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The obligatory intracellular bacterium Anaplasma phagocytophilum causes human granulocytic anaplasmosis, an emerging zoonosis. Anaplasma has limited biosynthetic and metabolic capacities, yet it effectively replicates inside of inclusions/vacuoles of eukaryotic host cells. Here, we describe a unique Type IV secretion system (T4SS) effector, ER-Golgi exit site protein of Anaplasma (EgeA). In cells infected by Anaplasma, secreted native EgeA, EgeA-GFP, and the C-terminal half of EgeA (EgeA-C)-GFP localized to Anaplasma-containing inclusions. In uninfected cells, EgeA-C-GFP localized to cis-Golgi, whereas the N-terminal half of EgeA-GFP localized to the ER. Pull-down assays identified EgeA-GFP binding to a transmembrane protein in the ER, Transport and Golgi organization protein 1 (TANGO1). By yeast two-hybrid analysis, EgeA-C directly bound Sec1 family domain-containing protein 1 (SCFD1), a host protein of the cis-Golgi network that binds TANGO1 at ER-Golgi exit sites (ERES). Both TANGO1 and SCFD1 localized to the Anaplasma inclusion surface. Furthermore, knockdown of Anaplasma EgeA or either host TANGO1 or SCFD1 significantly reduced Anaplasma infection. TANGO1 and SCFD1 prevent ER congestion and stress by facilitating transport of bulky or unfolded proteins at ERES. A bulky cargo collagen and the ER-resident chaperon BiP were transported into Anaplasma inclusions, and several ER stress marker genes were not up-regulated in Anaplasma-infected cells. Furthermore, EgeA transfection reduced collagen overexpression-induced BiP upregulation. These results suggest that by binding to the two ERES proteins, EgeA redirects the cargo-adapted ERES to pathogen-occupied inclusions and reduces ERES congestion, which facilitates Anaplasma nutrient acquisition and reduces ER stress for Anaplasma survival and proliferation. [ABSTRACT FROM AUTHOR]

Migratory birds play a dual role as potential reservoirs of tick-borne pathogens, and potential dispersers of pathogen-containing ticks during their migratory journeys. Ixodes ricinus, a prevalent tick species in Northern and Western Europe, serves as a primary vector for Anaplasma phagocytophilum—a bacterium with implications for human and animal health. There is limited information available regarding A. phagocytophilum in birds. Our investigation focused on A. phagocytophilum prevalence in ticks collected from migratory birds in southeastern Sweden. The identification of ticks involved both molecular analyses for species determination and morphological classification to ascertain the developmental stage. The presence of A. phagocytophilum was determined using real-time PCR. Of the 1115 ticks analyzed from 4601 birds, 0.9% (n = 10), including I. ricinus and Ixodes frontalis, tested positive for A. phagocytophilum. Notably, common blackbirds (Turdus merula) yielded the highest number of A. phagocytophilum-infected ticks. The findings suggest that A. phagocytophilum is present in a small proportion of ticks infesting migratory birds in southeastern Sweden. Consequently, the role of birds as hosts for ticks infected with A. phagocytophilum appears to be low, suggesting that birds seem to play a minor indirect role in the geographic dispersal of A. phagocytophilum. [ABSTRACT FROM AUTHOR]

Background: Human granulocytic anaplasmosis (HGA) is a vector-borne natural focal disease that is not officially registered in Ukraine. The first 13 cases of HGA in adults in Ukraine were identified in 2007. The purpose of our study was to develop a predictive model of HGA based on clinical and laboratory characteristics to develop a three-level standard case definition of HGA. Materials and Methods: Researchers examined 498 patients with suspected tick-borne infections and carried out a retrospective clinical and epidemiological analysis of 60 cases recruited from Lviv regional infectious disease hospitals. Logistic regression was used to create a model of the probability of the diagnosis of HGA depending on the presence of certain clinical and laboratory factors that, when examined, together may help to confirm a case of HGA. For logistic regression, eight clinical and laboratory factors were selected: history of tick bite, hyperthermia, signs of pharyngitis, changes in chest X-ray picture (enhancement of the pulmonary pattern and enlargement of the lung root boundaries), increased bilirubin (˃21 μmol/L), increased alanine aminotransferase (ALT ˃36 U/L), erythema migrans, and detected Lyme disease. Results: In the presence of all eight factors, the probability of HGA is 95.7%. When the five main signs are absent—signs of pharyngitis, changes in chest X-ray picture, increased bilirubin and ALT, and a history of tick bite—the probability of HGA in the patient dramatically decreases to 6.8%, meaning that HGA might be excluded. Conclusions: Based on the analysis of epidemiological, clinical, and laboratory signs, criteria for establishing a suspected, probable, and confirmed diagnosis of HGA have been developed to improve diagnosis. [ABSTRACT FROM AUTHOR]

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by the bacterium Anaplasma phagocytophilum. In this study, we report an indigenous case of clinically diagnosed HGA. The patient was a 41-year-old man who experienced a tick bite and later developed fever, chills, myalgia, malaise, thrombocytopenia, leukocytosis with a left shift, elevated hepatic transaminase levels, and splenomegaly upon admission to the hospital. Immunofluorescence assays detected seroconversion against A. phagocytophilum, whereas tests for spotted fever group rickettsiae, murine typhus, scrub typhus, Q fever, and ehrlichiosis were negative. ELISA and Western blot analysis using recombinant MSP2 protein confirmed the exposure to A. phagocytophilum. Oral doxycycline and intravenous ceftriaxone were prescribed, and the patient made a full recovery. Our findings indicate the presence of HGA on the main island of Taiwan. Precautions against tick bites should be taken when engaging in outdoor activities, and HGA should be considered by physicians in the differential diagnosis.

Introduction: Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum and transmitted through the deer tick. Most cases are mild and can be managed as an outpatient, but rare cases can produce severe symptoms.Case Report: A 43-year-old male presented with severe respiratory distress mimicking coronavirus disease 2019 (COVID-19). Labs and imaging were consistent with COVID-19; however, polymerase chain reaction was negative twice. Peripheral smear revealed inclusion bodies consistent with HGA.Conclusion: Human granulocytic anaplasmosis is an uncommon diagnosis and rarely causes severe disease. Recognition of unique presentations can aid in quicker diagnosis, especially when mimicking presentations frequently seen during the COVID-19 pandemic.

Migratory birds play a dual role as potential reservoirs of tick-borne pathogens, and potential dispersers of pathogen-containing ticks during their migratory journeys. Ixodes ricinus, a prevalent tick species in Northern and Western Europe, serves as a primary vector for Anaplasma phagocytophilum—a bacterium with implications for human and animal health. There is limited information available regarding A. phagocytophilum in birds. Our investigation focused on A. phagocytophilum prevalence in ticks collected from migratory birds in southeastern Sweden. The identification of ticks involved both molecular analyses for species determination and morphological classification to ascertain the developmental stage. The presence of A. phagocytophilum was determined using real-time PCR. Of the 1115 ticks analyzed from 4601 birds, 0.9% (n = 10), including I. ricinus and Ixodes frontalis, tested positive for A. phagocytophilum. Notably, common blackbirds (Turdus merula) yielded the highest number of A. phagocytophilum-infected ticks. The findings suggest that A. phagocytophilum is present in a small proportion of ticks infesting migratory birds in southeastern Sweden. Consequently, the role of birds as hosts for ticks infected with A. phagocytophilum appears to be low, suggesting that birds seem to play a minor indirect role in the geographic dispersal of A. phagocytophilum.

