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n engl j med 373;5 nejm.org July 30, 2015468

T h e n e w e ngl a nd j o u r na l o f m e dic i n e

Pr esen tation of C a se

Dr. Brian C. Zanoni (Infectious Disease): A 28-year-old pregnant woman (gravida 3, para 0020) was admitted to this hospital in the summer because of fever, chills, headache, and fatigue.

The patient had been well until approximately 5 days before admission, at 28 weeks of gestation, when she noted feeling warm, which she attributed to a malfunction-ing air-conditioning system at work. Three days before admission, malaise and head-aches occurred. The next day, she called her health care providers about her symp-toms and reported Braxton Hicks contractions and frequent fetal movement, with no fevers, vaginal bleeding, or leaking of fluid. She was advised to rest and in-crease her fluid intake. That night, she took diphenhydramine for sleep. The day before admission, she came to the outpatient obstetrics clinic of this hospital be-cause of a temperature of 37.4°C. She reported decreased fetal movement at home, which improved on arrival to the clinic. She was taking prenatal vitamins. She was allergic to cephalexin and trimethoprim–sulfamethoxazole, which caused a rash, and to multiple fruits and vegetables, which caused anaphylaxis.

On examination, the temperature was 36.7°C, the blood pressure 103/66 mm Hg, and the pulse 72 beats per minute. The abdomen was soft and nontender, without palpable uterine contractions. On a nonstress test, the average fetal heart rate was 125 beats per minute, with moderate variability and positive accelerations; these find-ings were interpreted as reassuring. On ultrasonography, fetal biometric measure-ments were consistent with a weight of 1244 g (51st percentile for 28 weeks 4 days of gestation), and there was appropriate gradual growth since a previous scan had been obtained, as well as a normal volume of amniotic fluid; the fetus was active. Later that day, the patient traveled to a coastal area in Massachusetts that she visited weekly. That evening, increased fatigue, diffuse body aches, low back pain, and an earache occurred, and the temperature rose to 38.6°C. The obstetrician who was on call that evening recommended that the patient go to a local emergency depart-ment for evaluation; the examination was reportedly normal. There was a platelet count of 125,000 per cubic millimeter, and a peripheral-blood smear showed no

From the Department of Geographical Medicine and Infectious Disease, Tufts Medical Center (L.T.H.), the Depart‑ments of Medicine (A.M.T.) and Patholo‑gy ( J.A.B.), Massachusetts General Hos‑pital, and the Departments of Medicine (A.M.T.) and Pathology (J.A.B.), Harvard Medical School — all in Boston.

N Engl J Med 2015;373:468-75.DOI: 10.1056/NEJMcpc1501763Copyright © 2015 Massachusetts Medical Society.

Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor Nancy Lee Harris, M.D., Editor Jo‑Anne O. Shepard, M.D., Associate Editor Alice M. Cort, M.D., Associate Editor Sally H. Ebeling, Assistant Editor Emily K. McDonald, Assistant Editor

Case 24-2015: A 28-Year-Old Pregnant Woman with Fever, Chills, Headache,

and FatigueLinden T. Hu, M.D., Athe M. Tsibris, M.D., and John A. Branda, M.D.

Case Records of the Massachusetts General Hospital

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Case Records of the Massachusetts Gener al Hospital

evidence of babesia; other laboratory test results were reportedly negative. Results of testing for Lyme disease were pending. The patient returned to her coastal vacation residence. Overnight, the temperature rose to 38.8°C. On the morning of admission, the patient called her obstetrician’s office at this hospital to report fever, with a cur-rent temperature of 37.4°C. She was advised to take acetaminophen, drink fluids, rest, and return for evaluation if she began feeling worse. Later that day, the temperature rose to 39.4°C and nausea developed. That evening, she presented to the labor and delivery unit of this hospital.

On presentation, the patient reported mild headache, neck stiffness, a left earache, intermit-tent contractions, and a possible erythematous rash on her right shin; she had no joint symp-toms, vomiting, ear drainage, hearing difficulty, or upper respiratory, gastrointestinal, or genito-urinary symptoms. She was gravida 3, had had two previous spontaneous miscarriages, and had received prenatal care, with testing that was posi-tive for rubella-specific antibodies and negative for syphilis, human immunodeficiency virus (HIV), hepatitis C virus, and hepatitis B virus surface antigen.

