Lyme-associated parkinsonism: a neuropathologic case study and review of the
Cassarino DS, Quezado MM, Ghatak NR, Duray PH.
Arch Pathol Lab Med, 127(9):1204-6. 2003.
Neurological complications of Lyme disease include meningitis, encephalitis,
dementia, and, rarely, parkinsonism. We present a case of striatonigral
degeneration, a form of multiple system atrophy, in Lyme-associated
parkinsonism. A 63-year-old man presented with erythema migrans rash, joint
pains, and tremors. Serum and cerebrospinal fluid antibodies and polymerase
chain reaction for Borrelia burgdorferi were positive. Clinical parkinsonism was
diagnosed by several neurologists. Despite treatment, the patient continued to
decline, with progressive disability, cognitive dysfunction, rigidity, and
pulmonary failure. At autopsy, the brain showed mild basal ganglia atrophy and
substantia nigra depigmentation, with extensive striatal and substantia nigral
neuronal loss and astrogliosis. No Lewy bodies were identified; however,
ubiquitin-positive glial cytoplasmic inclusions were identified in striatal and
nigral oligodendroglia. There were no perivascular or meningeal infiltrates, the
classic findings of neuroborreliosis. To our knowledge, this is the first report
of striatonigral degeneration in a patient with B burgdorferi infection of the
central nervous system and clinical Lyme-associated parkinsonism.
Despite continued antibiotic treatments (IV vancomycin, azithromycin, and
atovaquone), the patient's neurological status continued to decline, and he
finally succumbed to infection and respiratory failure in April 2001.
nervous system infection caused by Borrelia burgdorferi. Clinico-pathological
correlation of three post-mortem cases.
Bertrand E, Szpak GM, Pilkowska E, Habib N, Lipczynska-Lojkowska W, et al.
Folia Neuropatho, 37(1):43-51. 1999.
On necropsy gross examination brain edema
without focal changes was detected in two cases. Cerebral atrophy was seen in
Case 3. Microscopically, lymphocytic infiltrates, microglial diffuse and nodular
activation, spongiform changes, diffuse demyelination of the cerebral and
cerebellar white matter, and diffuse astrocytosis, were characteristic
pathological features in all presented cases. Multifocal, perivascular
degenerative changes in the cerebral and cerebellar white matter were observed
in the first case. Inflammatory changes in the nuclei and roots of cranial
nerves were present in the third case.
burgdoferi-seropositive chronic encephalomyelopathy: Lyme neuroborreliosis? An
Kobayashi K, Mizukoshi C, Aoki T, Muramori F, Hayashi M, et al.
Dement Geriatr Cogn Disord, 8(6):384-90. 1997.
36-year-old Japanese woman presented with progressive cerebellar signs and
mental deterioration of subacute course after her return from the USA. Her serum
antibody to spirochete Borrelia burgdorferi was significantly elevated.
necropsy 4 years after her initial neurological signs revealed multifocal
inflammatory change in the cerebral cortex, thalamus, superior colliculus,
dentate nucleus, inferior olivary nucleus and spinal cord. The lesions showed
spongiform change, neuronal cell loss, astrocytosis and proliferation of
activated microglial cells. The internal capsule was partially vacuolated and
the spinal cord, notably at the thoracic level, was demyelinated and cavitated
in the lateral funiculus. Microglial cells aggregated within and around the
spongiform lesions and microglial nodules were present in the medulla oblongata.
Use of Warthin-Starry stain demonstrated silver-impregnated organisms strongly
suggesting B. burgdorferi in the central nervous tissues. The dentate nucleus
and inferior olivary nucleus showed the most advanced lesions with profound
fibrillary gliosis. Occlusive vascular change was relatively mild, and fibrous
thickening of the leptomeninges with lymphocyte infiltrates was localized in the
basal midbrain. The ataxic symptoms were due to the dentate and olivary nucleus
lesions and mental deterioration was attributable to the cortical and thalamic
lesions. Spongiform change, neuronal cell loss, and microglial activation are
characteristic pathological features in the present case.
The cerebellar ataxia and subsequent mental deterioration are unusual clinical
features of Lyme neuroborreliosis. Spirochete B. burgdorferi can cause focal
inflammatory parenchymal change in the central nervous tissues and the present
case may be an encephalitic form of Lyme neuroborreliosis.
Inflammatory brain changes in Lyme borreliosis. A report on three patients and
review of literature.
Oksi J, Kalimo H, Marttila RJ, et al.
Brain, 199(Pt 6):2143-54. 1996.
Large areas of demyelination in periventricular white matter were detected
histologically and by MRI in one patient. The disease had a fatal outcome in
Progressive Encephalitis Following an untreated Deer Tick attachment on a 7
year-old Fairfield County, Connecticut child.
Liegner KB, Jones CR.
VIII International Conference on Lyme Borreliosis and other Emerging
Tick-borne Diseases, June 25,1999
deer tick was removed from the right aspect of the neck of a 6 year old
Fairfield County, Connecticut girl March 1995. Parental request for prophylactic
antibiotic treatment was refused by the child's physician. No eruption occurred
at the tick bite site.
flu-like symptoms and conjunctivitis developed and October 1995, headache, stiff
neck, and sleep disturbance. November 1995 right supraclavicular lymphadenitis,
fever, lethargy and hypersomnolence developed. Admitted to a local hospital,
focal seizures ensued. Phenytoin was administered. Lumbar puncture showed 3
white blood cells and normal glucose and protein. Phenytoin, ceftriaxone,
ampicillin, and acycolvir were administered. Tests for rabies and Lyme disease
were negative. MRI of brain was normal. Transfer was made to a tertiary care
facility where high dose pentobarbital coma was required to control status
epilepticus. Feeding gastrostomy and Boviac catheter were required for nutrition
and medications. Adenovirus serology, arbovirus serology and CSF serology and
culture and CSF serology, culture, and PCR for HSV-1, HSV-2, ANCA, ANA, ASO,
Bartonella, cold agglutinins, febrile agglutinins, influenza, para-influenza,
CSF india ink prep, malaria screen, measles, mycoplasma, Q fever, rabies, RMSF,
RSV, rotovirus, rubella, toxoplasmosis, typhus, varicella, Lyme disease
serologies and VDRL were negative. EBV antibodies were present. HSV IFA was
positive and rose following administration of IVIG. IgG for ehrlichia was
positive at 1:256 by the Centers for Disease Control. Intravenous
immunoglobulins were given for putative Rasmussen's Syndrome, steroids for
"vasculitis", and intravenous acyclovir for the possiblity of herpes
encephalitis. Intravenous nafcillin was given for coagulase negative
staphylococcal bacteremia. CT scans and MRIs of the brain, initially normal,
demonstrated evolution of cerebral atrophy and periventricular white matter
June 1996 the
patient demonstrated arthritis involving hands, wrists, ankles, knees, and hips,
was experiencing frequent seizures and was unable to walk, speak, respond to
verbal commands, or feed herself. Paired Lyme ELISAs in CSF and serum 7/96 were
negative, but Lyme IgG immunoblot in serum disclosed the presence of 30, 41, 66,
& 93 kiloDalton bands as well as 60 kDa band. CSF cell count, glucose protein,
and IgG were normal. CSF, blood, and urine Lyme PCRs were negative as was
culture for borrelia in BSK-H . Myelin basic protein and oligoclonal bands were
absent. Osp A antigen capture assay in CSF and Lyme-specific immune complexes in
CSF and serum were negative.
with intravenous ceftriaxone initially resulted in worsened seizure activity and
treatment was changed to cefotaxime. Arthritis resolved within one month of
starting antibiotics. A short course of doxycycline was given to cover the
possibility of co-infection with ehrlichia. During six months of treatment with
intravenous cephalosporins seizures, which had remained poorly tractable despite
intensive oral anticonvulsant therapy, diminished and became readily
controllable with lower dosage of anticonvulsants.
became able to walk, vocalize in simple sentences, feed herself, and use a swing
set but remained severely neurologically impaired with significant brain injury
evident on brain MRI and CT scan. Antibiotic therapy was stopped 12/3/96.
reoccurred within one week of cessation of antibiotics and became increasingly
difficult to manage despite continuation of anticonvulsant therapy. While in a
tertiary care hospital her condition deteriorated and she died 1/30/97. An autopsy was performed.
Ceftriaxone in the treatment of Lyme neuroborreliosis.
Rohacova H, Hancil J, Hulinska D, Mailer H, Havlik J.
Infection, 24(1):88-90. 1996.
46 patients with
neuroborreliosis were entered at the Infectious Diseases Teaching Hospital in
Prague 8. In 39 patients the diagnosis was early Lyme neuroborreliosis. Seven
patients suffered from late stage disease. Clinical results were 30% of patients
cured at the end of treatment and 85% after 9 months in early stage disease. In
late stage disease two patients out of seven were cured and four had improved
after 12 months. One patient died because of cardiac infarction.
1994 The long-term clinical outcomes of Lyme
disease. A population-based retrospective cohort study.
