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Gygax L, Schudel S, Kositz C, Kuenzli E, Neumayr A. Human monocytotropic ehrlichiosis-A systematic review and analysis of the literature. PLoS Negl Trop Dis 2024; 18:e0012377. [PMID: 39093857 PMCID: PMC11324158 DOI: 10.1371/journal.pntd.0012377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 08/14/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024] Open
Abstract
Human monocytotropic ehrlichiosis (HME) is a tick-borne bacterial infection caused by Ehrlichia chaffeensis. Most available data come from case reports, case series and retrospective studies, while prospective studies and clinical trials are largely lacking. To obtain a clearer picture of the currently known epidemiologic distribution, clinical and paraclinical presentation, diagnostic aspects, complications, therapeutic aspects, and outcomes of HME, we systematically reviewed the literature and analyzed and summarized the data. Cases of HME are almost exclusively reported from North America. Human infections due to other (non-chaffeensis) Ehrlichia spp. are rare. HME primarily presents as an unspecific febrile illness (95% of the cases), often accompanied by thrombocytopenia (79.1% of the cases), leukopenia (57.8% of the cases), and abnormal liver function tests (68.1% of the cases). Immunocompromized patients are overrepresented among reviewed HME cases (26.7%), which indicates the role of HME as an opportunistic infection. The incidence of complications is higher in immunocompromized compared to immunocompetent cases, with ARDS (34% vs 19.8%), acute renal failure (34% vs 15.8%), multi organ failure (26% vs 14.9%), and secondary hemophagocytic lymphohistiocytosis (26% vs 14.9%) being the most frequent reported. The overall case fatality is 11.6%, with a significant difference between immunocompetent (9.9%) and immunocompromized (16.3%) cases, and sequelae are rare (4.2% in immunocompetent cases, 2.5% in immunocompromised cases).
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Affiliation(s)
- Larissa Gygax
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Sophie Schudel
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Christian Kositz
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Esther Kuenzli
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Andreas Neumayr
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Department of Public Health and Tropical Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia
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Challenges of Diagnosing Severe Ehrlichiosis in Orthotopic Liver Transplant Recipients. Case Rep Transplant 2021; 2021:8285326. [PMID: 34840851 PMCID: PMC8612778 DOI: 10.1155/2021/8285326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 10/15/2021] [Indexed: 11/17/2022] Open
Abstract
In recent solid organ transplant recipients, acute febrile illness is usually a source of grave concern and a diagnostic dilemma, especially if no response is noted after initiation of broad antimicrobial therapy. Human Monocytic Ehrlichiosis (HME) is a tick-borne illness caused by Ehrlichia chaffeensis and is not considered an opportunistic infection in immunocompromised patients such as solid organ transplant patients. Ehrlichiosis in immunocompromised patients can be life-threatening, and a strong index of suspicion is needed, especially in patients who live in endemic areas, for proper treatment initiation with doxycycline. We report a case of a 40-year-old male who received an orthotopic liver transplant six months earlier secondary to primary sclerosing cholangitis, on chronic immunosuppressive medication, who presented with complaints of sudden onset fever associated with nausea, vomiting, and diarrhea. Initial extensive infectious workup was negative and no response to empiric antimicrobials. There was suspicion for ehrlichiosis prompting empiric doxycycline use. Subsequently, E. chaffeensis polymerase chain reaction (PCR) was positive, and the antibiotic regimen was de-escalated to only doxycycline with complete resolution of his symptoms and progressive improvement in previously abnormal biochemical indices.
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3
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Saha A, Browning C, Dandamudi R, Barton K, Graepel K, Cullity M, Abusalah W, Christine D, Rossi C, Drexler N, Basavaraju S, Annambhotia P, Guillamet RV, Eid AJ, Maliakkal J, Miller A, Hugge C, Dharnidharka VR, Kandula P, Moritz MJ. Donor-derived ehrlichiosis: two clusters following solid organ transplantation. Clin Infect Dis 2021; 74:918-923. [PMID: 34329411 DOI: 10.1093/cid/ciab667] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Indexed: 11/14/2022] Open
Abstract
Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor derived clusters of ehrlichiosis are described here. During the summer of 2020, two cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis (HLH). Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All three were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization (OPO) and the OPTN for further investigation by public health authorities.
