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PubMedDate not supplied

Cytophagic histiocytic panniculitis: a diagnostic dilemma.

Cytophagic histiocytic panniculitis (CHP) is a recently recognized entity that frequently poses a perplexing diagnostic problem. Although the classical case presents with a relapsing fever, subcutaneous nodules, pancytopenia and liver dysfunction, most patients have in addition a multitude of other manifestations which confuse the clinical picture. Notwithstanding the variable clinical course, the disease frequently terminates in fatal hemorrhage. Diagnosis is based on histological features. A lobular panniculitis with an infiltrate of cytologically benign cytophagocytic histiocytes in skin nodules is the sine qua non of CHP. Hence, a deep skin biopsy which includes subcutaneous fat is mandatory to establish the diagnosis. Published information regarding this newly described entity remains scarce and we report two cases of CHP, one occurring in a 30-year-old Kadazan man and another in a 17-year-old Chinese woman seen at the University Hospital, Kuala Lumpur. The latter case presented with exudative ascites, an unusual feature, possibly due to intra-abdominal panniculitis. In addition, we record the development of cirrhosis in the same patient.

Adolescent↗
PubMed1995

Molecular and immunological characterization of the p83/100 protein of various Borrelia burgdorferi sensu lato strains.

The complete coding regions of the chromosomally encoded p83/100 protein of four Borrelia garinii strains and one Borrelia burgdorferi sensu stricto strain have been amplified by the polymerase chain reaction (PCR), cloned and sequenced. From alignment studies with the deduced amino acid sequences presented here, and five other published p83/100 sequences, the most heterologous region of the p83/100 molecule was identified to be located between amino acid position 390-540. To study the structure of this heterogeneous region, and internal fragment of the p83/100 genes from 11 additional B. burgdorferi sensu lato strains was amplified by PCR. The PCR products were analyzed by DNA sequencing and restriction enzyme analysis. These internal p83/100 fragments varied in size and sequence. Cluster analysis of internal p83/100 fragments, as well as restriction enzyme analysis, revealed three major groups in accordance with grouping into the three species causing Lyme disease. Strains within the same species (six B. burgdorferi sensu stricto and six B. afzelii strains) showed similar p83/100 partial structures. Nevertheless, nine B. garinii strains showed more sequence variations and could be further divided into two major subgroups. One group is represented by OspA serotype 4 strains, the other more heterogeneous group is represented by OspA serotypes 3, 5, 6 and 7 strains. Phenotypic analysis with four p83/100-specific monoclonal antibodies revealed four distinct reactivity patterns. Antibody L100 1B4 recognized a common epitope of B. burgdorferi sensu stricto and B. afzelii. Antibodies L100 17D3 and L100 18B4 were reactive with an epitope shared by strains of all three species. The broadest reactivity was shown by L100 18B4 which, in contrast to L100 17D3, additionally recognized the relapsing fever borreliae B. turicatae and B. hermsii. L100 8B8 detected a subgroup of the B. burgdorferi sensu stricto strains. Since comparison of the p83/100 molecule with sequences from protein databases showed similarities with characteristics of eukaryotic cell structures, the p83/100 might mimic these structures and may, therefore, be involved in the immune escape mechanism of the pathogenic agent of Lyme disease.

Amino Acid Sequence↗
PubMedDate not supplied

In vitro susceptibility of thirty Borrelia strains from various sources against eight antimicrobial chemotherapeutics.

Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were evaluated of the antimicrobial chemotherapeutics amoxicillin, azithromycin, cefotaxime, ceftriaxone, doxycycline, penicillin G sodium, roxithromycin, and trimethoprim-sulfamethoxazole for 30 Borrelia strains from various sources (skin, cerebrospinal fluid, ticks). Of these strains 29 were Lyme disease agents of the species Borrelia afzelii (n = 12), Borrelia burgdorferi sensu stricto (n = 4), Borrelia garinii (n = 13), and one was the relapsing fever strain Borrelia turicatae (n = 1). Tests were performed in microtiter plates by broth dilution. MIC was determined after 72 hours of incubation by comparing growth control with the antibiotic dilutions by means of dark field microscopy. Strains tested were susceptible against amoxicillin, azithromycin, cefotaxime, ceftriaxone, doxycycline, and penicillin G sodium, partly susceptible to roxithromycin, and resistant to trimethoprim-sulfamethoxazole. No statistically significant differences in MIC and MBC were seen among the different antibiotics with the various Borrelia species.

