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.

Sociocultural descriptions of febrile syndromes in rural areas of Urabá, Colombia: An exploration of "tick fever" / Descrição sociocultural de síndromes febris em áreas rurais de Antioquia Urabá: um olhar sobre a "febre do carrapato"

Abstract Introduction: In 2006 and 2008 there were two lethal outbreaks of rickettsioses in the rural areas of Urabá, characterized by the lack of immediate diagnosis and antibiotic treatment. Objective: Describe sociocultural aspects about knowledge, attitudes and practices in relation to febrile syndromes and "tick fever" in rural areas of Urabá. Materials and methods: We conducted an exploratory study using knowledge, attitudes, and practices questionnaires and semi-structured interviews about febrile syndromes and "tick fever". We surveyed 246 heads of households and interviewed nine individuals. Results: We observed that people tended to identify febrile syndromes with signs and clinical symptoms of dengue, malaria, leptospirosis and rickettsioses. A considerable proportion of individuals (32.93%) knew very little about "tick fever", thinking that is was transmitted by mosquitos. They mentioned intestinal parasitoids, malaria, dengue, and "evil eye" among the causes of febrile syndromes. "Tick fever" is linked by its name to the bite of the tick. Furthermore, the treatments for febrile syndromes mentioned by interviewees are associated to those commonly used in western medicine and medicinal plants. Conclusions: There is a need for educational programs in rural areas, to raise awareness about these potential lethal conditions that can be effectively treated.

Resumo Introdução: Nos anos de 2006 e 2008, dois surtos letais de riquetsiose foram relatados em áreas rurais de Urabá, caracterizados pela falta de atenção imediata para o diagnóstico e tratamento com antibióticos. Objetivo: Descrever aspectos socioculturais do conhecimento, atitudes e práticas de síndromes febris e "febre do carrapato" em áreas rurais de Antioquia, Urabá. Materiais e métodos: Realizou-se estudo exploratório, através de inquéritos sobre CAP (conhecimentos, atitudes e práticas) e entrevistas semiestruturadas sobre síndromes febris e "febre do carrapato", um nome que se refere às doenças das riquetsioses na área. Foram aplicados 246 inquéritos sobre a CAP foram realizadas aos chefes de agregados familiares e nove pessoas foram entrevistadas. Resultados: Observou-se que as pessoas tendem a identificar os sinais e sintomas clínicos característicos da dengue, malária, leptospirose e até riquetsiose. Um grande número de pessoas demonstra baixo conhecimento sobre "febre do carrapato" e indicou que ela é transmitida por mosquitos (32,93%). Os entrevistados indicaram que as causas das diferentes síndromes febris se devem a parasitas intestinais, malária, dengue ou, como crença cultural, ao "mau olhado". A "febre do carrapato" o associa, pelo nome, com a mordida do carrapato. Além disso, o tratamento das síndromes febris referidas pelos entrevistados está intimamente relacionado ao uso comum da medicina ocidental e ao uso de "plantas medicinais". Conclusões. É necessário ter programas de educação nessas áreas rurais para que essas entidades potencialmente letais tenham um tratamento efetivo e acessível.

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.

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.

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.

Human spotted fever group rickettsioses are underappreciated in southern Taiwan, particularly for the species closely-related to Rickettsia felis.

BACKGROUND: Despite increased identification of spotted fever group rickettsioses (SFGR) in animals and arthropods, human SFGR are poorly characterized in Taiwan. METHODS: Patients with suspected Q fever, scrub typhus, murine typhus, leptospirosis, and dengue fever from April 2004 to December 2009 were retrospectively investigated for SFGR antibodies (Abs). Sera were screened for Rickettsia rickettsii Abs by indirect immunofluorescence antibody assay (IFA), and those with positive results were further examined for Abs against R. rickettsii, R. typhi, R. felis, R. conorii, and R. japonica using micro-immunofluorescence (MIF) tests. Polymerase chain reaction (PCR) for detection of SFGR DNA was applied in those indicated acute infections. Case geographic distribution was made by the geographic information system software. RESULTS: A total of 413 cases with paired serum, including 90 cases of Q fever, 47 cases of scrub typhus, 12 cases of murine typhus, 6 cases of leptospirosis, 3 cases of dengue fever, and 255 cases of unknown febrile diseases were investigated. Using IFA tests, a total of 49 cases with 47 (11.4%) and 4 (1.0%) cases had sera potentially positive for R. rickettsii IgG and IgM, respectively. In the 49 cases screened from IFA, MIF tests revealed that there were 5 cases of acute infections (3 possible R. felis and 2 undetermined SFGR) and 13 cases of past infections (3 possible R. felis and 10 undetermined SFGR). None of the 5 cases of acute infection had detectable SFGR DNA in the blood specimen by PCR. Possible acute infection of R. felis was identified in both one case of Q fever and scrub typhus. The geographic distribution of SFGR cases is similar with that of scrub typhus. CONCLUSIONS: Human SFGR exist and are neglected diseases in southern Taiwan, particularly for the species closely-related to R. felis.

First case series of emerging Rickettsial neonatal sepsis identified by polymerase chain reaction-based deoxyribonucleic acid sequencing.

