Newly Recognized Spotted Fever Group Rickettsia as Cause of Severe Rocky Mountain Spotted Fever-Like Illness, Northern California, USA.

The incidence of spotted fever group (SFG) rickettsioses in the United States has tripled since 2010. Rocky Mountain spotted fever, the most severe SFG rickettsiosis, is caused by Rickettsia rickettsii. The lack of species-specific confirmatory testing obfuscates the relative contribution of R. rickettsii and other SFG Rickettsia to this increase. We report a newly recognized rickettsial pathogen, Rickettsia sp. CA6269, as the cause of severe Rocky Mountain spotted fever-like illness in 2 case-patients residing in northern California. Multilocus sequence typing supported the recognition of this pathogen as a novel Rickettsia genotype most closely related to R. rickettsii. Cross-reactivity observed for an established molecular diagnostic test indicated that Rickettsia sp. CA6269 might be misidentified as R. rickettsii. We developed a Rickettsia sp. CA6269-specific real-time PCR to help resolve this diagnostic challenge and better characterize the spectrum of clinical disease and ecologic epidemiology of this pathogen.

Development of an all-in-one real-time PCR assay for simultaneous detection of spotted fever group rickettsiae, severe fever with thrombocytopenia syndrome virus and hantaan virus prevalent in central China.

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.

Japanese spotted fever complicated with pleural effusion in Zhejiang province, China: a case report and literature review.

INTRODUCTION: Japanese spotted fever (JSF) mainly occurs in Japan; however, it has been increasingly reported in China. JSF is typically characterized by fever, rash, and eschar, in addition to non-specific symptoms. Yet, reports on the pulmonary indicators in JSF are limited. Herein, we report an unusual case of JSF associated with pleural effusion and pneumonia, in which the pathogen was identified via blood next-generation sequencing (NGS). CASE PRESENTATION: We report a case of a 33-year-old woman who presented with fever for five days, rash for two days, and myalgia, fatigue, and edema for one day. She had recently been on vacation when an unknown insect bit her. The doctors at the local primary hospital considered a bacterial infection and administered dexamethasone, ceftriaxone, indomethacin, and anti-allergy agents, but the symptoms persisted. A rash without pruritus or pain developed gradually over the entire body and face. We considered rickettsial infection and administered doxycycline and levofloxacin. Metagenomic NGS from blood confirmed the presence of Rickettsia japonica (R. japonica). Abdominal computed tomography revealed bilateral pleural effusion with two atelectasis; patchy shadows with blurred edges, and uniform enhancement in both lower lungs. After several days of treatment, the symptoms and laboratory results improved. A literature review of the epidemiology of R. japonica and JSF in China, characteristics of JSF, and related pulmonary changes, and technology to diagnose JSF is provided. CONCLUSIONS: JSF has a variety of symptoms and is becoming increasingly popular in China. Clinical doctors need to identify it carefully.

Japanese spotted fever in an area endemic to SFTS virus: Case report and review of the literature.

RATIONALE: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS: Doxycycline treatment for 1 week. OUTCOMES: The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.

Spotted fever group rickettsial infection in dogs and their ticks from domestic-wildlife interface areas in southeastern Brazil / Infecção por rickettsias do Grupo da Febre Maculosa em cães e carrapatos de áreas de interface doméstico-silvestre no sudeste Brasileiro

Abstract Rickettsia rickettsii is the causative agent of Brazilian spotted fever (BSF), for which humans and dogs are both susceptible. Dogs are sentinels in serological surveys, however, canine disease is rarely reported. Therefore, we aimed to evaluate natural infection by spotted fever group (SFG) Rickettsia spp. in dogs and ticks collected from domiciles close to forest fragments, featuring domestic-wildlife interface areas. Samples from 115 dogs and 135 ixodids were assessed by polymerase chain reactions (PCR) targeting the gltA gene for Rickettsia spp. and the ompA gene for the SFG rickettsial species. One dog (0.87%; 1/115) was positive for R. rickettsii. This dog presented nonspecific laboratory and clinical abnormalities (thrombocytopenia, hyperproteinemia, lymph node enlargement, emaciation, anorexia, and lethargy). Rickettsia parkeri was identified in 2.96% (4/135) of the ticks (Amblyomma sculptum, A. aureolatum, and Rhipicephalus sanguineus). This study confirmed the presence of SFG bacteria in non-endemic and preserved locations, where domestic and wild populations interact. We reinforce the fact that the dog is susceptible to natural R. rickettsii infection. Although this is a rare finding, preventive measures should be taken against BSF in the studied areas. Finally, R. parkeri infection is possibly being demonstrated in A. sculptum for the first time.

