Rickettsia conorii subsp. israelensis infection in a pediatric patient presenting skin rash and abdominal pain: a case report from Southeast Iran.

BACKGROUND: The healthcare system in Iran appears to overlook Mediterranean spotted fever (MSF) as an endemic disease, particularly in pediatric cases, indicating the need for greater attention and awareness. CASE PRESENTATION: A six-year-old patient with fever, abdominal pain, headache, skin rashes, diarrhea, vomiting, and black eschar (tache noire) from southeast Iran was identified as a rickettsiosis caused by Rickettsia conorii subsp. israelensis through clinical and laboratory assessments, including IFA and real-time PCR. The patient was successfully treated with doxycycline. CONCLUSIONS: Symptoms like rash, edema, eschar, and abdominal pain may indicate the possibility of MSF during the assessment of acute febrile illness, IFA and real-time PCR are the primary diagnostic methods for this disease.

Serological and molecular epidemiological investigation of Mediterranean spotted fever in Yunnan Province, China.

OBJECTIVES: Given the limited research and its potential hazards, the study aimed to determine the prevalence of Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii), a tick-borne disease, in Yunnan Province, China. METHODS: Through stratified sampling across five distinct regions in Yunnan, 5358 blood samples were obtained from the general healthy population. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Polymerase chain reaction (PCR) were employed for analysis. RESULTS: IFA identified 27 (0.50%) subjects with immunoglobulin G (IgG) positivity; none were positive for immunoglobulin M (IgM) via ELISA. PCR detected one individual with R. conorii outer membrane protein A (ompA). Significant seroprevalence variation was observed, particularly in Southern Yunnan (P = 0.032), with R. conorii subsp. conorii confirmed in the PCR-positive sample. CONCLUSIONS: This research reveals a correlation between MSF prevalence, geography, and climate in Yunnan. The paucity of prior studies underscores MSF's potential diagnostic challenges in the region. Comprehensive understanding of the pathogen's distribution is pivotal for intervention. Given the study's scope and Yunnan's unique setting, additional research is advocated.

History and Current Status of Mediterranean Spotted Fever (MSF) in the Crimean Peninsula and Neighboring Regions along the Black Sea Coast.

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.

Mediterranean spotted fever as a non-endemic disease in the southeast of Iran: Diagnosis and treatment based on specific skin lesion.

Key Clinical Message: Rickettsia spp. should be investigated if Tache Noire, as a dark plaque covering a superficial ulcer surrounded by scale, edema, and erythema, are observed, even in non-endemic areas of Rickettsia spp. Abstract: A 31-year-old man with fever, dyspnea, abdominal pain, and jaundice has been admitted to the hospital in the southeast of Iran. Due to the presence of a pathognomonic skin lesion (Tache noire), the patient was diagnosed with Mediterranean spotted fever (MSF) and was treated with doxycycline, without waiting for PCR and IFA findings.

Use of eschar swab DNA to diagnose Rickettsia conorii subspecies conorii infection in Crimea: A case report.

Mediterranean spotted fever (MSF) has been diagnosed clinically in the Crimean Peninsula since the 1930s. We describe the recent illness of an elderly patient from Crimea who had developed a classic triad of MSF symptoms consisting of fever, maculopapular rash, and eschar. Clinical diagnosis of rickettsiosis was confirmed using real-time PCR and sequencing of 4 Rickettsia protein genes. The strain causing clinical illness was characterized as Rickettsia conorii subspecies conorii Malish 7. This report corroborates the utility of eschar swab material as a source of DNA for PCR-based diagnostics that enables timely patient treatment and management.

A case of Mediterranean spotted fever mimicking severe sepsis.

Mediterranean spotted fever (MSF) is a tick-borne acute endemic infectious disease caused by Rickettsia conorii. While MSF may progress asymptomatically, it may lead to clinical pictures like severe hemorrhagic fever. In this article, we are presenting an MSF case with signs of high fever, headache, nausea, weakness and generalized maculopapular rash. The diagnosis of the female patient who had a history of contact with a tick-infested dog was confirmed with her clinical and laboratory data. The clinical and laboratory findings of the patient who was given doxycycline by 200 mg/day for 7 days were improved in a short time. Rickettsia conorii serology by indirect immunofluorescence assay method confirmed the diagnosis of MSF. In cases of severe sepsis accompanied by high fever and generalized maculopapular rash where the source of the infection cannot be determined in the short term, carefully questioning exposure to ticks by considering the existing geographical, seasonal and endemic environmental factors may be life-saving in terms of early diagnosis and treatment of MSF, which may become fatal even in the absence of eschars (tache noire). The symptomatology of hemorrhagic fever associated with Rickettsia conorii may be confused with that of sepsis in clinical practice.

IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever.

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.

Natural Mediterranean Spotted Fever Foci, Qingdao, China.

We sequenced DNA from spleens of rodents captured in rural areas of Qingdao, East China, during 2013-2015. We found 1 Apodemus agrarius mouse infected with Rickettsia conorii, indicating a natural Mediterranean spotted fever foci exists in East China and that the range of R. conorii could be expanding.

Tick-Borne Rickettsioses in the Iberian Peninsula.

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.

Mediterranean spotted fever-like illness caused by Rickettsia sibirica mongolitimonae, North Macedonia, June 2022.

Mediterranean spotted fever-like illness (MSF-like illness) is a tick-borne disease caused by Rickettsia sibirica mongolitimonae first reported in France more than 25 years ago. Until today, more than 50 cases of MSF-like illness have been reported in different regions of Europe and Africa, highlighting variable clinical manifestation. Here we report a case of MSF-like illness following a bite from a Hyalomma tick in the Skopje region of North Macedonia.

