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[Changes in the village foci of tick-borne relapsing fever in Uzbekistan over a 10-year period].
The paper presents the results of repeated investigations in the tick relapsing fever nidus (TRF) conducted after a ten-year interval in Gava settlement situated in the foothill area of the Namangan Province of Uzbekistan. A considerable deterioration in the habitat conditions of the vector, Ornithodoros papillipes Bir., due to the intensified anthropogenic effect, and decrease in its number have been noted. The distribution range of the tick (percent of infested farmsteads) in this case did not reduce. The infection rate of the vector's population with the tick relapsing fever agent decreased that points indirectly to a higher mortality of infected ticks under unfavourable conditions. Wavy course of morbidity with TRF during the period between investigations shows that changes that took place in the nidus were not uniform in their character and may have resulted to some extent from natural cycles. A similar character of anthropogenic effect on the populations of ticks in the settlement natural nidi suggests that the above changes are common to the nidi of this infection.
The plasminogen activation system enhances brain and heart invasion in murine relapsing fever borreliosis.
The role of the plasminogen activation system (PAS) was investigated during the course of infection of a relapsing fever Borrelia species in plasminogen-deficient (plg -/-) and control (plg +/+ and plg +/-) mice. Subcutaneous inoculation of 10(4) spirochetes resulted in a peak spirochetemia five days after infection with 20-23 x 10(6) organisms per milliliter of whole blood in all mice, indicating that the PAS had no effect on the development of this phase of the infection. Anemia, thrombocytopenia, hepatitis, carditis, and splenomegaly were noted in all mice during and immediately after peak spirochetemia. Fibrin deposition in organs was noted in plg -/- mice but not in controls during these stages. Significantly greater spirochetal DNA burdens were consistently observed in the hearts and brains of control mice 28-30 days after infection, as determined by PCR amplification of this organism's flagellin gene (flaB), followed by quantitative densitometry. Furthermore, the decreased spirochetal load in brains of plg -/- mice was associated with a significant decrease in the degree of inflammation of the leptomeninges in these mice. These findings indicate a role for the PAS in heart and brain invasion by relapsing fever Borrelia, resulting in organ injury.
[The current status of foci of tick-borne relapsing fever in the western Pamirs].
For the first time in the last 20-50 years foci of tick-borne relapsing fever have been surveyed in the western Pamirs. Settlements in the Piandzha valley were shown to be (as in the 1930s and 1960s) affected by Ornithodoros papillipes Bir., the carrier of the infection. Though the number of ticks is still rather high, it is nowadays considerably reduced. The findings suggest a tendency towards a decrease in the infestation of the carrier population with the agent of the disease. The traditional type of construction (especially widespread in far-off regions), when houses are built in such a way that living rooms are joined with stables inhabited by ticks, ensures favourable conditions for the existence of tick-borne relapsing fever foci and the contact of people with the agent of the infection. This demonstrates high epidemiological danger of the infection foci in the western Pamirs.
The 44-kb linear plasmid molecule in the relapsing fever agent Borrelia duttonii strain Ly serve as a preservation of vmp genes.
Borrelia duttonii strain Ly, a causative agent of relapsing fever, contains a linear one megabase chromosome and 12 linear plasmid molecules. Here we report that the sequence of the 44-kb linear plasmid of strain Ly is found to contain variable major protein (vmp) genes for antigenic variation of relapsing fever borreliae. The determined sequence is of 44,010 bp except for both ends of the molecule. Of 39 open reading frames (ORFs) found in the sequence, 21 ORFs (named vmpA to U) showed moderate similarities with vmp genes for Borrelia hermsii. However, most of the vmp homologues are apparently nonfunctional because of their frameshifts within the sequence and/or absence of promoter and ribosome-binding signals upstream of their genes. RT-PCR experiments using the specific primer for each vmp gene revealed that vmpE, one of the vmp genes, was expressed at the location of the 44-kb plasmid molecule. The result suggests that the plasmid molecule may play a role in the preservation of the serotype switching of vmp genes in a mammalian host.
Absence of focal neurological involvement in tick-borne relapsing fever in northern Tanzania.
The aim of the study was to chart incidence and clinical features of tick-borne relapsing fever in Tanzania. Consecutive patients with fever and spirochetes demonstrated in a thick blood smear at Haydom Lutheran Hospital from 1 January to 31 December 2003 underwent clinical and cerebrospinal fluid (CSF) examination. Forty-four patients were included, making an estimated minimum annual incidence of 11 per 100 000 population in this region. The mortality rate was 2.3% (95% CI = 0-12). The most frequent complaints were generalized malaise (93%), headache (86%), nausea and vomiting (52%). None of the patients [0% (95% CI = 0-8)] had focal neurological symptoms. Cell count in CSF was normal in 22 and slightly elevated (6-12 leukocytes/mm(3)) in 20 patients. Two of three pregnancies had a poor outcome. Jarisch-Herxheimer reactions, bleeding complications and ocular manifestations were infrequent. In conclusion, tick-borne relapsing fever is a common disease in the Northern highland of Tanzania, but in contrast to other parts of the world, neurological involvement is uncommon in this area.
