Levels of certain endothelial biomarkers during the acute phase and convalescence in patients with different severity of mediterranean spotted fever

ABSTRACT INTRODUCTION: Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii subspp. conorii. It is transmitted by the bite of the tick Rhipicephalus sanguineus. Modified by the rickettsial invasion, the micro-vascular endothelium acquires an activated inflammatory phenotype and initiates secretion of cytokines and expression of cell adhesion molecules (CAMs) and chemoattractans. AIM: This study aims at investigating the alterations in the soluble cellular adhesion molecules (sCAMs) and chemokine MCP-1 levels in patients with MSF of varying severity in the acute and convalescence stage in order to assess their diagnostic and prognostic value. MATERIALS AND METHODS: The soluble forms of cellular adhesion molecules (sCAMs) - sЕ- selectin and sР-selectin, the intercellular (sICAM-1) and vascular (sVCAM-1) adhesion molecules as well as the monocyte chemoattractant protein-1 (MCP-1) were studied in the sera of 80 patients with MSF. The presence of MSF was confirmed serologically by indirect fluorescence assay (IFA). In order to study disease dynamics, serum samples from 80 patients were drawn on day 1 following the onset of rash; in 60 patients (part of the surveyed 80) a second sample was taken in the convalescence period - 14 days post hospital discharge. The investigation was focused on mild, moderate and severe forms of MSF. Enzyme linked immune-sorbent assay was used for sCAMs determination (Quantikine IVD colorimetric ELISA). RESULTS: Overall, in the acute stage, patients presented with increased levels of sЕ-selectin, sICAM-1, sVCAM-1 and MCP-1, whereas sР-selectin level was decreased. The levels of sЕ-selectin, sICAM-1 and sVCAМ-1 were significantly elevated in mild, moderate and severe forms of the disease with sE-selectin level exhibiting a plateau tendency and sICAM and sVCAM levels demonstrating an upward trend from mild towards severe MSF forms. MCP-1 level was elevated only in severe MSF. In all forms of MSF, in the convalescence period, sICAM-1, sVCAM-1 and МСР-1 concentration returned to reference levels whereas sE-selectin level persisted elevated. In the convalescence stage, sP- selectin concentration also showed an upward tendency, which in severe forms of MSF slightly exceeded the level in controls. sP-selectin levels correlated directly with platelet count, whereas sICAM-1 and sVCAM-1 levels showed a reverse correlation. sE-selectin, sICAM-1 and MCP-1 levels directly correlated with aminotransferase activity (ALT and/or AST). CONCLUSION: The soluble forms of CAMs reflect the endothelial inflammatory potential. There is evidence that endothelium activation is more potent in severe forms of MSF. Assessment of the endothelial response in the course of the disease is an important predictor of the outcome, the choice of therapeutic approach and disease prognosis.

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A Rare Case of Mediterranean Spotted Fever and Encephalitis

Case Reports in Infectious Diseases ◽

10.1155/2016/2421540 ◽

2016 ◽

Vol 2016 ◽

pp. 1-3

Author(s):

Raquel Sousa Almeida ◽

Petra M. Pego ◽

Maria João Pinto ◽

João Matos Costa

Keyword(s):

Rare Case ◽

Spotted Fever ◽

Rhipicephalus Sanguineus ◽

Clinical Suspicion ◽

Rickettsia Conorii ◽

Mediterranean Spotted Fever ◽

Neurological Manifestations ◽

Limited Disease ◽

Initiation Of Therapy ◽

Dog Tick

Mediterranean spotted fever is a tick-borne zoonotic disease caused byRickettsia conorii. It is transmitted by the dog tickRhipicephalus sanguineus. It usually presents as a benign self-limited disease characterized by a skin rash, high fever, and, sometimes, a characteristic ulcer at the tick bite site calledtache noir. The course of this disease is usually benign, although severe manifestations have been previously described, mainly in adults. Neurological manifestations are very unusual. We present a case of Mediterranean spotted fever with encephalitis to highlight the importance of clinical suspicion, mainly in endemic areas, the potential severity of this disease, and the need of early initiation of therapy in order to prevent severe complications.

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Mediterranean Spotted Fever: Current Knowledge and Recent Advances

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6040172 ◽

2021 ◽

Vol 6 (4) ◽

pp. 172

Author(s):

Nikolaos Spernovasilis ◽

Ioulia Markaki ◽

Michail Papadakis ◽

Nikolaos Mazonakis ◽

Despo Ierodiakonou

Keyword(s):

Clinical Features ◽

Current Knowledge ◽

Spotted Fever ◽

Rhipicephalus Sanguineus ◽

Molecular Techniques ◽

Rickettsia Conorii ◽

Mediterranean Spotted Fever ◽

Spotted Fever Group ◽

Serological Tests ◽

True Nature

Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar (“tache noire”). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF.

