Cases Of Human Granulocytic Anaplasmosis Research Articles

Tick-borne infections in the Leningrad oblast: incidence and seroprevalence

The study’s objective was to reveal trends in infections transmitted by ixodes ticks epidemic processes and the level of seroprevalence of the population to the tick-borne encephalitis virus, Borrelia burgdorferi sensu lato, Coxiella burnetii, Anaplasma phagocytophilum and Ehrlichia chaffeensis/ E. muris in the Leningrad Oblast.Materials and methods. A retrospective epidemiological analysis of the tick-bite incidence rate, the ixodic tick-borne borreliosis, tick-borne encephalitis, Q fever, human granulocytic anaplasmosis and human monocytic ehrlichiosis incidence rates, as well as vaccination against tick-borne encephalitis of the population of the Leningrad Oblast in 20112020. The official data of the tick-bite incidence rate, infections transmitted by ixodes ticks incidence rates and vaccination of the population was taken from the forms of federal statistical observation No. 2 and No. 5. Blood was sampled in 2019-2020 from randomly selected donors. Blood serum samples were examined by enzyme-linked immunosorbent assay for the presence of IgG antibodies to the pathogens of the studied infections using commercial test systems according to the manufacturer’s instructions.Results. In the Leningrad Oblast, in 2011-2020, there was a downward trend in the tick-bite incidence rate, as well as in the incidence rates of infections transmitted by ixodic ticks. The long-term average tick bite incidence rate was 369.0. The long-term average incidence rate of ixodic tick–borne borreliosis was 4.1; tick–borne encephalitis was 1.4; Q fever was 0.02. During the analyzed period, no cases of human granulocytic anaplasmosis and human monocytic ehrlichiosis were reported. The seroprevalence to tick-borne encephalitis virus was 1.7%; to B. burgdorferi s. l. – 3.7%; to C. burnetii – 1.8%; to A. phagocytophilum – 1.0%; to E. chaffeensis/ E.muris – 3.2%.Conclusion. The results obtained indicate the existence of active natural foci of infections transmitted by ixodes ticks, fairly frequent contact of the residents with these foci, and possible significant hypodiagnosis of these infections in the Leningrad Oblast.

Epidemiological, clinical, and laboratory characteristics of human granulocytic anaplasmosis in North India.

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.

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.

A Case of Human Granulocytic Anaplasmosis Suspected to be Complicated by Cholangitis

A Case of Human Granulocytic Anaplasmosis Suspected to be Complicated by Cholangitis

Human Granulocytic Anaplasmosis as a COVID-19 Mimicker.

IntroductionHuman 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 descriptionA 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.DiscussionThe 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).ConclusionHere 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.LEARNING POINTSHuman granulocytic anaplasmosis (HGA) has a widely variable clinical presentation and can be life-threatening.When presented with non-specific symptoms, it is critical to consider clinical and social histories, seasonality and geography while maintaining a broad differential.Cytokine storm can be seen in HGA and other diseases, but most recently it has been observed in the novel COVID-19. However, despite the prevalence of COVID-19, we recommend that HGA remain in the differential diagnosis of a pro-inflammatory state with an atypical respiratory presentation.

COVID-19 and the Consequences of Anchoring Bias.

Suspicion of coronavirus disease in febrile patients might lead to anchoring bias, causing misdiagnosis of other infections for which epidemiologic risks are present. This bias has potentially severe consequences, illustrated by cases of human granulocytic anaplasmosis and Lyme disease in a pregnant woman and human granulocytic anaplasmosis in another person.

Incompetence of the Asian Longhorned Tick (Acari: Ixodidae) in Transmitting the Agent of Human Granulocytic Anaplasmosis in the United States.

The Asian longhorned tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae), was recently introduced into the United States and is now established in at least 15 states. Considering its ability for parthenogenetic propagation and propensity for creating high-density populations, there is concern that this tick may become involved in transmission cycles of endemic tick-borne human pathogens. Human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum is one of the more common tick-borne diseases in the United States, especially in the northeastern and midwestern states. There is considerable geographical overlap between HGA cases and the currently known distribution of H. longicornis, which creates a potential for this tick to encounter A. phagocytophilum while feeding on naturally infected vertebrate hosts. Therefore, we evaluated the ability of H. longicornis to acquire and transmit the agent of HGA under laboratory conditions and compared it to the vector competence of I. scapularis. Haemaphysalis longicornis nymphs acquired the pathogen with the bloodmeal while feeding on infected domestic goats, but transstadial transmission was inefficient and PCR-positive adult ticks were unable to transmit the pathogen to naïve goats. Results of this study indicate that the Asian longhorned tick is not likely to play a significant role in the epidemiology of HGA in the United States.

