Sylvie De Martino

Lyme optic neuritis

Lyme optic neuritis (ON) is a rare disease and only a few cases have been reported. We describe two cases of isolated Lyme ON, one with recurrence 9 months after the appearance of initial symptoms. Diagnosis criteria for multiple sclerosis and neuromyelitis optica were not met. The etiological diagnosis was based on European case definition criteria for neuroborreliosis. Both patients had positive serum and cerebrospinal fluid serology, a positive intrathecal anti-Borrelia antibody index, and a good outcome on ceftriaxone. Specific diagnosis of Lyme ON is important since improvement of visual acuity is possible with specific antibiotherapy, even after many months.

Borrelia burgdorferi infection and cutaneous Lyme disease, Mexico.

Four patients who had received tick bites while visiting forests in Mexico had skin lesions that met the case definition of erythema migrans, or borrelial lymphocytoma. Clinical diagnosis was supported with histologic, serologic, and molecular tests. This study suggests the Borrelia burgdorferi infection is in Mexico.

Human granulocytic anaplasmosis in eastern France: clinical presentation and laboratory diagnosis.

Human granulocytic anaplasmosis (HGA) is a tick-borne infection characterised by an acute, nonspecific febrile illness. To date, few clinical cases have been supported by both a positive polymerase chain reaction (PCR) assay and subsequent seroconversion against Anaplasma phagocytophilum antigen all over Europe. We report here 3 consecutive cases of HGA that occurred during the summer of 2009 which fulfilled the epidemiologic, clinical, and biological criteria for HGA. These data highlight PCR assay on ethylenediaminetetraacetic acid blood rather than serology as the diagnostic test of choice during the acute phase of the disease. In endemic areas, HGA should be investigated in patients presenting an undifferentiated febrile illness with cytopenia, elevated rates of liver enzymes, and increased C-reactive protein values.

Proteomic analysis of three Borrelia burgdorferi sensu lato native species and disseminating clones: Relevance for Lyme vaccine design

Lyme borreliosis is the most important vector‐borne disease in the Northern hemisphere. It is caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans by the bite of hard ticks, Ixodes spp. Although antibiotic treatments are efficient in the early stage of the infection, a significant number of patients develop disseminated manifestations (articular, neurological, and cutaneous) due to unnoticed or absence of erythema migrans, or to inappropriate treatment. Vaccine could be an efficient approach to decrease Lyme disease incidence. We have developed a proteomic approach based on a one dimensional gel electrophoresis followed by LC‐MS/MS strategy to identify new vaccine candidates. We analyzed a disseminating clone and the associated wild‐type strain for each major pathogenic Borrelia species: B. burgdorferi sensu stricto, B. garinii, and B. afzelii. We identified specific proteins and common proteins to the disseminating clones of the three main species. In parallel, we used a spectral counting strategy to identify upregulated proteins common to the clones. Finally, 40 proteins were found that could potentially be involved in bacterial virulence and of interest in the development of a new vaccine. We selected the three proteins specifically detected in the disseminating clones of the three Borrelia species and checked by RT‐PCR whether they are expressed in mouse skin upon B. burgdorferi ss inoculation. Interestingly, BB0566 appears as a potential vaccine candidate. All MS data have been deposited in the ProteomeXchange with identifier PXD000876 (http://proteomecentral.proteomexchange.org/dataset/PXD000876).

A new hot spot for tick-borne encephalitis (TBE): A marked increase of TBE cases in France in 2016

