Cases Of Mediterranean Spotted Fever Research Articles

Metagenomic next generation sequencing of plasma RNA for diagnosis of unexplained, acute febrile illness in Uganda

Metagenomic next generation metagenomic sequencing (mNGS) has proven to be a useful tool in the diagnosis and identification of novel human pathogens and pathogens not identified on routine clinical microbiologic tests. In this study, we applied mNGS to characterize plasma RNA isolated from 42 study participants with unexplained acute febrile illness (AFI) admitted to tertiary referral hospitals in Mubende and Arua, Uganda. Study participants were selected based on clinical criteria suggestive of viral infection (i.e., thrombocytopenia, leukopenia). The study population had a median age of 28 years (IQR:24 to 38.5) and median platelet count of 114 x103 cells/mm3 (IQR:66,500 to 189,800). An average of 25 million 100 bp reads were generated per sample. We identified strong signals from diverse virus, bacteria, fungi, or parasites in 10 (23.8%) of the study participants. These included well recognized pathogens like Helicobacter pylori, human herpes virus-8, Plasmodium falciparum, Neisseria gonorrhoeae, and Rickettsia conorii. We further confirmed Rickettsia conorii infection, the cause of Mediterranean Spotted Fever (MSF), using PCR assays and Sanger sequencing. mNGS was a useful addition for detection of otherwise undetected pathogens and well-recognized non-pathogens. This is the first report to describe the molecular confirmation of a hospitalized case of MSF in sub-Saharan Africa (SSA). Further studies are needed to determine the utility of mNGS for disease surveillance in similar settings.

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.

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.

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.

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Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by Rickettsia conorii. This is transmitted to humans by the brown dogtick Rhipicephalus sanguineus. Although therapy is easy and unexpensive, the different clinical presentation, the lack tick bite in the history or the frequent absence of skin manifestations, often make diagnosis difficult. We here reported four clinical cases of MSF, occurred in a region of central Italy (Abruzzo) with different clinical characteristics, but common epidemiological and anamnestic characteristics.

Cases of Mediterranean spotted fever in southeast of Iran

In this study the clinical manifestations, laboratory findings, and management of five patients diagnosed with Mediterranean spotted fever (MSF) from southeast of Iran are presented. All patients but one had recent tick-bite histories which were noticeable as black eschars (tache noire). Patients' samples were tested by real-time PCR and serology (IFA). The disease was confirmed by fourfold rising of IgG antibodies against Rickettsia conorii. This is the first report of MSF cases in Iran.

Severe clinical forms of Mediterranean spotted fever: A case series from an endemic area in Bulgaria

Background/Aim. Mediterranean spotted fever (MSF) belongs to Rickettsioses, the Spotted fever group (SFG). The causal agent is Rickettsia conorii conorii and the transmission to humans occurs through dog tick Rhipicephalus sanguineus bites. The aim of this study was to describe clinical and laboratory characteristics in patients with severe form of Mediterranean spotted fever admitted to Bulgarian university hospital in endemic region. Methods. A retrospective study was conducted at Stara Zagora University Hospital (Southeastern Bulgaria) between April 2015 and August 2016. During the analyzed period, 58 cases had clinical and laboratory data for MSF. Serological tests were applied for the etiological diagnosis. MSF-specific immunoglobulin (IgM) and IgG antibodies were detected in serum by indirect immunoenzyme assay (ELISA IgG/IgM, Vircell, Spain) ? R. conorii ELISA IgG sensitivity 85%, specificity 100% and R. conorii ELISA IgM sensitivity 94%, specificity 95%. Statistical analysis was made by MS Excel 2007 and SPSS Statistics, version 19.0. Results. Eighteen patients presented as severe forms. The predominant gender of them were males (78%) and 22% were females. The median age of the analyzed group was 55 years (range: 14? 78 years). Ten patients developed hepatic disorder while 4 had neurological signs. Laboratory data showed thrombocytopenia in 15 patients, mean value of platelet (PLT) count for the whole group was 108.6 ? 53.8 ? 109/L. Liver enzymes were elevated with mean value of aspartate aminotransferase (AST) 161.4 ? 90.1 IU/L and alanine aminotransferase (ALT) 163.9 ? 81.5 IU/L. Acute phase reactant as C-reactive protein (CRP) had mean value of 140.3 mg/L (range: 9?230 mg/L). Kidney function was impaired in some cases; the mean value of creatinine for the studied group was 134.7 ?mol/L (range: 78?313 ?mol/L) and mean value of urea was 9.6 mmol/L (range: 4.2?27.4 mmol/L). Conclusion. Bulgaria is an endemic area for tick-borne diseases. Cases of MSF are reported annually. Severe forms of MSF are not rare. Typical clinical and laboratory markers for severity should be actively searched for. Early diagnosis and proper treatment is the key to avoid complications and enable patient recovery.

