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Relapsing fever-like spirochetes infecting European vector tick of Lyme disease agent.

To determine whether relapsing fever-like spirochetes associated with hard ticks may infect Ixodes ricinus ticks in central Europe, we screened questing ticks for 16S rDNA similar to that of Asian and American relapsing fever-like spirochetes. We compared the prevalence of these spirochetes to that of Lyme disease spirochetes transmitted by the same vector. Relapsing fever-like spirochetes infect 3.5% of questing vector ticks in our three central European sites near the Rhein Valley. These spirochetes differ genetically from their American and Asian analogs while being relatively homogeneous in the region we sampled. The Lyme disease genospecies most commonly detected in central Europe are distributed broadly, whereas those that are less frequently found appear to be place-specific. The absence of co-infected ticks suggests that relapsing fever-like and Lyme disease spirochetes may not share hosts. Exposure risk for relapsing fever-like spirochetes is similar to that of certain Lyme disease genospecies. Although many persons may be bitten by ticks infected by relapsing fever-like spirochetes, health implications remain unknown.

Animals↗

[Tick-borne human pathogenic microorganisms found in Europe and those considered nonpathogenic. Part II: Bacteria, parasites and mixed infections].

The importance of tick-borne diseases has significantly increased objectively and subjectively during the last few years. This fact was demonstrated by the description of tick-borne viruses, in particular with respect to tickborne encephalitis published in part I. Here in part II, tick-borne bacteria and parasites will be discussed as well the significance of these agents, their vectors, clinical course, diagnostics, prophylaxis, and therapy. Naturally, Lyme borreliosis, one of the most important tick-borne bacterial illnesses of humans, is the center of our interest. In addition to basic understanding, critical practice-relevant advice regarding all agents is presented. Similarly all tick-borne bacterial diseases such as relapsing fever, tularemia, ehrlichiosis, and rickettsiosis including Q fever will be discussed. Tick-borne zoonotic babesiae are parasites whose veterinary importance has been known for the last 100 years but whose relevance for human medicine only became evident in 1957. The fact that multiple and mixed infections caused by ticks are possible has been known for years. Taking into account such a high prevalence of the infectious agents in ticks, such multiple infections were to be expected. During the last few years it has become evident that double and multiple infections of humans caused by tick bites occur far more frequently than has been known so far. As a result, in cases of unclear anamnesis,new diagnostic and therapeutic approaches should be taken. In general one can say that considerable additional scientific research is necessary to effectively reduce the incidence of tick-borne diseases.

Anaplasmosis↗

Deep-seated resistance in relapsed paratyphoid fever.

We describe a case of relapsed paratyphoid fever in which the isolate had reduced susceptibility to ciprofloxacin due to a rare mutation within the gyrA gene. 18fluorodeoxyglucose positron emission tomography scanning identified deep-seated infection including unsuspected aortitis and highlights the utility of novel imaging techniques to improve our understanding and treatment of this disease.

Anti-Bacterial Agents↗

Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in a northern spotted owl.

Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird.

Animals↗

Antigenic variation and strain heterogeneity in Borrelia spp.

Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In relapsing fever, new borrelia serotypes emerge at a high rate spontaneously, a mechanism that is caused by DNA rearrangements on linear plasmid translocating genes coding for variable major proteins from previous silent to expression sites (i.e. from inner sites to telomeric sites of the plasmid). As a result of this variation, the borreliae escape the immune response of the host, thus leading to the relapse phenomenon. In B. burgdorferi, which is the causative agent of the multisystem disorder Lyme borreliosis, there is also a growing body of findings that antigenic variation is involved in pathogenesis of the disease. Phenotypic variation of strains in vitro concerns the size and the amount of surface-associated proteins (OspA, OspB and pC). There are indications that OspA and OspB truncations are due to deletions within the ospAB operon caused by recombination events, and that OspA/OspB-less mutants lack the 49-kb plasmid that bears the ospAB operon. With the increasing number of isolates obtained from various geographic and biological sources, it became apparent that B. burgdorferi is immunologically and genetically more heterogeneous, as previously believed. The major outer surface proteins OspA and OspB (which have been efficient antigens in vaccine studies) are heterogeneous at a genetic level. The same degree of genetic non-identity was observed for the pC protein. Other proteins like flagellin and the highly specific immunodominant p100 range protein show a lower degree of non-identity. Recombinant OspA, pC, p100 range protein and flagellin have been hyperexpressed in E. coli and these proteins are immunologically reactive. This allows further research for development of vaccines and diagnostic tools. B. burgdorferi isolates have been investigated with genotyping (DNA hybridization, PCR and 16S rRNA analysis) as well as serotyping by various authors. Comparison of the different methods has shown good agreement when the same strains have been investigated. No correlation could be found between different phenotypic and genotypic groups with respect to the ability to cause arthritis in SCID mice. A serotyping system based on immunological differences in OspA detected by a panel of monoclonal antibodies has been proposed. Serotyping a large number of B. burgdorferi isolates has shown a striking predominance of the OspA serotype 2 among European isolates from human skin, in contrast to isolates from ticks or CSF.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigenic Variation↗

Lyme borreliosis: a relapsing fever-like disease?

