Rickettsialpox in a Pediatric Patient.

Rickettsialpox is a rare vector-borne rickettsiosis that manifests in hosts living in urban populations, particularly in New York City. The following is a case discussion of a 12-year-old girl with history of fever and right-ankle swelling. She was initially evaluated and treated for cellulitis. She later developed a maculopapular rash completing the classic triad for rickettsialpox: black eschar, papular rash, and fever. Her convalescent rickettsial titers returned positive, confirming the diagnosis of rickettsialpox.

Development and Validation of an Improved PCR Method Using the 23S-5S Intergenic Spacer for Detection of Rickettsiae in Dermacentor variabilis Ticks and Tissue Samples from Humans and Laboratory Animals.

A novel nested PCR assay was developed to detectRickettsiaspp. in ticks and tissue samples from humans and laboratory animals. Primers were designed for the nested run to amplify a variable region of the 23S-5S intergenic spacer (IGS) ofRickettsiaspp. The newly designed primers were evaluated using genomic DNA from 11Rickettsiaspecies belonging to the spotted fever, typhus, and ancestral groups and, in parallel, compared to otherRickettsia-specific PCR targets (ompA,gltA, and the 17-kDa protein gene). The new 23S-5S IGS nested PCR assay amplified all 11Rickettsiaspp., but the assays employing other PCR targets did not. The novel nested assay was sensitive enough to detect one copy of a cloned 23S-5S IGS fragment from "CandidatusRickettsia amblyommii." Subsequently, the detection efficiency of the 23S-5S IGS nested assay was compared to those of the other three assays using genomic DNA extracted from 40 adultDermacentor variabilisticks. The nested 23S-5S IGS assay detectedRickettsiaDNA in 45% of the ticks, while the amplification rates of the other three assays ranged between 5 and 20%. The novel PCR assay was validated using clinical samples from humans and laboratory animals that were known to be infected with pathogenic species ofRickettsia The nested 23S-5S IGS PCR assay was coupled with reverse line blot hybridization with species-specific probes for high-throughput detection and simultaneous identification of the species ofRickettsiain the ticks. "CandidatusRickettsia amblyommii,"R. montanensis,R. felis, andR. belliiwere frequently identified species, along with some potentially novelRickettsiastrains that were closely related toR. belliiandR. conorii.

New York City's innovative epidemiologist: the life and career of Morris Greenberg.

Dr Morris Greenberg was an eminent American epidemiologist who served with the New York City Department of Health for a 40 year period, from 1920 until his passing in 1960. In 1946, he became Director of the department's Bureau of Preventable Diseases. In this role, he set very high standards for outbreak and epidemic investigations joined with a commitment to scholarly research and collaboration with the city's medical centers. He received his medical degree from Columbia University College of Physicians and Surgeons and then interned at Bellevue Hospital in New York City. He later trained in pediatrics in Vienna, Austria and received a Master of Science in Public Health degree from Columbia University School of Public Health. In 1942, he became a member of the teaching staff at the School of Public Health. During his years with the New York City Department of Health he led efforts to control outbreaks of smallpox and rickettsialpox, and initiated important studies of poliomyelitis, hepatitis, trichinosis, congenital cardiac anomalies in children, and the embryopathic effects of rubella in pregnancy. Dr. Greenberg's outbreak and epidemic investigations were popularized by The New Yorker writer, Berton Roueché, whose most widely read book remains, Eleven Blue Men and other Narratives of Medical Detection. The book's title is based on Greenberg's investigation of accidental sodium nitrite poisoning among eleven elderly men in Manhattan who as a result, became cyanotic. A pioneer in epidemiology and the prevention and control of communicable disease, Greenberg established very high performance standards for the discipline before there was a Center for Disease Control and Prevention and an Epidemic Intelligence Service in the United States.

Prevalence of rickettsioses in Poland in 2006-2012.

