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Mediterranean spotted fever (MSF) is a rickettsial disease caused by Rickettsia conorii, transmitted by brown dog ticks, and endemic in the Mediterranean region. Its incidence is increasing, with varied presentations and potential complications because of delayed diagnosis. This study retrospectively included 173 adult patients hospitalized for MSF at La Rabta University Hospital, Tunis, from 2000 to 2020. Patients, predominantly male (67.6%) and averaging 40 years of age, mostly resided in urban areas (82.7%). Animal exposure was reported in 74.6%, and cases peaked during the hot season (68.8%), with no cases in winter months. The classic triad of fever, rash, and eschar was observed in 69.9%, with maculopapular lesions affecting palms and soles in 83.8%. Headache (64.5%), myalgia (60.7%), and arthralgia (57.2%) were also common. Laboratory findings included elevated white blood cell count (36.4%), thrombocytopenia (48%), and increased aspartate aminotransferase (50.9%). Treatment with doxycycline (n = 161) resolved fever within 2.8±1.3 [1–5] days. Complications, including encephalitis, chorioretinitis, anterior uveitis and vasculitis, occurred in 2.3% of cases, but all patients recovered without relapse. No significant risk factors for severe forms were identified. Improved awareness of MSF’s clinical features may be the key to an early diagnosis and successful treatment.

Background Spotted fever group of rickettsial infections are emerging in Sri Lanka. We describe a patient with rapidly progressing ARDS and myocarditis secondary to spotted fever caused by Rickettsia conorii . ARDS and myocarditis are rare complications of Rickettsia conorii infections and only a few cases are reported to date. Case presentation A 53 years old manual worker presented with fever for 5 days and a skin rash. He was in circulatory failure on admission and developed severe hypoxaemia with gross changes in chest radiograph by next day requiring assisted ventilation. He had myocarditis causing left ventricular failure and acute respiratory distress syndrome. He was confirmed to have spotted fever rickettsial infection with rising titre of indirect immunofluorescence antibodies to Ricketssia conorii and made a complete recovery with appropriate antibiotic therapy and supportive care. Conclusion Rickettsial infections can present with diverse manifestations. Even the patients with severe organ involvements such as myocarditis and ARDS can be completely cured if timely identified and treated.

Introduction: The aim of this study was to describe the epidemiological patterns of Mediterranean spotted fever (MSF) as well as its treatment and outcomes in children in south Jordan. Methodology: A retrospective observational study was conducted from June 2013 to December 2015. Data regarding demographics, clinical presentation, laboratory findings, treatment, and outcomes were collected. Results: In total, 35 male and 20 female patients (mean age: 6 years ± 3.6) were included. The incidence of MSF was 7.9 cases/100,000 inhabitants/year; MSF affected 89% of individuals in the summer, 74.5% of those living in a rural area with tent housing, and 100% of those who had contact with animals. All cases presented with fever, and 94.5% had a skin rash. Serological tests were positive in 87.2% of cases, and Rickettsia conorii (the Moroccan strain) was present in all positive cases. All cases had thrombocytopenia, but none had leukocytosis. Hyponatremia was present in 71% of cases, and 49%, 61.8%, and 72.7% had increased urea, alanine transaminase, and aspartate aminotransferase levels, respectively. Doxycycline was administered to all patients, with a cure rate of 96.4% and mortality rate of 3.6%. Conclusions: MSF caused by R. conorii (the Moroccan strain) is prevalent in Jordan, and contact with animals is the route of transmission. The patients’ responses to doxycycline were excellent. A high index of suspicion, early diagnosis, and specific treatment considerably decrease mortality. MSF should be considered as a possible cause of febrile disease in those with a rash and in those living in rural areas.