Rickettsiae and rickettsial diseases in Croatia: Implications for travel medicine.

To review the current state of knowledge concerning rickettsiae and rickettsioses in Croatia and to discuss their implications for travellers. The PubMed database was searched from 1991 to 2015 by combining the words "rickettsia," "rickettsiosis", "travellers" and "Croatia". Since 1969, Croatia appears to be free of epidemic typhus (ET) caused by Rickettsia prowazekii and the last case of Brill-Zinsser disease was recorded in 2008. Mediterranean spotted fever (MSF) caused by Rickettsia conorii is the most frequent human rickettsial infection in Croatia, followed by murine typhus caused by Rickettsia typhi. Human cases of MSF and murine typhus have been predominantly observed along the eastern Adriatic coast from Zadar to Dubrovnik and between Zadar and Split, respectively. Rickettsia akari, etiologic agent of rickettsialpox, was isolated from blood of a patient diagnosed with MSF in Zadar, but no cases of rickettsialpox were reported. Several species of pathogenic (Rickettsia slovaca, Rickettsia aeschlimannii, Ricketsia helvetica, and Ricketsia raoultii) and species of undetermined pathogenicity (Ricketsia hoogstraalii sp. nov.) rickettsiae were identified in ticks collected in different ecological regions of Croatia. A search of the literature revealed no evidence of rickettsial infection in travellers visiting Croatia. Three imported cases of Rickettsia africae were observed in travellers returning from South Africa. Rickettsiae and rickettsial diseases continue to be present in Croatia. As they can be acquired while travelling, physicians should consider rickettsial infection in the differential diagnosis of patients returning from Croatia and presenting with febrile illness.

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

The 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.

The role of cats in the eco-epidemiology of spotted fever group diseases.

BackgroundMediterranean Spotted Fever (MSF), whose etiological agent is R. conorii, is one of the oldest described vector-borne infectious diseases. Although it is endemic in the Mediterranean area, clinical cases have also been reported in other regions. R. massiliae-Bar29 is related to MSF cases. This strain is distributed worldwide. R. conorii and R. massiliae-Bar29 are transmitted by ticks. Dogs are considered the sentinel of R. conorii infection. Cats could also be involved in their transmission. Rickettsia felis, etiological agent of Flea-borne spotted fever, is mainly transmitted by the cat flea, Ctenocephalides felis. Up to now, the role of cats in its transmission is not entirely elucidated. The aim of the study is to analyze the infection in cats by these microorganisms.MethodsThe study was undertaken in Northeastern Spain. Twenty municipalities of seven regions participated in the study. 212 cats (pets and stray cats) were analyzed. Variables surveyed were: date of collection, age, sex, municipality, source, living place, outdoor activities, health status, type of disease, contact with other animals, and ectoparasite infestation. Sera were evaluated by indirect immunofluorescence antibody assay (IFA). Molecular detection (real-time PCR and sequencing) and cultures were performed on blood samples.ResultsThere were 59 (27.8%) cats seroreactive to one or more microorganisms. Considering cross-reactions, the seroprevalences were 15.6%-19.5% (R. massiliae-Bar29), 1.9%-6.2% (R. conorii), and 5.2%-7.5% (R. felis). A weak association was observed between SFG seropositivity and tick infestation. Ticks found on seropositive cats were Rhipicephalus pusillus, R. sanguineus and R. turanicus. DNA of Rickettsia was detected in 23 cats. 21 of them could be sequenced. Sequences obtained were identical to those sequences of SFG rickettsiae similar to R. conorii and R. massiliae. No amplification of R. felis was obtained.ConclusionsCats can be infected by SFG rickettsiae and produce antibodies against them. Cats may play a role in the transmission cycle of R. conorii and R. massiliae-Bar29, although the role in the R. felis cycle needs further analysis.