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Deciphering the Relationships between Rickettsia conorii conorii and Rhipicephalus sanguineus in the Ecology and Epidemiology of Mediterranean Spotted Fever

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2009.04518.x ◽

2009 ◽

Vol 1166 (1) ◽

pp. 49-54 ◽

Cited By ~ 27

Author(s):

Philippe Parola ◽

Cristina Socolovschi ◽

Didier Raoult

Keyword(s):

Spotted Fever ◽

Rhipicephalus Sanguineus ◽

Rickettsia Conorii ◽

Mediterranean Spotted Fever

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Prevalence of antibodies to Rickettsia conorii in human beings and dogs from Catalonia: a 20-year perspective

Epidemiology and Infection ◽

10.1017/s0950268816000261 ◽

2016 ◽

Vol 144 (9) ◽

pp. 1889-1894 ◽

Cited By ~ 7

Author(s):

E. ESPEJO ◽

M. ANDRÉS ◽

J. PÉREZ ◽

J. PRAT ◽

C. GUERRERO ◽

...

Keyword(s):

Human Serum ◽

Indirect Immunofluorescence ◽

Human Population ◽

Spotted Fever ◽

Rickettsia Conorii ◽

Mediterranean Spotted Fever ◽

Human Beings ◽

Serum Samples ◽

Human Serum Samples ◽

Nineteen 5

SUMMARYThe incidence of Mediterranean spotted fever (MSF) in Catalonia (Spain) has decreased in the last two decades. The prevalence of antibodies to Rickettsia conorii in human beings and dogs in the region of Vallès Occidental (Catalonia) was assessed by indirect immunofluorescence, and the results compared with those obtained in a similar study from 1987. Nineteen (5·0%) out of 383 human serum samples had antibodies to R. conorii. This seroprevalence was significantly lower (11·5%) (P = 0·003) than that recorded in the 1987 survey. Forty-two out (42·0%) of 100 canine serum samples had antibodies to R. conorii. A high proportion of the studied dogs (91·0%) were receiving anti-tick treatment, mainly with permethrin-imidacloprid spot-on (Advantix, Bayer, Germany). The current canine seroprevalence was not significantly different from that recorded in the 1987 survey (36.9%). In conclusion, this study shows a significant decrease in the prevalence of antibodies to R. conorii in the human population of Catalonia in the last 20 years, which corresponds with a decrease in the number of cases of MSF. We suggest that the widespread use of anti-tick treatment in dogs could limit the introduction of ticks to humans due to a reduction of infestation duration in dogs, thus contributing to the decrease in MSF incidence.

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Multiple organ failure as onset of Mediterranean spotted fever: a review based on a case

Italian Journal of Medicine ◽

10.4081/itjm.2016.625 ◽

2016 ◽

Vol 10 (3) ◽

pp. 195 ◽

Cited By ~ 1

Author(s):

Pasquale Mansueto ◽

Aurelio Seidita ◽

Accursia Bongiovì ◽

Tiziana Catalano ◽

Giuseppe Pirrone ◽

...

Keyword(s):

Spotted Fever ◽

False Negative ◽

Rhipicephalus Sanguineus ◽

Multiple Organ ◽

Immunoglobulin M ◽

Rickettsia Conorii ◽

Mediterranean Spotted Fever ◽

Enzymelinked Immunosorbent Assay ◽

The Common ◽

Dog Tick

Mediterranean spotted fever (MSF) is an infectious disease endemic in the southern regions of Italy, with an incidence of about 400 cases/year. The bacteria responsible of the disease is Rickettsia conorii, transmitted to humans by Rhipicephalus sanguineus, the common dog tick. The infection usually manifests with a characteristic symptomatologic triad: fever, exanthema and the so called tache noire, which is the typical eschar at the site of the tick bite. Immunoglobulin M (IgM) and IgG enzymelinked immunosorbent assay and the gold standard micro-immunofluorescent assay, allow serological diagnosis. We report the case of a man suffering from MSF, whose atypical presentation and false-negative diagnostic tests delayed consistently diagnosis and therapy. Afterwards we review the literature about this topic.

