Successful vaccination for Lyme disease: a novel mechanism?

Borrelia burgdorferi sensu lato is the aetiologic agent of Lyme disease, which is a multi-system disorder resulting from the transmission of organisms from an infected tick. According to the US Centers for Disease Control, the incidence of Lyme disease in the US has increased 25-fold since national surveillance began and the geographical spread of Lyme disease causing spirochetes would indicate that the annual number of cases will continue to rise. Humoral immunity has been shown to play a role in protection and this has spurred efforts towards developing a Lyme disease vaccine. A number of protective immunogens have been characterised to date, but due to the heterogeneity of Lyme disease Borreliae, no single molecule has proven to be completely effective as a vaccinogen. This review will describe the immunogens that have been used to protect against B. burgdorferi infection, with a focus on the inherent challenges involved with providing successful immunity to B. burgdorferi. In addition, the promising aspects and the limitations of each protective immunogen will be discussed.     

Asunaprevir (BMS-650032) for the treatment of hepatitis C virus

Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist after antibiotic therapy is an area of ongoing controversy. In animal models, B. burgdorferi DNA can be detected in tissues after antibiotic therapy as well as by using the natural tick vector to acquire the organism through feeding (xenodiagnosis). Vector arthropods have been successfully used in xenodiagnosis to describe the etiology of infections such as malaria, typhus and Chagas disease. Our recent safety trial of xenodiagnosis demonstrates that ticks may be successfully fed on patients and may help determine the biological basis for post-treatment Lyme disease syndrome.     

广东首次分离到莱姆病螺旋体

目的：分离莱姆病螺旋体。方法：鼠、蜱标本接种ＢＳＫ培养基，分离病原体与单克隆抗体进行间接免疫荧光试验。结果：用ＢＳＫ培养基分离４９只野鼠和２５０匹蜱，从１只白腹巨鼠胚胎分离到１株螺旋体（ＬＰＲ３０）。结论：鉴定为莱姆病螺旋体     

Neuroborreliosis

Neuroborreliosis, a manifestation of infection with the spirochete Borellia burgdorferi, has become the most frequently recognised arthropod-borne infection of the nervous system in Europe and the USA. The best criterion of an early infection with B. burgdorferi is erythema migrans (EM), but this is present in only about 40–60 % of patients with validated borreliosis. Therefore use of the duration of the disease as a classification criterion for neuroborreliosis is increasing, the chronic form being distinguished from the acute when symptoms persist for more than 6 months. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. In Europe, meningopolyradiculoneuritis (Bannwarth’s syndrome) represents the most common manifestation of acute neuroborreliosis, with the facial nerve being affected much more frequently than the other cranial nerves. Clinical symptoms affecting the central nervous system are rarely observed and then mostly in chronic courses. By far the most common manifestation of chronic neuroborreliosis is encephalomyelitis with spastic-ataxic disturbances and a disturbance of micturition. The current diagnosis of neuroborreliosis is a clinical one, which has to be confirmed by laboratory testing. In most patients, examination of the cerebrospinal fluid (CSF) reveals lymphocytic pleocytosis, damage to the blood-CSF-barrier and an intrathecal synthesis immunoglobulin (Ig) M, IgG, and sometimes IgA. Confirmation of a borrelial infection of the nervous system requires demonstration of an intrathecal synthesis of borrelial-specific antibodies in the CSF or detection of borrelial DNA in the CSF by polymerase chain reaction (PCR). There is no generally accepted therapeutic regime for the treatment of neuroborreliosis, but recent studies have shown ceftriaxone 2 g/day and cefotaxime 6 g/day to be effective in acute and chronic courses. Penicillin G 20 mega units/day and doxycycline 200 mg/day may be suitable for uncomplicated meningopolyneuritis, without involvement of the central nervous system. The duration of treatment – at least 2 weeks in the acute forms and 3 weeks in the chronic forms of neuroborreliosis – is very important for successful treatment. Corticosteroids are recommended only for patients with severe pain that does not respond to antibiotics an analgesics. Received: 24 December 1997 Accepted: 6 January 1998     

Clinical and laboratory evidence of the importance of the tick D. marginatus as a vector of B. burgdorferi in some areas of sporadic Lyme disease in Bulgaria

56 adult ticks D. marginatus and 38 adult ticks H. punctata were sampled by the flagging method, transferred to the laboratory, dissected and tested for infection with Lyme disease spirochetes. 3 (7.9%) of the adult H. punctata and 2 (3.57%) of the adult D. marginatus were infected with B. burgdorferi (Bb). This report also presents the case of a patient, who developed Lyme disease symptoms after he had been bitten by a D. marginatus tick. The clinical diagnosis was confirmed by serological testing and by a biopsy, taken from the patient's skin lesion. The skin biopsy was examined under an electron microscope and Bb was found in the sections of the deeper strata of the dermis in two structural forms: (a) cylindrical bodies (protoplasm cylinder) with circular ends covered with a three-layered membrane; (b) granules, situated among the collagenous fibres either closely adhered to them or covered with a membrane. The result of the study demonstrates that in single cases in some ecosystems, ticks D. marginatus might be implicated in Bb transmission to humans as secondary vectors.     