Some epidemiological features of the mediterranean spotted fever re-emerging in Bulgaria

The Mediterranean spotted fever (MSF), caused by Rickettsia conorii conorii strain Malish, is transmitted by the brown dog tick Rhipicephalus sanguineus. In Bulgaria, cases of MSF occurred in two epidemic waves, the first in 1948-1970, (after there were no report of new cases more than for 20 years) and the second started in 1993 and is still going on. The AIM of the study was to investigate the epidemiological characteristics of the re-emerging MSF in Plovdiv city and its suburbs, which is the largest endemic region in the country. The MSF patients treated between 1993 and 2011 were 1254. MSF was confirmed by immunofluorescent assay (IFA) in the Reference Rickettsioses Laboratory. Descriptive and analytic epidemiological methods were used to determine the routes and ways of infection, the epidemiological locus, seasonality, patients' age, gender and social structure, and the clinical severity of the cases. We established that MSF spread in the region in two distinct phases: from 1993 to 2003 during which the disease was increasingly spreading and the second phase taking place from 2004 till 2011 during which the disease was gradually decreasing. The incidence is between 0.13 and 25.62, mean 10.91 per 100 000 populations (11.88 and 9.56 per 100 000 populations for phases I and II, respectively); between 1.14% and 6.25% of the infected people died (mean 2.07%, 3.46% and 1.25% for phases I and II, respectively). The age distribution of patients shows predominance of 40-59-year-olds (31.66%), reaching a peak in patients older than 60 years (37.5%). Children and adolescents under 19 years are less affected (18.12%), while the least affected are the young adults between 20-39 (12.7%). Urban population is almost twice as affected as rural population regardless of the gender. The disease has summer seasonality, peaking in August. Eschar (tache noire) was found in 77.91% of the patients. Despite the decline and predominance of mild forms (43.12%), the re-emerging MSF still presents with lots of severe forms (11.45%) and malignant forms (8.54%), which makes almost one fifth of all patients to be at serious risk of getting ill with a severe disease with complications and possible fatal outcome. Almost two decades after it re-emerged in Bulgaria, MSF is still potentially active despite the decreasing incidence and mortality rate. During the phase of decline, the re-emerging MSF kept the basic epidemiologic characteristics it had in the first phase of rapid increase. The epidemiologic characteristics of MSF in the region are in support of its prevention and control.

Influence of temperature on the attachment of Rhipicephalus sanguineus ticks on rabbits

The impact of climate on the vector’s behaviour of the worldwide brown dog tick, Rhipicephalus sanguineus, is a cause of concern. This tick has become the most widespread tick throughout the world due to its specialised feeding on domestic dogs. In addition to the dog’s pathogens, Babesia canis and Ehrlichia canis, Rh. sanguineus is known to transmit two life-threatening rickettsial diseases to humans, Mediterranean spotted fever (MSF) caused by Rickettsia conorii in the old world, and Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii in America [1]. Rh. sanguineus also transmits Rickettsia massiliae, a worldwide emerging pathogen with a single documented case of infection [2]. Rh. sanguineus lives in peridomestic environments shared with dogs but is known to have a low affinity for humans, particularly in temperate countries. Hosts other than dogs are usually only infested when dogs are present to maintain a tick population. However, in 2003, 22 Rh. sanguineus were found attached to an alcoholic homeless person who died of MSF in Marseille. This heavy infestation was associated with the highest summer temperatures noted in France during the past 50 years [1]. Also, the cases of MSF recognised in Oran, Algeria, in 1993 peaked in 2005 together with the hottest summer of the past decades [3]. More recently, maximum temperature levels during the previous summer were associated with increases in MSF incidence in Sardinia [4]. In this work we have tested the influence of increased temperatures on the attachment of Rh. sanguineus larvae, nymphs and adult ticks on a rabbit, an unusual host.

Spotted fever group rickettsioses documented in Morocco

Mediterranean spotted fever (MSF) is caused by Rickettsia conorii conorii transmitted by the brown dog tick Rhipicephalus sanguineus. It is endemic in the Mediterranean area, where most of the cases are encountered during the summer, when the tick vectors are highly active [1]. In Morocco, MSF has been the sole human tick-borne rickettsiosis known by clinicians, and cases that are clinically recognized are rarely documented [2]. Our aim is to describe the clinical and epidemiological characteristics of confirmed cases of MSF in Casablanca and in the surrounding regions of Morocco.

Mediterranean spotted fever in Algerian children

Mediterranean spotted fever (MSF) is a potentially life-threatening zoonosis caused by Rickettsia conorii and transmitted by the brown dog tick Rhipicephalus sanguineus [1]. Although MSF is one of the oldest recognised rickettsioses, there have been few reports about this rickettsiosis in North Africa [1,2]. The present work on MSF cases occurring in children is a subset of a larger study conducted within all age categories.

