No abstract

An immunocompromised patient presented with febrile episodes, an erysipelas-like rash, and thromboembolic complications. Amplification of 16S rRNA gene sequences from blood and sequence analysis revealed "Candidatus Neoehrlichia mikurensis." We report the first case of human disease caused by "Ca. Neoehrlichia mikurensis." CASE REPORTA 77-year-old man with B-cell chronic lymphocytic leukemia developed autoimmune anemia in 2007 and started long-term treatment with corticosteroids. In September of the same year, he had a transitory ischemic attack. Since his hemolytic anemia worsened despite treatment with corticosteroids, he was given courses of cyclophosphamide during the second half of 2008. The patient developed autoimmune thrombocytopenia (platelet count, 38 ϫ 10 9 /liter; reference range for healthy adults, 145 ϫ 10 9 to 355 ϫ 10 9 /liter) and was splenectomized laparoscopically on 4 June 2009, with subsequent normalization of platelet counts.While kayaking on 3 July 2009, the patient developed acute diarrhea, which was followed by fever and chills and a short episode of loss of consciousness the same night. When admitted to Kungälv Hospital, Kungälv, Sweden, the next day under suspicion of sepsis, he was hypotensive (blood pressure [BP], 85/60 mm Hg) and febrile (temperature, 38.5°C; reference, Ͻ38.0°C). Deep vein thrombosis in the left lower extremity encompassing the groin and pulmonary embolism were also discovered. The patient was treated intravenously (i.v.) with ceftazidime for 1 week, but no microbe was identified. The patient's systemic inflammatory reaction (C-reactive protein level of 92 mg/liter [reference, Ͻ5 mg/liter] and fever) was judged to result from widespread thromboembolism, and the patient was discharged on 10 July with low-molecular-weight heparin medication.A month later, the patient was readmitted to Sahlgrenska University hospital with a fever of 39.5°C, BP of 105/55 mm Hg, and an erysipelas-like rash on the inside of the left leg. The patient was anemic (hemoglobin [Hb], 85 g/liter; reference range, 134 to 170 g/liter) and had leukocytosis (white blood cell [WBC] count, 11 ϫ 10 9 /liter; reference range, 3.5 ϫ 10 9 to 8.8 ϫ 10 9 /liter) with a pronounced left shift, a normal platelet count, and a C-reactive protein level of 54 mg/liter (reference, Ͻ5 mg/liter). Hyponatremia was present (sodium level, 134 mmol/liter; reference range, 137 to 145 mmol/liter). The patient was taking warfarin, oral prednisolone, omeprazole, and vitamin B tablets. He was treated with i.v. cloxacillin for 2 days, followed by oral floxacillin (flucloxacillin) for 2 days and, finally, i.v. meropenem for 7 days (Fig. 1). Fever, elevated levels of C-reactive protein, and hyponatremia resolved within 1 week, apparently after the institution of meropenem (Fig. 1). All cultures (three blood cultures, two urinary cultures, and one oral swab culture) were negative. A chest X ray revealed scant infiltrates around the hili and in the basal part of the right lung, but computed tomography (CT) scans of the thorax and ...

Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.

In order to properly interpret receptor inhibition experiments, the precise receptor specificities of the employed antagonists are of crucial importance. Lately, a great number of agonists for various formyl peptide receptors have been identified using a selection of antagonists. However, some confusion exists as to the precise receptor specificities of many of these antagonists. We have investigated the effects of formyl peptide receptor family antagonists on the neutrophil response induced by agonists for the formyl peptide receptor (FPR) and the formyl peptide receptor like 1 (FPRL1). To determine FPR- and FPRL1-specific interactions, these antagonists should not be used at used at concentrations above 10 microM. Signaling through FPR was inhibited by low concentrations of the antagonists cyclosporin H, Boc-MLF (also termed Boc-1), and Boc-FLFLFL (also termed Boc-2), while higher concentrations also partly inhibited the signaling through FPRL1. The antagonist WRWWWW (WRW(4)) specifically inhibited the signaling through FPRL1 at low concentrations but at high concentrations also partly the signaling through FPR. Based on the difference in potency of cyclosporin H and the two Boc-peptides, we suggest using cyclosporin H as a specific inhibitor for FPR. To specifically inhibit the FPRL1 response the antagonist WRW(4) should be used.

Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p.pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.