The patient had a history of thrombophilia and gastroesophageal reflux disease associated with aspirin use and was heterozygous for factor V Leiden. She reported contact with an indoor cat at home and with outdoor cats and dogs at the home of relatives; she knew of bats in the vicinity of her home and mice in the basement of her coastal vacation residence. She had no known sick contacts, insect bites, or consumption of unpas-teurized dairy products. She had traveled to West-ern Europe, Central America, Mexico, and Asia within the previous 3 years. She worked in an office, had stopped smoking 5 years earlier, and had stopped drinking alcohol when she became pregnant.

On examination, the temperature was 36.3°C, the blood pressure 110/64 mm Hg, the pulse 98 beats per minute, and the respiratory rate 18 breaths per minute. The abdomen was gravid, soft, and nontender, and the fetal heart rate was 130 beats per minute, with accelerations. There was a faint area of lacy, blanching erythema (4 cm in diam-eter) on the right shin and no lymphadenopathy; the remainder of the examination was normal. The red-cell indexes and results of coagulation tests

were normal, as were blood levels of creatinine, total protein, albumin, globulin, alkaline phos-phatase, total and direct bilirubin, uric acid, and haptoglobin. Thick and thin Giemsa-stained smears of peripheral blood were negative for ba-besia; other test results are shown in Table 1. Uri-nalysis was negative. Cultures of the blood were obtained.

During the next 4.5 hours, the temperature rose to 38.9°C. Ceftriaxone and rifampin were admin-istered. During the next 3 days, results of testing for hepatitis A and B viruses were suggestive of protective immunity, and results of testing for Epstein–Barr virus were suggestive of past infec-tion; testing was negative for cytomegalovirus nucleic acids, HIV, heterophile antibodies, and IgM and IgG antibodies to Borrelia burgdorferi, Coxiella burnetii, ehrlichia, and anaplasma. The patient became afebrile within 48 hours and her headache resolved on the fourth hospital day.

On the fifth hospital day, a diagnostic test result was received.

Differ en ti a l Di agnosis

Dr. Linden T. Hu: A 28-year-old pregnant woman presented with an acute onset of fevers, myalgias, headache, and neck stiffness during the summer in Massachusetts. Summer fevers are a common occurrence in many parts of the United States (Table 2). Infection-related summer fevers are not commonly caused by the adenoviruses, rhinovi-ruses, and influenza that dominate during the winter months in temperate areas; instead, entero-viruses (e.g., coxsackievirus) and infections result-ing from outdoor exposure to environmental or zoonotic reservoirs of disease are prevalent. In Massachusetts, many of these agents are trans-mitted by mosquito or tick vectors.

Although this patient did not identify a spe-cific tick or mosquito bite, these are recognized in a minority of cases.1,2 She did have multiple opportunities for exposure to these agents, given her frequent travel to coastal Massachusetts and her participation in outdoor activities. Differen-tiating between potential causes of summer fe-vers is often difficult because of the nonspecific nature of the symptoms, particularly during the early stages of infection. However, certain features of this patient’s presentation — including head-ache, rash, thrombocytopenia, and hepatitis —





may offer clues to the most likely diagnoses (Table 3).

Headache

Headache is a common, nonspecific finding as-sociated with many febrile illnesses. Infections with pathogens that are able to cross the blood–brain barrier and directly infect cells of the cen-tral nervous system are typically manifested by severe headaches as a prominent early feature. From our list of infections that cause summer fever, Lyme disease, human granulocytic ana-plasmosis, Rocky Mountain spotted fever, lepto-spirosis, eastern equine encephalitis, West Nile virus, deer tick virus, tularemia, and enterovirus all commonly cause headache. Although this patient

reported a mild headache, we cannot rule out these diagnoses on the basis of the severity of this symp-tom, especially early during the course of the illness.

Meningitis with associated neck stiffness can be consistent with infections such as Lyme disease, human granulocytic anaplasmosis, Rocky Moun-tain spotted fever, and enterovirus, but it affects a minority of patients and headaches can occur in the absence of meningitis. Deer tick virus and eastern equine encephalitis typically cause severe meningoencephalitis and are not compatible with this patient’s presentation.

