Positive Lyme Disease Serology in Patients With Clinical and Laboratory Evidence of Human Granulocytic Ehrlichiosis

Wormser, Gary P.; Horowitz, Harold W.; Nowakowski, John; McKenna, Donna; Dumler, J. Stephen; Varde, Shobha; Schwartz, Ira; Carbonaro, Carol A.; Agüero-Rosenfeld, Maria E.

doi:10.1093/ajcp/107.2.142

Cited by 56 publications

(33 citation statements)

References 10 publications

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“…We can state that this group did not have an objective clinical manifestation of Lyme disease such as erythema migrans. We did not attempt to exclude coinfection based on serologic testing for antibodies to B. burgdorferi because of prior observations that false-positive IgM antibodies to B. burgdorferi may be detected in HGA patients without B. burgdorferi infection (15,16). A similar serologic phenomenon has been observed in a mouse model of Ehrlichia muris infection (17).…”

Section: Discussionmentioning

confidence: 99%

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

et al. 2013

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Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (P ‫؍‬ 0.003) and had a higher body temperature on presentation (P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho ‫؍‬ 0.389, P ‫؍‬ 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease. Human granulocytic anaplasmosis (HGA) and Lyme disease typically occur in the same geographic areas since both are acquired by the bite of infected Ixodes ticks (1-5). The etiologic agents, however, are quite different. HGA is caused by Anaplasma phagocytophilum, an obligate intracellular bacterium, whereas Lyme disease is caused by an extracellular spirochetal bacterium, Borrelia burgdorferi (1, 2).The hallmark of early Lyme disease is a distinctive annular erythematous skin lesion, called erythema migrans, that occurs at the site of tick inoculation of B. burgdorferi. Erythema migrans usually can be diagnosed clinically without the need for laboratory confirmation (1). In contrast, HGA is not known to be associated with a distinctive clinical feature, and therefore, laboratory testing is required to establish the diagnosis (2-5).Although A. phagocytophilum can be cultured in vitro, few laboratories offer such testing. Consequently, most of the reported cases have been diagnosed serologically or through PCR detection of A. phagocytophilum DNA. These laboratory methods, while generally reliable, are not necessarily equivalent to the diagnostic gold standard in microbiology of a positive culture. No systematic comparison of culture-confirmed HGA with Lyme disease has been reported. In this study, we compare the epidemiologic, clinical, and laboratory features of culture-confirmed HGA with those of early Lyme disease. MATERIALS AND METHODSStudy design. This was a prospective, observational study that recorded the baseline epidemiologic, clinical, and laboratory features of patients with culture-confirmed HGA ...

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Section: Discussionmentioning

confidence: 99%

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

et al. 2013

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“…This protocol, however, adds considerable cost and greatly increases the time necessary for testing. Western blots also require subjective interpretations, and some lack specificity (11,36) or are less sensitive than IFA or ELISA (6,18,35). This can cause confusion, especially during early Lyme disease or when patients have less specific symptoms or little risk of a tick bite (29,31).…”

Section: Discussionmentioning

confidence: 99%

C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease

Jobe

Lovrich

Schell

et al. 2003

Clin Vaccine Immunol

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Borreliacidal antibodies specific for outer surface protein C (OspC) are induced shortly after infection with Borrelia burgdorferi. In this study, we identified the region of OspC recognized by immunoglobulin M (IgM) and IgG borreliacidal antibodies. Sera from patients with early Lyme disease were screened for borreliacidal activity specific for B. burgdorferi 50772 and OspC antibodies. Seven sera that contained similarly high titers of each response were then chosen randomly and adsorbed with OspC or a truncated OspC (OspC-Dra) containing the 50 amino acids nearest the carboxy terminus. Adsorption with OspC or OspC-Dra completely eliminated the borreliacidal activity in six (86%) of seven sera and significantly decreased the activity in the remaining serum (titer of 10,240 to 1,280). Moreover, OspC antibodies were no longer detected by OspC enzyme-linked immunosorbent assay or in a Western blot that contained native OspC. The findings confirmed that sera from patients with early Lyme disease contain high concentrations of IgM or IgG borreliacidal antibodies that bind a conserved region of OspC.

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“…phagocytophilum coinfections that have been confirmed by molecular methods or visualization of intragranulocytic morulae. Serologic evidence alone is often insufficient for confirming dual infection, because patients with acute HA infection might have a false-positive LD serology (222). The presence of IgM or IgG antibodies to B. burgdorferi might also represent prior asymptomatic infection.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Coinfections Acquired from Ixodes Ticks

et al. 2006

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SUMMARY The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis can coexist in Ixodes ticks and cause human coinfections. Although the risk of human coinfection differs by geographic location, the true prevalence of coinfecting pathogens among Ixodes ticks remains largely unknown for the majority of geographic locations. The prevalence of dually infected Ixodes ticks appears highest among ticks from regions of North America and Europe where LD is endemic, with reported prevalences of ≤28%. In North America and Europe, the majority of tick-borne coinfections occur among humans with diagnosed LD. Humans coinfected with LD and babesiosis appear to have more intense, prolonged symptoms than those with LD alone. Coinfected persons can also manifest diverse, influenza-like symptoms, and abnormal laboratory test results are frequently observed. Coinfecting pathogens might alter the efficiency of transmission, cause cooperative or competitive pathogen interactions, and alter disease severity among hosts. No prospective studies to assess the immunologic effects of coinfection among humans have been conducted, but animal models demonstrate that certain coinfections can modulate the immune response. Clinicians should consider the likelihood of coinfection when pursuing laboratory testing or selecting therapy for patients with tick-borne illness.

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Positive Lyme Disease Serology in Patients With Clinical and Laboratory Evidence of Human Granulocytic Ehrlichiosis

Cited by 56 publications

References 10 publications

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease

C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease

Coinfections Acquired from Ixodes Ticks

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