Search Results (15)

Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF’s impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 female and 28 male FMF patients diagnosed according to the Tel Hashomer and Yalçınkaya criteria and a control group of 20 female and 10 male age-matched cases. Demographic characteristics, medical history (abdominal pain, fever, chest pain, and joint pain), and physical examination findings of the cases were assessed. FMF gene mutations, acute-phase reactants, urine analysis, and spot urine protein/creatinine ratios were evaluated. Nailfold capillaries were examined via capillaroscopy by the same dermatology specialist. Results: There was no significant age or gender difference between groups. The most common symptoms in the case group were abdominal pain (81.7%) and joint pain (65%). Pathological findings in capillaroscopy, such as microhemorrhages and avascular areas, were significantly more frequent in the FMF case group (p < 0.001; p < 0.001). Physiological findings, including hairpin-shaped capillaries and shortened loops, were significantly more common in the control group (p = 0.001; p = 0.034). No significant relationships were found between kidney involvement, subclinical inflammation, presence of microhemorrhages and avascular areas in capillaroscopy, and disease duration. Additionally, no significant differences were observed in capillaroscopic findings between those with exon-10 mutations in the MEFV gene and those with non-exon-10 mutations. Conclusions: In conclusion, our study demonstrated secondary microvascular findings due to inflammation in FMF patients using capillaroscopy, a cost-effective and safe tool. Full article

Vector-borne diseases represent a serious threat to human and animal health, especially where environmental conditions favor pathogen-carrying vectors. Dogs serve as natural hosts for two tick-borne pathogens: Ehrlichia canis, which causes canine monocytic ehrlichiosis, and spotted fever group (SFG) Rickettsia spp., a zoonotic threat in the Mediterranean region. Rhipicephalus sanguineus is the primary vector for these pathogens. Shelter dogs, due to increased exposure to ticks and confined living conditions, facilitate the spread of vector-borne pathogens, raising the risk of zoonotic transmission. This study conducted a serological survey of 1287 dogs from two shelters, assessing exposure to Rickettsia spp. and E. canis and examining the influence of demographic and environmental factors. Seroprevalence rates were 41.8% for Rickettsia spp. and 24.5% for E. canis, with 14% of dogs positive for both pathogens. No significant association was found with sex or breed. A higher seroprevalence was observed in dogs older than 12 months and in those from the shelter on the Mediterranean coast compared to those from the Tyrrhenian coast, likely due to climatic differences. The study highlights the role of climate in disease spread and the need for public health interventions, supporting One Health initiatives to prevent zoonotic disease transmission. Full article

Background: Mediterranean spotted fever (MSF) is an emerging tick-borne disease caused by Rickettsia conorii subsp. conorii, primarily prevalent in Mediterranean and Southern Europe. We aimed to evaluate MSF seroprevalence and risk factors in non-endemic rural areas of Romania. Methods: We conducted a serosurvey in five counties not under MSF surveillance by testing 459 serum samples from adult volunteers for specific IgG antibodies using ELISA. Participants answered a questionnaire regarding demographics and MSF risk factors. Results: The median age of the participants was 60 years and 329 (71.7%) were female. Overall, 64 (13.9%) samples tested positive for IgG anti-R. conorii, with rates ranging from 7.1% in Sibiu to 22.4% in Hunedoara. The median age of the positive individuals was 68 years, with a significantly higher seropositivity rate of 54.7% among those over 65 years (p = 0.01). Among those positive, 53 (82.8%) owned different household animals; 24 (37.5%) had daily contact with dogs, and 27 (42.2%) with livestock; 17 (26.6%) noted tick infestations of animals, and 23 (35.9%) reported tick bites. Conclusions: This study revealed an important seroprevalence of MSF in Romanian areas considered non-endemic, indicating an expansion of its geographical range, probably due to climate change, and emphasizing the importance of enhanced surveillance and diagnostic capabilities nationwide. Full article