Background. In spring and summer, the population of the Baikal region regularly comes into contact with the pathogens transmitted through the bites of ixodid ticks. In the Center for Diagnosis and Prevention of Tick-Borne Infections (Irkutsk, Russian Federation), we annually detect anaplasmas of the Anaplasma phagocytophilum species, as well as Ehrlichia chaffeensis/E. muris in both ixodid ticks and blood samples from people who have been bitten by ticks. At the same time, there are no data in open sources on the incidence of human granulocytic anaplasmosis and human monocytic ehrlichiosis in the Baikal region. Currently, there is very little information on the studies of intensity of the immune response to anaplasmas and ehrlichia in people living in the surveyed area, although this information is critical for assessing the frequency of contacts and the risk of infection of people in a territory endemic for tick-borne infections. The aim. To update information on the presence and prevalence of specific immunoglobulins M and G to A. phagocytophilum and Ehrlichia sp. among the population of the Irkutsk Region affected by tick bites. Materials and methods. In total, 204 samples of blood serum from the residents of the Irkutsk Region who were registered to be bitten by ticks were analyzed for the presence of IgM and IgG to human monocytic ehrlichiosis and human granulocytic anaplasmosis agents. Results. IgG to A. phagocytophilum were found in 9 samples, IgG to E. chaffeensis/E. muris – in 1 sample; no IgM to both pathogens were found in any sample. Conclusions. The results obtained indicate regular infection of the population with anaplasmas and ehrlichia which is a testifies to the existence of active natural foci of human monocytic ehrlichiosis and human granulocytic anaplasmosis in the Baikal region. To clarify the real epidemic role of these infections, a detailed study of the immune status is required both among healthy individuals and among patients with symptoms of an infectious disease.

Introduction. Knowledge about tick-borne disease (TBD) distribution is necessary to improve prevention, whereas detection of human serum IgG antibodies against relevant pathogens is a method for monitoring TBD prevalence in local population. The study objective was to estimate seroprevalence of IgG antibodies against tick-borne encephalitis virus (TBEV), Borrelia burgdorferi sensu lato, Coxiella burnetii, Anaplasma phagocytophilum, and Ehrlichia chaffeensis/E. muris in healthy residents from the five territories of the Northwestern Federal District of the Russian Federation (Arkhangelsk Oblast, Leningrad Oblast, Pskov Oblast, the Republic of Komi and the Republic of Karelia). Materials and methods. In 20172019, a total of 1244 serum samples from healthy residents, not vaccinated against TBDs or other flavivirus-caused infections was studied by ELISA. Results. 21.7% of the sera samples contained IgG antibodies against a single TBD pathogen, whereas 2.1% showed signs of coinfection with two or more pathogens. The most common were IgG antibodies against TBEV (5 territories, 12.2%), followed by Borrelia burgdorferi sensu lato (5 territories, 3.5%), C. burnetii (4 territories, 2.9%), Anaplasma phagoсytophilum (3 territories, 1.6%), E. chaffeensis/E. muris (5 territories, 1.5%). The IgG antibodies were more common in men (55.2%) than in women (44.8%), being found virtually evenly in age-independent manner (from juniors under 18 to seniors over 60). Conclusion. The results of this first comprehensive serosurveillance study in the Northwestern Federal District of the Russian Federation assessing serum IgG antibodies against tick-borne diseases indicate a wide distribution of such pathogens. Moreover, infections caused by C. burnetii, Anaplasma phagocytophilum, and Ehrlichia chaffeensis/E. muris might be highly underdiagnosed.

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by the bacterium Anaplasma phagocytophilum. In this study, we report an indigenous case of clinically diagnosed HGA. The patient was a 41-year-old man who experienced a tick bite and later developed fever, chills, myalgia, malaise, thrombocytopenia, leukocytosis with a left shift, elevated hepatic transaminase levels, and splenomegaly upon admission to the hospital. Immunofluorescence assays detected seroconversion against A. phagocytophilum , whereas tests for spotted fever group rickettsiae, murine typhus, scrub typhus, Q fever, and ehrlichiosis were negative. ELISA and Western blot analysis using recombinant MSP2 protein confirmed the exposure to A. phagocytophilum. Oral doxycycline and intravenous ceftriaxone were prescribed, and the patient made a full recovery. Our findings indicate the presence of HGA on the main island of Taiwan. Precautions against tick bites should be taken when engaging in outdoor activities, and HGA should be considered by physicians in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Background Tick-borne illness are becoming increasingly common, in a spreading geographic area. Lyme disease is a well-known cause of cardiovascular disease, but anaplasmosis has previously had relatively little reported association with conduction and myocardial disease. Case Summary A 65-year-old man with fever and malaise was admitted to the intensive care unit in shock. Electrocardiogram showed new atrial fibrillation and conduction abnormalities. Transthoracic echocardiogram demonstrated normal left ventricular ejection fraction but significant right ventricle dysfunction. Cardiac magnetic resonance imaging findings were consistent with myopericarditis. Workup revealed human granulocytic anaplasmosis without Lyme. He recovered with doxycycline. Conclusion To our knowledge, this is one of the first reported cases of anaplasmosis causing electrical conduction and myocardial disease with haemodynamic instability in an isolated infection. Treatment with appropriate antibiotics and supportive care allowed the patient to recover to his functional baseline within a month from being discharged from the hospital. Recognition of anaplasmosis in the absence of Lyme disease as a potential cause of electrical and myocardial disease is important in the context of increasing anaplasmosis incidence across the United States. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the epizootiological situation on bacterial vector-borne infections in Caucasian Mineral Waters area of the Stavropol Territory over the period of 2018–2020.Materials and methods. 3494 specimens of ticks (473 pools), 257 specimens of small mammals, 9 regurgitates of birds of prey and mammals, 7 excreta samples of small mammals, and 2 water samples were tested. Laboratory research of the field material was carried out using molecular-genetic, serological, biological methods. Statistical analysis of laboratory results was conducted using Microsoft Excel 2010. The data were mapped using QGIS 2.18 software.Results and discussion. The study revealed that the 44.8 % of collected ticks were positive for tick-borne borreliosis, 21.5 % – for tick-borne rickettsiosis, 10.3% – for human granulocytic anaplasmosis, 2.7 % – for Q fever, 0.84 % – for tularemia. There has been an increase in the percentage of positives for tick-borne borreliosis agent samples (more than three times) and a decrease in this indicator for human granulocytic anaplasmosis (1.5 times) as compared with 2010–2012. Investigation of tick infection with the agents of Q fever and tick-borne rickettsioses has not been previously conducted in the region. During the period under review, 19 pools of ticks had mixed infection, which indicates that there are combined foci of bacterial natural-focal infections with vector-borne transmission in the recreation zone of the Stavropol Territory. This necessitates preventive measures and systematical epizootiological surveys in the Caucasian Mineral Waters region.

