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Lyme-associated parkinsonism: a neuropathologic case study and review of the literature.
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.

 

Central 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.

 

Borrelia burgdoferi-seropositive chronic encephalomyelopathy: Lyme neuroborreliosis? An autopsied report.
Kobayashi K, Mizukoshi C, Aoki T, Muramori F, Hayashi M, et al.
Dement Geriatr Cogn Disord, 8(6):384-90. 1997.

A 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.

A 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 this patient.

 

Fatal 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

An engorged 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.

Summer 1995 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 disease.

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.

Treatment 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.

The patient 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.

Seizures 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 leptomeningeal vessel

 

Rapidly 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.

 

Borrelia 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 Guillain-Barre syndrome.

 

Lyme disease acquired in Europe and presenting in CONUS.
Welker RD, Narby GM, Legare EJ, Sweeney DM.
Military Medicine, Oct 158(10):684-5. 1993.

Diagnosis 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.



Fatal 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.

 

Fatal 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.

 

Borrelia in the brains of patients dying with dementia.
MacDonald A.
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 N.
Department of Nuclear Medicine, Kanazawa University School of Medicine, Japan.
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 differential diagnosis.

 

Fatal 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: cardiac manifestations.
Sigal LH.
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.



Adverse 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.

 

Wildlife, Exotic 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 vectorborne.[1]  

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.[10] 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. 

As 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.[11]

 

Borrelial lymphocytoma--a historical case.
Sonck CE, Viljanen M, Hirsimaki P, Soderstrom KO, Ekfors TO.
APMIS. Oct; 106(10):947-52. 1998. PMID: 9833696

We here 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 Med
Aug 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.
Middleton DB.
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 Borrelia-index.
Melkert PW.  
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 treatment (2x).

 

Fatal-Jarisch Herxheimer reaction in a case of relapsing fever misdiagnosed as lobar pneumonia.
Melkert PW.
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.

 

Fatal pancarditis associated with human granulocytic Ehrlichiosis in a 44-year-old man.
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.

 

Human 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.

 

Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging?
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.

 

Hidden 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.

Rocky Mountain 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.

During 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 E. Eremeeva
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 America.

 

Family cluster of Rocky Mountain spotted fever.
Jones TF, Craig AS, Paddock CD, McKechnie DB, Childs JE, Zaki SR, Schaffner W.
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.

Fifty-four persons 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.

 

The epidemiology of infectious myocarditis, lymphocytic myocarditis and dilated cardiomyopathy.
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.

 

Rocky Mountain spotted fever in the United States, 1997-2002.
Chapman AS, Murphy SM, Demma LJ, Holman RC, Curns AT, McQuiston JH, Krebs JW, Swerdlow DL.
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.

 

Specific clinical and epidemiological features of tick-borne encephalitis in Western Siberia.
Poponnikova TV.
Int J Med Microbiol. May;296 Suppl 40:59-62. Epub  Mar 9. 2006 PMID: 16524768

Severe progression and fatal outcomes of the disease have been recorded in all age groups.

 

Purification and crystallization of dengue and West Nile virus NS2B-NS3 complexes.
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.
Pogodina VV.
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.

 

The 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.

 

Fatal 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 hospitalized patients.
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, 1999.
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.

 

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. 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.

 

Human 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 WA.
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.  

Fifty-four hospitalized 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.

 

Rocky 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 been reported.

 

Is Human Granulocytic Ehrlichiosis (HGE) another Lyme Disease? A Comparison of Clinical, Laboratory, and Epidemiologic Features.
J. Stephen Dumler, M.D.

HGE has been diagnosed in about 100 patients so far - 4 have died.

 

Human 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.

 

The location of the infecting tick bite and the severity of the course of tick-borne encephalitis.
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).

 

Repeated 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 Elderly Host.
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.

 

Babesiosis.
Krause PJ.
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.

 

Vacation souvenirs: inoculation pathologies (cutaneous larva migrans, cutaneous leishmaniases, Lyme disease, rickettsioses).
Tas S.
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 presented.

 

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 antigen.

 

Babesia 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.

 

National 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.

Burgdorfer W.
Exp Parasitol. 1956 Nov;5(6):571-9. PMID: 13375683

Transmission 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.

Dual 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 needed research.

Clinical 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, death occurs.



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 ehrlichiosis.
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: 11568857 

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 patient.
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 chaffeensis.
Martin GS, Christman BW, Standaert SM.
N Engl J Med.
1999 Sep 2;341(10):763-4. PMID: 10475799 

Human ehrlichial 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 pathological correlation.
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.

Postmortem examination 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 pathogenesis.

 

Clinical diagnosis and treatment of human granulocytotropic anaplasmosis.
Bakken JS, Dumler JS.
Ann NY Acad Sci. 2006 Oct;1078:236-47.  PMID: 17114714

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). 

However, delayed 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 Europe.
Sreter T, Sreterne Lancz Z, Szell Z, Egyed L.
Orv Hetil. 2005 Dec 11;146(50):2547-52. PMID: 16440500

Rickettsia helvetica 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 valve disease.



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, Switzerland.
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 endocarditis.
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 relapsed.

 

Fetal:

Gestational Lyme borreliosis. Implications for the fetus.
MacDonald AB.
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.

 

Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy.
Weber K, Bratzke HJ, Neubert U, Wilske B, Duray PH.
Pediatric Infectious Disease Journal, 7:286-9. 1988.

 

Congenital infections and the nervous system.
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.

 

Culture 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.

"Transplacental 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 disease.
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.
MacDonald AB.
Zentralbl Bakteriol Mikrobiol Hyg [A]. Dec; 263(1-2):189-200. 1986. PMID: 3554838

 

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

The 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 gestational age.



Infections in Obstetrics: Lyme disease during Pregnancy

Helayne M. Silver, MD
Infectious Disease Clinics of North America
Vol 11 Number 1  1 March, 1997 

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: 17054065 

Relapsing-fever borreliosis caused by Borrelia duttonii is a common cause of complications of pregnancy, miscarriage, and neonatal death in sub-Saharan Africa.
 

Animal: 

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 PMID: 16417970

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 often fatal.

 

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 monocytotropic ehrlichiosis.
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.
Whitney MS, 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.

 

 


"Data over dogma, Evidence over egos, Patients over politics."

- Dr. Ed Masters
 

                                 
                                   � 2006 The National Lyme Disease Memorial Park Project