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July
2007: VOLUME
1, NUMBER 2
[EDITOR’S
NOTE: This issue discusses the
rash and skin manifestations associated with tick-borne infections.
Physicians treating patients with other dermatological conditions are
invited to visit our sister publication, eMedical
Dermatology Review, to access additional accredited programs.]
In
This Issue...
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JULY
PODCAST |
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eInfections
Review is proud to announce its first accredited
PODCAST for 2007. Listen
here. |
Participants
can now receive 0.5 credits per podcast after completing an online post-test
via the links provided on this page. In addition to our monthly newsletters,
there will be 6 podcasts throughout the coming year.
In this audio interview Paul
G. Auwaerter, MD of Johns Hopkins University School of Medicine will
discuss tick-borne illnesses from a clinical perspective.
To learn more about podcasting
and how to enjoy this exciting new feature of eInfections Review, please visit
this page.
Common Tick-borne Infections
in the United States
Since
its initial description 30 years ago, Lyme disease (LD) has become the
most commonly reported vector-borne disease in the United States. Due
in part to this notoriety, healthcare professionals as well as the public
have become increasingly aware of all tick-borne human infections. Although
most cases respond well to antibiotic therapy, early diagnosis as well
as determining appropriate therapy can be challenging.
In this issue, we discuss the
recently released guidelines from the Infectious Disease Society of
America (IDSA) and the American Association of Neurology (AAN) that
address diagnostic and treatment recommendations for LD; other papers
reviewed elucidate diagnosis of early LD, contrast the presentations
of Southern Tick-associated Rash Illness (STARI) with LD, describe a
new Rickettsial human infection, and detail changes in the expected
areas endemic for another rickettsial infection, Rocky Mountain spotted
fever (RMSF). |
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Course
Directors
John
G. Bartlett, MD
Professor of Medicine
Department of Medicine
The Johns Hopkins
University
School of Medicine
Baltimore, MD
Paul
G. Auwaerter, MD
Associate Professor
of Medicine
Clinical Director
Division of Infectious
Diseases
The Johns Hopkins
University
School of Medicine
Baltimore, MD
Sara
E. Cosgrove, MD, MS
Assistant Professor
of Medicine
Division of Infectious
Diseases
Director
Antibiotic Management
Program
Associate Hospital
Epidemiologist
The Johns Hopkins
University
School of Medicine
Baltimore, MD |
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GUEST
AUTHOR OF THE MONTH |
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Commentary
& Reviews: |
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Paul
G. Auwaerter, MD
Associate
Professor of Medicine
Clinical
Director
Division
of Infectious Diseases
The Johns
Hopkins University
School
of Medicine
Baltimore,
MD |
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Guest
Faculty Disclosures
Paul
G. Auwaerter, MD, has disclosed that he has served as a consultant
for Novartis, Pfizer, Ortho-McNeil, Schering-Plough, and Genzyme.
He is on the Speakers' Bureau for Schering-Plough and has also disclosed
that he is a Stock Shareholder for Johnson and Johnson.
Unlabeled / Unapproved Uses
Dr. Auwaerter has
indicated that his presentation will not contain any off-label information.
Course
Directors' Disclosures |
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the conclusion of this activity, participants should be able to: |
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Discuss
the new recommendations regarding the treatment of Lyme disease,
Human Granulocytic Anaplasmosis, and Babesiosis |
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Identify
new diagnostic procedures and therapeutic options for tick-borne
disease in the United States |
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Describe
reported changes in the range of tick-borne pathogens as well as
newly described causes of tick-borne infection |
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COMPLETE
THE
POST-TEST
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Click on the appropriate link
below. This will take you to the post-test.
Step
2.
If you have participated in a
Johns Hopkins on-line course, login. Otherwise, please register.
Step
3.
Complete the post-test and course
evaluation.
Step
4.
Print out your certificate.
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Clinicians
face some daunting hurdles when diagnosing tick-borne infections. Astute
knowledge of local tick populations and the diseases they carry is
critical, as is having a high index of suspicion in the differential
diagnosis. Some infections such as RMSF and ehrlichiosis can start
with non-specific flu-like symptoms before becoming more severe, with
multi-organ system involvement that may result in death, even with
appropriate initiation of antibiotics. LD has its own controversies;
many internet-educated patients believe they suffer from active Borrelia
burgdorferi infection as an explanation for chronic fatigue, musculoskeletal
pain, and subjective neurocognitive complaints. A good resource for
the basics of common tick-borne disease in the United States – including
endemic range of infections, photographs of tick vectors, diagnosis,
and treatment – can be found at the Centers for Disease Control website
(www.cdc.gov/ticks/index.html).