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Affiliation(s)
- Aditi Saha
- Renal and Pancreas Transplant Division and Department of Medicine, Saint Barnabas Medical Center, Livingston, New Jersey, USA
| | - Charles Browning
- Department of Transplant Surgery, Lehigh Valley Health Network, Allentown, Pennsylvania, USA
| | - Raja Dandamudi
- Division of Pediatric Nephrology, Washington University of Medicine St. Louis, Missouri, USA
| | - Kevin Barton
- Division of Pediatric Nephrology, Washington University of Medicine St. Louis, Missouri, USA
| | - Kevin Graepel
- Division of Pediatric Nephrology, Washington University of Medicine St. Louis, Missouri, USA
| | - Madeline Cullity
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Wala Abusalah
- Renal and Pancreas Transplant Division and Department of Medicine, Saint Barnabas Medical Center, Livingston, New Jersey, USA
| | - Du Christine
- Department of Transplant Surgery, Lehigh Valley Health Network, Allentown, Pennsylvania, USA
| | - Carla Rossi
- Department of Infectious Disease, Lehigh Valley Health Network, Allentown, Pennsylvania, USA
| | - Naomi Drexler
- Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sridhar Basavaraju
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Pallavi Annambhotia
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | | | - Albert J Eid
- Division of Infectious Diseases, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Joseph Maliakkal
- Division of Pediatric Nephrology, Saint Louis University, Missouri, USA
| | - Aaron Miller
- Division of Pediatric Infectious Disease, Saint Louis University, Missouri, USA
| | - Christopher Hugge
- Division of Pediatric Hematology Oncology, Saint Louis University, Missouri, USA
| | - Vikas R Dharnidharka
- Division of Pediatric Nephrology, Washington University of Medicine St. Louis, Missouri, USA
| | - Praveen Kandula
- Renal and Pancreas Transplant Division and Department of Medicine, Saint Barnabas Medical Center, Livingston, New Jersey, USA
| | - Michael J Moritz
- Department of Transplant Surgery, Lehigh Valley Health Network, Allentown, Pennsylvania, USA
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Masterson EM, Gupta S, Jakharia N, Peacock JE. Ehrlichiosis in a recent kidney transplant recipient: The repellent that did not repel! A case report and literature review of ehrlichiosis in solid organ transplant patients. Transpl Infect Dis 2020; 22:e13299. [PMID: 32306509 DOI: 10.1111/tid.13299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/05/2020] [Accepted: 04/13/2020] [Indexed: 11/29/2022]
Abstract
Ehrlichiosis has been infrequently reported in immunosuppressed patients such as solid organ transplants (SOT). We report a case of Ehrlichia chaffeensis infection in an immunosuppressed woman four months after deceased donor kidney transplantation. The diagnosis was confirmed by PCR testing in serum, and the patient responded promptly to treatment with doxycycline. To supplement our Case Report, a literature review encompassing 1995 to present was also performed using PubMed as the search vehicle. Search terms that were utilized include: ehrlichiosis, HME, E chaffeensis, kidney transplant(ation), renal transplant(ation), solid organ transplant(ation), and immunosuppression. The diagnosis of ehrlichiosis can be challenging in SOT patients since ehrlichiosis is not a classic opportunistic infection in SOT. Transplant physicians must have a high clinical suspicion for the diagnosis in patients with an acute febrile illness accompanied by headache, worsening cytopenias, and transaminitis who live in endemic areas, especially if they have tick exposure.