Ticks and the pathogens they transmit are an ever-present global health problem. In Poland, the most common species of these arachnids are Ixodes ricinus (castor bean tick) and Dermacentor reticulatus (ornate cow tick). There are risks associated with the parasitic effects of ticks. During their feedings, they can have direct and indirect effects on the affected host. Both arthropod species are characterized by a large number of species of microorganisms they transmit causing bacterial, viral, and parasitic diseases. Bacterial infections are the most common among tick-borne diseases. These include Lyme disease, human granulocytic anaplasmosis, tularemia, and Q fever. An increasingly common clinical issue prompting the current research is co-infections, i.e. simultaneous infection of the host by several pathogens. An infection caused by multiple pathogens results in severe and atypical symptoms, prolonged duration of disease, as well as reduced response to treatment. Taking into account the ubiquity of ticks in the environment, only a thorough understanding of tick-borne diseases, including infectious agents and vectors, can lead to better control of this problem worldwide.

Summary. Lyme borreliosis (LB) is a tick-borne infectious disease with multisystemic manifestations caused by the genes of the Borrelia burgdorferi s complex. l. From 2000 to 2020, more than 30,000 diseases were registered in Ukraine. LB occurs in two forms: erythema (migrating erythema) and erythema-free (EF) (lesions of the musculoske­letal, nervous, cardiovascular systems, eyes). The aim of the study – to improve the comprehensive treatment of patients with Lyme borreliosis, including those with concomitant human granulocytic anaplasmosis, by the combined use of ceftriaxone and doxycycline hydrochloride. Materials and Methods. 45 patients with Lyme borreliosis aged from 22 to 77 years who received outpatient or inpatient treatment were followed up in Ternopil Regional Clinical Hospital and the Infectious Department of Ternopil City Clinical Emergency Hospital. In 23 (51.1 %) examined, besides Lyme borreliosis, human granulocytic anaplasmosis was diagnosed. Two treatments of Lyme borreliosis regimens were tested: ceftriaxone for 28 days (Scheme I) and ceftriaxone for 14 days followed by doxycycline hydrochloride for 14 days (Scheme II). The efficacy of treatment was assessed by the activity of joint damage, using the DAS 28 index, the disappearance of clinical manifestations and the dynamics of pro-inflammatory TNF-α, IL-6 and anti-inflammatory IL-4 cytokine in the serum of patients. Results. The combination of ceftriaxone with doxycycline hydrochloride increased the number of low activity patients by a factor of 10 relative to the start of treatment and by a factor of 2 relative to therapy on day 14 with ceftriaxone alone, decreasing the percentage of high activity patients by a factor of 8 relative to the start of treatment and by a factor of 4 relative to that of the same group treated on day 14 with ceftriaxone alone. The use of this regimen to treat Lyme borreliosis patients with not-erythematous form of Lyme borreliosis and human granulocytic anaplasmosis resulted in the disappearance of fever, lymphadenopathy and fatigue/general weakness in the treated patients and achieved a 12-fold reduction in the percentage of patients with headache relative to the start of treatment and a 7-fold reduction relative to day 14 of therapy. Therapy with ceftriaxone and doxycycline hydrochloride using a tested regimen for the treatment of patients with co-infections (Lyme borreliosis and human granulocytic anaplasmosis) resulted in a statistically significant reduction of TNF-α and IL-6 proinflammatory cytokines by a factor of 2 and 3 in the blood, respectively. Conclusions. For the treatment of patients with Lyme borreliosis associated with human granulocytic anaplasmosis, two antibacterials (ceftriaxone and doxycycline hydrochloride) are recommended in sequence

The aim was to determine the prevalence of serum antibodies to tick-borne pathogens and other infectious agents in patients with lymphadenopathy. Materials and methods. 68 patients with lymphadenopathy aged 20 to 63 years who received outpatient or inpatient treatment were followed up at Ternopil University Hospital and Ternopil Regional Clinical Dermatological and Venereological Dispensary. There were 41 women (60.3 %) and 27 men (39.7 %). Two-stage serological detection (ELISA and immunoblot) was used for diagnosis of Lyme borreliosis (LB). Indirect immunofluorescence, including the BIOCHIP multiplex indirect immunofluorescence technique, was used for serological identification of human granulocytic anaplasmosis (HGA) and other infectious diseases, which could be associated with lymphadenopathy. Results. In total, 45.6 % of 68 enrolled patients were positive for the presence of specific antibodies IgM and/or IgG against B. burgdorferi s. l. Further examination demonstrated the presence of specific serum anti-A. phagocytophilum antibodies IgM and/or IgG in 33 patients with lymphadenopathy. It was found that 24.2 % of involved patients were positive for the presence of at least one type of anti-A. phagocytophilum antibodies; 12.1 % had positive or intermediate results only for B. burgdorferi s. l.; 60.6 % of patients were positive for the presence of antibodies against both pathogens. 46.9 % of patients were seropositive for EBV-CA, 40.6 % – for Parainfluenza virus type 1, 37.5 % – for HHV-6, 34.4 % – for HSV-1, 31.3 % – for EBV-EA and Toxoplasma gondii, 6.3 % – for Coxsackievirus type A9 and HIV-2. Conclusions. One-third of all involved patients with lymphadenopathy were positive for antibodies to B. burgdorferi s. l., causa tive agent of Lyme borreliosis. Co-infection of Lyme borreliosis and human granulocytic anaplasmosis was established in more than half of the patients. Besides, specific antibodies to 18 causative agents of other infectious diseases were detected with varying rate. Almost half of positive results detected were the antibodies to parainfluenza virus type 1 and Epstein–Barr virus.

Abstract Background Human granulocytic anaplasmosis (HGA) is a systemic inflammatory response caused by the rickettsial bacterium Anaplasma phagocytophilum. Rhabdomyolysis and acute kidney injury (AKI) are rare complications of HGA. Here, we report a case of HGA concurrent with rhabdomyolysis and AKI in an elderly patient. Case presentation An 84-year old woman with a medical history of hypertension was hospitalised after two days of fever, dizziness, whole body pain, and general weakness. Laboratory investigations showed severe thrombocytopenia, leukopenia, impaired renal function, and elevated cardiac enzyme and myoglobin levels. On the day after admission, peripheral blood smear revealed morula inclusions in neutrophils, a suggestive finding of HGA. Real-time polymerase chain reaction (PCR) results indicated the presence of A. phagocytophilum. Antibiotics were de-escalated to doxycycline monotherapy. After 10 days of antibiotic treatment, laboratory tests showed complete recovery from HGA complicated with rhabdomyolysis and AKI. Conclusions HGA can lead to serious complications in patients with associated risk factors. Therefore, in patients with HGA accompanied by rhabdomyolysis, management with antibiotics and hydration should be initiated immediately, and not delayed until diagnostic confirmation.

