Lääketieteellisissä lehdissä julkaistuja Borrelioosiin ja muihin punkkien välittämiin infektiotauteihin menehtyneiden henkilöiden tapausselostuksia. Ensimmäisessä artikkelissa potilaalla ilmeni Parkinson oireet. Antibioottihoidoista huolimatta potilas menehtyi.
Medical Abstracts- Deaths from Lyme and Tick Borne Diseases
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.
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.
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.
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
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 in the brains of patients dying with dementia.
MacDonald A.
JAMA, 256(16):2195-6. 1986.
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
Fatal meningoradiculoneuritis in Lyme disease.
Melet M, Gerard A, Voiriot P, Gayet S, May T, et al.
Presse Med, 15(41):2075. 1986.
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
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.
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.
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
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.
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.
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.
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.
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).
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.
Repeated case of tick-borne encephalitis with a fatal outcome.
Shasaitov ShSh, Chartorizhskii NA, Smekalov VP.
Sov Med. Jun;(6):146. 1978 PMID: 675340
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 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.
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
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.
Borrelia burgdorferi myositis: report of eight patients.
Reimers CD, de Koning J, Neubert U, Preac-Mursic V, Koster JG, Müller-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
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.
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.
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.
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; François-Xavier Meslin
Emerg Infect Dis. 2007;13(1) ©2007 Centers for Disease Control and Prevention (CDC) MedScape 02/06/2007
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.
Borrelial lymphocytoma--a historical case.
Sonck CE, Viljanen M, Hirsimaki P, Soderstrom KO, Ekfors TO.
APMIS. Oct; 106(10):947-52. 1998. PMID: 9833696
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.
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.
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.
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
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.
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; María Gabriela Aramburú; Xavier Sáez-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.
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.
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.
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%.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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
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.
Clinical diagnosis and treatment of human granulocytotropic anaplasmosis.
Bakken JS, Dumler JS.
Ann NY Acad Sci. 2006 Oct;1078:236-47. PMID: 17114714
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 Rosário 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.
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.
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
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.
Infective Endocarditis due to Bartonella spp. and Coxiella burnetii.
Experience at a Cardiology Hospital in São Paulo, Brazil
Ann. N.Y. Acad. Sci. 1078: 215?222 (2006). doi: 10.1196/annals.1374.123
A total of 61 patients with endocarditis diagnosis were evaluated, 17 (27%) were culture-negative. Two have had IgG titer greater than 800 (≥3,200) against Bartonella spp. and one against C. burnetii (phase I and II≥6,400). Those with Bartonella-induced endocarditis had a fatal disease. Necropsy showed calcifications and extensive destruction of the valve tissue, which is diffusely infiltrated with mononuclear inflammatory cells predominantly by foamy macrophages. The patient with C. burnetii endocarditis received specific antibiotic therapy. Reports of infective endocarditis due to Bartonella spp. and C. burnetii in Brazil reveal the importance of investigating the infectious agents in culture-negative endocarditis.
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.
We have found B. burgdorferi in human neonatal brain and liver although the mother had been treated with an orally administered penicillin for LB during early pregnancy.
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.
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.
Stillbirth following maternal Lyme disease.
MacDonald AB, Benach JL, Burgdorfer W.
N Y State J Med, Nov;87(11):615-6 1987
This report describes a clinicopathologic investigation of a stillborn fetus that led to a retrospective diagnosis of Lyme disease contracted during the first trimester of pregnancy.
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.
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.
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
Congenital relapsing fever (Borrelia hermsii).
William A. Dittman
Sr, Sacred Heart Medical Center, Spokane, WA.
Blood, 15 November 2000, Vol. 96, No. 10, pp. 3333-3333
The child was treated with fluids for the septic shock. Ampicillin and cefotaxime were given initially, and erythromycin was added when the spirochetes were found. Dexamethasone was administered for the septic shock and thrombocytopenia. Improvement was progressive until day 9 when hypotension, pallor, and abdominal distension occurred. Autopsy revealed bleeding into a liver abscess with subsequent rupture of a subcapsular hematoma. No organisms were found in the abscesses at autopsy.
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.
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.
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.
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.
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.
Aortic Valve Endocarditis in a Dog Due to Bartonella clarridgeiae.
Bruno B. Chomel et al.
J Clin Microbiol. 2001 October; 39(10): 3548?3554.
The dog died of cardiopulmonary arrest prior to pacemaker implantation. Necropsy confirmed severe aortic vegetative endocarditis. Blood culture grew a fastidious, gram-negative organism 8 days after being plated. Phenotypic and genotypic characterization of the isolate, including partial sequencing of the citrate synthase (gltA) and 16S rRNA genes indicated that this organism was B. clarridgeiae. DNA extraction from the deformed aortic valve and the healthy pulmonic valve revealed the presence of B. clarridgeiae DNA only from the diseased valve. No Borrelia burgdorferi or Ehrlichia sp. DNA could be identified. Using indirect immunofluorescence tests, the dog was seropositive for B. clarridgeiae and had antibodies against Ehrlichia phagocytophila but not against Ehrlichia canis, Ehrlichia ewingii, B. burgdorferi, or Coxiella burnetii.
LÄÄKETIETEELLISISSÄ LEHDISSÄ ESITETTYJÄ KUOLEMANTAPAUKSIA
Valvojat:Jatta1001, Borrelioosiyhdistys, Waltari, Bb
Re: LÄÄKETIETEELLISISSÄ LEHDISSÄ ESITETTYJÄ KUOLEMANTAPAUKSI
Neljän vuoden aikana (1999-2003) USA:ssa raportoitiin 114 borreliabakteerin aiheuttamaa kuolemantapausta. Osalla esiintyi useiden sairauksien oireita kuten ALS, Parkinson, keuhkosairauksia, diabetes jne. Kyseisten sairauksien yhteys infektioon?
http://cid.oxfordjournals.org/content/52/3/364.full
A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States
Kiersten J. Kugeler1,
Kevin S. Griffith1,
L. Hannah Gould1,
Ken Kochanek2,
Mark J. Delorey1,
Brad J. Biggerstaff1, and
Paul S. Mead1
+ Author Affiliations
1Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, and the location is Fort Collins, CO, USA
2Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD, USA
Correspondence: Kevin S. Griffith, MD, MPH, 3150 Rampart Road, Fort Collins, CO 80521 (kkg8@cdc.gov).
Abstract
Lyme disease was listed as an underlying or multiple cause of death on 114 death records during 1999–2003. Upon review, only 1 record was consistent with clinical manifestations of Lyme disease. This analysis indicates that Lyme disease is rare as a cause of death in the United States.
Lyme disease is a tickborne disease caused by Borrelia burgdorferi. In the United States, cases most commonly occur among persons aged 5–14 years and 45–54 years, and during the summer months in the northeastern, mid-Atlantic, and north-central states [1]. Clinically, early Lyme disease is characterized by fever, fatigue, headache, arthralgias, myalgias, and erythema migrans rash. Untreated, the infection may disseminate to cause various manifestations, including secondary skin lesions, cranial neuropathy, lymphocytic meningitis, radiculoneuritis, atrioventricular block, and oligoarthritis [2]. However, Lyme disease rarely has been reported as a cause of death in the United States [3–6].
