Diagnosis Of Human Granulocytic Anaplasmosis Research Articles

Development of a Model for Preliminary Diagnosis of Human Granulocytic Anaplasmosis.

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.

Clinically differential diagnosis of human granulocytic anaplasmosis and severe fever with thrombocytopenia syndrome

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0–4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949–0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Using Serum Specimens for Real-Time PCR-Based Diagnosis of Human Granulocytic Anaplasmosis, Canada

Whole blood is the optimal specimen for anaplasmosis diagnosis but might not be available in all cases. We PCR tested serum samples collected in Canada for Anaplasma serology and found 84.8%-95.8% sensitivity and 2.8 average cycle threshold elevation. Serum can be acceptable for detecting Anaplasma spp. when whole blood is unavailable.

Performance Assessment on Buffy Coat Examination for Human Granulocytic Anaplasmosis Diagnosis

Abstract Introduction/Objective Anaplasma phagocytophilum is an obligate gram-negative intracellular bacterium that causes human granulocytic anaplasmosis (HGA). The diagnostic tests for HGA include buffy coat examination, culture, PCR, and serology. In our lab, suspected patient will be subjected to buffy coat examination, and the result will be further confirmed with PCR. The aim of the study is to assess the epidemiology of HGA diagnosed at WMC during 06/2014- 08/2019, and as well as the performance accuracy of buffy coat examination as compared to PCR. Methods The results of buffy coat examination and in house HGA PCR from 06/2014 to 08/2019 were collected from SoftLAB and SoftMOL, respectively. Results A total of 1,057 blood specimens were tested by buffy coat examination from 06/2014-08/2019; among them, 658 specimens were also analyzed by HGA PCR assay (Fig. 1). Positivity for buffy coat examination and PCR was 2.6% and 6.1%, respectively. Overall, using PCR as reference diagnostic method, 42 new HGA cases were identified. The number of new HGA cases varied among years from 2 to 15, with year of 2017 having the greatest number of total cases (Fig. 2). Further analyzing new HGA cases by months reveal HGA starts in April and ends in December, and peaks at June and July (Fig. 3). When comparing buffy coat result to PCR, 17 positive buffy coat tests were confirmed positive in PCR test, and 619 negative buffy coat tests were also consistent with negative PCR test result. However, 21 cases which were initially negative in buffy coat examination were positive in PCR tests. On the other hand, 1 positive buffy coat examination case was negative in PCR (table 1). Overall, using PCR as a reference test, the sensitivity and specificity of buffy coat examination are 44.7% and 99.8%, respectively. Conclusion Buffy coat examination has high specificity but low sensitivity in detecting HGAcompared to PCR. Low sensitivity is most likely due to variable presence of intracytoplasmic aggregates of HGA in peripheral blood neutrophils and technically incompetency of testing personnel. Overall, it is a good test for laboratory confirmation of clinically suspected HGA cases. We suggest clinicians to add HGA PCR to all the buffy coat examination to avoid missing potential HGA diagnosis. Moreover, more training and competency on testing personnel may improve the sensitivity of buffy coat exam for diagnosis of HGA.

Morulae in neutrophils: A diagnostic clue for human granulocytic anaplasmosis.

Although there was no specific finding in peripheral blood smears performed on the second day after doxycycline administration in clinically suspected human granulocytic anaplasmosis (HGA) patients, we re-examed the peripheral blood smears performed at the time of admission and found morulaes in neutrophils. This case shows that the detection of morulae in a blood smear can be helpful in the diagnosis of HGA, especially in the acute phase of illness, prior to empirical antibiotic administration.

Accuracy of Diagnosis of Human Granulocytic Anaplasmosis in China.

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.

Clinical and laboratory features parameters of human granulocytic anaplasmosis (HGA) in patients admitted to hospital in Guangdong Province, China.

Human granulocytic anaplasmosis (HGA) is an acute tick-borne infectious disease with increasing morbidity and mortality, but is rarely considered in clinical practice. Because human-to-human transfusion or nosocomial transmission can occur, diagnosis is difficult when the history of tick bites is not clear. We present clinical features and laboratory data of HGA patients who had no clear tick bite history. All patients in the study presented with a high fever, petechiae, purpura, nose bleeding and leukopenia, and patients had abnormally high levels of serum ferritin and C-reactive protein. Morulae in leukocytes were observed in three patients. Foamy histiocytes and slight erythrophagocytic activity were only found in severely ill patients. In patients with fever and thrombocytopenia in whom no other diagnosis is evident on clinical assessment, HGA should be considered in the differential diagnosis, and tested for serologically if possible. For patients in whom the diagnosis of HGA is possible, and to whom tetracyclines can safely be given, it is apparent that these drugs hasten recovery and improve the prognosis.

Diagnosis of human granulocytic anaplasmosis in Belgium by combining molecular and serological methods.

We report here one new, hospitalized case of Anaplasma phagocytophilum in Belgium. The clinical presentation of anaplasmosis, its treatment and the molecular and serological relevant laboratory methods are briefly developed.

