Characteristics of in vitro infection of human monocytes, by Rickettsia helvetica.

Eighteen species of rickettsiae are reported to cause infections in humans. One of these is Rickettsia helvetica, which is endemic in European and Asian countries and transmitted by the tick Ixodes ricinus. Besides fever, it has been demonstrated to cause meningitis and is also associated with perimyocarditis. One of the initial targets for rickettsiae after inoculation by ticks is the macrophage/monocyte. How rickettsiae remain in the macrophages/monocytes before establishing their infection in vascular endothelial cells remains poorly understood. The main aim of the present study was to investigate the impact on and survival of R. helvetica in a human leukemic monocytic cell line, THP-1. Our results show that R. helvetica survives and propagates in the THP-1 cells. The infection in monocytes was followed for seven days by qPCR and for 30 days by TEM, where invasion of the nucleus was also observed as well as double membrane vacuoles containing rickettsiae, a finding suggesting that R. helvetica might induce autophagy at the early stage of infection. Infected monocytes induced TNF-α which may be important in host defence against rickettsial infections and promote cell survival and inhibiting cell death by apoptosis. The present findings illustrate the importance of monocytes to the pathogenesis of rickettsial disease.

Probable African Tick Bite Fever in the United States.

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a previously healthy 60-year-old woman who developed an illness strongly suggestive of ATBF after a missionary trip to Zimbabwe and discuss the disease's diagnostic challenges. Our paper also reviews the epidemiology of this disease and the currently available diagnostic laboratory tests and recommended treatment options.

Intra-aural tick bite causing unilateral facial nerve palsy in 29 cases over 16 years in Kandy, Sri Lanka: is rickettsial aetiology possible?

BACKGROUND: Over the last two decades intra-aural tick infestation (otoacariasis) has been a common occurrence in the hilly central region in Sri Lanka. Very occasional detection of isolated unilateral facial nerve palsy associated with otoacariasis attributed to toxin damage of the nerve prompted us to study the clinico-epidemiology and aetio-pathology of the problem. METHODS: All cases having isolated unilateral facial nerve palsy associated with otoacariasis presented to, Ear Nose and Throat clinic at General Hospital Kandy, Sri Lanka from 2001 to 2016 were included in the study. The facial palsies were assessed with nerve conduction studies and, harvested ticks were identified. RESULTS: There were 29 patients with mean age of 46 years (range 22-76 years) with male to female ratio of 1:1.9. First 12 patients without specific treatment took 1-55 months for recovery and 4 had axonal degeneration. Last 5 patients were treated with doxycycline and recovered in 4 weeks. They had strong sero-conversion of immunofluorescence antibodies against spotted fever rickettsioses and the tick harvested from the last patient was PCR positive for rickettsial DNA. Identified ticks belonged to Dermacentor, Amblyomma, Rhipicephalus and Hyalomma species. CONCLUSIONS: On contrary to popular toxin theory, we were able to demonstrate treatable rickettsial aetio-pathology as the cause of otoacariasis associated lower motor facial palsy in Sri Lanka.

Acute Myopericarditis Associated with Tickborne Rickettsia sibirica mongolitimonae.

We report an unusual case of myopericarditis caused by Rickettsia sibirica mongolitimonae. Because of increasing reports of Rickettsia spp. as etiologic agents of acute myopericarditis and the ease and success with which it was treated in the patient reported here, rickettsial infection should be included in the differential diagnosis for myopericarditis.

A Case of Human Infection by Rickettsia slovaca in Greece.

Although tick-borne rickettsiosis is endemic in Greece, until recently, human samples arriving at the National Reference Centre under suspicion of rickettsial infection were routinely tested only for Rickettsia typhi and R. conorii. However, identification of additional rickettsia species in ticks prompted revision of the protocol in 2010. Until that year, all human samples received by the laboratory were tested for antibodies against R. conorii and R. typhi only. Now, tests for R. slovaca, R. felis, and R. mongolotimonae are all included in routine analysis. The current description of a human R. slovaca case is possible as a result of these changes in routine testing.

Possible Rickettsia massiliae Infection in Greece: an Imported Case.

Tick-borne rickettsioses are endemic in Greece; however, until recently, only Rickettsia typhi and R. conorii were tested routinely in human samples arriving at the National Reference Center. During the last few years, the identification of different rickettsia species in ticks led to the introduction of other spotted fever group rickettsiae in routine analysis. Under the new scheme, R. massiliae is now tested routinely in human samples; herein, we describe a human case of this infection.

A Case of Rickettsia felis Infection Imported From Nepal.

Rickettsia felis is an emerging spotted fever group pathogen that may be responsible for potentially life-threatening infections. A cosmopolitan distribution has been postulated though most human cases were observed in Africa and the Americas. We report an imported case from Nepal that occurred in an Italian tourist who presented with a 1-week history of fever, headache, nausea, vomiting, and a mild maculopapular rash 14 days after return.