Amoxicillin↗
PubMed1999

CT scan patterns of pulmonary alveolar proteinosis in children.

BACKGROUND: To study computed tomographic (CT) findings in children with pulmonary alveolar proteinosis (PAP) more extensively. OBJECTIVE: To describe the CT features at the time of diagnosis and after therapeutic broncho-alveolar lavage (BAL). MATERIALS AND METHODS: We retrospectively reviewed the CT scans of five children (aged 3 months to 4 years) examined because of incidental bronchitis (n = 1), disease in a sibling (n = 1) and relapsing fever, cough and dyspnoea (n = 3). Each patient had an initial CT scan. Two asymptomatic cases were not treated but were followed up by plain chest films. The other three had BAL and follow-up CT. RESULTS: Initial CT in all cases showed a diffuse reticulomicronodular pattern associated in three cases with posterior bilateral alveolar infiltrates. CT in the two asymptomatic patients remained unchanged or slightly improved without BAL. After BAL, a variable decrease of lung infiltrates was observed. CONCLUSIONS: Correlation between the extent of alveolar consolidation and severity of disease was found. Anatomical and pathological considerations allow us to consider that the classical reticulomicronodular pattern is not due to an interstitial infiltration but to alveoli filled with the abnormal material characteristic of PAP.

Biopsy↗
PubMed2003

An ospA-polymerase chain reaction/restriction fragment length polymorphism-based method for sensitive detection and reliable differentiation of all European Borrelia burgdorferi sensu lato species and OspA types.

We describe a sensitive and reliable method for detection and differentiation of the five relevant European Borrelia burgdorferi sensu lato species ( B. burgdorferi sensu stricto, B. afzelii, B. garinii, B. valaisiana, and B. lusitaniae), based on a heminested ospA-PCR followed by restriction enzyme analysis. Sensitivity was one borrelia per PCR except for B. afzelii, where it was five per PCR. None of seven relapsing fever borreliae, eight Leptospira serovars or two Treponema species were amplified. Except B. garinii, each of the five B. burgdorferi s.l. species is represented by one or two characteristic restriction fragment length polymorphism (RFLP) patterns. Analysis of the heterogeneous group of B. garinii resulted in five different RFLP patterns, corresponding to the OspA types 3-7 associated with this species. In a pilot study on 529 Ixodes ricinus ticks from three different regions in Southern Germany, all species and OspA types were found except B. lusitaniae and B. garinii OspA type 7, arguing for a broad distribution of almost all OspA types. A further notable finding was the focal prevalence of OspA type 4, which has rarely been detected in ticks previously. Thus, the developed method provides a fast and simple tool for epidemiological studies on the heterogeneity of species and OspA types in Europe which has important implications for the development of vaccines and (microbiological) test systems for Europe.

Animals↗
PubMed2005

High-dose intravenous immunoglobulin infusion in polyarteritis nodosa: report on one case and review of the literature.

We describe a 58-year-old Japanese female who developed polyarteritis nodosa (PN). Her skin disease and systemic symptoms were resistant to dapsone (1.5 mg kg(-1) day(-1)), high-dose oral prednisone (1 mg kg(-1) day(-1)) and azathioprine (2 mg kg(-1) day(-1)), and intravenous cyclophosphamide pulse therapy (10 mg kg(-1) day(-1)). She was ultimately treated with infusion of high-dose intravenous immunoglobulin (IVIG) at a dose of 0.1 g kg(-1) daily for five consecutive days weekly for a period of 12 weeks, resulting in remission of his cutaneous and systemic symptoms and successful tapering of his prednisone and azathioprine dose. However, 12 months later, relapsing fever and polyarthritis recurred, and eventually, 24 months later, indurated erythema and punched-out ulcers appeared on the lower legs. These symptoms were reduced after increasing the dose of oral prednisone (1 mg kg(-1) day(-1)). Our case indicates that the high-dose IVIG infusion therapy may be useful for controlling PN in certain periods since the long-term observation revealed deterioration of symptoms. We review related articles and discuss its effectiveness in PN.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

