A systematic review and meta-analysis of the aetiological agents of non-malarial febrile illnesses in Africa.

BACKGROUND: The awareness of non-malarial febrile illnesses (NMFIs) has been on the rise over the last decades. Therefore, we undertook a systematic literature review and meta-analysis of causative agents of non-malarial fevers on the African continent. METHODOLOGY: We searched for literature in African Journals Online, EMBASE, PubMed, Scopus, and Web of Science databases to identify aetiologic agents that had been reported and to determine summary estimates of the proportional morbidity rates (PMr) associated with these pathogens among fever patients. FINDINGS: A total of 133 studies comprising 391,835 patients from 25 of the 54 African countries were eligible. A wide array of aetiologic agents were described with considerable regional differences among the leading agents. Overall, bacterial pathogens tested from blood samples accounted for the largest proportion. The summary estimates from the meta-analysis were low for most of the agents. This may have resulted from a true low prevalence of the agents, the failure to test for many agents or the low sensitivity of the diagnostic methods applied. Our meta-regression analysis of study and population variables showed that diagnostic methods determined the PMr estimates of typhoidal Salmonella and Dengue virus. An increase in the PMr of Klebsiella spp. infections was observed over time. Furthermore, the status of patients as either inpatient or outpatient predicted the PMr of Haemophilus spp. infections. CONCLUSION: The small number of epidemiological studies and the variety of NMFI agents on the African continent emphasizes the need for harmonized studies with larger sample sizes. In particular, diagnostic procedures for NMFIs should be standardized to facilitate comparability of study results and to improve future meta-analyses. Reliable NMFI burden estimates will inform regional public health strategies.

Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis.

Arthropod-borne rickettsial pathogens cause mild and severe human disease worldwide. The tick-borne pathogen Rickettsia parkeri elicits skin lesions (eschars) and disseminated disease in humans; however, inbred mice are generally resistant to infection. We report that intradermal infection of mice lacking both interferon receptors (Ifnar1-/-;Ifngr1-/-) with as few as 10 R. parkeri elicits eschar formation and disseminated, lethal disease. Similar to human infection, eschars exhibited necrosis and inflammation, with bacteria primarily found in leukocytes. Using this model, we find that the actin-based motility factor Sca2 is required for dissemination from the skin to internal organs, and the outer membrane protein OmpB contributes to eschar formation. Immunizing Ifnar1-/-;Ifngr1-/- mice with sca2 and ompB mutant R. parkeri protects against rechallenge, revealing live-attenuated vaccine candidates. Thus, Ifnar1-/-;Ifngr1-/- mice are a tractable model to investigate rickettsiosis, virulence factors, and immunity. Our results further suggest that discrepancies between mouse and human susceptibility may be due to differences in interferon signaling.

Tick bites allow disease-causing microbes, including multiple species of Rickettsia bacteria, to pass from arthropods to humans. Being exposed to Rickettsia parkeri, for example, can cause a scab at the bite site, fever, headache and fatigue. To date, no vaccine is available against any of the severe diseases caused by Rickettsia species. Modelling human infections in animals could help to understand and combat these illnesses. R. parkeri is a good candidate for such studies, as it can give insight into more severe Rickettsia infections while being comparatively safer to handle. However, laboratory mice are resistant to this species of bacteria, limiting their use as models. To explore why this is the case, Burke et al. probed whether an immune mechanism known as interferon signalling protects laboratory rodents against R. parkeri. During infection, the immune system releases molecules called interferons that stick to 'receptors' at the surface of cells, triggering defense mechanisms that help to fight off an invader. Burke et al. injected R. parkeri into the skin of mice that had or lacked certain interferon receptors, showing that animals without two specific receptors developed scabs and saw the disease spread through their body. Further investigation showed that two R. parkeri proteins, known as OmpB or Sca2, were essential for the bacteria to cause skin lesions and damage internal organs. Burke et al. then used R. parkeri that lacked OmpB or Sca2 to test whether these modified, inoffensive microbes could act as 'vaccines'. And indeed, vulnerable laboratory mice which were first exposed to the mutant bacteria were then able to survive the 'normal' version of the microbe. Together, this work reveals that interferon signalling protects laboratory mice against R. parkeri infections. It also creates an animal model that can be used to study disease and vaccination.

The first human case of Rickettsia slovaca from Turkey.

A three year-old girl was admitted to our university hospital with fever, muscle and abdominal pain, and painful cervical lymph nodes after a tick bite on scalp. Rickettsia slovaca DNA was detected in eschar tissue taken from the bite site. This is the first clinical case of a R. slovaca infection reported from Turkey.

