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Stephen J Dumler - One of the best experts on this subject based on the ideXlab platform.
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A morphological and molecular study of Anaplasma phagocytophilum transmission events at the time of Ixodes ricinus tick bite
Acta Veterinaria Scandinavica, 2010Co-Authors: Erik Georg Granquist, Stephen J Dumler, Mona Aleksandersen, Karin Bergström, Wenche O Torsteinbø, Snorre StuenAbstract:Background Anaplasma phagocytophilum is the causative agent of Human Granulocytic Anaplasmosis (HGA) in Humans and tick-borne fever (TBF) in ruminants. The bacterium invades and replicates in phagocytes, especially in polymorphonuclear granulocytes.
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current management of Human Granulocytic Anaplasmosis Human monocytic ehrlichiosis and ehrlichia ewingii ehrlichiosis
Expert Review of Anti-infective Therapy, 2009Co-Authors: Rachael J Thomas, Stephen J Dumler, Jason A CarlyonAbstract:Anaplasma phagocytophilum, Ehrlichia chaffeensis and Ehrlichia ewingii are emerging tick-borne pathogens and are the causative agents of Human Granulocytic Anaplasmosis, Human monocytic ehrlichiosis and E. ewingii ehrlichiosis, respectively. Collectively, these are referred to as Human ehrlichioses. These obligate intracellular bacterial pathogens of the family Anaplasmataceae are transmitted by Ixodes spp. or Amblyomma americanum ticks and infect peripherally circulating leukocytes to cause infections that range in clinical spectra from asymptomatic seroconversion to mild, severe or, in rare instances, fatal disease. This review describes: the ecology of each pathogen; the epidemiology, clinical signs and symptoms of the Human diseases that each causes; the choice methods for diagnosing and treating Human ehrlichioses; recommendations for patient management; and is concluded with suggestions for potential future research.
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Human Granulocytic Anaplasmosis
Infectious Disease Clinics of North America, 2008Co-Authors: Johan S Bakken, Stephen J DumlerAbstract:Tick-borne infections have been recognized in the United States for more than a century. Patients who present with nonspecific fever after exposure to ticks should be evaluated by clinical examination and routine laboratory testing to determine if the illness is potentially a tick-borne infection. This article focuses on the diagnosis and management of Human Granulocytic Anaplasmosis (HGA) caused by Anaplasma phagocytophilum.
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sequential analysis of anaplasma phagocytophilum msp2 transcription in murine and equine models of Human Granulocytic Anaplasmosis
Clinical and Vaccine Immunology, 2008Co-Authors: Diana G Scorpio, Nicole C Barat, Christian M Leutenegger, Jeannine M Berger, John E Madigan, Stephen J DumlerAbstract:Anaplasma phagocytophilum causes Human Granulocytic Anaplasmosis by inducing immunopathologic responses. Its immunodominant Msp2 protein is encoded by a family of >100 paralogs. Msp2 (msp2) expression modulates in the absence of immune pressure, and prolonged in vitro passage modulates in vivo virulence. Because programmed MSP2 expression occurs in Anaplasma marginale, we hypothesized a similar event in A. phagocytophilum in vivo, with specific Msp2 expression triggering immunopathologic injury or clinical manifestations of disease. We examined msp2 transcripts in 11 B6 mice and 6 horses inoculated with low- or high-passage A. phagocytophilum Webster strain. Blood was sequentially obtained through 3 weeks postinfection for msp2 reverse transcription-PCR. Horses were additionally assessed for clinical manifestations, seroconversion, complete blood count, blood chemistry, and cytokine gene transcription. In both species, there was no consistent emergence of msp2 transcripts, and all 22 msp2 variants were detected in both passage groups. Clinical severity was much higher for high-passage-infected than for low-passage-infected horses, preceded by higher levels of blood gamma interferon transcription on day 7. Antibody was first detected on day 7, and all horses seroconverted by day 22, with a trend toward lower antibody titers in low-passage-infected animals. Leukocyte and platelet counts were similar between experimental groups except on day 13, when low-passage-infected animals had more profound thrombocytopenia. These findings corroborate studies with mice, where msp2 diversity did not explain differences in hepatic histopathology, but differ from the paradigm of low-passage A. phagocytophilum causing more significant clinical illness. Alteration in transcription of msp2 has no bearing on clinical disease in horses, suggesting the existence of a separate proinflammatory component differentially expressed with changing in vitro passage.