INTRODUCTION: Tick-borne diseases, such as rickettsioses, anaplasmosis, Lyme boreliosis and bartonellosis are often difficult to correctly diagnose. All these disease are present in Poland. OBJECTIVES: The aim of the study was to estimate a prevalence of Rickettsia spp. infections in humans in Poland in 2006 to 2012 based on the results made in the Laboratory of Rickettsiae, Chlamydiae and Spirochetes, NIPH-NIH in Warsaw. MATERIAL AND METHODS: The levels of Rickettsia spp. and Anaplasma phagocytophilum IgM and IgG antibodies were determined by indirect immunofluorescent assay (IFA). From 2006 to 2012, serum samples derived from 180 humans suspected for rickettsioses, including 84 patients suspected for the infections with typhus and spotted fever group (SFG) rickettsiae, and 96 patients suspected for anaplasmosis. RESULTS: Specific serum antibodies to the SFG rickettsiae have been detected in 5 persons (2.7%). Granulocytic anaplasmosis has been recognized in 9 patients (4.9%). While the reporting and registration of rickettsioses are obligatory in Poland less than 50% of detected cases are reported. CONCLUSIONS: Presented date indicate that in Poland rickettsioses are often unrecognized resulting in their underestimation. If research for rickettsiosis are made immediately after infection, antibodies will not be detect.

[Rickettsial diseases in Switzerland, update for the general practitioner]. / Rickettsioses d'importation.

Rickettsial diseases are arthropod-borne zoonosis. They are still misdiagnosed in Switzerland. Since development in molecular genetics, number of pathogenic species increased dramatically. In recent years, the incidence rise worldwide. Climatic conditions and development of tropical travels could explain it. In a near future, the Swiss general practitioner may face an increase of cases. Clinical presentation is unspecified. The eschar is the key diagnostic element but can be easily overlooked. Serology, the indirect immunofluorescence assay is the reference method. PCR can give the diagnosis in acute phase. However empirical treatment should be prescribed as soon as diagnosis is suspected. No vaccine is currently available and use of repellent is still the best way of prevention.

Human rickettsialpox, southeastern Mexico.

The detection of Rickettsia akari in 2 human patients increased the diversity of rickettsioses affecting the public health in the southeast of Mexico. Rickettsialpox should be considered in the differential diagnosis with other febrile illnesses for the correct diagnosis and accurate treatment of this potential threat to human health.

Real-time multiplex PCR assay for detection and differentiation of rickettsiae and orientiae.

The high incidence of rickettsial diseases in Southeast Asia necessitates rapid and accurate diagnostic tools for a broad range of rickettsial agents, including Orientia tsutsugamushi (scrub typhus) and Rickettsia typhi (murine typhus), but also spotted fever group infections, which are increasingly reported. We present an SYBR-Green-based, real-time multiplex PCR assay for rapid identification and differentiation of scrub typhus group, typhus group and spotted fever group rickettsiae using 47kDa, gltA and ompB gene targets. Detection limits for amplification of these genes in reference strains ranged from 24 copies/microl, 5 copies/microl and 1 copy/microl in multiplex and 2 copies/microl, 1 copy/microl and 1 copy/microl in single template format, respectively. Differentiation by melt-curve analysis led to distinct melt temperatures for each group-specific amplicon. The assay was subjected to 54 samples, of which all cell-culture and 75% of characterised clinical buffy coat samples were correctly identified. Real-time PCR has the advantage of reliably detecting and differentiating rickettsial and orientia cell-culture isolates in a single-template assay, compared with the more time-consuming and laborious immunofluorescence assay. However, further optimisation and validation on samples taken directly from patients to assess its clinical diagnostic utility is required.

Hepatitis in association with rickettsialpox.

Rickettsialpox is an acute, self-limited, febrile illness caused by Rickettsia akari and transmitted by Liponyssoides sanguineus, a mite that infests the common house mouse, Mus musculus. Liver involvement in rickettsialpox has received little attention, although hepatitis has been reported in several other rickettsial infections. In this report, we describe two patients with rickettsialpox who had acute hepatitis that resolved completely. In the appropriate clinical setting, rickettsialpox should be considered in the differential diagnosis of hepatitis.

Fever after a stay in the tropics: diagnostic predictors of the leading tropical conditions.