Borrelia miyamotoi, which was first identified as a human pathogen in 2011, is now recognized as the fifth agent of human disease to be trans-

VariableReference Range,

Adults†On Admission, This Hospital

4th Day, This Hospital

Hematocrit (%) 36.0–46.0 (women) 34.1 30.4

Hemoglobin (g/dl) 12.0–16.0 (women) 12.1 11.0

White‑cell count (per mm3) 4500–11,000 5900 6800

Differential count (%)

Neutrophils 40–70 90.0 62.0

Lymphocytes 22–44 6.1 29.0

Monocytes 4–11 3.0 7.0

Eosinophils 0–8 0 2.0

Basophils 0–3 0.2 0

Platelet count (per mm3) 150,000–400,000 81,000 122,000

Sodium (mmol/liter) 135–145 134

Potassium (mmol/liter) 3.4–4.8 3.7

Chloride (mmol/liter) 100–108 99

Carbon dioxide (mmol/liter) 23.0–31.9 22.8

Plasma anion gap 3–15 12

Urea nitrogen (mg/dl) 8–25 6

Bilirubin (mg/dl)

Total 0.0–1.0 0.5 1.3

Direct 0.0–0.4 0.2 0.8

Aspartate aminotransferase (U/liter) 9–32 297 383

Alanine aminotransferase (U/liter) 7–33 329 468

Lactate dehydrogenase (U/liter) 110–210 283

* To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for bilirubin to micromoles per liter, multiply by 17.1.

† Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical condi‑tions that could affect the results. They may therefore not be appropriate for all patients.

Table 1. Laboratory Data.*





mitted by the Ixodes scapularis tick in the northeast-ern United States.3 The organism is most closely related to the borrelia species that causes relaps-ing fever. A limited amount of information about the symptomatic disease associated with B. miya-motoi is currently available, but it may cause a syndrome that is similar to relapsing fever, with prominent headaches and meningitis (reported in an immunocompromised patient), fevers, my-algias, and fatigue.4-6

Rash

The presence of a rash can be a distinguishing feature of a summer fever. Rocky Mountain spot-ted fever, tularemia, and Lyme disease are associ-ated with characteristic rashes that can be diag-nostic. This patient’s rash is described as a faint, lacy erythema; these features are not consistent with the rash associated with Rocky Mountain spotted fever or ulceroglandular tularemia. Fur-thermore, the rash is not consistent with the classic description of the erythema migrans rash of Lyme disease. However, less than 50% of erythema migrans rashes have target-shaped (bull’s-eye) lesions; the majority are homogeneous, erythema-tous, and usually round or oval in appearance.7 Nonspecific maculopapular or morbilliform rash-es are associated with leptospirosis, West Nile virus, and enterovirus and are occasionally report-ed in patients with human granulocytic anaplas-mosis. Southern tick–associated rash illness, which is transmitted by the Amblyomma americanum tick, causes a rash that is indistinguishable from the erythema migrans rash of Lyme disease. No in-fectious agent has been definitively linked with southern tick–associated rash illness, and the dis-ease appears to be very self-limited.8,9 An erythe-ma migrans–like rash was reported in two patients from Japan with B. miyamotoi disease, but there is not enough information to definitively deter-mine that rash is a common manifestation of this infection.10

Hepatitis

At the time of admission to this hospital, this pa-tient had clinically significant elevations in hepatic aminotransferase levels that were indicative of mild-to-moderate hepatitis. This is a common finding in patients with human granulocytic ana-plasmosis11 and has also been reported in patients with Lyme disease, although this patient’s hepa-

titis was more severe than would be expected with Lyme disease. Many of the initial descriptions of abnormal aminotransferase levels associated with Lyme disease were reported before the recogni-tion of coinfection with anaplasma; therefore, it is unclear how commonly hepatitis is associated with B. burgdorferi infection alone. Mild-to-mod-erate elevation in aminotransferase levels (as in this patient) has also been reported in patients with B. miyamotoi infection, but the frequency of this finding is not well established. Hepatitis and splenomegaly can be seen in patients with tula-remia or Rocky Mountain spotted fever but usually appear during fulminant evolution of the disease. Babesiosis is more commonly associated with rises in the bilirubin level due to hemolysis of red cells than with hepatocyte injury.

Thrombocytopenia

The other main distinguishing feature of this patient’s presentation is thrombocytopenia that worsened early in the course of her illness and then appeared to improve by the fourth hospital day. Mild thrombocytopenia that resolves quickly,

Tickborne

Lyme disease

Anaplasmosis

Ehrlichiosis

Babesiosis

Borrelia miyamotoi infection

Tularemia

Rocky Mountain spotted fever

Southern tick–associated rash illness

Powassan virus

Deer tick virus

Mosquito-borne

West Nile virus

Eastern equine encephalitis

Jamestown Canyon virus

Nonvectored

Enterovirus

Tularemia

Leptospirosis

Hantavirus

Table 2. Causes of Summer Fever in the United States.





either spontaneously or with treatment, is most notably seen in patients with human granulocytic anaplasmosis or B. miyamotoi disease. Thrombo-cytopenia is often accompanied by leukopenia, which this patient did not have. It can also occur in patients with leptospirosis, tularemia, and Rocky Mountain spotted fever, but such patients are typically critically ill by the time this feature is observed.