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Human Granulocytic Anaplasmosis and macrophage activation
Clinical Infectious Diseases, 2007Co-Authors: Stephen J Dumler, Nicole C Barat, Christopher E Barat, Johan S BakkenAbstract:Patients with Human Granulocytic Anaplasmosis present with fever, thrombocytopenia, leukopenia, and an elevated aspartate transaminase level. Clinical and histopathologic features of severe disease suggest macrophage activation. Twenty-nine patients with Human Granulocytic Anaplasmosis had higher ferritin, interleukin-10, interleukin-12 p70, and interferon-γ levels than did control subjects matched for age and sex; severity correlated with triglyceride, ferritin, and interleukin-12 p70 levels. Several severely affected patients had cases that fulfilled macrophage activation syndrome diagnostic criteria. Macrophage activation and excessive cytokine production may belie tissue injury associated with Ananplasma phagocytophilum infection.
Franc Strle - One of the best experts on this subject based on the ideXlab platform.
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comparison of clinical and laboratory characteristics of patients fulfilling criteria for proven and probable Human Granulocytic Anaplasmosis
Microbes and Infection, 2015Co-Authors: Stanka Lotricfurlan, Tatjana Avsiczupanc, Tereza Rojko, Miro Petrovec, Mateja Jelovsek, Lara Lusa, Franc StrleAbstract:To assess the value of clinical definitions for Human Granulocytic Anaplasmosis (HGA) epidemiological, clinical and laboratory findings in 50 adult patients with proven HGA (Anaplasma phagocytophilum isolated from blood, and/or positive PCR result, and/or seroconversion or ≥4−fold change in serum IFA antibody titres to A. phagocytophilum) and 46 patients with probable HGA (demonstration of serum antibodies to A. phagocytophilum in titres ≥1:256) were compared. Patients with proven HGA were older (55 versus 43.5 years; p = 0.001), were more often treated with doxycycline (31/50, 62% versus 11/46, 23.9%; p < 0.001), more frequently reported chills (40/50, 80% versus 17/46, 36.9%; p < 0.001), myalgia (37/50, 74% versus 21/46, 45.7%; p = 0.005) and cough (10/50, 20% versus 2/46, 4.4%; p = 0.02), and had more often abnormal laboratory findings such as thrombocytopenia (45/50, 90% versus 22/46, 47.8%; p < 0.001), abnormal liver function test results (45/50, 87% versus 22/46, 47.8%; p < 0.001), leukopenia (38/50, 76% versus 21/46, 45.7%; p = 0.002) and elevated serum CRP concentration (48/50, 96% versus 31/46, 67.4%; p < 0.001). The dissimilarities imply that in some patients fulfilling criteria for probable HGA the signs and symptoms most likely are not the result of a recent infection with A. phagocytophilum and indicate that clinical definitions used in the present study have a distinctive value.
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severe Human Granulocytic Anaplasmosis transmitted by blood transfusion
Emerging Infectious Diseases, 2012Co-Authors: Matjaz Jereb, Blaz Pecaver, Janez Tomazic, Igor Muzlovic, Tatjana Avsiczupanc, Tanja Premrusrsen, Snezna Levicnikstezinar, Primoz Karner, Franc StrleAbstract:Human Granulocytic Anaplasmosis (HGA), an emerging tickborne zoonosis caused by Anaplasma phagocytophilum, has been recognized in the United States since 1994 and in Europe since 1996 (1,2). Most patients acquire A. phagocytophilum infection by tick bite, although individual cases of nosocomial, perinatal, and transfusion-associated transmission have been reported (3–5). We report a case of severe HGA acquired from blood transfusion.