Boutonneuse fever (BF) is an eruptive disease and is classified as a spotted fever, which is endemic in the Mediterranean basin (i.e., Marseille fever or Mediterranean spotted fever) and the Black Sea, caused by Rickettsia conorii, with dog ticks being a vector (i.e., Rhipicephalus sanguineus). In Romania, although the first reported outbreak of BF occurred during the summer of 1931 in Constanta, the disease was discovered in 1910. Although the disease has occurred most frequently in the two counties of the Dobruja region (Constanta and Tulcea), a region of the Balkan Peninsula, during the last few years, other counties in southeastern Romania have started to report BF cases. In a period of 9 years, 533 cases were registered in Constanta county, while in a period of 11 years, 339 cases were registered in Bucharest county. In this review, we describe the bacterial tick-borne disease caused by R. conorii in southeastern Romania, focusing on its history and epidemiology, pathophysiology, clinical aspects, diagnosis, treatment and preventive measures in the context of climate changes. Although R. conorii is the principal etiologic agent of BF in southeastern Romania, we should take into consideration that other Rickettsia spp. could be present and involved in disease transmission. Full article

Mediterranean spotted fever (MSF) is a tick-borne rickettsiosis caused by Rickettsia conorii subspecies conorii and transmitted to humans by Rhipicephalus sanguineus ticks. The disease was first discovered in Tunisia in 1910 and was subsequently reported from other Mediterranean countries. The first cases of MSF in the former Soviet Union were detected in 1936 on the Crimean Peninsula. This review summarizes the historic information and main features of MSF in that region and contemporary surveillance and control efforts for this rickettsiosis. Current data pertinent to the epidemiology of the disease, circulation of the ticks and distribution of animal hosts are discussed and compared for each of the countries in the Black Sea basin where MSF occurs. Full article

Different vector-borne pathogens are present or have (re-)emerged in Croatia. Flaviviruses tick-borne encephalitis (TBEV), West Nile (WNV), and Usutu (USUV) are widely distributed in continental regions, while Toscana virus (TOSV) and sandfly fever viruses are detected at the Croatian littoral. Recently, sporadic clinical cases of Tahyna orthobunyavirus (TAHV) and Bhanja bandavirus infection and seropositive individuals have been reported in continental Croatia. Acute infections and serologic evidence of WNV, TBEV, USUV, and TAHV were also confirmed in sentinel animals and vectors. Autochthonous dengue was reported in 2010 at the Croatian littoral. Lyme borreliosis is the most widely distributed vector-borne bacterial infection. The incidence is very high in northwestern and eastern regions, which correlates with numerous records of Ixodes ricinus ticks. Acute human Anaplasma phagocytophilum infections are reported sporadically, but there are many records of serologic evidence of anaplasmosis in animals. Mediterranean spotted fever (Rickettsia conorii) and murine typhus (Rickettsia typhi) are the main rickettsial infections in Croatia. Human leishmaniasis is notified sporadically, while serologic evidence of leishmaniasis was found in 11.4% of the Croatian population. After the official eradication of malaria in 1964, only imported cases were reported in Croatia. Since vector-borne diseases show a growing trend, continuous monitoring of vectors is required to protect the population from these infections. Full article

Mediterranean Spotted Fever (MSF) is one of the most common spotted fever Rickettsioses. Most cases of MSF follow a benign course, with a minority of cases being fatal. The severity of the infection depends on bacterial virulence, dose and host factors such as effective immune response and genetic background. Herein, we reported data on typing by competitive allele-specific PCR of functionally relevant polymorphisms of genes coding for MyD88 adapter-like (Mal/TIRAP) protein (rs8177374), interleukin(IL)-1 cluster (IL-1A rs1800587, IL-1B rs16944 and rs1143634) and IL-18 (rs187238), which might be crucial for an efficient immune response. The results enlighten the role that IL-1 gene cluster variants might play in susceptibility against Rickettsia conorii infection. In particular, the IL-1A rs1800587TT genotype was significantly increased in patients alone and combined in a haplotype composed by minor alleles rs1800587T, rs16944A and rs1143634A. This result was confirmed using the decision tree heuristic approach. Using this methodology, IL-1A rs1800587TT genotype was the better discrimination key among MSF patients and controls. In addition, the IL-1 gene cluster SNP genotypes containing minor alleles and IL-18 rs187238G positive genotypes were found as associated with risk of severe complications such as sepsis, septic shock, acute respiratory distress syndrome and coma. In conclusion, these data suggest that the evaluation of IL-1A, IL-1B and IL-18 gene SNPs can add useful information on the clinical course of patients affected by Mediterranean Spotted Fever, even if further confirmatory studies will be necessary. Full article

