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Survey of three bacterial louse-associated diseases among rural Andean communities in Peru: prevalence of epidemic typhus, trench fever, and relapsing fever.

Typhus and other louse-transmitted bacterial infections in Peruvian sierra communities are known to occur but have not recently been assessed. In this study, 194 of 1,280 inhabitants of four villages in Calca Province in the Urubamba Valley were included. Thirty-nine (20%) of the 194 volunteers had antibodies to Rickettsia prowazekii, whereas 24 (12%) had antibodies to Bartonella quintana and 2 against Borrelia recurrentis. There was a significant correlation between the presence of infesting ectoparasites and antibodies to R. prowazekii, as well as between antibodies to R. prowazekii and ectoparasite infestation and fever in the previous 6 months. The proportion of inhabitants infested with ectoparasites was significantly higher in the highest-altitude village than in the other three villages. Two volunteers' antibody levels suggested a recent typhus infection, but only B. quintana DNA was amplified from lice. Epidemic typhus remains extant in the area, and B. quintana infections were encountered and documented for the first time in South America.

Adult↗

Lipid catabolism of relapsing fever borreliae.

Relapsing fever borreliae require lipid compounds for growth in vitro. In this study, the major pathways of lipid catabolism in three species of tick-borne relapsing fever borreliae were investigated. Thin-layer chromatography was used to compare chloroform-methanol extracts of fresh culture media with extracts of exhausted culture media after organisms were removed by centrifugation. The chromatographic data demonstrated that lysolecithin was removed from the culture media during growth of the spirochetes, whereas lecithin, sphingomyelin, triglycerides, and cholesterol esters were not affected by growth of the organisms. Sonic extracts of the organism were tested for the presence of specific enzymes of lipid catabolism. Lysolecithinase, glycerophosphorylcholine diesterase, and acid phosphatase activities were demonstrated. Thus, these organisms can sequentially dissimilate lysolecithin to fatty acids, choline, inorganic phosphate, and glycerol. Assays for phospholipases A, C, and D, alpha-glycerophosphate dehydrogenase, alkaline phosphatase, and lipase were negative.

Acid Phosphatase↗

Activation of a vmp pseudogene in Borrelia hermsii: an alternate mechanism of antigenic variation during relapsing fever.

The relapsing fever agent, Borrelia hermsii, undergoes multiphasic antigenic variation to evade its host's immune response. A frequently observed switch is serotype 7 to 26. Unlike silent vmp genes previously characterized, the transcriptionally silent vmp26 sequence was a pseudogene in lacking a start codon. In serotype 7 the location of the silent vmp26 sequence just downstream of vmp7 on the expression plasmid, as well as on the silent plasmid, was also unique. The demonstration of a predicted circular recombination product in serotype 7 but not serotype 21 populations indicates that the pseudogene was activated by an intramolecular recombination producing a deletion of DNA between 20-nucleotide direct repeats in vmp7 and psi vmp26.

Amino Acid Sequence↗

Isolation and characterization of Borrelia hermsii associated with two foci of tick-borne relapsing fever in California.

Relapsing fever, caused by the spirochete Borrelia hermsii and transmitted by the soft tick Ornithodoros hermsi, is endemic in many rural mountainous areas of California. Between 1996 and 1998, 12 cases of relapsing fever associated with two exposure sites in northern California were investigated. Follow-up at exposure sites included collection of soft ticks and serum specimens from sylvatic rodents. Attempts to cultivate spirochetes were made through inoculation of patient blood into mice and by feeding Ornithodoros ticks on mice. Three isolates of B. hermsii were recovered from two blood specimens and one pool of ticks. The protein and plasmid profiles of the three isolates were comparable to those of previous B. hermsii isolates from the western United States. Western immunoblotting of patient sera demonstrated an expanding immunologic response to antigens within four distinct molecular weight regions by 3 to 4 weeks postonset. Antibody to B. hermsii was detected in sera from 4 of 11 yellow-pine chipmunks (Tamias amoenus); no other rodent species collected were seropositive.

Adult↗

A focus of tick-borne relapsing fever in southern Zaire.

