Volume: 5 Table of Contents: I. ANN INTERN MED: Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. II. EUR J CLIN MICROBIOL INFECT DIS: Serological evidence of human granulocytic ehrlichiosis in Norway. III. AM J CLIN PATHOL: Positive Lyme disease serology in patients with clinical and laboratory evidence of human granulocytic ehrlichiosis. IV. SCAND J INFECT DIS: A case of concurrent Lyme meningitis with ehrlichiosis. V. J CLIN MICROBIOL: Immunoserologic evidence of coinfection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota. VI. J CLIN MICROBIOL: Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis in human sera. VII. JAMA: Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. VIII. EXP PARASITOL: Borrelia burgdorferi and Babesia microti: efficiency of transmission from reservoirs to vector ticks (Ixodes dammini). IX. About The LymeNet Newsletter Newsletter: *********************************************************************** * The National Lyme Disease Network * * http://www.lymenet.org/ * * LymeNet Newsletter * *********************************************************************** IDX# Volume 5 / Number 06 / 09-JUN-97 IDX# INDEX IDX# IDX# **** SPECIAL ISSUE **** IDX# ***** LYME DISEASE CO-INFECTIONS ***** IDX# IDX# I. ANN INTERN MED: Fatal pancarditis in a patient with IDX# coexistent Lyme disease and babesiosis. Demonstration of IDX# spirochetes in the myocardium. IDX# II. EUR J CLIN MICROBIOL INFECT DIS: Serological evidence of IDX# human granulocytic ehrlichiosis in Norway. IDX# III. AM J CLIN PATHOL: Positive Lyme disease serology in IDX# patients with clinical and laboratory evidence of human IDX# granulocytic ehrlichiosis. IDX# IV. SCAND J INFECT DIS: A case of concurrent Lyme meningitis IDX# with ehrlichiosis. IDX# V. J CLIN MICROBIOL: Immunoserologic evidence of coinfection IDX# with Borrelia burgdorferi, Babesia microti, and human IDX# granulocytic Ehrlichia species in residents of Wisconsin IDX# and Minnesota. IDX# VI. J CLIN MICROBIOL: Coexistence of antibodies to tick-borne IDX# pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis IDX# in human sera. IDX# VII. JAMA: Concurrent Lyme disease and babesiosis. Evidence for IDX# increased severity and duration of illness. IDX# VIII. EXP PARASITOL: Borrelia burgdorferi and Babesia microti: IDX# efficiency of transmission from reservoirs to vector ticks IDX# (Ixodes dammini). IDX# IX. About The LymeNet Newsletter IDX# "These results provide evidence for coinfection, perhaps explaining the variable manifestations and clinical responses noted in some patients with tick-transmitted diseases. " -- Mitchell, et al. =====*===== INTRODUCTION: The emergence of two previously obscure tick-borne diseases is causing many heath care professionals to re-examine how they diagnose and treat the condition we refer to as Lyme disease. Babesiosis and Human Granulocytic Ehrlichiosis (HGE) have recently made headlines in the popular press and are being hyped as the next generation of tick-borne illness. However, these diseases may have already added a new dimension of complexity to the diagnostic and treatment assessment process. Co-infection with two or more of these agents may present the physician with mixed signals that can lead to misdiagnosis. A single tick can carry more than one pathogen and transmit the infection to an unsuspecting human or canine victim. Indeed, a recent study last November of 100 ticks by the Hunterdon County Tickborne Disease Research Group confirmed the existence of co-infection in at least one New Jersey county. Forty-three ticks were infected with the Lyme disease agent, seventeen tested positive for HGE, and five for Babesiosis. Six ticks were co-infected with two or more agents. The ticks were tested at New York Medical College in Valhalla, NY. Until recently, little work had been done to investigate the clinical and therapeutic ramifications of co-infections. In this LymeNet Newsletter, we highlight the issue of co-infection in an effort to emphasize to physicians the importance of remaining vigilant. The first abstract demonstrates that concern