Tetracycline versus penicillin in the treatment of louse-borne relapsing fever.
A prospective study of 120 louse-borne relapsing fever (LBRF) patient admitted to Mekele Regional Hospital, Tigray, Ethiopia from September to November 1991 was done. The patients were assigned systematically to a single dose of either tetracycline or procaine penicillin (sixty each). Doses given were oral tetracycline 250 mg or intramuscular procaine penicillin 200,000 units for children ages 12 years or less, and 500 mg or 600,000 IU for adults, respectively. The aim of this study was to compare the clinical effectiveness of tetracycline to that of procaine penicillin. Both drugs induced a Jarisch-Herxheimer (JH) like reaction, which was clinically similar in the two treatment groups, but peaked later and was more prolonged in the patients treated with procaine penicillin. Spirochaetes cleared more slowly and relapses were noticed only in the procaine penicillin treated group. Thus, tetracycline is recommended as first choice therapy and a single dose is sufficient for treatment of LBRF patients.
Experimental infection of the mouse brain by a relapsing fever Borrelia species: a molecular analysis.
The spirochetal disease relapsing fever is notable not only for multiphasic antigenic variation but also for central neurologic manifestations. To further characterize involvement of the brain in this disorder, immunocompetent and -deficient mice were infected with Borrelia hermsii. Immunodeficient mice were treated while spirochetemic with neutralizing IgM monoclonal antibodies to the infecting serotype. Blood, cerebrospinal fluid, and brain tissue were examined by culture and polymerase chain reaction. In immunocompetent mice, antigenic variation occurred in the brain as well as in the blood. In immunodeficient mice, the infecting serotype was still present in the brain after it had been eliminated from the blood by the administered antibodies. These latter results cannot be accounted for by contamination of brain tissue and cerebrospinal fluid by blood and, hence, establish the direct involvement of the central nervous system in this experimental infection.
Characteristics of louse-borne relapsing fever in Ethiopian children and adults.
Louse-borne relapsing fever (LBRF) is endemic in Ethiopia. The epidemiological and clinical aspects of LBRF and the differences between the infection in children and that in adults were investigated in a rural hospital in Ethiopia. During the 5-year study (1997-2002), 197 patients had a confirmed diagnosis of LBRF. Most (62.1%) of the cases were children under 15 years of age. The adult cases (i.e. those aged > or =15 years) were far more likely to present with headache (76.9% v. 40%; P <0.001), musculo-skeletal pains (61.5% v. 30.5%; P <0.001), dizziness (64% v. 39%; P =0.002) and bleeding (16.9% v. 3.8%; P =0.005) than the paediatric. The overall level of case fatality was 6.4%. Death appeared to be significantly associated with adulthood (P =0.01), delay in consultation (P =0.026) and the presence of vomiting (P =0.023). LBRF is clearly still a public-health problem in Ethiopia, where the clinical manifestations of the disease differ according to the age of the case.
An overview of tick-borne relapsing fever with emphasis on outbreaks in Texas.
Tick-borne relapsing fever (TBRF), a disease of humans and other animals, has been recognized in North America since early in this century. Caused by Borrelia spirochetes, TBRF is transmitted by softshelled Ornithodoros ticks, which may also act as reservoirs for the etiologic agents. Initial symptoms include sudden onset of fever, chills, headache, arthralgias, and myalgias. Persons with TBRF may suffer several febrile episodes or relapses unless they are diagnosed and treated promptly because TBRF spirochetes are able to alter their outer surface proteins and, thus, escape the infected host's immune response. Laboratory diagnosis is made by detecting spirochetes in peripheral blood specimens or by inoculating laboratory mice with blood collected during febrile episodes. In the 1930s and '40s, TBRF was reported commonly in Texas. More recently, fewer cases have been reported, although 13 cases were confirmed between 1990 and the first half of 1994.
Surface protein variation by expression site switching in the relapsing fever agent Borrelia hermsii.