Endothelial Exosome Plays a Functional Role during Rickettsial Infection.

Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of rickettsial infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia-infected, EC-derived exosomes (Exos) during infection. Using size exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacterium-free media collected from Rickettsia parkeri-infected human umbilical vein ECs (HUVECs) (R-ECExos) and plasma of Rickettsia australis- or R. parkeri-infected mice (R-plsExos). We observed that rickettsial infection increased the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, both R-plsExos and R-ECExos induced dysfunction of recipient normal brain microvascular ECs (BMECs). The effect of R-plsExos on mouse recipient BMEC barrier function is dose dependent. The effect of R-ECExos on human recipient BMEC barrier function is dependent on the exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription-PCR (RT-qPCR) validation revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.IMPORTANCE Spotted fever group rickettsioses are devastating human infections. Vascular endothelial cells are the primary targets of infection. Edema resulting from endothelial barrier dysfunction occurs in the brain and lungs in most cases of lethal rickettsioses, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia-infected, endothelial cell-derived exosomes during infection. We observed that rickettsial infection increased the release of heterogeneous plasma Exos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Rickettsia-infected, endothelial cell-derived exosomes induced dysfunction of human recipient normal brain microvascular endothelial cells. The effect is dependent on the exosomal RNA cargo. Next-generation sequencing analysis revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.

The enigmatic biology of rickettsiae: recent advances, open questions and outlook.

Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses and are among the oldest known vector-borne pathogens. Members of this genus are extraordinarily diverse and exhibit a broad host range. To establish intracellular infection, Rickettsia species undergo complex, multistep life cycles that are encoded by heavily streamlined genomes. As a result of reductive genome evolution, rickettsiae are exquisitely tailored to their host cell environment but cannot survive extracellularly. This host-cell dependence makes for a compelling system to uncover novel host-pathogen biology, but it has also hindered experimental progress. Consequently, the molecular details of rickettsial biology and pathogenesis remain poorly understood. With recent advances in molecular biology and genetics, the field is poised to start unraveling the molecular mechanisms of these host-pathogen interactions. Here, we review recent discoveries that have shed light on key aspects of rickettsial biology. These studies have revealed that rickettsiae subvert host cells using mechanisms that are distinct from other better-studied pathogens, underscoring the great potential of the Rickettsia genus for revealing novel biology. We also highlight several open questions as promising areas for future study and discuss the path toward solving the fundamental mysteries of this neglected and emerging human pathogen.

Rickettsia-host interaction: strategies of intracytosolic host colonization.

Bacterial infection is a highly complex biological process involving a dynamic interaction between the invading microorganism and the host. Specifically, intracellular pathogens seize control over the host cellular processes including membrane dynamics, actin cytoskeleton, phosphoinositide metabolism, intracellular trafficking and immune defense mechanisms to promote their host colonization. To accomplish such challenging tasks, virulent bacteria deploy unique species-specific secreted effectors to evade and/or subvert cellular defense surveillance mechanisms to establish a replication niche. However, despite superficially similar infection strategies, diverse Rickettsia species utilize different effector repertoires to promote host colonization. This review will discuss our current understandings on how different Rickettsia species deploy their effector arsenal to manipulate host cellular processes to promote their intracytosolic life within the mammalian host.

Ultrastructure of intracytoplasmic Rickettsia-like infection of the gills of the teleost Archosargus probatocephalus (Sparidae) in northeastern Brazil.

A histopathological survey was conducted to investigate the presence of microparasites in fish Archosargus probatocephalus in a river near Maceió, Brazil. Light microscope observations of fragments of gill showed the presence of small cysts containing numerous myxospores that were morphologically identified as Henneguya. Transmission electron microscopy observations further revealed several gill cells containing groups of prokaryotic cells within large cytoplasmic vacuoles. Each infected host cell displayed a single vacuole containing a variable number of Rickettsia-like cells (up to 11), some of which presented the dumbbell shape characteristic of binary fission. The Rickettsia-like cells were pleomorphic, without a nucleus and with chromatin dispersed in the cytoplasm. They had a thin electron-dense wall of Gram-negative type. The morphology of these prokaryotic was similar to those of the order Rickettsiales and was described as a Rickettsia-like organism. Histopathological evaluation showed that several vacuole membranes had a lysed appearance. Some had ruptured, thus allowing direct contact between the Rickettsia-like organism and the cytoplasm of the host cell. The rupturing of the branchial epithelium may have contributed towards reduction of the surface area of the gills, but it is not possible to say that this was the cause of the host's death.

