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. 2016 May;16(5):556-564.
doi: 10.1016/S1473-3099(15)00464-8. Epub 2016 Feb 6.

Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study

Bobbi S Pritt  1 , Paul S Mead  2 , Diep K Hoang Johnson  3 , David F Neitzel  4 , Laurel B Respicio-Kingry  2 , Jeffrey P Davis  3 , Elizabeth Schiffman  4 , Lynne M Sloan  5 , Martin E Schriefer  2 , Adam J Replogle  2 , Susan M Paskewitz  6 , Julie A Ray  7 , Jenna Bjork  4 , Christopher R Steward  3 , Alecia Deedon  3 , Xia Lee  6 , Luke C Kingry  2 , Tracy K Miller  8 , Michelle A Feist  8 , Elitza S Theel  5 , Robin Patel  5 , Cole L Irish  5 , Jeannine M Petersen  2
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Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study

Bobbi S Pritt et al. Lancet Infect Dis. 2016 May.

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  • Corrections.
    [No authors listed] [No authors listed] Lancet Infect Dis. 2016 Jun;16(6):636. doi: 10.1016/S1473-3099(16)30065-2. Epub 2016 Apr 22. Lancet Infect Dis. 2016. PMID: 27117924 No abstract available.

Abstract

Background: Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is a multisystem disease caused by Borrelia burgdorferi sensu lato genospecies and characterised by tissue localisation and low spirochaetaemia. In this study we aimed to describe a novel Borrelia species causing Lyme borreliosis in the USA.

Methods: At the Mayo clinic, from 2003 to 2014, we tested routine clinical diagnostic specimens from patients in the USA with PCR targeting the oppA1 gene of B burgdorferi sensu lato. We identified positive specimens with an atypical PCR result (melting temperature outside of the expected range) by sequencing, microscopy, or culture. We collected Ixodes scapularis ticks from regions of suspected patient tick exposure and tested them by oppA1 PCR.

Findings: 100 545 specimens were submitted by physicians for routine PCR from Jan 1, 2003 to Sept 30, 2014. From these samples, six clinical specimens (five blood, one synovial fluid) yielded an atypical oppA1 PCR product, but no atypical results were detected before 2012. Five of the six patients with atypical PCR results had presented with fever, four had diffuse or focal rash, three had symptoms suggestive of neurological inclusion, and two were admitted to hospital. The sixth patient presented with knee pain and swelling. Motile spirochaetes were seen in blood samples from one patient and cultured from blood samples from two patients. Among the five blood specimens, the median oppA1 copy number was 180 times higher than that in 13 specimens that tested positive for B burgdorferi sensu stricto during the same time period. Multigene sequencing identified the spirochaete as a novel B burgdorferi sensu lato genospecies. This same genospecies was detected in ticks collected at a probable patient exposure site.

Interpretation: We describe a new pathogenic Borrelia burgdorferi sensu lato genospecies (candidatus Borrelia mayonii) in the upper midwestern USA, which causes Lyme borreliosis with unusually high spirochaetaemia. Clinicians should be aware of this new B burgdorferi sensu lato genospecies, its distinct clinical features, and the usefulness of oppA1 PCR for diagnosis.

Funding: US Centers for Disease Control and Prevention Epidemiology and Laboratory Capacity for Infectious Diseases (ELC) Cooperative Agreement and Mayo Clinic Small Grant programme.

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Figures

Figure 1
Figure 1. Diffuse macular rash in patient 1 and dark-field microscopic visualisation of a spirochaete in patient 6
(A) Diffuse macular rash seen 4 days after onset of symptoms in patient 1. Rash was reported by patient’s caregiver to involve the palms and soles, but this was not documented in the medical record. (B) Dark-field microscopic visualisation (400× magnification) of a single spirochaete in diluted blood from patient 6.
Figure 2
Figure 2. Representative oppA1 PCR melting temperature peaks of Borrelia genospecies
Representative melting temperature peaks in °C for B afzelii (A peak; acceptable range 51·7–56·7°C), novel B burgdorferi sensu lato genospecies (B peaks; 60·38–61·24°C), and B burgdorferi sensu stricto (C peaks; 61·7–66·7°C). Y-axis represents the negative derivative of the ratio of the FRET signal (LC-Red640 flouresence) and background fluorescein fluorescence.
Figure 3
Figure 3. Comparison of oppA1 PCR melting temperature, crossing points, and estimated oppA1 copy number in B burgdorferi–positive blood specimens
Comparison of melting temperature and crossing point for the five atypical oppA1 PCR positive blood specimens (open circles) and 13 B burgdorferi sensu stricto oppA1 PCR positive blood specimens (closed circles). (B) Comparison of melting temperature and estimated oppA1 copy number (genomes per mL of blood) for five atypical oppA1 PCR positive blood specimens (open circles) and 13 B burgdorferi sensu stricto oppA1 PCR positive blood specimens (closed circles).
Figure 4
Figure 4. Phylogenetic analyses
(A) Phylogenetic analysis of a 149 base pair fragment of the oppA1 gene amplified from patient specimens (MN14-1539, MN14-1420, WI133, ND132, and ND121) and tick specimens (CP12150 and EC10N1) compared with seven different species of the B burgdorferi sensu lato complex. There is no homologous sequence in relapsing fever borreliae. Bootstrap support values greater than 50% are shown. The scale bar corresponds to 0·01 substitutions per nucleotide position. Accession numbers are indicated for available Borrelia species oppA1 sequences retrieved from GenBank. The B americana BAA-1877 oppA1 gene sequence was generated in this study. GenBank does not allow deposition of sequences shorter than 200 bp; oppA1 sequences generated in this study are available by request. (B) Phylogenetic analysis of eight concatenated housekeeping genes: uvrA, rplB, recG, pyrG, pepX, clpX, clpA, and nifS, amplified from patient isolates (MN14-1539, MN14-1420) compared with 18 different B burgdorferi sensu lato genospecies and three relapsing fever species. Bootstrap support values greater than 50% are shown. The scale bar corresponds to 0·1 substitutions per nucleotide position. The source of other Borrelia species gene sequences is shown in the supplemental methods. Sequence nomenclature (eg, MN14-1539, WI133) represents the state from which the diagnostic specimens were submitted for testing and does not necessarily show the patient’s state of residence.
Figure 5
Figure 5. Probable counties of patient exposure to ticks in Minnesota and Wisconsin in relation to risk of diseases transmitted by I scapularis
I scapularis-transmitted diseases in the figure were Lyme borreliosis, babesiosis, and anaplasmosis. The county of residence for each patient (indicated with a circle) is deemed a county of potential exposure except for the patient from North Dakota, whose county of residence is not shown. Some patients had probable exposures in one or more county in addition to their county of residence (indicated with a triangle). The risk of disease transmitted by I scapularis is based on county-specific mean annual reported incidence of confirmed Lyme borreliosis and confirmed and probable human anaplasmosis and babesiosis in Minnesota and Wisconsin in 2007–13. Counties with 10·0 or fewer cases per 100 000 people were classified as low risk, counties with 10·1–24·9 cases per 100 000 people were classified as moderate risk, and counties with 25·0 or more cases per 100 000 people were classified as high risk.
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