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Affiliation(s)
| | - Siddhi Gupta
- Department of Internal Medicine, Section on Infectious Diseases, Wake Forest Baptist Health, Winston-Salem, North Carolina
| | - Niyati Jakharia
- Wake Forest School of Medicine, Winston-Salem, North Carolina.,Department of Internal Medicine, Section on Infectious Diseases, Wake Forest Baptist Health, Winston-Salem, North Carolina
| | - James E Peacock
- Wake Forest School of Medicine, Winston-Salem, North Carolina.,Department of Internal Medicine, Section on Infectious Diseases, Wake Forest Baptist Health, Winston-Salem, North Carolina
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Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L, Bogdanic M, Savic V, Mikulic D, Pavicic-Saric J, Stevanovic V, Vilibic-Cavlek T. Emerging and neglected zoonoses in transplant population. World J Transplant 2020; 10:47-63. [PMID: 32257849 PMCID: PMC7109593 DOI: 10.5500/wjt.v10.i3.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 03/15/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Many reports on donor-derived or naturally acquired (re-)emerging arboviral infections such as dengue, chikungunya, West Nile, tick-borne encephalitis and Zika virus infection have demonstrated atypical or more complicated clinical course in immunocompromised hosts. Hepatitis E virus has emerged as a serious problem after solid organ transplantation (SOT), leading to diverse extrahepatic manifestations and chronic hepatitis with unfavorable outcomes. Some neglected pathogens such as lymphocytic choriomeningitis virus can cause severe infection with multi-organ failure and high mortality. In addition, ehrlichiosis may be more severe with higher case-fatality rates in SOT recipients. Some unusual or severe presentations of borreliosis, anaplasmosis and rickettsioses were also reported among transplant patients. Moreover, toxoplasmosis as infectious complication is a well-recognized zoonosis in this population. Although rabies transmission through SOT transplantation has rarely been reported, it has become a notable problem in some countries. Since the spreading trends of zoonoses are likely to continue, the awareness, recognition and treatment of zoonotic infections among transplant professionals should be imperative.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Rafaela Novak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Nenad Pandak
- Depatment of Medicine, The Royal Hospital Muscat, Muscat 111, Oman
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | | | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Abdominal and Transplant Surgery, Merkur University Hospital, Zagreb 10000, Croatia
| | - Jadranka Pavicic-Saric
- Department of Anesthesiology and Intensive Medicine, Merkur University Hospital, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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Abstract
Human ehrlichiosis and anaplasmosis are acute febrile tick-borne infectious diseases caused by various members from the genera Ehrlichia and Anaplasma. Ehrlichia chaffeensis is the major etiologic agent of human monocytotropic ehrlichiosis (HME), while Anaplasma phagocytophilum is the major cause of human granulocytic anaplasmosis (HGA). The clinical manifestations of HME and HGA ranges from subclinical to potentially life-threatening diseases associated with multi-organ failure. Macrophages and neutrophils are the major target cells for Ehrlichia and Anaplasma, respectively. The threat to public health is increasing with newly emerging ehrlichial and anaplasma agents, yet vaccines for human ehrlichioses and anaplasmosis are not available, and therapeutic options are limited. This article reviews recent advances in the understanding of HME and HGA.
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Biggs HM, Behravesh CB, Bradley KK, Dahlgren FS, Drexler NA, Dumler JS, Folk SM, Kato CY, Lash RR, Levin ML, Massung RF, Nadelman RB, Nicholson WL, Paddock CD, Pritt BS, Traeger MS. Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States. MMWR Recomm Rep 2016; 65:1-44. [PMID: 27172113 DOI: 10.15585/mmwr.rr6502a1] [Citation(s) in RCA: 347] [Impact Index Per Article: 38.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.
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Affiliation(s)
- Holly M Biggs
- National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta, Georgia
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Phatharodom P, Limsrichamrern S, Kaewwinud J, Chayakulkeeree M. Murine typhus in a liver transplant recipient: report of a first case. Transpl Infect Dis 2015; 17:574-8. [PMID: 25867285 DOI: 10.1111/tid.12394] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 03/12/2015] [Accepted: 04/05/2015] [Indexed: 02/03/2023]
Abstract
Zoonoses, especially rickettsial diseases, are rarely reported in solid organ transplant recipients. We report here a case of murine typhus in a 69-year-old liver transplant recipient, who presented with acute febrile illness 5 years post transplantation. Although receiving treatment with broad-spectrum antibiotics, he was still febrile and developed progressive dyspnea. Laboratory results showed elevated transaminases and his chest radiograph revealed bilateral interstitial infiltration. The diagnosis of murine typhus was made by a 4-fold rise in specific Rickettsia typhi antibody, using indirect immunofluorescent assay. He dramatically improved after treatment with doxycycline for 7 days. To our knowledge, this is the first case report of murine typhus in a liver transplant recipient.