Objectives: We sought to assess the performance of 3 laboratory tests on blood specimens for direct detection of Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA), in patients tested at a single medical institution in New York State., Methods: Direct tests included microscopic blood smear examination for intragranulocytic inclusions, polymerase chain reaction (PCR), and culture using the HL-60 cell line. The HGA cases testing positive by only 1 direct test were not included, unless HGA was confirmed by acute or convalescent serology using an indirect immunofluorescent assay., Results: From 1997 to 2009, 71 patients with HGA were diagnosed by at least 1 of the 3 direct test methods. For the subgroup of 55 patients who were tested using all 3 methods, culture was positive for 90.9% (50/55) vs 81.8% (45/55) for PCR vs 63.6% (35/55) for blood smear (P =.002). Most cultures (79.3%) were detected as positive within 1 week of incubation., Conclusions: Although using culture to detect A phagocytophilum is likely not amenable for implementation in most hospital laboratories, in our experience, culture had the highest yield among the direct tests evaluated., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The obligatory intracellular bacterium Anaplasma phagocytophilum causes human granulocytic anaplasmosis, an emerging zoonosis. Anaplasma has limited biosynthetic and metabolic capacities, yet it effectively replicates inside of inclusions/vacuoles of eukaryotic host cells. Here, we describe a unique Type IV secretion system (T4SS) effector, E R- G olgi e xit site protein of A naplasma (EgeA). In cells infected by Anaplasma , secreted native EgeA, EgeA-GFP, and the C-terminal half of EgeA (EgeA-C)-GFP localized to Anaplasma- containing inclusions. In uninfected cells, EgeA-C-GFP localized to cis-Golgi, whereas the N-terminal half of EgeA-GFP localized to the ER. Pull-down assays identified EgeA-GFP binding to a transmembrane protein in the ER, Transport and Golgi organization protein 1 (TANGO1). By yeast two-hybrid analysis, EgeA-C directly bound Sec1 family domain-containing protein 1 (SCFD1), a host protein of the cis-Golgi network that binds TANGO1 at ER-Golgi exit sites (ERES). Both TANGO1 and SCFD1 localized to the Anaplasma inclusion surface. Furthermore, knockdown of Anaplasma EgeA or either host TANGO1 or SCFD1 significantly reduced Anaplasma infection. TANGO1 and SCFD1 prevent ER congestion and stress by facilitating transport of bulky or unfolded proteins at ERES. A bulky cargo collagen and the ER-resident chaperon BiP were transported into Anaplasma inclusions, and several ER stress marker genes were not up-regulated in Anaplasma- infected cells. Furthermore, EgeA transfection reduced collagen overexpression-induced BiP upregulation. These results suggest that by binding to the two ERES proteins, EgeA redirects the cargo-adapted ERES to pathogen-occupied inclusions and reduces ERES congestion, which facilitates Anaplasma nutrient acquisition and reduces ER stress for Anaplasma survival and proliferation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Anaplasma phagocytophilum is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and Borrelia burgdorferi was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% (n = 4/95) and 18.2% (n = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients. [ABSTRACT FROM AUTHOR]

Anaplasma phagocytophilum is the causative agent of tick-borne fever (TBF) and human granulocytic anaplasmosis (HGA) and is currently considered an emerging disease in the USA, Europe, and Asia. The increased prevalence of A. phagocytophilum as a human pathogen requires the detailed characterization of human isolates and the implementation of appropriate animal models. In this study, we demonstrated that the dynamics of infection with the human isolate of A. phagocytophilum NY-18 was variable in three different strains of mice (SCID, C3H/HeN, BALB/c). We further evaluated the ability of Ixodes ricinus to acquire and transmit A. phagocytophilum NY-18 and compared it with Ixodes scapularis. Larvae of both tick species effectively acquired the pathogen while feeding on infected mice. The infection rates then decreased during the development to nymphs. Interestingly, molted I. ricinus nymphs were unable to transmit the pathogen to naïve mice, which contrasted with I. scapularis. The results of our study suggest that I. ricinus is not a competent vector for the American human Anaplasma isolate. Further studies are needed to establish reliable transmission models for I. ricinus and European human isolate(s) of A. phagocytophilum. [ABSTRACT FROM AUTHOR]

Ixodid ticks are carriers of causative agents of infectious diseases dangerous to humans, including tick-borne encephalitis, ixodid tick-borne borrelioses, rickettsioses, human monocytic ehrlichiosis, human granulocytic anaplasmosis, Congo–Crimean hemorrhagic fever, Omsk hemorrhagic fever, Q fever, and tularemia. These natural focal diseases represent a significant medical problem. It is known that an organism's response to the effect of an infectious agent (and, as a consequence, peculiarities of the course and outcome of the disease) depends not only on the characteristics of the causative agent and external factors, but also significantly on the individual characteristics of the host (particularly, human) genome that predetermine the ability of its immune system to suppress the development of infection. There are two main approaches to the search for human genes predetermining the degree of his susceptibility/resistance to infectious agents. First, the analysis of candidate genes that are presumably relevant to the development of this disease based on known or putative functions of their protein products or on previous data on the orthologous genes in model organisms. Second, genome-wide association analysis, in which a large number of genetic markers evenly distributed across the human genome are simultaneously analyzed. The human genetic predisposition to such infectious diseases as AIDS, tuberculosis, malaria, hepatitis C and B, etc., has been intensively studied, and human genetic factors that specifically predetermine the efficiency of protective reactions against these infections have been already identified. As for infections transmitted by ixodid ticks, the genes of human predisposition to them are those far less studied, and the existing data are rather scattered. This review summarizes already-known genetic factors associated with predisposition to different infections transmitted by ixodid ticks in beings human and laboratory animals, as well as approaches to identification of these factors. [ABSTRACT FROM AUTHOR]

Background: Human granulocytic anaplasmosis (HGA) is a potentially severe tick-borne infection caused by the bacterium Anaplasma phagocytophilum (A. phagocytophilum) of the genus Rickettsia. Here, we describe the epidemiological and clinical characteristics of an unusual cluster of HGA cases detected in the Estrie region in Québec, Canada, during the 2021 transmission season. Methods: Confirmed cases of HGA were defined as individuals with typical clinical manifestations and a positive polymerase chain reaction assay. The cases were interviewed using a structured questionnaire and clinical data was obtained from medical records. Results: A total of 25 confirmed cases were identified during the 2021 transmission season, thus constituting the largest known cluster of HGA in Canada. The most common symptoms reported were fever, fatigue and headaches. Laboratory investigations found that 20 (80%) of the patients had thrombocytopenia and 18 (72%) had leukopenia at presentation. Almost half of the patients required hospitalization (n=11, 44%), with a median duration of four days (interquartile range [IQR] 2.5–5 days), including one patient who required intensive care. No deaths were recorded during the study. Epidemiological investigation found that all cases were domestically acquired, and yard maintenance was the most prevalent at-risk activity identified. Only seven (28%) cases had been aware of a tick bite in the previous two weeks. Conclusion: Detection of this unusual cluster of HGA cases provides further evidence that A. phagocytophilum may now be established along the southern border of Québec. Clinicians should consider HGA when assessing patients with typical symptoms and recent exposure to high-risk environments for tick bite. [ABSTRACT FROM AUTHOR]

Despite the increasing number of patients suffering from tick-borne encephalitis (TBE), Lyme disease, and their co-infection, the mechanisms of the development of these diseases and their effects on the human body are still unknown. Therefore, the aim of this study was to evaluate the changes in the proteomic profile of human plasma induced by the development of TBE and to compare it with changes in TBE patients co-infected with other tick-borne pathogens. The results obtained by proteomic analysis using a nanoLC-Q Exactive HF mass spectrometer showed that the most highly elevated groups of proteins in the plasma of TBE patients with co-infection were involved in the pro-inflammatory response and protein degradation, while the antioxidant proteins and factors responsible for protein biosynthesis were mainly downregulated. These results were accompanied by enhanced GSH- and 4-HNE-protein adducts formation, observed in TBE and co-infected patients at a higher level than in the case of patients with only TBE. In conclusion, the differences in the proteomic profiles between patients with TBE and co-infected patients indicate that these diseases are significantly diverse and, consequently, require different treatment, which is particularly important for further research, including the development of novel diagnostics tools. [ABSTRACT FROM AUTHOR]