Ultrastructure of intracytoplasmic Rickettsia-like infection of the gills of the teleost Archosargus probatocephalus (Sparidae) in northeastern Brazil / Ultraestrutura de Rickettsia intracitoplasmática infectando as brânquias do teleósteo Archosargus probatocephalus (Sparidae) no Nordeste do Brasil

Abstract A histopathological survey was conducted to investigate the presence of microparasites in fish Archosargus probatocephalus in a river near Maceió, Brazil. Light microscope observations of fragments of gill showed the presence of small cysts containing numerous myxospores that were morphologically identified as Henneguya. Transmission electron microscopy observations further revealed several gill cells containing groups of prokaryotic cells within large cytoplasmic vacuoles. Each infected host cell displayed a single vacuole containing a variable number of Rickettsia-like cells (up to 11), some of which presented the dumbbell shape characteristic of binary fission. The Rickettsia-like cells were pleomorphic, without a nucleus and with chromatin dispersed in the cytoplasm. They had a thin electron-dense wall of Gram-negative type. The morphology of these prokaryotic was similar to those of the order Rickettsiales and was described as a Rickettsia-like organism. Histopathological evaluation showed that several vacuole membranes had a lysed appearance. Some had ruptured, thus allowing direct contact between the Rickettsia-like organism and the cytoplasm of the host cell. The rupturing of the branchial epithelium may have contributed towards reduction of the surface area of the gills, but it is not possible to say that this was the cause of the host's death.

Resumo Um levantamento histopatológico foi realizado para pesquisar a presença de microparasitas, no peixe Archosargus probatocephalus, em um rio próximo a Maceió, Brasil. Observações ao microscópio óptico de fragmentos de brânquias mostraram a presença de pequenos cistos contendo numerosos mixósporos, identificados morfologicamente como Henneguya. Ocasionalmente, na microscopia eletrônica de transmissão, foram observados vários corpos citoplasmáticos de inclusão, grupo aparentemente de células procarióticas que vivem dentro de um grande vacúolo citoplasmático de algumas células branquiais. As células hospedeiras infectadas tinham um único vacúolo contendo um número variável de células do tipo Rickettsia, até 11, algumas das quais em forma do haltere, característica da fissão binária. Essas células eram pleomórficas sem núcleo, tendo a cromatina dispersa no citoplasma e possuíam uma parede densa de elétrons finos do tipo Gram-negativo. A morfologia dessas células procarióticas foi semelhante àquelas da ordem Rickettsiales e foram descritas como organismos tipo Rickettsiae. A histopatologia mostra várias membranas de vacúolos circundantes com aspetos lisados, enquanto outras apresentam rupturas que mostram contato direto do organismos tipo Rickettsiae com o citoplasma da célula hospedeira. A ruptura do epitélio branquial pode ter contribuído para a redução da superfície das brânquias, mas não é possível afirmar que foi a causa da morte do hospedeiro.

Pathological changes by Eosinophilic Rickettsia-like organism in Japanese oyster, Crassostrea gigas.

Rickettsia infection in adult Japanese oysters (Crassostrea gigas) was observed in 2015 at San Ignacio Lagoon, Baja California Sur, Mexico and characterized using molecular tools. In the present study, the degree of infection by Eosinophilic Rickettsia-Like Organism (E-RLO), characterized by intracellular inclusions in gill, mantle, labial palps, digestive tract and gonadal ducts, was evaluated using histological methods and was associated with visible injuries on body surface, such as blisters, shell damage and necrosis. Most of the oysters (92.2%) had some type of observable symptoms; 90.2% of all oysters had blisters in the mantle, and all oysters presented with E-RLO in the epithelia of at least one of the analyzed tissues (gills, labial palps, mantle, gonadal ducts and digestive tract). The highest intensity of infection (percent of E-RLO coverage) was observed in the labial palps (18.6%) and the lowest in digestive tract (2.6% of the examined tissue). Oysters with external injuries had higher infection intensities than the oysters without external injuries. Considering the clinical signs (observable symptoms and histological findings), we propose three infective stages of E-RLO disease development, a scale that could be used for early detection.

Escara como clave diagnóstica en un paciente con síndrome febril / Cutaneous crust as a key sign in the diagnosis of a patient with fever

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Cellulitis of the face associated with SENLAT caused by Rickettsia slovaca detected by qPCR on scalp eschar swab sample: An unusual case report and review of literature.