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Affiliation(s)
- P Phatharodom
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - S Limsrichamrern
- Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - J Kaewwinud
- Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - M Chayakulkeeree
- Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Breitschwerdt EB, Hegarty BC, Qurollo BA, Saito TB, Maggi RG, Blanton LS, Bouyer DH. Intravascular persistence of Anaplasma platys, Ehrlichia chaffeensis, and Ehrlichia ewingii DNA in the blood of a dog and two family members. Parasit Vectors 2014; 7:298. [PMID: 24984562 PMCID: PMC4089936 DOI: 10.1186/1756-3305-7-298] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 06/23/2014] [Indexed: 11/17/2022] Open
Abstract
Background Anaplasmosis, caused by Anaplasma phagocytophilum and Anaplasma platys, and ehrlichiosis, caused by Ehrlichia chaffeensis, Ehrlichia ewingii, the "Panola Mountain Ehrlichia" and Ehrlichia muris-like pathogens have been identified as emerging tick borne infectious diseases in dogs and human patients. Persistent intravascular infection with these bacteria is well documented in dogs, but is less well documented in human beings. Methods Serology and PCR targeting multiple microbial genes, followed by DNA sequencing, was used to test sequential blood samples. Tissue culture isolation was attempted in two laboratories. Results A. platys, E. chaffeensis, and E. ewingii DNA was amplified from two Anaplasma and Ehrlichia seronegative family members and their dog, all lacking typical symptoms of anaplasmosis or ehrlichiosis. Following treatment with doxycycline, the dog and mother were Anaplasma and Ehrlichia spp. PCR negative. Conclusions Sequential PCR testing provided molecular evidence supporting intravascular persistence of A. platys and Ehrlichia spp. in two humans and their dog. Diagnosticians and clinicians should consider the potential for co-infections due to these tick borne organisms.
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Affiliation(s)
- Edward B Breitschwerdt
- Intracellular Pathogens Research Laboratory and the Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
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Sachdev SH, Joshi V, Cox ER, Amoroso A, Palekar S. Severe life-threatening Ehrlichia chaffeensis infections transmitted through solid organ transplantation. Transpl Infect Dis 2013; 16:119-24. [PMID: 24330198 DOI: 10.1111/tid.12172] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 06/04/2013] [Accepted: 07/31/2013] [Indexed: 11/28/2022]
Abstract
BACKGROUND Donor-derived infections from organ transplantation are rare occurrences with preoperative screening practices. Ehrlichia chaffeensis, a tick-borne illness, transmitted through solid organ transplantation has not been reported previously to our knowledge. We present cases of 2 renal allograft recipients who developed severe E. chaffeensis infection after receipt of organs from a common deceased donor. METHODS The 2 renal transplant patients who developed E. chaffeensis infection are reported in case study format with review of the literature. RESULTS Approximately 3 weeks after renal transplantation, both patients developed an acute febrile illness and rapid clinical decline. Recipient A underwent an extensive infectious workup that revealed positive E. chaffeensis DNA from polymerase chain reaction on peripheral blood. Recipient B's clinical team obtained acute and convalescent antibody titers for E. chaffeensis, which demonstrated acute infection. Recipients A and B were treated with doxycycline and tigecycline, respectively, with clinical cure. CONCLUSIONS These cases demonstrate that tick-borne pathogens, such as E. chaffeensis, can be transmitted through renal transplantation. E. chaffeensis can be associated with excessive morbidity and mortality, commonly owing to delay in diagnosis and poor response to non-tetracycline antibiotics. In populations with endemic tick-borne illness, donors should be questioned about tick exposure, and appropriate antibiotics can be administered if indicated.
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Affiliation(s)
- S H Sachdev
- Nephrology, Department of Medicine, Newark Beth Israel Medical Center, Newark, New Jersey, USA
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Folkema AM, Holman RC, Dahlgren FS, Cheek JE, McQuiston JH. Epidemiology of ehrlichiosis and anaplasmosis among American Indians in the United States, 2000-2007. Am J Trop Med Hyg 2012; 87:529-37. [PMID: 22826495 DOI: 10.4269/ajtmh.2012.12-0060] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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.