The International Classification of Diseases (ICD) is the international standard for categorizing health and vital records, including death certificates. When the ICD was updated to version 10, which became effective in the United States in 1999, Lyme disease was given a unique code and thus could be captured as a cause of death on death certificates. During 1999–2003, the Morbidity and Mortality Weekly Report (MMWR) Summary of Notifiable Diseases listed 24 deaths (median per year, 5; range per year, 2–7) attributed to Lyme disease (available at http://www.cdc.gov/mmwr/mmwr_nd/index.html). To describe the epidemiology of deaths attributed to Lyme disease, we reviewed death records and death certificates in the United States during 1999–2003
METHODS
Death records from 1999 to 2003 for which Lyme disease was coded as an underlying or multiple cause of death were requested from the National Center for Health Statistics (NCHS). The underlying cause of death is defined as “the disease or injury which initiated the chain of morbid events leading directly to death” [7]. A multiple cause of death is defined as “any other significant condition which contributed to the fatal outcome, but was not related to the disease or condition directly causing death” [7]. Part I of a death certificate contains the causal sequence from the underlying cause to the terminal event, and Part II contains any other significant medical conditions that contributed, but were not directly related, to the causal sequence. Death certificates were coded according to the ICD-10 in state vital records departments using a computerized algorithm updated annually by NCHS. All records with ICD-10 codes assigned to Lyme disease (ie, A69.2 and L90.4) were requested. Data obtained included month and year of death, age, sex, state of residence, state of death, and ICD-10 codes for underlying and multiple causes of death. Copies of corresponding death certificates were requested from states and reviewed. Analyses were conducted using Microsoft Excel and SAS software, version 9.1. Death record analysis was exempt from human subjects review at CDC, but approval was obtained from states when required. Plausibility of association with Lyme disease was based on well-established clinical manifestations of Lyme disease published in the peer-reviewed literature.
RESULTS
Approval to release death records during the study period was received from all states except Idaho, Iowa, Louisiana, Maine, and Tennessee. Among the 45 remaining states, Lyme disease was coded as an underlying or multiple cause of death for 119 records from 25 states. When requesting corresponding death certificates, one certificate could not be located by the state, one was never requested in error, two certificates did not contain a diagnosis or any wording of Lyme disease or B. burgdorferi infection, and one certificate was destroyed and the corresponding data deleted during our analysis due to expiration of the state's human subjects approval per state guidelines. Analyses were conducted on the remaining 114 death certificates.
The median age of decedents was 71 years (range: 19–99 years); 66 (58%) were male. The relative age-group specific rates of persons with Lyme disease listed as an underlying or multiple cause of death, all-cause mortality in the United States and incident cases of Lyme disease are shown in Figure 1. Deaths were evenly distributed throughout the study period (1999: n = 25; 2000: n = 23; 2001: n = 14; 2002: n = 25; 2003: n = 27) and across seasons. Deaths were reported among residents of Connecticut (19), Pennsylvania (18), New Jersey (13), New York (12), California (8), Massachusetts (5), Minnesota (5), Wisconsin (5), Virginia (4), Florida (3), Missouri (3), Texas (3), Maryland (2), Michigan (2), West Virginia (2), Alabama (1), Arkansas (1), Colorado (1), Iowa (1) (The death record and certificate for this decedent were from Kansas, but Iowa was listed as the state of residence.), Illinois (1), Indiana (1), North Carolina (1), North Dakota (1), South Carolina (1), and Washington (1).
Figure 1.
Relative age-group specific rates of all-cause mortality, Lyme disease incidence, and Lyme disease listed as a multiple or underlying cause of death—United States, 1999–2003
Of 114 records, Lyme disease was coded as the underlying cause of death for 23 (20%) and as a multiple cause of death for 91 (80%) (Table 1). There were no significant differences between decedents with Lyme disease coded as an underlying versus multiple cause of death with respect to age, sex, or residence or death in a with respect to age, sex, or residence or death in a Healthy People 2010 highly endemic state as previously defined (Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin) [1]. Four (17%) records for which Lyme disease was coded as the underlying cause of death had Lyme disease listed in Part II of the death certificate, but it was coded as the underlying cause because the listed causal pathway in Part I of the death certificate lacked an accepted cause of death (eg, “presumed natural disease”). Eleven (48%) death certificates with Lyme disease coded as the underlying cause of death were improperly completed, as evidenced by an implausible or ill-defined causal sequence of events (Table 1) [8]. Of the 12 certificates considered properly completed, the terminal events in the causal sequences were cardiopulmonary or cardiorespiratory arrest (3), respiratory arrest, failure, or anoxia (3), Lyme disease (2), coronary thrombosis (1), encephalopathy (1), seizure disorder (1), and stroke (1). Of these 12 certificates, 6 (50%) lacked enough information to evaluate the plausibility of the causal sequence, 2 (17%) listed other more plausible clinical explanations for the terminal event in Part II of the certificate (eg, atherosclerotic heart disease and chronic atrial fibrillation for the decedent with stroke), 2 (17%) contained disease processes in intervals substantially longer than that described in the scientific literature (eg, Lyme disease 5–10 years prior to seizure disorder onset), 1 (8%) listed a causal sequence not previously associated with Lyme disease (ie, coronary thrombosis and hypercoagulable state), and 1 (8%) listed a causal sequence possibly consistent with a prior case report (ie, “respiratory failure” due to “probable aspiration” due to “severe cognitive deterioration” due to “central nervous system Lymes disease” [sic]) [3].
View this table:
Table 1.
Direct Extraction of Part I of Death Certificates for which Lyme Disease Was Coded as the Underlying Cause of Death
Among the 91 records for which Lyme disease was coded as a multiple cause of death, 45 different diseases were coded as the underlying cause of death, including infectious diseases (eg, tuberculosis), malignancies (eg, colon, prostate), diabetes mellitus, nervous system diseases (eg, motor neuron disease, Parkinson's disease), circulatory system diseases (eg, acute myocardial infarction, atherosclerotic heart disease), and chronic obstructive pulmonary disease.
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DISCUSSION
In contrast to the 96,068 cases of Lyme disease reported to CDC during 1999–2003, Lyme disease was coded as an underlying cause of death on only 23 records. Decedents were predominately of an advanced age and age distribution that more closely approximates that of all-cause mortality than that of reported Lyme disease cases. Most terminal events on death certificates for which Lyme disease was the underlying cause of death were inconsistent with the well-characterized complications of Lyme disease and the rare published case reports of Lyme disease-associated mortality [3–6]. Additionally, the underlying causes of death when Lyme disease was listed as a multiple cause of death varied widely and also were inconsistent with the well-characterized complications of Lyme disease. While this analysis included data only through 2003, the number of deaths attributed to Lyme disease as reported in the MMWR Summary of Notifiable Diseases has remained consistent (available at http://www.cdc.gov/mmwr/PDF/wk/mm5754.pdf).
Mortality data are a fundamental component of disease surveillance. While standard forms and procedures are developed and recommended for nationwide use, improper completion of death certificates is not unique to our analysis [9]. Common errors include listing underlying or multiple causes of death in the wrong section, listing nonspecific processes, and listing inappropriate events in the causal sequence [9]. Sparse dedicated resources at the state level may limit follow-up of improperly or inaccurately completed death certificates, thereby decreasing the public health utility of this data source.
