Ehrlichiosis and human anaplasmosis

Human ehrlichiosis and anaplasmosis are acute febrile tick-borne diseases caused by various species of the genera Ehrlichia and Anaplasma (Anaplasmataceae). To date, only cases of human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum (formerly human granulocytic Ehrlichia, Ehrlichia phagocytophila, and E. equi) have been diagnosed in Europe. HGA and Lyme borreliosis are closely related diseases that share vector and reservoirs. In addition to HGA, human monocytic ehrlichiosis caused by E. chaffeensis has been reported in North America, as well as cases of infection due to E. ewingii in immunocompromised hosts. Ehrlichia spp. and A. phagocytophilum have tropism for blood cells, especially leukocytes and platelets, causing a considerable decrease of both components in these patients. HGA should be suspected in tick-bitten patients or those who have visited an endemic area and show symptoms of flu-like fever, leukopenia and thrombocytopenia.     

Lyme disease followed by human granulocytic anaplasmosis in a kidney transplant recipient

We report the case of a kidney transplant recipient who developed Lyme disease, followed by human granulocytic anaplasmosis (HGA) 3 years later. A review of all previously published cases of Lyme disease (3 cases), HGA (5 cases), and human monocytic ehrlichiosis (HME) (5 cases) in transplant recipients is presented. Manifestations of the cases reviewed were similar to those of non-transplant patients. There appeared to be no obvious correlation between immunosuppression and the occurrence of the illness in the transplant recipients. Serologic testing failed to make a diagnosis in 1 patient with HME in the literature and in our patient with HGA, but molecular tests established the diagnosis in both cases. Tandem infection was observed in 1 patient with two episodes of HME 2 years apart. A high index of suspicion for tick-borne illnesses and appropriate prevention measures are needed for transplant patients with epidemiologic risk factors.     

Epidemiology of Ehrlichiosis and Anaplasmosis among American Indians in the United States, 2000-2007

Abstract. Ehrlichiosis and anaplasmosis infections among American Indians (AIs) have never been specifically examined, despite high rates of other tick-borne rickettsial diseases among AIs. The epidemiology of ehrlichiosis and anaplasmosis among AIs was analyzed using the National Electronic Telecommunications System for Surveillance (NETSS), Case Report Forms (CRFs), and Indian Health Service (IHS) inpatient and outpatient visits. The 2000-2007 average annual ehrlichiosis and anaplasmosis incidence among AIs reported to NETSS was almost 4-fold lower (4.0/1,000,000) than that using IHS data (14.9). American Indian cases reported from CRFs had a higher proportion of hospitalization (44%) compared with IHS (10%). American Indian incidence of ehrlichiosis and anaplasmosis was higher and showed a different age and geographical distribution than other races. These results highlight the need to improve collaboration between the ehrlichiosis and anaplasmosis surveillance systems for AIs so as to develop interventions that target the unique epidemiology and mitigate the burden of disease among this high-risk population.     

Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000-2007

Ehrlichia chaffeensis causes human monocytic ehrlichiosis, and Anaplasma phagocytophilum causes human granulocytic anaplasmosis. These related tick-borne rickettsial organisms can cause severe and fatal illness. During 2000-2007, the reported incidence rate of E. chaffeensis increased from 0.80 to 3.0 cases/million persons/year. The case-fatality rate was 1.9%, and the hospitalization rate was 49%. During 2000-2007, the reported incidence of A. phagocytophilum increased from 1.4 to 3.0 cases/million persons/year. The case-fatality rate was 0.6%, and the hospitalization rate was 36%. Rates among female patients were lower than among male patients for ehrlichiosis (rate ratio = 0.68) and anaplasmosis (rate ratio = 0.70). Most (80%) ehrlichiosis and anaplasmosis cases met only a probable case definition, although, use of a polymerase chain reaction to confirm infections increased during 2000-2007. Heightened reporting of these diseases will likely continue with improving recognition, changing surveillance practices, and appropriate application of diagnostic assays.     