This patient had many negative serologic tests for specific infectious agents. Although her work-up was extensive, it is difficult to put much weight on these results because the sensitivity of serologic testing early in the disease course is generally poor. The negative smears for babesia are infor-mative because the sensitivity of blood smears is relatively high (approximately 80%).12 On the basis of this patient’s clinical syndrome and negative smears for babesia, babesiosis could confidently be ruled out. Examination of buffy-coat prepara-tions of whole blood for morulae of anaplasma may provide a rapid diagnosis but is more dif-ficult than examination of red cells for babesia, and sensitivity is variable and highly dependent on the skill of the microscopist. Therefore, a nega-tive buffy-coat examination for anaplasma can-not be reliably used to rule out human granulo-cytic anaplasmosis.

This patient’s condition improved after she received ceftriaxone and rifampin. This regimen would have activity against the most likely diag-noses in this case, although it is difficult to say

whether improvement would have occurred even without therapy. In a nonpregnant patient, doxy-cycline would probably have been substituted for rifampin.

Pregnancy

How did this patient’s pregnancy factor into the differential diagnosis? Given the acuteness of the disease onset and subsequent resolution of her fevers, she almost certainly had an infection and not a process related to her pregnancy. None of the other infections under consideration occur more commonly during pregnancy.

Given the patient’s travel to coastal Massachu-setts, the two most likely causes of her illness are human granulocytic anaplasmosis and B. miyamo-toi infection. Of the two diseases, human granu-locytic anaplasmosis is currently more commonly reported; however, this may be due to availability of testing. Also, there is growing evidence that B. miyamotoi infection is more common than had been previously thought.13,14 It is not possible to distinguish between these diseases on the basis of clinical presentation, routine laboratory tests, or epidemiology. In this case, B. miyamotoi may be slightly more likely than human granulocytic anaplasmosis, if the patient’s neck stiffness rep-resented meningitis and the reports of an asso-ciation with an erythema migrans–like rash prove to be true. However, in Massachusetts, coinfection with multiple pathogens occurs in up to 15% of persons with infections transmitted by ixodes

Cause of Fever Headache Rash Thrombocytopenia Hepatitis

Lyme disease Common Very common Uncommon Somewhat common

Human granulocytic anaplasmosis Common Uncommon Common Common

Babesiosis Somewhat common Uncommon Uncommon Uncommon

Borrelia miyamotoi infection Common Uncertain Common Common

Deer tick virus Very common Uncommon Uncommon Uncommon

Rocky Mountain spotted fever Very common Very common Common Somewhat common

Tularemia Somewhat common Common Common Somewhat common

Southern tick–associated rash illness Somewhat common Very common Uncommon Uncommon

West Nile virus Common Common Somewhat common Uncommon

Eastern equine encephalitis Very common Uncommon Uncommon Uncommon

Enterovirus Very common Somewhat common Uncommon Somewhat common

Leptospirosis Very common Somewhat common Common Common

Table 3. Clinical Features Associated with Summer Fever.





species, and coinfection with B. burgdorferi could explain the rash. Lyme disease is unlikely to be the sole cause of the patient’s symptoms. I suspect that a polymerase-chain-reaction (PCR) assay of this patient’s blood for human granulocytic ana-plasmosis and B. miyamotoi infection was per-formed in this case. Serologic or PCR testing for the glpQ (glycerophosphodiester phosphodiester-ase) gene of B. miyamotoi can distinguish this organism from B. burgdorferi.

Dr. Eric S. Rosenberg (Pathology): Dr. Tsibris, what was your impression when you initially evaluated this patient?

Dr. Athe M. Tsibris: We thought a tickborne ill-ness, due to either Anaplasma phagocytophilum or the newly recognized human pathogen B. miya-motoi, was the most likely cause in this case. We also considered infections that might result from the patient’s exposure to mice and pets. Leptospi-rosis was unlikely in the absence of active urinary sediment. Patients with lymphocytic choriomen-ingitis virus infection typically present with an influenza-like illness, and toxoplasmosis can re-semble infectious mononucleosis; the patient’s pregnancy led us to test for both of these diseases.