Recently, 2 societies (the IDSA
and the AAN) have issued new guideline statements for LD diagnosis and
treatment.1,2 These 2 documents come at an important time,
since a small group of physicians (often referring to themselves as "Lyme
literate") advocate for a considerably more liberal diagnosis of LD
in patients with chronic subjective problems such as fatigue, musculoskeletal
complaints, and/or neurocognitive dysfunction who may not have any objective
history of LD such as erythema migrans (EM) or validated Lyme serologic
testing. Moreover, this group of physicians also believes that persistent B.
burgdorferi infection is responsible for these chronic symptoms
and that long-term antibiotic administration is helpful. They have even
had a non-peer-reviewed guideline published outlining their policies.3
It is important to distinguish
those patients with only subjective
symptoms from those with objective
evidence of late LD (such as
monoarthritis, radiculitis, or
true encephalopathy) who have
evidence of active infection.
Patients with such objective
evidence should be termed "late Lyme disease," while
those with subjective and persisting
complaints should fall under
the recently coined rubric "post-Lyme
disease syndrome." The term "chronic Lyme disease," while favored by
the so-called "Lyme literate" physicians, is not used by the IDSA or
AAN organizations, who find "post-Lyme disease syndrome" a more accurate
description of those patients
in whom there is an inability
to recover B.
burgdorferi but who have persisting subjective complaints after
appropriate antibiotic therapy
for Lyme disease.
Both guidelines (reviewed herein)
present the best available evidence that outlines diagnostic and treatment
recommendations for LD, including strong statements that LD is misdiagnosed
by many in the "Lyme literate" group and that long-term antibiotics
offer no important benefit to patients with persisting subjective symptoms.
Recommendations regarding occasional co-pathogens (Anaplasma phagocytophilum and Babesia
microti) are also reviewed.
Although EM is often considered
to specifically indicate LD, some patients, especially in southern regions
of the US, present with such lesions after a tick bite, yet do not have
evidence of B. burgdorferi infection. Wormser et al compare
and contrast early LD seen in New York with EM lesions identified in
Missouri.4 The Missouri patients appear to have a milder
illness than those with LD, without any of the persisting symptoms of
fatigue and musculoskeletal pain seen in a minority of LD patients even
after antibiotic treatment. This non-Bb EM illness should be
referred to as STARI, and not reported as LD to public health authorities.
The reports of community outbreaks
of RMSF in arid regions of Arizona – an area outside traditional endemic
boundaries – point to a tick vector heretofore never implicated in transmission.5 Clinicians
therefore need to be aware of potential RMSF even in previously non-endemic
regions. |
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UPDATED
GUIDELINES FOR LYME DISEASE, HGA AND BABESIOSIS |
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Wormser
GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment,
treatment, and prevention of lyme disease, human granulocytic
anaplasmosis, and babesiosis: clinical practice guidelines by
the Infectious Diseases Society of America. Clin
Infect Dis. 2006;43(9):1089-134.
(For non-journal subscribers, an additional fee may apply
for full text articles.) |
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Halperin
JJ, Shapiro ED, Logigian E, et al. Practice Parameter:
Treatment of nervous system Lyme disease (an evidence-based
review). Report of the Quality Standards Subcommittee of the
American Academy of Neurology. Neurology. 2007;
69(1):91-102. Epub 2007 May 23.
(For non-journal subscribers, an additional fee may apply
for full text articles.) |
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The
IDSA Guideline Paper represents an evidence-based review of over
400 articles, providing comprehensive diagnostic and treatment recommendations
from a group of scientific and clinical experts in tick-borne diseases.
The AAN appropriately focuses upon central nervous system involvement
by LD in a similar evidenced-based fashion.
LD, caused by B. burgdorferi, most commonly causes an ovoid,
enlarging erythematous rash called erythema migrans (EM), which may
be accompanied by systemic symptoms such as fever, headache, neck
stiffness, arthralgia, myalgia, and fatigue. Other manifestations
include certain neurologic, arthritic and cardiac disorders. The
tick-borne infection is most commonly seen in temperate costal and
riparian environs in Northeast, Mid-Atlantic and Upper Midwest states,
which account for over 85% of recent reports. The IDSA Guideline
updates recommendations first published in 2000, and uses the best
available evidence to guide diagnostic assessment, antibiotic selection,
and treatment duration, and offers a comprehensive look at all forms
of LD.