The clinical characteristics and outcomes of patients with human granulocytic anaplasmosis in China

The incidence of human granulocytic anaplasmosis (HGA), a tick-borne disease caused by the obligate intracellular bacterium Anaplasma phagocytophilum, has increased across the world. However, information on HGA is lacking in China. The purpose of this study was to investigate the clinical features and outcomes of HGA patients in China. A total of 83 patients with HGA from the provinces of Hubei and Henan in China, who were admitted to Union Hospital between March 2009 and September 2010, were included in this study. We investigated the epidemiology, clinical features, laboratory markers, and therapeutic effects in these patients. We also analyzed life-threatening complications such as systemic inflammatory response syndrome (SIRS)/multiple organ dysfunction syndrome (MODS) following HGA and assessed the risk factors for a poor clinical outcome. In our study, an HGA outbreak peak was observed for the months May to August. The highest age-specific incidence occurred among the group of patients aged 50-59 years. With regard to patient occupation and pathological origin, we found that 73 of the 83 patients with HGA had a peasant occupation. With respect to symptoms, 45 patients had no complications and 38 patients diagnosed with HGA met SIRS criteria, of whom 25 rapidly developed MODS. The mortality for the entire cohort was 26.5%. The factors predictive of patients developing MODS and an adverse outcome were advanced age, disturbance of consciousness, highly elevated lactate dehydrogenase, creatinine, and aspartate aminotransferase levels, and the presence of SIRS. Moreover, MODS was found to be an independent predictor of death. In China, HGA patients had severe clinical symptoms and high rates of complications and mortality. These findings may provide useful information so that physicians will be on the alert for severe complications after a diagnosis of HGA; they will also be useful for optimizing supportive care for HGA-related critical illness. Prompt treatment and close monitoring of severe complications such as SIRS and MODS are of great importance in saving patient lives.

Detection of antibodies against agents of human granulocytic anaplasmosis and human monocytic ehrlichiosis serum from patients from Novosibirsk Region

Serum samples from patients hospitalized with febrile illnesses occurring after tick bites were investigated for antibodies against agents of human granulocytic anaplasmosis (HGA) and human monocytic ehrlichiosis (HME). Ten from 205 patients were shown to contain HGA-specific antibodies, one patient — HME-specific antibodies, and one patient — both antibodies against agents of HGA and HME. Diagnosis of HGA was serologically and clinically confirmed for four patients. All patients with serologically confirmed HGA were shown to contain also antibodies againstBorrelia burgdorferisensu lato or HME-specific antibodies. Moreover, one patient was shown to be infected with tick-borne encephalitis virus. Thus, it seems reasonable to analyze patients with confirmed tick-borne encephalitis as well as with febrile illness after tick bites on the infection with HGA and HME.

Etiology of tick-borne febrile illnesses in adult residents of north-eastern Poland: Report from a prospective clinical study

Febrile tick-borne diseases can be caused by different pathogens. The study objective was to prospectively determine the etiology of infection among adults exposed to tick bite and to detect acute human granulocytic anaplasmosis (HGA), a recently emerging infection, in north-eastern Poland. We evaluated 68 patients (34 males and 34 females, mean age 44.2±15 years) who had fever within 4 weeks after a tick bite. Paired sera were tested for antibodies against tick-borne encephalitis virus, Borrelia burgdorferi and Anaplasma phagocytophilum. Microscopic examination of EDTA whole blood and nested PCR targeting A. phagocytophilum 16S rDNA gene fragment were carried out at enrolment. Tick-borne infections were diagnosed in 57 individuals (84%). Sixty-four patients were hospitalised. Tick-borne encephalitis (TBE) was revealed in 49 cases; in 39 patients as a single infection, in three patients concurrent with erythema migrans or other Lyme borreliosis symptoms, in five patients concurrent with probable or possible Lyme borreliosis, and in two patients concurrent with A. phagocytophilum infection. Diagnosis of HGA was confirmed in one patient by PCR (GenBank accession No. AY833407) and in another one by seroconversion. In two further individuals, A. phagocytophilum infection was confirmed by immunofluorescence (antibody titers ⩾1:128), which, however, does not fulfil the ESCAR (European Society of Clinical Microbiology and Infectious Diseases Study Group on Coxiella, Anaplasma, Rickettsia, and Bartonella) criteria for HGA case definition. Lyme borreliosis was diagnosed in 16 patients; in six of them as a single infection. Both confirmed HGA cases and seropositive individuals had A. phagocytophilum infection concurrent either with Lyme borreliosis (two cases) or with TBE (two cases). The clinical course was severe in three and moderate to mild in the remaining TBE cases, as well as in all Lyme borreliosis and HGA cases. TBE was found the most prevalent disease among adults with febrile illnesses occurring after a tick bite in north-eastern Poland. Concurrent tick-borne infections were frequent with multiple pathogens involved. Two confirmed acute HGA cases (fulfilling the European case definition criteria defined by ESCAR) were detected for the first time in a prospective manner in Poland.