION: Department of Entomology, Connecticut Agricultural
             Experiment Station, New Haven, USA.
REFERENCE: J Clin Microbiol 1995 Nov;33(11):3054-7
ABSTRACT:


Serum specimens from persons with or without Lyme borreliosis were
analyzed by indirect fluorescent antibody staining methods for total
immunoglobulins to Babesia microti, Ehrlichia chaffeensis (Arkansas
strain), and Ehrlichia equi (MRK strain).  There was serologic evidence
of human exposure to multiple tick-borne agents in 15 (6.6%) of 227
serum samples obtained in Connecticut and Minnesota.  Of these, 10
serum samples were from Connecticut patients who had erythema migrans
and antibodies to Borrelia burgdorferi (range, 1:160 to 1:40, 960).
A maximal antibody titer of 1:640 was noted for a B. microti infection,
whereas titration end points of 1:640 and 1:1,280 were recorded for E.
chaffeensis and E. equi seropositives, respectively.  In specificity
tests, there was no cross-reactivity among the antisera and antigens
tested for the four tick-borne pathogens.  On the basis of serologic
testing, a small group of persons who had Lyme borreliosis had
been exposed to one or more other tick-borne agents, but there was

no clinical diagnosis of babesiosis or ehrlichiosis.  Therefore, if
the clinical picture is unclear or multiple tick-associated illnesses
are suspected, more extensive laboratory testing is suggested.



=====*=====


VII.  JAMA: Concurrent Lyme disease and babesiosis. Evidence for
     increased severity and duration of illness.
----------------------------------------------------------------
AUTHORS: Krause PJ, Telford SR 3rd, Spielman A, Sikand V, Ryan R,
        Christianson D, Burke G, Brassard P, Pollack R, Peck J,
        Persing DH
ORGANIZATION: Department of Pediatrics, University of Connecticut
             School of Medicine, Farmington, USA.
REFERENCE: JAMA 1996 Jun 5;275(21):1657-60
ABSTRACT:


OBJECTIVE -- To determine whether patients coinfected with Lyme disease
and babesiosis in sites where both diseases are zoonotic experience
a greater number of symptoms for a longer period of time than those
with either infection alone.
DESIGN -- Community-based, yearly serosurvey and clinic-based cohort
study.
SETTING -- Island community in Rhode Island and 2 Connecticut medical
clinics from 1990 to 1994.
STUDY PARTICIPANTS -- Long-term residents of the island community and
patients seeking treatment at the clinics.
MAIN OUTCOME MEASURES -- Seroreactivity to the agents of Lyme disease
and babesiosis and number and duration of symptoms.
RESULTS -- Of 1156 serosurvey subjects, 97 (8.4%) were seroreactive
against Lyme disease spirochete antigen, of whom 14 (14%) also were
seroreactive against babesial antigen.  Of 240 patients diagnosed with
Lyme disease, 26 (11%) were coinfected with babesiosis.  Coinfected
patients experienced fatigue (P = .002), headache (P < .001), sweats
(P < .001), chills (P = .03), anorexia (P = .04), emotional lability

(P = .02), nausea (P = .004), conjunctivitis (P = .04), and
splenomegaly (P = .01) more frequently than those with Lyme disease
alone.  Thirteen (50%) of 26 coinfected patients were symptomatic for
3 months or longer compared with 7 (4%) of the 184 patients with
Lyme disease alone from whom follow-up data were available (P < .001).
Patients coinfected with Lyme disease experienced more symptoms and
a more persistent episode of illness than did those (n = 10)
experiencing babesial infection alone.  Circulating spirochetal DNA
was detected more than 3 times as often in coinfected patients as in
those with Lyme disease alone (P = .06).
CONCLUSIONS -- Approximately 10% of patients with Lyme disease in
southern New England are coinfected with babesiosis in sites where
both diseases are zoonotic.  The number of symptoms and duration of
illness in patients with concurrent Lyme disease and babesiosis are
greater than in patients with either infection alone.  In areas
where both Lyme disease and babesiosis have been reported, the

possibility of concomitant babesial infection should be considered
when moderate to severe Lyme disease has been diagnosed.



=====*=====


VIII. EXP PARASITOL:  Borrelia burgdorferi and Babesia microti:
     efficiency of transmission from reservoirs to vector ticks
     (Ixodes dammini).
----------------------------------------------------------------
AUTHORS: Mather TN, Telford SR 3d, Moore SI, Spielman A
ORGANIZATION: Department of Tropical Public Health, Harvard School
             of Public Health, Boston, Massachusetts
REFERENCE:  Exp Parasitol 1990 Jan;70(1):55-61
ABSTRACT:


In endemic regions, Peromyscus leucopus, the mouse reservoir of the
Lyme disease spirochete (Borrelia burgdorferi) and the piroplasm
causing human babesiosis (Babesia microti), is nearly universally
infected with both agents.  Paradoxically, spirochetal infection is
nearly twice as prevalent as is babesial infection in populations of
field-collected nymphal Ixodes dammini, the tick vector.  In the
laboratory, a similarly disproportionate rate of infection was
observed among nymphal ticks, feeding as larvae, on either B.
burgdorferi- or B. microti-infected mice.  Ticks which fed on mice
with concurrent spirochetal and babesial infections also exhibited
twice the incidence of spirochetal infection over that of the
piroplasm.  These data suggest that the efficiency of acquisition
and transstadial passage of B. burgdorferi and B. microti infection
differ by a factor of two. This discrepancy may explain differences
observed both in the prevalence of infection in ticks collected in the
field, as well as the apparently greater risk of spirochetal infection

to humans in endemic areas.


=====*=====


IX.   ABOUT THE LYMENET NEWSLETTER
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