Without approval from every state to receive death record data, some relevant death records may have been excluded. However, these 5 states accounted for ∼1% of Lyme disease cases reported during 1999–2003, and this analysis captured 23 of 24 reported underlying deaths due to Lyme disease. In contrast, deaths attributed to Lyme disease likely are overestimated in this report because 9 certificates (8%) had uncertain terms listed such as “Lyme disease?,” “Lyme disease—past history,” or “possible chronic Lyme disease.” Most importantly, we did not conduct medical chart reviews. Therefore, we were unable to confirm or deny the diagnosis of Lyme disease or the causal sequence leading to death.
Despite these limitations, our review of death records and death certificates supports the finding that Lyme disease is rare as a cause of death. Therefore, we strongly encourage health care providers to thoroughly document and report any death suspected to be caused by Lyme disease. Additionally, health care providers should be reminded to carefully and accurately complete death certificates as this data is a vital source of health information. Lastly, prompt diagnosis and treatment of persons infected with Borrelia burgdorferi are critical to the prevention of more serious illness and potential long-term complications.
Previous SectionNext Section
Acknowledgments
The authors would like to acknowledge all state government entities that provided death certificates for this analysis. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, US Department of Health and Human Services.
Financial support. Financial support was provided by CDC.
Received July 9, 2010.
Revision received October 19, 2010.
Revision received October 27, 2010.
Accepted November 18, 2010.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.
Previous Section
References
1.↵
Bacon RM,
Kugeler KJ,
Mead PS
. Surveillance for Lyme disease–United States, 1992–2006. MMWR Surveill Summ 2008;57:1-9.
Medline
2.↵
Steere AC,
Coburn C,
Glickstein L
. The emergence of Lyme disease. J Clin Invest 2004;113:1093-101.
CrossRefMedlineWeb of Science
3.↵
Waniek C,
Prohovnik I,
Kaufman MA,
Dwork AJ
. Rapidly progressive frontal-type dementia associated with Lyme disease. J Neuropsychiatry Clin Neurosci 1995. Summer; 7:345–7.
Search Google Scholar
4.
Marcus LC,
Steere AC,
Duray PH,
Anderson AE,
Mahoney EB
. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. Ann Intern Med 1985;103:374-6.
Abstract/FREE Full Text
5.
Kirsch M,
Ruben FL,
Steere AC,
Duray PH,
Norden CW,
Winkelstein A
. Fatal adult respiratory distress syndrome in a patient with Lyme disease. JAMA 1988;259:2737-9.
Abstract/FREE Full Text
6.↵
Tavora F,
Burke A,
Ling L,
Franks TJ,
Virmani R
. Postmortem confirmation of Lyme carditis with polymerase chain reaction. Cardiovasc Pathol 2008;17:103-7.
CrossRefMedlineWeb of Science
7.↵
WHO. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Geneva: WHO; 1992.
8.↵
Physician's Handbook on Medical Certification of Death. Hyattsville, MD: National Center for Health Statistics; 2004.
9.↵
Sehdev AES,
Hutchins GM
. Problems with proper completion and accuracy of the cause-of-death statement. Arch Intern Med 2001;161:277-84.
Abstract/FREE Full Text
Articles citing this article
The pain of "chronic Lyme disease": moving the discourse in a different direction FASEB J. (2012) 26 (1): 11-12
Abstract
Full Text (HTML)
Full Text (PDF)
http://cid.oxfordjournals.org/content/52/3/364.full
A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States
Kiersten J. Kugeler1,
Kevin S. Griffith1,
L. Hannah Gould1,
Ken Kochanek2,
Mark J. Delorey1,
Brad J. Biggerstaff1, and
Paul S. Mead1
+ Author Affiliations
1Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, and the location is Fort Collins, CO, USA
2Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD, USA
Correspondence: Kevin S. Griffith, MD, MPH, 3150 Rampart Road, Fort Collins, CO 80521 (kkg8@cdc.gov).
Abstract
Lyme disease was listed as an underlying or multiple cause of death on 114 death records during 1999–2003. Upon review, only 1 record was consistent with clinical manifestations of Lyme disease. This analysis indicates that Lyme disease is rare as a cause of death in the United States.
Lyme disease is a tickborne disease caused by Borrelia burgdorferi. In the United States, cases most commonly occur among persons aged 5–14 years and 45–54 years, and during the summer months in the northeastern, mid-Atlantic, and north-central states [1]. Clinically, early Lyme disease is characterized by fever, fatigue, headache, arthralgias, myalgias, and erythema migrans rash. Untreated, the infection may disseminate to cause various manifestations, including secondary skin lesions, cranial neuropathy, lymphocytic meningitis, radiculoneuritis, atrioventricular block, and oligoarthritis [2]. However, Lyme disease rarely has been reported as a cause of death in the United States [3–6].
The International Classification of Diseases (ICD) is the international standard for categorizing health and vital records, including death certificates. When the ICD was updated to version 10, which became effective in the United States in 1999, Lyme disease was given a unique code and thus could be captured as a cause of death on death certificates. During 1999–2003, the Morbidity and Mortality Weekly Report (MMWR) Summary of Notifiable Diseases listed 24 deaths (median per year, 5; range per year, 2–7) attributed to Lyme disease (available at http://www.cdc.gov/mmwr/mmwr_nd/index.html). To describe the epidemiology of deaths attributed to Lyme disease, we reviewed death records and death certificates in the United States during 1999–2003
METHODS
Death records from 1999 to 2003 for which Lyme disease was coded as an underlying or multiple cause of death were requested from the National Center for Health Statistics (NCHS). The underlying cause of death is defined as “the disease or injury which initiated the chain of morbid events leading directly to death” [7]. A multiple cause of death is defined as “any other significant condition which contributed to the fatal outcome, but was not related to the disease or condition directly causing death” [7]. Part I of a death certificate contains the causal sequence from the underlying cause to the terminal event, and Part II contains any other significant medical conditions that contributed, but were not directly related, to the causal sequence. Death certificates were coded according to the ICD-10 in state vital records departments using a computerized algorithm updated annually by NCHS. All records with ICD-10 codes assigned to Lyme disease (ie, A69.2 and L90.4) were requested. Data obtained included month and year of death, age, sex, state of residence, state of death, and ICD-10 codes for underlying and multiple causes of death. Copies of corresponding death certificates were requested from states and reviewed. Analyses were conducted using Microsoft Excel and SAS software, version 9.1. Death record analysis was exempt from human subjects review at CDC, but approval was obtained from states when required. Plausibility of association with Lyme disease was based on well-established clinical manifestations of Lyme disease published in the peer-reviewed literature.
RESULTS
Approval to release death records during the study period was received from all states except Idaho, Iowa, Louisiana, Maine, and Tennessee. Among the 45 remaining states, Lyme disease was coded as an underlying or multiple cause of death for 119 records from 25 states. When requesting corresponding death certificates, one certificate could not be located by the state, one was never requested in error, two certificates did not contain a diagnosis or any wording of Lyme disease or B. burgdorferi infection, and one certificate was destroyed and the corresponding data deleted during our analysis due to expiration of the state's human subjects approval per state guidelines. Analyses were conducted on the remaining 114 death certificates.