Defending the fort: a role for defensin-2 in limiting Rickettsia montanensis infection of Dermacentor variabilis.

The importance of tick defensins is evidenced by their expression in a wide variety of tick tissues and prevalence across many tick genera. To date, the functional and biological significance of defensin-2 as a rickettsiastatic or rickettsiacidal antimicrobial peptide has not been addressed. In a previous study, defensin-2 transcription was shown to increase in Dermacentor variabilis ticks challenged with Rickettsia montanensis. In the present study, the hypothesis that defensin-2 is functional as a rickettsiastatic and/or rickettsiacidal antimicrobial peptide is tested. We show that defensin-2 plays a role in reducing burden after acquisition of Rickettsia montanensis through capillary feeding. Moreover, defensin-2 is shown to associate with R. montanensis in vitro and in vivo, causing cytoplasmic leakiness.

Rickettsial diseases.

Rickettsiae are a rather diverse collection of organisms with several differences; this prohibits their description as a single homogenous group. Rickettsiae are maintained in nature through a cycle involving reservoir in mammals and arthropod vectors. The public health impact of these on lives or productivity lost is largely unmeasured, but suspected to be quite high worldwide. The diseases caused by Rickettsia and Orientia species are often collectively referred to as rickettsioses. Coxiella burnetii, the agent of Q fever is still frequently categorized as rickettsial disease. New or emerging rickettsial diseases; tickborne lymphadenopathy (TIBOLA) and Dermacentor-borne-necrosis-eschar- lymphadenopathy (DEBONEL) related to Rickettsia slovaca infection have been described. The rickettsial diseases were believed to have disappeared from India are reemerging and recently their presence has been documented in at least eleven states of our country. Many cases of rickettsial diseases go undiagnosed due to lack of diagnostic tools. Greater clinical awareness, a higher index of suspicion, better use of available diagnostic tools would increase the frequency with which rickettsial diseases are diagnosed.

Evaluation of Rickettsia japonica pathogenesis and reservoir potential in dogs by experimental inoculation and epidemiologic survey.

Rickettsia japonica pathogenesis and reservoir potential in dogs were evaluated by both experimental inoculation and epidemiologic survey. In the experimental inoculation study, dogs 1 and 2 were pretreated with an immunosuppressive dose of cyclosporine 14 days before inoculation and became ill after exposure to R. japonica. Dogs exhibited clinical signs, including fever, anorexia, depression, and decreased water consumption, between 36 and 96 h after inoculation, but these signs disappeared spontaneously by 5 days after inoculation. Dogs 3 and 4 were not pretreated with cyclosporine, and no clinical signs were detected in them throughout the 14-day observation period. The control dog was clinically normal and had a normal rectal temperature throughout the study period. We attempted to detect rickettsial DNA from peripheral blood and aspiration samples from kidney and spleen by nested PCR, but all samples examined were negative. The control dog lacked detectable titers to R. japonica antigen on day 14, while positive antibodies to R. japonica were detected in all four experimentally infected dogs, with titers of 1:160 to 1:80. In the epidemiologic survey, 24 (1.8%) of the 1,363 dogs examined throughout Japan had antibodies against R. japonica, with titers of 1:40 or more. However, we observed neither clinical signs at the time of sample collection nor nested PCR results indicative of rickettsial infection in these dogs. In conclusion, dogs in Japan can be exposed to R. japonica, and infected dogs with immunosuppressive conditions can temporarily develop clinical symptoms, including fever, anorexia, depression, and decreased water consumption.

Advances in rickettsia pathogenicity.

One century after the first description of rickettsiae as human pathogens, the rickettsiosis remained poorly understood diseases. These microorganisms are indeed characterized by a strictly intracellular location which has, for long, prohibited their detailed study. Within the last ten years, the completion of the genome sequences of several strains allowed gaining a better knowledge about the molecular mechanisms involved in rickettsia pathogenicity. Here, we summarized available data concerning the critical steps of rickettsia-host cell interactions that should contribute to tissue injury and diseases, that is, adhesion, phagosomal escape, motility, and intracellular survival of the bacteria.

Characterization of rickettsial diseases in a hospital-based population in central Tunisia.