Increasing Incidence of Ehrlichiosis in the United States: A Summary of National Surveillance of Ehrlichia chaffeensis and Ehrlichia ewingii Infections in the United States, 2008–2012

Human ehrlichiosis is a potentially fatal disease caused by Ehrlichia chaffeensis and Ehrlichia ewingii. Cases of ehrlichiosis are reported to Centers for Disease Control and Prevention through two national surveillance systems: Nationally Notifiable Diseases Surveillance System (NNDSS) and Case Report Forms. During 2008–2012, 4,613 cases of E. chaffeensis infections were reported through NNDSS. The incidence rate (IR) was 3.2 cases per million person-years (PYs). The hospitalization rate (HR) was 57% and the case fatality rate (CFR) was 1%. Children aged < 5 years had the highest CFR of 4%. During 2008–2012, 55 cases of E. ewingii infection were reported through NNDSS. The national IR was 0.04 cases per million PY. The HR was 77%; no deaths were reported. Immunosuppressive conditions were reported by 26% of cases. The overall rate for ehrlichiosis has increased 4-fold since 2000. Although previous literature suggests E. ewingii primarily affects those who are immunocompromised, this report shows most cases occurred among immunocompetent patients. This is the first report to show children aged < 5 years with ehrlichiosis have an increased CFR, relative to older patients. Ongoing surveillance and reporting of tick-borne diseases are critical to inform public health practice and guide disease treatment and prevention efforts.     

发热伴血小板减少综合征病例中无形体病鉴别诊断与治疗

目的 确定发热伴血小板减少综合征患者中是否存在人粒细胞无形体病(human granulocytic anaplasmosis,HGA),并进行HGA临床分析.方法 将2010年收治的42例发热伴血小板减少综合征患者血液标本,送中国疾病预防控制中心(Centers for Disease Control and Pre...     

中国人粒细胞无形体病流行现状及其影响因素

人粒细胞无形体病是威胁人类健康的新发蜱传自然疫源性疾病。近年来随着原生环境的加速开发以及人口流动加快,人粒细胞无形体病感染数量逐年上升且传播范围不断扩大。为了更有效的预防控制人粒细胞无形体病,本文就我国人粒细胞无形体病流行现状进行概述,并分析生物因素、自然因素、社会因素对人粒细胞无形体病发生和流行的影响。     

Habitat factors influencing distributions of Anaplasma phagocytophilum and Ehrlichia chaffeensis in the Mississippi Alluvial Valley

Human monocytotropic ehrlichiosis (HME), caused by the bacterium Ehrlichia chaffeensis, and human granulocytic anaplasmosis (HGA), caused by the bacterium Anaplasma phagocytophilum, are two emerging tick-borne zoonoses of concern. Factors influencing geographic distributions of these pathogens are not fully understood, especially at varying spatial extents (regional versus landscape) and resolutions (counties versus smaller land units). We used logistic regression to compare influences of physical environment, land cover composition, and landscape heterogeneity on distributions of A. phagocytophilum and E. chaffeensis at multiple spatial extents. Pathogen presence or absence was determined from white-tailed deer (Odocoileus virginianus) serum samples collected from 1981 to 2005. Ecological predictor variables were derived from spatial datasets that represented deer density, elevation, land cover, normalized difference vegetation index (NDVI), hydrology, and soil moisture. We used three strategies (a priori, exploratory, and spatial extent) to develop models. Best fitting models were applied within a geographic information system to create predictive probability surfaces for each bacterium. Ecological predictor variables generally resulted in better fitting models for E. chaffeensis than A. phagocytophilum (90.5% and 68% sensitivity, respectively), possibly as a result of differences in the natural histories of tick vectors. Although alternative model development strategies produced different models, in all cases bacteria presence or absence was affected by a combination of soil moisture or flooding variables (thought to affect primarily tick vectors) and forest cover or NDVI variables (thought to affect primarily mammalian hosts). This research demonstrates the potential for modeling the distributions of microscopic tick-borne pathogens using coarse regional datasets and emphasizes the importance of forest cover and flooding as environmental constraints, as well as the importance of considering ecological variables at multiple spatial extents.     