Clinic a l Di agnosis

Anaplasmosis or Borrelia miyamotoi infection.

Dr . Linden T. Hu’s Di agnosis

Tickborne illness due to Borrelia miyamotoi or Ana-plasma phagocytophilum.

Pathological Discussion

Dr. John A. Branda: A real-time PCR assay targeting the 23S ribosomal RNA gene of borrelia species,15 which was performed on a blood sample at a refer-ence laboratory, was positive. Additional PCR as-says targeting the glpQ gene16 and the flagellin gene,17 which can distinguish between B. burg-dorferi and B. miyamotoi, revealed that the infec-tious agent was B. miyamotoi.

PCR assays specific for A. phagocytophilum and Babesia microti that were performed on the same specimen were negative. Indirect enzyme-linked immunosorbent assay (ELISA) was initially nega-tive for IgM and IgG antibodies to the glpQ anti-gen of B. miyamotoi.13 However, 1 week later, ELISA was positive for the IgM antibodies but negative

for the IgG antibodies, findings that are consis-tent with recent B. miyamotoi infection. The glpQ antigen is present in borreliae that cause relaps-ing fever (including B. miyamotoi) but is absent in borreliae that cause Lyme disease; thus, ELISA for antibodies to the glpQ antigen helps to distin-guish between these categories of borrelia infec-tion.18 In contrast, reactivity to serologic assays for Lyme disease that were designed for use in Europe3 and North America13 has been reported in patients with B. miyamotoi infection.

In this patient, ELISA was negative for B. burg-dorferi on the day after admission to this hospi-tal, but 5 days later, a repeat test was positive. A supplemental Western immunoblot assay was pos-itive for IgM antibodies to B. burgdorferi, with all three relevant IgM bands detected (p23, p39, and p41), and was negative for IgG antibodies, with no bands detected. Although the serologic find-ings for B. burgdorferi could represent cross-reac-tivity from B. miyamotoi infection, they are also consistent with early Lyme borreliosis. Thus, the microbiologic diagnosis in this case was B. miya-motoi infection with a possible B. burgdorferi coin-fection.

Dr. Rosenberg: Dr. Tsibris, would you tell us how you treated this patient?

Dr. Tsibris: The patient had marked improve-ment during the first 24 hours of receiving anti-biotic therapy, and a lumbar puncture was de-ferred. The high probability of anaplasmosis led us to recommend an empirical 7-day course of oral rifampin, which was complicated by elevated hepatic aminotransferase levels that were eight to nine times as high as the upper limit of the normal range.

The ideal treatment for B. miyamotoi infection and the risk of transplacental fetal infection are unknown. We elected to treat the patient with intravenous ceftriaxone for 4 weeks. Persistent elevation of bile-salt levels resulted in a diagno-sis of intrahepatic cholestasis of pregnancy that improved with the administration of ursodiol. Labor was induced at 37 weeks of gestation, and the patient had a vaginal delivery of a boy with normal Apgar scores. At his 1-month and 4-month checkups, the infant and his mother were noted to be doing well.

Dr. Rosenberg: Since this is a relatively newly recognized infection, can you give us guidance on when it is appropriate to test for B. miyamotoi?





Dr. Hu: So little is known about B. miyamotoi that it is difficult to make recommendations. Some patients have a very severe presentation, similar to that of relapsing fever, but the majority of pa-tients probably have self-limited disease and will get better without treatment. At this point, we do not know whether routine testing should be rec-ommended. My suspicion is that testing for B. mi-yamotoi will be part of the standard panel for tickborne diseases, in contrast to deer tick virus, which is rare and should be tested for only when suspicion is high.

From a practical point of view, had this pa-tient not been pregnant, she would have been treated with doxycycline, which would have been active against both B. miyamotoi and anaplasma infection. Since both diseases are fairly easily treated with doxycycline, diagnostic testing for these pathogens may not be necessary.

Dr. Hasan Bazari (Medicine): Since serologic test-ing is unreliable early during the course of infec-tion, should we use PCR-based tests to diagnose these illnesses?

Dr. Branda: For that exact reason, the test of choice for the diagnosis of anaplasmosis or B. mi-yamotoi infection is PCR assay of the blood. How-ever, PCR assays of the blood (at least the cur-rently available assays) are not sensitive for Lyme disease during any stage, and therefore serologic

testing is still the test of choice for supporting the diagnosis of Lyme disease.

Dr. Rosenberg: How should we advise our patients to minimize their risk of acquiring tickborne in-fections?