To determine by xenodiagnosis length and concentrations of spirochetemias produced by Borrelia burgdorferi in white-footed mice (Peromyscus leucopus), laboratory reared mice were inoculated with either spirochete-containing tick suspensions or BSK II spirochete culture and were exposed for as long as three months to larval Ixodes dammini. Upon development to the nymphal stage, ticks were evaluated for spirochetal infections by direct immunofluorescence. All mice were found to circulate spirochetes for at least three months in concentrations sufficient to infect ticks. The percentage of infected ticks alternated from low to high, suggesting occurrence of episodes of mild and heavy spirochetemias. The results suggest that B. burgdorferi in its animal hosts and possibly also in humans causes prolonged spirochetemias characterized by episodes of alternating high and low concentrations of spirochetes as reflected by similar percentages of infected ticks. The long persistence of spirochetes in the peripheral blood stream and the cyclical form of Lyme borreliosis appear to be related, as in relapsing fevers, to the capacity of B. burgdorferi to undergo antigenic variations.

Animals↗

Pediculosis.

The 3 major lice that infest humans are Pediculus humanus capitis (head louse), Pthirus pubis (crab louse), and Pediculus humanus humanus (body louse). Patients with louse infestation present with scalp pruritus, excoriations, cervical lymphadenopathy, and conjunctivitis. A hypersensitivity rash, or pediculid, may mimic a viral exanthem. Head lice infestation crosses all economic and social boundaries, whereas body lice infestation preferentially affects the homeless and displaced. Body lice are major vectors of diseases such as typhus, trench fever, and relapsing fever. Pubic lice infestation often is acquired as a sexually transmitted disease and may be a marker to screen for other sexually transmitted diseases. Treatment of louse infestation can be challenging. Mechanical measures, such as combing, are helpful as adjunctive measures, but most studies suggest they are not as effective as chemical agents. Resistance to chemical agents is a growing problem. Major types of resistance include knock-down resistance, glutathione-S-transferase-based resistance, and monooxygenase-based resistance. Research is needed to identify new effective treatments.

Animals↗

Molecular characterization of Borrelia isolates from ticks and mammals from the southern United States.

Fifty Borrelia isolates from ticks and rodents from several geographic regions of the southern United States were analyzed by genomic macrorestriction analysis. Significant genetic diversity was observed among them. These isolates segregated into 4 major clusters and 10 subclusters, which are correlated with the genospecies distribution. Nineteen pulsed-field gel electrophoresis (PFGE) types were recognized among the isolates. The genospecies Borrelia andersonii and Borrelia bissettii consisted of 5 and 2 subclusters, respectively. Two subclusters comprised the Borrelia burgdorferi sensu stricto (s. s.) strains. These results indicated that PFGE is a suitable molecular typing method for B. burgdorferi at both the genospecies and strain levels. Seventeen representative isolates from different PFGE groups were analyzed by restriction fragment length polymorphism (RFLP) and sequence analysis of flaB. Twenty-three AluI, 3 CelII, and 11 DdeI RFLP patterns were found among strains from the B. burgdorferi sensu lato (s. l.) complex and the relapsing fever borreliae complex. Three genospecies in the B. burgdorferi s. l. complex and 1 species in the relapsing fever borreliae complex were recognized. Phylogenetic analysis based on nucleotide sequences of flaB indicated that all the Borrelia strains analyzed here could be divided into 2 parts, i.e., B. burgdorferi s. l. complex and the relapsing fever borreliae complex. The flaB appears to be a useful target gene to screen and identify strains from both B. burgdorferi s. l. and relapsing fever borreliae complexes.

Animals↗

Glycerol-3-phosphate acquisition in spirochetes: distribution and biological activity of glycerophosphodiester phosphodiesterase (GlpQ) among Borrelia species.

