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      Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

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          Abstract

          Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

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          Most cited references101

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          Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe.

          The genetic polymorphism of Borrelia burgdorferi and Borrelia afzelii, two species that cause Lyme borreliosis, was estimated by sequence typing of four loci: the rrs-rrlA intergenic spacer (IGS) and the outer-membrane-protein gene p66 on the chromosome, and the outer-membrane-protein genes ospA and ospC on plasmids. The major sources of DNA for PCR amplification and sequencing were samples of the B. burgdorferi tick vector Ixodes scapularis, collected at a field site in an endemic region of the north-eastern United States, and the B. afzelii vector Ixodes ricinus, collected at a similar site in southern Sweden. The sequences were compared with those of reference strains and skin biopsy isolates, as well as database sequences. For B. burgdorferi, 10-13 alleles for each of the 4 loci, and a total of 9 distinct clonal lineages with linkage of all 4 loci, were found. For B. afzelii, 2 loci, ospC and IGS, were examined, and 11 IGS genotypes, 12 ospC alleles, and a total of 9 linkage groups were identified. The genetic variants of B. burgdorferi and B. afzelii among samples from the field sites accounted for the greater part of the genetic diversity previously reported from larger areas of the north-eastern United States and central and northern Europe. Although ospC alleles of both species had higher nucleotide diversity than other loci, the ospC locus showed evidence of intragenic recombination and was unsuitable for phylogenetic inference. In contrast, there was no detectable recombination at the IGS locus of B. burgdorferi. Moreover, beyond the signature nucleotides that specified 10 IGS genotypes, there were additional nucleotide polymorphisms that defined a total of 24 subtypes. Maximum-likelihood and parsimony cladograms of B. burgdorferi aligned IGS sequences revealed the subtype sequences to be terminal branches of clades, and the existence of at least three monophyletic lineages within B. burgdorferi. It is concluded that B. burgdorferi and B. afzelii have greater genetic diversity than had previously been estimated, and that the IGS locus alone is sufficient for strain typing and phylogenetic studies.
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            A critical appraisal of "chronic Lyme disease".

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              Sexually acquired Zika virus: a systematic review.

              Zika virus (ZIKV) is transmitted to humans primarily by Aedes mosquito bites. However, circumstantial evidence points to a sexual transmission route.
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                Author and article information

                Journal
                Healthcare (Basel)
                Healthcare (Basel)
                healthcare
                Healthcare
                MDPI
                2227-9032
                14 April 2018
                June 2018
                : 6
                : 2
                : 33
                Affiliations
                [1 ]Atkins Veterinary Services, Calgary, AB T3B 4C9, Canada; middel@ 123456telus.net
                [2 ]Department of Biology and Environmental Science, University of New Haven, West Haven, CT 06516, USA; unh@ 123456evasapi.net (E.S.); katherine.r.filush@ 123456gmail.com (K.R.F.)
                [3 ]Australian Biologics, Sydney, NSW 2000, Australia; Jennie.burke@ 123456australianbiologics.com.au
                [4 ]School of Health Sciences, Universidad Catolica Santiago de Guayaquil, Guayaquil 090615, Ecuador; agustin.franco@ 123456optusnet.com.au
                [5 ]Union Square Medical Associates, 450 Sutter Street, Suite 1504, San Francisco, CA 94108, USA; melissacfesler@ 123456gmail.com
                Author notes
                [* ]Correspondence: rstricker@ 123456usmamed.com
                Author information
                https://orcid.org/0000-0003-3733-1455
                https://orcid.org/0000-0003-2149-8517
                Article
                healthcare-06-00033
                10.3390/healthcare6020033
                6023324
                29662016
                96fa8fed-aaeb-45cd-9bb9-5324060b9de6
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 March 2018
                : 11 April 2018
                Categories
                Article

                lyme disease,borrelia burgdorferi,tickborne disease,chronic infection,spirochete culture

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