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Affiliation(s)
- Arianne M Folkema
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention (CDC), United States
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12
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Abstract
Human ehrlichiosis and anaplasmosis are acute febrile tick-borne diseases caused by various members of the genera Ehrlichia and Anaplasma (Anaplasmataceae). Human monocytotropic ehrlichiosis has become one of the most prevalent life-threatening tick-borne disease in the United States. Ehrlichiosis and anaplasmosis are becoming more frequently diagnosed as the cause of human infections, as animal reservoirs and tick vectors have increased in number and humans have inhabited areas where reservoir and tick populations are high. Ehrlichia chaffeensis, the etiologic agent of human monocytotropic ehrlichiosis (HME), is an emerging zoonosis that causes clinical manifestations ranging from a mild febrile illness to a fulminant disease characterized by multiorgan system failure. Anaplasma phagocytophilum causes human granulocytotropic anaplasmosis (HGA), previously known as human granulocytotropic ehrlichiosis. This article reviews recent advances in the understanding of ehrlichial diseases related to microbiology, epidemiology, diagnosis, pathogenesis, immunity, and treatment of the 2 prevalent tick-borne diseases found in the United States, HME and HGA.
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Affiliation(s)
- Nahed Ismail
- Department of Pathology, Meharry Medical College, Nashville, TN 37208, USA. <>
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13
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Persistent infection contributes to heterologous protective immunity against fatal ehrlichiosis. Infect Immun 2009; 77:5682-9. [PMID: 19805532 DOI: 10.1128/iai.00720-09] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Human monocytotropic ehrlichiosis (HME), an emerging and often life-threatening tick-transmitted disease, is caused by the obligately intracellular bacterium Ehrlichia chaffeensis. HME is modeled in C57BL/6 mice using Ehrlichia muris, which causes persistent infection, and Ixodes ovatus Ehrlichia (IOE), which is either acutely lethal or sublethal depending on the dose and route of inoculation. A persistent primary E. muris infection, but not a sublethal IOE infection, protects mice against an ordinarily lethal secondary IOE challenge. In the present study, we determined the role of persistent infection in maintenance of protective memory immune responses. E. muris-infected mice were treated with doxycycline or left untreated and then challenged with an ordinarily lethal dose of IOE. Compared to E. muris-primed mice treated with doxycycline, untreated mice persistently infected with E. muris had significantly greater numbers of antigen-specific gamma interferon-producing splenic memory T cells, significant expansion of CD4(+) CD25(+) T regulatory cells, and production of transforming growth factor beta1 in the spleen. Importantly, E. muris-primed mice treated with doxycycline showed significantly greater susceptibility to challenge infection with IOE compared to untreated mice persistently infected with E. muris. The study indicated that persistent ehrlichial infection contributes to heterologous protection by stimulating the maintenance of memory T-cell responses.
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Lawrence KL, Morrell MR, Storch GA, Hachem RR, Trulock EP. Clinical outcomes of solid organ transplant recipients with ehrlichiosis. Transpl Infect Dis 2009; 11:203-10. [PMID: 19228344 DOI: 10.1111/j.1399-3062.2009.00373.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Because of our experience with severe Ehrlichia infections in lung transplant recipients, we reviewed all cases of ehrlichiosis in solid organ transplant recipients at Barnes-Jewish Hospital in St. Louis, Missouri. Between 1996 and 2007, 25 cases of ehrlichiosis were identified. We retrospectively collected demographic, clinical, laboratory, and outcomes data, and we compared the 5 cases in lung transplant recipients with 20 cases in other solid organ transplant recipients (heart, 2; kidney, 13; liver, 5). The presenting symptoms in the majority of both groups consisted of fever and headache. Clinical outcomes were worse in the lung transplant group and included a greater need for intensive care unit treatment (80% vs. 20%, P=0.02), longer length of hospital stay (21 vs. 5 days, P=0.02), and propensity to develop acute lung injury or acute respiratory distress syndrome (60% vs. 10%, P=0.04). No mortalities occurred in either group of patients. In an endemic area, ehrlichiosis is not unusual in solid organ transplant recipients, and lung transplant recipients tend to have a more severe illness.
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Affiliation(s)
- K L Lawrence
- Department of Medicine, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, USA.
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15
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Assi MA, Yao JDC, Walker RC. Lyme disease followed by human granulocytic anaplasmosis in a kidney transplant recipient. Transpl Infect Dis 2007; 9:66-72. [PMID: 17313478 DOI: 10.1111/j.1399-3062.2006.00177.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
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.