The median age of decedents was 71 years (range: 19–99 years); 66 (58%) were male. The relative age-group specific rates of persons with Lyme disease listed as an underlying or multiple cause of death, all-cause mortality in the United States and incident cases of Lyme disease are shown in Figure 1. Deaths were evenly distributed throughout the study period (1999: n = 25; 2000: n = 23; 2001: n = 14; 2002: n = 25; 2003: n = 27) and across seasons. Deaths were reported among residents of Connecticut (19), Pennsylvania (18), New Jersey (13), New York (12), California (8), Massachusetts (5), Minnesota (5), Wisconsin (5), Virginia (4), Florida (3), Missouri (3), Texas (3), Maryland (2), Michigan (2), West Virginia (2), Alabama (1), Arkansas (1), Colorado (1), Iowa (1) (The death record and certificate for this decedent were from Kansas, but Iowa was listed as the state of residence.), Illinois (1), Indiana (1), North Carolina (1), North Dakota (1), South Carolina (1), and Washington (1).
Figure 1.
Relative age-group specific rates of all-cause mortality, Lyme disease incidence, and Lyme disease listed as a multiple or underlying cause of death—United States, 1999–2003
Of 114 records, Lyme disease was coded as the underlying cause of death for 23 (20%) and as a multiple cause of death for 91 (80%) (Table 1). There were no significant differences between decedents with Lyme disease coded as an underlying versus multiple cause of death with respect to age, sex, or residence or death in a with respect to age, sex, or residence or death in a Healthy People 2010 highly endemic state as previously defined (Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin) [1]. Four (17%) records for which Lyme disease was coded as the underlying cause of death had Lyme disease listed in Part II of the death certificate, but it was coded as the underlying cause because the listed causal pathway in Part I of the death certificate lacked an accepted cause of death (eg, “presumed natural disease”). Eleven (48%) death certificates with Lyme disease coded as the underlying cause of death were improperly completed, as evidenced by an implausible or ill-defined causal sequence of events (Table 1) [8]. Of the 12 certificates considered properly completed, the terminal events in the causal sequences were cardiopulmonary or cardiorespiratory arrest (3), respiratory arrest, failure, or anoxia (3), Lyme disease (2), coronary thrombosis (1), encephalopathy (1), seizure disorder (1), and stroke (1). Of these 12 certificates, 6 (50%) lacked enough information to evaluate the plausibility of the causal sequence, 2 (17%) listed other more plausible clinical explanations for the terminal event in Part II of the certificate (eg, atherosclerotic heart disease and chronic atrial fibrillation for the decedent with stroke), 2 (17%) contained disease processes in intervals substantially longer than that described in the scientific literature (eg, Lyme disease 5–10 years prior to seizure disorder onset), 1 (8%) listed a causal sequence not previously associated with Lyme disease (ie, coronary thrombosis and hypercoagulable state), and 1 (8%) listed a causal sequence possibly consistent with a prior case report (ie, “respiratory failure” due to “probable aspiration” due to “severe cognitive deterioration” due to “central nervous system Lymes disease” [sic]) [3].
View this table:
Table 1.
Direct Extraction of Part I of Death Certificates for which Lyme Disease Was Coded as the Underlying Cause of Death
Among the 91 records for which Lyme disease was coded as a multiple cause of death, 45 different diseases were coded as the underlying cause of death, including infectious diseases (eg, tuberculosis), malignancies (eg, colon, prostate), diabetes mellitus, nervous system diseases (eg, motor neuron disease, Parkinson's disease), circulatory system diseases (eg, acute myocardial infarction, atherosclerotic heart disease), and chronic obstructive pulmonary disease.
Previous SectionNext Section
DISCUSSION
In contrast to the 96,068 cases of Lyme disease reported to CDC during 1999–2003, Lyme disease was coded as an underlying cause of death on only 23 records. Decedents were predominately of an advanced age and age distribution that more closely approximates that of all-cause mortality than that of reported Lyme disease cases. Most terminal events on death certificates for which Lyme disease was the underlying cause of death were inconsistent with the well-characterized complications of Lyme disease and the rare published case reports of Lyme disease-associated mortality [3–6]. Additionally, the underlying causes of death when Lyme disease was listed as a multiple cause of death varied widely and also were inconsistent with the well-characterized complications of Lyme disease. While this analysis included data only through 2003, the number of deaths attributed to Lyme disease as reported in the MMWR Summary of Notifiable Diseases has remained consistent (available at http://www.cdc.gov/mmwr/PDF/wk/mm5754.pdf).
Mortality data are a fundamental component of disease surveillance. While standard forms and procedures are developed and recommended for nationwide use, improper completion of death certificates is not unique to our analysis [9]. Common errors include listing underlying or multiple causes of death in the wrong section, listing nonspecific processes, and listing inappropriate events in the causal sequence [9]. Sparse dedicated resources at the state level may limit follow-up of improperly or inaccurately completed death certificates, thereby decreasing the public health utility of this data source.
Without approval from every state to receive death record data, some relevant death records may have been excluded. However, these 5 states accounted for ∼1% of Lyme disease cases reported during 1999–2003, and this analysis captured 23 of 24 reported underlying deaths due to Lyme disease. In contrast, deaths attributed to Lyme disease likely are overestimated in this report because 9 certificates (8%) had uncertain terms listed such as “Lyme disease?,” “Lyme disease—past history,” or “possible chronic Lyme disease.” Most importantly, we did not conduct medical chart reviews. Therefore, we were unable to confirm or deny the diagnosis of Lyme disease or the causal sequence leading to death.
Despite these limitations, our review of death records and death certificates supports the finding that Lyme disease is rare as a cause of death. Therefore, we strongly encourage health care providers to thoroughly document and report any death suspected to be caused by Lyme disease. Additionally, health care providers should be reminded to carefully and accurately complete death certificates as this data is a vital source of health information. Lastly, prompt diagnosis and treatment of persons infected with Borrelia burgdorferi are critical to the prevention of more serious illness and potential long-term complications.
Previous SectionNext Section
Acknowledgments
The authors would like to acknowledge all state government entities that provided death certificates for this analysis. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, US Department of Health and Human Services.
Financial support. Financial support was provided by CDC.
Received July 9, 2010.
Revision received October 19, 2010.
Revision received October 27, 2010.
Accepted November 18, 2010.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.
Previous Section
References
1.↵
Bacon RM,
Kugeler KJ,
Mead PS
. Surveillance for Lyme disease–United States, 1992–2006. MMWR Surveill Summ 2008;57:1-9.
Medline
2.↵
Steere AC,
Coburn C,
Glickstein L
. The emergence of Lyme disease. J Clin Invest 2004;113:1093-101.
CrossRefMedlineWeb of Science
3.↵
Waniek C,
Prohovnik I,
Kaufman MA,
Dwork AJ
. Rapidly progressive frontal-type dementia associated with Lyme disease. J Neuropsychiatry Clin Neurosci 1995. Summer; 7:345–7.
Search Google Scholar
4.
Marcus LC,
Steere AC,
Duray PH,
Anderson AE,
Mahoney EB
. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. Ann Intern Med 1985;103:374-6.
Abstract/FREE Full Text
5.
Kirsch M,
Ruben FL,
Steere AC,
Duray PH,
Norden CW,
Winkelstein A
. Fatal adult respiratory distress syndrome in a patient with Lyme disease. JAMA 1988;259:2737-9.