Dr. Hu: I recommend interventions that re-quire minimal adherence. In addition to wearing clothing that provides full coverage during po-tential exposures, showering after potential expo-sures has been proven to be effective. Clothing that is embedded with permethrin, which can last through many washes, also decreases the chance of tick and mosquito bites. Nightly tick checks, to remove the ticks before substantial feeding has occurred, is effective for preventing Lyme disease but difficult to do.

Fina l Di agnosis

Borrelia miyamotoi infection and possible Borrelia burgdorferi infection.

Presented at Medical Grand Rounds.Dr. Hu reports receiving consulting fees from Abzyme and

grant support to his institution from FoodSource Lure; Dr. Tsi-bris, consulting and editing fees from DynaMed/EBSCO; and Dr. Branda, consulting fees from AdvanDx and grant support to his institution from bioMerieux, Immunetics, Alere, and DiaSorin. No other potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

References1. Nadelman RB, Nowakowski J, Forse-ter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996; 100: 502-8.2. Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early Lyme disease in pa-tients with microbiologically confirmed erythema migrans. Ann Intern Med 2002; 136: 421-8.3. Platonov AE, Karan LS, Kolyasnikova NM, et al. Humans infected with relaps-ing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis 2011; 17: 1816-23.4. Chowdri HR, Gugliotta JL, Berardi VP, et al. Borrelia miyamotoi infection pre-senting as human granulocytic anaplas-mosis: a case report. Ann Intern Med 2013; 159: 21-7.5. Krause PJ, Narasimhan S, Wormser GP, et al. Human Borrelia miyamotoi infec-tion in the United States. N Engl J Med 2013; 368: 291-3.

6. Gugliotta JL, Goethert HK, Berardi VP, Telford SR III. Meningoencephalitis from Borrelia miyamotoi in an immuno-compromised patient. N Engl J Med 2013; 368: 240-5.7. Schutzer SE, Berger BW, Krueger JG, Eshoo MW, Ecker DJ, Aucott JN. Atypical erythema migrans in patients with PCR-positive Lyme disease. Emerg Infect Dis 2013; 19: 815-7.8. Masters EJ, Grigery CN, Masters RW. STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness. Infect Dis Clin North Am 2008; 22: 361-76.9. Wormser GP, Masters E, Nowakows-ki J, et al. Prospective clinical evaluation of patients from Missouri and New York with erythema migrans-like skin lesions. Clin Infect Dis 2005; 41: 958-65.10. Sato K, Takano A, Konnai S, et al. Hu-man infections with Borrelia miyamotoi, Japan. Emerg Infect Dis 2014; 20: 1391-3.11. Bakken JS, Dumler S. Human granu-locytic anaplasmosis. Infect Dis Clin North Am 2008; 22: 433-48.

12. Krause PJ, Telford S III, Spielman A, et al. Comparison of PCR with blood smear and inoculation of small animals for diagnosis of Babesia microti parasit-emia. J Clin Microbiol 1996; 34: 2791-4.13. Krause PJ, Narasimhan S, Wormser GP, et al. Borrelia miyamotoi sensu lato se-roreactivity and seroprevalence in the northeastern United States. Emerg Infect Dis 2014; 20: 1183-90.14. Molloy PJ, Telford Iii SR, Chowdri HR, et al. Borrelia miyamotoi disease in the northeastern United States: a case series. Ann Intern Med 2015 June 9 (Epub ahead of print).15. Courtney JW, Kostelnik LM, Zeidner NS, Massung RF. Multiplex real-time PCR for detection of Anaplasma phagocyto-philum and Borrelia burgdorferi. J Clin Mi-crobiol 2004; 42: 3164-8.16. Ullmann AJ, Gabitzsch ES, Schulze TL, Zeidner NS, Piesman J. Three multi-plex assays for detection of Borrelia burg-dorferi sensu lato and Borrelia miyamotoi





sensu lato in field-collected Ixodes nymphs in North America. J Med Ento-mol 2005; 42: 1057-62.17. Scoles GA, Papero M, Beati L, Fish D. A relapsing fever group spirochete trans-

mitted by Ixodes scapularis ticks. Vector Borne Zoonotic Dis 2001; 1: 21-34.18. Schwan TG, Schrumpf ME, Hin-nebusch BJ, Anderson DE Jr, Konkel ME. GlpQ: an antigen for serological dis-

crimination between relapsing fever and Lyme borreliosis. J Clin Microbiol 1996; 34: 2483-92.Copyright © 2015 Massachusetts Medical Society.

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