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

Prevalence of Ticks Infesting Dairy Cattle and the Pathogens They Harbour in Smallholder Farms in Peri-Urban Areas of Nairobi, Kenya

This study aimed at determining the tick species infesting dairy cattle in Nairobi, Kenya, and the pathogens they harbour. While ticks are well-known vectors of major bacterial pathogens of both veterinary importance and public health importance, few studies have investigated the range of the tick species and the associated pathogens, especially present in unique dairy production systems, which compromise animal welfare, such as those in peri-urban areas. A cross-sectional study was undertaken involving 314 randomly selected dairy cattle in 109 smallholder farms. Each animal was examined for attached ticks followed by morphological tick identification at the species level. Genomic DNA was extracted from each of the ticks, and 16S rDNA gene was amplified for pathogen identification. Sequencing of the amplicons and subsequent BLASTn analysis, multiple sequence alignment, and phylogenetic reconstruction were performed to confirm the species of the pathogens. Sixty-six (21.0%) of the cattle examined had ticks. A total of 94 adult ticks were found on the cattle, and of these, 63 (67.0%), 18 (19.1%), and 13 (13.8%) were in the genera Rhipicephalus, Amblyomma, and Hyalomma, respectively. Twelve tick species in Rhipicephalus genus and two in Amblyomma and Hyalomma genera were identified. Although Rh. decoloratus was the most prevalent tick (24.5% (23/94)), the emerging Rh. microplus (6.4% (6/94)) was also identified. The DNA of Rickettsia was detected in the ticks, with Rickettsia conorii in H. rufipes and A. variegatum, and Rickettsia aeschlimannii in Rh. microplus and H. rufipes, while Ehrlichia ruminantium and E. canis were in A. variegatum. In conclusion, the study reported a wide range of tick species present in the study area including Rhipicephalus microplus, which is an emerging tick species in parts of Kenya. The ticks harboured DNA of Rickettsia and Ehrlichia, highlighting possible animal and human health concerns. Hence, effective tick control strategies remain paramount to prevent potential diseases associated with the harboured pathogens.

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.

Simultaneous Exposure to Angiostrongylus vasorum and Vector-Borne Pathogens in Dogs from Italy

Several drivers have recently fostered the expansion of Angiostrongylus vasorum throughout Europe, where Vector-Borne Pathogens (VBPs) are also spreading. However, the level of simultaneous risk of infection is still unknown in canine populations. This study evaluated the simultaneous exposure to A. vasorum and major canine VBPs in dogs of Italy. Sera of 294 dogs were subjected to two ELISAs, detecting A. vasorum circulating antigens and antibodies against the parasite, and to the following assays: (i) SNAP® 4DX (IDEXX Laboratories Inc.) detecting Dirofilaria immitis antigens, and antibodies vs. Borrelia burgdorferi, Anaplasma spp. and Ehrlichia spp. and (ii) IFAT for the detection of antibodies vs. Leishmania infantum, Babesia canis and Rickettsia conorii. Twenty-two (7.5%, CI: 4.8–11.1%) and six (2%, CI: 0.7–4.4%) dogs scored positive for circulating A. vasorum antibodies and antigens, respectively. Seventeen dogs (5.8%, CI: 3.4–9.1%) were positive for A. vasorum antibodies + at least one VBP, three (1%, CI: 0.2–3%) for A. vasorum antigen + at least one VBP, while one dog (0.3%, CI: 0.01–1.88%) was positive for A. vasorum antigen + A. vasorum antibodies + B. canis antibodies. These results show that dogs living in different regions of Italy are at risk of simultaneous infections with both A. vasorum and VBPs. Despite the same scenario being likely in other countries of Europe, the current knowledge is scant. Therefore, further studies are warranted to amplify current epizootiological information and to understand whether control programs should be improved.