Relapsing fevers occur worldwide and are characterized by recurrent episodes of fever and spirochetemia. In central, eastern, and southern Africa, the disease is often caused by Borrelia duttonii, which is transmitted by the soft tick Ornithodors moubata. We conducted a field investigation in September 1994 at a hospital in Mitwaba, southern Zaire, which was the only medical facility within 150 km. The introduction of a rapid blood-smear staining technique allowed us to demonstrate that 4.3%-7.4% of the 25-50 new outpatients seen each day had relapsing fever. Because of the absence of malaria in this area, these patients account for most of the febrile patients. The incidence of relapsing fever among all pregnant women in the maternity ward was estimated to be 6.4%, and this condition often led to maternal death or to spontaneous abortion. The 16S rRNA gene of B. dutonii was sequenced after the spirochete was isolated from patients' blood samples and directly from Ornithodoros tick vectors. In this region of Africa, relapsing fever should now be considered an important public health priority.

Animals↗

Tick-borne relapsing fever in North America.

Relapsing fever is characterized by recurring episodes of fever and nonspecific symptoms (e.g., headache, myalgia, arthralgia, shaking chills, and abdominal complaints). The illness is caused by an infection from the Borrelia species (spirochetes) that may be acquired through the bite of an infected tick (Ornithodoros species) or contact with the hemolymph of an infected human body louse (Pediculus humanus). In North America, most cases have been acquired in the western United States, southern British Columbia, and few cases have been reported from Mexico. Most cases have been acquired from exposure to rustic tick-infested cabins and caves. This article reviews relapsing fever, especially tick-borne relapsing fever in North America.

Anti-Bacterial Agents↗

Variable small protein (Vsp)-dependent and Vsp-independent pathways for glycosaminoglycan recognition by relapsing fever spirochaetes.

Tick-borne relapsing fever, caused by pathogenic Borrelia such as B. hermsii and B. turicatae, features recurrent episodes of bacteraemia, each of which is caused by a population of spirochaetes that expresses a different variable major protein. Relapsing fever is also associated with the infection of a variety of tissues, such as the central nervous system. In this study, we show that glycosaminoglycans (GAGs) mediate the attachment of relapsing fever spirochaetes to mammalian cells. B. hermsii strain DAH bound to immobilized heparin, and heparin and dermatan sulphate blocked bacterial binding to host cells. Bacterial binding was diminished by inhibition of host cell GAG synthesis or sulphation, or by the enzymatic removal of GAGs. GAGs mediated the attachment of relapsing fever spirochaetes to potentially relevant target cells, such as endothelial and glial cells. B. hermsii was able to attach to GAGs independently of variable major proteins, because strains expressing the variable major proteins Vsp33, Vlp7 or no variable major protein at all each recognized GAGs. Nevertheless, we found that a variable major protein of B. turicatae directly promoted GAG binding by this relapsing fever spirochaete. B. turicatae strain Oz1 serotype B, which expresses the variable major protein VspB, bound to GAGs more efficiently than did B. turicatae Oz1 serotype A, which expresses VspA. Recombinant VspB, but not VspA, bound to heparin and dermatan sulphate. Previous studies have shown that strain Oz1 serotype B grows to higher concentrations in the blood than does Oz1 serotype A. Thus, relapsing fever spirochaetes have the potential to express Vsp-dependent and Vsp-independent GAG-binding activities and, for one pair of highly related B. turicatae strains, differences in GAG binding correlate with differences in tissue tropism.

Animals↗

[West African tick-borne relapsing fever].