The document also
discusses other tick-borne disorders that are transmitted by the B.
burgdorferi vector Ixodes scapularis (black-legged
deer tick), including Human Granulocytic Anaplasmosis (HGA due to Anaplasma
phagocytophilum) and Babesiosis. HGA may cause a flu-like syndrome
with fever, often along with leukopenia/neutropenia, thrombocytopenia,
and transaminase elevations. Diagnosis may be delayed if dependent
on serology or polymerase chain reaction (PCR), so a high index of
suspicion should prompt rapid empiric initiation of doxycycline.
HGA usually responds promptly to administration of doxycyline within
48-72 hours, and no chronic infection has been described. Babesia
microti is a parasite that causes a malaria-like illness infecting
red blood cells, capable of producing a severe illness, especially
in patients without spleens or who are immune-compromised.
While space limitations
in this forum do not allow for a thorough discussion of the wealth
of data presented, new information includes:
- Early LD may be treated with a 10-day oral course of doxycycline,
100mg twice daily, although either doxycycline or amoxicillin (500mg
three times daily) also remain recommended in a range of 14-21
days.6
- Primary prophylaxis with a single dose of doxycycline 200mg
may be offered to certain patients meeting important criteria:
bite by Ixodes tick, attachment for ≥36 hours in a
child over 8 years of age or an adult and engorgement, and/or local
rate of tick infection by B. burgdorferi surpassing 20%.7
- The term "chronic Lyme disease" is not favored: it is indistinct
in discriminating between late LD (monoarthritis, neuroborreliosis
typified by objective manifestations) and persisting symptoms after
appropriate antibiotic treatment for LD (subjective symptoms such
as fatigue, memory complaints, musculoskeletal pains). The terms "late
Lyme disease" and "post-Lyme disease syndrome" are preferred. Post-Lyme
disease syndrome may be an appropriate label for patients with
6 months or more of persisting symptoms after diagnosis and treatment
of LD. Since fatigue and musculoskeletal pains are common in so-called "normal" populations,
it is difficult to precisely define how often LD truly precipitates
these symptoms.
- Diagnosis of LD based solely on chronic, subjective symptoms
is inappropriate, as is the use of unvalidated tests as performed
in so-called "Lyme specialty research laboratories." Administration
of long-term antibiotics for these patients—often in combination
and by oral or parenteral routes—has shown no substantial benefit
in the 2 randomized, double-blinded trials published to date.8,9
- The weight of in vitro, animal, and human data does
not support the concept that B. burgdorferi establishes
a latent infection after antibiotic therapy—or that the organism
suppresses the immune system and therefore results in frequently
seronegative testing.
- Since antibiotics do not appear to help patients with chronic,
subjective symptoms of LD, their use cannot be justified. More
research is needed to understand the etiology of patients with
subjective complaints, to determine how often they are truly induced
by B. burgdorferi, as well as to develop therapies that
may have utility.
A completely new
section deals with patients who have persistent symptoms such as
fatigue, neurocognitive dysfunction, and musculoskeletal pain after
appropriate treatment for LD. A proposed case description is outlined
as below:
The description further notes that although testing by either culture or PCR for evidence of B. burgdorferi infection is not required, should such testing be done, it should be performed by reliable methods. A positive result should also be considered an exclusion
The role of long-term
antibiotic therapy is also addressed in the Guidelines published
by Halperin et al, with the similar conclusion that long-term antibiotics
have no compelling role in patients with post-Lyme disease syndrome
and in treating the subjective neuro-cognitive complaints believed
attributable to LD. Two independent panels have therefore reached
similar conclusions on this topic, which should mitigate an oft-cited
criticism by "Lyme-literate" physicians that the IDSA guidelines
reflect the view of only a small group of academic physicians. |
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CAN
HISTORY OR EXAMINATION FINDINGS BE DEPENDED UPON FOR THE DIAGNOSIS
OF ERYTHEMA MIGRANS? |
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Tibbles
CD, Edlow JA. Does this patient have erythema migrans? JAMA.
