UNASSIGNED: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation.
UNASSIGNED: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed.
UNASSIGNED: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings.
UNASSIGNED: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

BACKGROUND: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB.
METHODS: We searched PubMed, Web of Science, GenBank, CNKI, and eLibrary from Jan 1, 1874, to Dec 31, 2022, for published articles without language restriction to extract distribution data for RFGB detection in vectors, animals, and humans, and clinical information about human patients. Only articles documenting RFGB infection events were included in this study, and data for RFGB detection in vectors, animals, or humans were composed into a dataset. We used three machine learning algorithms (boosted regression trees, random forest, and least absolute shrinkage and selection operator logistic regression) to assess the environmental, ecoclimatic, biological, and socioeconomic factors associated with the occurrence of four major RFGB species: Borrelia miyamotoi, Borrelia lonestari, Borrelia crocidurae, and Borrelia hermsii; and mapped their worldwide risk level.
RESULTS: We retrieved 13 959 unique studies, among which 697 met the selection criteria and were used for data extraction. 29 RFGB species have been recorded worldwide, of which 27 have been identified from 63 tick species, 12 from 61 wild animals, and ten from domestic animals. 16 RFGB species caused human infection, with a cumulative count of 26 583 cases reported from Jan 1, 1874, to Dec 31, 2022. Borrelia recurrentis (17 084 cases) and Borrelia persica (2045 cases) accounted for the highest proportion of human infection. B miyamotoi showed the widest distribution among all RFGB, with a predicted environmentally suitable area of 6·92 million km2, followed by B lonestari (1·69 million km2), B crocidurae (1·67 million km2), and B hermsii (1·48 million km2). The habitat suitability index of vector ticks and climatic factors, such as the annual mean temperature, have the most significant effect among all predictive models for the geographical distribution of the four major RFGB species.
CONCLUSIONS: The predicted high-risk regions are considerably larger than in previous reports. Identification, surveillance, and diagnosis of RFGB infections should be prioritised in high-risk areas, especially within low-income regions.
BACKGROUND: National Key Research and Development Program of China.

The inflammatory response to viral infection is an important component of the antiviral response, a process that involves the activation and proliferation of CD8+ T, CD4+ T, and dendritic cells; thus, viral infection disrupts the immune homeostasis of the organism, leading to an increased release of inflammatory factors. Kikuchi-Fujimoto disease (KFD) is an inflammatory self-limited disorder of unknown etiology, and it is generally believed that the pathogenesis of this disease includes two aspects: viral infection and autoimmune response. Various immune cells, such as CD8+ T lymphocytes, CD4+ T lymphocytes, and CD123+ plasmacytoid dendritic cells, as well as the cytokines they induce and secrete, such as interferons, interleukins, and tumor necrosis factors, play a crucial role in the pathogenesis of KFD. In this article, we present a case study of a young female patient from China who exhibited typical symptoms of lymph node inflammation and fever. The diagnosis of KFD was confirmed through a lymph node biopsy. She presented with elevated ESR, IL-6, and IFN-γ. Viral markers showed elevated IgG and IgM of cytomegalovirus (CMV) and elevated IgG of Epstein-Barr virus (EBV), while changes occurred in the CD4+ T and CD8+ T cell counts. Eventually, the patient achieved disease relief through steroid treatment. Based on these findings, we conducted a comprehensive review of the involvement of viral infection-induced inflammatory response processes and autoimmunity in the pathogenesis of Kikuchi-Fujimoto disease.

Relapsing fever, caused by Borreliae of the relapsing fever groups, is an infectious disease, which would cause spirochaetaemia and repeated fever in human. To comprehensively understand the classification and distribution of relapsing fever, as well as correlated factors, this paper summarizes the progress in research of epidemiology of relapsing fever in the world, and suggests prevention and control measures. The disease is heterogenous and can be divided into three groups according to vectors, i.e. tick-borne relapsing fever, louse-borne relapsing fever and the avian relapsing fever. Tick borne relapsing fever can be further divided into two types: soft tick transmission and hard tick transmission. Soft tick-borne relapsing fever generally has obvious geographical distribution characteristics, while hard tick-borne relapsing fever is widely distributed all over the world. Louse-borne relapsing fever, also known as epidemic forms of relapsing fever, is caused by body lice, and the incidence is usually associated with war, famine, refugees and poor sanitation. The prevention and control of relapsing fever should be based on local conditions.
回归热是一种由回归热螺旋体引起的人感染性疾病。感染回归热一般会造成患者螺旋体血症和反复高热。为了全面了解该病的分类、分布及影响因素等相关内容，本文梳理了全球回归热流行病学研究进展，并提出了防制措施及建议。回归热的类型较为复杂，普遍认为有蜱传回归热、虱传回归热和禽回归热。蜱传回归热又分为软蜱传播和硬蜱传播两种，软蜱传播的回归热有明显的地域特点，而硬蜱传播的回归热在全球广泛分布；虱传回归热的传播媒介为体虱，发病一般与战乱、饥荒、难民、贫困和卫生条件差有关。防控措施的制定应根据当地情况而定。.