Abstract/FREE Full Text
6.↵
Tavora F,
Burke A,
Ling L,
Franks TJ,
Virmani R
. Postmortem confirmation of Lyme carditis with polymerase chain reaction. Cardiovasc Pathol 2008;17:103-7.
CrossRefMedlineWeb of Science
7.↵
WHO. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Geneva: WHO; 1992.
8.↵
Physician's Handbook on Medical Certification of Death. Hyattsville, MD: National Center for Health Statistics; 2004.
9.↵
Sehdev AES,
Hutchins GM
. Problems with proper completion and accuracy of the cause-of-death statement. Arch Intern Med 2001;161:277-84.
Abstract/FREE Full Text
Articles citing this article
The pain of "chronic Lyme disease": moving the discourse in a different direction FASEB J. (2012) 26 (1): 11-12
Abstract
Full Text (HTML)
Full Text (PDF)
Re: LÄÄKETIETEELLISISSÄ JULKAISUISSA ESITETTYJÄ TAPAUKSIA
CDC:n raportti Joulukuu 2013.
Kolme nuorta aikuista (26-38 v) kuoli borrelia-bakteerin aiheuttamiin sydäntulehduksiin äkillisesti.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6249a1.htm
Three Sudden Cardiac Deaths Associated with Lyme Carditis — United States, November 2012–July 2013
Weekly
December 13, 2013 / 62(49);993-996
Lyme disease* is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin) (1,2).† Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012–July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections.§
Case Reports and Public Health Investigation
Patient 1. In November 2012, a Massachusetts resident was found unresponsive in an automobile after it veered off the road. No evidence of traumatic injury was found. An electrocardiogram (EKG) performed by emergency responders showed no cardiac activity, and the patient was pronounced dead at a nearby hospital. The patient had no serious preexisting medical conditions. No rash was noted at autopsy, although some atherosclerosis was present. Interviews with next-of-kin revealed that the patient had described a nonspecific illness with malaise and muscle and joint pain during the 2 weeks preceding death. The patient lived alone with a dog that was reported to have ticks frequently.
The decedent's corneas and skin, musculoskeletal, cardiac, and vascular tissues were recovered for potential transplantation. The heart was sent to tissue bank A for valve recovery. Microscopic examination of cardiac tissue found extensive myocarditis with mixed perivascular lymphoplasmacytic inflammation suggestive of Lyme carditis. A postmortem serum sample tested at CDC yielded serologic evidence of recent infection with B. burgdorferi, reacting strongly in both whole cell sonicate (WCS) and C6 enzyme immunoassay (EIA), and against all three scored bands (23 kDa, 39 kDa, and 41 kDa) by immunoglobulin M (IgM) Western blot. Western blot testing for immunoglobulin G (IgG) antibodies demonstrated reactivity against four of 10 scored bands (23 kDa, 39 kDa, 41 kDa, and 45 kDa); these serologic findings were consistent with early disseminated Lyme disease.
Histopathologic evaluation of postmortem tissues at CDC also was suggestive of Lyme pancarditis (Figure 1) and abundant spirochetes were observed by Warthin-Starry silver stain (Figure 2). Spirochetes also were detected in the myocardium by immunohistochemistry (IHC). Polymerase chain reaction (PCR) assays detected B. burgdorferi in extracts of formalin-fixed, paraffin-embedded heart tissue based on outer surface protein A, flagellin, and plasminogen-binding protein gene targets. No donor tissues were transplanted.
Patient 2. In July 2013, a New York state resident experienced chest pain and collapsed at home. Cardiopulmonary resuscitation was unsuccessful, and the patient was pronounced dead at a local hospital. The patient's past medical history included a diagnosis of Wolff-Parkinson-White syndrome, a cardiac conduction abnormality. The patient had no known tick contact or rash but was reported to be a hiker. Evidence of hypertensive and atherosclerotic cardiovascular disease was noted at autopsy. The decedent's corneas and skin, musculoskeletal, vascular, and cardiac tissue were recovered for potential transplantation. Examination of cardiac tissue at tissue bank A revealed moderate diffuse, perivascular lymphoplasmacytic pancarditis, similar to that seen in patient 1. Serologic testing at CDC was consistent with recent infection with B. burgdorferi; WCS and C6 EIAs were strongly reactive, IgM Western blot demonstrated strong reactivity to all three scored bands, and IgG Western blot demonstrated reactivity to four scored bands (23 kDa, 41 kDa, 58 kDa, and 66 kDa). Rare spirochetes were identified in cardiac tissue by Warthin-Starry silver stain and IHC; heart tissues tested positive for B. burgdorferi by PCR.
Before diagnosis of B. burgdorferi infection, the decedent's corneas were transplanted to two recipients. The transplanting physicians and cornea recipients subsequently were notified of the donor's infection. Neither recipient 1 nor recipient 2 reported signs or symptoms of Lyme disease or problems with the transplanted cornea. Both recipients elected to receive antibiotic therapy with doxycycline. None of the remaining donated tissues were transplanted.
Patient 3. In July 2013, a Connecticut resident collapsed while visiting New Hampshire and was pronounced dead at a local hospital. The patient had complained of episodic shortness of breath and anxiety during the 7–10 days before death. No rash, arthralgia, or neurologic symptoms were noted. A physician consulted 1 day before death prescribed clonazepam for anxiety; an EKG was not performed, nor were any antibiotics prescribed. The patient lived on a heavily wooded lot and had frequent tick exposure; there was no known history of cardiovascular disease. Autopsy revealed myocarditis, and the medical examiner submitted heart tissues to CDC for evaluation of suspected viral myocarditis. Corneas and skin were recovered for donation, and one cornea was transplanted to recipient 3. No other tissue was transplanted. Recipient 3 was examined 1 week after corneal transplant and was recovering as anticipated. Examination of heart tissues at CDC again demonstrated diffuse mixed perivascular lymphoplasmacytic pancarditis. Warthin-Starry stain revealed spirochetes in the myocardium, and IHC and PCR assays confirmed the spirochete as B. burgdorferi. WCS and C6 EIAs were positive, IgM Western blot was positive for all three scored bands, and IgG Western blot demonstrated reactivity to one scored band (41 kDa).
The eye bank was informed of the Lyme disease status of the donor and the recommendations for therapy. Before notification of the Lyme disease status of the donor, recipient 3 died of unrelated causes. No tissues or serum from recipient 3 were available for evaluation.
Reported by
Gregory Ray, MD, Thadeus Schulz, MD, Wayne Daniels, DO, Cryolife, Inc. Kennesaw, GA. Elizabeth R. Daly, MPH, New Hampshire Dept of Health and Human Svcs; Thomas A. Andrew, MD, New Hampshire Office of the Chief Medical Examiner. Catherine M. Brown, DVM, Massachusetts Dept of Public Health; Peter Cummings, MD, Massachusetts Office of the Chief Medical Examiner. Randall Nelson, DVM, Matthew L. Cartter, MD, Connecticut Dept of Public Health. P. Bryon Backenson, MS, Jennifer L. White, MPH, Philip M. Kurpiel, MPH, Russell Rockwell, PhD, New York State Dept of Health; Andrew S. Rotans, MPH, Christen Hertzog, Linda S. Squires, Dutchess County Dept of Health; Jeanne V. Linden, MD, Wadsworth Center, New York State Dept of Health; Margaret Prial, MD, Office of the Medical Examiner, Orange County, New York. Jennifer House, DVM, Pam Pontones, MA, Indiana State Dept of Health. Brigid Batten, MPH, Dianna Blau, DVM, PhD, Marlene DeLeon-Carnes, Atis Muehlenbachs, MD, PhD, Jana Ritter, DVM, Jeanine Sanders, Sherif R. Zaki, MD, PhD, Div of High-Consequence Pathogens and Pathology; Paul Mead, MD, Alison Hinckley, PhD, Christina Nelson, MD, Anna Perea, MSc, Martin Schriefer, PhD, Claudia Molins, PhD, Div of Vector-Borne Infectious Diseases, National Center for Emerging and Zoonotic Infectious Disease; Joseph D. Forrester, MD, EIS Officer, CDC. Corresponding contributor: Joseph D. Forrester, jforrester@cdc.gov, 970-266-3587.