BACKGROUND: Tick-borne rickettsioses are infectious diseases caused by obligate intracellular Gram-negative bacteria belonging to the spotted fever groupof Rickettsia. METHODS: We describe an unusual case of SENLAT (Scalp eschar and neck lymphadenopathy after tick bite), caused byRickettsia slovaca, associated with a cellulitis of the face in a 70-year-old woman, and diagnosed using qPCR on a scalp eschar swab. We review the literature regarding cases of SENLAT-associated-cellulitis and case of SENLAT diagnosed by qPCR on scalp eschar swabs. RESULTS: We found only one previous report of SENLAT associated with a cellulitis of the face. It was a nine-year-old French girl diagnosed by seroconversion for Rickettsia sp. Our review of the literature showed that qPCR on eschar swab samples is a less invasive method than performing cutaneous biopsy of the eschar and has good sensitivity and specificity (90% and 100%, respectively). CONCLUSIONS: We report the second case of cellulitis of the face associated with the SENLAT syndrome. Detection of Rickettsia by qPCR on swab sample of the scalp eschar is a simple, noninvasive technique allowing rapid diagnosis and treatment when SENLAT is suspected.

Emerging and re-emerging rickettsial infections.

Rickettsial organisms are a diverse group of obligate intracellular bacteria; all species known to cause human disease are dependent on an arthropod vector and many are considered zoonotic diseases. Typical vectors of rickettsia are fleas, ticks, mites or lice. Humans become infected either when bitten or upon contact of broken skin or mucous membranes by infected secretions from an arthropod vector. The emergence and re-emergence of rickettsial diseases is a serious public health concern in the United States and abroad. Herein, the clinical and pathologic features of rickettsial diseases are described in tandem with the current scientific underpinnings. The histopathology of emerging and re-emerging rickettsiosis with species-specific discussion relating to vector issues and control are explored. Concepts of endemicity are addressed in the context of climate change and its impact on vector and sylvatic reservoirs, underscoring the need for clinical vigilance and broad consideration for encounters with these potentially life threating human pathogens.

Pathogenesis of Rickettsial Diseases: Pathogenic and Immune Mechanisms of an Endotheliotropic Infection.

Obligately intracytosolic rickettsiae that cycle between arthropod and vertebrate hosts cause human diseases with a spectrum of severity, primarily by targeting microvascular endothelial cells, resulting in endothelial dysfunction. Endothelial cells and mononuclear phagocytes have important roles in the intracellular killing of rickettsiae upon activation by the effector molecules of innate and adaptive immunity. In overwhelming infection, immunosuppressive effects contribute to the severity of illness. Rickettsia-host cell interactions involve host cell receptors for rickettsial ligands that mediate cell adhesion and, in some instances, trigger induced phagocytosis. Rickettsiae interact with host cell actin to effect both cellular entry and intracellular actin-based mobility. The interaction of rickettsiae with the host cell also involves rickettsial evasion of host defense mechanisms and exploitation of the intracellular environment. Signal transduction events exemplify these effects. An intriguing frontier is the array of rickettsial noncoding RNA molecules and their potential effects on the pathogenesis and transmission of rickettsial diseases.

Serum cytokine responses in Rickettsia felis infected febrile children, Ghana.

The intracellular pathogen Rickettsia felis causes flea-borne spotted fever and is increasingly recognized as an emerging cause of febrile illness in Africa, where co-infection with Plasmodium falciparum is common. Rickettsiae invade endothelial cells. Little is known, however, about the early immune responses to infection. In this study, we characterize for the first time the cytokine profile in the acute phase of illness caused by R. felis infection, as well as in plasmodial co-infection, using serum from 23 febrile children < 15 years of age and 20 age-matched healthy controls from Ghana. Levels of IL-8 (interleukin-8), IP-10 (interferon-γ-induced protein-10), MCP-1 (monocyte chemotactic protein-1), MIP-1α (macrophage inflammatory protein-1α) and VEGF (vascular endothelial growth factor) were significantly elevated in R. felis mono-infection; however, IL-8 and VEGF elevation was not observed in plasmodial co-infections. These results have important implications in understanding the early immune responses to R. felis and suggest a complex interplay in co-infections.

Under-diagnosis of rickettsial disease in clinical practice: A systematic review.