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concomitant Human Granulocytic Anaplasmosis and lyme neuroborreliosis
Clinical Microbiology and Infection, 2009Co-Authors: Stanka Lotricfurlan, Eva Ruzicsabljic, Franc StrleAbstract:Tick-transmitted zoonoses such as Human Granulocytic Anaplasmosis (HGA), Lyme borreliosis and tick-borne encephalitis (TBE) are endemic in several European countries, including Slovenia. Ixodes ricinus, the most prevalent species of hard ticks in Slovenia, is the principal vector for Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and TBE virus [1]. Information on clinically manifested co-infections with tick-transmitted pathogens is incomplete. Findings from the USA indicate that the frequency of simultaneous diseases caused by infection with more than one tick-borne pathogen is low and varies among geographic regions. Reports from the USA involve cases with concurrent erythema migrans (early localised borrelial skin infection) and HGA [2]. Data on co-infections with different tick-borne pathogens in Europe are limited to the reports on co-infections with TBE virus and B. burgdorferi s.l. in patients with acute meningitis [1] and on co-infection with TBE virus and A. phagocytophilum [3]. The other possible combinations in European populations, including infections with A. phagocytophilum and B. burgdorferi s.l., have been indicated mainly but not exclusively by serological findings [3–5]. Residents of Slovenia are often exposed to ticks and thus are at risk of acquiring infection with multiple tick-borne pathogens. Herein we present a patient with acute HGA, established by positive PCR result and seroconversion, in whom borrelial infection was ascertained by the isolation of Borrelia garinii from cerebrospinal fluid (CSF). C A S E P R E S E N T A T I O N
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epidemiological clinical and laboratory characteristics of patients with Human Granulocytic Anaplasmosis in slovenia
Wiener Klinische Wochenschrift, 2006Co-Authors: Stanka Lotricfurlan, Tatjana Avsiczupanc, Tereza Rojko, Miro Petrovec, Franc StrleAbstract:Human Granulocytic Anaplasmosis (HGA) has been recently recognized as an emerging tick-borne disease. Several reports indicate the presence of infection with Anaplasma phagocytophilum in Europe. Between January 1996 and December 2004, 24 adult patients with proven HGA were identified in a prospective study conducted at the Department of Infectious Diseases, University Medical Center Ljubljana, Slovenia, on the etiology of febrile illnesses occurring within 30 days after a tick bite. The diagnosis of acute HGA was established from seroconversion in 18 (75%) patients or at least a four-fold increase in antibody titers to A. phagocytophilum antigens in six (25%) patients and molecular identification of ehrlichial organisms in 15 (62.5%) patients. Clinical characteristics and laboratory findings were similar to those reported from the other European countries. All the patients had an acute febrile illness with headache, malaise, myalgia and/or arthralgia. Leukopenia was found in 16 (66.7%) patients, thrombocytopenia in 20 (83.3%), abnormal liver function test results in 23 (95.8%), elevated erythrocyte sedimentation rates in 18 (75%), and elevated concentration of C-reactive protein in 23 (95.8%). The disease course was relatively mild; none of the patients died and no long-term sequelae were found during a follow-up of one year even though only 15 (62.5%) were treated with doxycycline. At the examination one year after the first visit, 16/24 (66.7%) patients tested seropositive (≥1 : 256) for A. phagocytophilum antibody, and two years after the first visit positive titers were still present in 10/18 (55.6%) patients.
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the clinical assessment treatment and prevention of lyme disease Human Granulocytic Anaplasmosis and babesiosis clinical practice guidelines by the infectious diseases society of america
Clinical Infectious Diseases, 2006Co-Authors: Gary P. Wormser, Johan S Bakken, Franc Strle, Raymond J Dattwyler, Eugene D Shapiro, John J Halperin, Allen C Steere, Mark S Klempner, Peter J Krause, G StanekAbstract:Evidence-based guidelines for the management of patients with Lyme disease, Human Granulocytic Anaplasmosis (formerly known as Human Granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.
Myoungdon Oh - One of the best experts on this subject based on the ideXlab platform.
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co infection of scrub typhus and Human Granulocytic Anaplasmosis in korea 2006
Journal of Korean Medical Science, 2019Co-Authors: Chisook Moon, Myoungdon Oh, Yee Gyung Kwak, Jae Myung Kang, Wan Beom Park, Sang Won ParkAbstract:BACKGROUND: Scrub typhus, severe fever with thrombocytopenia syndrome (SFTS) and Human Granulocytic Anaplasmosis (HGA) are important arthropod-borne infectious diseases in Korea and share a common point that they are transmitted by arthropod bites mostly during outdoor activities and there are considerable overlaps of epidemiologic and clinical features at presentation. We investigated the co-infection of these infections. METHODS: The study subjects were patients with laboratory-confirmed scrub typhus who were enrolled retrospectively in 2006. SFTS virus (SFTSV) infection was confirmed by a reverse transcriptase polymerase chain reaction (PCR) to amplify partial L segment of SFTSV for molecular diagnosis. HGA was confirmed by a nested PCR to amplify 16S rRNA gene of Anaplasma phagocytophilum. Direct sequencing of the positive PCR products was performed. Clinical features of co-infected subjects were described. RESULTS: One-hundred sixty-seven patients with scrub typhus were included in the analysis. Co-infection of A. phagocytophilum was identified in 4.2% of scrub typhus patients (7/167). The route of co-infection was uncertain. The co-infected patients had not different clinical manifestations compared to the patients with scrub typhus only. All the study subjects were negative for SFTSV. CONCLUSION: We found retrospective molecular evidence of the co-infection of scrub typhus and HGA in Korea. HGA may be more prevalent than expected and need to be considered as an important differential diagnosis of febrile patients in Korea.