over co-infection was raised as early as 1985. =====*===== I. ANN INTERN MED: Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. -------------------------------------------------------------------- AUTHORS: Marcus LC, Steere AC, Duray PH, Anderson AE, Mahoney EB REFERENCE: Ann Intern Med 1985 Sep;103(3):374-6 ABSTRACT: A 66-year-old man developed fever, chills, myalgias, three erythematous skin lesions, and transient left eyelid lag. Because of persistent fever, he was hospitalized 4 weeks after the onset of disease; a peripheral blood smear showed Babesia microti in 3% of his erythrocytes. Eighteen hours later, he died unexpectedly. Autopsy showed pancarditis with a diffuse lymphoplasmacytic infiltrate, and spirochetes were found in the myocardium. Antibody titers to both the Lyme disease spirochete Borrelia burgdorferi and Babesia microti were elevated. The finding of spirochetes in the myocardium and the elevated antibody titers to Borrelia burgdorferi suggest that the patient died from cardiac involvement of Lyme disease. =====*===== II. EUR J CLIN MICROBIOL INFECT DIS: Serological evidence of human granulocytic ehrlichiosis in Norway. -------------------------------------------------------------------- AUTHORS: Bakken JS, Krueth J, Tilden RL, Dumler JS, Kristiansen BE ORGANIZATION: Section of Infectious Diseases, Duluth Clinic, Minnesota REFERENCE: Eur J Clin Microbiol Infect Dis 1996 Oct;15(10):829-32 ABSTRACT: Human granulocytic ehrlichoisis was first described in 1994. This tick-transmitted illness is increasingly recognized in the USA as well as in Europe in areas where ixodes ticks and Lyme borreliosis are endemic. Blood samples from 58 Norwegian patients with physician- diagnosed Lyme borreliosis were examined for the presence of antibodies to Ehrlichia equi, a surrogate marker of the agent of human granulocytic ehrlichiosis. The results indicated that 10.2% of the patients may have been co-infected with human granulocytic ehrlichiosis and Lyme borreliosis. Human granulocytic ehrlichiosis appears to be established in southern Norway. =====*===== III. AM J CLIN PATHOL: Positive Lyme disease serology in patients with clinical and laboratory evidence of human granulocytic ehrlichiosis. ------------------------------------------------------------------ AUTHORS: Wormser GP, Horowitz HW, Nowakowski J, McKenna D, Dumler JS Varde S, Schwartz I, Carbonaro C, Aguero-Rosenfeld M ORGANIZATION: Department of Medicine, New York Medical College, Valhalla, NY REFERENCE: Am J Clin Pathol 1997 Feb;107(2):142-7 ABSTRACT: In 10 consecutive patients with an acute febrile illness, human granulocytic ehrlichiosis was confirmed with specific polymerase chain reaction studies, serologic conversion, or both. Although no patients had the clinical features most suggestive of early Lyme disease (eg, erythema migrans or cranial nerve palsy), tests for antibody to Borrelia burgdorferi produced a reaction in most patients. In 6 of 7 patients (86%) with evaluable results, enzyme-linked immunosorbent assay yielded positive or equivocal findings, and an immunoblot technique yielded positive findings in 60% to 90% of patients, depending on the criteria used for interpretation. Inasmuch as approximately 25% of nymphal Ixodes scapularis ticks in Westchester County, New York, are infected with B burgdorferi, the probability that at least 9 of these patients were coinfected with B burgdorferi and human granulocytic ehrlichiosis by the same tick bite is estimated to be .00003. These observations suggest that serodiagnosis is insufficient to establish the presence of coinfection with B burgdorferi. =====*====== IV. SCAND J INFECT DIS: A case of concurrent Lyme meningitis with ehrlichiosis. ------------------------------------------------------------------- AUTHORS: Ahkee S, Ramirez J ORGANIZATION: Division of Infectious Diseases, University of Louisville School of Medicine, KY, USA. REFERENCE: Scand J Infect Dis 1996;28(5):527-8 ABSTRACT: We report on a case of concurrent Lyme meningitis and ehrlichiosis in a patient with occupational exposure to ticks as a