Shadick NA; Phillips CB; Logigian EL; Steere AC; Kaplan RF; Berardi AB;
Duray PH; Larson MG; Wright EA Ginsburg KS; Katz JN; Liang MH.
Annals of Internal Medicine 121(8): 560-7.
Patient 12 had had
high fever, meningeal symptoms, and subsequent arthritis in
1982. She was noted to have a positive serologic test result
for Lyme disease 4 years later and was treated with 2 weeks of
parenteral penicillin. She later developed a progressive speech
disorder, bradykinesia, and abnormal ocular motor function.
Magnetic resonance imaging of the brain showed scattered white
matter lesions in the hemispheres and pons, and she was diagnosed
with supranuclear palsy. Lumbar puncture showed no selective
concentration of antibody in the spinal fluid. Nevertheless,
she was re-treated with 2 weeks of parenteral ceftriaxone in
1989 that had no effect on her neurologic symptoms. During the
time of observation, this patient died. At autopsy, lymphoid
mononuclear cells were observed surrounding the intracerebral
vessels in one section. Using Dieterle silver stain, a spirochete
was present in the cortex and another was exterior to a
progressive frontal-type dementia associated with Lyme disease.
Waniek C, Prohovnik I, Kaufman MA, Dwork AJ.
Journal of Neuropsychiatry Clin Neurosci, 7(3):345-7. 1995.
The authors report a case of fatal neuropsychiatric Lyme disease (LD) that was
expressed clinically by progressive frontal lobe dementia and pathologically by
severe subcortical degeneration.
burgdorferi myositis: report of eight patients.
Reimers CD, de Koning J, Neubert U, Preac-Mursic V, Koster JG, M�ller-Felber
W, Pongratz DE, Duray PH.
J Neuro, 240(5):278-83. 1993.
Myositis is a rare manifestation of Lyme disease of unknown
pathogenesis� One patient died from cardiac arrest caused by myocarditis and
disease acquired in Europe and presenting in CONUS.
Welker RD, Narby GM, Legare EJ, Sweeney DM.
Military Medicine, Oct 158(10):684-5. 1993.
and treatment of the disease is essential to avoid the debilitating and
potentially life-threatening long-term effects of the infection; however, many
physicians may not be aware of the international scope of the disease.
Fatal encephalitis caused by concomitant infection
with tick-borne encephalitis virus and Borrelia burgdorferi.
Oksi J, Viljanen MK, Kalimo H, Peltonen R, Marttia R, et al.
Clinical Infectious Diseases, 16(3):392-6. 1993.
Nevertheless, the coinfection might have contributed
to the fatal outcome that has not been previously observed in Finnish
patients with TBE.
Lyme carditis and endodermal heterotopia of the atrioventricular node.
Cary NR, Fox B, Wright DJ, Cutler SJ, Shapiro LM, Grace AA.
Postgrad Med J, 66(773):258. 1990.
A fatal case of Lyme carditis
occurring in a Suffolk farmworker is reported. Post-mortem examination of the
heart showed pericarditis, focal myocarditis and prominent endocardial and
interstitial fibrosis. The additional finding of endodermal heterotopia ('mesothelioma')
of the atrioventricular node raises the possibility that this could also be
related to Lyme infection and account for the relatively frequent occurrence of
atrioventricular block in this condition. Lyme disease should always be
considered in a case of atrioventricular block, particularly in a young patient
from a rural area. The heart block tends to improve and therefore only temporary
pacing may be required.
Postmortem confirmation of Lyme carditis with polymerase chain reaction.
Tavora F, Burke A, Li L, Franks TJ, Virmani R.
Cardiovasc Pathol. 2008 Mar-Apr;17(2):103-7.
We describe the case of a 37-year-old Caucasian
man with a 1-month history of fevers, rash, and malaise who died unexpectedly on
the day after he underwent medical evaluation. The only clinical cardiac
abnormality found was that of second-degree atrioventricular block. At autopsy,
a diffuse carditis, characterized by infiltrates of macrophages, lymphocytes,
and eosinophils and primarily in an interstitial, endocardial, and perivascular
distribution, was found. Serologic testing from blood drawn on the day before
his death demonstrated IgG and IgM antibodies against B. burgdorferi, confirmed
by Western blot. Postmortem polymerase chain reaction (PCR) performed in
myocardial tissue amplified B. burgdorferi DNA encoding outer-surface protein A.
adult respiratory distress syndrome in a patient with Lyme disease.
Kirsch M, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A.
JAMA, 259(18):2737-9. 1988.
Ultimately, fatal adult respiratory distress syndrome developed; this
was believed to be secondary to Lyme disease.
in the brains of patients dying with dementia.
JAMA, 256(16):2195-6. 1986.
Brain perfusion SPECT in Lyme neuroborreliosis.
Sumiya H, Kobayashi K, Mizukoshi C, Aoki T, Koshino Y, Taki J, Tonami
Department of Nuclear Medicine, Kanazawa University School of Medicine,
J Nucl Med. 1997 Jul;38(7):1120-2. PMID: 9225802
SPECT imaging brain
perfusion using 99mTc-HMPAO was performed on a 38-yr-old women with Lyme
neuroborreliosis confirmed by autopsy. The patient had been suspected of
spinocerebellar degeneration. Cerebral blood flow was diffusely decreased
throughout cerebral cortices but cerebellar blood flow was not impaired,
which indicated that the diagnosis was unlikely spinocerebellar
degeneration. These findings suggested that brain perfusion SPECT provides
useful information in diagnosing the patients with Lyme neuroborreliosis,
especially when spinocerebellar degeneration is included in the
meningoradiculoneuritis in Lyme disease.
Melet M, Gerard A, Voiriot P, Gayet S, May T, et al.
Presse Med, 15(41):2075. 1986.
Early disseminated Lyme disease:
Am J Med Apr 24;98(4A):25S-28S; discussion 28S-29S 1995. PMID: 7726189
The cardiac features of Lyme disease usually occur within weeks to months of the
infecting tick bite; the result may be disruption of the conduction system,
leading to heart block and muscle dysfunction, causing a mild myopericarditis.
Lyme carditis is usually mild, although permanent heart block and a few
fatalities claimed to be due to Lyme carditis have been reported. Recent reports
have suggested that Lyme disease may be a cause of chronic congestive
cardiomyopathy. Lyme carditis should be considered in the proper clinical
setting with appropriate use of diagnostic tests, recalling that patients with
carditis early in Lyme disease may be seronegative.
Gastrointestinal and hepatic manifestations of
tickborne diseases in the United States.
Zaidi SA, Singer C.
Clin Infect Dis. May 1;34(9):1206-12. Epub 2002 Apr 2. Review.
2002. PMID: 11941547
If detected early, many
of these potentially serious illnesses can be easily and effectively
treated, thereby avoiding serious morbidity and even death.
event reports following vaccination for Lyme disease: December 1998-July 2000.
Lathrop SL, Ball R, Haber P, Mootrey GT, Braun MM, Shadomy SV, Ellenberg SS,
Chen RT, Hayes EB.
Vaccine. Feb 22;20(11-12):1603-8. 2002. PMID: 11858868
Sixty-six (7.4%) events were classified as serious, involving
life-threatening illness, hospitalization, prolongation of hospitalization,
persistent or significant disability/incapacity, or death.
Pets, and Emerging Zoonoses
Bruno B. Chomel; Albino Belotto; Fran�ois-Xavier Meslin
Emerg Infect Dis. 2007;13(1) �2007 Centers for Disease Control and
Prevention (CDC) MedScape 02/06/2007
Emerging and reemerging infectious diseases have received increasing
attention since the end of the 20th century. An estimated 75% of emerging
infectious diseases are zoonotic, mainly of viral origin, and likely to be
When first described in 1957, Kyasanur Forest disease was restricted to a
much smaller area (300 square miles) in India than the actual 2,000 square
miles of endemic zone. This tickborne disease occurs in evergreen rain
forests interspersed with deciduous patches and clearings for rice
cultivation and human habitations. Forest workers are particularly at
risk; their mortality rates may reach 10%. In 1983, a major epidemic
occurred during which several monkeys died, 1,555 humans were infected,
and 150 humans died.
many as 1,000 human cases occur each year, and this number has increased
in the past 5 years. Most cases occur during the dry season (January-May),
when nymphal activity is maximal. Such a zoonosis is a good example of
deforestation and agricultural development leading to human habitat
expansion into natural foci of a viral infection. Because cleared areas
were widely used for grazing of cattle, a major host for adult ticks,
these areas favored the proliferation of the tick Haemaphysalis spinigera.
Conversely, the reduction of traditional agricultural land and its
replacement with forested areas, home to the main reservoirs and hosts of
Borrelia burgdorferi, in association with the settlement of persons in
periurban areas, led to a considerable increase in human cases of Lyme
disease in the United States.
Borrelial lymphocytoma--a historical case.
Sonck CE, Viljanen M, Hirsimaki P, Soderstrom KO, Ekfors TO.