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.

Spatio-Temporal Dynamics of Tick-Borne Diseases in North-Central Wisconsin from 2000-2016.

Lyme disease is a well-recognized public health problem in the USA, however, other tick-borne diseases also have major public health impacts. Yet, limited research has evaluated changes in the spatial and temporal patterns of non-Lyme tick-borne diseases within endemic regions. Using laboratory data from a large healthcare system in north-central Wisconsin from 2000–2016, we applied a Kulldorf’s scan statistic to analyze spatial, temporal and seasonal clusters of laboratory-positive cases of human granulocytic anaplasmosis (HGA), babesiosis, and ehrlichiosis at the county level. Older males were identified as the subpopulation at greatest risk for non-Lyme tick-borne diseases and we observed a statistically significant spatial and temporal clustering of cases (p < 0.05). HGA risk shifted from west to east over time (2000–2016) with a relative risk (RR) ranging from 3.30 to 11.85, whereas babesiosis risk shifted from south to north and west over time (2004–2016) with an RR ranging from 4.33 to 4.81. Our study highlights the occurrence of non-Lyme tick-borne diseases, and identifies at-risk subpopulations and shifting spatial and temporal heterogeneities in disease risk. Our findings can be used by healthcare providers and public health practitioners to increase public awareness and improve case detection.

The absence of the drhm gene is not a marker for human-pathogenicity in European Anaplasma phagocytophilum strains

BackgroundAnaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes. It is transmitted by ticks of the Ixodes ricinus complex and causes febrile illness in humans and animals. The geographical distribution of A. phagocytophilum spans the Americas, Europe, Africa and Asia. However, human disease predominantly occurs in North America but is infrequently reported from Europe and Asia. In North American strains, the absence of the drhm gene has been proposed as marker for pathogenicity in humans whereas no information on the presence or absence of the drhm gene was available for A. phagocytophilum strains circulating in Europe. Therefore, we tested 511 European and 21 North American strains for the presence of drhm and compared the results to two other typing methods: multilocus sequence typing (MLST) and ankA-based typing.ResultsAltogether, 99% (478/484) of the analyzable European and 19% (4/21) of the North American samples from different hosts were drhm-positive. Regarding the strains from human granulocytic anaplasmosis cases, 100% (35/35) of European origin were drhm-positive and 100% (14/14) of North American origin were drhm-negative. Human strains from North America and Europe were both part of MLST cluster 1. North American strains from humans belonged to ankA gene clusters 11 and 12 whereas European strains from humans were found in ankA gene cluster 1. However, the North American ankA gene clusters 11 and 12 were highly identical at the nucleotide level to the European cluster 1 with 97.4% and 95.2% of identity, respectively.ConclusionsThe absence of the drhm gene in A. phagocytophilum does not seem to be associated with pathogenicity for humans per se, because all 35 European strains of human origin were drhm-positive. The epidemiological differences between North America and Europe concerning the incidence of human A. phagocytophilum infection are not explained by strain divergence based on MLST and ankA gene-based typing.

A Hail Mary Diagnostic Success

Abstract With the advent of newer methodologies, it has become possible to detect previously unsuspected pathogens. We wish to present a case of human granulocytic anaplasmosis that was diagnosed using 16S ribosomal RNA gene sequencing while originally investigating possible culture-negative endocarditis. This case is the first reported in humans from the province of Quebec. A brief review of means of transmission and clinical and laboratory findings as well as treatment is provided.

A walk through the tall grass: A case of transaminitis, thrombocytopenia, and leukopenia resulting from an emerging zoonotic infection in Nova Scotia

Tick born zoonotic infections spread by Ixodes scapularis are on the rise in Canada. Tick-borne illnesses have a large constellation of symptoms associated with them which can often overlap and cloud diagnostic certainty. Human granulocytic anaplasmosis (HGA) is an emerging infectious disease in Canada, with tick carriage rates as high as 15% in some parts of the country. The majority of cases are associated with fever, headache, myalgia and malaise, thrombocytopenia, and transaminitis. The diagnosis is made through indirect fluorescent antibody titres, examination of peripheral smear, or polymerase chain reaction. Here we present the case of an otherwise health 71-year-old male presenting with fevers, thrombocytopenia, leukopenia, and a mixed transaminitis following a tick bite. He was subsequently diagnosed as the first case of HGA in Nova Scotia confirmed by indirect fluorescent antibody titre.