Borrelia hermsii, an agent of relapsing fever, undergoes antigenic variation of serotype-specifying membrane proteins during mammalian infections. When B. hermsii is cultivated in broth medium, one serotype, 33, eventually predominates in the population. Serotype 33 has also been found to be dominant in ticks but not in mammalian hosts. We investigated the biology and genetics of two independently derived clonal populations of serotype 33 of B. hermsii. Both isolates infected immunodeficient mice, but serotype 33 cells were limited in number and were only transiently present in the blood. Probes for vsp33, which encodes the serotype-specifying Vsp33 outer membrane protein, revealed that the gene was located on a 53-kb linear plasmid and that there was only one locus for the gene in serotype 33. The vsp33 probe and probes for other variable membrane protein genes showed that expression of Vsp33 was determined at the level of transcription and that when the vsp33 expression site was active, an expression site for other variable proteins was silent. The study confirmed that serotype 33 is distinct from other serotypes of B. hermsii in its biology and demonstrated that B. hermsii can change its major surface protein through switching between two expression sites.
[Risk of human infection with Ixodes tick-borne relapsing fever in different regional subzones of the Perm region].
Serological and epidemiological surveys covered 2407 persons in 20 populated localities situated in all large geographical and regional subdivisions (subzones) in the Perm Region. Indirect immunofluorescence tests revealed serum immunoglobulins to Borrelia burgdorferi sensu lato. Antibodies in 1:40 or higher dilution were found in nearly 5 to 11% of the dwellers of localities in the subzones of south taiga, coniferous broad-leaved forests, and forest steppe; about 3-7% and 1-6% of them were present in the populations of mountain and middle taigas, respectively. According to the frequency of tick suction and the proportion of an immune interlayer among the population within the Perm Region, four districts were identified by varying risks for infection (epidemic hazard) with Ixodes tick-borne relapsing fever. The populations living in the subzones of south taiga, coniferous, broad-leaved forests, and forest steppe run the greatest risk. An area at average infection risk area corresponds to the south part of a mountain taiga subzone and that at lower risk does to the south part of a middle taiga subzone. There is no possibility of relapsing fever contamination outside the area of Ixodes persulcatus ticks at all. Comparison of their own findings and official statistics has made the authors conclude that there is a great hyperdiagnosis of relapsing fever in the region in question.
Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever.
Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce tumor necrosis factor. We show that the predominant factor inducing tumor necrosis factor is a variable lipoprotein homologous to the variable major protein of B. hermsii. We found antibodies to different forms of variable major protein in two patients with louse-borne relapsing fever. The three purified variable major proteins studied here differ in their ability to induce tumor necrosis factor production, which may partly explain the variable clinical severity of borrelial infection. These results may be of considerable relevance for the pathogenesis of Lyme disease and other forms of human borreliosis.
Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp.
Borrelia recurrentis, the cause of louse-borne relapsing fever, has until recently been considered noncultivable, which has prevented characterization of this spirochete. We successfully cultivated 18 strains from patients with louse-borne relapsing fever and present the initial characterization of these isolates. Electron microscopy revealed spirochetal cells with pointed ends, an average wavelength of 1.8 microns, an amplitude of 0.8 micron, and 8 to 10 periplasmic flagella. The G+C ratio was 28.4 mol%. Whole DNA-DNA hybridizations showed similarity between the isolates of B. recurrentis but not with Borrelia hermsii, Borrelia parkeri, Borrelia turicatae, or the Lyme-associated borreliae. Sequencing studies of both the flagellin and 16S RNA genes revealed that the greatest similarity was between B. recurrentis and Borrelia duttonii. Analysis of the sodium dodecyl sulfate-polycarylamide gel electrophoresis profiles of strains revealed four groups based on the position of a major protein band (one of the groups showed some heterogeneity and was subdivided into four subgroups). Pulsed-field gel electrophoresis revealed five distinct patterns.
On the occult infection in relapsing fevers.
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Antigenic variation is associated with DNA rearrangements in a relapsing fever Borrelia.
Borrelia hermsii, an agent of relapsing fever, undergoes antigenic variation in its host. Surface-exposed proteins with differing primary structures determine the serotype of each organism. Using amino acid sequence data from two of these variable proteins, we synthesized two mixed-sequence oligonucleotides and then used the oligonucleotides to probe mRNA and DNA of three isogenic serotypes of B. hermsii. In Northern blots the probes were specific for the mRNA of the homologous serotype. Southern blots revealed two classes of hybridizing fragments: those common to the three serotypes and those specific for a particular serotype. A serotype-specific DNA fragment, which had hybridized to both oligonucleotide probes, was cloned. Subsequent use of the cloned fragment as a probe provided further evidence that antigenic variation in B. hermsii is associated with DNA rearrangements and with occurrence of expression-linked copies of all, or part, of an antigen-specifying gene.
[Bone marrow disease revealed by leukocyte scintigraphy in a patient with relapsing fever of unknown origin].
A patient with relapsing fever of unknown origin and initially normal findings on bone-marrow biopsy was further investigated by leucocyte scintigraphy, which showed lack of uptake in the bone-marrow. Repeated bone-marrow biopsy and histological examination of a peripheral lymph node established the diagnosis of Hodgkin's disease.
Aureomycin in relapsing fever.
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