BACKGROUND: Rickettsial diseases present as acute febrile illnesses, sometimes with inoculation eschars. METHODS: We performed a systematic review of studies published between 1997 and 2017 to assess the underestimation of non-eschar rickettsial disease (NERD) relative to eschar rickettsial disease (ERD), as a cause of acute fever in patients with rickettsial diseases that commonly present with eschar(s): scrub typhus (ST), Mediterranean spotted fever (MSF), and African tick-bite fever. We compared ERD/NERD ratios according to study design: 'complete approach' studies, with testing performed in all patients with 'unspecified febrile illness'; versus 'clinical judgement' studies, with testing performed if patients presented with specific symptoms. RESULTS: In 'complete approach' studies, ERD/NERD ratios were significantly lower, suggesting a considerable under-diagnosis of NERD in 'clinical judgement' studies. Based on these results, we estimate that the diagnosis of rickettsial disease was missed in 66.5% of patients with ST, and in 57.9% of patients with MSF. CONCLUSIONS: Study design influences the reported eschar rates in ST and MSF significantly. NERD is likely to be a vastly underdiagnosed entity, and clinicians should consider and test for the disease more often. PROSPERO REGISTRATION NUMBER: CRD 42016053348.

Detection of causative agents of tick-borne rickettsioses in Western Siberia, Russia: identification of Rickettsia raoultii and Rickettsia sibirica DNA in clinical samples.

OBJECTIVES: The main causative agent of tick-borne rickettsioses in Siberia is considered to be Rickettsia sibirica; however, only a few cases have been genetically confirmed. Other pathogenic species of Rickettsia have been detected in ixodid ticks in Western Siberia. The aim of this study was to detect the aetiological agents of tick-borne rickettsioses in Western Siberia and compare their clinical manifestations. METHODS: A total of 273 blood and 44 cerebrospinal fluid (CSF) samples from 273 patients hospitalized because of tick-transmitted infection in April-September 2016 were examined for the presence of Rickettsia spp., using nested PCR with subsequent sequencing. RESULTS: DNA of Rickettsia spp. was found in samples from 10 patients. The gltA gene fragment sequence analysis revealed R. sibirica DNA in seven patients (blood samples) and Rickettsia raoultii DNA in three patients (two blood and one CSF sample). Most patients infected with R. sibirica showed typical clinical symptoms, including high-grade fever (38.9-39.5°Ð¡), myalgia, rash, eschar at the site of the tick bite, and elevated levels of serum aminotransferases. In contrast, patients infected with R. raoultii showed nonspecific symptoms with short-term fever (37.2-37.7°Ð¡); one patient had a short episode of meningeal syndrome. CONCLUSIONS: We report the first finding of R. raoultii DNA in clinical samples from Russian patients. The clinical manifestations of this rickettsiosis were nonspecific and differed from those caused by R. sibirica.

Widespread subcutaneous necrosis in spotted fever group Rickettsioses from the coastal belt of Sri Lanka- a case report.

BACKGROUND: Spotted fever group rickettsioses (SFGR) transmitted mostly by ticks are increasingly discovered around the World and some of them are either re-emerging or emerging in Sri Lanka. Accidental human infections caused by these vector borne zoonotic diseases generally give rise to nonspecific acute febrile illnesses which can be complicated by multi organ involvement carrying high morbidity and mortality. Nonspecific clinical features and non-availability of early diagnostic facilities are known to result in delay in the diagnosis of rickettsial infections. Therefore, awareness of their prevalence and more importantly their clinical features would be help in the early diagnosis and institution of appropriate therapy. CASE PRESENTATION: A 39-year-old otherwise healthy female presented with an acute febrile illness complicated by severe small joint and large joint arthritis, jaundice, acute kidney injury and disseminated intravascular coagulation (DIC) mimicking palindromic rheumatism or severe sepsis. She later developed a widespread fern-leaf pattern necrotic skin rash with evidence of vasculitis on the palms and soles, aiding the clinical diagnosis of SFGR. She had very high antibody titres against R. conorii antigen confirming the diagnosis and recovered completely with anti-rickettsial therapy. CONCLUSION: We feel that clinicians should be aware of the unusual clinical presentations such as purpura fulminans and 'fern-leaf' pattern necrotic skin rash of SFGR infection. Such knowledge would not only benefit those who practice in tropics with limited diagnostic facilities but also would improve the management of acute febrile illness in returning travelers who visit endemic areas.

Rickettsia infection could be the missing piece of the Buerger's disease puzzle.