Editorial Note
This report describes three cases of sudden cardiac death associated with Lyme carditis, with subsequent transplantation of corneas from two of the decedents into three recipients. Only rarely has death been attributed to Lyme carditis (3–6), and review of pathology reports at tissue bank A did not identify any additional confirmed cases among 20,000 cardiac specimens received since 2004. Whether the preexisting heart conditions found in two patients increased their risk for death is unclear.
Borrelia burgdorferi has been shown to affect all layers of the heart, but tends to spare the great vessels and heart valves (7). Inflammation is characteristically diffuse, perivascular, lymphohistiocytic, and plasma cell-rich. Spirochetes can be found within the myocardial cellular infiltrates; IHC and PCR testing can provide additional evidence of infection. Although Lyme carditis usually is present in conjunction with other features of the disease, such as erythema migrans, arthritis, or neurologic disease, it can be observed independently (8). The most common cardiac manifestation is atrioventricular block, which can fluctuate between first, second, and third degree (7,8). Second-degree or third-degree atrioventricular block occurs in approximately 0.8% of all Lyme disease cases reported to CDC (2). Symptoms of atrioventricular block, including lightheadedness, palpitations, shortness of breath, chest pain, and syncope can occur 4 days to 7 months after onset of disease, with a median of 21 days (7,8). With appropriate therapy (9), prognosis is excellent, and signs of cardiac involvement typically resolve within 1–6 weeks, depending on the degree of conduction disturbance (10). Some cases of complete heart block might require temporary pacing.
Although no cases of Lyme disease transmission through organ or tissue transplantation have been reported, the identification of organisms in tissue suggests the risk for transmission could exist. Ophthalmologic manifestations of Lyme disease are rare but can involve any of the ocular structures and occur during any stage of Lyme disease.¶ Given the rarity of ocular Lyme disease, and of corneal Lyme disease in particular, and the absence of ocular symptoms in the deceased patients, the need for antibiotics in this setting was equivocal. However, if administered, oral doxycycline would be expected to penetrate eye structures well.
Medical examiners and pathologists should be aware that Lyme carditis is a potential, albeit rare, cause for sudden cardiac death in persons from high-incidence Lyme disease areas. Diffuse, mixed perivascular lymphoplasmacytic infiltrates seen on pathologic examination of heart tissue from patients who have sudden cardiac death in high-incidence Lyme disease areas should prompt serologic evaluation for Lyme disease and further histopathologic examination for spirochetes, including IHC evaluation and PCR. Lyme disease is a nationally notifiable disease; all suspected cases of fatal Lyme carditis should be reported to state or local public health authorities, and the cases should be investigated.
Prompt recognition and early, appropriate therapy for Lyme disease is essential. Health-care providers should ask patients with suspected Lyme disease about cardiac symptoms and obtain an EKG if indicated. Conversely, they should ask patients with unexplained heart block about possible exposure to infected ticks. Health-care providers also should remind their patients of steps to prevent infection, including use of repellent, daily tick checks, prompt showering after potential exposure, and landscape management. The three deaths described in this report underscore the need for better methods of primary prevention of Lyme disease and other tickborne infections.
References
CDC. Notice to readers: final 2012 reports of nationally notifiable infectious diseases. MMWR 2013;62:669–82.
CDC. Surveillance for Lyme disease—United States, 1992–2006. MMWR 2008;57(No. SS-10):1–9.
Cary NR, Fox B, Wright DJ, Cutler SJ, Shapiro LM, Grace AA. Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node. Postgrad Med J 1990;66:134–6.
Marcus LC, Steere AC, Duray PH, Anderson AE, Mahoney EB. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. Ann Intern Med 1985;103:374–6.
Tavora F, Burke A, Li L, Franks TJ, Virmani R. Postmortem confirmation of Lyme carditis with polymerase chain reaction. Cardiovasc Pathol 2008;17:103–7.
Reimers CD, de Koning J, Neubert U, et al. Borrelia burgdorferi myositis: report of eight patients. J Neurol 1993;240:278–83.
Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1980;93:8–16.
Fish AE, Pride YB, Pinto DS. Lyme carditis. Infect Dis Clin N Am 2008;22:275–88.
Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43:1089–134.
McAlister HF, Klementowicz PT, Andrews C, Fisher JD, Feld M, Furman S. Lyme carditis: an important cause of reversible heart block. Ann Intern Med 1989;1110:339–45.
* Additional information available at http://www.cdc.gov/lyme.
† Additional information regarding how many persons receive a diagnosis each year of Lyme disease is available at http://www.cdc.gov/lyme/faq/index.html#humancases.
§ Additional information available at http://www.cdc.gov/lyme/prev/index.html.
¶ Additional information available at http://www.sciencedirect.com/science/ar ... 81External Web Site Icon.
What is already known on this topic?
Carditis with heart block is a known but uncommon complication of early disseminated Lyme disease that is generally treated effectively with appropriate antibiotic therapy. Four deaths from Lyme carditis have been reported.
What is added by this report?
This report describes three new cases of sudden cardiac death associated with Lyme carditis. The decedents were aged 26 to 38 years and lived in high-incidence Lyme disease areas.
What are the implications for public health practice?
Pathologists and medical examiners should be aware that Lyme carditis can be a cause of sudden cardiac death. All suspected cases of fatal Lyme carditis should be reported to state or local public health authorities, and the cases should be investigated. Physicians and health-care providers should ask patients with suspected Lyme disease about cardiac symptoms, and conversely, ask patients with acute, unexplained cardiac symptoms about possible tick exposure and symptoms of Lyme disease. Clinicians should encourage all patients to practice recommended tick bite prevention strategies.
FIGURE 1. Hematoxylin and eosin stain at 6.25X magnification demonstrating interstitial perivascular lymphoplasmacytic pancarditis in postmortem tissue of one of three patients whose death was associated with Lyme carditis — United States, 2013
The figure above shows Hematoxylin and eosin stain, demonstrating interstitial perivascular lymphoplasmacytic pancarditis in postmortem tissue of one of three patients whose death was associated with Lyme carditis in the United States in 2012.
Alternate Text: The figure above shows Hematoxylin and eosin stain, demonstrating interstitial perivascular lymphoplasmacytic pancarditis in postmortem tissue of one of three patients whose death was associated with Lyme carditis in the United States in 2012.