logger. The patient had a febrile Illness with a reticulate erythematous rash on his upper torso, meningoencephalitis, thrombocytopenia, and hepatitis. Acute and convalescent serologies were consistent with a dual infection with Lyme disease and ehrlichiosis. Ixodes scapularis is the tick that is associated with Lyme disease in our area and this tick has also been reported to harbor the species of Ehrlichia that causes human granulocytic ehrlichiosis. Empiric therapy for both Lyme disease and ehrlichiosis should be considered in any patient suspected of having a tick-borne illness and presenting with signs and symptoms compatible with both infections. =====*===== V. J CLIN MICROBIOL: Immunoserologic evidence of coinfection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota. -------------------------------------------------------------------- AUTHORS: Mitchell PD, Reed KD, Hofkes JM ORGANIZATION: Microbiology Section, Marshfield Laboratories, WI [email protected] REFERENCE: J Clin Microbiol 1996 Mar;34(3):724-7 ABSTRACT: In Wisconsin and Minnesota, Ixodes scapularis (Ixodes dammini) ticks are the vector of three microorganisms that may cause significant disease in humans and lower mammals. These diseases include Lyme borreliosis, which is caused by Borrelia burgdorferi, babesiosis, which is caused by Babesia microti, and human granulocytic ehrlichiosis (HGE), which is caused by an apparently new species in the genus Ehrlichia. Immunoserologic testing was performed on sera from patients with a diagnosis of one of these diseases to determine if there was evidence of coinfection with one or more of the other agents. Of 96 patients with Lyme borreliosis, 9 (9.4%) demonstrated immunoserologic evidence of coinfection: 5 (5.2%) with the agent of HGE, 2 (2.1%) with B. microti, and 2 (2.1%) with both microorganisms. Of 19 patients diagnosed with HGE, 3 (15.8%) showed immunoserologic evidence of coinfection: 1 (5.3%) with B. burgdorferi, 1 (5.3%) with B. microti, and 1 (5.3%) with both microorganisms. One patient diagnosed with babesiosis was also seropositive for ehrlichiosis. These results provide evidence for coinfection, perhaps explaining the variable manifestations and clinical responses noted in some patients with tick-transmitted diseases. In certain clinical settings, laboratory testing for coinfection is indicated to ensure that appropriate antimicrobial treatment is given. ======*===== VI. J CLIN MICROBIOL: Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis in human sera. -------------------------------------------------------------------- AUTHORS: Magnarelli LA, Dumler JS, Anderson JF, Johnson RC, Fikrig E ORGANIZATION: Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, USA. REFERENCE: J Clin Microbiol 1995 Nov;33(11):3054-7 ABSTRACT: Serum specimens from persons with or without Lyme borreliosis were analyzed by indirect fluorescent antibody staining methods for total immunoglobulins to Babesia microti, Ehrlichia chaffeensis (Arkansas strain), and Ehrlichia equi (MRK strain). There was serologic evidence of human exposure to multiple tick-borne agents in 15 (6.6%) of 227 serum samples obtained in Connecticut and Minnesota. Of these, 10 serum samples were from Connecticut patients who had erythema migrans and antibodies to Borrelia burgdorferi (range, 1:160 to 1:40, 960). A maximal antibody titer of 1:640 was noted for a B. microti infection, whereas titration end points of 1:640 and 1:1,280 were recorded for E. chaffeensis and E. equi seropositives, respectively. In specificity tests, there was no cross-reactivity among the antisera and antigens tested for the four tick-borne pathogens. On the basis of serologic testing, a small group of persons who had Lyme borreliosis had been exposed to one or more other tick-borne agents, but there was no clinical diagnosis of babesiosis or ehrlichiosis. Therefore, if the clinical picture is unclear or multiple tick-associated illnesses are suspected, more extensive laboratory testing is suggested. =====*===== VII. JAMA: Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. ---------------------------------------------------------------- AUTHORS: Krause PJ, Telford SR 3rd, Spielman A, Sikand V, Ryan R, Christianson D, Burke G, Brassard P, Pollack R, Peck J, Persing DH ORGANIZATION: Department of Pediatrics, University of Connecticut School of Medicine, Farmington, USA. REFERENCE: JAMA 1996 Jun 5;275(21):1657-60 ABSTRACT: OBJECTIVE -- To determine whether patients coinfected with Lyme disease and babesiosis in sites where both diseases are zoonotic experience a greater number of symptoms for a longer period of time than those with either infection alone. DESIGN -- Community-based, yearly serosurvey and clinic-based cohort study. SETTING -- Island community in Rhode Island and 2 Connecticut medical clinics from 1990 to 1994. STUDY PARTICIPANTS -- Long-term residents of the island community and patients seeking treatment at the clinics. MAIN OUTCOME MEASURES -- Seroreactivity to the agents of Lyme disease and babesiosis and number and duration of symptoms. RESULTS -- Of 1156 serosurvey subjects, 97 (8.4%) were seroreactive against Lyme disease spirochete antigen, of whom 14 (14%) also were seroreactive against babesial antigen. Of 240 patients diagnosed with Lyme disease, 26 (11%) were coinfected with babesiosis. Coinfected patients experienced fatigue (P = .002), headache (P < .001), sweats (P < .001), chills (P = .03), anorexia (P = .04), emotional lability (P = .02), nausea (P = .004), conjunctivitis (P = .04), and splenomegaly (P = .01) more frequently than those with Lyme disease alone. Thirteen (50%) of 26 coinfected patients were symptomatic for 3 months or longer compared with 7 (4%) of the 184 patients with Lyme disease alone from whom follow-up data were available (P < .001). Patients coinfected with Lyme disease experienced more symptoms and a more persistent episode of illness than did those (n = 10) experiencing babesial infection alone. Circulating spirochetal DNA was detected more than 3 times as often in coinfected patients as in those with Lyme disease alone (P = .06). CONCLUSIONS -- Approximately 10% of patients with Lyme disease in southern New England are coinfected with babesiosis in sites where both diseases are zoonotic. The number of symptoms and duration of illness in patients with concurrent Lyme disease and babesiosis are greater than in patients with either infection alone. In areas where both Lyme disease and babesiosis have been reported, the possibility of concomitant babesial infection should be considered when moderate to severe Lyme disease has been diagnosed. =====*===== VIII. EXP PARASITOL: Borrelia burgdorferi and Babesia microti: efficiency of transmission from reservoirs to vector ticks (Ixodes dammini). ---------------------------------------------------------------- AUTHORS: Mather TN, Telford SR 3d, Moore SI, Spielman A ORGANIZATION: Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts REFERENCE: Exp Parasitol 1990 Jan;70(1):55-61 ABSTRACT: In endemic regions, Peromyscus leucopus, the mouse reservoir of the Lyme disease spirochete (Borrelia burgdorferi) and the piroplasm causing human babesiosis (Babesia microti), is nearly universally infected with both agents. Paradoxically, spirochetal infection is nearly twice as prevalent as is babesial infection in populations of field-collected nymphal Ixodes dammini, the tick vector. In the laboratory, a similarly disproportionate rate of infection was observed among nymphal ticks, feeding as larvae, on either B. burgdorferi- or B. microti-infected mice. Ticks which fed on mice with concurrent spirochetal and babesial infections also exhibited twice the incidence of spirochetal infection over that of the piroplasm. These data suggest that the efficiency of acquisition and transstadial passage of B. burgdorferi and B. microti infection differ by a factor of two. This discrepancy may explain differences observed both in the prevalence of infection in ticks collected in the field, as well as the apparently greater risk of spirochetal infection to humans in endemic areas. =====*===== IX. 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