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Segregation of cell adhesion molecules into membrane microdomains facilitates leukocyte-endothelial interactions

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140270 ◽

1995 ◽

Vol 53 ◽

pp. 780-781

Author(s):

S.L. Erlandsen

Keyword(s):

Cell Surface ◽

Adhesion Molecules ◽

Colloidal Gold ◽

High Spatial Resolution ◽

Low Voltage ◽

Cellular Adhesion ◽

Membrane Microdomains ◽

Immunogold Label ◽

Cellular Adhesion Molecules ◽

Electron Detection

Cells interact with their extracellular environments by means of a variety of cellular adhesion molecules (CAM) and surface ligands. In many instances, CAMs interact in a sequential temporal fashion which suggests that these adhesion molecules may occupy or be polarized to various membrane microdomains on the cell surface. Detection of CAMs can be accomplished by a variety of methods including immunofluorescent microscopy and flow cytometry, and by the use of immunocytochemical markers (i.e. colloidal gold) in electron microscopy. The development of high resolution field emission SEM in the mid 1980's and the Autrata modification of the YAG detector for backscatter electron detection at low voltage has greatly facilitated the recognition of colloidal gold probes for detection of surface CAMs. Low voltage FESEM with Bse imaging provides increased resolution of cell surface topography (~3nm at 3-4 keV) which can be observed in 3-dimensions, and simultaneously permits detection/high spatial resolution of immunogold label by atomic number contrast.

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Increased Levels of Soluble TNF-α Receptors and Cellular Adhesion Molecules in Patients Undergoing Bioincompatible Hemodialysis

American Journal of Nephrology ◽

10.1159/000095902 ◽

2006 ◽

Vol 26 (5) ◽

pp. 437-444 ◽

Cited By ~ 18

Author(s):

Jacek Rysz ◽

Ewa Majewska ◽

Robert A. Stolarek ◽

Maciej Banach ◽

Aleksandra Ciałkowska-Rysz ◽

...

Keyword(s):

Adhesion Molecules ◽

Cellular Adhesion ◽

Cellular Adhesion Molecules ◽

Tnf Α

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THE ROLE OF CELLULAR ADHESION MOLECULES IN SURGERY

ANZ Journal of Surgery ◽

10.1111/j.1445-2197.1995.tb00573.x ◽

1995 ◽

Vol 65 (12) ◽

pp. 838-847 ◽

Cited By ~ 6

Author(s):

A. F. Breidahl ◽

M. J. Hickey ◽

A. G. Stewart ◽

P. G. Hayward ◽

W. A. Morrison

Keyword(s):

Adhesion Molecules ◽

Cellular Adhesion ◽

Cellular Adhesion Molecules

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Assessment of the Percentages of T-lymphocyte Subsets in the Peripheral Blood of Mediterranean Spotted Fever Patients

Trakia Journal of Sciences ◽

10.15547/tjs.2020.02.004 ◽

2020 ◽

Vol 18 (2) ◽

pp. 111-119

Author(s):

Iv. Baltadzhiev ◽

P. Pavlov

Keyword(s):

T Cells ◽

Disease Severity ◽

T Lymphocyte ◽

Lymphocyte Subsets ◽

Spotted Fever ◽

Healing Process ◽

Cell Subset ◽

Rickettsia Conorii ◽

Mediterranean Spotted Fever ◽

T Lymphocyte Subsets

Purpose: Mediterranean spotted fever (MSF) is a rickettsial disease. The aim was to evaluate the host immunе response to Rickettsia conorii. Material and methods: 62 patients were assigned into three groups: with mild, moderate or severe clinical forms of MSF. Controls were 32 healthy individuals. The diagnosis of MSF was confirmed by the indirect immunofluorescence assay. Immunophenotyping was performed using Epics XL-MCL Coulter. Results: The percentage of immune competent (CD3+) cells decreased, whereas that of helper/inducer (CD3+CD4+) and suppressor/cytotoxic (CD3+CD8+) did not change compared to controls. All three T-cell subset percentages did not parallel the disease severity. Naïve T-cells (CD4+CD45RA+) showed reduced levels, whereas activated memory (CD4+CD45RO+) T-cells did not change significantly. The percentage of activated (CD3+HLA-DR+) T-cells increased regardless of the disease severity, till the rise of stimulatory molecules (CD38+total) matched the disease severity forms. The percentage of costimulatory CD28-molecules corresponded to the disease severity as their levels increased significantly in mild forms and showed an evident downward trend towards the severe ones. Conclusion: Reduced T-lymphocyte subsets are likely related to trans-migration into perivascular inflammatory foci. The increased percentage of T-lymphocytes armed with stimulatory molecules probably reflects the mobilization of cell-mediated immune response in the healing process.

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