The case of Mediterranean spotted fever of the traveler returned from Zambia.

We report the case of a traveler who returned from Zambia and was diagnosed with Mediterranean spotted fever (MSF), an infectious disease caused by Rickettsia conorii conorii. The patient presented to Sapporo City General Hospital with symptoms of fever, malaise, headache, and rash. The pathogen was identified by Polymerase Chain Reaction assays and subsequent analyses. The patient improved with 10-day treatment of oral doxycycline. Although some cases of MSF have been reported in sub-Saharan Africa, none have been reported in Zambia. Rhipicephalus sanguineus sensu lato, the vector of the Rickettsia conorii conorii, has been found in various areas of Zambia. Our case report highlights the potential threat of Mediterranean spotted fever in urban areas of Zambia.

Cervids as Sentinels for Rickettsia spp. in Portugal.

Cervids are highly exposed to ticks, however, their role in the life cycle of these rickettsiae has not been fully elucidated. Given the expanding distribution and growing population of deer species in Portugal, coupled with their direct and indirect interactions with humans during hunting, it becomes crucial to explore their role as sentinels and potential reservoirs of Rickettsia. The present investigation aimed to detect and evaluate exposure to Rickettsia in free-living deer from Portugal. Blood samples (n = 77) were collected from hunted game animals (red deer and fallow deer) from different areas throughout Portugal (Idanha-a-Nova, Monte Fidalgo, Montalvão and Arraiolos) and sera were tested by immunofluorescence assay, to detect antibodies. Additionally, blood DNA samples were screened for SFGR by nested-polymerase chain reaction targeting a fragment of the outer membrane protein B (ompB) gene, as well as for Anaplasma and Ehrlichia spp. targeting the 16S rRNA gene. Thirty-five per cent (25 deer and two fallow deer) tested positive (sera with a titer ≥1:64) for IgG antibodies against Rickettsia conorii. No rickettsial DNA was detected by PCR for the ompB gene, and all DNA samples tested negative for Anaplasma and Ehrlichia. As far as we know, this study is the first screening of cervid species in Portugal for Rickettsia antibodies. The findings suggest that these animals serve as useful sentinel indicators for the circulation of rickettsiae, offering a complementary perspective to studies focused on ticks. The increasing numbers of hunted deer in Portugal and the potential zoonotic features of Rickettsia spp. highlight the importance of continued surveillance directed at tick-borne diseases, especially those involving wild animals.

Rhipicephalus sanguineus from Hungarian dogs: Tick identification and detection of tick-borne pathogens.

The brown dog tick, Rhipicephalus sanguineus is a complex of tick species with an unsettled species concept. In Europe, R. sanguineus is considered mainly a Mediterranean tick with sporadic findings in central and northern Europe. R. sanguineus is known as a vector of a range of pathogens of medical and veterinary importance, most of which not yet reported as autochthonous in Hungary. A total of 1839 ticks collected by veterinarians from dogs and cats were obtained in Hungary. The study aims at precise determination of ticks identified as R. sanguineus and detection of pathogens in collected ticks. All ticks were morphologically determined and 169 individuals were identified as R. sanguineus. A subset of 15 ticks was selected for molecular analysis (16S rDNA, 12S rDNA, COI). Phylogenetic analyses invariably placed sequences of all three markers into a single haplotype identified as R. sanguineus sensu stricto. All 169 brown dog ticks were tested for the presence of A. platys, E. canis, R. conorii, B. vogeli and H. canis. None of the investigated ticks was positive for the screened pathogens, though A. phagocytophilum sequence was detected in a single tick.