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Human Granulocytic Anaplasmosis as a cause of febrile illness in korea since at least 2006
American Journal of Tropical Medicine and Hygiene, 2017Co-Authors: Jongyoun Yi, Su Jin Choi, Mee Kyung Ko, Myoungdon OhAbstract:Human Granulocytic Anaplasmosis (HGA) is a tick‐borne rickettsial zoonosis with fever, thrombocytopenia, and leukopenia. HGA has been reported in Korea in 2013 but it is uncertain how long it has existed. A retrospective study was conducted on patients who underwent bone marrow examination due to fever and cytopenia, with no clear hematologic or microbiologic causes, from 2003 through 2012. Laboratory diagnosis was made by detecting 16S rRNA genes of Anaplasma phagocytophilum from the stored blood samples. Among the 70 patients, five (7.1%) HGA cases were found, and the earliest case dated back to 2006. Two cases met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH) and were fatal. Although HGA has been prevalent in Korea since at least 2006, it is not always diagnosed and has posed a possible lethal health risk to the people in Korea. HGA should be considered as a cause of fever with cytopenia or HLH.
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Human Granulocytic Anaplasmosis south korea 2013
Emerging Infectious Diseases, 2014Co-Authors: Jongyoun Yi, Won Sup Oh, Su Jin Choi, Pyoeng Gyun Choe, Myoungdon OhAbstract:We report a patient with Human Granulocytic Anaplasmosis in South Korea. The patient had fever and thrombocytopenia. Human Granulocytic Anaplasmosis was confirmed by seroconversion, PCR, and sequence analysis for Anaplasma phagocytophilum. Morulae were observed in the cultured HL-60 cells inoculated with blood from the patient.
Gary P. Wormser - One of the best experts on this subject based on the ideXlab platform.
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accuracy of diagnosis of Human Granulocytic Anaplasmosis in china
Emerging Infectious Diseases, 2016Co-Authors: Gary P. WormserAbstract:: In 2008, Human Granulocytic Anaplasmosis (HGA) was reported from China. However, the clinical and laboratory findings, including reports of nosocomial transmission, were inconsistent with those reported for HGA in the United States. In 2012, it was demonstrated that the patients described in the 2008 report had all been infected with a newly discovered bunyavirus, severe fever with thrombocytopenia syndrome virus, which causes an illness with the same clinical features described for the patients in the 2008 report. This finding raises the question of HGA misdiagnosis in China and establishes the need for further studies to determine whether HGA occurs there.
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Diagnosis, treatment, and prevention of lyme disease, Human Granulocytic Anaplasmosis, and babesiosis: A review
JAMA - Journal of the American Medical Association, 2016Co-Authors: Edgar Sánchez, Edouard Vannier, Gary P. Wormser, Linden T HuAbstract:Importance: Lyme disease, Human Granulocytic Anaplasmosis (HGA), and babesiosis are emerging tick-borne infections.\n\nObjective: To provide an update on diagnosis, treatment, and prevention of tick-borne infections.\n\nEvidence Review: Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015.\n\nFindings: The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration-approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment.\n\nConclusions and Relevance: Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription of a 14-day course of oral doxycycline for early neurologic Lyme disease in ambulatory patients. The duration of antimicrobial therapy for babesiosis in severely immunocompromised patients should be extended to 6 weeks or longer.
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differences and similarities between culture confirmed Human Granulocytic Anaplasmosis and early lyme disease
Journal of Clinical Microbiology, 2013Co-Authors: Gary P. Wormser, Lois Zentmaier, Maria E Aguerorosenfeld, John Nowakowski, Robert B Nadelman, Diane Holmgren, Donna Mckenna, Susan Bittker, Denise Cooper, Dionysios LiverisAbstract:Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum, the cause of Human Granulocytic Anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (P = 0.003) and had a higher body temperature on presentation (P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389, P = 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.
