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Borreliaceae is a family of the phylum Spirochaetales and includes two genera, Borrelia and Cristispira genus. Borrelia genus is divided into three groups, namely Lyme group (LG), Echidna‐Reptile group (REPG) and Relapsing Fever group (RFG). All Borrelia species have an obligate parasitic lifestyle, as they depend on their hosts for most of their nutritional needs. Borreliæ are transmitted among vertebrate hosts by arthropod vectors (ticks and lice). Transtadial transmission within their carriers occurs for the Borreliæ RF Group, while this does not (or rarely occurs) for the Borreliæ Lyme Group. Phylogenetic data demonstrated that these two groups are genetically similar but distinct, forming independent clades sharing a common ancestor. In nature, the vectors of LB belong to the genus Ixodes spp. frequently found in the Northern Hemisphere, while the vectors of RF are usually the soft-ticks (Ornithodoros spp.). Borreliae share a unique genomic structure consisting of a single highly conserved linear chromosome and several linear and circular extrachromosomal plasmids which can vary widely between strains. In addition to Lyme and RF borreliosis, an intermediate group, called Echidna-Reptile borreliosis, has recently been identified. Lyme disease (LD) is caused by the spirochæte Borrelia burgdorferi sensu lato (s.l.) and transmitted to humans by the bite of a hard tick of the genus Ixodes, and LD reservoir are usually small rodents. LD is present in America, Eurasia, Africa, while its presence in Australia is not yet well documented. Not all Borreliæ Lyme Groups cause this disease in humans. Of the 23 Borreliæ burgdorferi s.l. currently known only 9 have been identified in human infection, namely Borrelia burgdorferi sensu stricto, B. afzelii, B. bavarensis, B. bissettii, B. garinii, B. lusitaniae, B. spielmani, B. valaisiana, and B. mayonii. LD is an organotropic infection, but there is also a spirochætemic form, caused by Borrelia mayonii, which gives fever similarly to the Borreliosis RF Group. A third variant of LD is Baggio-Yoshinari Syndrome (BYS), which is transmitted by another hard tick, Amblyomma cajennense. This Borrelia has not been isolated in culture, therefore its membership in the Lyme Group is not yet proven. All three of these Sub-Groups can manifest early with erythema migrans. Clinical features of LD are wide and variable, with clinical manifestations linked to distinct tissue tropisms of specific Borrelia burgdorferi s.l. genospecies. The early infection is localized and, in the absence of treatment, the spirochete can spread. The organs most frequently involved are skin, joints, muscles, nervous system, heart and eyes. B. burgdorferi s.s. is more often associated with Lyme arthritis, Borrelia garinii with neuroborreliosis and B. afzelii with acrodermatitis chronica atrophicans.

Lyme Borreliosis (LB) is an infection transmitted by Ixodes sp. ticks. Its early manifestation includes erythema migrans rash. Since the discovery of LB in 1975, the question arose as to whether this infection could be vertically transmitted from mother to fetus during pregnancy, as transplacental transmission has already been known for other spirochetoses, such as syphilis, relapsing fever and leptospirosis. The first confirmed case with positive Lyme serology was described in 1985 in a 28-year- old mother who had acquired Lyme in the first trimester and then developed an erythema migrans rash. Subsequently, transmission of Borrelia burgdorferi sl. in humans from mother to fetus has been documented through identification of Borrelia spirochetes in fetal tissues/and or placenta by various methods including culture, PCR and indirect immunofluorescence. Adverse birth outcomes, which are limited in case of prompt LB treatment, included spontaneous miscarriage, preterm birth and hyperbilirubinemia, but also cardiac involvement and cutaneous angiomas have been documented although rarely. No significant associations were found between adverse outcomes at birth and the trimester of infection. Patients treated for gestational LB had a lower frequency of miscarriages and premature births, as also the frequency of congenital malformations was similar to that observed in the normal population. The recommended treatment for LB in pregnancy is Amoxicillin, 1 g 3 times a day for 14–21 days. In the present study, we report our case series, which includes 11 pregnant women, 6 of which developed erythema migrans during pregnancy (between week 8 and 34), 3 had myoarticular or neurological symptoms and 2 had positive serology, but did not develop any clinical symptoms. Our data stress on the importance of early antibiotic treatment also in seropositive gestating women without symptoms in order to avoid any possible complication to fetus and newborns.