Rickettsia conorii: Unusual case of acute aortic thrombosis.

OBJECTIVES: Mediterranean spotted fever is a common zoonosis in Europe caused by Rickettsia conorii bacterium. Among its wide range of clinical presentations, arterial thrombosis of large vessels has never been described before. METHODS: We report a case of a complete acute infrarenal aortic thrombosis in a 61-year-old male with R. conorii infection. RESULTS AND CONCLUSION: The patient was successfully operated using open aortic surgery and subsequent treatment with doxycycline. To our knowledge, this is the first report of aortic thrombosis associated with infection by this parasite, extending the clinical spectrum of the disease.

Investigation of Rickettsia conorii in Patients Suspected of Having Crimean-Congo Hemorrhagic Fever.

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.

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.

Rickettsia conorii subsp. israelensis infection: a case report from southeast Iran.

BACKGROUND: Mediterranean spotted fever (MSF) is a zoonotic and vector-borne disease caused by Rickettsia conorii. We report a case (36 year-old-woman) of MSF caused by Rickettsia conorii from Iran. CASE PRESENTATION: In September 2019, the patient was admitted to the hospital in Kerman province with flu-like symptoms and maculopapular lesions. According to the laboratory results, thrombocytopenia, elevated liver enzymes, and cardiac enzymes were observed. Skin biopsy was examined for Crimean-Congo Hemorrhagic Fever (CCHF) and MSF using the Real-Time-PCR and ELISA method. Finally, the sample was positive for Rickettsia conorii subsp. israelensis and treated with doxycycline and completely recovered. CONCLUSIONS: This study showed that MSF could be present in Iran. Therefore, identifying endemic areas in Iran for this disease should be on the agenda.

Molecular detection and identification of Rickettsia spp. in collected ticks from domestic animals in Southeastern of Iran.

Ticks are considered as the reservoirs for pathogenic Rickettsia for humans and domestic animals. Recently, clinical cases of rickettsiosis have been reported from Iran and its surrounding countries. This study was aimed at investigating the prevalence of Rickettsia spp. in ticks in Southeastern Iran.All ticks were collected April to September 2019 from the domestic animals and stray dogs from different villages of Kerman province. For the primary detection of Rickettsia spp., Real-Time PCR was carried out on extracted DNA from ticks by targeting the 16 S rRNA gene. From the PCR-sequencing method of 16 S rRNA, citrate synthase (gltA), antigen 17 kDa, and ompA genes were used for identification of Rickettsia spp. in Real-Time PCR positive samples. A total of 185 ticks were examined and belonged to the genus Hyaloma and Rhipicephallus. Ticks with most frequencies included Rhipicephallus sanguineous (30.9%). In total, six samples (3.24%) were positive for Rickettsia spp. using the Real-Time PCR. According to the results of sequencing and phylogeny, samples were closely related to R. rhipicephali (2 samples) and R. massiliae (four samples). These results are important in the detection and epidemiology of Rickettsia spp. in Iran and indicate the necessity of detection and prevention approaches for rickettsiosis.

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.

Rickettsiosis with Pleural Effusion: A Systematic Review with a Focus on Rickettsiosis in Italy.

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.

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.

A severe case of Israeli spotted fever with pleural effusion in Italy.

BACKGROUND: The most common Italian rickettsiosis is Mediterranean Spotted Fever (MSF). MSF is commonly associated with a symptom triad consisting of fever, cutaneous rash, and inoculation eschar. The rash is usually maculopapular but, especially in severe presentations, may be petechial. Other typical findings are arthromyalgia and headache. Herein, we describe for the first time an unusual case of Israeli spotted fever (ISF) associated with interstitial pneumonia and pleural effusion in which R. conorii subsp. israelensis was identified by molecular methods in the blood, as well as in the pleural fluid. CASE PRESENTATION: A 72-year-old male presented with a 10-day history of remittent fever. On admission, the patient's general condition appeared poor with confusion and drowsiness; the first assessment revealed a temperature of 38.7°, blood pressure of 110/70 mmHg, a blood oxygen saturation level of 80% with rapid, frequent, and superficial breathing using accessory muscles (28 breaths per minute), and an arrhythmia with a heart rate of 90 beats per minute. qSOFA score was 3/3. Chest CT revealed ground-glass pneumonia with massive pleural effusion. Petechial exanthema was present diffusely, including on the palms and soles, and a very little eschar surrounded by a violaceous halo was noted on the dorsum of the right foot. Awaiting the results of blood cultures, broad-spectrum antibiotic therapy with meropenem 1 g q8h, ciprofloxacin 400 mg q12h, and doxycycline 100 mg q12h was initiated. Doxycycline was included in the therapy because of the presence of petechial rash and fever, making us consider a diagnosis of rickettsiosis. This suspicion was confirmed by the positivity of polymerase chain reaction on whole blood for R. conorii subsp. israelensis. Thoracentesis was performed to improve alveolar ventilation. R. conorii subsp. israelensis was again identified in the pleural fluid by PCR technique. On day 4 the clinical condition worsened. Blood exams showed values suggestive of secondary hemophagocytic lymphohistiocytosis; 4 out of 8 diagnostic criteria were present and empirical treatment with prednisone was started resulting in a gradual improvement in general condition. CONCLUSIONS: Israeli spotted fever 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.