Retiform purpura secondary to Rickettsia conorii / Púrpura retiforme secundaria a Rickettsia conorii

Retiform purpura consists of branching purpuric lesions caused by a complete blockage of blood flow in the dermal/subcutaneous vasculature. It is an acute life-threatening disorder characterized by intravascular thrombosis and hemorrhagic infarction of the skin complicated with disseminated intravascular coagulation. It is commonly seen in acute infections following meningococcal and streptococcal infections. Few cases have been described of retiform purpura following rickettsial infections in the literature and rarely with this magnitude. The purpose of this report is to highlight the possibility of this situation in critically ill patients. We report a case of a 62-year-old woman admitted in the intensive care unit with septic shock from Rickettsia conorii. She developed quickly an intense retiform purpura requiring several surgical interventions to control the necrosis. The dermatologic situation was only completely controlled with treatment of underlying situation. This is a severe complication of a critical infectious disease. (AU)

La púrpura retiforme consiste en lesiones purpúricas ramificadas causadas por un bloqueo completo del flujo sanguíneo en la vasculatura dérmica/subcutánea. Es un trastorno agudo potencialmente mortal caracterizado por trombosis intravascular e infarto hemorrágico de la piel complicado con coagulación intravascular diseminada. Se ve comúnmente en infecciones agudas después de infecciones meningocócicas y estreptocócicas. Se han descrito pocos casos de púrpura retiforme tras infecciones por rickettsiosis en la literatura y rara vez de esta magnitud. El propósito de este informe es resaltar la posibilidad de esta situación en pacientes críticamente enfermos. Presentamos el caso de una mujer de 62 años ingresada en la unidad de cuidados intensivos con shock séptico por Rickettsia conorii. Rápidamente desarrolló una intensa púrpura retiforme que requirió varias intervenciones quirúrgicas para controlar la necrosis. La situación dermatológica solo se controló por completo con el tratamiento de la situación subyacente. Esta es una complicación grave de una enfermedad infecciosa crítica. (AU)

Single particle cryo-EM analysis of Rickettsia conorii Sca2 reveals a formin-like core.

Spotted fever group Rickettsia undergo actin-based motility inside infected eukaryotic cells using Sca2 (surface cell antigen 2): an âˆ¼ 1800 amino-acid monomeric autotransporter protein that is surface-attached to the bacterium and responsible for the assembly of long unbranched actin tails. Sca2 is the only known functional mimic of eukaryotic formins, yet it shares no sequence similarities to the latter. Using structural and biochemical approaches we have previously shown that Sca2 uses a novel actin assembly mechanism. The first âˆ¼ 400 amino acids fold into helix-loop-helix repeats that form a crescent shape reminiscent of a formin FH2 monomer. Additionally, the N- and C- terminal halves of Sca2 display intramolecular interaction in an end-to-end manner and cooperate for actin assembly, mimicking a formin FH2 dimer. Towards a better structural understanding of this mechanism, we performed single-particle cryo-electron microscopy analysis of Sca2. While high-resolution structural details remain elusive, our model confirms the presence of a formin-like core: Sca2 indeed forms a doughnut shape, similar in diameter to a formin FH2 dimer and can accommodate two actin subunits. Extra electron density, thought to be contributed by the C-terminal repeat domain (CRD), covering one side is also observed. This structural analysis allows us to propose an updated model where nucleation proceeds by encircling two actin subunits, and elongation proceeds either by a formin-like mechanism that necessitates conformational changes in the observed Sca2 model, or via an insertional mechanism akin to that observed in the ParMRC system.

Rickettsia conorii Subspecies israelensis in Captive Baboons.

Hamadryas baboons (Papio hamadryas) may transmit zoonotic vector-borne pathogens to visitors and workers frequenting zoological parks. We molecularly screened 33 baboons for vector-borne pathogens. Three (9.1%) of 33 animals tested positive for Rickettsia conorii subspecies israelensis. Clinicians should be aware of potential health risks from spatial overlapping between baboons and humans.

A Small Non-Coding RNA Mediates Transcript Stability and Expression of Cytochrome bd Ubiquinol Oxidase Subunit I in Rickettsia conorii.