Abstract Background Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum. To date, there have been no reported cases of A. phagocytophilum infection found in both the biting tick and the patient following a tick bite. Case presentation An 81-year-old woman presented with fever following a tick bite, with the tick still intact on her body. The patient was diagnosed with HGA. The tick was identified as Ixodes nipponensis by morphological and molecular biological detection methods targeting the 16S rRNA gene. The patient’s blood was cultured after inoculation into the human promyelocytic leukemia cell line HL-60. A. phagocytophilum growth was confirmed via culture and isolation. A. phagocytophilum was identified in both the tick and the patient’s blood by Anaplasma-specific groEL- and ankA-based nested polymerase chain reaction followed by sequencing. Moreover, a four-fold elevation in antibodies was observed in the patient’s blood. Conclusion We report a case of a patient diagnosed with HGA following admission for fever due to a tick bite. A. phagocytophilum was identified in both the tick and the patient, and A. phagocytophilum was successfully cultured. The present study suggests the need to investigate the possible incrimination of I. nipponensis as a vector for HGA in Korea.

Ticks and the pathogens they transmit are an ever-present global health problem. In Poland, the most common species of these arachnids are Ixodes ricinus (castor bean tick) and Dermacentor reticulatus (ornate cow tick). There are risks associated with the parasitic effects of ticks. During their feedings, they can have direct and indirect effects on the affected host. Both arthropod species are characterized by a large number of microorganisms species they transmit causing bacterial, viral, and parasitic diseases. Bacterial infections are the most common among tick-borne diseases. These include Lyme disease, human granulocytic anaplasmosis, tularemia, and Q fever. An increasingly common clinical issue prompting the current research is co-infections, i.e. simultaneous infection of the host by several pathogens. An infection caused by multiple pathogens results in severe and atypical symptoms, prolonged duration of disease, as well as reduced response to treatment. Taking into account the ubiquity of ticks in the environment, only a thorough understanding of tick-borne diseases, including infectious agents and vectors, can lead to better control of this problem worldwide. [ABSTRACT FROM AUTHOR]

Background: Human granulocytic anaplasmosis (HGA) is a systemic inflammatory response caused by the rickettsial bacterium Anaplasma phagocytophilum. Rhabdomyolysis and acute kidney injury (AKI) are rare complications of HGA. Here, we report a case of HGA concurrent with rhabdomyolysis and AKI in an elderly patient.Case Presentation: An 84-year old woman with a medical history of hypertension was hospitalised after two days of fever, dizziness, whole body pain, and general weakness. Laboratory investigations showed severe thrombocytopenia, leukopenia, impaired renal function, and elevated cardiac enzyme and myoglobin levels. On the day after admission, peripheral blood smear revealed morula inclusions in neutrophils, a suggestive finding of HGA. Real-time polymerase chain reaction (PCR) results indicated the presence of A. phagocytophilum. Antibiotics were de-escalated to doxycycline monotherapy. After 10 days of antibiotic treatment, laboratory tests showed complete recovery from HGA complicated with rhabdomyolysis and AKI.Conclusions: HGA can lead to serious complications in patients with associated risk factors. Therefore, in patients with HGA accompanied by rhabdomyolysis, management with antibiotics and hydration should be initiated immediately, and not delayed until diagnostic confirmation. [ABSTRACT FROM AUTHOR]

Introduction: Human granulocytic anaplasmosis (HGA) is a tick-borne illness caused by the bacterium Anaplasma phagocytophilum. HGA has a widely variable clinical presentation and can be life-threatening. Case description: A 77-year-old man was transferred from an outside facility with altered mental status, a fever of up to 40.5°C, and shortness of breath. Laboratory analysis revealed a progressively worsening pro-inflammatory state and abnormalities in the patient’s coagulation studies. With clinical and laboratory evidence concerning for potential COVID-19 infection, the patient was placed in isolation as a precaution. The results of two COVID-19 tests, given approximately 24 hours apart, were negative. The patient’s spouse confirmed a bug bite to his upper extremity while working outdoors. His symptoms resolved completely after a 10-day course of empiric doxycycline. Discussion: The diverse clinical presentations of HGA necessitate a broad differential diagnosis, including viral, bacterial and non-infectious aetiologies. In severe cases, a cytokine-mediated immune cascade can occur (namely, cytokine storm) leading to devastating downstream effects. This cytokine storm can be seen in many other diseases, but most recently it has been demonstrated in the novel coronavirus disease 2019 (COVID-19). Conclusion: Here we present a case of HGA in which diagnosis was delayed due to mimicry of COVID-19 infection. This case highlights the importance of taking clinical and social histories, seasonality and geography into account during diagnosis, and maintaining a broad differential with non-specific symptoms. Despite the current COVID-19 pandemic, we recommend that HGA remains in the differential diagnosis of a pro-inflammatory state with an atypical respiratory presentation.

Anaplasma phagocytophilum is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and Borrelia burgdorferi was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% (n = 4/95) and 18.2% (n = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients.

Human granulocytic anaplasmosis (HGA) is an emerging, rickettsial tick-borne disease caused by Anaplasma phagocytophilum . Sero-epidemiological data demonstrate that this pathogen has a worldwide distribution. The diagnosis of HGA requires a high index of clinical suspicion, even in endemic areas. In recent years, HGA has increasingly been reported from Asia and described in China, Japan, and Korea. We serologically and molecularly screened 467 patients with clinical suspicion of Anaplasmosis. The present study describes the epidemiology, clinical, and laboratory details of 6 confirmed and 43 probable cases of human granulocytic anaplasmosis. One of the HGA patients developed secondary invasive opportunistic Aspergillus fumigatus and Acinetobacter baumanii infection during the illness, which resulted in a fatal infection. The HGA patients without severe complications had excellent treatment responses to doxycycline. The emergence of this newly recognized tick-borne zoonotic HGA in North India is a significant concern for public health and is likely underdiagnosed, underreported, and untreated. Hence, it is also essential to establish a well-coordinated system for actively conducting tick surveillance, especially in the forested areas of the country.IMPORTANCEThe results of the present study show the clinical and laboratory evidence of autochthonous cases of Anaplasma phagocytophilum in North India. The results suggest the possibility of underdiagnosis of HGA in this geographical area. One of the HGA patients developed secondary invasive opportunistic Aspergillus fumigatus and Acinetobacter baumanii infection during the illness, which resulted in a fatal infection., Competing Interests: The authors declare no conflict of interest.

