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.

Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern Hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). Borrelia miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus, has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein, we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi.

Tick borne relapsing fever (TBRF) is a zoonosis caused by various Borrelia species transmitted to humans by both soft-bodied and (more recently recognized) hard-bodied ticks. In recent years, molecular diagnostic techniques have allowed to extend our knowledge on the global epidemiological picture of this neglected disease. Nevertheless, due to the patchy occurrence of the disease and the lack of large clinical studies, the knowledge on several clinical aspects of the disease remains limited. In order to shed light on some of these aspects, we have systematically reviewed the literature on TBRF and summarized the existing data on epidemiology and clinical aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of TBRF published in English, French, Italian, German, and Hungarian were included. Maps showing the epidemiogeographic mosaic of the different TBRF Borrelia species were compiled and data on clinical aspects of TBRF were analysed. The epidemiogeographic mosaic of TBRF is complex and still continues to evolve. Ticks harbouring TBRF Borrelia have been reported worldwide, with the exception of Antarctica and Australia. Although only molecular diagnostic methods allow for species identification, microscopy remains the diagnostic gold standard in most clinical settings. The most suggestive symptom in TBRF is the eponymous relapsing fever (present in 100% of the cases). Thrombocytopenia is the most suggestive laboratory finding in TBRF. Neurological complications are frequent in TBRF. Treatment is with beta-lactams, tetracyclines or macrolids. The risk of Jarisch-Herxheimer reaction (JHR) appears to be lower in TBRF (19.3%) compared to louse-borne relapsing fever (LBRF) (55.8%). The overall case fatality rate of TBRF (6.5%) and LBRF (4-10.2%) appears to not differ. Unlike LBRF, where perinatal fatalities are primarily attributable to abortion, TBRF-related perinatal fatalities appear to primarily affect newborns.

The overall failure rate of standard therapeutic options for late/chronic/persistent borreliosis emphasizes the need for novel therapeutic strategies. In this report, we are presenting a novel therapeutic option based on a new technology, Induced Native Phage Therapy (INPT; PhagenCorp, LLC, Sarasota, FL), and its ability to facilitate the elimination of infection more rapidly, efficiently, and with less harm to the patient than conventional treatments. Borrelia species in the environment are themselves always infected by their own type of Borrelia bacteriophages. Both the Borrelia spirochete and the Borrelia bacteriophages are transmitted into humans via the bite of a vector, such as ticks. The Borrelia bacteriophages (phages) are called native phages in that they coexist naturally within the human body, and only infect the specific bacteria host population. Native phages persist in humans only as long as there are host bacteria of the correct type to continue replicating more phages. The purposeful manipulation of native phages to kill their host bacteria is the basis of INPT. INPT is a patent-pending technology that uses a proprietary adjunctive assay called Biospectral Emission Sequencing to identify and isolate the specific complex electromagnetic signatures necessary to induce the native phages to epigenetically revert from their normal quiescent, lysogenic activity to virulent, lytic activity, thereby killing their host bacteria. The strategic subtle, low-frequency/low-energy signatures are imprinted into a proprietary oral formula, Inducen-LD, which serves as a carrier to introduce the signals therapeutically into the body. As a proof-of-concept method validation, a total of 26 patients with post-treatment (antibiotic) Lyme disease syndrome, who initially were found upon Phelix Borrelia-phage testing (R.E.D. Laboratories, Belgium) to have one or more Borrelia species, were submitted to INPT treatment. A total of 20 patients (77%) were found to be negative after two weeks of the total program of care. Six patients who remained positive after the initial therapy received an extended INPT treatment and were retested. Four were subsequently found to be negative for one or more of their previously diagnosed Borrelia strains. Thus a total of 24 out of 26 (92%) patients were successfully treated with INPT. Mild to substantial clinical improvements were reported by all participants without noticeable adverse reactions to the INPT treatments. We have demonstrated a possible mechanism in which native bacteriophages can be induced to epigenetically switch from lysogenic to lytic actions, thereby eliminating the targeted bacteria efficiently, with little to no harm to tissues or the microbiome.