2007;297(23):2617-27.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Seeking
to determine how sensitive history or physical examination may be for
the diagnosis of EM, Tibbles and Edlow performed a Medline search for
English written studies containing at least 15 consecutive patients
with a diagnosis of EM where historical and physical exam characteristics
were descriptive enough to contribute to a sensitivity assessment. The
authors found a total of 53 studies representing 8493 patients for analysis,
with 32 from Europe and the balance from the United States. In the US
studies, the sensitivity of systemic symptoms overall was 0.65 (95%
CI 0.52-0.76), while individual historical variables were all less,
including headache 0.36 (0.27-0.46), myalgia or arthralgia ~0.35 (0.25-0.46),
fever 0.33 (0.23-0.46), and history of tick bite 0.26 (0.18-0.37). While
a solitary cutaneous lesion yielded a summary sensitivity of 0.81 (95%
CI 0.72-0.87), the typical “bull’s eye” central clearing was only 0.19
(0.11-0.32).
EM has been a characteristic
finding of LD transmitted by Ixodes scapularis (black-legged
deer tick). In recent years, similar lesions have been described as
a consequence of Amblyomma americanum (Lone star tick) bites.
This new apparent infection has been coined STARI, and does not appear
to be due to B. burgdorferi, the agent of LD.10,11 The
authors report one such patient with an EM-like rash had B. lonestari isolated,
but this has not been found as yet in other patients.12 Since
LD remains a clinical diagnosis, concern arises whether a specific constellation
could yield a definitive diagnosis of EM. The case definition used by
the Centers for Disease Control defines EM as an expanding skin lesion
of at least 5 cm, often accompanied by fatigue, fever, headache, mild
stiff neck, arthralgia and myalgia.13
Reviewing and summarizing the
data, the authors looked for variables that might precisely define EM;
without surprise, they conclude that no single component of the history
or physical is sufficient enough to secure the diagnosis of EM. Rather,
physicians must depend upon synthesizing information from endemic LD
acquisition risks and other historical or exam elements—all of which
can increase diagnostic probability over single or few variables. Moreover,
Lyme disease serology is often negative early in the infection. Equivocal
lesions are more likely to be EM if the suspect process expands rather
than diminishes. In such instances, convalescent Lyme serology may prove
useful.
Observed skin rashes of any type
rarely are sufficient alone to be completely pathognomic for any process,
much less an infectious one. Tibbles and Edlow also emphasize the well-described
but under-acknowledged fact that only a minority of EM rashes are with
central clearing, representing a "bull’s eye" rash. While this may be
classically described lesion of LD, the more common EM rash is a solitary,
ovoid homogeneously erythematous lesion without central clearing.14 Ultimately,
LD remains a clinical diagnosis whereby a variable presentation of EM
must be factored into a full picture of history and endemic risks, physical
exam findings and possibly laboratory data. Since prospective studies
of rash, generally, have not been carried out, the true diagnostic accuracy
of EM remains unknown. |
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SOUTHERN
TICK-ASSOCIATED RASH ILLNESS VERSUS LYME DISEASE |
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Wormser
GP, Masters E, Nowakowski J, et al. Prospective clinical
evaluation of patients from Missouri and New York with erythema
migrans-like skin lesions. Clin Infect Dis. 2005;41(7):958-65.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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STARI,
also sometimes referred to as Master’s disease, describes patients in
the Southeast and Southcentral parts of the US who have an EM-like rash.
Although these lesions resemble those of typical LD, evidence of B.
burgdorferi infection has not typically been found by serology
in these patients.15-18 Moreover, the tick known to transmit
LD, Ixodes scapularis, is rarely infected with the spirochete B.
burgdorferi in the southern US.19 Further, the lone
star tick (A. americanum), the most common agent of human tick
bites in this region, is not capable of supporting B. burgdorferi.20 While
the agent of STARI is not conclusively known, a single patient in whom
an EM-rash developed after a bite by A. americanum was found
by PCR techniques to be infected with a novel but closely related organism: B.
lonestari.21 Despite this report in 2001, this organism
has never been described in another STARI patient.22
This 2005 prospective study by
Wormser et al was designed to compare the clinical characteristics of
early Lyme disease with those of patients with suspected STARI, and
examined 21 cases of EM-like lesions in patients from Missouri (STARI
patients) compared to 101 cases of EM in patients in New York (Lyme
disease). The comparison of the 2 patient populations yielded significant
differences, some of which are selected below:
These comparison data show that
patients from Missouri with STARI had their illness earlier in the season,
and that they more often recollected a tick bite, a common historical
consequence as A. americanum bites are often painful as opposed
to the usually innocuous bite of I. scapularis. Generally,
the illness associated with the EM-like lesions in Missouri was milder
than cases described in New York. The Missouri patients were less likely
to have constitutional and subjective complaints such as fatigue, joint
pain, headache, and neck stiffness, as well as fewer objective findings
such as multiple EM lesions or regional lymphadenopathy. The skin lesions
of the Missouri EM-like cases often had central clearing (bull’s eye)
at a small diameter, whereas in the New York cases, this "bull’s eye" was
more often seen in older, maturing lesions. Although the rashes resolved
with antibiotic therapy, persisting symptoms were much more common in
New York patients than Missouri patients at a 3 month assessment. None
of the Missouri patients had serological evidence of B. burgdorferi infection.