OBJECTIVES Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. In 2016, in Northeastern France, we faced a TBEV infection increase, leading to a warning from the Regional Health Agency. Here, we report the confirmed TBE cases diagnosed between January 2013 and December 2016, with particular emphasis on the year 2016. METHODS A total of 1643 blood and cerebrospinal fluid (CSF) samples from everywhere in France, corresponding to 1460 patients, were prospectively tested for anti-TBEV-specific IgM and IgG antibodies by ELISA. Additional 39 blood and CSF samples from patients with suspected Lyme neuroborreliosis were retrospectively investigated. RESULTS The TBEV seropositivity rate was estimated to 5.89% and 54 patients were diagnosed as TBE-confirmed cases. A significant increase in TBE cases was observed during the year 2016 with 29 confirmed cases, instead of a mean of eight cases during the three previous years (p=0.0006). Six imported cases and 48 autochthonous cases, located in the Alsace region (n=43) and in the Alpine region (n=5) were reported. Forty-six patients experienced neurological impairment. Nine patients showed an incomplete recovery at last follow-up (from 15days to eight months post-infection). TBE diagnosis was performed earlier for patients taken in charge in the Alsace region than those hospitalized elsewhere in France (p=0.0087). Among the 39 patients with suspected Lyme neuroborreliosis retrospectively investigated, one showed a TBEV recent infection. CONCLUSION The TBE increase that occurred in France in 2016 highlights the need to improve our knowledge about the true burden of TBEV infection and subsequent long-term outcomes.

Homogeneous Inflammatory Gene Profiles Induced in Human Dermal Fibroblasts in Response to the Three Main Species of Borrelia burgdorferi sensu lato

In Lyme borreliosis, the skin is the key site for bacterial inoculation by the infected tick and for cutaneous manifestations. We previously showed that different strains of Borrelia burgdorferi sensu stricto isolated from tick and from different clinical stages of the Lyme borreliosis (erythema migrans, and acrodermatitis chronica atrophicans) elicited a very similar transcriptional response in normal human dermal fibroblasts. In this study, using whole transcriptome microarray chips, we aimed to compare the transcriptional response of normal human dermal fibroblasts stimulated by 3 Borrelia burgdorferi sensu lato strains belonging to 3 main pathogenic species (B. afzelii, B. garinii and B. burgdorferi sensu stricto) in order to determine whether “species-related” inflammatory pathways could be identified. The three Borrelia strains tested exhibited similar transcriptional profiles, and no species-specific fingerprint of transcriptional changes in fibroblasts was observed. Conversely, a common core of chemokines/cytokines (CCL2, CXCL1, CXCL2, CXCL6, CXCL10, IL-6, IL-8) and interferon-related genes was stimulated by all the 3 strains. Dermal fibroblasts appear to play a key role in the cutaneous infection with Borrelia, inducing a homogeneous inflammatory response, whichever Borrelia species was involved.

Multilocus sequence typing of clinical Borreliella afzelii strains: population structure and differential ability to disseminate in humans

BackgroundLyme borreliosis in humans results in a range of clinical manifestations, thought to be partly due to differences in the pathogenicity of the infecting strain. This study compared European human clinical strains of Borreliella afzelii (previously named Borrelia afzelii) using multilocus sequence typing (MLST) to determine their spatial distribution across Europe and to establish whether there are associations between B. afzelii genotypes and specific clinical manifestations of Lyme borreliosis. For this purpose, typing was performed on 63 strains, and data on a further 245 strains were accessed from the literature.ResultsAll 308 strains were categorized into 149 sequence types (STs), 27 of which are described here for the first time. Phylogenetic and goeBURST analyses showed short evolutionary distances between strains. Although the main STs differed among the countries with the largest number of strains of interest (Germany, the Netherlands, France and Slovenia), the B. afzelii clinical strains were less genetically structured than those previously observed in the European tick population. Two STs were found significantly more frequently in strains associated with clinical manifestations involving erythema migrans, whereas another ST was found significantly more frequently in strains associated with disseminated manifestations, especially neuroborreliosis.ConclusionsThe MLST profiles showed low genetic differentiation between B. afzelii strains isolated from patients with Lyme borreliosis in Europe. Also, clinical data analysis suggests the existence of lineages with differential dissemination properties in humans.

No evidence of Borrelia mayonii in an endemic area for Lyme borreliosis in France

BackgroundBorrelia mayonii is currently the latest species belonging to the Borrelia burgdorferi (sensu lato) complex to be discovered. Interestingly it is involved in human pathology causing a high fever. We looked for its presence in post- tick bite febrile patients as well as in Ixodes ricinus ticks in an endemic area of France.ResultsAfter ensuring that our molecular technics correctly detected B. mayonii, 575 patients and 3,122 Ixodes ricinus nymphs were tested. Neither B. mayonii nor another species of the B. burgdorferi (s.l.) complex previously not reported in Europe has been identified.ConclusionsFor now, B. mayonii seems to be an epiphenomenon. However, its discovery broadens the etiology of post-Ixodes bite febrile syndromes.