Preliminary Evidence of Rickettsia slovaca and Rickettsia conorii Infection in the Sera of Sheep, Dogs and Deer from an Area of Northern Spain

Limited information is available on the presence of rickettsial infection in animal reservoirs in Spain. Antibodies against Rickettsia slovaca and Rickettsia conorii were therefore sought in the sera of farm, domestic and wild animals (n = 223 samples) in an area of northern Spain. Indirect immunofluorescence assays showed: (A) 17/120 and 16/120 (14.2% and 13.3%) of serum samples from sheep (farm animals) reacted with R. slovaca and R. conorii antigens, respectively; (B) 10/73 and 10/73 (13.7% and 13.7%) of samples from dogs (domestic animals) did the same; (C) as did 22/30 and 20/30 (73.3% and 66.6%) of samples from deer (wild animals) (overall titre range: 1/40 to 1/1280). The prevalence of both types of infection was significantly greater in the wild animals than either the farm or domestic animals. The largest titres were recorded for R. slovaca in all three groups.

Serological Survey on the Occurrence of Rickettsia spp., Neospora caninum, Bartonella henselae and Toxoplasma gondii in Cats from Tuscany (Central Italy)

Asymptomatic cats often harbor pathogens, some of which have not been largely investigated in feline populations. The aim of this study was to evaluate the occurrence of antibodies against Rickettsia conorii, Rickettsia felis, Rickettsia typhi, Neospora caninum, Bartonella henselae and Toxoplasma gondii in cats from Tuscany. Ninety-five blood serum samples, previously collected, were analyzed by indirect immunofluorescence assay. Fifty-six (58.94%) cats had antibodies to at least one investigated pathogen: 28 (29.47%) cats were positive for B. henselae, 17 (17.89%) for R. felis, 14 (14.73%) for R. conorii, 14 (14.73%) for T. gondii, 2 (2.1%) for N. caninum. No cats were positive for R. typhi. Positive reactions to two or more pathogens were detected in 18 (18.94%) cats. The occurrence of antibodies against these microorganisms suggests that cats, even though asymptomatic, may be infected by pathogens, often zoonotic, and thus may be a source of infections for other animals and humans.

Seropositivity to canine tick-borne pathogens in a population of sick dogs in Italy

Background Canine vector-borne diseases (CVBDs) associated to ticks are among the most important health issues affecting dogs. In Italy, Ehrlichia canis, Anaplasma spp., Rickettsia conorii and Borrelia burgdorferi (s.l.) have been studied in both healthy canine populations and those clinically ill with suspected CVBDs. However, little information is currently available on the overall prevalence and distribution of these pathogens in the country. The aim of this study was to assess the prevalence and distribution of tick-borne pathogens (TBPs) in clinically suspect dogs from three Italian macro areas during a 15-year period (2006–2020). Methods A large dataset (n = 21,992) of serological test results for selected TBPs in three macro areas in Italy was analysed using a Chi-square test to evaluate the associations between the categorical factors (i.e. macro area, region, year, sex and age) and a standard logistic regression model (significance set at P = 0.05). Serological data were presented as annual and cumulative prevalence, and distribution maps of cumulative positive cases for TBPs were generated. Results Of the tested serum samples, 86.9% originated from northern (43.9%) and central (43%) Italy. The majority of the tests was requested for the diagnosis of E. canis (47%; n = 10,334), followed by Rickettsia spp. (35.1%; n = 7725), B. burgdorferi (s.l.) (11.6%; n = 2560) and Anaplasma spp. (6.2%; n = 1373). The highest serological exposure was recorded for B. burgdorferi (s.l.) (83.5%), followed by Rickettsia spp. (64.9%), Anaplasma spp. (39.8%) and E. canis (28.7%). The highest number of cumulative cases of Borrelia burgdorferi (s.l.) was recorded in samples from Tuscany, central Italy. Rickettsia spp. was more prevalent in the south and on the islands, particularly in dogs on Sicily older than 6 years, whereas Anaplasma spp. was more prevalent in the north and E. canis more prevalent in the south and on the islands. Conclusions The results of this study highlight the high seroprevalence and wide distribution of the four TBPs in dogs with clinically suspected CVBDs from the studied regions of Italy. The very high seroprevalence of B. burgdorferi (s.l.) exemplifies a limitation of this study, given the use of clinically suspect dogs and the possibility of cross-reactions when using serological tests. The present research provides updated and illustrative information on the seroprevalence and distribution of four key TBPs, and advocates for integrative control strategies for their prevention. Grapic abstract