APMIS. Oct; 106(10):947-52. 1998. PMID: 9833696
describe a patient with a tick bite in the areola mammae in 1953 followed by
erythema migrans. Twenty years later, after another tick bite in the axillary
skin, also followed by erythema migrans, a large lymphatic infiltrate developed
in the mammary skin, when the margin of the erythema reached the areola. The
infiltrate resolved within a year without any therapy.
Borrelial DNA was detected by polymerase chain reaction in the
paraffin blocks of the lymphatic skin infiltrate. The patient died 9 years later
of generalized lymphoma.
Rocky Mountain spotted fever from an
unexpected tick vector in Arizona.
Demma LJ, Traeger MS, Nicholson WL, Paddock CD, Blau DM,Eremeeva ME, Dasch
GA, Levin ML, Singleton J Jr, Zaki SR, Cheek JE, Swerdlow DL, McQuiston JH.
N Engl J MedAug 11;353(6):587-94 . 2005 PMID: 16093467
A total of 16 patients with Rocky
Mountain spotted fever infection (11 with confirmed and 5 with probable
infection) were identified. Of these patients, 13 (81 percent) were children 12
years of age or younger, 15 (94 percent) were hospitalized, and 2 (12 percent)
died. Dense populations of Rhipicephalus sanguineus ticks were found on dogs and
in the yards of patients' homesites.
Fatal pancarditis in a
patient with co-existent Lyme disease and babesiosis: Demonstration of
spirochetes in the heart.
Marcus LC, Steere AC, Duray PH.
Annals of Internal Medicine, 103:374-6. 1985.
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.
Tick-borne infections. What starts as
a tiny bite may have a serious outcome.
Postgrad Med Apr; 95(5):131-9 1994.
Tick-borne illnesses are being reported increasingly often. Unlike
Rocky Mountain spotted fever and ehrlichiosis can kill and so must be recognized
and treated promptly. These diseases require clinical diagnosis, because
laboratory confirmation with antibody tests takes too long. Other diseases (eg,
babesiosis, tularemia) are encountered occasionally and can also be fatal but
are treatable with antibiotics.
Assessment of maternal mortality in Tanzania.
Walraven GE, Mkanje RJ, van Roosmalen J, van Dongen PW, Dolmans WM.
Br J Obstet Gynaecol. May; 101(5):414-7. 1994. PMID: 8018613
Relapsing fever or Borrelia infection was an indirect cause of death
common to the region and particularly hazardous to pregnant women.
Mortality in high risk patients with tick-borne relapsing fever analysed by the
East Afr Med J. Nov; 68(11):875-9. 1991. PMID: 1800081
Causes of death were septicaemia (3x), severe spirochaetemia in a
neonate (1x), and successive relapses in complicated cases without adequate
Herxheimer reaction in a case of relapsing fever misdiagnosed as lobar
Trop Geogr Med. Jan; 39(1):92-3. 1987. PMID: 3603698
A fatal Jarisch-Herxheimer reaction developed after treatment with
high doses of penicillin in a case of lobar pneumonia caused by Borrelia duttoni�.
Treatment may have contributed to the death of this patient.
pancarditis associated with human granulocytic Ehrlichiosis in a 44-year-old
Jahangir A, Kolbert C, Edwards W, Mitchell P, Dumler JS, Persing DH.
Clin Infect Dis. Dec; 27(6):1424-7. 1998. PMID: 9868655
We describe a case of fatal pancarditis during the course of human
granulocytic ehrlichiosis (HGE) in a 44-year-old outdoor worker who was
previously treated for presumptive Lyme disease.
granulocytic ehrlichiosis in Connecticut: report of a fatal case.
Hardalo CJ, Quagliarello V, Dumler JS.
Clin Infect Dis. Oct; 21(4):910-4. 1995. PMID: 8645839
We report a
case of granulocytic ehrlichiosis in a 71-year-old man who presented with an
acute febrile illness and subsequently developed multisystem organ dysfunction
and sudden severe anemia with thrombocytopenia requiring intensive care,
mechanical ventilation, hemodialysis, and transfusions�.This, to our knowledge,
represents to first documented case of human granulocytic ehrlichiosis to occur
outside the Upper Midwest.
granulocytic ehrlichiosis in the upper Midwest United States. A new species
Bakken JS, Dumler JS, Chen SM, Eckman MR, Van Etta LL, Walker DH.
JAMA. Jul 20; 272(3):212-8. 1994. PMID: 8022040
Two of the 12 patients died.
mortality attributable to Rocky Mountain spotted fever: immunohistochemical
detection of fatal, serologically unconfirmed disease.
Paddock CD, Greer PW, Ferebee TL, Singleton J Jr, McKechnie DB, Treadwell
TA, Krebs JW, Clarke MJ, Holman RC, Olson JG, Childs JE, Zaki SR.
J Infect Dis Jun;179(6):1469-76. 1999.
spotted fever (RMSF) is the most severe tickborne infection in the United States
and is a nationally notifiable disease. Since 1981, the annual case-fatality
ratio for RMSF has been determined from laboratory-confirmed cases reported to
the Centers for Disease Control and Prevention (CDC). Herein, a description is
given of patients with fatal, serologically unconfirmed RMSF for whom a
diagnosis of RMSF was established by immunohistochemical (IHC) staining of
tissues obtained at autopsy.
1996-1997, acute-phase serum and tissue samples from patients with fatal disease
compatible with RMSF were tested at the CDC. As determined by indirect
immunofluorescence assay, no patient serum demonstrated IgG or IgM antibodies
reactive with Rickettsia rickettsii at a diagnostic titer (i.e., >/=64);
however, IHC staining confirmed diagnosis of RMSF in all patients. Polymerase
chain reaction validated the IHC findings for 2 patients for whom appropriate
samples were available for testing.
These findings suggest that dependence on serologic assays and limited
use of IHC staining for confirmation of fatal RMSF results in underestimates of
mortality and of case-fatality ratios for this disease.
Rocky Mountain Spotted Fever, Panama
Dora Estripeaut; Mar�a Gabriela Arambur�; Xavier S�ez-Llorens; Herbert
A. Thompson; Gregory A. Dasch; Christopher D. Paddock; Sherif Zaki; Marina
Emerg Infect Dis. 2007;13(11):1763-1765. �2007 Centers for Disease
Control and Prevention (CDC)
We describe a fatal
pediatric case of Rocky Mountain spotted fever in Panama, the first, to
our knowledge, since the 1950s. Diagnosis was established by
immunohistochemistry, PCR, and isolation of Rickettsia rickettsii
from postmortem tissues. Molecular typing demonstrated strong relatedness
of the isolate to strains of R. rickettsii from Central and South
cluster of Rocky Mountain spotted fever.
Jones TF, Craig AS, Paddock CD, McKechnie DB, Childs JE, Zaki SR, Schaffner
Clin Infect Dis Apr;28(4):853-9. 1999. PMID: 10825050
Soon after a patient from Tennessee died of Rocky Mountain spotted
fever (RMSF), several family members developed symptoms suggestive of the
disease and were treated presumptively for RMSF.
visiting the index patient's home were interviewed; serum samples were collected
from 35. Three additional cases of RMSF were confirmed, all of which occurred in
first-degree relatives. Time spent at the family home and going into the
surrounding woods were significantly associated with developing antibodies to
Rickettsia rickettsii. Ticks were collected and examined for rickettsiae by
polymerase chain reaction analysis. Because hyperendemic foci and family
clusters of RMSF can occur, when a case is suspected clinicians should be
vigilant for signs and symptoms consistent with R. rickettsii infection in other
persons who may have been similarly exposed.
epidemiology of infectious myocarditis, lymphocytic myocarditis and dilated
Friman G, Wesslen L, Fohlman J, Karjalainen J, Rolf C
Eur Heart J Dec;16 Suppl O:36-41. 1995.
Borrelia burgdorferi infection is accompanied by cardiac involvement in 1-8% of
cases, where myocarditis with conduction disturbances is the most prominent
feature. ...Borrelia burgdorferi may occasionally be implicated in DCM. In this
contribution we focus also on sudden unexpected death (SUD) in young athletes,
since, in Sweden, an increased frequency of SUD has recently been observed in
young orienteers and myocarditis was a common feature.
Mountain spotted fever in the United States, 1997-2002.
Chapman AS, Murphy SM, Demma LJ, Holman RC, Curns AT, McQuiston JH, Krebs JW,
Vector Borne Zoonotic Dis. Summer;6(2):170-8. 2006 PMID: 16796514
Rocky Mountain spotted fever (RMSF) is the most commonly reported fatal
tick-borne disease in the United States.
clinical and epidemiological features of tick-borne encephalitis in Western
Int J Med Microbiol. May;296 Suppl 40:59-62. Epub Mar 9. 2006 PMID:
Severe progression and fatal outcomes of the disease have been recorded in all
Purification and crystallization of dengue and West Nile virus NS2B-NS3
D'Arcy A, Chaillet M, Schiering N, Villard F, Lim SP, Lefeuvre P, Erbel P.
Acta Crystallograph Sect F Struct Biol Cryst Commun. 2006 Feb 1;62(Pt
2):157-62. Epub Jan 27. 2006 PMID: 16511290
These viral infections are generally transmitted by mosquitoes, but may also be
tick-borne. Infection usually results in mild flu-like symptoms, but can also
cause encephalitis and fatalities.