A comparative study of three methods of detection of Borrelia crocidurae in wild rodents in Senegal.

In a rural area in Sénégal with a high incidence of tick-borne relapsing fever in humans, Borrelia crocidurae was studied in the blood and brain of wild rodents (Mastomys erythroleucus, Arvicanthis niloticus and Rattus rattus) using 3 methods: (i) direct examination of thick blood films; (ii) intraperitoneal inoculation of blood into white mice; (iii) intraperitoneal inoculation of homogenized cerebral tissue into white mice. Of the 82 rodents examined, the proportion of infected animals was respectively 2.4%, 7.3% and 14.6% for each method, and 18.3% for all 3 methods combined. Of the 12 animals with infected cerebral tissue, only 3 were found to have infected blood. These results suggest that isolated infections of the brain occur frequently in Senegalese wild rodents. Measurement of the real prevalence of B. crocidurae should therefore take into account these infections in addition to blood infections.

Animals↗
PubMed1996

Homology of variable major protein genes between Borrelia hermsii and Borrelia miyamotoi.

Antigenic variation has been studied in detail for the etiological agent of relapsing fever, Borrelia hermsii. The variable major proteins (vmps) are found at its cell surface, enabling it to avoid the host's immune response. We have cloned and sequenced the vmp-gene (vmp)-like sequences from the Borrelia miyamotoi strains HT31 and FR64b and the deduced amino acid sequences were compared with the published vmp proteins vmp3, vmp24, and vmp33 of B. hermsii. The sequences were aligned and revealed pairwise sequence identities ranging from 45 to 51%, and differences were scattered throughout the sequences. Southern hybridization using the cloned vmp-like sequence of strain HT31 as a probe suggested that the vmp homologues reside on the linear plasmids of B. miyamotoi. The probe hybridized weakly with B. hermsii linear plasmids and restriction digests. These results suggest that B. miyamotoi has sequences resembling the vmp genes in B. hermsii.

Amino Acid Sequence↗
PubMed1994

Homology between Borrelia burgdorferi OspC and members of the family of Borrelia hermsii variable major proteins.

Synthesis of the Borrelia burgdorferi outer surface protein C (OspC) is quite variable. We have cloned and sequenced the ospC gene from B. burgdorferi isolate CA-11.2A, a clone in which ospC expression varies. The 5' flanking region of the gene contains at least two consensus promoter regions, as well as two large overlapping inverted repeats. Sequence comparison to other OspC proteins indicated that the CA-11.2A OspC is as closely related to OspC from two different genospecies of Lyme disease spirochetes as it is to OspC from the prototype B. burgdorferi strain, B31. Comparisons of the OspC amino acid (aa) sequence with those in aa sequence databases revealed partial identity with the variable major proteins Vmp3 and Vmp24 of B. hermsii, a causative agent of tick-borne relapsing fever. An ospC probe hybridized to B. hermsii restriction fragments and linear plasmids that also were recognized by the vmp3 and vmp24 probes. OspC and these Vmp appear to be related, but their synthesis is regulated differently in the two species of spirochetes. This represents a fascinating example of the evolution of the number, position, regulation and perhaps function of homologous genes in two related pathogens. These parameters may relate to characteristic properties of the pathogens and their separate tick vectors.

Amino Acid Sequence↗
PubMed1990

Two genomic species in Borrelia burgdorferi.