Diagnosis and molecular characteristics of human infections caused by Anaplasma phagocytophilum in South Korea.

Human granulocytic anaplasmosis (HGA) is a tick borne infection caused by Anaplasma phagocytophilum. HGA cases in South Korea have been identified since the first report in 2014. In this study, we investigated the serological response in 594 clinical samples of patients with acute febrile illness and molecular characteristics of A. phagocytophilum clinical isolates obtained from HGA patients. In serological test for A. phagocytophilum, 7.91% (47/594 cases) were positive for IgG and Ig M and 13 of 47 cases showed seroconversion. In the detection rate of the 16S rRNA, msp2(p44), and ankA, genes were showed 3.68% (14/380 cases) for A. phagocytophilum-specific 16S rRNA gene. Phylogenetic analysis of three clinical isolates demonstrated high sequence similarity (98.58-100%) with A. phagocytophilum 16S rRNA sequences identified from public databases. Analysis of the msp2(p44) gene showed highly variable similarity rates (7.24-98.85%) even within isolated countries and host ranges. These results provide clues into the bacterial characterization of A. phagocytophilum originating from Korean patients, providing useful guidance for treatment and improving clinical outcomes.

Anaplasmosis: An emerging tick-borne disease of importance in Canada.

Human Granulocytic Anaplasmosis (HGA) is an infection caused by the intracellular bacterium Anaplasma phagocytophilum. As a tick-borne disease, the public health impact of HGA continues to increase with range expansion of the disease vector. The clinical presentation of HGA is often a non-specific febrile illness. The presence of leukopenia, thrombocytopenia, and mild hepatic injury are frequently noted on laboratory investigations, which can be important diagnostic clues in attaining an appropriate diagnosis. Herein we present three cases of HGA, highlighting the spectrum of disease by which HGA can manifest. Although each case has their unique features, we outline important shared clinical elements to facilitate an empiric diagnosis while definitive laboratory investigations are pending. Our case series further serves to highlight the critical importance of prompt antimicrobial treatment to reduce morbidity and potential mortality.

Anaplasmosis in pediatric patients: Case report and review

Human granulocytic anaplasmosis (HGA) is a tick-borne infection, characterized as an acute and sometimes severe febrile illness which may be associated with leukopenia and thrombocytopenia. Most case reports of HGA have been in adults, with only 8 case reports of HGA in children. We add a ninth case of HGA, which occurred in a 5-year-old. The paucity of pediatric HGA case reports maybe because publication bias, or HGA in children is a mild illness and children with HGA are less likely than adults to seek medical care, or the diagnosis of HGA requires a blood draw and adults (versus children) are more likely to get diagnostic testing. The 9 case reports in children suggest that pediatric HGA is usually a mild infection and that doxycycline and rifampin are effective therapies. Like adults, children with HGA frequently present with fever, headache, and malaise; however, children are more likely than adults to have abdominal pain as a prominent complaint.

Assessment of antibodies against surface and outer membrane proteins of Anaplasma phagocytophilum in Lyme borreliosis and tick-borne encephalitis paediatric patients.

To examine evidence of positive antibodies against immunogenic proteins of Anaplasma phagocytophilum in patients with other tick-borne infections and to diagnose possible co-infections, 412 serum specimens were tested by immunoblotting using three specific Anaplasma antigens: surface proteins p44 and Asp62 and outer membrane protein A (OmpA). In total, 284 serum samples from children with Lyme borreliosis and 12 serum samples from children with tick-borne encephalitis were tested. Sera from patients with viral aseptic meningitis (n = 47) and from blood donors (n = 69) were used as controls. Among all serum specimens from patients with tick-borne infections submitted for this study, six samples (2·0%) showed positive IgM reactions and seven samples (2·4%) were IgG positive for A. phagocytophilum by immunoblot. Borderline reactivity was found in 30 samples (10·14%) for IgM and 36 samples (12·2%) for IgG. The difference between patients and blood donors was statistically significant for IgM (P = 0·006) and for IgG (P = 0·0007) antibodies. A statistically significant result was obtained for IgG (P = 0·02) but not for IgM between patients and children with aseptic meningitis. Immunoblot using three specific antigens provides novel information about the positivity of antibodies to A. phagocytophilum in children with other tick-borne infections. Taking into account clinical and laboratory findings of children despite antibody positivity, no case of human granulocytic anaplasmosis was demonstrated.