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Affiliation(s)
- M A Assi
- Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905-0002, USA
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Abstract
To characterize the impact of immunosuppression on human ehrlichiosis, we reviewed cases of ehrlichiosis occurring in transplant recipients and immunocompetent patients at three hospitals in Nashville, Tennessee. Between 1998 and 2006, 15 transplant patients were identified as having ehrlichiosis, diagnosed either by whole blood polymerase chain reaction (PCR) (n = 14) or serology (n = 1). They were compared with 43 immunocompetent patients diagnosed by whole blood PCR. We retrospectively collected demographic and clinical information. The species of Ehrlichia (E. ewingii or E. chaffeensis) was determined for patients diagnosed by PCR. The 15 transplant recipients with ehrlichiosis included 7 kidney recipients, 6 heart recipients, 1 liver recipient and 1 lung recipient. Transplant recipients had more infections with E. ewingii than immunocompetent patients (23% vs. 5%, p = 0.08). Transplant recipients experienced less rash (0% vs. 36%, p = 0.006) and presented with significantly lower hepatic enzymes, but more leukopenia and renal dysfunction than immunocompetent patients. Doxycycline therapy was started within 48 h of presentation in 73% of transplant recipients and 78% of immunocompetent patients (p = 0.7). No patient died in either group. Ehrlichia infections can occur in transplant recipients who live in an endemic area. With prompt treatment, the infected transplant recipients in our study had similar, favorable outcomes compared to immunocompetent patients.
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Affiliation(s)
- L D Thomas
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
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Kotton CN. Zoonoses in Solid-Organ and Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis 2007; 44:857-66. [PMID: 17304461 DOI: 10.1086/511859] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2006] [Accepted: 11/25/2006] [Indexed: 02/05/2023] Open
Abstract
Numerous reports exist of the transmission of zoonoses to humans during and after solid-organ and hematopoietic stem cell transplantation. Donor-derived infections of numerous etiologies, including West Nile virus infection, Chagas disease, toxoplasmosis, rabies, lymphocytic choriomeningitis virus infection, and infection due to Brucella species have been reported. Most zoonoses occur as a primary infection after transplantation, and immunocompromised patients are more likely to experience significant morbidity and mortality from these infections. Risks of zoonotic infection in the posttransplantation period could be reduced by patient education. Increased recognition of the risks of zoonoses, as well as the advent of molecular biology-based testing, will potentially augment diagnostic aptitude. Documented zoonotic infection as it affects transplantation will be the primary focus of this review.
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Affiliation(s)
- Camille N Kotton
- Transplant and Immunocompromised Host Section, Infectious Diseases Division, Massachusetts General Hospital, Boston, MA 02114, USA.
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Abstract
Ehrlichiosis in the United States is caused by three closely related bacterial species (Ehrlichia chaffeensis, Ehrlichia ewingii, and Anaplasma phagocytophilum), all transmitted through tick bite. Although there is variation with respect to geography and tick vector, the clinical manifestations are similar, and treatment of these infections is identical. Ehrlichiosis can present with a spectrum of neurologic manifestations, ranging in severity from headache to meningoencephalitis. Treatment is straightforward if the diagnosis is suspected, but antibiotic therapy should not be delayed pending laboratory confirmation. Doxycycline, the treatment of choice for adults and children with suspected ehrlichiosis, has high bioavailability and can be administered orally in most cases. Therapy is typically continued at least 3 days after the last documented fever. Although there have been no studies specifically evaluating duration or dosing of doxycycline for Ehrlichia meningoencephalitis, anecdotal reports suggest 100 mg doxycycline administered twice daily is effective, despite limited penetration into the cerebrospinal fluid. Because doxycycline interacts with CYP3A4 enzymes, there is potential for drug interactions with a number of medications. In endemic areas, documentation of coinfection with Borrelia burgdorferi, the etiologic agent of Lyme disease, may require prolonging the duration of doxycycline therapy.
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Affiliation(s)
- Igen Hongo
- Division of Infectious Diseases, Vanderbilt University School of Medicine, A-2200 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232, USA.