Many of the Lyme disease cases
reported outside of the usual endemic region (Northeast, Mid-atlantic,
and Upper Midwest US) may be due to STARI, and clinicians should consider
the STARI diagnosis for EM-like lesions in the Southeast, Gulf Coast,
and Western states. It is also likely, given the extensive range of A.
americanum, that some cases of Lyme disease in endemic states may
actually be due to STARI. Although the clinical finding of EM is the
most common way Lyme disease is diagnosed, it is clearly not the only
cause of EM-like lesions.
Some patients who are diagnosed
with "chronic" LD in non-endemic states and subject to long-term antibiotic
therapy may indeed have had a history of STARI, but their persisting
symptoms are likely due to other causes. Although the actual pathogen
of STARI remains unknown in most cases, once discovered and commercial
test assays developed, the STARI diagnosis will be helpful to reassure
patients about the more benign nature of this infection as opposed to
B. burgdorferi. |
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ROCKY
MOUNTAIN SPOTTED FEVER RANGE EXPANDS DUE TO A NEWLY IMPLICATED TICK
VECTOR |
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Demma
LJ, Traeger MS, Nicholson WL, et al. Rocky Mountain spotted
fever from an unexpected tick vector in Arizona. N
Engl J Med. 2005;353(6):587-94.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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RMSF,
although first discovered in the northern states associated with that
mountain range, is now most commonly described in the central and southeastern
United States, especially the Carolinas. This tick-borne infection is
transmitted in the east by Dermacentor variabilis (American
dog tick) and in the west by D. andersoni (Rocky Mountain wood
tick). The number of RMSF cases has increased in recent years, leading
to calls for a heightened awareness of this potentially fatal infection
that commonly causes fever, myalgia, headache and rash in its earlier
stages.23,24
In this 2005 report, Demma et
al present a case series describing RMSF in rural eastern Arizona – a
region heretofore not considered part of the usual range of infection.
These patients appeared to have acquired the infection from the common
brown dog tick (Rhipicephalus sanguineus), which has not been
thought to be a vector for the Rickettsia rickettsii, the organism
responsible for RMSF.
Sixteen RMSF patients from rural
eastern Arizona were identified in 2003-2004 through active surveillance
of regional hospitals as well as through anecdotal reporting. Verification
of infection was accomplished through traditional serology (IgM or IgG),
immunohistochemical staining, or PCR. Thirteen (81%) of these patients
were under 12 years of age. Most (15) patients were hospitalized (64%)
and 2 died (12%). None of the ill patients had traveled outside of their
local communities recently. All patients had a history of contact with
tick-ridden dogs, and 25% recollected a history of a recent tick bite.
One patient was found to have a R. sanguineus nymph attached.
Additional investigations were
performed at the patients’ homesites to collect ticks for analysis.
No Dermacentor ticks (the usual vector for RMSF) were found.
Although over 1000 R. sanguineus ticks were collected, only
2 were found to be positive for R. rickettsii. Serum obtained
from 4 dogs owned by infected patients also showed high titers to R.
rickettsii; one dog yielded an engorged R. sanguineus tick
that was both culture and PCR positive for R. rickettsii.
Though RMSF is unusual in Arizona – due to the hot and arid climate,
the region does not host D. variabilis or D. andersoni – evidence
collected from this investigation suggests that the local tick R.
sanguineus (common brown dog tick) was the responsible vector,
as R. rickettsii was found in such ticks as well as in dogs
living in the involved communities. Although R. sanguineus is
well-known to transmit infection, it is known mostly for infecting humans
with R. conorii, the agent of Mediterranean or Boutonneuse
spotted fever, a usually mild infection found in Asia, Africa and Europe.
Why this tick is now carrying R. rickettsii and what may be
the usual animal reservoirs in Arizona are unknown; however, the population
attack rate for children is approximately 300 times the national average,
leading the investigators to speculate that these children may have
been frequently playing with tick-infested dogs.
Because of the wide-ranging distribution
of R. sanguineus, this tick vector may be capable of causing
RMSF in areas not previously thought to be endemic for this infection.
