Case Report: The First Borrelia yangtzensis Infection in a Human in Korea

ABSTRACT.

Borrelia yangtzensis has been identified in rodents and ticks in China and Japan. A 57-year-old woman with bite mark was diagnosed with B. yangtzensis infection via molecular and serological testing. Here, we report the first case of human infection caused by B. yangtzensis in Korea.

Lyme disease is a systemic spirochete infection, mediated by a hard tick infected with Borrelia burgdorferi sensu lato species complex, comprising at least 20 genospecies, such as B. burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii. The genospecies of this complex are responsible for causing Lyme borreliosis in humans in different geographical regions.¹ Borrelia burgdorferi sensu stricto causing Lyme borreliosis has been reported in the United States; however, B. burgdorferi, B. afzelii, and B. garinii are the major pathogens in Europe. Additionally, B. afzelii and B. garinii are known pathogens of Lyme disease in Asia.²

Borrelia yangtzensis has been identified in rodents and ticks in China and Japan.³ In Korea, B. yangtzensis was identified in Apodemus agrarius through the multilocus sequence typing analysis and also found in engorged ticks attached to wild rodent captured in Jeju Island.^1,4 This report describes the first human infection caused by B. yangtzensis.

CASE

A 57-year-old woman traveled to the Taean Peninsula approximately 3 weeks prior to presentation in early September. While sitting on the grass, she noticed a bite mark on her right leg but did not see any ticks. Two weeks later, a papular rash developed throughout her body. One week later, she presented to the Dermatology Department at Chosun University Hospital, where she was prescribed with 12 mg of methylprednisolone for 14 days. Five days later, she was referred to the Division of Infectious Diseases for assessment of headaches, and a photograph was taken (Figure 1A); however, aside from the headache, there were no other symptoms, including fever.

Figure 1. (A) A skin lesion, suspected to be a tick bite, on the right leg of a 57-year-old woman. (B) The phylogenetic tree, using amplicon sequencing, confirmed the presence of a Borrelia species-specific CTP synthase (pyrG) gene, targeting nested polymerase chain reaction (N-PCR), in the blood of the 57-year-old woman. This figure appears in color at www.ajtmh.org.

Complete blood count testing at this hospital revealed the following: leukocytes, 7,140/mm³; hemoglobin, 13.8 g/dL; platelets, 224,000/mm³; and creatinine, 0.61 mg/dL. Her liver function test results were overall normal, with aspartate aminotransferase/alanine transaminase of 19.3/20.4 (IU)/L and total bilirubin of 0.54 mg/dL. However, due to the epidemiological situation and the bite mark, which resembled a tick bite (Figure 1A), a tick-borne infection was suspected. Doxycycline 100 mg bid was prescribed for 7 days, and polymerase chain reaction (PCR) and indirect immunofluorescence antibody (IFA) tests were performed to identify various vector-borne infections, such as rickettsiosis, Lyme disease, scrub typhus, and anaplasmosis (Table 1).^5–7

Table 1.

PCR and IFA antibody test results of a 57-year-old female patient

Sample collection day	PCR				IFA
	OT	RC	AP	BB	OT		RC		AP		BB
	56-kDa	ompA	ankA	pyrG
					IgG	IgM	IgG	IgM	IgG	IgM	IgG	IgM
	N-PCR	N-PCR	N-PCR	N-PCR
September 27, 2018	–	–	–	+	< 1:16	< 1:16	< 1:64	< 1:64	< 1:80	< 1:16	< 1:16	< 1:16
October 4, 2018					< 1:16	< 1:16	< 1:64	< 1:64	< 1:80	< 1:16	< 1:16	< 1:16
October 25, 2018	–			–	< 1:16	< 1:16	< 1:64	< 1:64	< 1:80	< 1:16	1:32	< 1:16

AP = Anaplasma phagocytophilum; BB = Borrelia burgdorferi; IFA = indirect immunofluorescence antibody assay; N-PCR = nested polymerase chain reaction; OT = Orientia tsutsugamushi; PCR = polymerase chain reaction; RC = Rickettsia conorii.

The Borrelia species-specific cytidine 5′-triphosphate (CTP) synthase (pyrG) gene targeting nested PCR (N-PCR) test, conducted using B. burgdorferi as a positive control, was positive. The BlastN results matched 100% (603/603 base pair [bp]) with the B. yangtzensis strain R5 (accession no. KT353730) identified in the Apodemus mouse in China, and 99.67% (601/603bp) with the B. yangtzensis isolate Okinawa-MC8B05 (accession no. AB526001) found in wild rats in Japan (Figure 1B). The phylogenetic tree result showed clustering with B. yangtzensis. However, the PCR results were negative for all vector-borne infections, excluding Borrelia. After 1 week of doxycycline treatment, the patient’s symptoms only partially improved, and she was prescribed with 100 mg of doxycycline for an additional 7 days as an outpatient. B. burgdorferi targeting IFA was conducted in coordination with the Korea Disease Control and Prevention Agency, with samples from the patient’s hospital presentation. No antibodies were identified with both IgM and IgG antibodies at 1:16. The IFA test was conducted approximately 1 month after the patient demonstrated a 1:32 IgG against the B. burgdoferi antigen (Table 1).

DISCUSSION

Lyme disease is a vector-borne infectious disease that occurs predominantly in North America, Europe, and Asia when a tick infected with B. burgdorferi, B. afzelii, or B. garinii bites a human. Numerous Borrelia samples were isolated from rodents and ticks in the Yangtze River in China. Because Borrelia, which is similar to Borrelia valaisiana, is often found in birds, the pathogen was named B. yangtzensis.³

In a study conducted in Malaysia, 72 out of 156 adult ticks were positive for Borrelia species on PCR. All Borrelia PCR-positive ticks were Ixodes granulatus ticks, not other tick species, including Dermacentor or Amblyomma species. Moreover, phylogenetic analyses based on partial flaB gene sequences from Borrelia PCR-positive tick samples showed Borrelia spp. clustered with B. yangtzensis.⁸

To date, predominant Borrelia species identified in South Korea include B. afzelii and B. garinii. Borrelia miyamotoi has been identified in Ixodes nipponensis ticks by some researchers,^9,10 and B. yangtzensis has not been identified in humans in South Korea.^1,4

In conclusion, B. yangtzensis has been reported in ticks and rodents originating in China, Japan, and Malaysia. This is the first case of a B. yangtzensis infection in a human in Korea. Therefore, future studies on ticks that carry this bacterium and its reservoirs as well as studies on the role of this pathogen are needed.