Relapsing-fever spirochetes achieve high cell densities (>10(8)/ml) in their host's blood, while Lyme disease spirochetes do not (<10(5)/ml). This striking contrast in pathogenicity of these two groups of bacteria suggests a fundamental difference in their ability to either exploit or survive in blood. Borrelia hermsii, a tick-borne relapsing-fever spirochete, contains orthologs to glpQ and glpT, genes that encode glycerophosphodiester phosphodiesterase (GlpQ) and glycerol-3-phosphate transporter (GlpT), respectively. In other bacteria, GlpQ hydrolyzes deacylated phospholipids to glycerol-3-phosphate (G3P) while GlpT transports G3P into the cytoplasm. Enzyme assays on 17 isolates of borreliae demonstrated GlpQ activity in relapsing-fever spirochetes but not in Lyme disease spirochetes. Southern blots demonstrated glpQ and glpT in all relapsing-fever spirochetes but not in the Lyme disease group. A Lyme disease spirochete, Borrelia burgdorferi, that was transformed with a shuttle vector containing glpTQ from B. hermsii produced active enzyme, which demonstrated the association of glpQ with the hydrolysis of phospholipids. Sequence analysis of B. hermsii identified glpF, glpK, and glpA, which encode the glycerol facilitator, glycerol kinase, and glycerol-3-phosphate dehydrogenase, respectively, all of which are present in B. burgdorferi. All spirochetes examined had gpsA, which encodes the enzyme that reduces dihydroxyacetone phosphate (DHAP) to G3P. Consequently, three pathways for the acquisition of G3P exist among borreliae: (i) hydrolysis of deacylated phospholipids, (ii) reduction of DHAP, and (iii) uptake and phosphorylation of glycerol. The unique ability of relapsing-fever spirochetes to hydrolyze phospholipids may contribute to their higher cell densities in blood than those of Lyme disease spirochetes.

Animals↗

Phylogenetic analysis of Borrelia species based on flagellin gene sequences and its application for molecular typing of Lyme disease borreliae.

We determined almost complete flagellin gene sequences of various Borrelia species and aligned them with previously published sequences. A neighbor-joining phylogenetic analysis showed that the genus Borrelia was divided into the following three major clusters: New World relapsing fever borreliae (Borrelia turicatae, Borrelia parkeri, and Borrelia hermsii), Old World relapsing fever borreliae (Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica), and Lyme disease borreliae (Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii). Agents of animal spirochetosis (Borrelia coriaceae and Borrelia anserina) and species of unknown pathogenicity (Borrelia miyamotoi and Borrelia lonestari) were related to relapsing fever borreliae. Although the Lyme disease borreliae, two related species (Borrelia japonica and Borrelia andersonii), and some newly described genomic groups (groups PotiB2, VS116, DN127, Hk501, and Ya501) were closely related to each other, each taxon formed an independent branch on the phylogenetic tree. The data obtained in this study indicate that the flagellin genes are useful in Borrelia taxonomy. To distinguish the Lyme disease borreliae from related organisms easily, we designed an oligonucleotide primer set for the flagellin gene and performed a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. The primer set amplified an approximately 580-bp DNA fragment that included species-specific restriction sites, and HapII, HhaI, CelII, HincII, or DdeI digestion of the product resulted in distinctively different PCR-RFLP patterns. The PCR-RFLP typing method which we developed should facilitate rapid identification of Lyme disease borreliae and related organisms obtained from biological and clinical specimens.

Animals↗

[International health regulations--evaluation and trends].

The current International Health Regulations (IHR) were adopted by the Twenty-second World Health Assembly in 1969 and amended in 1973 and 1981. They are a revised and consolidated version of the International Sanitary Regulations which were adopted by the Fourth World Health Assembly in 1951, themselves based on the previous International Sanitary Conventions. The purpose of the IHR is to ensure maximum security against the international spread of diseases with a minimum interference to world traffic. Over the years the IHR included cholera, yellow fever, plague, smallpox, typhus and relapsing fever, and then dropped the last three as a result of the global eradication of smallpox and the decline of typhus and relapsing fever as international threats. The IHR have played and still play an important part with respect to the diseases for which they were drawn up. The international spread of yellow fever has been contained by the application of a highly effective vaccine to travellers, and of plague by the inspection of ships and aircrafts for rats, and improvements in the design of air and sea cargo carriers to make them increasingly uninhabitable for rats. The role of the IHR was questioned as far as smallpox and cholera are concerned by arguing that smallpox was eradicated by rigorous national local vaccination programmes and cholera must be defeated by improved environmental sanitation. However, one must not lose sight of the fact that an important element of the IHR is the obligation to notify cases of the diseases listed, together with as much epidemiological information as possible, in order to permit other countries to take appropriate action.(ABSTRACT TRUNCATED AT 250 WORDS)

Communicable Disease Control↗

Comparative analysis of Borrelia isolates from southeastern USA based on randomly amplified polymorphic DNA fingerprint and 16S ribosomal gene sequence analyses.