Evidence supporting this concern was recently published using a serosurvey
of banked blood from 1996.25 In 1996, only 5% of canine blood
samples had R. rickettsii antibodies, while samples from 2003-2004
found positive serologies in 70% of dogs and 16% of children in the
outbreak community, as well as 57% of dogs in a neighboring community.
Further, a recent report describes R. rickettsii isolates from
Arizona carried by R. sanguineus as distinct from organisms
retrieved from Montana in the traditional range of RMSF.26
At least for this area of eastern
Arizona, R. rickettsii has clearly expanded its range through
the common brown dog tick and is now endemic. Whether climatic changes
or facile geographic relocation of infected ticks is responsible is
unknown, but clinicians need to be aware of potential RMSF even in previously
non-endemic regions. |
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RICKETTSIA
PARKERI: A NEW HUMAN PATHOGEN IN THE UNITED STATES |
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Whitman
TJ, Richards AL, Paddock CD, et al. Rickettsia parkeri infection
after tick bite, Virginia. Emerg Infect Dis. 2007;13(2):334-6.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Although
there are many members of the spotted fever group rickettsiae family
worldwide, there are only three well known in the US: R. rickettsii,
the cause of RMSF; R. felis, responsible for the recently described
fleaborne spotted fever; and R. akari, which causes rickettsialpox.27 In
2002, a patient from Virginia was described with fever and multiple
eschars from which R. parkeri was cultured. This organism was
first isolated in the 1930s from the Gulf Coast tick (Amblyomma
maculatum), and while thought to be a possible pathogen of cattle,
had not been implicated as an agent of human disease.28 A
second case of human infection with this rickettsial organism identified
in Mississippi has been presented in 2006 at the International Conference
on Emerging Infectious Diseases Conference (Atlanta, Georgia).
This 2007 case report describes
an illness similar to the 2002 case also diagnosed in the same Tidewater
region of Virginia (around the southern portion of the Chesapeake Bay).
A 53-year-old service man presented with a 2-day illness consisting
of fever to 39°C, night sweats, and a rash that consisted of an
eschar on his right leg along with papules arising over his thorax and
limbs. The patient had a mild leukopenia (3400 cells/ml). A skin biopsy
performed at the site of the eschar yielded PCR amplicons representing R.
parkeri, although PCR of blood and serum samples were negative.
The patient was placed on doxycycline 100mg twice daily, with fever
quickly resolving within one day, and the rash disappearing by day 4
of treatment.
Knowledge of R. parkeri may be important since some cases of
what may have been diagnosed as mild RMSF in southeastern states could,
in fact, be due to this organism. Research examining serology has suggested
that R. parkeri may crossreact with antigens used for R.
rickettsii assays. The eschar may be the clinical distinguishing
feature of R. parkeri infection – although if only fever
and maculopapular rash are detected, RMSF may be diagnosed instead (which
may be supported by serological studies). Clinicians should therefore
consider R. parkeri as part of their differential diagnosis
of mild, febrile illness with rash, especially if one or more eschars
are present. There are no commercial assays currently available, so
diagnosis is best made by cell culture techniques or PCR of skin biopsy
specimens.
While the extent of R. parkeri infection is unknown, with greater
knowledge of the organism and better diagnostic techniques, it may turn
out to be a frequent infection in the southeastern United States.29 Moreover,
the number of rickettsial infections affecting humans is growing – with
focused research efforts and use of PCR technology,30 R.
parkeri is unlikely to be the last newly described tick-borne pathogen.
