• View in gallery

    The clinical course of the case. Day: the days after the hospitalization.

  • View in gallery

    The hospitalized medical data. Day: the days after the hospitalization. The normal ranges of each item are as follows; C-reactive protein (CRP): less than 0.3 mg/dL, aspartate aminotransferase (AST): 8–38 U/L, alanine aminotransferase (ALT): 4–44 U/L, red blood cell (RBC): 410–540 × 104 cells/μL, white blood cell (WBC): 4–8 × 103 cells/μL, platelet: 12–40 × 104 cells/μL and neutrophilia (Neut): 45–74%.

  • View in gallery

    Immunoblot analysis of serum reactivity to glycerophosphoryl diester phosphodiesterase antigen. A; acute phase serum and C: convalescent phase serum.

  • 1.

    Fukunaga M, Takahashi Y, Tsuruta Y, Matsushita O, Ralph D, Michael M, Nakao M, 1995. Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov. isolated from the ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol 45: 804810.

    • Search Google Scholar
    • Export Citation
  • 2.

    Okino T, Ushirogawa H, Matoba K, Hatsushika R, 2009. Bibliographical studies on human cases of hard tick (acarina: ixodidae) bites in Japan (3) cases of Ixodes persulcatus infection. Kawasaki Med J. 35: 6780.

    • Search Google Scholar
    • Export Citation
  • 3.

    Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA, Toporkova MG, Maleev VV, Fish D, Krause PJ, 2011. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis 17: 18161823.

    • Search Google Scholar
    • Export Citation
  • 4.

    Krause PJ, Fish D, Narasimhan S, Barbour AG, 2015. Borrelia miyamotoi infection in nature and in humans. Clin Microbiol Infect 21: 631639.

  • 5.

    Sato K, Takano A, Konnai S, Nakao M, Ito T, Koyama K, Kaneko M, Ohnishi M, Kawabata H, 2014. Human infections with Borrelia miyamotoi, Japan. Emerg Infect Dis 20: 13911393.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ohashi N, Gaowa Wuritu, Kawamori F, Wu D, Yoshikawa Y, Chiya S, Fukunaga K, Funato T, Shiojiri M, Nakajima H, Hamauzu Y, Takano A, Kawabata H, Ando S, Kishimoto T, 2013. Human granulocytic anaplasmosis, Japan. Emerg Infect Dis 19: 289292.

    • Search Google Scholar
    • Export Citation
  • 7.

    Zamoto-Niikura A, Morikawa S, Hanaki KI, Holman PJ, Ishihara C, 2016. Ixodes persulcatus ticks as vectors for the Babesia microti U.S. lineage in Japan. Appl Environ Microbiol 82: 66246632.

    • Search Google Scholar
    • Export Citation
  • 8.

    Barbour AG, Bunikis J, Travinsky B, Hoen AG, Diuk-Wasser MA, Fish D, Tsao JI, 2009. Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector mammalian reservoir species. Am J Trop Med Hyg 81: 11201131.

    • Search Google Scholar
    • Export Citation
  • 9.

    Molloy PJ, Telford SR 3rd, Chowdri HR, Lepore TJ, Gugliotta JL, Weeks KE, Hewins ME, Goethert HK, Berardi VP, 2015. Borrelia miyamotoi disease in the northeastern United States: a case series. Ann Intern Med 163: 9198.

    • Search Google Scholar
    • Export Citation
  • 10.

    Krause PJ, Narasimhan S, Wormser GP, Barbour AG, Platonov AE, Brancato J, Lepore Dardick K, Mamula M, Rollend L, Steeves TK, Diuk-Wasser M, Usmani-Brown S, Williamson P, Sarksyan DS, Fikrig E, Fish DTick Borne Diseases Group, 2014. Borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern United States. Emerg Infect Dis 20: 11831190.

    • Search Google Scholar
    • Export Citation
  • 11.

    Parola P, Raoult D, 2001. Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis 32: 897928.

  • 12.

    Takano A, Muto M, Sakata A, Ogasawara Y, Ando S, Hanaoka N, Tsurumi M, Sato F, Nakamura N, Fujita H, Watanabe H, Kawabata H, 2009. Relapsing fever spirochete in seabird tick, Japan. Emerg Infect Dis 15: 15281530.

    • Search Google Scholar
    • Export Citation
  • 13.

    Schwan TG, Schrumpf ME, Hinnebusch BJ, Anderson DE Jr, Konkel ME, Glp Q, 1996. An antigen for serological discrimination between relapsing fever and Lyme borreliosis. J Clin Microbiol 34: 24832492.