A total of 13 Borrelia burgdorferi strains (responsible for Lyme borreliosis) and representatives of 3 other Borrelia species (B. hermsii, B. parkeri, B. turicatae) associated with relapsing fever were studied by DNA/DNA hybridization and rRNA gene-restriction patterns. Two genomic DNA hybridization groups were observed which could be differentiated by rRNA gene-restriction patterns. Moreover, the number and size of restriction fragments suggest the existence of a single set of 16 and 23 S rRNA genes in Borrelia.

Borrelia burgdorferi Group↗
PubMedDate not supplied

Antigenic variation in Borrelia.

Antigenic variation was demonstrated for the agent of relapsing fever, Borrelia hermsii. The phenomenon is correlated with changes in major surface proteins called Vmp. The genes encoding these antigens are located on linear plasmids. Expression occurs by transposition of genes encoding Vmp to a telomeric expression site located on another linear plasmid. Activation of a vmp gene occurs by placing it downstream from a promoter. Resemblance to the antigenic variation of trypanosomes is discussed.

Animals↗
PubMed1993

Linear DNA of Borrelia species and antigenic variation.

Members of the genus Borrelia may be unique among prokaryotic organisms in having a polyploid genome that is mostly linear. The smaller linear duplex replicons in these organisms have been called plasmids, but there is justification for designating them minichromosomes instead. The antigenic identities of the agents of Lyme disease and relapsing fever are largely determined by these extrachromosomal genes.

Antigenic Variation↗
PubMed2004

Outer membrane proteins of pathogenic spirochetes.

Pathogenic spirochetes are the causative agents of several important diseases including syphilis, Lyme disease, leptospirosis, swine dysentery, periodontal disease and some forms of relapsing fever. Spirochetal bacteria possess two membranes and the proteins present in the outer membrane are at the site of interaction with host tissue and the immune system. This review describes the current knowledge in the field of spirochetal outer membrane protein (OMP) biology. What is known concerning biogenesis and structure of OMPs, with particular regard to the atypical signal peptide cleavage sites observed amongst the spirochetes, is discussed. We examine the functions that have been determined for several spirochetal OMPs including those that have been demonstrated to function as adhesins, porins or to have roles in complement resistance. A detailed description of the role of spirochetal OMPs in immunity, including those that stimulate protective immunity or that are involved in antigenic variation, is given. A final section is included which covers experimental considerations in spirochetal outer membrane biology. This section covers contentious issues concerning cellular localization of putative OMPs, including determination of surface exposure. A more detailed knowledge of spirochetal OMP biology will hopefully lead to the design of new vaccines and a better understanding of spirochetal pathogenesis.

Amino Acid Sequence↗
PubMed2004

B1b lymphocytes confer T cell-independent long-lasting immunity.

Many microbial pathogens employ antigenic variation as a strategy to evade the immune system, posing a challenge in vaccine development. To understand the requirements for immunity against such pathogens, we studied Borrelia hermsii, a relapsing fever bacterium. We found that mice deficient in T, follicular B, marginal zone B, or B1a lymphocytes resolved B. hersmii bacteremia and became resistant to reinfection. The resolution of bacteremia coincided with an expansion and persistence of B1b lymphocytes, and purified B1b lymphocytes from convalescent wild-type or TCR-betaxdelta-/- mice conferred immunity to Rag1-/- mice. The B1b lymphocytes in the reconstituted Rag1-/- mice provided long-lasting immunity by rapidly generating B. hermsii-specific IgM but not IgG upon bacterial challenge. Unmutated IgM is sufficient to eliminate B. hermsii, because AID-/- mice deficient in somatic hypermutation and class switch recombination efficiently resolved all bacteremic episodes. These data demonstrate that B1b lymphocytes can provide long-lasting T cell-independent IgM memory.

Adoptive Transfer↗
PubMed2005

Fusion of hairpin telomeres by the B. burgdorferi telomere resolvase ResT implications for shaping a genome in flux.

