BACKGROUND: Tick- and louse-borne relapsing fever are highly-neglected, vector-borne diseases caused by diverse Borrelia species. Presently, there are no data available on the endemicity of tick- and louse-borne relapsing fever spirochetes in Kenya. Here, we present data of a retrospective study on the seroprevalence of louse-borne relapsing fever (LBRF) in northern Kenya.
METHODS: A novel immunoassay, recently established for the diagnosis of LBRF was utilized to screen 2005 blood samples collected from individuals with fever without a source in Turkana County, Kenya between May 2009 and November 2010 for anti-LBRF antibodies.
RESULTS: Out of the 2005 sera analyzed, 287 samples (14.3 %) were considered anti-LBRF IgG positive. Subsequent analyses revealed that 87 out of 152 sera randomly selected from these 2005 samples were tested positive (57.2 %) for anti-LBRF IgM antibodies. Most of the IgG and IgM positive samples were from individuals living in northern regions of Turkana County.
CONCLUSIONS: Our serological finding provides strong evidence for the occurrence of LBRF in Kenya.

Louse-borne relapsing fever (LBRF) caused by B. recurrentis is a poverty-related and neglected infectious disease with an endemic focus in the Horn of Africa. Re-emergence of the disease occurred in Europe during the refugee crisis in 2015 and sporadic outbreaks were frequently reported in Eastern Africa where poor settings lack affordable diagnostics. Currently, there are no validated in vitro assays available for the serodiagnosis of LBRF. The aim of this study was to develop novel and reliable immunoassays by investigating clinically suspected and culture-confirmed serum samples from LBRF patients and a broad panel of serum samples from patients with other spirochetal, bacterial, and parasitic diseases. We identified two immunoreactive antigens (complement-inhibiting protein CihC and the glycerophosphodiester phosphodiesterase GlpQ of B. recurrentis) as the most promising target candidates leading to the evaluation of two immunoassays (line immunoblot and ELISA) for IgM and IgG. To optimize the IgM immunoassay, we conducted a bioinformatic approach to localize the relevant immunogenic regions within CihC. By utilizing a N-terminal CihC fragment, the sensitivity and specificity of both immunoassays (CihC and GlpQ) were high (IgM: sensitivity 100%, specificity of 89.9%, IgG: sensitivity 100%, specificity 99.2%). In conclusion, our findings indicate the diagnostic potential of CihC and GlpQ as valuable markers for the serodiagnosis of LBRF even at early time points of infection. Here, we provide strong evidence for the utilization of these immunoassays as reliable tools in clinical practice.

Borrelia recurrentis is the causative agent of louse-borne relapsing fever and the only Borrelia species transmitted by an insect rather than a tick vector. While bed bugs (Cimex lectularius L.) are not established vectors of any human pathogens, a recent study reported that they may be competent vectors of B. recurrentis. However, many aspects of infection and transmission remain unclear in this possible secondary vector. Here, we carried out several quantitative laboratory studies to gain a better understanding of the host suitability of bed bugs relative to the established body louse vector as well as the factors that may affect the ability of bed bugs to transmit the pathogen. We fed bed bugs B. recurrentis and estimated the level and duration of infection in the hemolymph using live imaging. We performed quantitative PCR (qPCR) to examine whole-body spirochete levels and the occurrence of vertical transmission to progeny. We also developed an assay to compare the amounts of force required to release infectious hemolymph from recently engorged bed bugs and body lice. Finally, we analyzed humoral antibacterial activity in the hemolymph, hemolymph pH, and hemocyte activity in both insect species. Our results confirm that within 24 h of ingestion, B. recurrentis can penetrate the midgut epithelium of bed bugs and enter the hemolymph, overcoming a major host barrier, as in body lice. Once in the hemolymph, spirochetes remain visible for at least 4 days. Moreover, we show that bed bugs are more physically susceptible to crushing than body lice, suggesting that crushing is a feasible route for the natural dissemination of B. recurrentis from the hemolymph of bed bugs, as for body lice. Nonetheless, our data also indicate that bed bugs are suboptimal hosts for B. recurrentis, as the bacterium does not appear to proliferate to high levels or stably colonize the hemolymph and exhibits pleomorphism in this environment. In particular, our data suggest that hemolymph pH and unique cellular immune responses, rather than humoral effectors, may be involved in limiting spirochete survival in bed bugs. Notably, we document the formation of extracellular DNA traps by bed bug hemocytes for the first time. For these reasons, while bed bugs may be capable of limited transmission given their ecology, vector competence is probably minimal relative to body lice. Additional mechanistic studies of human pathogen infection of bed bugs may provide much-needed insight into the biological factors that restrict their ability to act as vectors and may reveal novel mechanisms of immunity.