Monitoring of tick-borne encephalitis virus populations and etiological
structure of morbidity over 60 years.
Vopr Virusol. May-Jun;50(3):7-13. 2005 PMID: 16078427
The Siberian and Far Eastern subtypes in the area of joint circulation were
found to cause the whole spectrum of infection manifestations from unapparent to
severe focal forms with a fatal outcome.
Golden Agers and Tick-borne encephalitis. Conference report and position paper
of the International Scientific Working Group on Tick-borne encephalitis.
Kunze U, Baumhackl U, Bretschneider R, Chmelik V, Grubeck-Loebenstein B,
Haglund M, Heinz F, Kaiser R, Kimmig P, Kunz C, Kunze M, Mickiene A,
Misic-Majerus L, Randolph S, Rieke B, Stefanoff P, Suss J, Wimmer R.
Wien Med Wochenschr.Jun;155(11-12):289-94. 2005 PMID: 16035390
The incidence of the disease is increasing with age, also the clinical course is
more severe, they suffer significantly more sequelae, need a longer
rehabilitation and have a higher case fatality.
Ehrlichia chaffeensis (Rickettsiales: Ehrlichieae) infection in Amblyomma
americanum (Acari: Ixodidae) at Aberdeen Proving Ground, Maryland.
Stromdahl EY, Randolph MP, O'Brien JJ,Gutierrez AG.
J Med Entomol. May;37(3):349-56. 2000 PMID: 15535577
Human monocytic ehrlichiosis (HME) is a sometimes fatal, emerging tick-borne
disease caused by the bacterium Ehrlichia chaffeensis.
spotted fever rickettsiosis, Kenya.
Rutherford JS, Macaluso KR, Smith N, Zaki SR, Paddock CD, Davis J, Peterson
N, Azad AF, Rosenberg R.
Emerg Infect Dis. May;10(5):910-3 2004 PMID: 15200829
We report a fatal case of rickettsiosis in a woman from the United States living
in Kenya, who had a history of tick exposure.
Physician knowledge of the diagnosis and management of Rocky Mountain spotted
fever: Mississippi, 2002.
O'Reilly M, Paddock C, Elchos B, Goddard J, Childs J, Currie M.
Ann N Y Acad Sci. Jun;990:295-301. 2003 PMID: 12860642
RMSF has a high case fatality rate among untreated individuals, and the median
time from onset of symptoms to death is only eight days, making early
recognition and treatment of RMSF crucial.
Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105
de Sousa R, Nobrega SD, Bacellar F, Torgal J.
Ann N Y Acad Sci. Jun;990:285-94. 2003 PMID: 12860641
Although recognized as a benign acute disease and treated mainly with ambulatory
procedures, some cases are severe and fatalities have increased in the last few
years. In 1997, MSF mortality became more evident in Beja, a Portuguese southern
district, with a case fatality rate of 32.3% in hospitalized patients.
Tick-borne encephalitis with hemorrhagic syndrome, Novosibirsk region, Russia,
Ternovoi VA, Kurzhukov GP, Sokolov YV, Ivanov GY, Ivanisenko VA, Loktev AV,
Ryder RW, Netesov SV, Loktev VB.
Emerg Infect Dis. Jun;9(6):743-6. 2003 PMID: 12781020
Eight fatal cases of tick-borne encephalitis with an unusual hemorrhagic
syndrome were identified in 1999 in the Novosibirsk Region, Russia.
diagnosis of Ehrlichia chaffeensis in patients with fatal ehrlichiosis by use of
immunohistochemistry, in situ hybridization, and polymerase chain reaction.
Dawson JE, Paddock CD, Warner CK, Greer PW, Bartlett JH, Ewing SA, Munderloh
UG, Zaki SR.
Am J Trop Med Hyg. Nov;65(5):603-9. 2001 PMID: 11716122
In the United States, human ehrlichiosis is a complex of emerging tick-borne
diseases caused by 3 distinct Ehrlichia species: Ehrlichia chaffeensis,
Ehrlichia ewingii, and the human granulocytotropic ehrlichiosis agent.
Ehrlichioses are characterized by a mild to severe illness, and approximately 4%
of cases are fatal.
babesiosis: an emerging tick-borne disease.
Kjemtrup AM, Conrad PA.
Int J Parasitol. Nov;30(12-13):1323-37. 2000 PMID: 11113258
This parasite is closely related to babesial parasites isolated from large wild
ungulates in California. Like B. microti, WA1-type parasites cause mild to
severe disease and the immunopathogenesis of these parasites is distinctly
different from each other in experimental infections of hamsters and mice. A B.
divergens-like parasite was also identified as the cause of a fatal human
babesiosis case in Missouri.
Babesiosis in Wisconsin: a potentially fatal disease.
Herwaldt BL, Springs FE, Roberts PP, Eberhard ML, Case K, Persing DH, Agger
Am J Trop Med Hyg. Aug;53(2):146-51. 1995 PMID: 7677215
Three cases (30% of 10) we now report were fatal and occurred in elderly
patients (65-75 years old) who died after complicated hospital courses� Medical
personnel should be knowledgeable about this zoonosis, which is not limited to
the northeastern United States, and is potentially serious, sometimes fatal.
Human Babesiosis in New York State: Review of 139
Hospitalized Cases and Analysis of Prognostic Factors.
Dennis J. White, PhD; John Talarico, DO; Hwa-Gan
Chang, MS; Guthrie S. Birkhead, MD, MPH; Tracey Heimberger, MD; Dale L.
Morse, MD, MS
Arch Intern Med. 1998;158:2149-2154.
Babesiosis infections are
infrequent, occur in limited geographic locations, and range from
asymptomatic infection to severe illness and death. The most common signs
and symptoms on admission were nonspecific symptoms of
fatigue/malaise/weakness (91.2%), fever (90.6%), shaking chills (76.6%),
diaphoresis (69.2%), and nausea/anorexia (57.3%) (Table
2). Clinical findings on physical examination included
temperature higher than 38�C (55.8%), heart murmur (20.1%), hepatomegaly
(14.4%), and splenomegaly (10.8%). Only 6 patients (4.3%) had jaundice
listed. A review of medical records indicated that 51.8% had a history of
chronic disease, 11.9% had a history of Lyme disease, and 11.7% had
undergone splenectomies. No patient had evidence of human immunodeficiency
virus infection. More than one third (37.5%) of the patients reported
having a tick bite within 30 days prior to their hospitalization.
patients (38.8%) had some type of complication (Table
4). Congestive heart failure (n=15, 10.9%) and acute
respiratory distress syndrome (n=11, 8.0%) were the most common
complications. Nine patients died during hospitalization, for a fatality
rate of 6.5%. The death certificate analysis identified 29 patients who
died from 1982-1995.
Mountain spotted fever in an endemic area in Minas Gerais, Brazil.
de Lemos ER, Machado RD, Coura JR.
Mem Inst Oswaldo Cruz. Oct-Dec;89(4):497-501. 1994 PMID: 8524052
In order to obtain information on tick-borne rickettsiosis, a study was
performed in the County of Santa Cruz do Escalvado, State of Minas Gerais,
Brazil, where a fatal clinical case confirmed by specific immunofluorescence had
Human Granulocytic Ehrlichiosis (HGE) another Lyme Disease? A Comparison
of Clinical, Laboratory, and Epidemiologic Features.
J. Stephen Dumler, M.D.
has been diagnosed in about 100 patients so far - 4 have died.
ehrlichiosis: a newly recognized tick-borne disease.
Goldman DP, Artenstein AW, Bolan CD.
Am Fam Physician. Jul;46(1):199-208. 1992 PMID: 162163
Since then, more than 215 cases have been reported, including some fatalities.
Ehrlichia species belong to the same family as the organism that causes Rocky
Mountain spotted fever.
location of the infecting tick bite and the severity of the course of tick-borne
Okulova NM, Chunikhin SP, Vavilova VE, Maiorova AD.
Med Parazitol (Mosk). Sep-Oct;(5):78-85. 1989 PMID: 2615717
�fatal outcomes are most frequent in case of the bites in the axilla, arms
(14-16%), head and neck (11.2%), and less frequent in case of the bites in the
lower limbs (5.9%) and groin (0).
case of tick-borne encephalitis with a fatal outcome.
Shasaitov ShSh, Chartorizhskii NA, Smekalov VP.
Sov Med. Jun;(6):146. 1978 PMID: 675340
Concurrent Babesiosis and Ehrlichiosis in an
Muhammad Z. Javed, MD; Manjul Srivastava, MD; Shengle Zhang, MD;
Mathew Kandathil, MD
Mayo Clin Proc. 2001 May;76(5):563-5. PMID: 11357805
An 85-year-old man,
actively infected with Babesia microti and Ehrlichia chaffeensis,
presented with fatigue and thrombocytopenia. He developed rhabdomyolysis
and multiple organ failure, which led to death 6 days after initial
presentation. To our knowledge, concurrent acute disease due to these 2
organisms has not been reported previously, although serologic studies
have shown that some patients acquire both infections in life.