Splenic Rupture and Malignant Mediterranean Spotted Fever

Splenic Rupture and Malignant Mediterranean Spotted Fever

Early diagnosis of severe Mediterranean spotted fever cases by nested-PCR detecting spotted fever Rickettsiae 17-kD common antigen gene

We describe 3 cases of Mediterranean spotted fever (MSF) who presented with severe sepsis, in 2 of which the clinical diagnosis was unclear at presentation. In each case the diagnosis of MSF was made using a nested-PCR assay for Rickettsia conorii 17-kD protein gene. The nested-PCR based diagnosis preceded the serological results of MSF that were all negative at admission. The early diagnosis of MSF by specific PCR will facilitate an early institution of appropriate therapy, saving unnecessary tests and medications.

Epidemiologic features of Mediterranean spotted fever in Portugal

Mediterranean spotted fever (MSF) is a tick-borne rickettsial disease. It is endemic in Portugal and Ricardo Jorge recognized it in 1930. Rhipicephalus sanguineus is the main vector and reservoir of the disease. In Portugal the etiologic agents are two strains of Rickettsia conorii complex: R. conorii Malish and "Israeli tick typhus". MSF is clinically characterized by a vasculitis process with the classical clinical triad of fever, rash, and lesion at the site of tick bite. Although the majority MSF cases are considered benign, last years some districts presented more severe cases than expected. The reported incidence of MSF in Portugal for 1989 to 2000 was 9.8/10(5) inhabitants, the highest incidence compared to other mediterranean countries. Alentejo was the region who presents the highest incidence with 31/10(5) inhabitants. Nevertheless, Bragança was the district which appears with greater number of cases, 62/10(5) inhabitants. The highest annual incidence rate reported was among children, peaking in those 1-4 years of age with 60.2/10(5) inhabitants. Observation of mortality rates have shown that Beja district have the highest mortality rates for MSF in Portugal, but in 1997 in this district, mortality have unexpected values with 7.6 deaths per 100,000 inhabitants have occurred. Although is an obligatory notifiable disease, high number of underreported cases are detected.

Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105 hospitalized patients.

Mediterranean spotted fever (MSF) is the most important tick-borne disease in Portugal. It is a notifiable disease and during 1989-2000 the annual incidence rate in Portugal was 9.8/10(5) inhabitants. Although recognized as a benign acute disease and treated mainly with ambulatory procedures, some cases are severe and fatalities have increased in the last few years. In 1997, MSF mortality became more evident in Beja, a Portuguese southern district, with a case fatality rate of 32.3% in hospitalized patients. Analysis of 55 variables regarding epidemiologic, clinical, laboratory, and therapeutic data of fatal and nonfatal MSF cases were compared to identify risk factors in 105 patients hospitalized in Beja District Hospital, between 1994 and 1998. It was statistically significant that the patients dying in 1997 were younger than those in other years. The risk of dying is statistically significant in those who presented with diabetes, vomiting, dehydration, and uremia. The interval between the onset of symptoms to administration of anti-rickettsial therapy was the same for all patients. Therapy delay, reported by some authors to be associated with mortality of MSF, was not a risk factor in our study. The patients who died in 1997 died faster than those in other years. The variables studied could not explain the higher mortality rates observed in our study. Although one may speculate that the pathogenic strain of Israeli tick typhus, isolated in 1997, could be responsible for this increase of fatality rate, inherited patient factors might also be strongly associated with mortality.

Demographic and Epidemiologic Features of Mediterranean Spotted Fever Cases in the Region of Split, Croatia

Demographic and Epidemiologic Features of Mediterranean Spotted Fever Cases in the Region of Split, Croatia

Associations between dogs that were serologically positive for Rickettsia conorii relative to the residences of two human cases of Mediterranean spotted fever in Piemonte (Italy)

A geographic information system and K-function analysis were used to evaluate the spatial association of canine serological results for Rickettsia conorii, the causative agent of Mediterranean spotted fever (MSF), and clinical cases of MSF in humans in Piemonte, northwest Italy. The residences of dog owners were clustered in two rural villages in the province of Cuneo, where two human cases of MSF occurred in 1997 and 1998. Eighteen out of 116 dogs examined were positive by indirect immunofluorescent assay (IFA+, titre≥1:160) for MSF. K-functions were compared for IFA+ dogs and for all dogs sampled. Monte Carlo and bootstrap simulations demonstrated that clustering of IFA+ dogs was significantly greater than clustering of all dogs, at distances of less than 0.6 km from human cases of MSF. Logistic regression analysis indicated that the risk of being IFA+ was highest for dogs residing within the first quartile of distance (0.7 km) from human cases of the disease, and for dogs that were not confined. However, year and season of blood collection were not associated with IFA status. It was concluded that a relatively high dog population density along with a rural or semi-rural environment favours the occurrence of emergent foci of MSF in the province of Cuneo.