Fifty-three southern USA Borrelia isolates were characterized using randomly amplified polymorphic DNA fingerprinting analysis (RAPD). Twenty-nine types were recognized among 37 B. andersonii strains, seven types among eight B. bissettii strains, and seven types among seven B. burgdorferi sensu stricto strains. Strain TXW-1 formed a separate RAPD type. Nearly complete sequences of the rrs genes from 17 representative southern Borrelia were determined. The similarity values were found to be 96-100% within the B. burgdorferi sensu lato (s.l.) complex, 94-99% among the relapsing fever borreliae, and 93-99% between the two complexes. Phylogenetic analysis indicated that all the Borrelia strains we analyzed could be divided into two parts: the B. burgdorferi s.l. complex and the relapsing fever borreliae complex. TXW-1 segregated with the North American relapsing fever borreliae and formed a separate subbranch.

Animals↗

The enlarging spectrum of tick-borne spirochetoses: R. R. Parker Memorial Address.

The author reviews his changing interest in tick-borne spirochetoses during his career (1951-1985) as a medical entomologist at the U.S. Public Health Service's Rocky Mountain Laboratory. The discoveries of relapsing fevers in the western United States in the 1930s and 1940s led to well-supported epidemiologic research, including studies on the relationships between vectors and spirochetes. When tick-borne relapsing fever in the United States was shown to be a relatively rare and readily treatable disease, financial support was withdrawn, and ongoing research was limited or terminated. Interest in relapsing fever spirochetes, particularly the relation to the relapse phenomenon in animal hosts, resurfaced in the 1960s and 1970s with the introduction of immunofluorescence assays and with the development of Kelly's medium for continuous cultivation of certain spirochetes. This interest increased significantly in 1981 when the author discovered a tick-borne spirochete to be the causative agent of Lyme disease and of several clinically related disorders in Europe. The discovery of this agent, now known as Borrelia burgdorferi, has led not only to intensive clinical, epidemiologic, and ecologic investigations in the United States and abroad but also to the identification of molecular and immunochemical techniques necessary for the study of the complex biology of tick-borne spirochetes. Reference is also made to a new species of Borrelia that may be the etiologic agent of epizootic bovine abortion in the western United States.

Animals↗

Cross-reactivity in serological tests for Lyme disease and other spirochetal infections.

Serum specimens from 163 persons with Lyme disease, tick-borne or louse-borne relapsing fever, yaws, syphilis, leptospirosis, or Rocky Mountain spotted fever were analyzed to assess the specificity of indirect fluorescent antibody (IFA) tests, an enzyme-linked immunosorbent assay (ELISA), and microscopic agglutination (MA) procedures. Strong cross-reactivity occurred when sera from individuals with Lyme disease, tick-borne relapsing fever, and louse-borne relapsing fever were tested against heterologous Borrelia antigens. Antibodies to Borrelia burgdorferi bound to Treponema pallidum in immunofluorescence tests for syphilis. Sera from subjects with syphilis cross-reacted in IFA tests and the ELISA for Lyme disease. Immunoglobulin antibodies to Borrelia or Treponema spirochetes, however, did not react with serovars of Leptospira interrogans in MA or IFA tests, and the prevalence of false-positive results in the reciprocal analyses was negligible.

Antibodies, Bacterial↗

Pentoxifylline fails to prevent the Jarisch-Herxheimer reaction or associated cytokine release.

The Jarisch-Herxheimer reaction (JHR) observed after antibiotic treatment of relapsing fever caused by Borrelia recurrentis is associated with the systemic appearance of cytokines. The decrease of cytokine production and block of JHR was attempted by administering pentoxifylline prior to antibiotic treatment. Fifteen patients with confirmed relapsing fever were infused intravenously with pentoxifylline 90 min before intramuscular injection of penicillin; 4 patients were not treated with pentoxifylline. All patients developed JHR to varying degrees. Treatment with pentoxifylline failed to prevent fever, increase in pulse, respiration, or blood pressure, or decrease in white blood cell count. No reduction of circulating levels of tumor necrosis factor, interleukin 6, or interleukin-8 was observed with pentoxifylline treatment. Pentoxifylline did not prevent clearance of the B. recurrentis spirochetes. Thus, pentoxifylline treatment of patients with relapsing fever fails to prevent or diminish JHR or the associated cytokine release observed after appropriate antibiotic treatment.

Adolescent↗

Tick-borne diseases in Texas: a 10-year retrospective examination of cases.

The occurrence of Rocky Mountain spotted fever, human monocytotropic ehrlichiosis, tularemia, tick-borne relapsing fever, and a southern erythema migrans-like illness (Lyme/Lyme-like disease) is determined by the geographic distribution and seasonal activity of the particular vector tick(s). The flulike signs and symptoms early in the course of spotted fever rickettsiosis, ehrlichiosis, tularemia, and relapsing fever are nonspecific and do not readily suggest a particular diagnosis. Laboratory diagnosis, particularly during the acute stage of illness, often is elusive. Empiric treatment with doxycycline can be lifesaving for Rocky Mountain spotted fever and ehrlichiosis. This article provides insight into the significance of each of these tick-transmitted diseases in Texas.

Animals↗