Babesosis--difficulty of diagnosis.
Cichocka A, Skotarczak B.
Wiad Parazytol.;47(3):527-33. 2001 PMID: 16894770
Clinical manifestation varied widely from asymptomatic infection to a serve
rapidly fatal disease.
Med Clin North Am. Mar;86(2):361-73. 2002 PMID: 11982307
Those at greatest risk of fatal disease include individuals older than age 50
years; asplenic individuals; and immunocompromised individuals as a result of
immunosuppressive drugs, malignancy, or HIV infection.
souvenirs: inoculation pathologies (cutaneous larva migrans, cutaneous
leishmaniases, Lyme disease, rickettsioses).
Rev Med Brux. Sep;21(4):A257-65. 2000 PMID: 11068477
If untreated this infection may expose to chronic debilitating rheumatologic,
cardiac and neurological complications. Rickettsiosis, especially boutonneuse
fever, are a potentially fatal multisystemic infectious diseases transmitted
through the bite of a dog tick.
Tick-borne encephalitis: possibly a fatal disease in its acute stage. PCR
amplification of TBE RNA from postmortem brain tissue.
Tomazic J, Poljak M, Popovic P, Maticic M, Beovic B, Avsic-Zupanc T, Lotric
S, Jereb M, Pikelj F, Gale N.
Infection. Jan-Feb;25(1):41-3. 1997 PMID: 9039538
Tick-borne encephalitis has occurred regularly in Europe since it was first
diagnosed in 1931 by Schneider. The mortality rate of patients with this disease
is 1-2%. Death usually occurs in the acute stage of illness. A case report of a
28-year-old patient from Slovenia, who died shortly after the onset of
tick-borne encephalitis, is described. The clinical course of disease, results
of serological tests, neuropathological findings and polymerase chain reaction
amplification of parts of viral genome from postmortem brain tissues are
A Fatal Case of Babesiosis in Missouri:
Identification of Another Piroplasm That Infects Humans
Barbara L. Herwaldt, MD, MPH; David H. Persing, MD, PhD; Eric A.
Precigout, PhD; W. L. Goff, PhD; Dane A. Mathiesen, BS; Philip W. Taylor,
MD; M. L. Eberhard, PhD; and Andre F. Gorenflot, PhD
Ann Intern Med. 1996 Apr 1;124(7):643-50.
A 73-year-old man who had had a splenectomy and had a
fatal case of babesiosis.
Although MO1 is probably
distinct from B. divergens, the two share morphologic, antigenic, and
genetic characteristics; MO1 probably represents a Babesia species not
previously recognized to have infected humans. Medical personnel should be
aware that patients in the United States can have life-threatening
babesiosis even though they are seronegative to B. microti and WA1
microti, human babesiosis, and Borrelia burgdorferi in Connecticut.
Anderson JF, Mintz ED, Gadbaw JJ, Magnarelli LA.
J Clin Microbiol. Dec;29(12):2779-83. 1991 PMID: 1757548
Two patients died with active infections, and one patient died from chronic
obstructive pulmonary disease soon after treatment with clindamycin and quinine.
A fatal case of human babesiosis in Portugal:
molecular and phylogenetic analysis.
Centeno-Lima S, do Ros�rio V, Parreira R, Maia AJ, Freudenthal AM,
Nijhof AM, Jongejan F.
Trop Med Int Health. 2003 Aug;8(8):760-4. PMID: 12869099
We report the first case
of human babesiosis in Portugal. A 66-year-old splenectomized man was
admitted to a Lisbon hospital after 1 week of fever, abdominal pain,
anorexia and nausea. A high parasitaemia (30%) of Babesia parasites was
found in Giemsa-stained blood smears and, despite treatment, the patient
died several weeks later of renal failure. Ethylenediaminetetraacetic acid
blood samples were processed for polymerase chain reaction (PCR) and
reverse line blot hybridization to confirm and characterize the Babesia
infection. The amplified PCR product was cloned and subsequently
sequenced. Molecular analysis showed that the infection was caused by
Babesia divergens and that other blood parasites were not involved.
Phylogenetic analysis showed that the 18 S ribosomal RNA gene sequence was
similar to three other European isolates of B. divergens. In view of the
high risk for splenectomized individuals, strict measures should be taken
to avoid tick bites.
surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary
and evaluation of risk factors for fatal outcome.
Dalton MJ, Clarke MJ, Holman RC, Krebs JW, Fishbein DB, Olson JG, Childs JE.
Am J Trop Med Hyg. May;52(5):405-13. 1995 PMID: 7771606
The case-fatality ratio was 4.0%.
The possible role of ticks as vectors of leptospirae.
Exp Parasitol. 1956 Nov;5(6):571-9. PMID: 13375683
of Leptospira pomona by the argasid tick, Ornithodoros turicata, and the
persistance of this organism in its tissues.
Scrub typhus and tropical rickettsioses.
Watt G, Parola P.
Curr Opin Infect Dis. 2003 Oct;16(5):429-36. PMID: 14501995
Department of Retrovirology, Armed Forces Research Institute of Medical
Sciences, Bangkok, Thailand.
Recent developments in molecular taxonomic methods have led to a
reclassification of rickettsial diseases. The agent responsible for scrub typhus
(Orientia tsutsugamushi ) has been removed from the genus Rickettsia and a
bewildering array of new rickettsial pathogens have been described. An update of
recent research findings is therefore particularly timely for the nonspecialist
physician. An estimated one billion people are at risk for scrub typhus and an
estimated one million cases occur annually. The disease appears to be
re-emerging in Japan, with seasonal transmission. O. tsutsugamushi has evolved a
variety of mechanisms to remain viable in its intracellular habitat. Slowing the
release of intracellular calcium inhibits apoptosis of macrophages. Subsets of
chemokine genes are induced in infected cells, some in response to transcription
factor activator protein 1. Cardiac involvement is uncommon and clinical
complications are predominantly pulmonary. Serious pneumonitis occurred in 22%
of Chinese patients.
infections with leptospirosis have been reported. Standardized diagnostic tests
are being developed and attempts to improve treatment of women and children are
being made. Of the numerous tick-borne rickettsioses identified in recent years,
African tick-bite fever appears to be of particular importance to travellers.
The newly described flea-borne spotted fever caused by Rickettsia felis may be
global in distribution. Rash and fever in a returning traveler could be
rickettsial and presumptive doxycycline treatment can be curative. Recent
research findings raise more questions than answers and should stimulate much
Features Symptoms include fever, headache, chills, muscle aches, vomiting,
jaundice, anemia, and sometimes a rash. The incubation period usually is 7 days,
with a range of 2-29 days. If not treated, the patient could develop kidney
damage, meningitis, liver failure, and respiratory distress. In rare cases,
Rocky Mountain Spotted
Fever caused by blood transfusion.
Wells GM, Woodward TE, Fiset P, Hornick RB.
JAMA. 1978 Jun 30;239(26):2763-5 PMID: 418193
Transfusion of 500 ml of blood, contributed by a donor three days before the
onset of Rocky Mountain spotted fever and refrigerated for nine days, caused
this disease in the recipient.
The blood donor died of Rocky Mountain spotted fever after six days; rickettsia
were identified in various tissues by immunofluorescence techniques.
The recipient of the blood became mildly ill and recovered fully; specific
antibiotic treatment was initiated on the fourth day of illness. Diagnosis of
Rocky Mountain spotted fever was confirmed in the recipient by positive
serologic reactions and isolation of Rickettsia rickettsii from blood after
inoculation in animals and tissue culture.
Fatal seronegative human
ehrlichiosis in a patient with human immunodeficiency virus disease.
Paddock C, Suchard D, Hadley WK, Kerschmann R, Grumbach K, Dawson J,
Dumler JS, Anderson B, Sims K, Herndier B.
Abstr Gen Meet Am Soc Microbiol.
1993; 93: 110 (abstract no. D-87).
The first confirmed case of disease due to
Ehrlichia chaffeensis occurring in a patient with human immunodeficiency
virus type 1 (HIV-1) is reported. A 42 year-old Arkansas woman with HIV-1
disease (CD4 lymphocyte count = 64 cells per cmm) died of pulmonary
hemorrhage approximately 2 weeks following acute onset of a febrile
illness characterized by pancytopenia, particularly rapidly progressive
thrombocytopenia, and elevated hepatic aminotransferase levels.
Intracytoplasmic ehrlichial morulae were identified within mononuclear
cells from a bone marrow biopsy obtained shortly prior to death.
At autopsy, ehrlichiae were identified by
electron microscopy within bone marrow leukocytes and by an
immunoperoxidase stain for Ehrlichia in leukocytes of the bone marrow,
lung, spleen and lymph nodes. Distinct histopathological lesions included
depletion and destruction of periarteriolar splenic lymphocytes with
replacement by nodular histiocytic aggregates; focal lymph node necrosis;
hemophagocytosis of erythrocytes in the bone marrow; and extensive
alveolar hemorrhage within the lungs. Polymerase chain reaction techniques
using probes to the 16S rRNA gene of E. chaffeensis revealed E.
chaffeensis DNA in a sample of the patient's blood, although an antibody
titer to Ehrlichia was absent by indirect fluorescent antibody testing.