FIGURE 2. Warthin-Starry stain of cardiac tissue at 158X magnification demonstrating Borrelia burgdorferi spirochetes (arrow) in one of three patients whose death was associated with Lyme carditis — United States, 2013
The figure above shows a Warthin-Starry stain of cardiac tissue demonstrating Borrelia burgdorferi spirochetes in one of three patients whose death was associated with Lyme carditis during November 12–July 2013.
Alternate Text: The figure above shows a Warthin-Starry stain of cardiac tissue demonstrating Borrelia burgdorferi spirochetes in one of three patients whose death was associated with Lyme carditis during November 12–July 2013.
Kolme nuorta aikuista (26-38 v) kuoli borrelia-bakteerin aiheuttamiin sydäntulehduksiin äkillisesti.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6249a1.htm
Three Sudden Cardiac Deaths Associated with Lyme Carditis — United States, November 2012–July 2013
Weekly
December 13, 2013 / 62(49);993-996
Lyme disease* is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin) (1,2).† Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012–July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections.§
Case Reports and Public Health Investigation
Patient 1. In November 2012, a Massachusetts resident was found unresponsive in an automobile after it veered off the road. No evidence of traumatic injury was found. An electrocardiogram (EKG) performed by emergency responders showed no cardiac activity, and the patient was pronounced dead at a nearby hospital. The patient had no serious preexisting medical conditions. No rash was noted at autopsy, although some atherosclerosis was present. Interviews with next-of-kin revealed that the patient had described a nonspecific illness with malaise and muscle and joint pain during the 2 weeks preceding death. The patient lived alone with a dog that was reported to have ticks frequently.
The decedent's corneas and skin, musculoskeletal, cardiac, and vascular tissues were recovered for potential transplantation. The heart was sent to tissue bank A for valve recovery. Microscopic examination of cardiac tissue found extensive myocarditis with mixed perivascular lymphoplasmacytic inflammation suggestive of Lyme carditis. A postmortem serum sample tested at CDC yielded serologic evidence of recent infection with B. burgdorferi, reacting strongly in both whole cell sonicate (WCS) and C6 enzyme immunoassay (EIA), and against all three scored bands (23 kDa, 39 kDa, and 41 kDa) by immunoglobulin M (IgM) Western blot. Western blot testing for immunoglobulin G (IgG) antibodies demonstrated reactivity against four of 10 scored bands (23 kDa, 39 kDa, 41 kDa, and 45 kDa); these serologic findings were consistent with early disseminated Lyme disease.
Histopathologic evaluation of postmortem tissues at CDC also was suggestive of Lyme pancarditis (Figure 1) and abundant spirochetes were observed by Warthin-Starry silver stain (Figure 2). Spirochetes also were detected in the myocardium by immunohistochemistry (IHC). Polymerase chain reaction (PCR) assays detected B. burgdorferi in extracts of formalin-fixed, paraffin-embedded heart tissue based on outer surface protein A, flagellin, and plasminogen-binding protein gene targets. No donor tissues were transplanted.
Patient 2. In July 2013, a New York state resident experienced chest pain and collapsed at home. Cardiopulmonary resuscitation was unsuccessful, and the patient was pronounced dead at a local hospital. The patient's past medical history included a diagnosis of Wolff-Parkinson-White syndrome, a cardiac conduction abnormality. The patient had no known tick contact or rash but was reported to be a hiker. Evidence of hypertensive and atherosclerotic cardiovascular disease was noted at autopsy. The decedent's corneas and skin, musculoskeletal, vascular, and cardiac tissue were recovered for potential transplantation. Examination of cardiac tissue at tissue bank A revealed moderate diffuse, perivascular lymphoplasmacytic pancarditis, similar to that seen in patient 1. Serologic testing at CDC was consistent with recent infection with B. burgdorferi; WCS and C6 EIAs were strongly reactive, IgM Western blot demonstrated strong reactivity to all three scored bands, and IgG Western blot demonstrated reactivity to four scored bands (23 kDa, 41 kDa, 58 kDa, and 66 kDa). Rare spirochetes were identified in cardiac tissue by Warthin-Starry silver stain and IHC; heart tissues tested positive for B. burgdorferi by PCR.
Before diagnosis of B. burgdorferi infection, the decedent's corneas were transplanted to two recipients. The transplanting physicians and cornea recipients subsequently were notified of the donor's infection. Neither recipient 1 nor recipient 2 reported signs or symptoms of Lyme disease or problems with the transplanted cornea. Both recipients elected to receive antibiotic therapy with doxycycline. None of the remaining donated tissues were transplanted.
Patient 3. In July 2013, a Connecticut resident collapsed while visiting New Hampshire and was pronounced dead at a local hospital. The patient had complained of episodic shortness of breath and anxiety during the 7–10 days before death. No rash, arthralgia, or neurologic symptoms were noted. A physician consulted 1 day before death prescribed clonazepam for anxiety; an EKG was not performed, nor were any antibiotics prescribed. The patient lived on a heavily wooded lot and had frequent tick exposure; there was no known history of cardiovascular disease. Autopsy revealed myocarditis, and the medical examiner submitted heart tissues to CDC for evaluation of suspected viral myocarditis. Corneas and skin were recovered for donation, and one cornea was transplanted to recipient 3. No other tissue was transplanted. Recipient 3 was examined 1 week after corneal transplant and was recovering as anticipated. Examination of heart tissues at CDC again demonstrated diffuse mixed perivascular lymphoplasmacytic pancarditis. Warthin-Starry stain revealed spirochetes in the myocardium, and IHC and PCR assays confirmed the spirochete as B. burgdorferi. WCS and C6 EIAs were positive, IgM Western blot was positive for all three scored bands, and IgG Western blot demonstrated reactivity to one scored band (41 kDa).
The eye bank was informed of the Lyme disease status of the donor and the recommendations for therapy. Before notification of the Lyme disease status of the donor, recipient 3 died of unrelated causes. No tissues or serum from recipient 3 were available for evaluation.
Reported by
Gregory Ray, MD, Thadeus Schulz, MD, Wayne Daniels, DO, Cryolife, Inc. Kennesaw, GA. Elizabeth R. Daly, MPH, New Hampshire Dept of Health and Human Svcs; Thomas A. Andrew, MD, New Hampshire Office of the Chief Medical Examiner. Catherine M. Brown, DVM, Massachusetts Dept of Public Health; Peter Cummings, MD, Massachusetts Office of the Chief Medical Examiner. Randall Nelson, DVM, Matthew L. Cartter, MD, Connecticut Dept of Public Health. P. Bryon Backenson, MS, Jennifer L. White, MPH, Philip M. Kurpiel, MPH, Russell Rockwell, PhD, New York State Dept of Health; Andrew S. Rotans, MPH, Christen Hertzog, Linda S. Squires, Dutchess County Dept of Health; Jeanne V. Linden, MD, Wadsworth Center, New York State Dept of Health; Margaret Prial, MD, Office of the Medical Examiner, Orange County, New York. Jennifer House, DVM, Pam Pontones, MA, Indiana State Dept of Health. Brigid Batten, MPH, Dianna Blau, DVM, PhD, Marlene DeLeon-Carnes, Atis Muehlenbachs, MD, PhD, Jana Ritter, DVM, Jeanine Sanders, Sherif R. Zaki, MD, PhD, Div of High-Consequence Pathogens and Pathology; Paul Mead, MD, Alison Hinckley, PhD, Christina Nelson, MD, Anna Perea, MSc, Martin Schriefer, PhD, Claudia Molins, PhD, Div of Vector-Borne Infectious Diseases, National Center for Emerging and Zoonotic Infectious Disease; Joseph D. Forrester, MD, EIS Officer, CDC. Corresponding contributor: Joseph D. Forrester, jforrester@cdc.gov, 970-266-3587.