    • Search Google Scholar
    • Export Citation
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Case Report: Clinical Features of a Case of Suspected Borrelia miyamotoi Disease in Hokkaido, Japan

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  • 1 Department of Infectious Diseases, Hokkaido Institute of Public Health, Sapporo Japan;
  • | 2 Clinical Laboratory, Higashiasahikawa Hospital, Higashiasahikawa, Asahikawa, Japan;
  • | 3 General Internal Medicine, Higashiasahikawa Hospital, Higashiasahikawa, Asahikawa, Japan;
  • | 4 Department of Food and Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan;
  • | 5 Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan;
  • | 6 Department of Bacteriology-I, National Institute of Infectious Diseases, Tokyo, Japan

We herein report a case of suspected Borrelia miyamotoi disease in Hokkaido, Japan. The patient complained of lassitude, arthralgia, and high fever after a tick bite. Furthermore, at the time of consultation, the patient exhibited momentary loss of consciousness and low blood pressure. Laboratory tests revealed elevation of liver enzymes, thrombocytopenia, and increased C-reactive protein. Seroconversion to B. miyamotoi glycerophosphoryl diester phosphodiesterase antigen suggested the patient was infected with a relapsing fever group Borrelia species.

Introduction

Borrelia miyamotoi is a spirochete belonging to the relapsing fever group Borrelia, and is distantly related to the borreliae that cause Lyme disease. It was first discovered in Japan in 1995 by Fukunaga and others1 and is transmitted there by the tick species Ixodes persulcatus, which is also the primary vector tick of Lyme disease in Japan.2 Borrelia miyamotoi infection (B. miyamotoi disease: BMD) causes a variety of symptoms including relapsing fever. The first human cases were reported in Russia in 2011.3 Since 2013, BMD cases have been reported in northern hemisphere countries.4 In 2014, through retrospective investigation of confirmed Lyme disease patients in Japan, sera from two patients were shown to also contain B. miyamotoi DNA in their serum.5 Since 2013, we have conducted prospective serodiagnosis for Lyme disease and/or BMD and have now detected the first symptomatic case in Japan of BMD without coinfection with Lyme disease Borrelia, Babesia spp., or Anaplasma phagocytophilum.

Case

The patient was a previously healthy 64-year-old Japanese man surveyor living in Hokkaido, Japan, where Lyme disease is endemic. He entered the hills and fields for outdoor work routinely. He did not have any history of travel abroad. His latest field activity was 10 days before onset. The patient was later able to recall a hard tick bite to his left shoulder during this latest excursion. However, he was unable to identify the tick species or whether the tick was visibly engorged.

At the time of consultation on August 17, 2013, the main complaint was lassitude, arthralgia, and relapsing fever (Figure 1

Figure 1.
Figure 1.

The clinical course of the case. Day: the days after the hospitalization.

Citation: The American Society of Tropical Medicine and Hygiene 97, 1; 10.4269/ajtmh.16-0699

). Furthermore, in the waiting room of the hospital, the patient was observed by health-care works to exhibit momentary loss of consciousness and low blood pressure (84–40 mmHg). He had a fever of 38.6°C and his Glasgow Coma Scale score was 14 (E3V5M6), requiring hospitalization. His body temperature increased to 39.2°C during the night of hospitalization (day 1). A diffuse macular erythematous rash was noted on his torso (day 1), which disappeared within a week. Magnetic resonance imaging of the brain showed no abnormalities. Evidence of tick bite or erythema migrans was not found.

Medical and laboratory data during the hospital stay are listed in Figure 2

Figure 2.
Figure 2.

The hospitalized medical data. Day: the days after the hospitalization. The normal ranges of each item are as follows; C-reactive protein (CRP): less than 0.3 mg/dL, aspartate aminotransferase (AST): 8–38 U/L, alanine aminotransferase (ALT): 4–44 U/L, red blood cell (RBC): 410–540 × 104 cells/μL, white blood cell (WBC): 4–8 × 103 cells/μL, platelet: 12–40 × 104 cells/μL and neutrophilia (Neut): 45–74%.

Citation: The American Society of Tropical Medicine and Hygiene 97, 1; 10.4269/ajtmh.16-0699

. Elevated C-reactive protein (panel B), alanine aminotransferase (panel C), and aspartate aminotransferase (panel C) were noted. Red blood cell (panel D) and white blood cell (panel E) counts were almost within reference range. Neutrophilia (panel F) was noted only on day 2 of hospitalization, but neutrophils fell to below reference range on day 4. Thrombocytopenia was noted from days 1 to 5 of hospitalization.