Given the potential for absence of a diagnostic serologic response, a high
index of suspicion for human ehrlichiosis should be maintained in HIV-1
patients from endemic areas of E. chaffeensis who present acutely with
fever and hematologic cytopenias.
Central nervous system manifestations of human
Ratnasamy N, Everett ED, Roland WE, McDonald G, Caldwell CW.
Clin Infect Dis. 1996 Aug;23(2):314-9. PMID: 8842270
Since 1989, we have
confirmed the diagnosis of human ehrlichiosis in 57 patients. Although
routine radiological studies of the central nervous system (CNS) or
analyses of cerebrospinal fluid (CSF) samples were not done for these
patients, primary care physicians detected symptoms or signs that prompted
them to perform such studies. CSF samples were examined for 15 of the 57
patients. Findings in eight of the 15 CSF samples were abnormal, and the
most common abnormalities were lymphocytic pleocytosis and elevated
protein levels. A search of the English-language literature revealed 21
additional cases in which CSF examinations were performed; in 13 of these
cases, CSF findings were abnormal. The most common clinical finding that
predicted CSF abnormalities was a change in mental status. A total of 14
patients underwent computerized tomographic studies, and none of these
studies showed abnormalities. Four (19%) of the 21 patients with CNS
manifestations of ehrlichiosis and abnormal CSF findings died.
Infections with Ehrlichia chaffeensis and
Ehrlichia ewingii in persons coinfected with human immunodeficiency virus.
Paddock CD, Folk SM, Shore GM, Machado LJ, Huycke MM, Slater LN,
Liddell AM, Buller RS, Storch GA, Monson TP, Rimland D, Sumner JW,
Singleton J, Bloch KC, Tang YW, Standaert SM, Childs JE.
Clin Infect Dis. 2001 Nov 1;33(9):1586-94. Epub 2001 Sep 24. PMID:
The clinical course and
laboratory evaluation of 21 patients coinfected with human
immunodeficiency virus (HIV) and Ehrlichia chaffeensis or Ehrlichia
ewingii are reviewed and summarized, including 13 cases of ehrlichiosis
caused by E. chaffeensis, 4 caused by E. ewingii, and 4 caused by either
E. chaffeensis or E. ewingii. Twenty patients were male, and the median
CD4(+) T lymphocyte count was 137 cells/microL.
Exposures to infecting
ticks were linked to recreational pursuits, occupations, and peridomestic
activities. For 8 patients, a diagnosis of ehrlichiosis was not considered
until > or =4 days after presentation. Severe manifestations occurred more
frequently among patients infected with E. chaffeensis than they did among
patients infected with E. ewingii, and all 6 deaths were caused by E.
chaffeensis. Ehrlichiosis may be a life-threatening illness in
HIV-infected persons, and the influence of multiple factors, including
recent changes in the epidemiology and medical management of HIV
infection, may increase the frequency with which ehrlichioses occur in
this patient cohort.
Tissue diagnosis of Ehrlichia chaffeensis in
patients with fatal ehrlichiosis by use of immunohistochemistry, in situ
hybridization, and polymerase chain reaction.
Dawson JE, Paddock CD, Warner CK, Greer PW, Bartlett JH, Ewing SA,
Munderloh UG, Zaki SR.
Am J Trop Med Hyg. 2001 Nov;65(5):603-9. PMID: 11716122
In the United States,
human ehrlichiosis is a complex of emerging tick-borne diseases caused by
3 distinct Ehrlichia species: Ehrlichia chaffeensis, Ehrlichia ewingii,
and the human granulocytotropic ehrlichiosis agent. Ehrlichioses are
characterized by a mild to severe illness, and approximately 4% of cases
are fatal. Because these obligate intracellular bacteria are difficult to
resolve with routine histologic techniques, their distribution in tissues
has not been well described. To facilitate the visualization and detection
of ehrlichiae, immunohistochemistry (IHC), in situ hybridization (ISH),
and polymerase chain reaction (PCR) assays were developed by use of
tissues from 4 fatal cases of E. chaffeensis infection. Evidence of E.
chaffeensis via IHC, ISH, and PCR was documented in all 4 cases. Abundant
immunostaining and in situ nucleic acid hybridization were observed in
spleen and lymph node from all 4 patients. Significantly, in 2 of these
patients, serologic evidence of infection was absent. Use of IHC, ISH, and
PCR to visualize and detect Ehrlichia in tissues can facilitate diagnosis
of ehrlichial infections.
Severe Ehrlichia chaffeensis infection in a lung
transplant recipient: a review of ehrlichiosis in the immunocompromised
Safdar N, Love RB, Maki DG.
Emerg Infect Dis. 2002 Mar;8(3):320-3. PMID: 11927032
We describe a case of
human ehrlichiosis in a lung transplant recipient and review published
reports on ehrlichiosis in immunocompromised patients. Despite early
therapy with doxycycline, our patient had unusually severe illness with
features of thrombotic thrombocytopenic purpura. Of 23 reported cases of
ehrlichiosis in immunocompromised patients, organ failure occurred in all
patients and 6 (25%) died.
Rapidly Fatal Infection with Ehrlichia
Martin GS, Christman BW, Standaert SM.
N Engl J Med. 1999 Sep 2;341(10):763-4. PMID: 10475799
infections are increasingly being recognized as common tick-borne diseases
in the United States. Clinical characteristics of ehrlichiosis include
fever, headache, and malaise with leukopenia, thrombocytopenia, and
elevated levels of hepatic aminotransferases. In rare instances, infection
may result in multiple organ failure and death, particularly in
immunosuppressed patients. Despite the potential severity of disease,
death is uncommon in normal human hosts. We report two cases of rapidly
fatal Ehrlichia chaffeensis infection in patients who presented to our
institution in early June.
Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and
Marty AM, Dumler JS, Imes G, Brusman HP, Smrkovski LL, Frisman DM.
Hum Pathol. 1995 Aug;26(8):920-5. PMID: 7635455
Human ehrlichiosis is a
tick-borne zoonosis caused by the newly described human hematotropic
rickettsiae, Ehrlichia chaffeensis. The pathology and pathogenesis of
human ehrlichiosis have not been adequately studied. Even with
immunoperoxidase, the only previously known method to detect these
organisms in tissue, ehrlichae are difficult or impossible to identify.
This led many investigators to speculate that the pathogenesis of
ehrlichiosis was not caused directly by the organism but could be caused
by host-mediated injury. In this case study, a patient presented with
rapidly progressive central nervous system symptoms and severe
thrombocytopenia, prompting a presumptive diagnosis of thrombotic
thrombocytopenic purpura (TTP). Despite corticosteroids, and later,
antibiotics, the patient rapidly deteriorated and died.
showed hemorrhages in multiple organs and mononuclear inclusions of
infection with a monocytic ehrlichia. Other findings included widespread
lymphohistiocytic perivascular infiltrates, focal hepatic necroses,
interstitial pneumonitis, interstitial nephritis, mononuclear phagocyte
invasion and proliferation in splenic, liver, and bone marrow, and
hemophagocytosis. The diagnosis was proven by serology, immunohistology
with both polyclonal and monoclonal anti E chaffeensis, and polymerase
chain reaction on paraffin-embedded tissues using E chaffeensis-specific
oligonucleotide primers. The presence of numerous ehrlichia with notable
tissue and cellular injury but without a marked host response indicate
that unlike other cases of documented human ehrlichiosis, this patient
died after significant direct ehrlichia-mediated injury, and that immune
mechanisms initiated after ehrlichiosis played little if any role in the
and treatment of human granulocytotropic anaplasmosis.
Bakken JS, Dumler JS.
Ann NY Acad Sci. 2006 Oct;1078:236-47.
Tick-borne rickettsiae in
the genera Ehrlichia and Anaplasma are intracellular bacteria that infect
wild and domestic mammals and, more recently, man. The increased desire of
humans for recreational activities outdoors has increased the exposure to
potential human pathogens that previously cycled almost exclusively within
natural, nonhuman enzootic hosts. Anaplasma phagocytophilum causes an
acute, nonspecific febrile illness of humans previously known as human
granulocytotropic ehrlichiosis (HGE) and now called human
granulocytotropic anaplasmosis (HGA).
diagnosis in older and immunocompromised patients may place those
individuals at risk for an adverse outcome, including death. Thus, prompt
institution of antibiotic therapy is advocated for any patient who is
suspected to have HGA and for all patients who have confirmed HGA.
Rickettsia helvetica: an emerging tick-borne pathogen in Hungary and
Sreter T, Sreterne Lancz Z, Szell Z, Egyed L.