Tick-borne rickettsioses (TBR) are caused by obligate, intracellular bacteria of the spotted-fever group (SFG) of the genus Rickettsia (Order Rickettsiales), transmitted by hard ticks. TBR are one of the oldest known vector-borne zoonoses and pose a threat to both human and animal health, as over the years, new SFG Rickettsia spp. have been reported worldwide with the potential to be human pathogens. In Portugal and Spain, the countries that constitute the Iberian Peninsula, reported TB rickettsiae causing human disease include Rickettsia conorii conorii, Rickettsia conorii israelensis, Rickettsia slovaca, Rickettsia raoultii, Candidatus Rickettsia rioja, Rickettsia sibirica mongolitimonae, and Rickettsia monacensis. An allochthonous case of TBR caused by Rickettsia massiliae, described in Spain, points to the need to monitor disease epidemiology, to predict risks of exposure and spread of disease, and taking into account globalization and climate changes. This review aims to provide up-to-date information on the status of TBR in the Iberian Peninsula, as well as to show the importance of a national and international collaborative epidemiology surveillance network, towards monitoring Rickettsia spp. circulation in both Portugal and Spain. Full article

Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Misdiagnosis of MSF may occur with febrile syndromes associated with rash and thrombocytopenia, such as Crimean-Congo hemorrhagic fever (CCHF). This study aimed to determine the prevalence of R. conorii among serum samples obtained from 260 suspected CCHF patients with features of MSF in Iran (2018–2020). The quantitative polymerase chain reaction (qPCR) method detected three (1.15%) positive 16S rDNA Rickettsia spp. samples that were classified as R. conorii subsp. conorii, R. conorii subsp. Israelensis, and R. helvetica using the sequencing of gltA, ompA, and 17kDa genes. Furthermore, R. conorii IgM antibodies presented in 38 (14.62%) patients by the enzyme-linked immunosorbent assay (ELISA) method. Out of 97 MSF patients with available paired serum samples, IgM seroconversion and a four-fold increase were observed in 14 (14.43%) and 12 (12.37%) patients, respectively. We concluded that rickettsial agents are present in Iran and may be misdiagnosed with other febrile syndromes. Full article

The migratory behavior of wild birds contributes to the geographical spread of ticks and their microorganisms. In this study, we aimed to investigate the dispersal and co-occurrence of Francisella and spotted fever group Rickettsia (SFGR) in ticks infesting birds migrating northward in the African-Western Palaearctic region (AWPR). Birds were trapped with mist nests across the Mediterranean basin during the 2014 and 2015 spring migration. In total, 575 ticks were collected from 244 birds. We screened the ticks for the species Francisella tularensis, the genus Francisella, and SFGR by microfluidic real-time PCR. Confirmatory analyses and metagenomic sequencing were performed on tick samples that putatively tested positive for F. tularensis during initial screenings. Hyalomma rufipes was the most common tick species and had a high prevalence of Francisella, including co-occurrence of Francisella and SFGR. Metagenomic analysis of total DNA extracted from two H. rufipes confirmed the presence of Francisella, Rickettsia, and Midichloria. Average nucleotide identity and phylogenetic inference indicated the highest identity of the metagenome-assembled genomes to a Francisella-like endosymbiont (FLE), Rickettsia aeschlimannii, and Midichloria mitochondrii. The results of this study suggest that (i) FLE- and SFGR-containing ticks are dispersed by northbound migratory birds in the AWPR, (ii) H. rufipes likely is not involved in transmission of F. tularensis in the AWPR, and (iii) a dual endosymbiosis of FLEs and Midichloria may support some of the nutritional requirements of H. rufipes. Full article