Although the etiology was not identified during initial evaluation, the patient was prescribed penicillin derivative antibiotics (sultamicillin and amoxicillin) from day 2 to day 17 (Figure 1). Serological examination for Lyme disease, BMD, anaplasmosis, and babesiosis were performed on late acute (day 31) and convalescent (day 60) phase serum samples. Lyme disease was ruled out by serodiagnosis using the commercial immunoblot kit: recomLine Borrelia IgG/IgM (MIKROGEN DIAGNOSTIK, Neuried, Germany). The patient sera reacted only to p41 antigen from Borrelia burgdorferi sensu stricto in both IgM and IgG and were therefore seronegative. On the other hand, the patient was seropositive against a recombinant glycerophosphoryl diester phosphodiesterase (rGlpQ) antigen5 in paired serum samples. For the serological test to BMD, rGlpQ originated from B. miyamotoi strain HT31 (accession number. AB900798) was used. The purified rGlpQ (0.1 μg) was used for immunoblotting assay. The dilution of each patient's serum sample was 1:200. By this assay, a rise in IgG level was noted: acute phase serum showed IgG (−)/IgM (+) and convalescent phase serum showed IgG (+)/IgM (+) (Figure 3

Figure 3.
Figure 3.

Immunoblot analysis of serum reactivity to glycerophosphoryl diester phosphodiesterase antigen. A; acute phase serum and C: convalescent phase serum.

Citation: The American Society of Tropical Medicine and Hygiene 97, 1; 10.4269/ajtmh.16-0699

). The patient was diagnosed with BMD based on the seroconversion to anti-B. miyamotoi GlpQ antibody. In retrospect, the medical data, with the exception of the neutropenia, were considered consistent with the characteristics of BMD. Based on negative serologic testing,6,7 there was no evidence of coinfection A. phagocytophilum or Babesia spp. (data not shown). On antibiotics, the fever gradually subsided, and the symptoms abated. Antibiotics, sultamicillin and amoxicillin, were thought to be effective for this case.

Real-time PCR for detection of Borrelia DNA and quantitative PCR for estimation of the number of copies of DNA were also performed on late acute phase serum as previously described.5,8 In this case, borrelial DNA was not detected and may have been below the detection limit. Molloy and others9 suggested detection of a borrelial DNA from clinical specimens is likely a superior method of diagnosis compared with serology. However, they also reported serological diagnosis (e.g., seroconversion) is an acceptable alternative when bacterial DNA is not detected.9,10

The patient was able to recall a tick bite, and he did not have any history of travel abroad, including to endemic areas of classical relapsing fever (e.g., African countries, south European countries, and North America).11 A domestic case of relapsing fever due to other Borrelia species has not been reported in Japan since the 1950s.12 Serodiagnosis using B. miyamotoi GlpQ-antigen is specific to relapsing fever group borreliae,13 and the clinical and epidemiological data are consistent with B. miyamotoi infection.

Conclusion

Hokkaido is located in the northern part of Japan, and I. persulcatus, which is thought to transmit B. miyamotoi, is ubiquitously found throughout Hokkaido. This is the first report in Japan of human B. miyamotoi illness without coinfection. In this case, laboratory tests were performed and monitored for 40 days after onset of disease. This report should alert physicians in the region to be aware of BMD when examining patients with suggestive symptoms.

Acknowledgment:

We thank Kyle R. Taylor for critical reading and editing of this manuscript.

REFERENCES

  • 1.

    Fukunaga M, Takahashi Y, Tsuruta Y, Matsushita O, Ralph D, Michael M, Nakao M, 1995. Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov. isolated from the ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol 45: 804810.

    • Search Google Scholar
    • Export Citation
  • 2.

    Okino T, Ushirogawa H, Matoba K, Hatsushika R, 2009. Bibliographical studies on human cases of hard tick (acarina: ixodidae) bites in Japan (3) cases of Ixodes persulcatus infection. Kawasaki Med J. 35: 6780.

    • Search Google Scholar
    • Export Citation
  • 3.

    Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA, Toporkova MG, Maleev VV, Fish D, Krause PJ, 2011. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis 17: 18161823.

    • Search Google Scholar
    • Export Citation
  • 4.

