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

Epidemiological Community and Differences of Transmissive Infections in Astrakhan Region

Relevance. The territory of the Astrakhan region hosts natural foci of severe infections of arbovirus etiology – Crimean-Congo hemorrhagic fever (CCHF) and Astrakhan fever (spotted fever resembling the Mediterranean spotted fever, Astrakhan spotted fever (ASF). The long-term average incidence of CCHF and ASF in the Astrakhan region is to 11 and 135 times higher, respectively, than the average incidence in the Russian Federation. Aims. To present, based on epidemiological data, a comparative characterization of transmissible infections of CCHF and ASF in the Astrakhan region. Materials & Methods. The main method of the study was epidemiological. The data for 2000−2016 of primary medical documentation Ф.058/у «Emergency notification of infectious disease, food, acute occupational poisoning, unusual reaction to vaccination», federal statistical observation Ф. 2 «Information on infectious and parasitic diseases», Ф. 357/у «Epidemiological examination card of infectious disease focus», Ф. .003/у «Medical card of inpatient patient», presented by Center of hygiene and epidemiology in Astrakhan region. For retrospective epidemiological analysis, we studied the absolute and intensive morbidity indicators (per 100 ths population), by age, professional groups, and among the urban and rural population. Based on the average long-term morbidity indicators of the population, a mapping of the territory of the Astrakhan region was carried out. The influence of natural and climatic conditions on the epidemic process of CCHF and ASF was assessed by meteorological data (amount of precipitation, air temperature, etc.). Materials of long-term observation over 11 districts of Astrakhan region and Astrakhan city were analyzed, including data on the spread of Ixodid ticks, population contact with them (according to the attendance of people to treatment-and-prophylactic organizations of the region). Statistical data processing was carried out using the method of straight-line alignment of dynamic series of morbidity indicators, calculation of the average annual rate of decrease/increase. Correlation analysis was used to assess the direction and strength of the relationship between the indicators, and quantitative dependence between epidemic process characteristics. Differences between the indicators were considered to be reliable if p < 0.05. Results. During the analyzed period 151 cases of CCHF and 3951 cases of ASF were identified. By 2016. CCHF was registered in all 11 districts of the region and the area of foci covered 44,000 km2 and 44,100 km2, respectively. There are no differences significantly affecting the epidemic process of CCHF and ASF, so preventive measures are mainly aimed at controlling the vectors of the pathogens of these infections. The comprehensive study of the territory of Astrakhan region carried out in 2000–2016 revealed expansion of CCHF and ASF areal of disease (by 11.8% and 23.4% respectively) and determined the territories with the highest risk of infection, which allowed to increase and redistribute the volumes of acaricide treatments of the territories with the highest infection risk and ensure the decrease of CCHF and ASF morbidity rates. Conclusion. As a result of the comprehensive study conducted in 2000–2016 in the territory of Astrakhan region, the expansion of CCHF and ASF areal of disease was revealed (by 11.8% and 23.4% respectively) and the areas of highest infection risk were identified, which allowed to increase and redistribute the volume of acaricide treatments of the areas of highest infection risk and ensure the reduction of CCHF and ASF morbidity.

The Retropepsin-Type Protease APRc as a Novel Ig-Binding Protein and Moonlighting Immune Evasion Factor of Rickettsia

Many Rickettsia organisms are pathogenic to humans, causing severe infections, like Rocky Mountain spotted fever and Mediterranean spotted fever. However, immune evasion mechanisms and pathogenicity determinants in rickettsiae are far from being resolved.

Mediterranean Spotted Fever: Current Knowledge and Recent Advances

Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar (“tache noire”). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF.

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.

Renal involvement in Mediterranean spotted fever – clinical and histopathological data

Background: 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 non-endemic countries and regions. Objective: 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: 350 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 two 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% and 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 more than two times less in survivors. The postmortem performed 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.

Mediterranean spotted fever associated with leucocytoclastic vasculitis and acute pancraeatitis

A young healthy gardener became febrile with abdominal pain, nausea, vomiting and diarrhoea followed by palpable purpura, mostly on the legs and buttocks with associated arthralgia. Dehydration, azotemia and hyponatraemia resolved with fluid replacement. Tests demonstrated acute pancreatitis, hepatitis, thrombocytopenia, microscopic haematuria and proteinuria. He improved with doxycycline, but bipedal pitting oedema and punctate rash involving the soles/hands appeared. Microbiological tests revealed positive IgM and IgG serology for rickettsiae spotted fever. Skin biopsy of the purpura confirmed leucocytoclastic vasculitis, positive for Rickettsiae conorii by PCR amplification. Palpable purpura is a rare important manifestation of Mediterranean spotted fever (MSF), due to either secondary leucocytoclastic vasculitis or associated Henoch-Schonlein purpura (HSP), which best explains the distribution of the rash, arthralgia, gastrointestinal symptoms, and microhaematuria not usually seen in R. conorii infections. Likewise, the patient’s acute pancreatitis may be interpreted as a rare presentation of HSP or a seldom-encountered feature of MSF.