Background Microvascular endothelial barrier dysfunction is the central enigma in spotted fever group (SFG) rickettsioses. Angiogenin (ANG) is one of the earliest identified angiogenic factors, of which some are relevant to the phosphorylation of VE-cadherins that serve as endothelial adherens proteins. Although exogenous ANG is known to translocate into the nucleus of growing endothelial cells (ECs) where it plays a functional role, nuclear ANG is not detected in quiescent ECs. Besides its nuclear role, ANG is thought to play a cytoplasmic role, owing to its RNase activity that cleaves tRNA to produce small RNAs. Recently, such tRNA-derived RNA fragments (tRFs) have been shown to be induced under stress conditions. All these observations raise an intriguing hypothesis about a novel cytoplasmic role of ANG, which is induced upon infection with Rickettsia and generates tRFs that may play roles in SFG rickettsioses. Methods C3H/HeN mice were infected intravenously with a sublethal dose of R. conorii . At days 1, 3, and 5 post infection (p.i.), liver, lung and brain were collected for immunofluorescence (IF) studies of R. conorii and angiogenin (ANG). Human umbilical vein endothelial cells (HUVECs) were infected with R. conorii for 24, 48, and 72 hrs before incubation with 1μg/ml recombinant human ANG (rANG) in normal medium for 2 hrs. HUVEC samples were subjected to IF, exogenous ANG translocation, endothelial permeability, and immunoprecipitation phosphorylation assays. To identify small non-coding RNAs (sncRNAs) upon rickettsial infection, RNAs from pulverized mouse lung tissues and HUVECs were subjected to library preparation and deep sequencing analysis using an Illumina 2000 instrument. Identified sncRNAs were confirmed by Northern hybridization, and their target mRNAs were predicted in silico using BLAST and RNA hybrid programs. Results In the present study, we have demonstrated endothelial up-regulation of ANG, co-localized with SFG rickettsial infection in vivo . We also have provided direct evidence that rickettsial infection sensitizes human ECs to the translocation of exogenous ANG in a compartmentalized pattern at different times post-infection. Typically, exogenous ANG translocates into the nucleus at 24 hrs and to the cytoplasm at 72 hrs post-infection. The ANG cytoplasmic translocation enhances phosphorylation and destabilization of VE-cadherin and attenuates endothelial barrier function. Of note, deep sequencing analysis detected tRFs, mostly derived from the 5'-halves of host tRNAs, that are induced by ANG. Northern hybridization validates the two most abundantly cloned tRFs derived from tRNA-ValGTG and tRNA-GlyGCC, in both mouse tissues and human cells. Bioinformatics analysis predicted that these tRFs may interact with transcripts associated with the endothelial barrier, the host cell inflammatory response, and autophagy. Conclusions Our data provide new insight into the role of compartmentalized ANG during SFG rickettsioses, and highlight its possible mediation through tRFs.

Although cases of Mediterranean spotted fever (MSF) have been reported for decades in southeastern Romania, there are few published data. We retrospectively studied 339 patients, diagnosed with MSF at the National Institute of Infectious Diseases “Prof. Dr. Matei Bals” between 2000 and 2011, in order to raise awareness about MSF in certain regions of Romania. According to the Raoult diagnostic criteria 171 (50.4%) had a score >25 points. Mean age was 52.5 years. One hundred and fifty-five (90.6%) patients were from Bucharest and the surrounding region. Almost all patients presented with fever (99.4%) and rash (98.2%), and 57.9% had evidence of a tick bite. There were no recorded deaths. Serologic diagnosis was made by indirect immunofluorescence assay. Of the 171 patients, serology results for R. conorii were available in 147. One hundred and twenty-three (83.7%) of them had a titer IgG ≥1 : 160 or a fourfold increase in titer in paired samples. MSF is endemic in southeastern Romania and should be considered in patients with fever and rash even in the absence of recognized tick exposure. Since the disease is prevalent in areas highly frequented by tourists, travel-associated MSF should be suspected in patients with characteristic symptoms returning from the endemic area.