West African tick-borne relapsing fever is an endemic disease due to Borrelia crocidurae. The tick Alectorobius sonrai is the only known vector of this bacterium. Several species of rodents and insectivores may be reservoir for this spirochete. The geographic distribution of Borrelia crocidurae is not well known. The zone where the presence of the vector has been recorded is situated in Sahelian regions, from Mauritania and northern Senegal up to Chad. In Senegal, it has been shown that the persistence of drought is responsible for a considerable spread of tick-borne relapsing fever to the south. Few epidemiological data are available about West African tick-borne relapsing fever. In Senegal, epidemiological investigations indicate that Borrelia crocidurae is a major cause of morbidity (annual incidence rate of 5.1%). The relapsing nature of tick-borne borreliosis depends on Borrelia's antigenic variability. Except relapsing febrile episodes, this illness presents no pathognomonic signs. Borrelia crocidurae relapsing fever is generally benignant but neurologic or ocular complications can occur. The diagnosis of tick-borne relapsing fever is made by demonstrating the presence of Borrelia in peripheral blood in thick smear, by intraperitoneal inoculation of mice or more recently with quantitative buffy coat method (QBC test). The best treatment for relapsing fever is tetracycline or doxycycline. When tetracyclines are contraindicated, the alternative is erythromycin. In neurologic complications, the effective treatment is intravenous penicillin G or ceftriaxone. West African tick-borne relapsing fever must be systematically mentioned in case of fever in a patient returning from the endemic area.

Africa, Western↗

Bloodstream- versus tick-associated variants of a relapsing fever bacterium.

The relapsing fever spirochete, Borrelia hermsii, alternates infections between a mammal and a tick vector. Whether the spirochete changes phenotypically in the different hosts was examined by allowing the tick vector Ornithodoros hermsi to feed on mice infected with serotype 7 or serotype 8 of B. hermsii. Upon infection of ticks, the spirochetal serotype-specific variable major proteins (Vmps) 7 and 8 became undetectable and were replaced by Vmp33. This switch from a bloodstream- to tick-associated phenotype could be induced in culture by a decrease in temperature. After tick-bite transmission back to mice, the process was reversed and the spirochetes resumed expression of the same Vmp present in the previous infectious blood meal.

Animals↗

GlpQ: an antigen for serological discrimination between relapsing fever and Lyme borreliosis.

Tick-borne relapsing fever is caused by numerous Borrelia species maintained in nature by Ornithodoros tick-mammal cycles. Serological confirmation is based on either an immunofluorescence assay or an enzyme-linked immunosorbent assay using whole cells or sonicated Borrelia hermsii as the antigen. However, antigenic variability of this bacterium's outer surface proteins and antigens shared with the Lyme disease spirochete (B. burgdorferi), may cause both false-negative and false-positive results when testing sera of patients suspected to have either relapsing fever or Lyme disease. To develop a specific serological test for relapsing fever, we created a genomic DNA library of B. hermsii, screened transformed Escherichia coli cells for immunoreactivity with high-titered (> or = 1:2,048) human anti-B. hermsii antiserum, and selected an immunoreactive clone (pSPR75) expressing a 39-kDa protein. DNA sequencing, subcloning, and serum adsorption experiments identified the immunoreactive protein as a homolog of GlpQ, a glycerophosphodiester phosphodiesterase identified previously in E. coli, Haemophilus influenzae, and Bacillus subtilis. Serum samples from humans and mice infected with B. hermsii or other species of relapsing fever spirochetes contained antibodies recognizing GlpQ, whereas serum samples from Lyme disease and syphilis patients were nonreactive. Serologic tests based on this antigen will identify people exposed previously to relapsing fever spirochetes and help clarify the distribution of relapsing fever and Lyme disease in situations in which the occurrence of their causative agents is uncertain.

Amino Acid Sequence↗

Generation of a complement-independent bactericidal IgM against a relapsing fever Borrelia.

The spirochetemia of relapsing fever in mice is cleared by a complement-independent, polyclonal IgM response with reactivity to two prominent Ags of 20 and 35 kDa. In this study, we have dissected the polyclonal IgM Ab response against a relapsing fever spirochete to determine the specificity of its complement-independent bactericidal properties. Our experimental approach selectively generated an IgM murine mAb from the early specific immune response to a variable outer membrane protein. This IgM is bactericidal in the absence of complement and is part of the polyclonal Ab response that mediates the clearance of this bacterium from the blood. Purified monoclonal IgM caused direct structural damage to the outer membrane of the spirochete, in the absence of complement, and protected both B cell- and C5-deficient mice from challenge when administered passively. The direct, complement-independent, bactericidal activity of Abs is a critical mechanism of host defense against infection.