Spatial analysis of the distribution of Ehrlichia chaffeensis, causative agent of human monocytotropic ehrlichiosis, across a multi-state region

Ehrlichia chaffeensis, which causes human monocytotrophic ehrlichiosis (HME), is an important emerging tick-borne pathogen in the southeastern and southcentral United States. The endemnicity probability of E. chaffeensis and, by implication, locations with risk for HME, was predicted by using two modeling methods. This is first large-scale study to use geospatial analyses to estimate the distribution of E. chaffeensis, and it was conducted using data from a prototypic surveillance system that used white-tailed deer as natural sentinels. Analyses included the E. chaffeensis serostatus for 563 counties from 18 states. Both kriging and logistic regression models provided very reliable portrayals of E. chaffeensis occurrence and predicted that E. chaffeensis distribution had good concordance with human case data. The integration of a deer surveillance system with geospatial analyses was useful in developing HME risk maps that will be useful for identifying high-risk areas for public health interventions such as prevention and control efforts.     

Efficient use of a small genome to generate antigenic diversity in tick-borne ehrlichial pathogens

Ehrlichiae are responsible for important tick-transmitted diseases, including anaplasmosis, the most prevalent tick-borne infection of livestock worldwide, and the emerging human diseases monocytic and granulocytic ehrlichiosis. Antigenic variation of major surface proteins is a key feature of these pathogens that allows persistence in the mammalian host, a requisite for subsequent tick transmission. In Anaplasma marginale pseudogenes for two antigenically variable gene families, msp2 and msp3, appear in concert. These pseudogenes can be recombined into the functional expression site to generate new antigenic variants. Coordinated control of the recombination of these genes would allow these two gene families to act synergistically to evade the host immune response.     

Human granulocytic anaplasmosis

Tick-borne infections have been recognized in the United States for more than a century. Patients who present with nonspecific fever after exposure to ticks should be evaluated by clinical examination and routine laboratory testing to determine if the illness is potentially a tick-borne infection. This article focuses on the diagnosis and management of human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum.     

Short report: Race and rickettsiae: a United States perspective

US surveillance programs for Rocky Mountain spotted fever (RMSF), ehrlichiosis, and anaplasmosis collect demographic data on patients, including race and ethnicity. Reporting of these diseases among race groups is not uniform across the United States. Because a laboratory confirmation is required to meet the national surveillance case definition, reporting may be influenced by a patient's access to healthcare. Determining the association between race and ethnicity with incidence of rickettsial infections requires targeted, active surveillance.     

Human granulocytic ehrlichiosis in a renal allograft recipient: review of the clinical spectrum of disease in solid organ transplant patients

Background. Ehrlichiosis is a recently described zoonotic infection with two major expressions: human granulocytic ehrlichiosis (HGE) and human monocytic ehrlichiosis (HME). The organisms associated with HGE and HME have been detected in a tick vector in several regions of United States and cases of ehrlichiosis have been reported in the general population. Methods. We report a case of HGE in a renal allograft recipient and review the clinical spectrum of disease in solid organ transplant recipients and the epidemiological basis for risk. Results. Our patient demonstrated the typical epidemiological, clinical and laboratory features of human granulocytic ehrlichiosis and responded to treatment with doxycycline. Conclusions. Human ehrlichiosis should be considered in the differential diagnosis of patients with solid organ transplants, who present with fever and thrombocytopenia. The incidence of ehrlichiosis in the solid organ transplant population is similar to that in the United States general population. As reported in immunocompetent patients, prompt diagnosis and treatment results in the rapid resolution of symptoms in transplanted individuals.     