Resumo Rickettsia rickettsii é o agente causador da Febre Maculosa Brasileira (FMB), doença na qual humanos e cães são susceptíveis. Os cães são sentinelas nos inquéritos sorológicos, contudo, a doença canina é raramente descrita. Assim sendo, objetivou-se avaliar a infecção natural por Rickettsia spp. do Grupo da Febre Maculosa (GFM) em cães e carrapatos obtidos de domicílios próximos a fragmentos de mata, caracterizando áreas de interface doméstico-silvestre. Amostras de 115 cães e 135 ixodídeos foram avaliadas pela reação em cadeia da polimerase (PCR) tendo como alvo o gene gltA de Rickettsia spp. e o gene ompA das espécies do GFM. Um cão (0,87%; 1/115) foi positivo para R. rickettsii. Este animal apresentou alterações clínicas e laboratoriais inespecíficas (trombocitopenia, hiperproteinemia, linfonodos edemaciados, emagrecimento, anorexia e letargia). Rickettsia parkeri foi identificada em 2,96% (4/135) dos carrapatos (Amblyomma sculptum, A. aureolatum e Rhipicephalus sanguineus). Este estudo confirmou a presença de bactérias do GFM em locais preservados e não endêmicos, onde populações domésticas e silvestres interagem. Reforçamos o fato do cão ser susceptível à infecção natural por R. rickettsii. Embora este seja um achado raro, medidas preventivas devem ser tomadas contra a FMB nas áreas estudadas. Em última análise, a infecção por R. parkeri possivelmente está sendo demonstrada pela primeira vez em A. sculptum.

Fiebre manchada de evolución fatal en la provincia de Salta / Fatal spotted fever in Salta province

Describimos el caso de un varón de 17 años oriundo de la ciudad de Salta quien, 10 días después de visitar una zona rural de la provincia homónima, ingresó a nuestro hospital por convulsiones febriles. Durante la internación presentó exantema seguido de disfunción orgánica múltiple, la que evolucionó rápidamente hacia shock séptico irreversible y muerte a las 48 horas de su admisión. El diagnóstico serológico -altos títulos de IgM e IgG anti-Rickettsia spp. por inmunofluorescencia indirecta- arribó post mortem. Las rickettsiosis del grupo de las fiebres manchadas son transmitidas por garrapatas, tienen distribución global y en varios países continúan siendo subdiagnosticadas debido a una baja sospecha clínica. En las provincias del noroeste argentino se agrega la carencia de un laboratorio regional capacitado para efectuar el diagnóstico etiológico. Esta limitación es crítica porque en esa región del país ya ha sido documentada la presencia de las formas graves de la enfermedad, usualmente debidas a R. rickettsii. Dado que las fiebres manchadas se presentan como sindromes febriles inespecíficos y los componentes del ciclo enzoótico están presentes en vastas áreas geográficas, incluso en algunas aún no consideradas endémicas para rickettsiosis, su diagnóstico nunca debe ser subestimado. Con el tratamiento antibiótico adecuado instaurado en tiempo oportuno, el pronóstico de este grupo de enfermedades potencialmente mortales mejora en forma drástica.

We describe the case of a 17-year-old male patient living in Salta city who, 10 days after visiting a rural area in Salta province, was hospitalized for febrile seizures. Shortly after admission, he developed an exanthema followed by a multiple organ dysfunction that evolved to irreversible septic shock followed by death 48 hours after admission. Serological diagnosis -high IgM and IgG anti-Rickettsia spp. antibody titres as detected by indirect immunofluorescence- arrived post mortem. Spotted fever group rickettsioses are tick-borne diseases distributed worldwide and continue being under diagnosed in several countries mainly due to a low clinical suspicion. In the north-western provinces of Argentina there is also the limitation of not counting with a regional laboratory to perform the etiological diagnosis. This is crucial because the severe forms of the disease, which are commonly caused by R. rickettsii, have been already documented in the region. Given that spotted fevers have broadly unspecific febrile presentations and the components of the enzootic cycle are present even in geographic areas not yet considered to be endemic for tick borne diseases, their diagnosis should not be underestimated. If the adequate antibiotic treatment is administered timely, the prognosis of this group of life-threatening diseases improves drastically.

