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The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes.

The rate of pathogen clearance is a critical determinant of morbidity and mortality. We sought to characterize the immune response responsible for the remarkably rapid clearance of individual episodes of bacteremia caused by the relapsing fever bacterium, Borrelia hermsii. SCID or Rag(-/-) mice were incapable of resolving B. hermsii infection, indicating a critical role for T and/or B cells. TCR(-/-) mice, which lack T cells, and IL-7(-/-) mice, which are deficient in both T cells and follicular B cells, but not in B1 cells and splenic marginal zone (MZ) B cells, efficiently cleared B. hermsii. These findings suggested that B1 cells and/or MZ B cells, two B cell subsets that are known to participate in rapid, T-independent responses, might be involved. The efficient resolution of the episodes of moderate level bacteremia by splenectomized mice suggested that MZ B cells do not play the primary role in clearance of this bacterium. In contrast, xid mice, which are deficient in B1 cells, suffered more severe episodes of bacteremia than wild-type mice. The hypothesis that B1 cells are critical for clearance of B. hermsii was further supported by a selective expansion of the B1b (i.e., IgM(high), IgD(-/low), Mac1(+) CD23(-), and CD5(-)) cell subset in infected xid mice, which coincided with the eventual resolution of infection. Finally, mice selectively incapable of secreting IgM, the dominant isotype produced by B1 cells, were completely unable to clear B. hermsii. Together these results support the model that B1b cells generate the T-independent IgM required for the control and resolution of relapsing fever borreliosis.

Animals↗

Uptake and killing of Lyme disease and relapsing fever borreliae in the perfused rat liver and by isolated Kupffer cells.

In situ-perfused rat livers were infused with a single dose of 1.5 x 10(7) radiolabeled borreliae. Significant (P < 0.00005) differences in the liver uptake of the agents of Lyme borreliosis, Borrelia burgdorferi IRS, Borrelia afzelii VS461, and Borrelia garinii PBi, and that of the agents of relapsing fever, Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae, were observed. The liver uptakes ranged between 65.9% for B. burgdorferi IRS and 40.5% for B. turicatae. Neither relapsing fever nor Lyme disease borreliae were recovered from infected livers when the livers were cultured in Barbour-Stoenner-Kelly II medium. The in vitro uptake of B. burgdorferi IRS by isolated rat Kupffer cells was rapid, and within 30 min of the infection, large intracellular aggregates of amorphous material were detectable by immunofluorescence with specific anti-B. burgdorferi antibody. The reculturing of B. burgdorferi IRS from Kupffer cells incubated for 24 h in RPMI medium before inoculation with bacteria was negative. The results obtained in this study indicated that borreliae are efficiently taken up and killed by rat hepatic macrophages in the absence of serum factors.

Animals↗

New World relapsing fever Borrelia found in Ornithodoros porcinus ticks in central Tanzania.

Ticks were collected from 8 houses in Mvumi Mission village, near Dodoma, Tanzania. All ticks were examined for Borrelia infestation by flagellin gene-based nested polymerase chain reaction. All houses were highly infested with ticks, and all ticks collected were of the Ornithodoros porcinus species. Fifty-one out of 120 ticks were infected with spirochetes, and a flagellin gene sequence comparison showed that most of the spirochetes belonged to Borrelia duttonii, which is the causative agent of tick-borne relapsing fever in East Africa. The rest of the spirochetes were quite different from B. duttonii and instead resembled the New World tick-borne relapsing fever borreliae. Phylogenetic analysis using 16S ribosomal RNA gene sequences also supported the interpretation that the spirochete was a Borrelia species distinct from previously described members of the genus.

Animals↗

[Relapsing fever seen in Europe: epidemiology, diagnosis, course and treatment].

In most European countries relapsing fevers, caused by different Borrelia species, are imported diseases. This diagnosis should be considered in a patient with fever recently back from an endemic region, especially if he went through several febrile episodes or if he has jaundice, spleen enlargement, a rash and signs of haemorrhage or meningoencephalitis.

Anti-Bacterial Agents↗

An interstate outbreak of tick-borne relapsing fever among vacationers at a Rocky Mountain cabin.

In July 1995, an outbreak of acute febrile illness affected 11 (48%) of 23 family members from Nebraska and Kansas who had vacationed at a Colorado cabin in June. Similar symptoms were identified among five (17%) of 30 additional persons from Nebraska, Kansas, Florida, and Texas who had vacationed at the same cabin. Symptoms suggested tick-borne relapsing fever (TBRF). Although no spirochetes were detected in available blood smears from five case-patients, Borrelia hermsii was cultured from the blood of one case-patient and two chipmunks trapped near the cabin. Case-patients were more likely than non-ill cabin visitors to have slept on the floor (odds ratio [OR] = 28.0, 95% confidence interval [CI] = 3.0-258) or in the top bunk bed (OR = 5.2, 95% CI = 1.1-25.1). Tick-borne relapsing fever should considered in the differential diagnosis of fever in patients who have stayed overnight in mountain cabins in the western United States.