Rocky Mountain spotted fever in the United States, 1997-2002

Rocky Mountain spotted fever (RMSF) is the most commonly reported fatal tick-borne disease in the United States. During 1997-2002, 3,649 cases of RMSF were reported to the Centers for Disease Control and Prevention via the National Electronic Telecommunications System for Surveillance; 2,589 case report forms, providing supplemental information, were also submitted. The average annual RMSF incidence during 1997-2002 was 2.2 cases/million persons. The annual incidence increased during 1997-2002 to a rate of 3.8 cases/million persons in 2002. The incidence was lowest among persons aged<5 and 10-29 years, and highest among adults aged 60-69 years. The overall case-fatality rate was 1.4%; the rate peaked in 1998 at 2.9% and declined to 0.7% in 2001 and 2002. Children<5 years of age had a case-fatality rate (5%) that was significantly greater than the rates for age groups<60 years of age, except for that for 40-49 years of age. Continued national surveillance is needed to assess the effectiveness of prevention efforts and early treatment in decreasing severe morbidity and mortality associated with RMSF.     

Dissociation between inhibition and killing by levofloxacin in human granulocytic anaplasmosis

Human granulocytic anaplasmosis (HGA) is a potentially fatal tick-borne infection caused by Anaplasma phagocytophilum. Treatment options are limited for this entity, with doxycycline being the drug of choice. Certain fluoroquinolones such as levofloxacin are active against A. phagocytophilum in vitro. We report a hospitalized patient with HGA who improved coincident with a 13-day course of levofloxacin therapy, but clinically and microbiologically relapsed 15 days after completion of treatment. Relapse of infection after levofloxacin therapy was reproduced in a severe combined immune-deficient (SCID) mouse infection model. Quinolone therapy should not be considered curative of HGA.     

Hemophagocytic Lymphohistiocytosis Secondary to Ehrlichia Chaffeensis in Adults: A Case Series From Oklahoma

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation that occurs as either a familial disorder or as a sporadic condition in association with a variety of triggers. Infections are the most common cause of HLH in adults and should be searched for as early treatment usually results in a favorable outcome. Human monocytotropic ehrlichiosis (HME) is a very rare cause of HLH. Failure to consider ehrlichiosis can result in misdiagnosis and an increased length of hospitalization and healthcare cost as described in our report. Treatment for secondary HLH is aimed at reducing hypercytokinemia and eradicating inflammatory and infected cells. It is important to promptly initiate doxycycline when tick-borne diseases are being entertained as a possible trigger, as the antibiotic is effective, safe and inexpensive.     

Undetermined Human Ehrlichiosis and Anaplasmosis in the United States, 2008–2012: A Catch-All for Passive Surveillance