Orv Hetil. 2005 Dec 11;146(50):2547-52.
belonging to spotted fever group rickettsiae was recently detected by
polymerase chain reaction followed by sequencing in European sheep ticks
(Ixodes ricinus) from Hungary. Current knowledge on these rickettsiae and
the clinical and diagnostic aspects of R. helvetica infection is
summarized. In acute cases, R. helvetica is generally responsible for
flu-like symptoms. Nevertheless, recent data indicate that in chronic
cases, these rickettsiae can be responsible for perimyocarditis resulting
sudden cardiac death and might play a role in the pathogenesis of aortic
Meningovascular form of Neuroborreliosis:
similarities between neuropathological findings in a case of Lyme disease
and those occurring in tertiary neurosyphilis.
Miklossy J, Kuntzer T, Bogousslavsky J, Regli F, Janzer RC.
University Institute of Pathology, Division of Neuropathology, Lausanne,
Acta Neuropathol (Berl). 1990;80(5):568-72. PMID: 2251916
Recent observations have
delineated the neurological manifestations of Lyme disease, but, to our
knowledge, no detailed neuropathological study from autopsy cases has been
reported. In this report we describe the neuropathological findings in a
case of Lyme neuroborreliosis. The chronic meningitis, the occlusive
meningovascular and secondary parenchymal changes that we found are
similar to those occurring in the meningovascular form of neurosyphilis.
Thus, we suggest that the case described here represents the
meningovascular form of tertiary Lyme neuroborreliosis.
Natural Infection of the Tick, Amblyomma Cajennense, with Rickettsia
Rickettsii in Panama.
Enid C. de Rodaniche.
Am. J. Trop. Med. Hyg., 2(4), 1953, pp. 696-699
The occurrence of Rocky Mountain spotted fever on the Isthmus of
Panama was established for the first time in 1950 when a highly virulent
strain of Rickettsia rickettsii was isolated by the author from the blood
of a 26 year old Panamanian farmer who died February 8 of that year,
shortly after admission to the hospital. The patient evidently had
contracted his infection near the town of Ollas Arriba about seven miles
north of Capira in the Province of Panama.
Since then similarly
virulent strains of R. rickettsii have been isolated from two additional
cases, hospitalized in May 1950 and February 1951, both male, aged 13 and
26 years respectively, who were employed in agricultural work on farms
located in the same area as the previous case. The 13-year old boy died.
The 26-year old man survived after a severe and protracted illness. His
blood showed complement-fixing antibodies against Rocky Mountain spotted
fever antigen in high titer during convalescence.
Fatal meningitis and
encephalitis due to Bartonella henselae bacteria.
Gerber JE, Johnson JE, Scott MA, Madhusudhan KT.
J Forensic Sci. 2002 May;47(3):640-4. PMID: 12051353
Bacterial infection due
to Bartonella henselae commonly develops in children and young adults
following cat/dog contacts and/or cat/dog scratches. Regional
lymphadenopathy is its most common clinical expression. However,
encephalitis and Parinaud's syndrome (oculoglandular syndrome) have also
been reported as has systemic illness. A review of the international
literature in all languages revealed no fatal complications in
immunocompetent hosts. A four-year-old white child with no underlying
illness began to have seizure-like activity. She was taken to a local
hospital and subsequently transferred to a medical center. The child was
treated aggressively for seizures and fever of unknown origin. However,
her condition rapidly declined and she died without a specific diagnosis.
At autopsy there was marked cerebral edema with no gross evidence of acute
meningitis. Microscopic exams revealed multiple granulomatous lesions as
well as a meningitis and encephalitis. A variety of cultures and stains
were negative for acid fast and fungal organisms. Warthin-Starry stains of
involved tissue including brain and liver revealed pleomorphic rod shaped
bacilli consistent with Bartonella henselae. Analysis of brain tissue with
polymerase chain reaction (PCR) and Southern blot for the deoxyribonucleic
acid (DNA) was definitive for DNA of Bartonella henselae bacteria.
Diagnosis of 22 new cases of Bartonella
Raoult D; Fournier PE; Drancourt M; Marrie TJ; Etienne J; Cosserat J;
Cacoub P; Poinsignon Y; Leclercq P; Sefton AM
Ann Intern Med 1996 Oct 15;125(8):646-52. PMID- 8849149
22 patients had definite
endocarditis. Five were infected with B. quintana, 4 with B. henselae, and
13 with an undetermined Bartonella species. These cases were compared with
the 11 previously reported cases. Of the patients with the newly reported
cases, 19 had valvular surgery and 6 died.
Outcome and treatment of Bartonella endocarditis.
Raoult D; Fournier PE; Vandenesch F; Mainardi JL; Eykyn SJ; Nash J;
James E; Benoit-Lemercier C; Marrie TJ
Arch Intern Med 2003 Jan 27;163(2):226-30.
Endocarditis caused by
Bartonella species is a potentially lethal infection characterized by a
subacute evolution and severe valvular lesions. We performed a
retrospective study on 101 patients who were diagnosed in our laboratory
as having Bartonella endocarditis between January 1, 1995, and April 30,
2001. Bartonella infection was diagnosed using immunofluorescence with a
1:800 cutoff, polymerase chain reaction amplification of DNA, and/or
culture findings of Bartonella species from whole blood, serum, and/or
valvular biopsy specimens. A standardized questionnaire was completed by
investigators for each patient. Twelve of the 101 patients died and 2
Gestational Lyme borreliosis. Implications for the fetus.
Rheum Dis Clin North Am, 15(4):657-77. 1989.
Autopsy and clinical studies have associated gestational Lyme borreliosis with
various medical problems including fetal death, hydrocephalus, cardiovascular
anomalies, neonatal respiratory distress, hyperbilirubinemia, intrauterine
growth retardation, cortical blindness, sudden infant death syndrome, and
maternal toxemia of pregnancy.
burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during
Weber K, Bratzke HJ, Neubert U, Wilske B, Duray PH.
Pediatric Infectious Disease Journal, 7:286-9. 1988.
Congenital infections and the nervous
Bale JF Jr, Murph JR.
Pediatr Clin North Am Aug;39(4):669-90 1992
Despite vaccines, new antimicrobials, and improved hygienic practices,
congenital infections remain an important cause of death and long-term
neurologic morbidity among infants world-wide. In addition, several other
agents, such as the varicella zoster virus, human parvovirus B19, and Borrelia
burgdorferi, can potentially infect the fetus and cause adverse fetal outcomes.
Maternal-fetal transmission of
the Lyme disease spirochete, Borrelia burgdorferi.
Schlesinger PA, Duray PH, Burke BA, Steere AC, Stillman MT.
Ann Intern Med.
1985 Jul;103(1):67-8. PMID: 4003991
We report the case of a
woman who developed Lyme disease during the first trimester of pregnancy.
She did not receive antibiotic therapy. Her infant, born at 35 weeks
gestational age, died of congenital heart disease during the first week of
life. Histologic examination of autopsy material showed the Lyme disease
spirochete in the spleen, kidneys, and bone marrow.
positive seronegative transplacental Lyme borreliosis infant mortality.
Lavoie PE, Lattner BP, Duray PH, Barbour AG, Johnson HC.
Arthritis Rheum, Vol 30 No 4, 3(Suppl):S50. 1987.
infection by Borrelia burgdorferi (Bb), the agent of Lyme Borreliosis (LB), has
recently been documented (L.E. Markowitz, et al; P.A. Schlesinger, et al). Fetal
infection confirmed by culture has been reported by A.B. MacDonald (in press)
from a highly endemic region (Long Island, NY).
We report a culture positive neonatal death occurring in California, a low
endemic region. The boy was born by C-section because of fetal distress. He
initially appeared normal. He was readmitted at age 8 days with profound
lethargy leading to unresponsiveness. Marked peripheral cyanosis, systemic
hypertension, metabolic acidosis, myocardial dysfunction, & abdominal aortic
thrombosis were found. Death ensued. Bb was grown from a frontal cerebral cortex
inoculation. The spirochete appeared similar to the original Long Island tick
isolate. Silver stain of brain & heart was confirmatory of tissue infection.
The infant was the second born to a California native. The 20 m/o sibling was
well. The mother had been having migratory arthralgias and malaise since
experiencing horse fly & mosquito bites while camping on the Maine coast in
1971. The family was seronegative for LB by ELISA at Yale. Cardiolipin
antibodies were also not found."
Stillbirth following maternal Lyme
MacDonald AB, Benach JL, Burgdorfer W.
N Y State J Med, Nov;87(11):615-6 1987
The infectious origins of stillbirth.
Goldenberg RL, Thompson C.
Am J Obstet Gynecol. 2003 Sep; 189(3):861-73. 2003. PMID: 14526331
Toxoplasma gondii, leptospirosis, Listeria monocytogenes, and the organisms that
cause leptospirosis, Q fever, and Lyme disease have all been implicated as
etiologic for stillbirth.
Lyme disease during pregnancy.
Markowitz LE, Steere AC, Benach JL, Slade JD, Broome CV.
JAMA Jun 27;255(24):3394-6. 1986.
Of the 19 pregnancies, five had adverse outcomes, including syndactyly,
cortical blindness, intrauterine fetal death, prematurity, and rash in the
newborn. Adverse outcomes occurred in cases with infection during each of the
trimesters. Although B burgdorferi could not be implicated directly in any of
the adverse outcomes, the frequency of such outcomes warrants further
surveillance and studies of pregnant women with Lyme disease.