Adolescent↗

[Tick-borne relapsing fever morbidity in Namangan].

The authors discuss the incidence of tick-borne relapsing fever in the town of Namangan (Uzbekistan) in 1976-1991 and the possible sites of human infection; the agent, Ornithodoros papillipes, has never been detected over this period. Analysis of many-year and seasonal time course of the disease incidence, of the age of the patients and their residence, characterization of the possible habitats of the agents, and comparison of the situation in the town with that in the adjacent rural territories permit a suggestion that the majority of the patients were infected at home.

Adolescent↗

Outbreak of louse-borne relapsing fever in Jimma, south western Ethiopia.

Some epidemiological aspects of louse-borne relapsing fever during the epidemic of 1991 in Ethiopia are described. There was male preponderance and the age ranged from two months to 58 years (mean, sd = 18.05,11.19). There was no sex differential in children. Students, soldiers and jobless contributed the majority. There were two peaks (August and March) in the seasonal pattern. About two-thirds was infested with lice and significant associations were found among adults, soldiers, ethnicity, illiterate persons and family size above seven. The household attack rate was 15.1%, the attack being higher among children. Promotion of preventive measures are recommended.

Adolescent↗

The spectrum of relapsing fever in the Rocky Mountains.

Between 1940 and 1976, two cases of tick-borne relapsing fever were reported in Colorado, but since 1977, 23 confirmed cases have occurred. All patients had fever, with a mean of 2.8 febrile episodes (range, one to six). Complications included thrombocytopenia, endophthalmitis, meningitis, abortion, in utero infection, and erythema multiforme. All treated patients were eventually cured with antibiotics, although two pregnant patients failed to be cured by their initial courses of antibiotics. Seven of 21 treated patients had Jarisch-Herxheimer reactions, three of whom required intensive care. Five of nine patients who received tetracycline at an initial dose of 5 mg/kg or more had reactions v none of four patients treated with lower doses. Possible causes of the recent increased incidence include increased physician awareness and reporting, improved diagnostic techniques, and an actual increase due to a larger population at risk. Because summertime visits to the Rocky Mountains are becoming increasingly popular, physicians elsewhere should know how to recognize and treat this condition.

Adolescent↗

Intragenic recombination and a chimeric outer membrane protein in the relapsing fever agent Borrelia hermsii.

The spirochete Borrelia hermsii, a relapsing fever agent, evades the host's immune response through multiphasic antigenic variation. Antigen switching results from sequential expression of genes for serotype-specific outer membrane proteins known as variable major proteins (Vmp's); of the 25 serotypes that have been identified for the HS1 strain, serotypes 7 and 21 have been studied in greatest detail. In the present study, an atypical variant was predominant in the relapse from a serotype 21 infection in mice; relapse cells were bound by monoclonal antibodies specific for Vmp21 as well as antibodies specific for Vmp7. In Western blots (immunoblots), the variant had a single Vmp that was reactive with monoclonal antibodies representing both serotypes. The gene encoding this Vmp, vmp7/21, was cloned and characterized by restriction mapping and sequence analysis to determine the likely recombination event. Whereas the 5' end of vmp7/21 was identical to that of vmp21, its 3' end and flanking sequences were identical to the 3' end of vmp7. Unlike other vmp genes examined thus far, the vmp7/21 gene existed only in an expressed form; a silent, storage form of the gene was not detected. We conclude that the vmp7/21 gene was created by an intragenic recombination between the formerly expressed vmp21 gene and a silent vmp7 gene. This finding suggests that the lack of cross-reactivity between variants, which is usually observed, results from immunoselection against variants possessing chimeric Vmp's rather than from a switching mechanism that excludes partial gene replacements.

Antigens, Bacterial↗

Immunodominant epitope in the C-terminus of a variable major protein in Borrelia duttonii, an agent of tick-borne relapsing fever.

Borrelia duttonii strain Ly was isolated from a child with tick-borne relapsing fever in Tanzania. B. duttonii produces variable major proteins (Vmps), which undergo antigenic variation. We previously reported transcription of the vmpP gene, which is one of the Vmp genes in strain Ly, detected in vitro cultivation. In the current study, we purified the recombinant non-lipidated VmpP protein by affinity chromatography and produced VmpP polyclonal antibodies. Antigenicity of VmpP was examined by Western immunoblot analysis and peptide-based enzyme-linked immunosorbent assays. Antigenic epitopes were shown to comprise five regions interspersed within the VmpP primary amino acid sequence. Synthetic peptides spanning residues of three of five regions, 232-237 (LASIVD), 280-285 (AGGIAL), and 350-355 (KAADQQ), reacted strongly with the VmpP-specific antibody and these residues were identified as epitopes. In particular, the C-terminal domain (KAADQQ) of this protein was immunoreactive. Further research based on our results will promote the development of a recombinant vaccine for B. duttonii infection.

