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[Display omitted] • Japanese spotted fever (JSF) is potentially fatal infection transmitted by tick bites which vectors Rickettsia (R.) Japonica. • As representative symptom of external findings, skin rashes were seen on the trunk and extremities, and tick-bite eschars on the left upper arm. • Histopathological examination demonstrated massive inflammatory cell infiltrates in the dermis beneath the external eschar, kidney and lung. • Subsequently polymerase chain reaction revealed specifically amplified signals for R. Japonica from the samples of tick-bites eschar and blood. • We diagnosed the deceased's cause of death as JSF which had been occurred multiorgan failure such as acute renal failure and possibly acute respiratory failure. Japanese spotted fever (JSF) is potentially fatal infection transmitted by tick bites which vectors Rickettsia (R.) japonica. Since JSF was first described in 1984, the incidence has gradually been increased. We experienced a case of JSF of fatal outcome. A female in 70′s was found dead on her bed, whose house was so called 'hoarding house' filled with many waists and unused items. The following day, the autopsy was performed. As representative symptom of external findings, skin rashes were seen on the trunk and extremities, and there were tick-bite eschars on the left upper arm. Internal findings showed no specific findings in each organ. Histopathological examination demonstrated massive inflammatory cell infiltrates mainly consisted of neutrophils in the dermis beneath the external eschar. Furthermore, destruction of glomeruli in kidney with microhemorrhage from mesangial regions was observed. The numerous inflammatory infiltrates were also observed in pulmonary interstitium, which were accompanied with histopathologic features of vasculitis. Biochemical examination showed severe systemic inflammation as monitored by elevated CRP of 16 mg/dL and renal dysfunction by BUN of 171.2 mg/dL and creatinine of 6.07 mg/dL. Subsequently polymerase chain reaction revealed specifically amplified signals for R. japonica from the samples of tick-bites eschar and blood. Thus, we diagnosed her cause of death as JSF which had been occurred multiorgan failure such as acute renal failure and possibly acute respiratory failure. (224 terms) [ABSTRACT FROM AUTHOR]

Background: Rocky Mountain spotted fever (RMSF) is potentially deadly and can present subtly with signs and symptoms overlapping with other clinical conditions. Delayed diagnosis can be fatal.Objective: This review provides an evidence-based summary of the current data for the evaluation and management of RMSF in the emergency department.Discussion: RMSF occurs through transmission of Rickettsia rickettsii by an infected tick. Exposure in the United States occurs most commonly from April to September, and high-risk locations include wooded, shrubby, or grassy areas. Approximately half of patients with infection do not recall tick exposure. Symptoms can include fever, headache, photophobia, malaise, myalgias, and a petechial rash that begins on the wrists and ankles and spreads to the trunk. Rash may not occur in ≤15% of patients, and the classic triad of fever, headache, and rash is also not definitive. Laboratory evaluation may demonstrate hyponatremia, anemia, thrombocytopenia, abnormal liver enzymes, and elevated coagulation tests. Antibody testing can be helpful, but these results are not typically available to the emergency clinician. Doxycycline is the treatment of choice in adults, children, and pregnant patients. Patients should be advised about prevention strategies and effective techniques for removing ticks.Conclusions: RMSF is a potentially deadly disease that requires prompt recognition and management. Focused history, physical examination, and testing are important in the diagnosis of this disease. Understanding the clinical features, diagnostic tools, and proper treatment can assist emergency clinicians in the management of RMSF. [ABSTRACT FROM AUTHOR]

Background Antibiotic resistance is increasing rapidly in pathogenic organisms, creating more complications for treatment of diseases. Rocky Mountain spotted fever (RMSF) is a neglected tropical disease in humans caused by Rickettsia rickettsii for which no effective therapeutic is available. Subtractive genomics methods facilitate the characterization of non-homologous essential proteins that could be targeted for the discovery of potential therapeutic compounds against R. rickettsii to combat RMSF. Present study followed an in-silico based methodology, involving scanning and filtering the complete proteome of Rickettsia rickettsii by using several prioritization parameters in the search of potential candidates for drug development. Further the putative targets were subjected to series of molecular dockings with ligands obtained from PDB ligand database to identify suitable potential inhibitors. The comparative genomic analysis revealed 606 non-homologous proteins and 233 essential non-homologous proteins of R. rickettsii . The metabolic pathway analysis predicted 120 proteins as putative drug targets, out of which 56 proteins were found to be associated with metabolic pathways unique to the bacteria and further subcellular localization analysis revealed that 9 proteins as potential drug targets which are secretion proteins, involved in peptidoglycan biosynthesis, folate biosynthesis and bacterial secretion system. As secretion proteins are more feasible as vaccine candidates, we have selected a most potential target i.e. tolC, an outer membrane efflux protein that belongs to type I secretion system and has major role in pathogen survival as well as MDR persistence. So for case study, we have modelled the three dimensional structure of tolC (tunnel protein). The model was further subjected to virtual screening and in-silico docking. The study identified three potential inhibitors having PDB Id 19V, 6Q8 and 39H. Further we have suggested that the above study would be most important while considering the selection of candidate targets and drug or vaccine designing against R. rickettsii. [ABSTRACT FROM AUTHOR]