Human lice have always been a major public health concern due to their vector capacity for louse-borne infectious diseases, like trench fever, louse-borne relapsing fever, and epidemic fever, which are caused by Bartonella quintana, Borrelia recurrentis, and Rickettsia prowazekii, respectively. Those diseases are currently re-emerging in the regions of poor hygiene, social poverty, or wars with life-threatening consequences. These louse-borne diseases have also caused outbreaks among populations in jails and refugee camps. In addition, antibodies and DNAs to those pathogens have been steadily detected in homeless populations. Importantly, more bacterial pathogens have been detected in human lice, and some have been transmitted by human lice in laboratories. Here, we provide a comprehensive review and update on louse-borne infectious diseases/bacterial pathogens.

Relapsing fever due to Borrelia hermsii is characterized by recurrent bacteremia episodes. However, infection of B. hermsii, if not treated early, can spread to various organs including the central nervous system (CNS). CNS disease manifestations are commonly referred to as relapsing fever neuroborreliosis (RFNB). In the mouse model of B. hermsii infection, we have previously shown that the development of RFNB requires innate immune cells as well as T cells. Here, we found that prior to the onset of RFNB, an increase in the systemic proinflammatory cytokine response followed by sustained levels of IP-10 concurrent with the CNS disease phase. RNA sequencing analysis of the spinal cord tissue during the disease phase revealed an association of the interleukin (IL)-17 signaling pathway in RFNB. To test a possible role for IL-17 in RFNB, we compared B. hermsii infection in wild-type and IL-17A-/- mice. Although the onset of bacteremia and protective anti-B. hermsii antibody responses occurred similarly, the blood-brain barrier permeability, proinflammatory cytokine levels, immune cell infiltration in the spinal cord, and RFNB manifestations were significantly diminished in IL-17A-/- mice compared to wild-type mice. Treatment of B. hermsii-infected wild-type mice with anti-IL-17A antibody ameliorated the severity of spinal cord inflammation, microglial cell activation, and RFNB. These data suggest that the IL-17 signaling pathway plays a major role in the pathogenesis of RFNB, and IL-17A blockade may be a therapeutic modality for controlling neuroborreliosis.

We identified relapsing fever (RF) Borrelia in 1.45% (145/10426) of the ticks and 1.40% (40/2850) of the wild mammals in a field investigation in China. Three RF Borrelia species, including human-pathogenic Borrelia miyamotoi, Borrelia persica and unclassified Babesia sp. were determined. Main species determined from ticks was B. miyamotoi (44.14%), followed by the unclassified Borrelia sp. (42.76%), and Borrelia theileri (13.10%). In wild mammals, main species found was B. persica (57.50%), followed by the unclassified Borrelia sp. (40.00%), and B. miyamotoi (2.50%). We determined B. theileri and B. persica in China for the first time. The coexistence of RF Borrelia species in one tick species in a given region was observed, with the most frequent coexistence seen for B. miyamotoi and the unclassified Borrelia sp. in Dermacentor silvarum, Haemaphysalis japonica, Haemaphysalis longicornis, and Ixodes persulcatuss respectively. The wide distribution and high variety of RF Borrelia in China pose a potential threat to public health.