Caso autóctono de fiebre manchada por Rickettsia parkeri en Ensenada, Buenos Aires / Autochthonous case of spotted fever caused by Rickettsia parkeri in Ensenada, Buenos Aires

Se comunica un caso autóctono de fiebre manchada por Rickettsia parkeri en un adulto residente en Ensenada, Provincia de Buenos Aires ocurrido en el verano de 2016. El cuadro, secundario a una mordedura de garrapata en la pierna izquierda, se presentó como un síndrome febril agudo con deterioro del estado general, cefalea, mialgias, artralgias y exantema maculopapular. El sitio de la mordedura presentaba una úlcera con escara necrótica. El diagnóstico se confirmó por conversión serológica IgG anti-antígenos del género Rikettsia. La secuencia de un fragmento del gen gltA amplificado a partir de la lesión de piel presentó 100% identidad nucleotídica con las secuencias de cepas de R. parkeri aisladas en Argentina y en varios países de América. El paciente evolucionó favorablemente al tratamiento con doxiciclina.

We present a case of spotted fever occurred in an adult residing in Ensenada, Buenos Aires province in February 2016. The patient presented with an acute febrile syndrome associated with a skin necrotic lesion on the left leg secondary to a tick bite. The general symptoms were a maculopapular rash, headache, myalgia, and arthralgias. Seroconversion of anti-Rickettsia specific IgG antibodies confirmed recent infection. The nucleotidic and aminoacidic sequences of a gltA gen fragment matched 100% the sequences of R. parkeri strains from Argentina and other countries of America. The patient responded well to treatment with doxycycline.

Una serie de casos fatales de fiebre manchada de las Montañas Rocosas en Sonora, México / A fatal case series of Rocky Mountain spotted fever in Sonora, México

Resumen Introducción. La fiebre manchada de las Montañas Rocosas es una infección muy letal, particularmente si no se diagnostica y se trata oportunamente. Objetivo. Describir el perfil clínico de los casos fatales de pacientes con fiebre manchada de las Montañas Rocosas, hospitalizados en Sonora, México. Materiales y métodos. Se analizó una serie de 47 defunciones por fiebre manchada de las Montañas Rocosas en el periodo de 2013 a 2016. El diagnóstico se confirmó mediante reacción en cadena de la polimerasa (PCR) o la cuadruplicación de los títulos de inmunoglobulina G (IgG) en muestras de suero pareadas analizadas mediante inmunofluorescencia indirecta. Se compararon las características clínicas y de laboratorio, estratificando a los sujetos en dos grupos: pediátricos y adultos. Resultados. No hubo diferencias en las manifestaciones clínicas entre los grupos; el exantema petequial fue el signo más frecuente (96 %), seguido por cefalea (70 %) y mialgias (67 %). La muerte ocurrió en el 55 % de los sujetos a pesar de haber recibido doxiciclina antes del quinto día del inicio de los síntomas. Los marcadores de laboratorio más frecuentes fueron trombocitopenia, falla hepática e insuficiencia renal. Conclusión. La fiebre manchada de las Montañas Rocosas es una enfermedad muy letal, lo cual puede estar relacionado con la ausencia de sospecha del diagnóstico y el retraso en la administración de doxiciclina, pero también con características atribuibles a Rickettsia rickettsii que inciden en la variabilidad de los resultados adversos que se han observado en regiones donde la enfermedad es frecuente.

Abstract Introduction: Rocky Mountain spotted fever is a highly lethal infectious disease, particularly if specific treatment with doxycycline is given belatedly. Objective: To describe the clinical profile of fatal Rocky Mountain spotted fever cases in hospitalized patients in the state of Sonora, México. Materials and methods: We conducted a cross-sectional study on a series of 47 deaths caused by Rickettsia rickettsii from 2013 to 2016. The diagnosis of Rocky Mountain spotted fever was confirmed in a single blood sample by polymerase chain reaction (PCR) or by a four-fold increase in immunoglobulin G measured in paired samples analyzed by indirect immunofluorescence. Clinical and laboratory characteristics were compared stratifying subjects into two groups: pediatric and adult. Results: There were no differences in clinical characteristics between groups; petechial rash was the most frequent sign (96%), followed by headache (70%) and myalgia (67%). Although that doxycycline was administered before the fifth day from the onset of symptoms, death occurred in 55% of patients. In clinical laboratory, thrombocytopenia, and biomarkers of liver acute failure and acute kidney failure were the most frequent. Conclusion: Rocky Mountain spotted fever remains as one of the most lethal infectious diseases, which may be related not only to the lack of diagnostic suspicion and delayed administration of doxycycline, but to genotypic characteristics of Rickettsia rickettsii that may play a role in the variability of the fatality rate that has been reported in other geographical regions where the disease is endemic.