PURPOSE: To detect and identify the aetiological agent in the peripheral blood from the cases of neonatal sepsis. MATERIALS AND METHODS: Four neonates from geographically different regions of South India presented with signs of neonatal sepsis and all the routine clinical and laboratory investigations were performed. Blood culture by Bac T Alert 3D was negative. To establish the aetiology, polymerase chain reaction (PCR) for eubacterial genome and subsequent amplification with Gram positive and Gram negative primers were performed followed by deoxyribonucleic acid (DNA) sequencing. RESULTS: PCR for the detection of eubacterial genome was positive in all the four neonates and further amplification with designed Gram positive and Gram negative primers revealed the presence of Gram negative bacteria. The amplicons were identified as Orientia tsutsugamushi in three neonates and Coxiella burnetti in the other neonate. Multalin analysis was done to further characterise the strain variation among the three strains. CONCLUSION: PCR-based DNA sequencing is a rapid and reliable diagnostic tool to identify the aetiological agents of neonatal sepsis. This is the first case series of emerging Rickettsial neonatal sepsis in India .

Rickettsioses in the central hills of Sri Lanka: serological evidence of increasing burden of spotted fever group.

OBJECTIVES: To study the epidemiology, clinical features, and changing pattern of rickettsial infections on the western slopes of the hilly Central Province of Sri Lanka over 6 years. METHODS: All patients with rickettsial infections who presented to the Teaching Hospital, Peradeniya were studied prospectively from January 2002 to December 2007. An immunofluorescent antibody assay (IFA) was used to confirm the diagnosis. RESULTS: Of the 371 clinical cases of rickettsial infection, 122 underwent IFA to confirm the diagnosis. Species-specific IgG antibodies were positive in 105/122 (86.1%) cases: 43/105 (40.9%) to Rickettsia conorii and 6/105 (5.7%) to Orientia tsutsugamushi, with mixed antibody reactivity to more than one antigen in 56/105 (53.3%) cases, including Rickettsia typhi in 27/105 (25.7%). Among those with mixed IgG reactivity, IgM assays were used to detect pathogens responsible for acute infections. Finally, a total of 55 spotted fever group (SFG) infections, seven scrub typhus infections, and one case of murine typhus were identified. Of the 105 positive cases, 53 (50.5%) were male and 52 (49.5%) were female, and the mean age was 40 years (range 11-83 years). In the SFG patients, 13/55 (24%) had severe vasculitis with fern leaf type skin necrosis and 17/55 (31%) had arthritis. Three patients (5%) had an altered level of consciousness. A patient with scrub typhus had transient deafness. None of the 105 patients had an eschar. CONCLUSIONS: It appears that SFG rickettsioses are on the rise in the hilly Central Province of Sri Lanka, whilst murine typhus and scrub typhus are present at a lower rate.

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.

Arthropod-borne bacterial diseases in pregnancy.

Arthropod-borne bacterial diseases affect more than 25,000 Americans every year and thousands more around the world. These infections present a diagnostic dilemma for clinicians because they mimic many other pathologic conditions and are often low on or absent from the differential diagnosis list. Diagnosis is particularly challenging during pregnancy, as these infections may mimic common pregnancy-specific conditions, such as typical and atypical preeclampsia, or symptoms of pregnancy itself. Concerns regarding the safety in pregnancy of some indicated antibiotics add a therapeutic challenge for the prescriber, requiring knowledge of alternative therapeutic options for many arthropod-borne bacterial diseases. Physicians, especially those in endemic areas, must keep this class of infections in mind, particularly when the presentation does not appear classic for more commonly seen conditions. This article discusses presentation, diagnosis, and treatment of the most common of these arthropod-borne bacterial diseases, including Lyme disease, Rocky Mountain spotted fever, tick-borne relapsing fever, typhus, plague, cat-scratch disease, and Carrión disease.

Imaging of rickettsial, spirochetal, and parasitic infections.

This article is an update and literature review of the clinical and neuroimaging findings of the commonly known rickettsial, spirochetal, and eukaryotic parasitic infections. Being familiar with clinical presentation and imaging findings of these infections is crucial for early diagnosis and treatment especially in patients who live in or have a travel history to endemic regions or are immunocompromised.

[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.

A case of rickettsialpox in Northern Europe.

We report the first case of rickettsialpox caused by Rickettsia akari in the Netherlands. The diagnosis was suspected based on clinical grounds and was confirmed by Western blot analysis with cross-adsorption. Because the arthropod vector (Liponyssoides sanguineus) is ubiquitous, we suspect that the disease is under-diagnosed in non-endemic areas.

A clear and present danger: tick-borne diseases in Europe.

Ticks can transmit a variety of viruses, bacteria or parasites that can cause serious infections or conditions in humans and animals. While tick-borne diseases are becoming an increasing and serious problem in Europe, tick-borne diseases are also responsible for major depressions in livestock production and mortality in sub-Saharan Africa, Latin America and Asia. This review will focus on the most important circulating tick-transmitted pathogens in Europe (Borrelia spp., Anaplasma phagocytophilum, Babesia spp., tick-borne encephalitis virus, Rickettsia spp. and Crimean-Congo hemorrhagic fever virus).

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.