The spirochetal bacterium Borrelia recurrentis causes louse-borne relapsing fever (LBRF). B. recurrentis is unique because, as opposed to other Borrelia spirochetes, this strictly human pathogen is transmitted by lice. Despite the high mortality and historically proven epidemic potential and current outbreaks in African countries and Western Europe, research on LBRF has been obstructed by the lack of suitable animal models. The previously used grivet monkey model is associated with ethical concerns, among other issues. An existing immunodeficient mouse model does not limit bacteremia due to its impaired immune system. In this study, we used genetically diverse Collaborative Cross (CC) lines to develop the first LBRF immunocompetent mouse model. Out of 12 CC lines tested, CC046 mice consistently developed B. recurrentis-induced spirochetemia during the first 3 days postchallenge as concordantly detected by dark-field microscopy, culture, and quantitative PCR. However, spirochetemia was not detected from day 4 through day 10 postchallenge. The high-level spirochetemia (>107 cells/ml of blood) observed in CC046 mice was similar to that recorded in LBRF patients as well as immunocompetent mouse strains experimentally infected by tick-borne relapsing fever (RF) spirochetes, Borrelia hermsii and Borrelia persica. In contrast to the Old World and New World RF spirochetes, which develop multiple relapses (n = 3 to 9), B. recurrentis produced only single culture-detectable spirochetemia in CC046 mice. The lack of relapses may not be surprising, as LBRF patients and the grivet monkey model usually develop no or only 1 to 2 spirochetemic relapses. The novel model will now allow scientists to study B. recurrentis in the context of intact immunity.

We obtained two blood samples from relapsing fever patients residing in Jask County, Hormozgan Province, southern Iran in 2013. Sequencing of a partial fragment of glpQ from two samples, and further characterization of one of them by analyzing flaB gene, and 16S-23S spacer (IGS) revealed the greatest sequence identity with East African borreliae, Borrelia recurrentis, and Borrelia duttonii, and Borrelia microti from Iran. Phylogenetic analyses of glpQ, flaB, and concatenated sequences (glpQ, flab, and IGS) clustered these sequences amongst East African Relapsing fever borreliae and B. microti from Iran. However, the more discriminatory IGS disclosed a unique 8-bp signature (CAGCCTAA) separating these from B. microti and indeed other relapsing fever borreliae. In southern Iran, relapsing fever cases are mostly from localities in which O. erraticus ticks, the notorious vector of B. microti, prevail. There are chances that this argasid tick serves as a host and vector of several closely related species or ecotypes including the one we identified in the present study. The distribution of this Borrelia species remains to be elucidated, but it is assumed to be endemic to lowland areas of the Hormozgan Province, as well as Sistan va Baluchistan in the southeast and South Khorasan (in Persian: Khorasan-e Jonobi) in the east of Iran.

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BACKGROUND: Due to the increasing number of refugees from East Africa, louse-borne relapsing fever (LBRF) has become an emergent disease in Europe. No single case of LBRF has been reported in Europe in refugees from other parts of Africa.
METHODS: We report a case of LBRF in a refugee from Mali, likely acquired in Libya, where several migration routes into Europe meet. The disease must be considered in any febrile refugee regardless the country of origin.

We report two cases of louse-borne relapsing fever (LBRF) in young Somali asylum seekers having recently arrived to Finland. They had sought medical attention for a febrile illness. Blood smears were examined for suspected malaria, but instead, spirochete shaped bacteria were observed. The bacteria were confirmed as Borrelia recurrentis by PCR and sequencing. The patients survived, but their treatment was complicated by Jarisch-Herxheimer reaction. We conclude that LBRF must be considered as a diagnostic option in febrile refugees also in the northernmost parts of Europe.

The increasing migration into Europe may confront clinicians with diseases barely known any more in this part of the world. We present a case of louse-borne relapsing fever in a Somali refugee. Blood smears led to the diagnosis of relapsing fever and DNA sequencing was positive for Borrelia recurrentis. This disease should be considered in all patients with unclear fever and a compatible travel or migration history. Blood smears are employed as the primary diagnostic method. Therapy harbors the danger of a Jarisch-Herxheimer reaction, a complication that may require intensive medical care.

OBJECTIVE: Currently louse-borne relapsing fever (LBRF) is primarily found in limited endemic foci in Ethiopia, Somalia and Sudan; no case of imported LBRF has been reported in Europe in the 9 years prior to 2015. The aim of our paper is to describe a new case of imported LBRF detected in Sicily, Italy, and to review all cases reported in migrants arrived in Europe in the last 10 years.
METHODS: Mini review of all published cases of louse-borne relapsing fever in Europe in the last 10 years.
METHODS: A computerized search without language restriction was conducted using PubMed combining the terms \'(louse-borne relapsing fever or LBRF or recurrentis) and (refugee or Europe or migrant)\' without limits. Furthermore, the \'Ahead-of-Print Articles\' of the top 10 journals (ranked by Impact factor - Web of Science) of Infectious diseases and of Epidemiology were checked.
RESULTS: Our search identified 26 cases of LBRF between July and October 2015 in migrants recently arrived in Europe: 8 had been described in Italy; 1 in Switzerland; 2 in the Netherlands; 15 in Germany. We describe data regarding the clinical characteristics, diagnostic methods, therapy and outcome of these patients and of the new case.
CONCLUSIONS: LBRF by Borrelia recurrentis should be considered among the clinical hypotheses in migrants presenting with fever, headache, chills, sweating, arthralgia, myalgia, dizziness, nausea and vomiting.