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease\'s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch-Herxheimer reaction (JHR), and impact on pregnancy. Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown. Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases. LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease\'s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus. Since the disease has had its heyday before the days of modern medicine, many of its aspects have never been formally studied and to date, remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF, since the recognition of its mode of transmission in 1907, and summarized the existing data on epidemiology and diagnostic aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. Historically, Ethiopia is considered a stronghold of LBRF. The recognition of LBRF among East African migrants (originating from Somalia, Eritrea, and Ethiopia) arriving to Europe in the course of the recent migration flow from this region suggests that this epidemiological focus ostensibly persists. Currently, there is neither evidence to support or refute active transmission foci of LBRF elsewhere on the African continent, in Latin America, or in Asia. Microscopy remains the most commonly used method to diagnose LBRF. Data are lacking on sensitivity and specificity of most diagnostic methods.

BACKGROUND: It is not uncommon that a child with a febrile illness of unknown etiology is admitted to the hospital. When the complete blood count reveals a pancytopenia, the diagnostic process can be a real challenge.
METHODS: A 13-year girl of Arab-Berber descent presented with abdominal pain and fever after a holiday in northwestern Morocco. A complete blood count revealed a pancytopenia and blood smear test results revealed spirochetes. Borrelia hispanica was identified by sequencing the 16S ribosomal ribonucleic acid gene. Our patient was treated with tetracyclines and during this treatment we saw full clinical and hematological recovery.
CONCLUSIONS: Borrelia hispanica is a known cause of tick-borne relapsing fever and is transmitted to humans through the bite of soft ticks of the genus Ornithodoros (Alectorobius). Although the link between tick-borne relapsing fever and thrombocytopenia has been documented, there are only a few case reports of tick-borne relapsing fever presenting with pancytopenia. To the best of our knowledge, there is no previous report of Borrelia hispanica presenting with pancytopenia.

OBJECTIVE: Currently louse-borne relapsing fever (LBRF) is primarily found in limited endemic foci in Ethiopia, Somalia and Sudan; no case of imported LBRF has been reported in Europe in the 9 years prior to 2015. The aim of our paper is to describe a new case of imported LBRF detected in Sicily, Italy, and to review all cases reported in migrants arrived in Europe in the last 10 years.
METHODS: Mini review of all published cases of louse-borne relapsing fever in Europe in the last 10 years.
METHODS: A computerized search without language restriction was conducted using PubMed combining the terms \'(louse-borne relapsing fever or LBRF or recurrentis) and (refugee or Europe or migrant)\' without limits. Furthermore, the \'Ahead-of-Print Articles\' of the top 10 journals (ranked by Impact factor - Web of Science) of Infectious diseases and of Epidemiology were checked.
RESULTS: Our search identified 26 cases of LBRF between July and October 2015 in migrants recently arrived in Europe: 8 had been described in Italy; 1 in Switzerland; 2 in the Netherlands; 15 in Germany. We describe data regarding the clinical characteristics, diagnostic methods, therapy and outcome of these patients and of the new case.
CONCLUSIONS: LBRF by Borrelia recurrentis should be considered among the clinical hypotheses in migrants presenting with fever, headache, chills, sweating, arthralgia, myalgia, dizziness, nausea and vomiting.

Relapsing fever borreliae were notorious and feared infectious agents that earned their place in history through their devastating impact as causes of both epidemic and endemic infection. They are now considered more as an oddity, and their burden of infection is largely overshadowed by other infections such as malaria, which presents in a similar clinical way. Despite this, they remain the most common bacterial infection in some developing countries. Transmitted by soft ticks or lice, these fascinating spirochetes have evolved a myriad of mechanisms to survive within their diverse environments.