Epidemiology and Genetic Diversity of Anaplasma phagocytophilum in the San Francisco Bay Area, California.

In California, the agent of human granulocytic anaplasmosis (HGA), Anaplasma phagocytophilum, is transmitted by western black-legged ticks (Ixodes pacificus). Cases of HGA are infrequent in California but do occur annually. We investigated nymphal and adult western black-legged tick populations in 20 recreational areas in California's San Francisco Bay Area (Marin, Napa, San Mateo, Santa Clara, Santa Cruz, and Sonoma counties). Overall, prevalence of A. phagocytophilum in adult ticks was 0.8% (11/1,465), and in nymphal ticks was 4.2% (24/568), though presence was patchy and prevalence varied locally. We detected significant sequence variation in our quantitative polymerase chain reaction (qPCR)-positive samples. This included four sequences that grouped within a clade that contains clinical human and veterinary isolates as well as four others that grouped with sequences from PCR-positive lizards from northern California. Tick populations in our study sites harbor genetically diverse strains of A. phagocytophilum, which may influence potential risk in the region.

Serological and molecular detection of Anaplasma phagocytophilum in horses reared in Korea

The objective of this study was to investigate the nationwide prevalence of Anaplasma phagocytophilum in horses reared in Korea using a commercial ELISA kit and two different nested PCR (nPCR) analyses. Our analysis showed that 2.9% (true prevalence: 3.1%, 16/549) of the horses were seropositive by ELISA, and none were positive by the two nPCR analyses. Significant differences were observed in the ELISA results when the data were analysed according to breed and geographic region. In light of a recent case of human granulocytic anaplasmosis in Korea and the predicted increase in the number and distribution of ticks due to global warming, continuous monitoring and appropriate control programs for Anaplasma spp. and other tick-borne pathogens need to be established.

“Orange” You Glad You Checked the Buffy Coat?

The incidence of tick-borne human infectious syndromes has dramatically risen in the last 2 decades, leading to significant morbidity and mortality. The importance of a rapid and accurate diagnosis to distinguish anaplasmosis from other febrile illnesses is paramount for the prompt administration of appropriate antibiotics and is imperative for the successful treatment of the tick-borne infections. We summarize the current literature describing the biology, clinical presentation, and epidemiology of human granulocytic anaplasmosis. In addition, we report a case of human granulocytic anaplasmosis in one of the less common geographical areas (Pennsylvania) during the winter month of December. Laboratory methods, including use of an acridine orange buffy coat fluorescent stain that helped decreased the time to result and increased confidence in the diagnosis, are also described.

Anaplasma phagocytophilumAntibodies in Humans, Japan, 2010–2011

To the Editor: Human granulocytic anaplasmosis (HGA) is an emerging tick-borne infectious disease caused by Anaplasma phagocytophilum, an obligatory intracellular bacterium (1). Recently, 2 cases of HGA were identified by a retrospective study in Japan (2). For serodiagnosis of HGA, A. phagocytophilum propagated in HL60 cells is usually used as an antigen, especially by indirect immunofluorescent assay (IFA) (3). However, the serum from these 2 patients in Japan reacted with antigens of A. phagocytophilum cultured in THP-1 cells rather than in HL60 cells in IFA (2). In A. phagocytophilum, a p44/msp2 multigene family encoding multiple 44-kDa immunodominant major outer membrane protein species (so-called P44) exists on the genome, and these multigenes are similar, but not identical, to each other, and the bacterium generates antigenic variations because of gene conversion (4). The previous studies showed that A. phagocytophilum expresses predominantly 2 species of p44/msp2 transcripts in THP-1 cells, but it produces the variation of P44 protein species in HL60 cells (2,5). This finding strongly suggested that A. phagocytophilum grown in THP-1 cells differs serologically from that in HL60 cells. Our serologic analysis found 4 recent cases of HGA in Japan by using infected THP-1 and HL60 cells as antigens, and some P44 immunoreactive protein species of A. phagocytophilum that were associated with the respective cell line cultures, binding to antibodies from the 4 patients’ serum, also were identified.