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Feng HM, Walker DH. Mechanisms of immunity to Ehrlichia muris: a model of monocytotropic ehrlichiosis. Infect Immun 2004; 72:966-71. [PMID: 14742542 PMCID: PMC321622 DOI: 10.1128/iai.72.2.966-971.2004] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Ehrlichia species can cause life-threatening infections or chronic persistent infections. Mechanisms of protective immunity were examined in an Ehrlichia muris mouse model of monocytotropic ehrlichiosis. C57BL/6 mice possessed strong genetic resistance to E. muris of an undetermined mechanism. CD8 T lymphocytes were particularly important, as revealed by 81% fatalities for E. muris-infected, major histocompatibility complex class I gene knockout mice compared with no deaths for wild-type C3H mice. Moreover, 80% of C3H mice depleted of CD8 and CD4 cells died of E. muris infection compared with only 44% of CD4 cell-depleted mice. CD8 T lymphocytes were demonstrated for the first time in an Ehrlichia infection to exhibit cytotoxic T-lymphocyte activity against Ehrlichia-infected target cells. Both gamma interferon and tumor necrosis factor were shown to play synergistic roles in protective immunity in vivo for the first time, as demonstrated by 75% fatalities when both cytokines were neutralized compared with minimal mortality when they were depleted separately. Passive transfer of antibodies, but not Fab fragments, to E. muris protected C3H/SCID mice against lethal infection. The mechanism of increased susceptibility (22% lethality) of C57BL/6 major histocompatibility complex class II gene knockout mice and CD4 cell-depleted C3H mice (i.e., through a gamma interferon or antibody mechanism), as well as the more important role of CD8 T lymphocytes (in the form of cytotoxic T-lymphocyte activity and/or gamma interferon production), remains to be elucidated. Protective immunity against monocytotropic E. muris is mediated by a combination of CD8 and CD4 T lymphocytes, gamma interferon, tumor necrosis factor alpha, and antibodies.
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Affiliation(s)
- Hui-Min Feng
- Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA
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Yabsley MJ, Little SE, Sims EJ, Dugan VG, Stallknecht DE, Davidson WR. Molecular variation in the variable-length PCR target and 120-kilodalton antigen genes of Ehrlichia chaffeensis from white-tailed deer (Odocoileus virginianus). J Clin Microbiol 2004; 41:5202-6. [PMID: 14605163 PMCID: PMC262520 DOI: 10.1128/jcm.41.11.5202-5206.2003] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Genes encoding two surface-expressed antigens of Ehrlichia chaffeensis, the variable-length PCR target (VLPT) and the 120-kDa antigen, which contain variable numbers of tandem repeats, were characterized for E. chaffeensis from white-tailed deer (Odocoileus virginianus). Both genes from infected deer contained numbers of repeats similar to those reported in genes from humans and ticks, although a new variant of the 120-kDa antigen gene containing five repeat units and coinfection with multiple VLPT and 120-kDa antigen gene genetic types were detected. Sequence analysis of both genes revealed more nucleotide variation than previously reported for E. chaffeensis from infected humans or ticks. This is the most extensive study of E. chaffeensis VLPT and 120-kDa antigen gene genetic variation to date and is the first to examine genetic variation in E. chaffeensis from a nonhuman vertebrate host.
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Affiliation(s)
- Michael J Yabsley
- Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, The University of Georgia, Athens, Georgia 30602, USA.
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Abstract
Ehrlichia chaffeensis is an obligately intracellular, tick-transmitted bacterium that is maintained in nature in a cycle involving at least one and perhaps several vertebrate reservoir hosts. The moderate to severe disease caused by E. chaffeensis in humans, first identified in 1986 and reported for more than 1,000 patients through 2000, represents a prototypical "emerging infection." Knowledge of the biology and natural history of E. chaffeensis, and of the epidemiology, clinical features, and laboratory diagnosis of the zoonotic disease it causes (commonly referred to as human monocytic ehrlichiosis [HME]) has expanded considerably in the period since its discovery. In this review, we summarize briefly the current understanding of the microbiology, pathogenesis, and clinical manifestations associated with this pathogen but focus primarily on discussing various ecological factors responsible for the recent recognition of this important and potentially life-threatening tick-borne disease. Perhaps the most pivotal element in the emergence of HME has been the staggering increases in white-tailed deer populations in the eastern United States during the 20th century. This animal serves as a keystone host for all life stages of the principal tick vector (Amblyomma americanum) and is perhaps the most important vertebrate reservoir host for E. chaffeensis. The contributions of other components, including expansion of susceptible human populations, growth and broadening geographical distributions of other potential reservoir species and A. americanum, and improvements in confirmatory diagnostic methods, are also explored.
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Affiliation(s)
- Christopher D Paddock
- Viral and Rickettsial Zoonoses Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
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