Simple Summary Borreliae are spirochaetes, which represent a heterogeneous phylum within bacteria. Spirochaetes are indeed distinguished from other bacteria for their spiral shape, which also characterizes Borreliae. This review describes briefly the organization of the phylum Spirocheteales with a digression about its pathogenicity and historical information about bacteria isolation and characterization. Among spirochaetes, Borrelia genus is here divided into three groups, namely the Lyme group (LG), the Echidna-Reptile group (REPG) and the Relapsing Fever group (RFG). Borreliae Part 1 deals with Lyme group and Echidna-Reptile group Borreliae, while the subject of Borreliae Part 2 is Relapsing Fever group and unclassified Borreliae. Lyme group Borreliae is organized here in sections describing ecology, namely tick vectors and animal hosts, epidemiology, microbiology, and Borrelia genome organization and antigen characterization. Furthermore, the main clinical manifestations in Lyme borreliosis are also described. Although included in the Lyme group due to their particular clinical features, Borrelia causing Baggio Yoshinari syndrome and Borrelia mayonii are described in dedicated paragraphs. The Borrelia Echidna-Reptile group has been recently characterized including spirochaetes that apparently are not pathogenic to humans, but infect reptiles and amphibians. The paragraph dedicated to this group of Borreliae describes their vectors, hosts, geographical distribution and their characteristics. Abstract Borreliae are divided into three groups, namely the Lyme group (LG), the Echidna-Reptile group (REPG) and the Relapsing Fever group (RFG). Currently, only Borrelia of the Lyme and RF groups (not all) cause infection in humans. Borreliae of the Echidna-Reptile group represent a new monophyletic group of spirochaetes, which infect amphibians and reptiles. In addition to a general description of the phylum Spirochaetales, including a brief historical digression on spirochaetosis, in the present review Borreliae of Lyme and Echidna-Reptile groups are described, discussing the ecology with vectors and hosts as well as microbiological features and molecular characterization. Furthermore, differences between LG and RFG are discussed with respect to the clinical manifestations. In humans, LG Borreliae are organotropic and cause erythema migrans in the early phase of the disease, while RFG Borreliae give high spirochaetemia with fever, without the development of erythema migrans. With respect of LG Borreliae, recently Borrelia mayonii, with intermediate characteristics between LG and RFG, has been identified. As part of the LG, it gives erythema migrans but also high spirochaetemia with fever. Hard ticks are vectors for both LG and REPG groups, but in LG they are mostly Ixodes sp. ticks, while in REPG vectors do not belong to that genus.

Simple Summary Following Borreliae Part 1, this second review describes Borreliae of the relapsing fever group (RFG) and unclassified Borreliae. The RFG is further divided according to vector transmission and geographical distribution in other subgroups, namely the soft-tick-borne relapsing fever (STBRF) group, the hard-tick-borne relapsing fever (HTBRF) one, the louse-borne relapsing fever (LBRF) group, and the Avian relapsing fever group. Where possible, according to the literature description, each sub-group of the RFG Borreliae is organized here in sections explaining the geographical distribution, the vectors, the hosts, the epidemiology, and the microbiology. In case of human infectiveness, clinical aspects are also discussed. Isolation and sequencing of Borrelia species is ongoing, and in addition to the groups mentioned in these reviews, there are Borreliae that at present cannot be cultivated, but according to sequencing data they share some characteristics with one specific group. Nevertheless, they still cannot be classified in one of them. This is the case of Borreliae with not-yet-identified pathogenicity for humans or animals, which are here named “unclassified Borreliae” and described separately, recalling the similarities with Borreliae already classified. In the future, we expect that those Borreliae are going to be characterized, including them in one of the previous groups. Abstract Borreliae of the relapsing fever group (RFG) are heterogenous and can be divided mainly into three groups according to vectors, namely the soft-tick-borne relapsing fever (STBRF) Borreliae, the hard-tick-borne relapsing fever (HTBRF) Borreliae, the louse-borne relapsing fever (LBRF) Borreliae, and the avian relapsing fever ones. With respect to the geographical distribution, the STBRF Borreliae are further subdivided into Old World and New World strains. Except for the Avian relapsing fever group Borreliae, which cause avian spirochetosis, all the others share infectivity in humans. They are indeed the etiological agent of both endemic and epidemic forms of relapsing fever, causing high spirochaetemia and fever. Vectors are primarily soft ticks of Ornithodoros spp. in the STBRF group; hard ticks, notably Ixodes sp., Amblyomma sp., Dermacentor sp., and Rhipicephalus sp., in the HTBRF group; and the louse pediculus humanus humanus in the TBRF one. A recent hypothesis was supported for a common ancestor of RFG Borreliae, transmitted at the beginning by hard-body ticks. Accordingly, STBRF Borreliae switched to use soft-bodied ticks as a vector, which was followed by the use of lice by Borrelia recurrentis. There are also new candidate species of Borreliae, at present unclassified, which are also described in this review.

The present monitoring project aimed at detecting the prevalence of Borrelia burgdorferi in ticks in the Friuli Venezia Giulia (FVG) Region (north-eastern Italy) and along the western border of Slovenia and to determine the Borrelia circulating genospecies. Since Anaplasma phagocytophilum had been found in the study area, we also evaluated the co-infection of the two pathogens in tick (Ixodes ricinus) populations. The ticks collected during 2005 in 15 sites located in the study area were analyzed to detect the presence of B. burgdorferi by amplifying the intergenic spacer 5S–23S. Genotyping was performed using a new nested-PCR–RFLP method, targeting the ospA gene. A. phagocytophilum was searched for by amplifying the epank1 gene. The average infection rate of ticks with B. burgdorferi varied from 11.8% to 45.5% in the different study sites. A. phagocytophilum was present in the 1.6% of the investigated ticks and apparently homogeneously distributed. The percentage of co-infection with B. burgdorferi sensu lato was 3.4%. At least four different Borrelia species were found: B. afzelii (54.9%), B. garinii (31.7%), B. burgdorferi sensu stricto (6.1%), and 4.9% of a species unidentified whose phylogenetic analysis showed no similarity with any of the known Borrelia genospecies.