Differential diagnosis of fever in travelers returning from the tropics is extremely diverse. Apart from the travel destination, other diagnostic predictors of tropical infections are poorly documented in returning travelers. From April 2000 to December 2005, we prospectively enrolled all patients presenting at our referral centers with fever within 1 year after visiting a tropical or subtropical area. For clinical relevance, the diagnostic predictors of the leading tropical conditions were particularly investigated in the febrile episodes occurring during travel or within 1 month after return (defined as early-onset fever). In total, 2071 fever episodes were included, occurring in 1962 patients. Most patients were western travelers (60%) or expatriates (15%). Regions of exposure were mainly sub-Saharan Africa (68%) and southern Asia/Pacific (14%). Early-onset fever accounted for 1619 episodes (78%). Most tropical infections were related to specific travel destinations. Malaria (mainly Plasmodium falciparum) was strongly predicted by the following features: enlarged spleen, thrombocytopenia (platelet count <150 x 10(3)/microL), fever without localizing symptoms, and hyperbilirubinemia (total bilirubin level >or=1.3 mg/dL). When malaria had been ruled out, main predictors were skin rash and skin ulcer for rickettsial infection (mainly African tick bite fever); skin rash, thrombocytopenia, and leukopenia (leukocyte count <4 x 10(3)/microL) for dengue; eosinophil count >or=0.5 x 10(3)/microL for acute schistosomiasis; and enlarged spleen and elevated alanine aminotransferase level (>or=70 IU/L) for enteric fever. The initial clinical and laboratory assessment can help in selecting appropriate investigations and empiric treatments for patients with imported fever.

Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals.

Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy. The greatest challenge to clinicians is the difficult diagnostic dilemma posed by these infections early in their clinical course, when antibiotic therapy is most effective. Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses Branch, in consultation with 11 clinical and academic specialists of Rocky Mountain spotted fever, human granulocytotropic anaplasmosis, and human monocytotropic ehrlichiosis, developed guidelines to address the need for a consolidated source for the diagnosis and management of TBRD. The preparers focused on the practical aspects of epidemiology, clinical assessment, treatment, and laboratory diagnosis of TBRD. This report will assist clinicians and other health-care and public health professionals to 1) recognize epidemiologic features and clinical manifestations of TBRD, 2) develop a differential diagnosis that includes and ranks TBRD, 3) understand that the recommendations for doxycycline are the treatment of choice for both adults and children, 4) understand that early empiric antibiotic therapy can prevent severe morbidity and death, and 5) report suspect or confirmed cases of TBRD to local public health authorities to assist them with control measures and public health education efforts.

Fever of unknown origin due to rickettsioses.

Most common rickettsioses do not fill the criteria for fever of unknown origin, with fever often inferior to lasting less than 1 week. Q fever, scrub typhus, murine typhus, human monocytic ehrlichiosis, and Bartonellosis could fill these criteria, however, notably in uncommon presentations. Moreover, in patients returning from tropical areas or from geographic endemic areas for rickettsiosis, or in patients in contact with animals or ticks, theses etiologies should be kept in mind by physicians challenged to diagnose cause of fever. In this context, even without confirmation of diagnosis, treatment with doxycycline should be used.

Isolation of Rickettsia akari from eschars of patients with rickettsialpox.

Rickettsialpox is a cosmopolitan, mite-borne, spotted fever rickettsiosis caused by Rickettsia akari. The disease is characterized by a primary eschar, fever, and a papulovesicular rash. Rickettsialpox was first identified in New York City in 1946 and the preponderance of recognized cases in the United States continues to originate from this large metropolitan center. The most recently isolated U.S. strain of R. akari was obtained more than a half century ago. We describe the culture and initial characterization of five contemporaneous isolates of R. akari obtained from eschar biopsy specimens from New York City patients with rickettsialpox. This work emphasizes the importance and utility of culture-and molecular-based methods for the diagnosis of rickettsialpox and other eschar-associated illnesses.

Leptospirosis y rickettsiosis, reto diagnóstico para el síndrome febril en zonas endémicas / Leptospirosis and rickettsiosis, a diagnostic challenge for febrile syndrome in endemic areas

Resumen. Se presenta el caso de un hombre de 50 años de edad proveniente de la región de Urabá, Colombia, con una infección mixta por Rickettsia rickettsii y Leptospira interrogans serovar Copenhageni ST78, y pruebas negativas para malaria y dengue. El paciente presentó un síndrome febril que no mejoró con el tratamiento antibiótico sistémico y, finalmente, falleció en la unidad de cuidados intensivos. El diagnóstico post mortem se hizo mediante tipificación molecular de los dos agentes etiológicos. En la inspección del domicilio del paciente, se encontró un ejemplar de Rattus rattus infectado con L. interrogans del mismo serovar detectado en él. No se encontraron garrapatas en los animales domésticos que habitaban con el paciente. Se reporta una infección mixta con síntomas clínicos progresivos y fatales en un paciente con antecedentes laborales de riesgo en una zona endémica para enfermedades tropicales, lo que obliga a tener presente la posibilidad de infecciones simultáneas en personas procedentes de áreas endémicas que consulten reiteradamente por síndrome febril sin resolución y tengan riesgo laboral relacionado con actividades agrícolas.