BACKGROUND: Borrelia miyamotoi is a newly described relapsing fever spirochete transmitted by ixodid tick species. Little is known about the prevalence of B. miyamotoi infections in humans and ticks in Inner Mongolia, China. Therefore, we investigated the prevalence of B. miyamotoi in Ixodes persulcatus ticks, and we aimed to isolateB. miyamotoi from I. persulcatus from four regions of Greater Khingan, Inner Mongolia, China.
METHODS: From May to June each year during the period 2016-2019, host-seeking adult I. persulcatus ticks were collected from vegetation. Genomic DNA was prepared from half of each tick body for PCR template, and the remaining half was used to cultivate B. miyamotoi in BSK-M medium. We employed quantitative real-time PCR (qPCR) to detect Borrelia DNA in the ticks and to calculate the prevalence of B. miyamotoi and infections with other borreliae. For characterization of the isolated B. miyamotoi, we performed draft genome sequencing and multilocus sequencing analysis (MLSA).
RESULTS: A total of 2656 adult I. persulcatus ticks were collected. The overall prevalence of relapsing fever (RF) borreliae in ticks was 5.0% (134/2656) and that of Lyme disease (LD) borreliae was 43.8% (1164/2656). Co-infection with RF and LD borreliae was observed in 63 ticks (2.4%). Ticks that were positive for RF borreliae by qPCR were subjected to glycerophosphodiester diester phosphodiesterase gene (glpQ) PCR amplification and sequencing, through which we identified the RF borrelia specimens as B. miyamotoi. Furthermore, the B. miyamotoi strain Hetao-1 was isolated from I. persulcatus, and a draft genome sequence was obtained from the isolate. Sequencing determined the strain Hetao-1 genome to be approximately 906.1 kbp in length (28.9% average GC content), and MLSA identified the strain as ST633, which has previously been reported in Japan and Mongolia.
CONCLUSIONS: We detected B. miyamotoi from I. persulcatus ticks collected in Inner Mongolia, and successfully isolated a B. miyamotoi strain. To our knowledge, this is the first study to culture a B. miyamotoi isolate from China. The data on the prevalence of B. miyamotoi and other borreliae in I. persulcatus ticks will be fundamental for future epidemiological studies of B. miyamotoi disease in Inner Mongolia.

Borrelia miyamotoi, a member of the tick-borne relapsing fever spirochetes, shows a serum-resistant phenotype in vitro. This ability of B. miyamotoi may contribute to bacterial evasion of the host innate immune system. To investigate the molecular mechanism of serum-resistance, we constructed a membrane protein-encoding gene library of B. miyamotoi using Borrelia garinii strain HT59G, which shows a transformable and serum-susceptible phenotype. By screening the library, we found that bom1093 and bom1515 of B. miyamotoi provided a serum-resistant phenotype to the recipient B. garinii. These B. miyamotoi genes are predicted to encode P35-like antigen genes and are conserved among relapsing fever borreliae. Functional analysis revealed that BOM1093 bound to serum vitronectin and that the C-terminal region of BOM1093 was involved in the vitronectin-binding property. Importantly, the B. garinii transformant was not serum-resistant when the C terminus-truncated BOM1093 was expressed. We also observed that the depletion of vitronectin from human serum enhances the bactericidal activity of BOM1093 expressing B. garinii, and the survival rate of BOM1093 expressing B. garinii in vitronectin-depleted serum is enhanced by the addition of purified vitronectin. Our data suggests that B. miyamotoi utilize BOM1093-mediated binding to vitronectin as a mechanism of serum resistance.

Bats can harbor zoonotic pathogens causing emerging infectious diseases, but their status as hosts for bacteria is limited. We aimed to investigate the distribution, prevalence and genetic diversity of Borrelia in bats and bat ticks in Hubei Province, China, which will give us a better understanding of the risk of Borrelia infection posed by bats and their ticks. During 2018-2020, 403 bats were captured from caves in Hubei Province, China, 2 bats were PCR-positive for Borrelia. Sequence analysis of rrs, flaB and glpQ genes of positive samples showed 99.55%-100% similarity to Candidatus Borrelia fainii, a novel human-pathogenic relapsing fever Borrelia species recently reported in Zambia, Africa and Eastern China, which was clustered together with relapsing fever Borrelia species traditionally reported only in the New World. Multilocus sequence typing (MLST) and pairwise genetic distances further confirmed the Borrelia species in the bats from Central China as Candidatus Borrelia fainii. No Borrelia DNA was detected in ticks collected from bats. The detection of this human-pathogenic relapsing fever Borrelia in bats suggests a wide distribution of this novel relapsing fever Borrelia species in China, which may pose a threat to public health in China.