Small regulatory RNAs (sRNAs) are now widely recognized for their role in the post-transcriptional regulation of bacterial virulence and growth. We have previously demonstrated the biogenesis and differential expression of several sRNAs in Rickettsia conorii during interactions with the human host and arthropod vector, as well as the in vitro binding of Rickettsia conorii sRNA Rc_sR42 to bicistronic cytochrome bd ubiquinol oxidase subunits I and II (cydAB) mRNA. However, the mechanism of regulation and the effect of sRNA binding on the stability of the cydAB bicistronic transcript and the expression of the cydA and cydB genes are still unknown. In this study, we determined the expression dynamics of Rc_sR42 and its cognate target genes, cydA and cydB, in mouse lung and brain tissues during R. conorii infection in vivo and employed fluorescent and reporter assays to decode the role of sRNA in regulating cognate gene transcripts. Quantitative RT-PCR revealed significant changes in the expression of sRNA and its cognate target gene transcripts during R. conorii infection in vivo, and a greater abundance of these transcripts was observed in the lungs compared to brain tissue. Interestingly, while Rc_sR42 and cydA exhibited similar patterns of change in their expression, indicating the influence of sRNA on the mRNA target, the expression of cydB was independent of sRNA expression. Further, we constructed reporter plasmids of sRNA and cydAB bicistronic mRNA to decipher the role of sRNA on CydA and CydB expression. We observed increased expression of CydA in the presence of sRNA but detected no change in CydB expression in the presence or absence of sRNA. In sum, our results demonstrate that the binding of Rc_sR42 is required for the regulation of cydA but not cydB. Further studies on understanding the influence of this interaction on the mammalian host and tick vector during R. conorii infection are in progress.

Fatal complicated infection by Rickettsia conorii: role of cerebral involvement, antiphospholipid antibodies, and multiple comorbidities.

An intriguing case of lethal rickettsiosis caused by Rickettsia conorii complicated by brain involvement and the presence anti-phospholipid antibodies is presented and discussed, on the ground of recent literature evidences.

Mediterranean spotted fever with multiorgan involvement.

A previously well man in his 50s returned to the UK after a trip to the Mediterranean. The day after returning he developed malaise, fevers, rigors and severe headache. He was hospitalised with sepsis, multiorgan involvement, a maculopapular rash and an eschar on each hip. Serology was positive for Rickettsia spp (spotted fever group) with a rise in titre from 1:64 to 1:1024 eight days later. Blood and tissue PCR were also positive for Rickettsia spp. He had cardiac, pulmonary, renal, ocular and neurological involvement. He completed a 14-day course of doxycycline and recovered well. This is a case of likely Mediterranean spotted fever (MSF) caused by Rickettsia conorii, which is endemic to the Mediterranean basin. We highlight the need for awareness and early treatment to prevent severe complications. This case is also the first to describe Purtscher-like retinopathy in the context of likely MSF.

An update on spotted fever group serology in Kerman Province, Iran.

Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF) and reports of its geographical distribution are spreading every day. Recently, some cases of the MSF have been reported from Iran. However, little information is available about the MSF epidemiology in Iran. The aim of the current study was to investigate anti-R. conorii IgG seroprevalence among farmers living in the rural regions of Kerman province (in southeastern Iran). In this study, 281 blood samples were collected from farmers in Zarand and Jiroft counties and tested for detection of anti-R. conorii IgG antibodies using the ELISA method. Among the 281 samples, 14 farmers (4.98%, CI 95%; 2.45-7.55%) had anti-R. conorii IgG antibodies. Seroprevalence of MSF in Zarand and Jiroft counties were 4.58% and 5.33%, respectively. The serological evidence of this study indicates the seroprevalence of R. conorii in rural areas of the Kerman province of Iran. So, it is recommended that the Iranian health care system pay attention to the MSF.

Mediterranean spotted fever and peripheral facial nerve palsy: a rare neurological complication.