Human fetal borreliosis, toxemia of
pregnancy, and fetal death.
Zentralbl Bakteriol Mikrobiol Hyg [A]. Dec; 263(1-2):189-200. 1986. PMID:
Tick-borne relapsing fever and
pregnancy outcome in rural Tanzania.
Jongen VH, van Roosmalen J, Tiems J, Van Holten J, Wetsteyn JC.
Acta Obstet Gynecol Scand. Oct; 76(9):834-8. 1997. PMID: 9351408
impact of tick-borne relapsing fever (TBRF) on pregnancy outcome was
investigated in a case-control study of 137 pregnant women and 120 non-pregnant
women infected with this condition and treated at a rural hospital in Tanzania's
Tabora region during 1985-95. The risk of premature delivery during TBRF was
58%, with a perinatal mortality of 436 per 1000 births. Total pregnancy loss,
including abortions, was 475 per 1000. The case-fatality rate was 1.5% in
pregnant women compared with 1.7% in non-pregnant controls. The relapse rate was
3.6% in pregnant women and 1.7% in controls. Pregnant women with TBRF had higher
densities of spirochetes than controls, and the risk of delivery during an
attack was significantly correlated with increasing spirochete density and
Infections in Obstetrics: Lyme disease during Pregnancy
Helayne M. Silver, MD
Infectious Disease Clinics of North America Vol 11 Number 1 1 March,
The infant had severe
congenital cardiac defects resulting in neonatal death at 39 hours of
life. The neonatal autopsy revealed hypoplastic left side of heart and
other cardiac anomalies. Spirochetes compatible with B. burgdorferi were
found in the spleen, kidneys, and bone marrow; however, no inflammatory
response to the organisms was seen.
Complications of pregnancy and transplacental
transmission of relapsing-fever borreliosis.
Larsson C, Anderson M, Guo BP, Nordstrand A, Hagerstrand I, Carlsson
S, Bergstrom S.
J Infect Dis. 2006 Nov 15;194(10):1367-74. Epub 2006 Oct 3. PMID:
borreliosis caused by Borrelia duttonii is a common cause of complications
of pregnancy, miscarriage, and neonatal death in sub-Saharan Africa.
Morphologic, immunohistochemical, and
ultrastructural characterization of a distinctive renal lesion in dogs
putatively associated with Borrelia burgdorferi infection: 49 cases (1987-1992).
Dambach DM, Smith CA, Lewis RM, Van Winkle TJ.
Vet Pathol, Mar;34(2):85-96. 1997.
A distinctive renal lesion consisting of glomerulonephritis, diffuse
tubular necrosis with regeneration, and interstitial inflammation was found in
49 biopsy/necropsy cases obtained from 1987 to 1992. This lesion is manifested
clinically as a rapidly progressive glomerular disease that was uniformly fatal.
...Previous reports have associated this lesion with Borrelia burgdorferi
exposure. All dogs in this study were from Lyme disease-endemic areas. Of 18
dogs serologically tested, all were positive for exposure. Silver stain
examination of kidneys revealed rare spirochetes, suggesting that the presence
of spirochetes in the kidney is apparently unrelated to lesion development. The
role of vaccination in development of the renal lesion is undetermined. The
association of this histologically and clinically unique lesion, Lyme nephritis,
with Borrelia burgdorferi infection is significant because it is the only fatal
form of canine Lyme borreliosis.
Fetal outcome in murine Lyme disease.
Silver RM, Yang L, Daynes RA, Branch DW, Salafia CM, Weis JJ.
Infect Immun. Jan; 63(1):66-72. 1995. PMID: 7806385
Histologic analysis of gestational tissues from infected animals
demonstrated nonspecific pathology consistent with fetal death. These findings
indicate an association between murine fetal death and acute infection with B.
burgdorferi early in gestation but not with chronic infection. Our data suggest
that fetal death is due to a maternal response to infection rather than fetal
infection. These findings could provide an explanation for observations in
humans in which sporadic cases of fetal death in women infected with B.
burgdorferi during pregnancy have been reported, while previous infection has
not been associated with fetal death.
Development and evaluation of a PCR
assay for the detection of Cytauxzoon felis DNA in feline blood samples.
Birkenheuer AJ, Marr H, Alleman AR, Levy MG, Breitschwerdt EB.
Vet Parasitol. Apr 15;137(1-2):144-9. 2006 Epub Jan 18. 2006
In naturally infected domestic cats the disease is almost always fatal.
Implications of presumptive fatal
Rocky Mountain spotted fever in two dogs and their owner.
Elchos BN,Goddard J.
J Am Vet Med Assoc. Nov 15;223(10):1450-2, 1433. 2003 PMID: 14627095
A dog was examined because of petechiation, an inability to stand, pale mucous
membranes, a possible seizure, and thrombocytopenia. Tick-borne illness was
suspected, but despite treatment, the dog died. Eight days later, a second dog
owned by the same individual also died. The dog was not examined by a
veterinarian, but Rocky Mountain spotted fever (RMSF) was suspected on the basis
of clinical signs. Two weeks after the second dog died, the owner was examined
because of severe headache, fever, nausea, vomiting, decreased appetite,
lethargy, and a fine rash on the body, face, and trunk. Despite intensive
treatment for possible RMSF, the owner died. Although results of an assay for
antibodies to Rickettsia rickettsii were negative, results of polymerase chain
reaction assays of liver, spleen, and kidney samples collected at autopsy were
positive for spotted fever group Rickettsia spp. These cases illustrate how dogs
may serve as sentinels for RMSF in humans and point out the need for better
communication between physicians and veterinarians when cases of potentially
zoonotic diseases are seen.
American canine hepatozoonosis.
Ewing SA, Panciera RJ.
Clin Microbiol Rev. Oct;16(4):688-97. 2003 PMID: 14557294
American canine hepatozoonosis (ACH) is a tick-borne disease that is spreading
in the southeastern and south-central United States. Characterized by marked
leukocytosis and periosteal bone proliferation, ACH is very debilitating and
Fatal cases of Tick-borne fever (TBF)
in sheep caused by several 16S rRNA gene variants of Anaplasma phagocytophilum.
Stuen S, Nevland S, Moum T.
Ann N Y Acad Sci. Jun;990:433-4. 2003 PMID: 12860670
A longitudinal study of disease
incidence and case-fatality risks on small-holder dairy farms in coastal Kenya.
Maloo SH, Rowlands GJ, Thorpe W, Gettinby G, Perry BD.
Prev Vet Med. Nov 2;52(1):17-29. 2001 PMID: 11566375
Cattle managed in the herded-grazing system had a 60% higher mortality, although
not significantly so, than those fed in stalls. Deaths due to ECF accounted for
over two-thirds of the deaths.
Animal model of fatal human
Sotomayor EA, Popov VL, Feng HM, Walker DH, Olano JP.
Am J Pathol. Feb;158(2):757-69. 2001 PMID: 11159213
Human monocytotropic ehrlichiosis caused by Ehrlichia chaffeensis is a
life-threatening, tick-borne, emerging infectious disease for which no
satisfactory animal model has been developed. Strain HF565, an ehrlichial
organism closely related to E. chaffeensis isolated from Ixodes ovatus ticks in
Japan, causes fatal infection of mice. C57BL/6 mice became ill on day 7 after
inoculation and died on day 9.
Spirochetemia caused by
Borrelia turicatae infection in 3 dogs in Texas.
Schwan TG, Sultemeier KB, McDonald PS, Brillhart MN.
Vet Clin Pathol. 2007 Jun;36(2):212-6 PMID: 17523100
Spirochetemia was diagnosed in 2 Siberian Huskies and a Rottweiler from the
northwestern region of Texas between June 1999 and October 2001. Clinical
findings were nonspecific; tick exposure was documented in 2 of the dogs.
Hematologic abnormalities included anemia (n=2), neutrophilia (n=2, including 1
with a left shift), lymphopenia (n=3), eosinopenia (n=3), and thrombocytopenia (n=2).
One anemic dog had a positive Coombs' test. In 1 dog, Western blot analysis of
serum yielded multiple positive bands with B turicatae lysate, indicating the
spirochetemia most likely was due to B turicatae infection. In 2 dogs,
spirochetes were cultured from the blood and identified using DNA analysis as
Borrelia turicatae; 1 of these dogs also was seropositive for Ehrlichia canis
and B burgdorferi. In 2 cases, spirochetemia was more prominent in blood smears
prepared immediately after sample collection than in smears prepared from EDTA
blood. Two dogs recovered with doxycycline treatment; 1 dog declined clinically
despite treatment and was euthanized.
B turicatae is the agent of tick-borne (endemic) relapsing fever in humans and
is distinct from B burgdorferi, the agent of Lyme disease; however, serologic
cross-reactivity may occur. B turicatae is transmitted by the soft tick,
Ornithodoros turicata, and infection should be considered in dogs with
spirochetemia and possible exposure to the tick vector.