Human ehrlichiosis and anaplasmosis are potentially severe illnesses endemic in the United States. Several bacterial agents are known causes of these diseases: Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia muris-like agent, Panola Mountain Ehrlichia species, and Anaplasma phagocytophilum. Because more than one agent may be present in one area, cases of human ehrlichiosis and anaplasmosis may be reported as “human ehrlichiosis/anaplasmosis undetermined” when the available evidence does not suggest an etiology to the species level. Here, we present a brief summary of these undetermined cases with onset of symptoms from 2008 to 2012 reported to two passive surveillance systems in the United States. The reported incidence rate during this time was 0.52 cases per million person-years. Many cases (24%) had positive polymerase chain reaction results. Enhanced surveillance in an area where several of these etiologic agents are endemic may provide a better understanding of the epidemiology of ehrlichiosis and anaplasmosis in the United States.Recently, we summarized data from passive surveillance on case reports of infections caused by Ehrlichia chaffeensis, Ehrlichia ewingii, and Anaplasma phagocytophilum.^1,2 Although human ehrlichiosis and anaplasmosis are clinically similar, the enzootic cycle and epidemiology of these illnesses are distinct.³ In particular, Amblyomma americanum (the lone star tick) vectors E. chaffeensis, E. ewingii, and the Panola Mountain Ehrlichia, whereas Ixodes scapularis (the black-legged tick) is the primary vector for A. phagocytophilum and also a possible vector for Ehrlichia muris-like (EML) agent.^4–8 The range of both the lone star tick and the black-legged tick have recently expanded, and both human ehrlichiosis and anaplasmosis may be endemic where both tick vectors are present.^9,10 The discovery of human infections with the EML agent in the Upper Midwest, and with the Panola Mountain Ehrlichia species in Georgia, adds another layer to understanding the epidemiology of ehrlichiosis and anaplasmosis in the United States.^7,8 Because definitive diagnostic laboratory evidence is not always available for cases of human ehrlichiosis and anaplasmosis, a catch-all reporting category—human ehrlichiosis/anaplasmosis undetermined—is used for passive surveillance, in addition to the specific reporting categories for infections with E. chaffeensis, E. ewingii, and A. phagocytophilum.¹¹ Here, we present a summary of these undetermined cases reported in the United States with onset of symptoms during 2008–2012.Two passive surveillance systems collect data on these undetermined cases. The Nationally Notifiable Diseases Surveillance System (NNDSS) collects data on demographics and whether the case is classified as confirmed or probable. Additional information is reported on supplemental case report forms (CRFs): whether the case was clinically compatible, whether the case was hospitalized, whether the case survived, and diagnostic laboratory results. The distribution of case demographics reported is similar between the two systems, suggesting that one system is representative of the other (12^,13 County-level incidence rates are highest in the Upper Midwest where human anaplasmosis and EML incidence is highest; other states where multiple etiologic agents are endemic report undetermined cases (Figure 1 ). A total of 175 cases (24%) were reported with both unknown race and ethnicity through NNDSS and 106 cases (20%) were reported with both unknown race and ethnicity through CRFs. This incomplete reporting of race and ethnicity is similar to cases of human ehrlichiosis and anaplasmosis with determined etiology.^1,2Open in a separate windowFigure 1.Map of reported county incidence rates of human ehrlichiosis/anaplasmosis undetermined with onset of symptoms during 2008–2012. The number of cases is from the Nationally Notifiable Diseases Surveillance System, and person-time at risk is calculated using the U.S. Census Bureau population estimates.^12,13 States are designated “NN” when undetermined cases were not notifiable for the duration of 2008–2012.

Table 1

Demographics of reported cases of human ehrlichiosis/anaplasmosis undetermined with onset of symptoms during 2008–2012 to the NNDSS and through supplemental CRFs

Human granulocytic ehrlichiosis in pancreas transplant recipients

Abstract: Human ehrlichioses are tick‐borne infections caused by bacteria in the genus Ehrlichia of the family Rickettsiaceae. To date there have been three cases of ehrlichiosis reported in the transplant population, a human monocytic ehrlichiosis (HME) infection in a liver transplant recipient and two cases of human granulocytic ehrlichiosis (HGE) in kidney transplant recipients. We report three pancreas transplant patients who developed HGE in the last two years at a single southeastern center in the United States. All three patients had clinical, laboratory, and pathophysiologic findings on bone marrow biopsy and peripheral blood smears consistent with HGE, and responded to doxycycline therapy. In the setting of potent immunosuppression, ehrlichiosis should be considered in the differential diagnosis of transplant patients presenting with persistent fever, pancytopenia, and abnormal liver function. Patients with ehrlichiosis infection may be at risk for developing other opportunistic infections or lymphoproliferative disease.     

Anaplasma phagocytophilum presenting with orchitis in a renal transplant recipient

Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, is an emerging tick‐borne disease. It is spread by the black‐legged deer tick Ixodes scapularis that serves as the vector for six human pathogens. HGA is still rarely reported in solid organ transplant recipients. In solid organ transplant recipients, orchitis has been reported secondary to chickenpox, tuberculosis and infections due to Listeria monocytogenes and Nocardia asteroides. Orchitis as a presenting feature of HGA infection has only been reported in animals. We present a unique case of a renal transplant recipient with HGA that presented as orchitis. We also compare the clinical presentation and laboratory findings of our patient with other cases of HGA in transplant recipients. To the best of our knowledge, our patient is one of the first cases of A phagocytophilum mono‐infection causing a classical presentation of orchitis in a transplant patient.