Spirochetes of the genus Borrelia include the causative agents of Lyme disease and relapsing fever. These bacteria have a highly segmented genome where most replicons are linear molecules terminated by covalently closed hairpin telomeres. Moreover, these genomes appear to be in a state of flux with extensive and ongoing DNA rearrangements by unknown mechanisms. The B. burgdorferi telomere resolvase ResT generates the hairpin telomeres from replication intermediates in a reaction with mechanistic similarities to that catalyzed by type IB topoisomerases and tyrosine recombinases. We report here the unexpected ability of ResT to catalyze the fusion of hairpin telomeres in a reversal of the telomere resolution reaction. We propose that stabilized ResT-mediated telomere fusions are an underlying force for maintaining the B. burgdorferi genome in a state of flux.

Bacterial Proteins↗
PubMed2005

Antigens from the midgut membranes of Ornithodoros erraticus induce lethal anti-tick immune responses in pigs and mice.

Ornithodoros erraticus is an argasid tick that can transmit severe diseases such as human relapsing fever and African swine fever. In southern Europe O. erraticus lives in close association with swine on free-range pig farms. Application of acaricides for the eradication of O. erraticus from pig farms is inefficient. This is the reason why we tried to develop an anti-O. erraticus vaccine as alternative method of control. Accordingly, we were prompted to investigate the protective possibilities of a midgut membrane extract from the parasite (GME) that has not been studied hitherto. Administration of the GME with Freund's adjuvants (FAs) to pigs and mice induced a protective response able to kill 80% of the immature forms of the parasite in the first 72 h post-feeding and to reduce the fecundity of females by more than 50%. The action of the vaccine is the result of damage to the midgut wall of the argasid, and, in mice, it has been shown that this damage is mediated by activation of the complement system. In pigs, the administration of GME with alum, instead of with FAs, reduced the degree of protection. The protective antigens of the GME were expressed by all the developmental stages examined and are probably proteins from the luminal membrane of midgut epithelial cells. These antigens were seen to be more abundant in recently fed parasites than in fasting specimens, suggesting that their expression is induced after blood ingestion.

African Swine Fever↗
PubMed1994

The pathology of experimental Trypanosoma evansi infection in the Indonesian buffalo (Bubalus bubalis).

Six Indonesian buffaloes (Bubalus bubalis) were inoculated intravenously with 10(5) Trypanosoma evansi, examined clinically, haematologically and serologically, and then killed 1, 2, 3, 4, 8 or 12 weeks after infection for detailed pathological study. Relapsing fever was related to the waves of parasitaemia and fluctuations of pulse and respiration rates. Anaemic mucous membranes, depression, weakness, refusal to walk, loss of appetite and emaciation were seen. Body weight, packed cell volume, total platelet and red cell counts, and haemoglobin values were below those of two uninfected control buffaloes, as well as below the normal range; on the other hand antibody titres against T. evansi in infected animals were all above those in controls. Emaciation, serous atrophy of fat, hydropericardium, petechial to larger haemorrhages in the pericardium, pneumonia, congested liver and spleen, oedematous enlargement of the superficial lymph nodes and hyperplastic bone marrow were the major gross pathological changes. Histologically, the severity of the disease increased from 1 to 7 weeks after infection and became less obvious at 12 weeks. The most consistent lesions were interstitial pneumonia, interstitial myocarditis, splenic multifocal necrosis, interstitial myositis and hyperplastic bone marrow. The last three lesions appear not to have been reported previously in T. evansi infection in buffaloes or other animals. The clinicopathological findings in this study show that T. evansi is both an intravascular and extravascular parasite.

Animals↗
PubMed1991

A case of granulomatous hepatitis after intravesical bacillus Calmette-Guerin administration.

A 61-year-old man received intravesical bacillus Calmette-Guerin (BCG) as treatment for superficial bladder carcinoma. High spiking relapsing fevers began 39 days after the initial treatment. A liver biopsy revealed noncaseating granuloma. Deoxyribonucleic acid hybridization of the bone marrow was positive for Mycobacterium tuberculosis complex. Pressure exerted to instill the BCG may have favored dissemination.

Administration, Intravesical↗