The main clinical signs and symptoms caused by a rickettsial infection typically begin 6-10 days after the bite and are accompanied by nonspecific findings such as fever, headache and muscle pain. The diagnosis is mainly based on serological tests, however antibody presentation may be delayed, at least at the early stages of the disease, while seroconversion is usually detected 10-15 days after disease onset. Culture is difficult, requires optimized facilities and often proves negative. Under this scope, the presence of a characteristic inoculation eschar at the bite site may prove a useful clinical tool towards the early suspicion and diagnosis/differential diagnosis of tick-borne rickettsioses, even before the onset of rash and fever or serological confirmation. We describe herein the presence of skin lesions and/or an inoculation eschar at the tick bite site in 17 patients diagnosed, by molecular means, as suffering from spotted fever group rickettsioses. The detection of the pathogen's DNA in biopsy samples proved to be a useful means for early rickettsiae detection and identification. Moreover, the presence of an infiltrated erythema always seemed to precede the appearance of an eschar by 2-5 days and the initiation of fever by 1-10 days; these two signs might also prove useful in the context of the final diagnosis.

The diagnosis of multiple sclerosis (MS), despite well defined clinical criteria is not always simple. On many occasions it is difficult to differentiate MS from various non-MS idiopathic demyelinating disorders, specific and infectious inflammatory diseases or non-inflammatory demyelinating diseases. Clinicians should be aware of various clinical and MRI “red flags” that may point to the other diagnosis and demand further diagnostic evaluation. It is generally accepted that atypical clinical symptoms or atypical neuroimaging signs determine necessity for broad differential diagnostic work up. Of the infectious diseases that are most commonly mistaken for MS the clinician should take into account Whipple's disease, Lyme disease, Syphilis, HIV/AIDS, Brucellosis, HHV-6 infection, Hepatitis C, Mycoplasma and Creutzfeld-Jacob disease, among others. Cat scratch disease caused by Bartonella hensellae, Mediterranean spotted fever caused by Riketssia connore and Leptospirosis caused by different Leptospira serovars rarely cause focal neurological deficit and demyelinating MRI changes similar to MS. When atypical clinical and neuroimaging presentations are present, serology on rare infectious diseases that may mimic MS may be warranted. This review will focus on the infectious diseases mimicking MS with presentation of rare illustrative cases.

Mediterranean spotted fever (MSF) is widely prevalent in many endemic regions in Bulgaria. The disease is still not quite thoroughly studied as to some aspects of its pathogenesis and especially to issues that concern the crucial signals for apoptosis in the target microvascular endothelial cells. To study the expression of Bcl-2 family proteins and Caspase-3 in the dermal capillary endothelial cells from skin papules and in the eschar (tache noire) epidermal layers of patients with MSF so that we can establish apoptotic processes and the time of their occurrence and deployment. Immunohistochemical reactions for Bcl-2, Bax and Caspase-3 were obtained in slices of punch-biopsies taken from papules of the skin rash and from the eschars of eight patients with MSF. The average intensity of the reactions was compared with that in control punch-biopsy slices from four healthy subjects. MSF was etiologically confirmed in all patients by positive antibody response to a specific antigen, Rickettsia conorii, with indirect immunofluorescent assay performed by the Rickettsial Reference Laboratory. The immune reaction for Bcl-2 was found to be poorly expressed in the capillary endothelial cells of skin papules of patients without any differences from controls. The expression of Bax and Caspase-3 was strongly upregulated in comparison with the controls. The Bcl-2/Bax ratio was significantly decreased. Microvascular endothelial cells of the eschar showed similar changes. While the Bcl-2/Bax ratio decreased in the epidermal layers of the eschar \"tache noire\", there were no changes in the intensity of the immunoreactivity of Caspase-3 as compared with controls. The upregulation of Bax and Caspase-3 is an indication of ongoing apoptotic processes in the dermal microvascular endothelial cells of MSF patients. The epidermal layers of the eschar showed increased sensitivity to apoptosis, however, executive phase of apoptosis did not occur.

Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by Rickettsia conorii. MSF is considered a relatively benign disease, but severe complications occur occasionally. However, reports of ocular involvement are few. We describe a case of retinal manifestation in a patient with R. conorii infection.