Abstract Background The studies on the occurrence and diversity of tick-borne infections in HIV-infected individuals have been few, and the subject has been relatively neglected when compared with other common infections associated with HIV. In HIV-positive patients in whom a serological diagnostics is complicated due to reduced positive predictive value, a method where the microorganism is detected directly is of great value. Therefore, we performed a molecular study to ascertain the prevalence and incidence of tick-borne infections in HIV-infected persons in Poland, an endemic area for Ixodes ricinus ticks. Methods Genomic DNA was isolated from whole blood of tested patients. Detection of tick-borne pathogens was performed by amplification and sequencing of different loci. Molecular and phylogenetic analyses of obtained nucleotide sequences were performed. Serum samples were analyzed for antibodies against tick-borne pathogens by using commercial tests in all patients. Results Among 148 studied blood samples from HIV-infected patients, two cases (1.4%) of infection with tick-borne pathogen were reported. No symptoms of tick-borne infection were observed in these cases. In one case a patient was infected with Anaplasma phagocytophilum – the agent of human granulocytic anaplasmosis (HGA) and in the other with Borrelia garinii. Conclusions Our study revealed the first case of HIV positive patient infected with A. phagocytophilum. Asymptomatic tick-borne infection can occur in HIV-positive patients. The detailed history of tick bites, especially in endemic tick areas, should be considered as part of anamnesis in routine clinical care of HIV-positive patients.

Background. Early detection of tick-borne pathogens in blood samples of infected people prevents the disease before clinical manifestations using antibiotic and immunoglobulin treatment. As far as tick-borne diseases are associated with significant activation of innate immune response, the changes in the cytokine profile soon after a tick bite could be used as an indicator of early tick-borne infection. Aims. The goal of this study was to characterize the production of cytokines during first 2-4 days after a tick bite in asymptomatic people infected with tick-borne pathogens. Materials and methods. The infection of tick-borne encephalitis virus, B. burgdorferi sensu lato, A. phagocytophilum and E. chaffeensis / E. muris was detected in blood of bitten humans using appropriate commercial real time RT-PCR and ELISA assays. Concentration of 14 cytokines in plasma of 89 infected and 45 non-infected people was established using quantitative ELISA kits. Results. Between 2nd and 4th days after tick bite, the prevalence and concentration of certain cytokines in blood of infected people significantly differed from those of the control group. Bacterial pathogens exhibited very similar patterns of cytokine profiles with induction of IL-1a, IL-8 и IFN-a and suppression of SOD, IL-1Ra и IL-17A. For virus infection the increased concentrations of IL-1 a, IL-8, IL-10, IL-17A, IFN-y and SOD were detected. The only suppressed cytokine was IL-1Ra receptor antagonist. Conclusions. The results suggest that evaluation of innate immune response between 2nd and 4th days after the tick bite could be a useful tool for evaluation of the risk of tick-borne disease for the humans bitten by ticks.

In HIV (human immunodeficiency virus) infected people, the immunodeficiency caused by a reduced level of CD4 (cluster of differentiation 4) T-lymphocytes increases the risk of infectious diseases. Additionally, in individuals with immunologically compromising conditions, tick-borne or some parasitic pathogens may cause chronic, debilitating opportunistic infections and even death. The study aimed at determining the IgG seropositivity of HIV-infected patients to Toxoplasma gondii, Toxocara spp., Echinococcus multilocularis, and E. granulosus s.l. and performing the molecular identification of T. gondii and some tick-borne pathogens, namely, Borrelia spp., Babesia spp., Anaplasma phagocytophilum, Rickettsia spp., and Bartonella spp. Out of 89 HIV-positive patients, specific IgG antibodies to T. gondii were detected in 17 (19.1%) and to Borrelia spp. in 12 (13.5%) individuals. Seropositivity to Toxocara spp., E. multilocularis, and E. granulosus s.l. was not recorded. Molecular approaches showed positivity to T. gondii in two (2.2%) patients, and 11 (12.4%) individuals had positive PCR signal for the msp2 gene of A. phagocytophilum. Relatively high prevalence of A. phagocytophilum in HIV-positive patients suggests that these people are more susceptible to some vector-borne pathogens. The presence of opportunistic infections may pose a health risk for patients with weakened immune systems, and should not be neglected during the regular monitoring of the patient’s health status.

Human granulocytic anaplasmosis (HGA) is one of the leading vector-borne diseases in the world. This article presents a brief review of the scientific literature. Various points of view have been considered: etiology, clinical manifestation, laboratory diagnosis, etiologic diagnosis, therapy and prevention. Improving the knowledge of the HGA is an important step in dealing with this infection. [ABSTRACT FROM AUTHOR]

L'anaplamose granulocytaire humaine, due à Anaplasma phagocytophilum , est une maladie émergente en Europe. Elle survient dans toutes les zones où la borréliose de Lyme est endémique puisque son vecteur (tique du genre Ixodes) est le même. Le diagnostic doit être évoqué pour un patient exposé aux tiques et qui présente des signes cliniques non spécifiques qui ressemblent à un syndrome grippal estival tel que de la fièvre, des céphalées, des myalgies associées à des résultats biologiques anormaux : leucopénie, thrombopénie et/ou augmentation des enzymes hépatiques. Le traitement fait appel aux cyclines, antibiotiques de choix. Human granulocytic anaplasmosis caused by Anaplasma phagocytophilum is an emergent disease in Europe. It occurs in all Lyme disease endemic areas because the same vector (Ixodes tick) can transmit Borrelia, Anaplasma. The diagnosis should be considered for a patient with tick exposure who presents non spécific symptoms such as fever, headache, myalgies and abnormal laboratory features (leukopenia, thrombocytopenia and/or elevation of liver enzyme levels). The treatment of choice is doxycycline. [ABSTRACT FROM AUTHOR]

Introduction: Tick-borne encephalitis virus (TBEV) and Borrelia burgdorferi, the causative agent of Lyme disease (LD), are widespread in Western Ukraine. However, relatively little is known about Anaplasma phagocytophilum in this region. This study examined patterns of infection with A. phagocytophilum in two tick vectors compared with the better studied TBEV and B. burgdorferi. Materials: Ticks were collected in three different ecosystems of the Western Ukraine during 2009–2014. Samples were examined for pathogen detection using real-time polymerase chain reaction (PCR), and logistic regression models were developed to assess the significance of different factors. Results: Among the three selected ecological systems of the Western region of Ukraine, 5130 ticks belonging to Ixodes ricinus and Dermacentor reticulatus were collected between 2009 and 2014. They were grouped into 366 pools and were tested by PCR for A. phagocytophilum. A subsample (1620 ticks, 162 pools) of the ticks was concurrently tested by PCR for A. phagocytophilum, B. burgdorferi, and TBEV. Overall, there was no trend in the proportion of positive ticks across years (p > 0.05). However, the prevalence of A. phagocytophilum was higher (27.4%) in I. ricinus than in D. reticulatus (15.9%) (OR = 2.69; 95% CI, 1.52–4.94 (Lower, Upper 95% CI)). Infection was more common in forested habitats (OR = 1.89; 95% CI, 1.07–3.36) and during the later summer–early autumn (3.78; 95% CI, 1.79–8.06). B. burgdorferi was found in 29.3% and 31.9% of I. ricinus and D. reticulatus, respectively; and TBEV was found in 6.3% and 14.5% of I. ricinus and D. reticulatus. Coinfection of A. phagocytophilum and B. burgdorferi occurred more often than chance and was more frequent than any other combination of pathogens (p = 0.031). Conclusions: Our study is the first to explore the potential relationship between the ecosystems, vectors, and the presence of Human Granulocytic Anaplasmosis (HGA) and other tick-borne infections in Western Ukraine. Anaplasma demonstrated a greater prevalence in I. ricinus in the forested area in Western Ukraine. Altogether, HGA, LD, and tick-borne encephalitis (TBE) pathogens are actively circulating in these ecosystems and have the potential to coinfect vectors that might increase the risk of transmitting multiple pathogens to humans during host feeding by individual ticks. [ABSTRACT FROM AUTHOR]

Objective of the study is to investigate natural focality of Ixodidae tick borreliosis, granulocytic anaplasmosis, monocytic ehrli-chiosis in humans in the Republic of Tatarstan. Materials and methods. Utilized were the data from tick studies conducted between 2010–2015. Applying immune-enzymatic analysis, investigated were the blood sera from residents (donors) of Kazan and municipal districts of the Republic of Tatarstan for the presence of specific antibodies to borreliosis, ehrlichiosis, and anaplasmosis pathogens. Results and conclusions. For the first time ever, the data on spontaneous carriage of Ehrlichiosis pathogens in Ixodidae ticks have been obtained. The information received is an indicative of the active circulation of Borrelia, Ehrlichia and Anaplasma in the territory of the region and of necessity to expand the research on the “novel” for the Republic nosological forms of natural-focal infections.

