Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis” Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases

We present a comprehensive study of a new infectious disease in immune compromised patients, neoehrlichiosis. The clinical picture of the disease can be misleading because the symptoms may be misinterpreted to be a worsening of the underlying diseas

Modulation of the inflammatory responses in Staphylococcus aureus arthritis and sepsis

Bacterial arthritis is a severe, rapidly progressing erosive disease with high mor-bidity and mortality. Staphylococcus aureus is the most common bacterium causing this ailment. Systemic antibiotic treat-ment, with or without drainage, is the dominant therapeutic procedure. However, despite the use of antimicrobial treatment, a mortality rate of up to 20% and joint destruction are typical. The host immune response accounts for many of the consequences of infection.Using the model of haematogenously acquired S. aureus arthritis and sepsis we analysed host response mechanisms, and performed therapeutic approaches. Manipulations directed towards mediators of inflammation affect the course of the disease. Inhibitors of nitric oxide synthase aggravated S. aureus arthritis, presumably by impairing bactericidal capacity of macrophages. Furthermore, complement depletion disturbed the opsonization of bacteria yielding impaired phagocytic activity of phagocytes, and interacted with the process of extravasation and migration of polymorphonuclear cells, thus aggravating the clinical course of the disease. Blocking of complement receptor 1 (CD35) induced an increased severity of arthritis, probably via vasodilatation and neutrophil migration/extravasation augmenting action. Treatment with heparin aggravated S. aureus arthritis, possibly interacting with the complement system and opsonophagocytosis. We provide the evidence that co-treatment of systemic corticosteroids with the conventional therapy of septic arthritis diminishes disability and severity of the disease and increases survival. This effect seems to be dependent on the downregulatory effect of corticosteroids on the proliferation/differentiation of lymphocytes.Altogether, this thesis adds to the comprehension of the overall complexity of immune responses during sepsis and septic arthritis and indicates potential therapeutic modalities

Infections with the tick-borne bacterium "Candidatus Neoehrlichia mikurensis" mimic noninfectious conditions in patients with B cell malignancies or autoimmune diseases

BACKGROUND Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. METHODS We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. RESULTS The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. CONCLUSIONS 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