Amino Acid Sequence↗

Detection of Borrelia duttonii, a tick-borne relapsing fever agent in central Tanzania, within ticks by flagellin gene-based nested polymerase chain reaction.

Argasid ticks collected in the site near Mvumi Hospital, Dodoma, Tanzania, were subjected to flagellin gene-based nested polymerase chain reaction (PCR) amplification for examination of borrelial infections. Eight of 13 ticks gave a strong 350-bp signal; three had a weak signal at the same size, and the rest were negative. Sequence determination of eight of the positive samples resulted in three types of flagellin gene sequences. The first type of sequence (shown by three individuals) was identical to that of Borrelia duttonii strain Ly. The second type of sequence from PCR products from four individual ticks had only one base substitution without amino acid alteration in deduced protein sequence. The third type of sequence was different from that of any other Old World relapsing fever borreliae, and the tick was thought to be infected with an unknown Borrelia species. Ticks were also examined to determine the nucleotide sequence of the mitochondrial 16S rRNA gene. The partial sequence of approximately 470 bases was aligned for comparison with previously published sequences to identify the species. The sequences of 13 individual ticks were all identical, and the sequence similarity analysis revealed the ticks should be classified as members of the Ornithodoros porcinus species. The PCR method described in this report appears to be a reliable tool for the detection of borreliae and epidemiological study of tick-borne relapsing fever.

Amino Acid Sequence↗

Cutting edge: the spirochetemia of murine relapsing fever is cleared by complement-independent bactericidal antibodies.

Abs are the major effectors of host defense against infections with BORRELIA: Bactericidal murine mAbs and their Fabs destroy B. burgdorferi, the agent of Lyme disease, and relapsing fever Borrelia in the absence of complement. These in vitro observations led to the expansion of a search for functionally similar Abs in vivo. In this study, we demonstrate that functionally unique IgM Abs develop in vivo and are responsible for the elimination of spirochetemia in murine models of relapsing fever, without the assistance of complement. Mice deficient in the fifth or third component of complement can clear the spirochetemia, whereas B cell-deficient mice cannot. The B cell-deficient mice developed spirochetemia that was an order of magnitude higher and persisted for a longer period of time in comparison to the wild-type mice. Additionally, B cell-deficient mice passively immunized with immune IgM and with immune serum were protected from challenge.

Animals↗

Relapsing fever in pregnancy: analysis of high-risk factors.

The diagnosis of tick-borne relapsing fever was established in 27 pregnant patients by demonstration of Borrelia spirochaetes in a thick blood smear and the borrelia index was estimated to calculate the density of the spirochaetaemia. Clinical findings are described and compared with those reported from Rwanda. The results suggest that the density of the spirochaetaemia and the gestational age are the main high-risk factors.

Adolescent↗

Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin.

Twelve men with louse-borne relapsing fever were treated with single doses of procaine penicillin plus aluminum monostearate (PAM) intramuscularly or of tetracycline intravenously. All patients experienced a definite Jarisch-Herxheimer-like reaction. Fever and spirochetemia were significantly prolonged and peak temperature was lower and occurred later in the PAM-treated group. Peak pulmonary ventilation, metabolic rate, and arterial PO2 were significantly higher in the tetracycline-treated group. Circulatory changes were similar in the two groups but were prolonged in the PAM-treated patients. Thus, tetracycline is recommended for treatment because it is more rapidly effective in eliminating Borrelia spirochetes and produces a reaction no more stressful physiologically than the one after PAM. There was no evidence of complement activation, and there was no change in immunoglobulin levels throughout the reaction. Immune complexes were detected in serum of five patients before treatment, but in fewer patients at the peak of the reaction and subsequently.

Adult↗

Tick-borne relapsing fever and pregnancy outcome in rural Tanzania.

OBJECTIVE: To assess the impact of tick-borne relapsing fever (TBRF) on the outcome of pregnancy. DESIGN: Case control study of 137 pregnant women (cases) and 120 non-pregnant women (controls) with TBRF between 1985 and 1995. SETTING: A rural hospital in Tabora Region, Tanzania. RESULTS: Risk of birth during the attack of TBRF was 58.0%, with an extremely high perinatal mortality of 436 per 1000 births. The total loss of pregnancies including abortions was 475. per 1000. Case-fatality rate in pregnant women was 1.5%, compared to 1.7% in the non-pregnant women. A Jarisch-Herxheimer reaction was seen in 1.5% of the cases and in 1.7% of controls. Relapse rate was 3.6%, compared to 1.7% in non-pregnant women. Pregnant women with TBRF show higher densities of spirochetes than non-pregnant women (p < 0.001). The risk of delivery during the attack was positively correlated to increasing density of the spirochetemia (p < 0.001) and to gestational age (p < 0.001). Perinatal death was related to low birthweight (p < 0.001) and low gestational age (p < 0.001) and not to degree of spirochetemia. CONCLUSIONS: The extremely high perinatal mortality rate during an attack asks for prevention and early effective management of TBRF. This is a challenge where access to health services in rural areas of developing countries is hampered by many factors.

Adult↗