The order Rickettsiales includes species that cause a range of human diseases such as human granulocytic anaplasmosis (Anaplasma phagocytophilum), human monocytic ehrlichiosis (Ehrlichia chaffeensis), scrub typhus (Orientia tsutsugamushi), epidemic typhus (Rickettsia prowazekii), murine typhus (R. typhi), Mediterranean spotted fever (R. conorii), or Rocky Mountain spotted fever (R. rickettsii). These diseases are gaining a new momentum given their resurgence patterns and geographical expansion due to the overall rise in temperature and other human-induced pressure, thereby remaining a major public health concern. As obligate intracellular bacteria, Rickettsiales are characterized by their small genome sizes due to reductive evolution. Many pathogens employ moonlighting/multitasking proteins as virulence factors to interfere with multiple cellular processes, in different compartments, at different times during infection, augmenting their virulence. The utilization of this multitasking phenomenon by Rickettsiales as a strategy to maximize the use of their reduced protein repertoire is an emerging theme. Here, we provide an overview of the role of various moonlighting proteins in the pathogenicity of these species. Despite the challenges that lie ahead to determine the multiple potential faces of every single protein in Rickettsiales, the available examples anticipate this multifunctionality as an essential and intrinsic feature of these obligates and should be integrated into available moonlighting repositories. Full article

Background: Motivated by a case finding of Mediterranean spotted fever (MSF) associated with atypical pneumonia and pleural effusion in which Rickettsia conorii subsp. israelensis was identified by molecular methods in the pleural fluid, we wanted to summarize the clinical presentations of rickettsiosis in Italy by systematic research and to make a systematic review of all the global cases of rickettsiosis associated with pleural effusion. Methods: For the literature search, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. We chose to select only the studies published in last 25 years and confirmed both with serological and molecular assays. Results: Human cases of rickettsiosis in Italy were reported in 48 papers describing 2831 patients with very different clinical presentations; the majority was MSF accounted to R. conorii and was reported in Sicily. Pleural effusion associated with infection with microorganisms belonging to Rickettsiales was described in 487 patients. It was rarely associated with microorganisms different from O. tsutsugamushi; also rarely, cases of scrub typhus were reported outside Southeast Asia and in the largest majority, the diagnosis was achieved with serology. Conclusions: MSF, especially when caused by R. conorii subsp. israelensis, may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis Full article

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. Full article

Phlebotomine sand flies are generalist vectors with significant implications for public health. They are able to transmit phleboviruses that cause sand fly fever, headaches, or meningitis in humans. Albania is a country in Southeast Europe with a typical Mediterranean climate which provides convenient conditions for the presence of sand flies. Hence, the circulation of phleboviruses, such as the Toscana and Balkan viruses, has been recently described in the country. We followed a virus discovery approach on sand fly samples collected in 2015 and 2016 in seven regions of Albania, with the aim to investigate and characterize potentially circulating phleboviruses in phlebotomine sand flies. A presumed novel phlebovirus was detected in a pool consisting of 24 Phlebotomus neglectus males. The virus was provisionally named the Drin virus after a river near the locality of Kukës, where the infected sand flies were trapped. Genetic and phylogenetic analysis revealed that the Drin virus is closely related to the Corfou (CFUV) virus, isolated in the 1980s from Phlebotomus major sand flies on the eponymous island of Greece, and may also be involved in human infections because of its similarity to the sand fly fever Sicilian virus. The latter justifies further studies to specifically address this concern. Together with recent findings, this study confirms that Albania and the Balkan peninsula are hot spots for phleboviruses. Full article

Mediterranean spotted fever develops from an infection with Rickettsia conorii, an obligate intracellular, Gram-negative, endotheliotropic, and tick-transmitted bacterial pathogen, and is an acute, febrile illness that can progress to life-threatening complications if not diagnosed and treated early with effective antibiotics. Despite significant morbidity and mortality, little is known about changes in gene expression that determine the host responses during in vivo infection. We have investigated the transcriptional landscape of host lungs as a prominently affected organ system in an established murine model of infection by RNA-sequencing. Ingenuity pathway analysis resulted in the identification of 1332 differentially expressed genes and 292 upstream regulators. Notably, genes encoding for ubiquitin D, aconitate decarboxylase, antimicrobial peptides, calgranulins, cytokines and chemokines, and guanylate binding proteins were highly up-regulated, whereas those involved in hemoglobin biosynthesis and heme homeostasis were significantly down-regulated. Amongst response regulators, nucleotide-binding oligomerization domain-containing protein 2 and killer cell lectin-like receptors were differentially expressed, and gene clustering revealed eukaryotic initiation factor-2, oxidative phosphorylation, and ubiquitination as the predominantly activated biological pathways. Collectively, this first global transcriptomic profiling has identified R. conorii-induced regulation of novel genes and pathways in the host lungs, further in-depth investigation of which will strengthen our understanding of the pathogenesis of human rickettsioses. Full article