Mediterranean spotted fever (MSF) caused by the bacterium Rickettsia conorii is one of the oldest known tick-borne diseases. It is transmitted by the brown dog tick Rhipicephalus sanguineus and occurs mainly in the Mediterranean area. MSF usually presents with a skin rash, high fever, and characteristic eschar at the site of the tick bite. The course of this disease may be benign or life-threatening. Focal neurological manifestations are unusual. We report the case of a patient who presented with an isolated peripheral facial nerve palsy complicating R conorii conorii infection.

Fatal Case of Mediterranean Spotted Fever Associated with Septic Shock, Iran.

A fatal case of Mediterranean spotted fever associated with septic shock was reported in a 61-year-old man living in a village in southeastern Iran. The patient had a history of tick bite a few days before symptom onset. Phylogenetic analysis confirmed infection by Rickettsia conorii subspecies israelensis.

Confirmation of Rickettsia conorii Subspecies indica Infection by Next-Generation Sequencing, Shandong, China.

We describe 3 similar cases of rickettsial disease that occurred after tick bites in a mountainous rural area of Shandong Province, China. Next-generation sequencing indicated the etiologic agent of 1 patient was Rickettsia conorii subspecies indica. This agent may be more widely distributed across China than previously thought.

Concomitant Mediterranean spotted fever and systemic lupus erythematosus: a rare case report.

Infections are an important cause of morbidity and mortality in Systemic Lupus Erythematosus (SLE). Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii. This infection is endemic in Tunisia with summer seasonality. Herein, the case of a 45 years old woman, admitted to hospital with fever and erythema nodosum. On examination, she had a diffuse skin rash, malar rash, and polyarthritis. Serology demonstrated Rickettsia Conoriiinfection. The diagnosis of MSF was made and the patient had a course of doxycycline for 5 days with a prompt improvement of the fever, the skin lesions but she had a persistent malar rash, polyarthritis, and lymphopenia. The immunological profile was positive for antinuclear antibodies (ANA), anti-DNA antibodies, anti-nucleosomes antibodies, and anti-citrullinated protein antibodies (ACPA). The diagnosis of SLE was established. We report the first case of SLE associated with MSF and with erythema nodosum as the initial presentation.

Rickettsia conorii survival in THP-1 macrophages involves host lipid droplet alterations and active rickettsial protein production.

Rickettsia conorii is a Gram-negative, cytosolic intracellular bacterium that has classically been investigated in terms of endothelial cell infection. However, R. conorii and other human pathogenic Rickettsia species have evolved mechanisms to grow in various cell types, including macrophages, during mammalian infection. During infection of these phagocytes, R. conorii shifts the host cell's overall metabolism towards an anti-inflammatory M2 response, metabolically defined by an increase in host lipid metabolism and oxidative phosphorylation. Lipid metabolism has more recently been identified as a key regulator of host homeostasis through modulation of immune signalling and metabolism. Intracellular pathogens have adapted mechanisms of hijacking host metabolic pathways including host lipid catabolic pathways for various functions required for growth and survival. In the present study, we hypothesised that alterations of host lipid droplets initiated by lipid catabolic pathways during R. conorii infection is important for bacterial survival in macrophages. Herein, we determined that host lipid droplet modulation is initiated early during R. conorii infection, and these alterations rely on active bacteria and lipid catabolic pathways. We also find that these lipid catabolic pathways are essential for efficient bacterial survival. Unlike the mechanisms used by other intracellular pathogens, the catabolism of lipid droplets induced by R. conorii infection is independent of upstream host peroxisome proliferator-activated receptor-alpha (PPARα) signalling. Inhibition of PPARÉ£ signalling and lipid droplet accumulation in host cells cause a significant decrease in R. conorii survival suggesting a negative correlation with lipid droplet production and R. conorii survival. Together, these results strongly suggest that the modulation of lipid droplets in macrophage cells infected by R. conorii is an important and underappreciated aspect of the infection process. TAKE AWAYS: Host lipid droplets are differentially altered in early and replicative stages of THP-1 macrophage infection with R. conorii. Lipid droplet alterations are initiated in a bacterial-dependent manner and do not require host peroxisome proliferator-activated receptors α or É£ activation. Pharmacological inhibition of host lipid catabolic processes during R. conorii infection indicates a requirement of lipid catabolism for bacterial survival and initiation of lipid droplet modulation. A significant increase in host lipid droplets during infection has a negative impact on R. conorii survival in THP-1 macrophages.

