There is no updated information on the spread of Rickettsiales in Italy. The purpose of our study is to take stock of the situation on Rickettsiales in Italy by focusing attention on the species identified by molecular methods in humans, in bloodsucking arthropods that could potentially attack humans, and in animals, possible hosts of these Rickettsiales. A computerized search without language restriction was conducted using PubMed updated as of December 31, 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Overall, 36 species of microorganisms belonging to Rickettsiales were found. The only species identified in human tissues were Anaplasma phagocytophilum,Rickettsia conorii, R. conorii subsp. israelensis, R. monacensis, R. massiliae, and R. slovaca. Microorganisms transmissible by bloodsucking arthropods could cause humans pathologies not yet well characterized. It should become routine to study the pathogens present in ticks that have bitten a man and at the same time that molecular studies for the search for Rickettsiales can be performed routinely in people who have suffered bites from bloodsucking arthropods.

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.

Background: In the currently ongoing coronavirus pandemic, coinfections with unrelated life-threatening febrile conditions may pose a particular challenge to clinicians. Leishmaniasis is a zoonosis that may present general symptoms, including fever, malaise, and arthralgia, rendering it indistinguishable from COVID-19. Methods: In this paper, we aim to draw attention to this issue and analyze the clinical characteristics of the coinfection SARS-CoV-2/Leishmania through a systematic review of the literature. We were motivated by the observation of the first case of visceral leishmaniasis and COVID-19 in a paediatric patient. Conclusion: Our case is a reminder for healthcare providers to consider the diagnosis of visceral leishmaniasis in patients presenting with febrile syndrome in endemic regions during the COVID-19 pandemic.

Background The availability of molecular techniques has significantly increased our understanding of bacteria of the order Rickettsiales, allowing the identification of distinct species in both vector and host arthropods. However, the literature lacks studies that comprehensively summarize the vast amount of knowledge generated on this topic in recent years. The purpose of this study was to conduct a comprehensive analysis of the distribution of Rickettsiales in arthropod vectors, animals and humans in the WHO European Region in order to provide useful information to predict the emergence of certain diseases in specific geographical areas and to formulate hypotheses regarding the possible pathogenetic role of some rickettsial species in the etiology of human pathological conditions. Methods A systematic review of the literature in the PubMed and EMBASE databases was conducted following the PRISMA methodology using the search terms “Spotted fever” OR “rickettsiosis” OR “ricketts*” AND all the countries of the WHO European Region, from 1 January 2013 to 12 February 2022. Only studies that identified rickettsiae in human, animal or arthropod samples using molecular techniques were included in the review. Results A total of 467 articles considering 61 different species of Rickettsiales with confirmed or suspected human pathogenicity were analyzed in the review. More than 566 identifications of Rickettsiales DNA in human samples were described, of which 89 cases were assessed as importation cases. A total of 55 species of ticks, 17 species of fleas, 10 species of mite and four species of lice were found infected. Twenty-three species of Rickettsiales were detected in wild and domestic animal samples. Conclusion The routine use of molecular methods to search for Rickettsiales DNA in questing ticks and other blood-sucking arthropods that commonly bite humans should be encouraged. Molecular methods specific for Rickettsiales should be used routinely in the diagnostics of fever of unknown origin and in all cases of human diseases secondary to an arthropod bite or animal contact. Graphical Abstract

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