In Tunisia, 2 rickettsial groups, spotted fever group and typhus group, have been described since the beginning of the 20th century. Mediterranean spotted fever (MSF), also known as Boutonneuse fever, caused by Rickettsia conorii and transmitted by the dog tick Rhipicephalus sanguineus, is the most frequent rickettsial infection observed. Its seroprevalence in our region is 9% among blood donors and 23% in hospitalized febrile patients. Typhus group rickettsioses, caused by R. typhi and R. prowazekii, are less frequently reported than in the 1970s. Only sporadic cases of typhus were reported in the last decade. However, R. typhi antibodies were present in 3.6% among healthy people and 40% in patients with acute fever of undetermined origin. In the unit of Infectious Diseases at Farhat Hached University Hospital in Sousse, during 2007, 5% of hospitalized patients had eruptive fever, and half of the cases met clinical criteria of MSF and/or were confirmed by rickettsial serology. The majority of cases (90%) were noted in hot seasons, and contact with domestic animals was found in 76%. The most common symptoms were fever (present in all cases), skin rash (in 85% to 98% of cases), and headache (in 69.5% of cases). The clinical triad (fever + rash +"tache noire") was noted in 32 to 61%. Normal blood cells or leukopenia, cytolysis, and thrombopenia were the most frequent biological abnormalities. Complications and malignant forms of rickettsial infections were reported in 3.5 to 6% among hospitalized adult patients. When specific serology was performed, MSF was confirmed in 15%, and we noted an emergence of murine typhus (MT) mistaken for R. conorii or viral infection. Rickettsia felis was identified in 1 patient, whereas 17% of cases remained undetermined. Rickettsia conorii Malish was identified by PCR in skin biopsies. Doxycycline was the antibiotic of choice for rickettsial infections; it was prescribed in the majority of patients, associated with fever defervescence, in a mean of 72 hours. The mean length of stay among hospitalized patients with rickettsial infections was 5.9 days. In conclusion, in our region, MSF and murine typhus are endemic. Doxycycline should be prescribed in patients with acute fever and skin rash, especially in hot seasons. These rickettsioses were characterized by benign prognosis. More skin biopsies are needed to identify other SFG rickettsies.

Epidemiology and clinical aspects of rickettsioses in Thailand.

Scrub typhus and murine typhus are widespread in Thailand. Clinical manifestations of both diseases are nonspecific and vary widely. Acute undifferentiated fever (AUF), with or without organ dysfunction, is a major clinical presentation of these two diseases. The epidemiology and clinical manifestations including severe complications of scrub typhus and murine typhus in Thailand are summarized. Sixteen hundred and sixty-three patients with AUF were studied in six hospitals in Thailand between 2000 and 2003. Scrub typhus and murine typhus were diagnosed in 16.1% and 1.7% of them, respectively. Clinical spectrum of murine typhus was similar to scrub typhus. Hepatic dysfunction and pulmonary involvement were common complications. Multi-organ dysfunction mimicking sepsis syndrome occurred in 11.9% of patients with scrub typhus. The mortality of severe scrub typhus varied from 2.6% to 16.7%. Awareness that scrub typhus and murine typhus are prominent causes of AUF in adults in Thailand improves the probability of an accurate clinical diagnosis. Early recognition and appropriate treatment reduces morbidity and mortality. Results from recent clinical studies from Thailand indicated that rational antimicrobial therapy would be doxycycline in mild cases and a combination of either cefotaxime or ceftriaxone and doxycycline in severe cases. Azithromycin could be considered as an alternative treatment when doxycycline allergy is suspected. This would be either curative, or have no ill effect, in the majority of instances. Failure to improve or defervesce within 48 hours would indicate the need to perform a thorough re-evaluation of clinical findings and initial laboratory investigation results, as well as a need to change antibiotic.

Host-cell interactions with pathogenic Rickettsia species.

Pathogenic Rickettsia species are Gram-negative, obligate intracellular bacteria responsible for the spotted fever and typhus groups of diseases around the world. It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of the pathogen's affinity for endothelium lining the blood vessels, the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability, collectively termed 'Rickettsial vasculitis'. Signaling mechanisms leading to transcriptional activation of target cells in response to Rickettsial adhesion and/or invasion, differential activation of host-cell signaling due to infection with spotted fever versus typhus subgroups of Rickettsiae, and their contributions to the host's immune responses and determination of cell fate are the major subtopics of this review. Also included is a succinct analysis of established in vivo models and their use for understanding Rickettsial interactions with host cells and pathogenesis of vasculotropic rickettsioses. Continued progress in these important but relatively under-explored areas of bacterial pathogenesis research should further highlight unique aspects of Rickettsial interactions with host cells, elucidate the biological basis of endothelial tropism and reveal novel chemotherapeutic and vaccination strategies for debilitating Rickettsial diseases.

Septicaemia with Rickettsia helvetica in a patient with acute febrile illness, rash and myasthenia.

The spotted fever rickettsia, Rickettsia helvetica, is mostly reported to present a flu-like self-limiting disease. In the present case, however, where the presence of R. helvetica in the blood was verified by PCR together with serologic evidence of infection, the patient presented a different clinical picture with acute febrile illness, rash and long-lasting myasthenia.