No serological evidence for Borrelia burgdorferi sensu lato infection in patients with dilated cardiomyopathy in Northern France

We read with interest a recent review article in the present journal in which evidence in favour of Borrelia burgdorferi as an aetiological agent of vasculitis and stroke was presented.[1] A more controversial issue seems to be the possible role of Borrelia burgdorferi sensu lato (BBSL) in the development of dilated cardiomyopathy (DCM).[2–5] The pathophysiological process leading to DCM is presumed to be due to the persistence of BBSL in myocardium of infected patients after an episode of myocarditis leading to the production of anti-endothelial or/and anti-heart antibodies and therefore to the development of an apparently ‘idiopathic’ DCM (iDCM).[4] The arguments for such process were: BBSL positive serology, BBSL detection in endomyocardial biopsies (EMBs) using microscopy or polymerase chain reaction (PCR) assays and improvement of patient’s cardiac condition after treatment by ceftriaxone.[6] However, at the opposite end of cardiac conduction abnormalities,[7] the response to such antibiotic treatment was not present in all iDCM patients suggesting an absence of active BBSL infection despite positive serological and/or molecular detection assays.[6] Moreover, systematic treatment of iDCM patients could not be considered in clinical practice because exposure to ceftriaxone may lead to acquiring extended-spectrum b-lactamase-producing gram-negative rods that are now one of the main health concerns worldwide. Taking into account all these elements, physicians in care of iDCM patients shall try to predict which patient may benefit from an antibiotic treatment by ceftriaxone only with the help of clinical context and biological investigations. This point remains difficult in clinical practice because previously reported cases [2–4] were based on direct bacteriological examination, culture or PCR assays on EMBs, whose indications are limited in clinical practice, according to the current American Heart Association (AHA) and European Society of Cardiology (ESC) recommendations.[8] Because serological screening remains the sole non-invasive test in this setting, we performed a BBSL serological screening of IgG and IgM using ELISA Enzygnost borreliosis Vlse (SiemensR ) in the serum or plasma of 15 patients suffering from iDCM and followed regularly in Reims University Hospital. All of these patients were living in North-eastern France where Lyme borreliosis is endemic.[9] EMBs had been prospectively performed in 10 out of the 15 study iDCM patients, according to AHA and ESC recommendations.[8] All sera with positive or borderline BBSL antibody results were tested by Western blot analysis (Borreliosis reference centre’s in-house immunoblot assay using Borrelia garinii IB6 antigens). Western blot analysis was interpreted as positive in case of reactivity to more than 4 BBSL antigens. EMBs were also routinely screened by PCR for the presence of common cardiotropic viruses (Enterovirus, Parvovirus B19, Human Herpes Virus) using Argene BiomerieuxR commercial kits, according to manufacturer’s instructions. Clinical data were extracted from medical records. The Hospital Ethics Committee approved the study, and informed consent had previously been obtained from each of the patients. Results are depicted in the Table 1. BBSL seroprevalence reported in our study’s population was zero [95% confidence interval: 0.07 to 0.19]; excluding the implication of BBSL in the development of DCM in any of our 15 study patients that were all living in Northern France. Therefore, we did not perform BBSL detection by PCR assays in available EMBs because

La borréliose de Lyme

Resume La borreliose de Lyme est une spirochetose transmise par piqure de tique. La manifestation clinique la plus frequente est l’erytheme migrant. Le pathogene peut disseminer par voie hematogene vers differents tissus et organes, incluant principalement le systeme nerveux, les articulations, et la peau. Les tests biologiques, principalement bases sur la serologie, sont essentiels au diagnostic de la maladie, a l’exception de l’erytheme migrant dont le diagnostic doit rester strictement clinique. Le traitement est base sur l’utilisation d’une des 3 classes d’antibiotiques suivante : β-lactamines, cyclines ou macrolides, pour une duree de 2 a 4 semaines en fonction du contexte clinique. Outre la protection contre les piqures de tiques, la mesure de prevention individuelle la plus efficace repose, en cas d’exposition, sur le depistage et le retrait precoces des tiques fixees a la peau.