The urgent detection of tick-borne pathogens in attached ticks or in human blood followed by the prophylaxis of infection with specific immunoglobulin and/or antibiotics is one of the most reliable measures to prevent human disease. The aim of this work was to evaluate the usability of real-time PCR (RT-PCR) assay in early detection of tick-borne infections. Using commercial RT-PCR assay (Amplisens, Russia) we studied 361 Ixodes persulcatus ticks, 33 Dermacentor sp. ticks and 448 samples of human blood delivered by people attacked by ticks in Irkutsk region during 2013-2014for presence of DNA/RNA of tick-borne encephalitis virus (TBEV), Borrelia burgdorferi sensu lato (B.b.s.l.), Anaplsma phagocytophilum and Ehrlichia chaffeensis/E. muris. The ELISA assay and direct microscopy were used to validate the detection of TBEV and B.b.s.l. respectively. The highest prevalence of tick-borne infections was observed for I. persulcatus ticks - 6,9; 23,8; 6,9; and 11,9 % for TBEV, B.b.s.l., A. phagocytophillum and E. chaffeensis/E. muris respectively. The Dermacentor sp. ticks were less frequently infected with abovementioned pathogens - 3,0; 6,1; 3,0 and 9,1 % respectively. The prevalence of infection in blood samples was lowest and comprised 2,5; 4,2; 2,2 and 4,5 % respectively. Mixed infections were documented in 6,5 % of ticks and 0,7 % of human blood samples. The testing of blood samples in ELISA and testing of ticks in ELISA and direct microscopy corresponded to the results, obtained by RT-PCR. Thus, RT-PCR is valuable and reliable approach for urgent detection and prophylaxis of tick-borne infections.

Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum. Indirect immunofluorescence assay (IFA) is generally used for HGA serodiagnosis. A. phagocytophilum immunodominant P44 major outer membrane proteins are encoded by p44/msp2 multigene family, responsible for IFA reactivity. However, because multiple P44-related proteins may involve immunoreactivity in IFA, the available diagnostic antigens remain obscure. In this study, we identified 12 B-cell epitopes on triple P44-related proteins using peptide array that reacted with 4 HGA patients' sera. Then, peptide spot immunoassay using 14 synthetic peptides derived from those 12 epitopes as antigens was applied for the detection of antibody to A. phagocytophilum from patients with fever of unknown origin. The sensitivities and diagnostic efficiencies of this immunoassay were higher than those of Western blot analysis using 3 recombinant proteins previously developed. Thus, the immunoassay using our epitope-derived antigens, which has higher diagnostic performances, may have significant benefit for HGA serodiagnosis. [ABSTRACT FROM AUTHOR]

Background: Human granulocytic anaplasmosis, a tick-borne infection caused by Anaplasma phagocytophilum, has received scant attention, while scrub typhus, a mite-transmitted disease caused by Orientia tsutsugamushi, is the most common rickettsiosis in Taiwan. The clinical presentations of both diseases are characterized by undifferentiated fever, headache and malaise. Moreover, both pathogens have been detected in small mammals that serve as hosts for chiggers and ticks in the wild. The objective of the present study was to investigate whether human granulocytic anaplasmosis occurs in Taiwan. Methodology/Principal findings: Blood samples from 274 patients suspected of having scrub typhus in Kinmen, an offshore island of Taiwan, in 2011 and 2012 were retrospectively examined by immunofluorescence assays. IgG antibodies reactive with Anaplasma phagocytophilum was found in 31.8% (87/274) of the patients. Paired serology identified 3 patients with human granulocytic anaplasmosis and 8 patients with coinfection with O. tsutsugamushi and A. phagocytophilum. Laboratory tests showed that elevated serum ALT/AST, creatinine, and BUN levels were observed in patients with anaplasmosis and coinfection, but elevated serum CRP levels, thrombocytopenia, and anemia were only observed in coinfected patients. PCR detected A. phagocytophilum 16S rDNA and p44/msp2 in 2 patients. The phylogenetic analysis suggested that the replicons of the 16S rDNA shared high sequence similarity with the reference sequences in the Korea, USA, Japan, and China. The amplicons of p44/msp2 were close to those of the human variants identified in the USA and Japan. Conclusions: Our findings indicated that A. phagocytophilum infection was prevalent but unrecognized in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Natural-focal diseases are serious diseases that endanger human health. They threaten about 100 million people in Shandong Province, and cause illness in thousands of people each year. However, information on the epidemiological characteristics of natural-focal diseases in Shandong Province has been limited. The purpose of the study was to describe and analyze the epidemiological characteristics of natural-focal diseases in Shandong Province, 2009–2017. Methods: We describe the incidence and distribution of four natural-focal diseases in Shandong Province using surveillance data from 2009–2017. Results: From 2009–2017, 11123 cases of four natural-focal diseases including 257 deaths were reported in Shandong Province, China. The four natural-focal diseases were severe fever with thrombocytopenia syndrome (SFTS), human granulocytic anaplasmosis (HGA), typhus, and scrub typhus. The high-risk groups of the four diseases were farmers and the elderly. The incidence rate of scrub typhus was significantly higher in females. However, this difference was not seen in the other three diseases. The four diseases were mainly clustered in the middle-southern part of Shandong Province and the Shandong Peninsula. The annual incidence of SFTS and scrub typhus increased, typhus was relatively stable, and HGA declined. However, the range of SFTS expanded, while HGA shrunk, and typhus and scrub typhus were unchanged. The epidemic period of SFTS and HGA was from May to October, typhus was from October to November, and scrub typhus was from September to November. The fatality rates of SFTS, typhus, scrub typhus, and HGA were 9.19%, 0%, 0.01%, and 2.24%, respectively. Conclusions: Our study described and analyzed the prevalence of natural-focal diseases in Shandong Province, and confirmed that age was closely related to the SFTS fatality rate. This study may help to improve the understanding of the prevalence of natural-focal diseases in Shandong Province in recent years and to better develop accurate prevention and control strategies for natural-focal diseases. [ABSTRACT FROM AUTHOR]