References
| 1. |
Wormser
GP, Dattwyler RJ, Shapiro ED, et al. The
clinical assessment, treatment, and prevention of lyme disease,
human granulocytic anaplasmosis, and babesiosis: clinical practice
guidelines by the Infectious Diseases Society of America. Clin
Infect Dis. 2006;43:1089-134. |
|
| 2. |
Halperin
JJ, Shapiro ED, Logigian E, et al. Practice
parameter: treatment of nervous system Lyme disease (an evidence-based
review): report of the Quality Standards Subcommittee of the American
Academy of Neurology. Neurology. 2007;69:91-102. |
|
| 3. |
Cameron
D, Gaito A, Harris N, et al. Evidence-based
guidelines for the management of Lyme disease. Expert Rev
Anti Infect Ther. 2004;2:S1-13. |
|
| 4. |
Wormser
GP, Masters E, Nowakowski J, et al. Prospective
clinical evaluation of patients from Missouri and New York with
erythema migrans-like skin lesions. Clin Infect Dis. 2005;41:958-65. |
|
| 5. |
Demma
LJ, Traeger MS, Nicholson WL, et al. Rocky
Mountain spotted fever from an unexpected tick vector in Arizona. N
Engl J Med. 2005;353:587-94. |
|
| 6. |
Wormser
GP, Ramanathan R, Nowakowski J, et al. Duration
of antibiotic therapy for early Lyme disease. A randomized, double-blind,
placebo-controlled trial. Ann Intern Med.2003;138:697-704. |
|
| 7. |
Nadelman
RB, Nowakowski J, Fish D, et al. Prophylaxis
with single-dose doxycycline for the prevention of Lyme disease
after an Ixodes scapularis tick bite. N Engl J Med. 2001;345:79-84. |
|
| 8. |
Klempner
MS, Hu LT, Evans J, et al. Two
controlled trials of antibiotic treatment in patients with persistent
symptoms and a history of Lyme disease. N Engl J Med. 2001;345:85-92. |
|
| 9. |
Krupp
LB, Hyman LG, Grimson R, et al. Study
and treatment of post Lyme disease (STOP-LD): a randomized double
masked clinical trial. Neurology. 2003;60:1923-30. |
|
| 10. |
Masters
EJ, Donnell HD. Lyme
and/or Lyme-like disease in Missouri. Mo Med. 1995;92:346-53. |
|
| 11. |
Armstrong
PM, Brunet LR, Spielman A and Telford SR, 3rd. Risk
of Lyme disease: perceptions of residents of a Lone Star tick-infested
community. Bull World Health Organ. 2001;79:916-25. |
|
| 12. |
Varela
AS, Luttrell MP, Howerth EW, et al. First
culture isolation of Borrelia lonestari, putative agent of southern
tick-associated rash illness. J Clin Microbiol. 2004;42:1163-9. |
|
| 13. |
Case
definitions for infectious conditions under public health surveillance. MMWR
Morb Mortal Wkly Rep. 1997;46:1-51. |
|
| 14. |
Smith
RP, Schoen RT, Rahn DW, et al. Clinical
characteristics and treatment outcome of early Lyme disease in patients
with microbiologically confirmed erythema migrans. Ann Intern
Med. 2002;136:421-8. |
|
| 15. |
Campbell
GL, Paul WS, Schriefer ME, Craven RB, Robbins KE, Dennis DT. Epidemiologic
and diagnostic studies of patients with suspected early Lyme disease,
Missouri, 1990-1993. J Infect Dis. 1995;172:470-80. |
|
| 16. |
Kirkland
KB, Klimko TB, Meriwether RA, et al. Erythema
migrans-like rash illness at a camp in North Carolina: a new tick-borne
disease? Arch Intern Med. 1997;157:2635-41. |
|
| 17. |
Masters
E, Granter S, Duray P and Cordes P. Physician-diagnosed
erythema migrans and erythema migrans-like rashes following Lone
Star tick bites. Arch Dermatol. 1998;134:955-60. |
|
| 18. |
Felz
MW, Chandler FW, Jr., Oliver JH, Jr., Rahn DW and Schriefer ME. Solitary
erythema migrans in Georgia and South Carolina. Arch Dermatol. 1999;135:1317-26. |
|
| 19. |
Felz
MW, Durden LA, Oliver JH, Jr. Ticks
parasitizing humans in Georgia and South Carolina. J Parasitol. 1996;82:505-8. |
|
| 20. |
Ryder
JW, Pinger RR, Glancy T. Inability
of Ixodes cookei and Amblyomma americanum nymphs (Acari: Ixodidae)
to transmit Borrelia burgdorferi. J Med Entomol. 1992;29:525-30. |
|
| 21. |
James
AM, Liveris D, Wormser GP, Schwartz I, Montecalvo MA and Johnson
BJ. Borrelia
lonestari infection after a bite by an Amblyomma americanum tick. J
Infect Dis. 2001;183:1810-4. |
|
| 22. |
Wormser
GP, Masters E, Liveris D, et al. Microbiologic
evaluation of patients from Missouri with erythema migrans. Clin
Infect Dis. 2005;40:423-8. |
|
| 23. |
Chapman
AS, Bakken JS, Folk SM, et al. Diagnosis
and management of tickborne rickettsial diseases: Rocky Mountain
spotted fever, ehrlichioses, and anaplasmosis--United States: a
practical guide for physicians and other health-care and public
health professionals. MMWR Recomm Rep. 2006;55:1-27. |
|
| 24. |
Chapman
AS, Murphy SM, Demma LJ, et al. Rocky
Mountain spotted fever in the United States, 1997-2002. Vector
Borne Zoonotic Dis. 2006;6:170-8. |
|
| 25. |
Demma
LJ, Traeger M, Blau D, et al. Serologic
evidence for exposure to Rickettsia rickettsii in eastern Arizona
and recent emergence of Rocky Mountain spotted fever in this region. Vector
Borne Zoonotic Dis. 2006;6:423-9. |
|
| 26. |
Eremeeva
ME, Bosserman E, Zambrano M, Demma L and Dasch GA. Molecular
typing of novel Rickettsia rickettsii isolates from Arizona. Ann
N Y Acad Sci. 2006;1078:573-7. |
|
| 27. |
Parola
P, Paddock CD and Raoult D. Tick-borne