Rickettsia sp. strain Atlantic rainforest causes a less severe rickettsiosis, with two cases confirmed until now. The tick species Amblyomma ovale is appointed as the main vector of this bacterium. The southern region of Brazil has reported patients with spotted fever who have milder symptoms. In 2013, during an investigation of rickettsiosis cases, an A. ovale tick was found attached to a man in an area where there were two cases. The parasite was processed for molecular analysis and the rickettsial infection was confirmed based on phylogenetic analysis of genes ompA , ompB and geneD (sca4). In the present study the human pathogenic Rickettsia sp. strain Atlantic rainforest was identified in the state of Rio Grande do Sul, Southern Brazil. Since A. ovale , its main vector, is found frequently parasitizing dogs, animals that can cross international borders freely in southern Brazil, this bacteria can bring major concerns in terms of public health. [ABSTRACT FROM AUTHOR]

Rickettsioses present a threat to human health worldwide, but relatively little is known on their epidemiology and ecology in Oceania. These bacteria are the cause of potentially fatal febrile illnesses in humans (categorized into scrub typhus, typhus group and spotted fever group rickettsioses). They are transmitted by arthropod vectors such as ticks, mites, fleas and lice, which are associated with vertebrate host animals including rodents and companion animals. We conducted a search in the scientific and grey literature of Rickettsia spp. and Orientia tsutsugamushi within the Oceania region. Human case reports, human serosurveys and PCR-based testing of vectors and host animals reviewed here highlight the widespread distribution of these pathogens in the region, with the majority of human serological and vector surveys reporting positive results. These findings suggest that rickettsioses may have a significantly higher burden of disease in Oceania than is currently appreciated due to diagnostic challenges. Furthermore, consideration of the ecology and risk factors for rickettsioses reported for Oceania suggests that their importance as a cause of undifferentiated acute febrile illness may grow in the future: environmental and social changes driven by predicted climate change and population growth have the potential to lead to the emergence of rickettsioses as a significant public health problem in Oceania. [ABSTRACT FROM AUTHOR]

We present advancements in microfluidic technology for rapid detection of as few as 10 rickettsial organisms in complex biological samples. An immuno-reactive filter, macroporous polyacrylamide monolith (PAM), fabricated within a microfluidic channel enhances solid-phase immuno-capture, staining and detection of targeted bacteria. Bacterial cells in samples flowing through the channel are forced to interact with the PAM filter surface due to size exclusion, overcoming common transport and kinetic limitations for rapid (min), high-efficiency (~100%) capture. In the process, targeted cells in sample volumes of 10μl to >100μl are concentrated within a sub-50nl region at the PAM filter edge in the microchannel, thus concentrating them over 1000-fold. This significantly increases sensitivity, as the hydrophilic PAM also yields low non-specific immuno-fluorescence backgrounds with samples including serum, blood and non-targeted bacteria. The concentrated target cells are detected using fluorescently-labeled antibodies. With a single 2.0×2.0×0.3mm PAM filter, as few as 10 rickettsial organisms per 100µl of lysed blood sample can be analyzed within 60min, as compared to hours or even days needed for conventional detection methods. This method is highly relevant to rapid, multiplexed, low-cost point of care diagnostics at early stages of infection where diagnostics providing more immediate and actionable test results are needed to improve patient outcomes and mitigate potential natural and non-natural outbreaks or epidemics of rickettsial diseases. [ABSTRACT FROM AUTHOR]

Abstract: Two commercially available immunofluorescence assays (IFA) were compared using historical sera evaluated for rickettsial antibodies by the Weil-Felix test. An IFA test produced by Focus Diagnostics prepared with Rickettsia rickettsii and R. typhi antigens was compared with a custom made kit from Fuller Laboratories with R. rickettsii, R. typhi, R. conorii and R. helvetica as antigens. The serum panel used for the comparison included Weil-Felix-positive and -negative samples. Cross-reactions were analyzed using serum samples from patients with clinical symptoms similar to those of rickettsiosis. When analyzing the data using the manufacturers'' cut-off values, 41% of samples from presumably healthy blood donors were found positive for spotted fever group Rickettsia antibodies. This does not correlate to the general picture of rickettsiosis in Denmark. Furthermore, sera with Coxiella burnetii antibodies were found to be cross-reacting in both tests. When applying cut-off values calculated on the 95% percentile on data from blood donor serum samples, there was no significant difference between the two kits. Moreover, when using the newly established cut-off, cross-reactions were eliminated. [Copyright &y& Elsevier]