Abstract. This is the case of a 50-year-old male from the region of Urabá, Colombia, with a mixed infection by Rickettsia rickettsii and Leptospira interrogans serovar Copenhageni ST78 and negative test for malaria and dengue fever. The patient presented with febrile syndrome and was unresponsive to systemic antibiotic treatment, who finally died in the intensive care unit. We established the postmortem diagnosis through molecular typification of the two etiological agents. In the inspection at the patient's home, we found a Rattus rattus specimen infected with L. interrogans of the same serovar found in him. We found no ticks parasitizing the domestic animals cohabitating with the patient. This case of a mixed infection with progressive and fatal symptoms in a patient with occupational risk in a tropical disease endemic zone highlights the importance of considering the potential presentation of simultaneous etiologies in patients with multiple medical visits for unresolved febrile syndromes associated with risky exposure during agricultural activities.

Rickettsial skin disease: uncommon presentations.

Rickettsioses occurring worldwide show a significant morbidity and mortality when not properly treated. Early diagnosis is mandatory for better outcome. Clinical symptoms and patient's history are essential, but uncommon presentation of these arthropod-borne diseases may be a challenge.

Mediterranean spotted fever in an American woman.

Mediterranean spotted fever is common in southern Europe, the Middle East, and North Africa, but is unknown in the United States. It has a clinical picture resembling Rocky Mountain spotted fever, but it is a milder disease. We report a case of Mediterranean spotted fever in a young American woman returning from Morocco and review the clinical picture of this disease.

The role of CD8 T lymphocytes in rickettsial infections.

Arthropod-borne obligately intracellular bacteria pose a difficult challenge to the immune system. The genera Rickettsia, Orientia, Ehrlichia, and Anaplasma evolved mechanisms of immune evasion, and each interacts differently with the immune system. The roles of CD8 T cells include protective immunity and immunopathology. In Rickettsia infections, CD8 T cells are protective mediated in part by cytotoxicity toward infected cells. In contrast, TNF-α overproduction by CD8 T cells is pathogenic in lethal ehrlichiosis by induction of apoptosis/necrosis in hepatocytes. Yet, CD8 T cells, along with CD4 T cells and antibodies, also contribute to protective immunity in ehrlichial infections. In granulocytic anaplasmosis, CD8 T cells impact pathogen control modestly but could contribute to immunopathology by virtue of their dysfunction. While preliminary evidence indicates that CD8 T cells are important in protection against Orientia tsutsugamushi, mechanistic studies have been neglected. Valid animal models will enable experiments to elucidate protective and pathologic immune mechanisms. The public health need for vaccines against these agents of human disease, most clearly O. tsutsugamushi, and the veterinary diseases, canine monocytotropic ehrlichiosis (Ehrlichia canis), heartwater (Ehrlichia ruminantium), and bovine anaplasmosis (A. marginale), requires detailed immunity and immunopathology investigations, including the roles of CD8 T lymphocytes.

Rickettsialpox: report of an outbreak and a contemporary review.

Rickettsialpox is a mild illness characterized by the appearance of a primary eschar at the site of a mite bite followed by fever, headache, and a papulovesicular rash. It can be confused with a variety of illnesses including several other rickettsial diseases and chickenpox. R. akari, the etiologic agent, is a rickettsia belonging to the spotted fever group (SFG) of rickettsial illnesses. In spite of significant serologic cross-reactivity with other SFG agents, there is no convincing evidence of cross-immunity to these agents after recovery from rickettsialpox. Tetracyclinie is the drug of choice in the treatment of this disease.

Ehrlichiosis in children.

Tick-borne rickettsiae of the genus Ehrlichia have recently been recognized as a cause of human illness in the United States. In the years 1986-1988, 10 cases of ehrlichiosis were diagnosed in children in Oklahoma. Fever and headache were universal: myalgias, nausea, vomiting, and anorexia were also common. Rash was observed in six patients but was a prominent finding in only one. Leukopenia, lymphopenia, and thrombocytopenia were common laboratory abnormalities. Six patients were treated with tetracycline, three with chloramphenicol, and one was not treated with antibiotics: all recovered. The onset of illness in spring and early summer for most cases paralleled the time when Amblyomma americanum and Dermacentor variabilis are most active, suggesting that one or both ticks may be vectors of human ehrlichiosis in Oklahoma.