Anaplasma phagocytophilum—the causative agent of human granulocytic anaplasmosis (HGA)—is a tick-borne pathogen transmitted by Ixodid ticks infecting wild and domestic mammals as well as humans. Despite the availability of evidence regarding this emerging infection among vectors, host animals, and individuals in China, there is limited knowledge on the prevalence and distribution of A. phagocytophilum in the Yunnan Province. The aim of this study was to assess the seroprevalence of A. phagocytophilum in healthy adults and patients with acute undifferentiated fever from four regions in the Yunnan Province. The enzyme-linked immunosorbent assay and indirect immunofluorescence assay were used to detect immunoglobulin (Ig) G and IgM antibodies against A. phagocytophilum in sera obtained from 1185 healthy blood donors and 245 patients with acute undifferentiated fever, respectively. Demographic variables were assessed as potential risk factors using the chi-squared test. The rates of seropositivity rates were 7.59% and 4.49% in healthy donors and fever patients, respectively. Analysis of risk factors such as gender, age groups, and place of residence showed statistically significant differences. Infections with A. phagocytophilum occur widely among individuals residing in southwestern China. Our results indicate that there is serological evidence of HGA in this population and presence of acute A. phagocytophilum infections in patients with undifferentiated fever in the Yunnan Province. [ABSTRACT FROM AUTHOR]

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Nitrogen metabolism in citrus has received increased attention due to its effects on plant growth and productivity. However, little is known about the effects of nitrogen fertilization on nitrogen metabolism in young trees of citrus cultivar 'Huangguogan' (Citrus reticulata × Citrus sinensis). Here, genes encoding nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate dehydrogenase (GDH), and asparagine synthetase (AS), represented as HgNR, HgNiR, HgGS, HgGDH, and HgAS, respectively, were cloned from Huangguogan. Deduced protein sequences were analyzed and proteins were confirmed to be localized in their respective cellular organelles. Moreover, pot-cultured 'Huangguogan' seedlings were fertilized with 0 (N1), 1.36 (N2), 1.81 (N3), 2.26 (N4), or 2.72 (N5) kg N/year, for 12 months. Enzyme activity and enzyme-gene expression were studied in roots, leaves, and fruits at different stages. Finally, the effects of N application rate on root activity, leaf N, soluble protein, yield, and fruit quality at the ripening stage were measured. The results showed that: 1) HgNR, HgNiR, HgGDH, and HgAS gene products were found mainly in the cytoplasm and plasma membrane, while HgGS gene product was found mainly in cytoplasm and mitochondria. 2) Gene expression and enzyme activity differed among plant organs. As the root is in permanent direct contact with the soil we suggest that root gene expression and enzyme activity can be used as reference to determine N application rate. 3) Yield, fruit quality, enzyme activity, and enzyme-related gene expression were considerably lower at low than at high-N supply. However, they were all inhibited by excess nitrogen (i.e., 2.72 kg/year). Therefore, we recommend 1.81 kg N/year as the optimal N application rate for young 'Huangguogan' trees. [ABSTRACT FROM AUTHOR]

Atypical myopathy (AM) in horses is caused by ingestion of seeds of the Acer species (Sapindaceae family). Methylenecyclopropylacetyl-CoA (MCPA-CoA), derived from hypoglycin A (HGA), is currently the only active toxin in Acer pseudoplatanus or Acer negundo seeds related to AM outbreaks. However, seeds or arils of various Sapindaceae (e.g., ackee, lychee, mamoncillo, longan fruit) also contain methylenecyclopropylglycine (MCPG), which is a structural analogue of HGA that can cause hypoglycaemic encephalopathy in humans. The active poison formed from MCPG is methylenecyclopropylformyl-CoA (MCPF-CoA). MCPF-CoA and MCPA-CoA strongly inhibit enzymes that participate in β-oxidation and energy production from fat. The aim of our study was to investigate if MCPG is involved in Acer seed poisoning in horses. MCPG, as well as glycine and carnitine conjugates (MCPF-glycine, MCPF-carnitine), were quantified using high-performance liquid chromatography-tandem mass spectrometry of serum and urine from horses that had ingested Acer pseudoplatanus seeds and developed typical AM symptoms. The results were compared to those of healthy control horses. For comparison, HGA and its glycine and carnitine derivatives were also measured. Additionally, to assess the degree of enzyme inhibition of β-oxidation, several acyl glycines and acyl carnitines were included in the analysis. In addition to HGA and the specific toxic metabolites (MCPA-carnitine and MCPA-glycine), MCPG, MCPF-glycine and MCPF-carnitine were detected in the serum and urine of affected horses. Strong inhibition of β-oxidation was demonstrated by elevated concentrations of all acyl glycines and carnitines, but the highest correlations were observed between MCPF-carnitine and isobutyryl-carnitine (r = 0.93) as well as between MCPA- (and MCPF-) glycine and valeryl-glycine with r = 0.96 (and r = 0.87). As shown here, for biochemical analysis of atypical myopathy of horses, it is necessary to take MCPG and the corresponding metabolites into consideration. [ABSTRACT FROM AUTHOR]

Abstract Ticks are vectors of several microorganisms responsible for infectious diseases in human and animals, such as Anaplasma phagocytophilum and Coxiella burnetii. In this study, we investigated the prevalence of these two bacteria in 62 889 Ixodes ricinus ticks in selected regions covering all Switzerland. A high prevalence of 11.9% of A. phagocytophilum DNA was observed by real-time PCR on 8534 pools of ticks. This pool prevalence corresponds to an estimated prevalence of 1.71% in individual tick. A total of 144 of the 171 collection sites (84.2%) were positive for the presence of A. phagocytophilum, and these sites were homogenously distributed throughout Switzerland. Such prevalence and geographical distribution underline the risk of human and animal exposure to A. phagocytophilum and highlight the need to assess the epidemiology and clinical diagnosis of human and animal anaplasmosis in Switzerland. However, DNA of C. burnetii was never found in any tick pool. This absence suggests a very low role of I. ricinus ticks as vector and reservoir of C. burnetii in Switzerland, and it supports previous reports demonstrating the role of sheep and goats in the epidemiology of Q fever. However, considering its pathogenic potential, it is necessary to keep monitoring for the possible reemergence of this bacterium in ticks in the future. [ABSTRACT FROM AUTHOR]

Abstract Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum. Because of nonspecific clinical manifestations, diagnosis of HGA highly depends on laboratory tests. Identification of immunoreactive proteins is prerequisite for development of specific and sensitive immunoassays for HGA. In this study, we identified novel immunoreactive proteins of A. phagocytophilum. Previous studies indicated that secreted proteins of A. phagocytophilum and other bacteria can be immunoreactive antigens. Here we in silico screened A. phagocytophilum genome for encoding proteins which bear features of type IV secretion system substrates. Among seventy seven predicted proteins, fourteen proteins were determined for antigenicity and nine proteins were showed to be immunoreactive antigens. In addition, an APH1384 peptide harboring a B cell epitope predicted by bioinformatics was found specifically reacting with anti- A. phagocytophilum sera. Hereby, we identified novel immunoreactive proteins and delineated a specific epitope of A. phagocytophilum , which might be employed for HGA diagnosis. Highlights • Type IV secretion substrate feature-bearing A. phagocytophilum proteins were identified by bioinformatics approaches. • Majority of investigated type IV secretion substrate feature-bearing A. phagocytophilum proteins are immunoreactive. • A specific epitope of A. phagocytophilum protein, APH1384 was identified. [ABSTRACT FROM AUTHOR]