BACKGROUND: Rickettsia was suggested as a possible etiology of Buerger's disease (BD) in the 1980s but this suggestion was never ruled out or proven. Recently, we found evidence of Rickettsia by polymerase chain reaction in 3 out of 25 biopsy samples from the amputated limb of a young man diagnosed with BD. The aim of this paper was to investigate the presence of anti-rickettsial antibodies in the sera of BD patients. METHODS: To detect the IgG class antibody against Rickettsia rickettsii, which has cross reactions with the spotted fever group (RSFG), and Rickettsia typhi, which has cross reactions with typhus fever group, the sera of patients and controls were diluted to 1:64 and analyzed by indirect micro fluorescence immunoassay (MIF). RESULTS: The MIF study showed that 26 of the 28 patients were positive for Rickettsia rickettsii antibodies and MIF had the same appearance as the positive control, which was provided with the kit. In all members of the healthy control group, Rickettsia rickettsii was negative and had the appearance of the negative control. Rickettsia typhi was negative for all patients and members of the control group. CONCLUSIONS: A species of Rickettsia associated with the RSFG, which might not be pathogenic for the entire population, may induce BD in the context of a specific genetic or environmental background. RSFG infection could explain key questions about BD, including its gender and geographical distribution, clinical manifestation, angiography pattern, and pathological findings. Evaluating antibodies against RSFG in BD patients from different countries is now highly recommended.

Assessment of Domestic Goats as Models for Experimental and Natural Infection with the North American Isolate of Rickettsia slovaca.

Rickettsia slovaca is a tick-borne human pathogen that is associated with scalp eschars and neck lymphadenopathy known as tick-borne lymphadenopathy (TIBOLA) or Dermacentor-borne necrosis erythema and lymphadenopathy (DEBONEL). Originally, R. slovaca was described in Eastern Europe, but since recognition of its pathogenicity, human cases have been reported throughout Europe. European vertebrate reservoirs of R. slovaca remain unknown, but feral swine and domestic goats have been found infected or seropositive for this pathogen. Recently, a rickettsial pathogen identical to R. slovaca was identified in, and isolated from, the American dog tick, Dermacentor variabilis. In previous experimental studies, this organism was found infectious to guinea pigs and transovarially transmissible in ticks. In this study, domestic goats (Capra hircus) were experimentally inoculated with the North American isolate of this R. slovaca-like agent to assess their reservoir competence-the ability to acquire the pathogens and maintain transmission between infected and uninfected ticks. Goats were susceptible to infection as demonstrated by detection of the pathogen in skin biopsies and multiple internal tissues, but the only clinical sign of illness was transient fever noted in three out of four goats, and reactive lymphoid hyperplasia. On average, less than 5% of uninfected ticks acquired the pathogen while feeding upon infected goats. Although domestic goats are susceptible to the newly described North American isolate of R. slovaca, they are likely to play a minor role in the natural transmission cycle of this pathogen. Our results suggest that goats do not propagate the North American isolate of R. slovaca in peridomestic environments and clinical diagnosis of infection could be difficult due to the brevity and mildness of clinical signs. Further research is needed to elucidate the natural transmission cycle of R. slovaca both in Europe and North America, as well as to identify a more suitable laboratory model.

[Rickettsiosis - Early skin biopsy is essential because of latency in serological findings]. / Rickettsiose.

BACKGROUND: Global travel increasis practitioner's confrontation with very special infectious diseases, like hemorrhagic viral diseases that are traditionally rare in European countries. Prompt diagnosis and subsequent induction of therapy are essential to prevent high rates of severe and lethal complications. ANAMNESIS: A 59-year-old man complained deterioration of general health after a 3-week vacation to South Africa. He presented fever and hemorrhagic erythema with pustula surrounded by necrotic margin on the right calf. COURSE AND THERAPY: On the second day of inpatient treatment, a papulovesiculous, partly hemorrhagic exanthema appeared. With a tentative diagnosis of Rickettsiosis, we performed specific diagnostics by serology and biopsy. Therapy was initiated with doxycycline (200 mg/d) for 7 days. Under this regimen clinical symptoms healed without consequences. Rickettsioses are ubiquitious zoonoses that are caused by various Rickettsia subtypes. The stay in endemic regions together with signs of fever, reduced general health, eschar and exanthema are suspicious for this disease. Therapy should be initiated immediately in cases of clinical suspicion with a characteristic case history. The seroconversion, which appears later in course, should not give reason for avoiding early skin biopsy due to the potentially fatal course of the disease. Biopsy enables early histological proof of a dermal vasculitic inflammation pattern and PCR analysis before subsequent serological controls and proofs.