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lyme disease and Human Granulocytic Anaplasmosis coinfection impact of case definition on coinfection rates and illness severity
Clinical Infectious Diseases, 2013Co-Authors: Harold W Horowitz, Maria E Aguerorosenfeld, Diane Holmgren, Donna Mckenna, Ira Schwartz, Gary P. WormserAbstract:BACKGROUND: Lyme disease is transmitted by the bite of the Ixodes scapularis tick, which can also transmit Anaplasma phagocytophilum, the cause of Human Granulocytic Anaplasmosis (HGA). Conflicting data exist on the frequency of coinfection and on whether Lyme-HGA coinfected patients have more symptoms than patients with Lyme disease alone. METHODS: Blood culture and serology were used to detect HGA infection in patients with early Lyme disease who presented with erythema migrans. The rate of coinfection was determined using different definitions. The clinical and laboratory features of Lyme-HGA coinfection were compared with that of the individual infections. RESULTS: Among 311 patients with erythema migrans, the frequency of coinfection with HGA varied from 2.3% to 10.0%, depending on the definition used (P < .001). Only 1 of 4 groups with presumed coinfection had significantly more symptoms than patients with Lyme disease alone P < .05. High fever and cytopenia were less common in Lyme-HGA coinfection than in patients with HGA alone. CONCLUSION: The results of this study indicate that how HGA is defined in patients with early Lyme disease has an impact on the apparent rate of coinfection and the severity of illness. The findings also suggest that HGA may be less severe than is usually believed, suggesting the existence of referral bias in testing patients preferentially who present with high fever or cytopenia.
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dissociation between inhibition and killing by levofloxacin in Human Granulocytic Anaplasmosis
Vector-borne and Zoonotic Diseases, 2006Co-Authors: Gary P. Wormser, Sam R Telford, Alina Filozov, Sandeepa Utpat, Russell S Kamer, Dionysios Liveris, Guiqing Wang, Lois Zentmaier, Ira B Schwartz, Maria E AguerorosenfeldAbstract:Human Granulocytic Anaplasmosis (HGA) is a potentially fatal tick-borne infection caused by Anaplasma phagocytophilum. Treatment options are limited for this entity, with doxycycline being the drug of choice. Certain fluoroquinolones such as levofloxacin are active against A. phagocytophilum in vitro. We report a hospitalized patient with HGA who improved coincident with a 13-day course of levofloxacin therapy, but clinically and microbiologically relapsed 15 days after completion of treatment. Relapse of infection after levofloxacin therapy was reproduced in a severe combined immune-deficient (SCID) mouse infection model. Quinolone therapy should not be considered curative of HGA.
Seon Do Hwang - One of the best experts on this subject based on the ideXlab platform.
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recent increase of Human Granulocytic Anaplasmosis and co infection with scrub typhus or korean hemorrhagic fever with renal syndrome in korea
Journal of Korean Medical Science, 2019Co-Authors: Joohee Hwang, Seung Hee Choi, Mir Jeon, Seon Do HwangAbstract:: We report 17 patients with Human Granulocytic Anaplasmosis between January 2015 and September 2018 at two tertiary university hospitals in Korea. Monthly incidence peaked in May and June. Among these patients, we identified three who were co-infected with scrub typhus, and one patient with hemorrhagic fever with renal syndrome.
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case report polymerase chain reaction testing of tick bite site samples for the diagnosis of Human Granulocytic Anaplasmosis
American Journal of Tropical Medicine and Hygiene, 2017Co-Authors: Nara Yoon, Sook Jin Jang, Seon Do HwangAbstract:Human Granulocytic Anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium that was first identified as a Human pathogen in 1994.1 In Korea, the first case of HGA was reported in 2013 as an emerging infectious disease.2 HGA is mainly transmitted by ticks of the Ixodes species, which are common vectors of Lyme disease and babesiosis.3 As patients with HGA develop nonspecific symptoms such as fever, malaise, headache, and chills, the diagnosis may be challenging. As such, differential diagnoses typically include rickettsial diseases, infectious mononucleosis, Lyme disease, and West Nile virus infection.4 Isolation of A. phagocytophilum in culture is difficult and usually takes longer than 30 days.5 Therefore, the use of polymerase chain reaction (PCR) testing for the rapid diagnosis of HGA is important. Herein, we aimed to evaluate the usefulness of a crust tissue at the tick-bite site for the diagnosis of HGA via PCR testing.