Use of enzyme-labelled protein G assay for the detection of anti Borrelia burgdorferi antibodies in wild animal sera

A modified ELISA was developed for the detection of anti-Borrelia burgdorferi (Bb) IgG antibodies in wild animal sera based on an Enzyme-Labelled-protein G Assay (ELGA). Microplates were coated with an extract of Bb sensu stricto strain (SV1) as antigen. Specific antibodies of the serum samples were detected by a peroxidase-labelled-protein G. Using comparative immunodiagnosis by means of a passive hemagglutination test (HA), ELGA was tested on 82 roe-deer blood samples. A correlation was found between the two methods (r = 0,66). Good reproducibility of titers was observed by ELGA technique. A minimal cross-reactivity was discovered with Leptospira. ELGA could facilitate the recognition of specific antibodies in collections of wild animal sera.Abbreviations MA microscopic agglutination - OD optical density - ELGA enzyme labelled protein G assay - HA passive hemagglutination - BSA bovine serum albumin - PBS phosphate buffered saline - Bb Borrelia burgdorferi     

广西莱姆病螺旋体5s-23srRNA间隔区基因的克隆和序列分析

目的：对广西莱姆病螺旋体分离株基因型鉴定。方法：应用聚合酶链反应从3株广西莱杂病螺旋体及1株贵州分离株全基因组DNA中将5S－23SrRNA间隔区基因调出，并克隆至质粒PGEM－T中，构建重组质粒，测序后与国外其它分离株进行同源性比较。结果：4例莱杂病螺旋体均扩增出约242bp的5s-23srRNA间隔区基因，同源性99％以上，与B.valaisiana基因型的同源性均比其他基因型高，同源性97．1％－97．9％。结论：4莱姆病螺旋体均属于B.valaisiana基因型，此基因型在为我国为首次报道。     

Cutaneous borreliosis in Northern Greece

Our study is the first international report on cutaneous Lyme disease in Greece. Our purpose was, firstly, to assess the advisability of carrying out specific serological testing in the case of skin conditions certainly or possibly related to Borrelia burgadorferi (Bb) and, secondly, to evaluate the necessity and efficacy of treatment. Our research was carried out between 1988 and 1991 on 68 patients suffering from cutaneous diseases generally related to Bb and 57 control subjects. Specific IgM and IgG antibodies were detected by indirect immunofluorescence assay (IFA) and titers > 1/256 were considered as positive. All 57 control subjects were negative. Eighteen out of the 68 patients (26.5%) were positive. Five out of the eight patients (62.5%) with cutaneous diseases certainly related to Bb, and 13 out of the 60 patients (21.6%) with skin diseases possibly related to Bb, were positive. The high percentage (26.5%) in skin diseases generally related to Bb suggests that patients with all these diseases should be tested by IFA. Negative results in control patients confirm the specificity of IFA and indicate that it is unnecessary to perform this investigation in the absence of specific clinical manifestations. Even though we regard scleroderma to be a late form of cutaneous borreliosis, it shows a favorable response to therapy, whereas granuloma annulare, even after liter elimination, remains clinically unchanged. Treatment should be administered not only to patients with high titers, but must he regarded as essential in all seropositive cases with dermatoses generally related to borreliosis, in view of the possibility of a late manifestation of the disease     

Lyme borreliosis in children

A total of 27 children with clinical symptoms indicative of Lyme borreliosis are described, 21 of which were seropositive. CNS symptoms were found in 17 of the seropositive childen (81%). Of these 21, 7 were CSF negative. Another 3 (with Bell's palsy and/or aseptic meningitis) were initially CSF negative but developed specific CSF titres 80, 65 and 120 days after the first lumbar puncture, respectively. Thus, seropositive children with aseptic meningitis and without initial signs of an infectious aetiology should be checked for a neuroborreliosis even when CSF negative in the first lumbar puncture. Antibiotic therapy undertaken in 26 children showed clinical recovery (Sodium penicillin, 300,000–500,000 units/kg per day for 14 days). One developed residual hypoacusis. Comparison of enzyme-linked immunosorbent assay (ELISA) IgG values from 27 cases with those of 30 healthy controls showed that elevated ELISA titres are a good indication of the disease. However, Lyme borreliosis can only be diagnosed correctly if the clinical symptoms conform with specific titres.Abbreviations Bb Borrelia burgdorferi - CNS central nervous system - CSF cerebrospinal fluid - EBV Epstein-Barr virus - ECM erythema chronicum migrans - ELISA enzyme-linked immunosorbent assay - Ig immunoglobulin - Lb Lyme borreliosis