rickettsioses around the world: emerging diseases challenging old
concepts. Clin Microbiol Rev. 2005;18:719-56. |
|
| 28. |
Paddock
CD, Sumner JW, Comer JA, et al. Rickettsia
parkeri: a newly recognized cause of spotted fever rickettsiosis
in the United States. Clin Infect Dis. 2004;38:805-11. |
|
| 29. |
Paddock
CD. Rickettsia
parkeri as a paradigm for multiple causes of tick-borne spotted
fever in the western hemisphere. Ann N Y Acad Sci. 2005;1063:315-26. |
|
| 30. |
Parola
P, Davoust B and Raoult D. Tick-
and flea-borne rickettsial emerging zoonoses. Vet Res. 2005;36:469-92. |
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Johns Hopkins University School of Medicine is accredited by The
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Physicians
eNewsletter: The Johns Hopkins University School
of Medicine designates this educational activity for a maximum of
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should only claim credit commensurate with the extent of their participation
in the activity.
Podcast: The Johns Hopkins University School of
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PRA Category 1 Credit(s)TM. Physicians should only
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| Post-Test
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| To
take the post-test for eInfections Review you will need to visit The
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Johns Hopkins University School of Medicine takes responsibility
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| This
activity has been developed for the Primary Care Physician, Internist,
and Infectious Disease Specialist. |
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| Learning
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At
the conclusion of this activity, participants should be able to:
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|
Discuss
the new recommendations regarding the treatment of Lyme disease,
Human Granulocytic Anaplasmosis, and Babesiosis |
|
|
|
Describe
reported changes in the range of tick-borne pathogens as well
as newly described causes of tick-borne infection |
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Identify
new diagnostic procedures and therapeutic options for tick-borne
disease in the United States |
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The
Office of Continuing Medical Education (CME) at The Johns Hopkins
University School of Medicine is committed to protect the privacy
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maintains its Internet site as an information resource and service
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Continuing Medical
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As
a provider accredited by The ACCME, it is the policy of The Johns
Hopkins University School of Medicine to require the disclosure
of the existence of any significant financial interest or any other
relationship a faculty member or a provider has with the manufacturer(s)
of any commercial product(s) discussed in an educational presentation.
The Program Directors reported the following:
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John
G. Bartlett, MD, has disclosed that he has served on
the HIV Advisory Board for GlaxoSmithKline, Abbott, Bristol-Myers
Squibb, Pfizer and Tibotec. He is also on the Policy Board for
Johnson & Johnson. |
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Paul
G. Auwaerter, MD, has disclosed that he has served
as a consultant for Novartis, Pfizer, Ortho-McNeil, Schering-Plough,
and Genzyme. He is on the Speakers' Bureau for Schering-Plough
and has also disclosed that he is a Stock Shareholder for Johnson
& Johnson. |
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Sara
E. Cosgrove, MD, MS, has disclosed that as a co-investigator,
she has received grants or research support from Merck and served
on the Advisory Boards for Ortho-McNeil and Cadence Pharmaceuticals. |
Guest
Authors Disclosures |
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opinions and recommendations expressed by faculty and other experts
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Johns Hopkins University School of Medicine name implies review
of educational format design and approach. Please review the complete
prescribing information of specific drugs or combination of drugs,
including indications, contraindications, warnings and adverse effects
before administering pharmacologic therapy to patients. |
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COMPLETE
THE
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1.
Click on the appropriate link below. This
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Step
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If you have participated in a Johns Hopkins
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Step
3.
Complete the post-test and course evaluation.
Step
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Print out your certificate.
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