Animals↗

Tick-borne relapsing fever in a premature infant.

Relapsing fever is caused by the Borrelia species of spirochetes. Louse-born epidemics of the disease may occur but the endemic disease is usually transmitted to humans by the bite of an infected tick (Ornithodorus). Transplacental infection was suggested more than 75 years ago (1) but has been rarely documented (2). We describe a case of neonatal relapsing fever where maternal infection was the probable cause of the premature delivery and infection in the infant.

Adult↗

Extensive interplasmidic duplications change the virulence phenotype of the relapsing fever agent Borrelia turicatae.

The relapsing fever agent Borrelia turicatae has two antigenically distinct serotypes, A and B, which differ in their variable small proteins (Vsps) and in their degree of virulence and neurotropism in mice. Each Vsp gene (vspA or vspB) had an expression-linked copy that was unique to the serotype expressing it. This was located on one linear plasmid, which was defined by the upstream sequence. The archived copies of vspA and vspB were each located on different linear plasmids that were the same in both serotypes. In this feature, the mechanism of antigenic variation is similar to that of another relapsing fever agent, B. hermsii. However, in other features, the mechanisms of the two organisms differ. The expressed and archived loci for vspA and vspB of B. turicatae were near the centre of linear plasmids instead of near the telomeres. The vspA and vspB expression loci were duplicate copies of their respective silent loci: from the vsp itself to at least 13-14 kb downstream. Despite the extensive interplasmidic duplications and the internal position of the expression locus, the only detectable difference between serotypes A and B was in whether they expressed VspA or VspB.

Animals↗

Relapsing fever in Gondar, Ethiopia.

OBJECTIVE: To determine the magnitude of relapsing fever, the rate of Jarisch-Herxheimer reaction (JHR) and its outcome and compare these parameters between adults and children in the same setting, time period and more or less similar management. DESIGN: A retrospective descriptive record analysis. SETTING: Gondar College of Medical Sciences (GCMS) hospital, paediatric ward and medical wards, northwest Ethiopia. SUBJECTS: Clinical records of 262 patients discharged with confirmed diagnosis of primary relapsing fever admitted between September 1995 and August 2000. RESULTS: Of the 13,177 patients admitted during the study period, 262 (1.99%) had a primary diagnosis of relapsing fever of which 70.6% were males. Children below 14 years of age comprised 41.2%. Of the total admissions, 83.6% were from Gondar town and the rest from outside. JHR was observed in 31.7% of the patients. The overall case fatality rate was 4.6%. Bad outcome was observed more frequently in adult patients. CONCLUSIONS AND RECOMMENDATIONS: Relapsing fever is still a public health problem. Because of the potential danger of the epidemic and its outcome it should not be neglected. Preventive programmes must be integrated with other services. Though the JHR is the most feared part of the management of relapsing fever, if health personnel are trained and competent, the management of relapsing fever can be delegated to the peripheral health workers, especially when it occurs in children. Moreover, the reason for bad outcome in adult patients than in children needs to be established.

Adolescent↗

Neonatal Borrelia infections (relapsing fever): report of 5 cases and review of the literature.

Tick borne relapsing fever is an endemic disease in Sengerema district, Mwanza region, Tanzania, East Africa. Five cases of neonatal relapsing fever occurring in this endemic area are described. Two neonates showed signs of septicaemia, clumping of spirochetes (Borrelia index is uncountable) in the thick blood smear and they died the day of admission. Two neonates showed severe spirochetaemia (Borrelia index: 3). The neonate treated with low dose penicillin died, the other neonate, treated with erythromycin, survived. One neonate had only a mild spirochetaemia (Borrelia index is 0.5) and responded well to penicillin treatment. Jaundice was seen in four of the five cases, three of them died. Only twenty cases of neonatal relapsing fever were previously reported. Findings are discussed in comparison with those of former reports on relapsing fever in the literature. Based on the fact that in a relatively short time (1 year), 5 cases of neonatal relapsing fever were diagnosed in an endemic area in East Africa, we conclude that neonatal relapsing fever is probably underdiagnosed.

Anti-Bacterial Agents↗