Spotted Fever Group Rickettsioses in Israel, 2010-2019.

In a multicenter, nationwide, retrospective study of patients hospitalized with spotted fever group rickettsiosis in Israel during 2010-2019, we identified 42 cases, of which 36 were autochthonous. The most prevalent species was the Rickettsia conorii Israeli tick typhus strain (n = 33, 79%); infection with this species necessitated intensive care for 52% of patients and was associated with a 30% fatality rate. A history of tick bite was rare, found for only 5% of patients; eschar was found in 12%; and leukocytosis was more common than leukopenia. Most (72%) patients resided along the Mediterranean shoreline. For 3 patients, a new Rickettsia variant was identified and had been acquired in eastern, mountainous parts of Israel. One patient had prolonged fever before admission and clinical signs resembling tickborne lymphadenopathy. Our findings suggest that a broad range of Rickettsia species cause spotted fever group rickettsiosis in Israel.

Acute disseminated encephalomyelitis due to Rickettsia conorii infection.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated acute inflammatory demyelinating disorder, which typically occurs after viral infections or immunisation. We present a case of a man with acute Rickettsia conorii infection whose diagnosis was delayed. He presented with fever, headache, an eschar and an acute paraplegia. The R. conorii IgM serum titre was 1:128. Magnetic resonance imaging showed multifocal lesions in the brain and spinal cord consistent with inflammatory demyelination. The patient responded well to doxycycline and a short course of high-dose corticosteroids. To our knowledge this is the first case of ADEM associated with Mediterranean spotted fever - we found a previous report of ADEM in a child with Rocky Mountain spotted fever, whose diagnosis of rickettsial infection was also delayed. We hypothesise that delayed diagnosis of spotted fever group rickettsial infections could rarely result in ADEM.

Renal Involvement in Mediterranean Spotted Fever: Clinical and Histopathological Data.

OBJECTIVE: Mediterranean spotted fever (MSF) is a tick-borne rickettsial infection endemic to the Mediterranean coastline countries. As a result of growing tourism, imported cases have been registered in many nonendemic countries and regions. We present clinical laboratory parameters and histopathological data on renal impairment in patients with MSF. The study meets our goal of identifying kidney involvement and detecting renal damage in people with MSF. SUBJECTS AND METHODS: Three hundred fifty patients with MSF with a diagnosis confirmed by immunofluorescence analysis were tested for serum urea, creatinine, and albumin. Fifty-five patients with malignant form of MSF were divided into 2 groups: 19 fatalities and 36 survivors. The percentage of patients with acute renal failure (ARF) was compared in both groups. RESULTS: Subjects with elevated urea and creatinine levels increased from 5.21 to 3.47% in mild to 48.78 and 29.26% in severe MSF, respectively. Loss of serum albumin also increased from mild to severe MSF. Renal impairment comprised 60% of the cohort of 55 patients with malignant MSF: 89.4% in the group of deaths and almost twice less in the survivors. ARF developed in 84.2% of fatal cases and was >2 times less in survivors. Postmortem light microscopy of renal samples of 9 fatal cases revealed perivascular mononuclear inflammatory infiltrates, vasculitis with fibrinoid necrosis, acute tubular necrosis, interstitial edema, hemorrhage, and thrombosis. CONCLUSION: Renal pathology associated with MSF rickettsial infection consists of systemic small vessel vasculitis and vascular injury, leading to ARF in the most severe cases.