Editorial Note
This report describes three cases of sudden cardiac death associated with Lyme carditis, with subsequent transplantation of corneas from two of the decedents into three recipients. Only rarely has death been attributed to Lyme carditis (3–6), and review of pathology reports at tissue bank A did not identify any additional confirmed cases among 20,000 cardiac specimens received since 2004. Whether the preexisting heart conditions found in two patients increased their risk for death is unclear.
Borrelia burgdorferi has been shown to affect all layers of the heart, but tends to spare the great vessels and heart valves (7). Inflammation is characteristically diffuse, perivascular, lymphohistiocytic, and plasma cell-rich. Spirochetes can be found within the myocardial cellular infiltrates; IHC and PCR testing can provide additional evidence of infection. Although Lyme carditis usually is present in conjunction with other features of the disease, such as erythema migrans, arthritis, or neurologic disease, it can be observed independently (8). The most common cardiac manifestation is atrioventricular block, which can fluctuate between first, second, and third degree (7,8). Second-degree or third-degree atrioventricular block occurs in approximately 0.8% of all Lyme disease cases reported to CDC (2). Symptoms of atrioventricular block, including lightheadedness, palpitations, shortness of breath, chest pain, and syncope can occur 4 days to 7 months after onset of disease, with a median of 21 days (7,8). With appropriate therapy (9), prognosis is excellent, and signs of cardiac involvement typically resolve within 1–6 weeks, depending on the degree of conduction disturbance (10). Some cases of complete heart block might require temporary pacing.
Although no cases of Lyme disease transmission through organ or tissue transplantation have been reported, the identification of organisms in tissue suggests the risk for transmission could exist. Ophthalmologic manifestations of Lyme disease are rare but can involve any of the ocular structures and occur during any stage of Lyme disease.¶ Given the rarity of ocular Lyme disease, and of corneal Lyme disease in particular, and the absence of ocular symptoms in the deceased patients, the need for antibiotics in this setting was equivocal. However, if administered, oral doxycycline would be expected to penetrate eye structures well.
Medical examiners and pathologists should be aware that Lyme carditis is a potential, albeit rare, cause for sudden cardiac death in persons from high-incidence Lyme disease areas. Diffuse, mixed perivascular lymphoplasmacytic infiltrates seen on pathologic examination of heart tissue from patients who have sudden cardiac death in high-incidence Lyme disease areas should prompt serologic evaluation for Lyme disease and further histopathologic examination for spirochetes, including IHC evaluation and PCR. Lyme disease is a nationally notifiable disease; all suspected cases of fatal Lyme carditis should be reported to state or local public health authorities, and the cases should be investigated.
Prompt recognition and early, appropriate therapy for Lyme disease is essential. Health-care providers should ask patients with suspected Lyme disease about cardiac symptoms and obtain an EKG if indicated. Conversely, they should ask patients with unexplained heart block about possible exposure to infected ticks. Health-care providers also should remind their patients of steps to prevent infection, including use of repellent, daily tick checks, prompt showering after potential exposure, and landscape management. The three deaths described in this report underscore the need for better methods of primary prevention of Lyme disease and other tickborne infections.
References
CDC. Notice to readers: final 2012 reports of nationally notifiable infectious diseases. MMWR 2013;62:669–82.
CDC. Surveillance for Lyme disease—United States, 1992–2006. MMWR 2008;57(No. SS-10):1–9.
Cary NR, Fox B, Wright DJ, Cutler SJ, Shapiro LM, Grace AA. Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node. Postgrad Med J 1990;66:134–6.
Marcus LC, Steere AC, Duray PH, Anderson AE, Mahoney EB. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. Ann Intern Med 1985;103:374–6.
Tavora F, Burke A, Li L, Franks TJ, Virmani R. Postmortem confirmation of Lyme carditis with polymerase chain reaction. Cardiovasc Pathol 2008;17:103–7.
Reimers CD, de Koning J, Neubert U, et al. Borrelia burgdorferi myositis: report of eight patients. J Neurol 1993;240:278–83.
Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1980;93:8–16.
Fish AE, Pride YB, Pinto DS. Lyme carditis. Infect Dis Clin N Am 2008;22:275–88.
Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43:1089–134.
McAlister HF, Klementowicz PT, Andrews C, Fisher JD, Feld M, Furman S. Lyme carditis: an important cause of reversible heart block. Ann Intern Med 1989;1110:339–45.
* Additional information available at http://www.cdc.gov/lyme.
† Additional information regarding how many persons receive a diagnosis each year of Lyme disease is available at http://www.cdc.gov/lyme/faq/index.html#humancases.
§ Additional information available at http://www.cdc.gov/lyme/prev/index.html.
¶ Additional information available at http://www.sciencedirect.com/science/ar ... 81External Web Site Icon.
What is already known on this topic?
Carditis with heart block is a known but uncommon complication of early disseminated Lyme disease that is generally treated effectively with appropriate antibiotic therapy. Four deaths from Lyme carditis have been reported.
What is added by this report?
This report describes three new cases of sudden cardiac death associated with Lyme carditis. The decedents were aged 26 to 38 years and lived in high-incidence Lyme disease areas.
What are the implications for public health practice?
Pathologists and medical examiners should be aware that Lyme carditis can be a cause of sudden cardiac death. All suspected cases of fatal Lyme carditis should be reported to state or local public health authorities, and the cases should be investigated. Physicians and health-care providers should ask patients with suspected Lyme disease about cardiac symptoms, and conversely, ask patients with acute, unexplained cardiac symptoms about possible tick exposure and symptoms of Lyme disease. Clinicians should encourage all patients to practice recommended tick bite prevention strategies.
FIGURE 1. Hematoxylin and eosin stain at 6.25X magnification demonstrating interstitial perivascular lymphoplasmacytic pancarditis in postmortem tissue of one of three patients whose death was associated with Lyme carditis — United States, 2013
The figure above shows Hematoxylin and eosin stain, demonstrating interstitial perivascular lymphoplasmacytic pancarditis in postmortem tissue of one of three patients whose death was associated with Lyme carditis in the United States in 2012.
Alternate Text: The figure above shows Hematoxylin and eosin stain, demonstrating interstitial perivascular lymphoplasmacytic pancarditis in postmortem tissue of one of three patients whose death was associated with Lyme carditis in the United States in 2012.
FIGURE 2. Warthin-Starry stain of cardiac tissue at 158X magnification demonstrating Borrelia burgdorferi spirochetes (arrow) in one of three patients whose death was associated with Lyme carditis — United States, 2013
The figure above shows a Warthin-Starry stain of cardiac tissue demonstrating Borrelia burgdorferi spirochetes in one of three patients whose death was associated with Lyme carditis during November 12–July 2013.
Alternate Text: The figure above shows a Warthin-Starry stain of cardiac tissue demonstrating Borrelia burgdorferi spirochetes in one of three patients whose death was associated with Lyme carditis during November 12–July 2013.