    Krause PJ, Fish D, Narasimhan S, Barbour AG, 2015. Borrelia miyamotoi infection in nature and in humans. Clin Microbiol Infect 21: 631639.

  • 5.

    Sato K, Takano A, Konnai S, Nakao M, Ito T, Koyama K, Kaneko M, Ohnishi M, Kawabata H, 2014. Human infections with Borrelia miyamotoi, Japan. Emerg Infect Dis 20: 13911393.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ohashi N, Gaowa Wuritu, Kawamori F, Wu D, Yoshikawa Y, Chiya S, Fukunaga K, Funato T, Shiojiri M, Nakajima H, Hamauzu Y, Takano A, Kawabata H, Ando S, Kishimoto T, 2013. Human granulocytic anaplasmosis, Japan. Emerg Infect Dis 19: 289292.

    • Search Google Scholar
    • Export Citation
  • 7.

    Zamoto-Niikura A, Morikawa S, Hanaki KI, Holman PJ, Ishihara C, 2016. Ixodes persulcatus ticks as vectors for the Babesia microti U.S. lineage in Japan. Appl Environ Microbiol 82: 66246632.

    • Search Google Scholar
    • Export Citation
  • 8.

    Barbour AG, Bunikis J, Travinsky B, Hoen AG, Diuk-Wasser MA, Fish D, Tsao JI, 2009. Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector mammalian reservoir species. Am J Trop Med Hyg 81: 11201131.

    • Search Google Scholar
    • Export Citation
  • 9.

    Molloy PJ, Telford SR 3rd, Chowdri HR, Lepore TJ, Gugliotta JL, Weeks KE, Hewins ME, Goethert HK, Berardi VP, 2015. Borrelia miyamotoi disease in the northeastern United States: a case series. Ann Intern Med 163: 9198.

    • Search Google Scholar
    • Export Citation
  • 10.

    Krause PJ, Narasimhan S, Wormser GP, Barbour AG, Platonov AE, Brancato J, Lepore Dardick K, Mamula M, Rollend L, Steeves TK, Diuk-Wasser M, Usmani-Brown S, Williamson P, Sarksyan DS, Fikrig E, Fish DTick Borne Diseases Group, 2014. Borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern United States. Emerg Infect Dis 20: 11831190.

    • Search Google Scholar
    • Export Citation
  • 11.

    Parola P, Raoult D, 2001. Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis 32: 897928.

  • 12.

    Takano A, Muto M, Sakata A, Ogasawara Y, Ando S, Hanaoka N, Tsurumi M, Sato F, Nakamura N, Fujita H, Watanabe H, Kawabata H, 2009. Relapsing fever spirochete in seabird tick, Japan. Emerg Infect Dis 15: 15281530.

    • Search Google Scholar
    • Export Citation
  • 13.

    Schwan TG, Schrumpf ME, Hinnebusch BJ, Anderson DE Jr, Konkel ME, Glp Q, 1996. An antigen for serological discrimination between relapsing fever and Lyme borreliosis. J Clin Microbiol 34: 24832492.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Hiroki Kawabata, Department of Bacteriology-I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. E-mail: kbata@nih.go.jp

Financial support: The research was supported by the Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (AMED).

Authors' addresses: Kimiaki Yamano, Department of Biological Science, Hokkaido Institute of Public Health, Sapporo, Japan, E-mail: yamano@iph.pref.hokkaido.jp. Takuya Ito, Department of Infectious Diseases, Hokkaido Institute of Public Health, Sapporo, Japan, E-mail: takuya@iph.pref.jokkaido.jp. Kaori Kiyanagi, Clinical Laboratory, Higashiasahikawa Hospital, Asahikawa, Japan, E-mail: labo@abox.so-net.ne.jp. Hirotaka Yamazaki, Mutsubu Sugawara, and Takashige Saito, General Internal Medicine, Higashiasahikawa Hospital, Asahikawa, Hokkaido, Japan, E-mails: hiroy123@gmail.com, gbc03625@nifty.ne.jp, and t-saito@mvb.biglobe.ne.jp. Norio Ohashi, Department of Food and Nutritional Science, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan, E-mail: ohashi@u-shizuoka-ken.ac.jp. Aya Zamoto-Niikura, Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo, Japan, E-mail: zamoto@nih.go.jp. Kozue Sato and Hiroki Kawabata, Department of Bacteriology-I, National Institute of Infectious Diseases, Tokyo, Japan, E-mails: sokozue@nih.go.jp and kbata@nih.go.jp.

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