Physicians may encounter unfamiliar diseases as a result of international travel. Fever with rash is an important sign that usually represents initial manifestation of infectious disorders. A 62-year-old Taiwanese woman presented with multiple eschars, a papulovesicular rash, and fever 5 days after returning from South Africa. A biopsy specimen of an eschar had wedge-shaped tissue necrosis, hemorrhage, necrotizing vasculitis of the small venules and arterioles, and a dense perivascular lymphocytic infiltrate in the dermis. Serologically, there was cross reaction with both Rickettsia conorii and R. rickettsii. DNA sequencing demonstrated R. africae, confirming the diagnosis of African tick bite fever. The patient responded well to minocycline. Recognition of the symptoms and signs, and diagnostic tools for different types of rickettsiosis are essential for correct diagnosis and treatment. [Copyright &y& Elsevier]

The article focuses on the use of nested Polymerase Chain Reaction (PCR) for testing human serum samples to diagnose Spotted Fever Group (SFG) rickettsiae and Brazilian Spotted Fever (BSF). PCR involves the process of bacterial isolation and DNA sequencing. Serum samples collected from fatal human cases were tested in the laboratory to detect SFG.

The article focuses on a study done to evaluate the diagnosis of Coxiella burnetii pericarditis by using a systematic prescription kit tests in the cases of pericardial effusion. It describes how the diagnostic procedure included a questionnaire with items underlying conditions and epidemiological factors and a list of tests to be performed systematically. It mentions that the inclusion of systematic testing in the kit can result in unexpected diagnosis of the cases of Q fever.

Mediterranean spotted fever (MSF) is caused by Rickettsia conorii, an obligate intracellular parasite of eukaryotic cells. Although, usually this disease has a benign course, a rapidly fatal outcome can occur even in young healthy adults. We describe a case of a 40-year-old Bedouin woman gravida 11, para 10, who was admitted at 36 weeks gestation with this rickettsial disease. During pregnancy, the treatment of choice for Mediterranean spotted fever is chloramphenicol, but it seems that Azithromycin could be another possible option. [Copyright &y& Elsevier]

Background: Interest in the relationship between infection and atherosclerosis induced coronary heart disease has recently increased. Rickettsiae are a group of obligate intracellular pathogens who invade endothelial cells and cause vasculopathy. In a longitudinal nation wide study conducted in Thaiwan, the incidence of acute coronary syndromes (ACS) in patients with scrub typhus was found to be higher than a comparison cohort (3.10 vs 1.92 per 1000 person-years). A 37% increased risk in subse quesnt development of ACS has been demonstrated compared to general population after adjusting for age, sex and other indipendant risk factors; hypertension, diabetes, hyperlipidaemia, chronic obstructive pulmonary disease and coronary artery disease. The prominent effect of scrub typhus on subsequent ACS development has appeared within 1 year after infection. Aims: To assess the prevalence of Rickettsial infections in patients with ACS who live in the Western province, Sri Lanka. Methods & Materials: Patients admitted with ACS to the Professorial Medical Unit, Colombo North Hospital, Ragama, Sri Lanka from April to December 2011 were studied for the serological prevalence of rickettsial infections and were compared with a matched control group; who had no fever or ACS and admitted during the same period. 2 ml serum samples were obtained at enrolment and 2 weeks after, to assess exposure to rickettseal infections by IFA-IgG antibody titres against Orientia Tsutsugamushi (OT) and Spotted fever group (SFG) rickettsioses. An IgG titre ?1:128 or a rising/declining titre were considered positive for acute rickettsioses. A static titre was considered previous exposure to Rickettsioses. Results: 46 ACS [males n(23.9%), mean age (SD) 61.1(13.1) y] and 52 controls (males n (50%), mean age(SD) 56.0(13.6) y] were studied. None had evidence of acute rickettsiel infection. Seroprevalence of IgG (OT) was 6.4% and IgG-SFG was 15.2% among ACS patients while that of control group were 3.8% and 11.5% respectively. There was no significant difference in sero-prevalence of OT [OR =0.74 (CI, 0.28-10.93), p=0.66] or SFG [OR=1.376 (CI, 0.43-4.44), p=0.59] in patients with ACS compared to controls. Conclusion: We observed no significant difference in seroprevalence of rickettsioses in patients with acute coronary syndromes compared to controls in this study. [ABSTRACT FROM AUTHOR]

Background: Rickettsial infections are known to present mimicking autoimmune disorders. The gold standard diagnostic test for rickettsial diseases is based on the detection of IgM and or IgG antibodies against these infections by immuno-fluorescent technique (IFA). While confirmation of rickettsial diseases warrant demonstration of rising or declining antibody titres between acute and convalescent samples, high titres of either IFA-IgM or IFA-IgG in acute phase serum in patients with a compatible clinical illness may help in the presumptive diagnosis and introduction of antirickettsial antibiotics. During the IFA test, patient sera containing anti rickettsial antibodies are made to react with rickettsial antigens that are grown in cell culture media. However, presence of nuclear material in these cell cultures may react with anti-nuclear antibodies that are produced in autoimmune disorders and cause a false positive immunofluorescent signal. Methods&Materials: In order to evaluate the reactivity of rickettsial disease IFA-IgG test [IFA-IgG-OT (Orientia tsutsugamushi) and IFA-IgG-SFG (spotted fever group)] among patients with autoimmune diseases, an analytical cross-sectional study was carried out using sera of 38 patients with confirmed auto-immune diseases. Results: The 38 patients included 15 systemic lupus erythematosus (SLE), 5 autoimmune-thyroiditis, 13 idiopathicthrombocytopenia (ITP), 4 autoimmune-haemolytic-anaemia (AIHA), 1 polymyositis, 1 polyglandular syndrome and 1 Antiphospholipid syndrome. The IFA-IgG reactivity of = 1:128 was noted in 14/38 (37%); IFA-IgG-SFG in 7, IFA-IgG-OT in 3 and for both in 4. Of the 14; titre of 1:128 in 2, 1:256 in 4, 1:512 in 5, >1: 1024 in 3 and 8/14 (57%) were SLE, 3/14 (21.4%%) were ITP, 2/14 (14.3%) were AIHA, 1/14 (7.1%) were polymyositis and none were thyroiditis. 8/14 had received anti-rickettsial antibiotics during the early stages of illness based on the clinical presentation and high IFA-IgG titres. Conclusion: There was a significant reactivity of Rickettsial disease IFA-IgG assay in auto-immune diseases. Further studies are needed in order to ascertain whether this is due to recent rickettsial infections, false positive cross reactivity of autoimmune antibodies with rickettsial antigens or with cell culture nuclear antigens. We did not carry out IFA-IgM due to non-availability and nonaffordability. [ABSTRACT FROM AUTHOR]

Rickettsial infections are increasing in all regions of Southeast Asia where sought. Given the non-specific presenting symptoms resembling those of other endemic infections, diagnosis can be challenging, even to the most experienced clinician. Available tests have limitations, with no good gold standard diagnostic test. Serological tests are the mainstay of diagnosis with the IgM indirect immunofluorescence assay being the reference test. However, the enzyme-linked immuno-sorbent assay is used more commonly due to the ease of performance and a good sensitivity and specificity. Paired samples, obtained at least two weeks apart, demonstrating a minimum 4 fold titre rise, are needed for improved serologic specificity, limiting its clinical feasibility. Other methods of testing have become available, but at this time, these remain insufficient to provide the rapid point-of-care diagnostics that would be necessary to significantly change the management of this infection by providers in endemic areas. The mainstay of treatment is Doxycycline although the intravenous formulations are unavailable in several countries. Macrolides have proven efficacy in mild cases and intravenous Azithromycin is used along with oral Doxycycline in seriously ill with suboptimal gastrointestinal absorption and bioavailability. This presentation reviews the challenges in the laboratory diagnosis and management of rickettsial infections unique to Southeast Asia, and examines data on emerging resistance to antimicrobial drugs. [ABSTRACT FROM AUTHOR]

The article presents information on the development of multiplex 5'-nuclease real-time Polymerase chain Reaction (PCR) and its effectiveness in diagnosing the spotted fever and typhus group rickettsioses. Multiplex quantitative PCR assay is an epidemiologic tool for the diagnosis of rickettsial infections, which detects pathogen accurately and are able to distinguish between existing Rickettsia species. It also detects two OT DNA gene copies in blood, closely related to rickettsiae.

The article focuses on a study done to investigate the suitability of a new DNA microarray chip for the detection of Coxiella burnetii (C. burnetii) and the diagnosis of Q-fever. It states that the new rapid low cost and density (LCD) DNA microarray chip allowed rapid, sensitive, specific and economic detection of polymerase chain reaction (PCR)-amplified products and all 22 C. burnetii isolates investigated in the study yielded positive reactions.